222 results on '"L. Moss"'
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2. Determination of a neurologic safe zone for bicortical S1 pedicle screw placement
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Ergin Coskun, Ian J. Wellington, Nicholas Bellas, Hardeep Singh, Scott S. Mallozzi, Mark P. Cote, and Isaac L. Moss
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Sacrum ,Lumbar Vertebrae ,Spinal Fusion ,Pedicle Screws ,Humans ,Surgery ,Orthopedics and Sports Medicine ,Neurology (clinical) ,Retrospective Studies - Abstract
Lumbosacral fixation is commonly used for the management of lumbosacral instability. As the sacrum mainly consists of cancellous bone, bicortical fixation, in which the pedicle screw penetrates the anterior sacral cortex, can help increase the strength of fixation. However, this method carries a risk to the L5 nerves which lie anterior to the sacrum at this level.The goal of this study is to determine a safe zone for the placement of S1 pedicle screws to decrease the likelihood of L5 nerve injury.Retrospective imaging review.This study evaluated imaging data of patients who underwent lumbar spine magnetic resonance imaging (MRI) at our institute between September 1, 2020 and September 1, 2021.T1-weighted axial MRIs were measured at the level of S1 pedicle screw placement. The space medial and lateral to the L5 nerve root on the anterior sacrum were measured and defined as safe zones. Additionally, the nerve width and sacral lengths were measured at this level.The distribution of the measurements were evaluated to determine a medial and lateral safe zone, as well as the average nerve width at the level of S1 pedicle screw placement. Correlation analysis was performed to determine a relationship between safe zone sizes and sacral size.A total of 400 MRIs were analyzed. The average medial safe zone measured was 32.8 mm (95% CI: 32.2-33.4) with no nerves lying within 22.3 mm of the midline sacrum. The average lateral safe zone measured was 17.7 mm (95% CI: 17.1-18.2), with no nerves within 5.3 mm of the lateral border of the sacrum. The average nerve root width was 6.2 mm (95% CI: 6.13-6.34). An increased sacral length was associated with a larger medial (p.001) and lateral (p.001) safe zone.Our study revealed lateral and medial safe zones for the placement of S1 pedicle screws to avoid iatrogenic nerve injury in a retrospective cohort of 400 patients. There were no L5 nerve roots found within 22.3 mm of the sacrum's mid-axis or within 5.3 mm of the sacrum's anterolateral border. These defined safe zones can be used during pedicle screw planning and placement to decrease the risk of injury to the L5 nerve root. more...
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- 2022
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3. Association Between Dense Breast Legislation and Cancer Stage at Diagnosis
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Mack T. Ruffin, Daleela Dodge, Shouhao Zhou, Chan Shen, Kelly A. Stahl, Roger Klein, Eugene J. Lengerich, Douglas L. Leslie, Jennifer L. Moss, and Alison L. Chetlen
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medicine.medical_specialty ,Epidemiology ,business.industry ,Cancer stage ,Public Health, Environmental and Occupational Health ,Ethnic group ,Cancer ,Breast Neoplasms ,Legislation ,medicine.disease ,Odds ,Breast cancer ,medicine ,Humans ,Mass Screening ,Female ,Stage (cooking) ,business ,Early Detection of Cancer ,Breast Density ,Mammography ,Demography - Abstract
Introduction Many states have mandated breast density notification and insurance coverage for additional screening; yet, the association between such legislation and stage of diagnosis for breast cancer is unclear. This study investigates this association and examines the differential impacts among different age and race/ethnicity subgroups. Methods The Surveillance, Epidemiology, and End Results database was queried to identify patients with breast cancer aged 40–74 years diagnosed between 2005 and 2016. Using a difference-in-differences multinomial logistic model, the odds of being diagnosed at different stages of cancer relative to the localized stage depending on legislation and individual characteristics were examined. Analyses were conducted in 2020–2021. Results The study included 689,641 cases. Overall, the impact of notification legislation was not significant, whereas insurance coverage legislation was associated with 6% lower odds (OR=0.94, 95% CI=0.91, 0.96) of being diagnosed at the regional stage. The association between insurance coverage legislation and stage of diagnosis was even stronger among women aged 40–49 years, with 11% lower odds (OR=0.89, 95% CI=0.82, 0.96) of being diagnosed at the regional stage and 12% lower odds (OR=0.88, 95% CI=0.81, 0.96) of being diagnosed at the distant stage. Hispanic women benefited from notification laws, with 11% lower odds (OR=0.89, 95% CI=0.82, 0.97) of being diagnosed at distant stage. Neither notification nor supplemental screening insurance coverage legislation showed a substantial impact on Black women. Conclusions The findings imply that improving insurance coverage is more important than being notified overall. Raising awareness is important among Hispanic women; improving communication about dense breasts and access to screening might be more important than legislation among Black women. more...
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- 2021
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4. Innovative Follow-up Strategies for Endometrial Cancer
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David S. Guttery, A. Taylor, Esther L. Moss, and Anna Collins
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Oncology ,Cancer survivorship ,medicine.medical_specialty ,business.industry ,Endometrial cancer ,medicine.disease ,Endometrial Neoplasms ,030218 nuclear medicine & medical imaging ,Review article ,Risk category ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,Risk stratification ,medicine ,Humans ,Clinicopathological features ,Female ,Radiology, Nuclear Medicine and imaging ,Neoplasm Recurrence, Local ,Liquid biopsy ,business ,Follow-Up Studies - Abstract
Increasing recognition of the heterogeneous nature of endometrial cancer, the excellent prognosis of low-risk cases and improvements in risk stratification offer opportunities for innovative, personalised follow-up strategies. This review article outlines the evidence base for alternative follow-up strategies in the different risk categories of endometrial cancer, cancer survivorship programmes and considers future directions in endometrial cancer follow-up, including emerging new techniques, such as the liquid biopsy, and opportunities for combining molecular and clinicopathological features to personalise endometrial cancer follow-up. more...
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- 2021
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5. Letter comments on: Mainstreaming informed consent for genomic sequencing: A call for action
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Maurice Dungey, Esther L. Moss, Julian Barwell, and Mark C. Dalby
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Cancer Research ,Medical education ,Service (systems architecture) ,medicine.diagnostic_test ,business.industry ,Genomic sequencing ,Mainstreaming ,Focus (linguistics) ,Single centre ,Oncology ,Action (philosophy) ,Informed consent ,medicine ,business ,Genetic testing - Published
- 2021
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6. Development of a patient-derived explant model for prediction of drug responses in endometrial cancer
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Marion MacFarlane, Gareth J Miles, Esther L. Moss, Ian R. Powley, Catrin Pritchard, Roger Hew, J. Howard Pringle, and Anna Collins
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0301 basic medicine ,Paclitaxel ,Pilot Projects ,Context (language use) ,Pembrolizumab ,Antibodies, Monoclonal, Humanized ,Hysterectomy ,Carboplatin ,Tissue Culture Techniques ,Endometrium ,Genetic Heterogeneity ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Antineoplastic Combined Chemotherapy Protocols ,Biomarkers, Tumor ,Tumor Microenvironment ,Humans ,Medicine ,Apoptosis Marker ,Proliferation Marker ,Precision Medicine ,Immune Checkpoint Inhibitors ,business.industry ,Obstetrics and Gynecology ,Immune checkpoint ,Endometrial Neoplasms ,030104 developmental biology ,Oncology ,chemistry ,Chemotherapy, Adjuvant ,030220 oncology & carcinogenesis ,Cancer research ,Feasibility Studies ,Biomarker (medicine) ,Female ,Drug Screening Assays, Antitumor ,business - Abstract
Objective To undertake a pilot study to develop a novel Patient-Derived-Explant (PDE) model system for use in endometrial cancer (EC) that is capable of monitoring differential drug responses in a pre-clinical setting. Methods Fresh tumour was obtained post-hysterectomy from 27 patients with EC. Tumours were cut into 1–3 mm3 explants that were cultured at the air-liquid interface for 16–24 h in culture media. Explants were cultured in different media conditions to optimise viability. Explants were also treated with carboplatin/paclitaxel or pembrolizumab for 24 h and processed into histology slides. Multiplexed immunofluorescence for Ki67 (proliferation marker), cPARP (apoptosis marker) and CAM 5.2 (tumour mask) was performed followed by image analysis and quantitation of biomarker expression. Results EC samples are amenable to PDE culture with preserved histological architecture and PDE viability for up to 48 h, with the addition of autologous serum in culture media facilitating EC-PDE viability. Our PDE platform provides evidence of differential drug-response to conventional chemotherapeutics and immune checkpoint inhibition, and these responses can be assessed in the context of a preserved tumour microenvironment. Conclusions Our PDE platform represents a rapid, low-cost pre-clinical model which can be easily integrated into drug development pipelines. PDE culture preserves original tumour architecture and enables evaluation of spatial relationships in the tumour microenvironment. PDE culture has the potential for personalised drug-testing in a pre-clinical setting which is increasingly important in an era of personalised medicine in the treatment of EC. more...
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- 2021
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7. Identification of European-wide clinical priorities for guideline development in the management of pre-invasive cervical disease
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Charles W.E. Redman, Esther L. Moss, Anna Collins, Pekka Nieminen, and Simon Leeson
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medicine.medical_specialty ,Best practice ,Uterine Cervical Neoplasms ,Context (language use) ,Cervical disease ,Cervical intraepithelial neoplasia ,Likert scale ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Humans ,Medicine ,030212 general & internal medicine ,Papillomaviridae ,Colposcopy ,030219 obstetrics & reproductive medicine ,medicine.diagnostic_test ,business.industry ,Papillomavirus Infections ,HPV infection ,Obstetrics and Gynecology ,medicine.disease ,3. Good health ,Identification (information) ,Reproductive Medicine ,Family medicine ,Female ,business - Abstract
Objective Addressing management controversies in the treatment of pre-invasive cervical disease is a key priority for the European Federation for Colposcopy/European Society of Gynaecologic Oncology who aim to develop a practical handbook of European centred guidelines to address areas where there is a lack of high-quality evidence or identifiable practice variation. Clinical opinion across the EFC network was sought to identify topics likely to have the most impact on clinical practice for systematic review and development of practice recommendations. Study design A scoping exercise comprising of a three-iteration modified Delphi with representation from each member society of the EFC was conducted in 2018. Round one identified 19 potential topics which were scored for importance using a five-point Likert scale by EFC members in round two and ranked. Results from round two were discussed at an open EFC satellite meeting resulting in exclusion of five topics. A third round of the 14 remaining topics was conducted to allow members to modify scores after viewing the second-round rankings. Responses were analysed and topics were allocated a weighted score. Results Strategies for management of persistent HPV infection in the context of normal colposcopy and negative cytology was the highest overall weighted topic (4.40) followed by identification of appropriate length of follow up for ASCUS or LSIL prior to excisional treatment (3.95) and the impact of length of excision on patient outcomes (3.95). Topics to identify best practice for management of challenging topics scored highly including optimising follow up strategies for cervical stenosis (3.91) and management of HSIL in the under 25 year olds (3.64) or pregnancy (3.64). Conclusion A European wide systematic modified-Delphi has prioritised six topics for systematic review and generation of clinical practice recommendations aiming to assist management in areas of controversy in pre-invasive cervical disease. more...
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- 2020
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8. Anticipating the Next Generation of Powerful Digital Players: Implications for Competition Policy
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Diana L. Moss and David Hummel
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- 2022
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9. Patient-derived explants, xenografts and organoids: 3-dimensional patient-relevant pre-clinical models in endometrial cancer
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Gareth J Miles, Marion MacFarlane, Anna Collins, Joanna P. Wood, Catrin Pritchard, and Esther L. Moss
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Tumour heterogeneity ,medicine.medical_treatment ,Population ,Cell Culture Techniques ,Patient characteristics ,Translational research ,Translational Research, Biomedical ,03 medical and health sciences ,0302 clinical medicine ,Spheroids, Cellular ,Internal medicine ,medicine ,Advanced disease ,Animals ,Humans ,education ,Cytotoxic Therapy ,education.field_of_study ,business.industry ,Endometrial cancer ,Obstetrics and Gynecology ,Immunotherapy ,medicine.disease ,Endometrial Neoplasms ,Organoids ,030104 developmental biology ,030220 oncology & carcinogenesis ,Heterografts ,Female ,Drug Screening Assays, Antitumor ,business ,Carcinoma, Endometrioid ,Neoplasm Transplantation - Abstract
The majority of endometrial cancers are detected early with a favourable prognosis. However, for patients with advanced disease, chemotherapy response rates and overall survival remains poor. The endometrial cancer population is typically elderly with multiple co-morbidities and aggressive cytotoxic therapy may be hazardous. Therefore, there is an urgent need to define optimal treatment strategies for advanced and recurrent disease and personalise therapy based on individual tumour and patient characteristics. Three-dimensional (3D) models that preserve the tumour microenvironment and tumour-stromal interactions are increasingly important for translational research with the advent of immunotherapy and molecularly targeted agents. 3D patient-relevant pre-clinical models in endometrial cancer include spheroids, patient-derived organoids, microfluidic systems, patient-derived xenografts and patient-derived explants. Here we present a review of available 3D modelling systems in endometrial cancers, highlighting their current use, advantages, disadvantages and applications to translational research with a focus on the power of the patient-derived explant platform. more...
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- 2020
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10. Differentiated Thyroid Cancer in Children: A UK Multicentre Review and Review of the Literature
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Katie L. Newbold, Georgina Gerrard, R. Sindhu, Karla A. Lee, D. Tumino, Vanessa Gill, Jonathan Wadsley, M.T.A. Sharabiani, Mark N. Gaze, and L. Moss
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Male ,Pediatrics ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Disease ,030218 nuclear medicine & medical imaging ,Thyroid carcinoma ,03 medical and health sciences ,0302 clinical medicine ,Adenocarcinoma, Follicular ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Thyroid Neoplasms ,External beam radiotherapy ,Child ,Thyroid cancer ,Historical record ,Proportional Hazards Models ,Proportional hazards model ,business.industry ,medicine.disease ,United Kingdom ,Oncology ,Thyroid Cancer, Papillary ,Child, Preschool ,030220 oncology & carcinogenesis ,Female ,Thyroglobulin ,Radioactive iodine ,business - Abstract
Aims To obtain an overview of the management and outcomes of children aged 18 years or younger diagnosed with differentiated thyroid carcinoma of follicular cell origin across the UK, by collecting and analysing data from the limited number of centres treating these patients. This multicentre data might provide a more realistic perspective than single-institution series. Materials and methods Six centres submitted data extracted from historical records on patients aged 18 years or younger, diagnosed between 1964 and 2017. The univariate and multivariable Cox proportional hazard model was used to identify potential predictors of progression-free survival, using national data as a control. Results Data on 166 patients were available for analysis. Females (74%) were predominant, and the age ranged from 3 to 19 years at diagnosis, mean 14.1 years. Nodal metastases were present in 51%; 12% had distant metastases. After surgery, 95% received radioactive iodine (39% on more than one occasion) and 4% received external beam radiotherapy. With a median follow-up duration of 5 years, 69% are alive with no evidence of disease; 20% are alive with a raised thyroglobulin level as the only evidence of residual disease; 6% have residual structural disease detectable on imaging; 2% have died, from cerebral metastases. Conclusion Despite most patients having advanced disease at presentation, outcomes are very good. A national prospective registry should allow systematic collection of good-quality data and may facilitate research to further improve outcomes. more...
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- 2019
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11. Deimmunizing substitutions in Pseudomonas exotoxin domain III perturb antigen processing without eliminating T-cell epitopes
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Samuel J. Landry, Ramgopal R. Mettu, Hee-Won Park, and Daniel L. Moss
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CD4-Positive T-Lymphocytes ,0301 basic medicine ,Biochemistry & Molecular Biology ,Protein Folding ,Protein Conformation ,Antigen presentation ,Exotoxins ,Major histocompatibility complex ,Biochemistry ,Epitope ,Epitopes ,Mice ,03 medical and health sciences ,Antigen ,Pseudomonas ,Animals ,Pseudomonas exotoxin ,Antigens ,Molecular Biology ,Antigen Presentation ,030102 biochemistry & molecular biology ,biology ,Antigen processing ,Chemistry ,Immunogenicity ,Cell Biology ,Endolysosome ,Cell biology ,RAW 264.7 Cells ,030104 developmental biology ,Mutation ,Proteolysis ,biology.protein - Abstract
© 2019 Moss et al. Effective adaptive immune responses depend on activation of CD4 T cells via the presentation of antigen peptides in the context of major histocompatibility complex (MHC) class II. The structure of an antigen strongly influences its processing within the endolysosome and potentially controls the identity of peptides that are presented to T cells. A recombinant immunotoxin, comprising exotoxin A domain III (PE-III) from Pseudomonas aeruginosa and a cancer-specific antibody fragment, has been developed to manage cancer, but its effectiveness is limited by the induction of neutralizing antibodies. Here, we observed that this immunogenicity is substantially reduced by substituting six residues within PE-III. Although these substitutions targeted T-cell epitopes, we demonstrate that reduced conformational stability and protease resistance were responsible for the reduced antibody titer. Analysis of mouse T-cell responses coupled with biophysical studies on single-substitution versions of PE-III suggested that modest but comprehensible changes in T-cell priming can dramatically perturb antibody production. The most strongly responsive PE-III epitope was well-predicted by a structure-based algorithm. In summary, single-residue substitutions can drastically alter the processing and immunogenicity of PE-III but have only modest effects on CD4 T-cell priming in mice. Our findings highlight the importance of structure-based processing constraints for accurate epitope prediction. more...
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- 2019
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12. Update on Digital Technology: The Failure of Merger Enforcement and Need for Reform
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Diana L. Moss
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Competition (economics) ,White paper ,Dominance (economics) ,Public policy ,Social media ,Business ,Marketing ,Monopolization ,Monopoly ,Enforcement - Abstract
The American Antitrust Institute (AAI) has released the White Paper, Update on Digital Technology: The Failure of Merger Enforcement and Need for Reform. The new White Paper updates and expands on analysis AAI originally released in July 2019. The widely cited 2019 AAI White Paper, The Record of Weak U.S. Merger Enforcement in Digital Technology, was the subject of AAI testimony before the Senate Judiciary Committee and drew attention to the acquisitive history of the five largest multinational online service or computer hardware or software companies: Amazon, Apple, Facebook, Google, and Microsoft (“Big Tech”). It also unpacked the history of merger enforcement under Section 7 of the Clayton Act in a major segment of the digital technology sector. The White Paper concluded that, as compared to enforcement across all sectors, the rate of merger challenges in digital technology is exceptionally low. Since then, much has happened in the digital technology sector. Big Tech has solidified its hold on the top-most slots, by market value, in the Fortune 500. Federal and state monopolization cases have been filed against Google and Facebook. Among other things, the Facebook complaints allege that acquisitions of small rivals, such as social media firms Instagram (2012) and WhatsApp (2014), were a strategy to snuff out potential competition to maintain a monopoly in personal social networking services. The public policy debate over the dominance of Big Tech has also generated numerous proposals to remedy competitive and consumer harm, including breakups and digital market regulation. A 2020 House Judiciary Committee report examined competitive issues raised by the platforms that are at the core of many of the large digital ecosystems. Moreover, the digital ecosystems have been the subject of ongoing economic, business, and policy research, which has advanced the state of thinking over potential policy solutions to the problems they raise. Results of AAI’s updated analysis indicate that expansion by acquisition continues to be a leading method by which the large digital ecosystems grow. Enforcers can expect to see further growth that, when juxtaposed with persistent, weak merger enforcement in the sector, will likely exacerbate competition problems. Indeed, stronger merger enforcement over the last two decades would have mitigated the monopolization concerns that AAI sees now. As it stands, however, Section 2 of the Sherman Act is virtually the only antitrust tool left to combat dominance in the digital technology sector. This White Paper turns first to updating data on acquisitions by Big Tech through 2020 and merger enforcement statistics through the latest available reporting year, 2019. It then examines the implications of Big Tech’s likely trajectory of further expansion through acquisition and growth in critical cloud infrastructure capability. It closes with an analysis of reforms necessary to revitalize merger enforcement in digital technology. more...
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- 2021
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13. Market Power and Digital Business Ecosystems: Assessing the Impact of Economic and Business Complexity on Competition Analysis and Remedies
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Diana L. Moss, Greg Gundlach, and Riley T. Krotz
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- 2021
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14. Radical Cancer Treatment is Safe During COVID-19: The Real World Experience of a Large London-Based Comprehensive Cancer Centre During the First Wave
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Beth Russell, Charlotte L. Moss, Maria Monroy-Inglesias, Graham Roberts, Harvey Dickinson, Kate Haire, Kathryn Innes, Bansi Mulji-Shah, Fiona Castell, Omar Al-Salihi, Mary Lei, Angela Francis, Bill Dann, Vikash Jogia, Hisham Hamed, Ben Challacombe, Ricard Simo, Stephanie Fraser, Mieke Van Hemelrijk, Saoirse Dolly, and Victoria Harris more...
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2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Cancer centre ,medicine ,Medical emergency ,medicine.disease ,business ,Cancer treatment - Published
- 2021
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15. The Critical Role of Private Antitrust Enforcement in the United States Commentary on: 2020 Antitrust Annual Report: Class Action Filings in Federal Court
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American Antitrust Institute, Laura M. Alexander, Randy Stutz, Diana L. Moss, and Josh Paul Davis
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Price fixing ,Damages ,Legislature ,Business ,Monopolization ,Enforcement ,Settlement (litigation) ,Class action ,Supreme court ,Law and economics - Abstract
With all of the attention currently focused on public enforcement and legislative reform of the antitrust laws, less attention is being paid to private enforcement. But Congress considered private antitrust enforcement indispensable for promoting competition. The judiciary has so recognized time and time again. In California v. American Stores Co., for example, the Supreme Court proclaimed, “Private enforcement of the [Clayton] Act was in no sense an afterthought; it was an integral part of the congressional plan for protecting competition.” Private enforcement is not a substitute for vigorous public enforcement. Both are necessary to foster competition. But private enforcement plays an important part, one that becomes more significant when public enforcement recedes. And, unlike public enforcers, private enforcers can obtain significant damages on behalf of the victims of antitrust violations. This serves as a crucial source of deterrence for illegal anticompetitive conduct and the primary means of compensating victims for harms suffered at the hands of cartelists and dominant firms. The importance of the antitrust class action, a major private enforcement device, is clear. The recently released 2020 Antitrust Annual Report: Class Action Filings in Federal Court (“2020 Report”) by Huntington National Bank and the University of San Francisco School of Law (“USF Law”) reflects that the cumulative total settlement amount recovered for victims in antitrust class actions from 2009-2020 was over $27 billion. Antitrust class actions recover damages from companies engaged in harmful, illegal conduct, such as price fixing and attempted monopolization, in markets for important and essential products and services. The most active defendants during the period, for example, included companies providing financial services, pharmaceuticals, automobile parts, and electronics parts. In light of the vital role played by private antitrust enforcement, and the antitrust class action in particular, continued empirical analysis of trends in activity is essential. This analysis aids in understanding and evaluating proposals for reforming the antitrust laws in the U.S. and such proposals’ impact on private enforcement, the public-private partnership, and ultimately on competition and consumers. more...
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- 2021
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16. Market Power and Digital Business Ecosystems: Assessing the Impact of Economic and Business Complexity on Competition and Remedies
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Diana L. Moss, Riley T. Krotz, and Gregory T. Gundlach
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Competition (economics) ,Information asymmetry ,Value proposition ,Organizational structure ,Business ,Market power ,Monopolization ,Business model ,Industrial organization ,Market failure - Abstract
“Digital business ecosystems” (DBEs) reflect the culmination of progressive changes in business models and organizational structure over the last 40 years. The ubiquity of many large DBEs in our economy, society, and political system is troubling, as is their significant market power, which is the subject of competition investigations in the U.S. and abroad. But the DBE business model, which far surpasses other models and structures in its scope, scale, and complexity, remains largely under-analyzed. DBEs feature unique economic, technological, and business characteristics that increase their opacity to consumers, competition enforcers, and lawmakers. These include information as the currency of exchange and a range of market failures such as positive network effects, information asymmetries around user data and privacy, and data externalities. As the “engine” of commerce and growth in DBEs, cloud computing technology adds further complexity to the analysis of market power. This is particularly true of data analytics, supported by artificial intelligence (AI) and machine learning, which powers the DBE “value proposition” of maximizing user engagement and monetizing user data. This report examines the unique characteristics of DBEs and assesses their implications for competition enforcement and policy. This analysis raises numerous questions around the adequacy of conventional competition analysis in evaluating market power concerns. The widening gap between the complexity and growth of DBEs—and the likely inadequacy of policy responses to the market power problems they raise—elevates the importance of such questions. However, they cannot be answered by relying solely on a legal-economic framework. We therefore adopt a multidisciplinary approach, incorporating economics, law, and business theory and research in our analysis. Not surprisingly, it reveals important caveats and cautions regarding the application of conventional competition analysis to DBEs, with implications for how competition enforcers and legislators assess market power and design remedies, particularly in the merger and monopolization contexts. The report begins with the evolution of the DBE business model and its rapid and expansive growth. We then turn to an analysis of the major structural and behavioral features of DBEs. Next are implications for competition analysis, such as how markets are defined, how market power is exercised, and remedies. The final section concludes with recommendations. As public and private antitrust cases against large DBEs mount, the U.S. Department of Justice (DOJ), Federal Trade Commission (FTC), state Attorneys General, and courts will continue to grapple with their unique features. This report provides important analysis, insights, and recommendations for enforcers and policymakers as they explore the full complement of tools available to rein in the market power of DBEs. more...
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- 2021
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17. Fulminant hepatic failure after simultaneous kidney-pancreas transplantation: a case report
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Benjamin W. Brown, Jimmy L. Moss, Klaus D. Torp, Stephen Aniskevich, and Sher-Lu Pai
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Isoflurane toxicity ,medicine.medical_specialty ,medicine.medical_treatment ,Adverse drug reaction ,Kidney-pancreas transplant ,Liver transplantation ,Volatile agents ,lcsh:RD78.3-87.3 ,03 medical and health sciences ,0302 clinical medicine ,Fulminant hepatic failure ,Anesthesiology ,medicine ,RD78.3-87.3 ,Kidney pancreas transplantation ,Liver transplant ,Unusual case ,business.industry ,Liver failure ,General Medicine ,Perioperative ,Surgery ,Drug reaction ,lcsh:Anesthesiology ,030220 oncology & carcinogenesis ,Inhalational anesthesia ,030211 gastroenterology & hepatology ,business - Abstract
We describe an unusual case of hyperacute hepatic failure following general anesthesia in a patient receiving a simultaneous kidney-pancreas transplant. Despite an aggressive evaluation of structural, immunological, viral, and toxicological causes, a definitive cause could not be elucidated. The patient required a liver transplant and suffered a protracted hospital course. We discuss the potential causes of fulminant hepatic failure and the perioperative anesthesia management of her subsequent liver transplantation. Resumo: Descrevemos um caso incomum de insuficiência hepática hiperaguda após a anestesia geral em uma paciente que recebeu um transplante simultâneo de rim-pâncreas. Apesar de uma avaliação agressiva das causas estruturais, imunológicas, virais e toxicológicas, uma causa definitiva não pôde ser identificada. A paciente precisou de um transplante de fígado que resultou em prolongamento da internação hospitalar. Discutimos as potenciais causas da insuficiência hepática fulminante e o manejo da anestesia no período perioperatório de seu subsequente transplante de fígado. Keywords: Liver failure, Kidney-pancreas transplant, Volatile agents, Liver transplant, Drug reaction, Isoflurane toxicity, Adverse drug reaction, Inhalational anesthesia, Palavras-chave: Insuficiência hepática, Transplante de rim-pâncreas, Agentes voláteis, Transplante de fígado, Reação medicamentosa, Toxicidade por isoflurano, Reação medicamentosa adversa, Anestesia inalatória more...
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- 2018
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18. Insuficiência hepática fulminante após transplante simultâneo de rim‐pâncreas: um relato de caso
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Klaus D. Torp, Jimmy L. Moss, Stephen Aniskevich, Sher‐Lu L. Pai, and Benjamin W. Brown
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Gynecology ,03 medical and health sciences ,medicine.medical_specialty ,0302 clinical medicine ,Anesthesiology and Pain Medicine ,business.industry ,030220 oncology & carcinogenesis ,medicine ,Liver failure ,030211 gastroenterology & hepatology ,Drug reaction ,business ,Inhalational anesthesia - Abstract
Resumo Descrevemos um caso incomum de insuficiencia hepatica hiperaguda apos a anestesia geral em uma paciente que recebeu um transplante simultâneo de rim‐pâncreas. Apesar de uma avaliacao agressiva das causas estruturais, imunologicas, virais e toxicologicas, uma causa definitiva nao pode ser identificada. A paciente precisou de um transplante de figado que resultou em prolongamento da internacao hospitalar. Discutimos as potenciais causas da insuficiencia hepatica fulminante e o manejo da anestesia no periodo perioperatorio de seu subsequente transplante de figado. more...
- Published
- 2018
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19. Knowledge of the risk factors and symptoms associated with endometrial cancer in British South Asian and British White women
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Esther L. Moss, Nafisa Patel, Priyanga Kumarakulasingam, Louise Boutler, Hilary McDermott, and Douglas G Tincello
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Health Knowledge, Attitudes, Practice ,medicine.medical_specialty ,Asia ,South asia ,Malignancy ,White People ,03 medical and health sciences ,0302 clinical medicine ,Survivorship curve ,medicine ,Humans ,Vaginal bleeding ,030212 general & internal medicine ,Aged ,Cervical cancer ,Cervical screening ,Obstetrics ,business.industry ,Endometrial cancer ,Obstetrics and Gynecology ,Middle Aged ,medicine.disease ,United Kingdom ,Endometrial Neoplasms ,Reproductive Medicine ,030220 oncology & carcinogenesis ,Female ,medicine.symptom ,Thematic analysis ,business - Abstract
Objective To explore differences in the background knowledge of Endometrial Cancer (EC), its risk factors, symptoms and prognosis of Endometrial Cancer (EC) between British White (BW) and British South Asian (BSA) women who had undergone treatment for stage I endometrial cancer within the past 3-years. Study design Face-to-face, semi-structured interviews exploring knowledge; diagnosis; treatment; follow-up; and survivorship were undertaken and analysed using Thematic Analysis. Results Twenty-one women were interviewed (13 BW and 8 BSA). BW and BSA women reported similar views, experiences and concerns with regards to EC. Knowledge appeared to differ amongst the two groups with BSA women reporting being more aware that unscheduled vaginal bleeding could be associated with a malignancy but having lower levels of knowledge of the risk factors that can lead to EC, compared to BW women. There was a lack of understanding of the difference between cervical cancer and EC and as a result, many women reported taking reassurance from negative cervical cytology as excluding EC. There was also the misconception amongst some of the women that there was a link between sexual behaviour and EC. Women from both groups used the lay healthcare system to discuss their situation/symptoms, however BSA women reported to have specifically sought out women within their social network who had previously undergone treatment for EC. Conclusions Greater effort is needed to raise awareness in both the BW/BSA communities of the symptoms associated with EC that should prompt medical review. Educational efforts are required to overcome the reported perception that EC is synonymous with cervical cancer and cannot be detected by cervical screening. more...
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- 2018
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20. County-level characteristics associated with incidence, late-stage incidence, and mortality from screenable cancers
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Jennifer L. Moss, Kelsey C. Stoltzfus, Tracy Onega, Alain Kameni, Ming Wang, and Menglu Liang
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Rural Population ,Cancer Research ,Cervical screening ,Epidemiology ,Colorectal cancer ,business.industry ,Incidence ,Mortality rate ,Incidence (epidemiology) ,Uterine Cervical Neoplasms ,Cancer ,medicine.disease ,National Death Index ,Article ,American Community Survey ,Oncology ,Cancer screening ,medicine ,Humans ,Mass Screening ,Female ,business ,Early Detection of Cancer ,Demography - Abstract
Background Cancer screening differs by rurality and racial residential segregation, but the relationship between these county-level characteristics is understudied. Understanding this relationship and its implications for cancer outcomes could inform interventions to decrease cancer disparities. Methods We linked county-level information from national data sources: 2008–2012 cancer incidence, late-stage incidence, and mortality rates (for breast, cervical, and colorectal cancer) from U.S. Cancer Statistics and the National Death Index; metropolitan status from U.S. Department of Agriculture; residential segregation derived from American Community Survey; and prevalence of cancer screening from National Cancer Institute’s Small Area Estimates. We used multivariable, sparse Poisson generalized linear mixed models to assess cancer incidence, late-stage incidence, and mortality rates by county-level characteristics, controlling for density of physicians and median household income. Results Cancer incidence, late-stage incidence, and mortality rates were 6–18% lower in metropolitan counties for breast and colorectal cancer, and 2–4% lower in more segregated counties for breast and colorectal cancer. Generally, reductions in cancer associated with residential segregation were limited to non-metropolitan counties. Cancer incidence, late-stage incidence, and mortality rates were associated with screening, with rates for corresponding cancers that were 2–9% higher in areas with more breast and colorectal screening, but 2–15% lower in areas with more cervical screening. Discussion Lower cancer burden was observed in counties that were metropolitan and more segregated. Effect modification was observed by metropolitan status and county-level residential segregation, indicating that residential segregation may impact healthcare access differently in different county types. Additional studies are needed to inform interventions to reduce county-level disparities in cancer incidence, late-stage incidence, and mortality. more...
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- 2021
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21. Identification of European-wide clinical priorities for guideline development in the management of pre-invasive cervical disease
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Collins, Anna, primary, L Moss, Esther, additional, Nieminen, Pekka, additional, Leeson, Simon, additional, and Redman, Charles WE, additional
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- 2020
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22. Novel Sarcopenia-related Alterations in Sarcomeric Protein Post-translational Modifications (PTMs) in Skeletal Muscles Identified by Top-down Proteomics
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Gary M. Diffee, Wenxuan Cai, Yutong Jin, Judd M. Aiken, Ziqing Lin, Liming Wei, Susan H. McKiernan, Sean J. McIlwain, Ying Ge, Zachery R. Gregorich, and Richard L. Moss
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Male ,Proteomics ,Sarcomeres ,0301 basic medicine ,Aging ,Sarcopenia ,Myofilament ,Quantitative proteomics ,Biology ,Biochemistry ,Analytical Chemistry ,03 medical and health sciences ,Troponin I ,medicine ,Animals ,Muscle, Skeletal ,Molecular Biology ,Research ,Skeletal muscle ,musculoskeletal system ,medicine.disease ,Rats ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,Proteome ,Phosphorylation ,Protein Processing, Post-Translational - Abstract
Sarcopenia, the age-related loss of skeletal muscle mass and strength, is a significant cause of morbidity in the elderly and is a major burden on health care systems. Unfortunately, the underlying molecular mechanisms in sarcopenia remain poorly understood. Herein, we utilized top-down proteomics to elucidate sarcopenia-related changes in the fast- and slow-twitch skeletal muscles of aging rats with a focus on the sarcomeric proteome, which includes both myofilament and Z-disc proteins-the proteins that constitute the contractile apparatuses. Top-down quantitative proteomics identified significant changes in the post-translational modifications (PTMs) of critical myofilament proteins in the fast-twitch skeletal muscles of aging rats, in accordance with the vulnerability of fast-twitch muscles to sarcopenia. Surprisingly, age-related alterations in the phosphorylation of Cypher isoforms, proteins that localize to the Z-discs in striated muscles, were also noted in the fast-twitch skeletal muscle of aging rats. This represents the first report of changes in the phosphorylation of Z-disc proteins in skeletal muscle during aging. In addition, increased glutathionylation of slow skeletal troponin I, a novel modification that may help protect against oxidative damage, was observed in slow-twitch skeletal muscles. Furthermore, we have identified and characterized novel muscle type-specific proteoforms of myofilament proteins and Z-disc proteins, including a novel isoform of the Z-disc protein Enigma. The finding that the phosphorylation of Z-disc proteins is altered in response to aging in the fast-twitch skeletal muscles of aging rats opens new avenues for the investigation of the role of Z-discs in age-related muscle dysfunction. more...
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- 2018
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23. The ergonomic impact of patient body mass index on surgeon posture during simulated laparoscopy
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Esther L. Moss, Stephen Ward, Ryan Sers, Massimiliano Zecca, and Steph Forrester
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Laparoscopic surgery ,medicine.medical_specialty ,medicine.medical_treatment ,Posture ,Physical Therapy, Sports Therapy and Rehabilitation ,Human Factors and Ergonomics ,Body Mass Index ,03 medical and health sciences ,0302 clinical medicine ,Humans ,Medicine ,0501 psychology and cognitive sciences ,Safety, Risk, Reliability and Quality ,Laparoscopy ,Engineering (miscellaneous) ,050107 human factors ,Laparoscopic training ,Surgeons ,medicine.diagnostic_test ,business.industry ,Upper body ,Surgical care ,05 social sciences ,Human factors and ergonomics ,030210 environmental & occupational health ,Physical therapy ,Ergonomics ,business ,Body mass index - Abstract
Laparoscopy is a cornerstone of modern surgical care, with clear advantages for the patients. However, it has also been associated with inducing upper body musculoskeletal disorders amongst surgeons due to their propensity to assume non-neutral postures. Further, there is a perception that patients with high body mass indexes (BMI) exacerbate these factors. Therefore, surgeon upper body postures were objectively quantified using inertial measurement units and the LUBA ergonomic framework was used to assess posture during laparoscopic training on patient models that simulated BMIs of 20, 30, 40 and 50 kg/m2. In all surgeons the posture of the upper body significantly worsened during simulated laparoscopic surgery on the BMI 50 kg/m2 model as compared to the baseline BMI model of 20 kg/m2. These findings suggest that performing laparoscopic surgery on patients with high BMIs increases the prevalence of non-neutral posture and may further increase the risk of musculoskeletal disorders in surgeons. more...
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- 2021
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24. Incomplete excision of cervical precancer as a predictor of treatment failure: a systematic review and meta-analysis
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Freija Verdoodt, Maria Kyrgiou, Jean Gondry, Marc Arbyn, Christine Bergeron, Karl Ulrich Petry, Olaf Reich, Esther L. Moss, Charles W.E. Redman, Simon Leeson, Menelaos Tzafetas, Pekka Nieminen, Sadaf Ghaem-Maghami, and Imperial College Healthcare Charity more...
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TRANSFORMATION ZONE LLETZ ,Neoplasm, Residual ,Uterine Cervical Neoplasms ,Gastroenterology ,0302 clinical medicine ,Treatment Failure ,Colposcopy ,030219 obstetrics & reproductive medicine ,medicine.diagnostic_test ,COLD-KNIFE CONIZATION ,NEOPLASIA GRADE-III ,Margins of Excision ,Middle Aged ,Prognosis ,3. Good health ,Oncology ,CARCINOMA IN-SITU ,030220 oncology & carcinogenesis ,Meta-analysis ,Predictive value of tests ,ELECTROSURGICAL EXCISION ,Female ,Risk assessment ,Life Sciences & Biomedicine ,Adult ,medicine.medical_specialty ,Cervical intraepithelial neoplasia ,Risk Assessment ,03 medical and health sciences ,SQUAMOUS INTRAEPITHELIAL LESIONS ,Predictive Value of Tests ,Internal medicine ,medicine ,Humans ,1112 Oncology and Carcinogenesis ,Oncology & Carcinogenesis ,Cervical Intraepithelial Neoplasia ,TERM-FOLLOW-UP ,Survival analysis ,Aged ,Quality Indicators, Health Care ,Science & Technology ,business.industry ,Carcinoma in situ ,HUMAN-PAPILLOMAVIRUS INFECTION ,Uterine Cervical Dysplasia ,medicine.disease ,Survival Analysis ,Surgery ,LARGE-LOOP EXCISION ,Relative risk ,LASER CONIZATION ,Neoplasm Recurrence, Local ,business ,Precancerous Conditions - Abstract
Summary Background Incomplete excision of cervical precancer is associated with therapeutic failure and is therefore considered as a quality indicator of clinical practice. Conversely, the risk of preterm birth is reported to correlate with size of cervical excision and therefore balancing the risk of adequate treatment with iatrogenic harm is challenging. We reviewed the literature with an aim to reveal whether incomplete excision, reflected by presence of precancerous tissue at the section margins, or post-treatment HPV testing are accurate predictors of treatment failure. Methods We did a systematic review and meta-analysis to assess the risk of therapeutic failure associated with the histological status of the margins of the tissue excised to treat cervical precancer. We estimated the accuracy of the margin status to predict occurrence of residual or recurrent high-grade cervical intraepithelial neoplasia of grade two or worse (CIN2+) and compared it with post-treatment high-risk human papillomavirus (HPV) testing. We searched for published systematic reviews and new references from PubMed-MEDLINE, Embase, and CENTRAL and did also a new search spanning the period Jan 1, 1975, until Feb 1, 2016. Studies were eligible if women underwent treatment by excision of a histologically confirmed CIN2+ lesion, with verification of presence or absence of CIN at the resection margins; were tested by cytology or HPV assay between 3 months and 9 months after treatment; and had subsequent follow-up of at least 18 months post-treatment including histological confirmation of the occurrence of CIN2+. Primary endpoints were the proportion of positive section margins and the occurrence of treatment failure associated with the marginal status, in which treatment failure was defined as occurrence of residual or recurrent CIN2+. Information about positive resection margins and subsequent treatment failure was pooled using procedures for meta-analysis of binomial data and analysed using random-effects models. Findings 97 studies were eligible for inclusion in the meta-analysis and included 44 446 women treated for cervical precancer. The proportion of positive margins was 23·1% (95% CI 20·4–25·9) overall and varied by treatment procedure (ranging from 17·8% [12·9–23·2] for laser conisation to 25·9% [22·3–29·6] for large loop excision of the transformation zone) and increased by the severity of the treated lesion. The overall risk of residual or recurrent CIN2+ was 6·6% (95% CI 4·9–8·4) and was increased with positive compared with negative resection margins (relative risk 4·8, 95% CI 3·2–7·2). The pooled sensitivity and specificity to predict residual or recurrent CIN2+ was 55·8% (95% CI 45·8–65·5) and 84·4% (79·5–88·4), respectively, for the margin status, and 91·0% (82·3–95·5) and 83·8% (77·7–88·7), respectively, for high-risk HPV testing. A negative high-risk HPV test post treatment was associated with a risk of CIN2+ of 0·8%, whereas this risk was 3·7% when margins were free. Interpretation The risk of residual or recurrent CIN2+ is significantly greater with involved margins on excisional treatment; however, high-risk HPV post-treatment predicts treatment failure more accurately than margin status. Funding European Federation for Colposcopy and Institut national du Cancer (INCA). more...
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- 2017
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25. Human Factors Evaluation of Surgeons' Working Positions for Gynecologic Minimal Access Surgery
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Diane E. Gyi, Sue Hignett, Lisa Calkins, Laura Jones, and Esther L. Moss
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Adult ,Male ,medicine.medical_specialty ,Posture ,Pilot Projects ,Choice Behavior ,Task (project management) ,Teaching hospital ,03 medical and health sciences ,Gynecologic Surgical Procedures ,0302 clinical medicine ,Robotic Surgical Procedures ,Surveys and Questionnaires ,Humans ,Minimally Invasive Surgical Procedures ,Medicine ,Musculoskeletal Diseases ,Laparoscopy ,Surgeons ,Laparotomy ,030219 obstetrics & reproductive medicine ,medicine.diagnostic_test ,Minimal access surgery ,business.industry ,Obstetrics and Gynecology ,Flexibility (personality) ,Middle Aged ,Anthropometry ,United Kingdom ,Preference ,Occupational Diseases ,Gynecology ,030220 oncology & carcinogenesis ,Workforce ,Physical therapy ,Female ,business - Abstract
Study Objective To investigate work-related musculoskeletal disorders (WRMSD) in gynaecological minimal access surgery (MAS), including bariatric (plus size) patients Design Mixed methods (Canadian Task Force classification III). Setting Teaching hospital in the United Kingdom. Measurements Survey, observations (anthropometry, postural analysis), and interviews. Results Work-related musculoskeletal disorders (WRMSDs) were present in 63% of the survey respondents (n = 67). The pilot study (n = 11) identified contributory factors, including workplace layout, equipment design, and preference of port use (relative to patient size). Statistically significant differences for WRMSD-related posture risks were found within groups (average-size mannequin and plus-size mannequin) but not between patient size groups, suggesting that port preference may be driven by surgeon preference (and experience) rather than by patient size. Conclusion Some of the challenges identified in this project need new engineering solutions to allow flexibility to support surgeon choice of operating approach (open, laparoscopic or robotic) with a workplace that supports adaptation to the task, the surgeon, and the patient. more...
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- 2017
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26. Urban/Rural Differences in Breast and Cervical Cancer Incidence: The Mediating Roles of Socioeconomic Status and Provider Density
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Benmei Liu, Eric J. Feuer, and Jennifer L. Moss
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Adult ,Rural Population ,Mediation (statistics) ,medicine.medical_specialty ,Health (social science) ,Urban Population ,Uterine Cervical Neoplasms ,Breast Neoplasms ,Rural Health ,Social class ,Article ,Health Services Accessibility ,White People ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Residence Characteristics ,Maternity and Midwifery ,Epidemiology ,Cancer screening ,Health care ,medicine ,Humans ,030212 general & internal medicine ,Healthcare Disparities ,Socioeconomic status ,Early Detection of Cancer ,Aged ,Vaginal Smears ,Gynecology ,business.industry ,Incidence ,Incidence (epidemiology) ,Urban Health ,Public Health, Environmental and Occupational Health ,Obstetrics and Gynecology ,Health Status Disparities ,Middle Aged ,medicine.disease ,Social Class ,Socioeconomic Factors ,030220 oncology & carcinogenesis ,Female ,business ,Mammography ,Demography - Abstract
Breast and cervical cancer incidence vary by urbanicity, and several ecological factors could contribute to these patterns. In particular, cancer screening or other sociodemographic and health care system variables could explain geographic disparities in cancer incidence.Governmental and research sources provided data on 612 counties in the Surveillance, Epidemiology, and End Results program for rural-urban continuum code, socioeconomic status (SES) quintile, percent non-Hispanic White residents, density of primary care physicians, cancer screening, and breast and cervical cancer incidence rates (2009-2013). Ecological mediation analyses used weighted least squares regression to examine whether candidate mediators explained the relationship between urbanicity and cancer incidence.As urbanicity increased, so did breast cancer incidence (βˆ = 0.23; p .001). SES quintile and density of primary care physicians mediated this relationship, whereas percent non-Hispanic White suppressed it (all p .05); county-level mammography levels did not contribute to the relationship. After controlling for these variables, urbanicity and breast cancer incidence were no longer associated (βˆ = 0.11; p .05). In contrast, as urbanicity increased, cervical cancer incidence decreased (βˆ = -0.33; p .001). SES quintile and density of primary care physicians mediated this relationship (both p .05); percent non-Hispanic White and Pap screening levels did not contribute to the relationship. After controlling for these variables, the relationship between urbanicity and cervical cancer incidence remained significant (βˆ = -0.13; p .05).County-level SES and density of primary care physicians explained the relationships between urbanicity and breast and cervical cancer incidence. Improving these factors in more rural counties could ameliorate geographic disparities in breast and cervical cancer incidence. more...
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- 2017
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27. From Competition to Conspiracy: Accessing the Federal Trade Commission’s Merger Policy in the Pharmaceutical Sector
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Diana L. Moss
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Competition (economics) ,Oligopoly ,Market economy ,Transparency (market) ,Collusion ,Mergers and acquisitions ,Merger control ,Market power ,Business ,Market concentration - Abstract
Prescription drugs safeguard Americans from numerous life-threatening maladies. Competition in pharmaceutical R&D, and for generic entry, produces essential drugs and ensures that medications are accessible and affordable. That promise is fading. There is mounting evidence that connects high market concentration and high drug prices. Price gouging for important drugs, conspiracies to fix generic drug prices, and ever more innovative schemes by branded drug manufacturers to keep generic rivals out of the market put merger control at center stage. The AAI White Paper “From Competition to Conspiracy: Accessing the Federal Trade Commission’s Merger Policy in the Pharmaceutical Sector” examines a major root of this problem—the Federal Trade Commission’s (FTC’s) policy of settling virtually all challenged horizontal pharmaceutical mergers with consent orders requiring divestitures. This stands in contrast to agency decisions to seek injunctions to stop highly concentrative, harmful mergers—arguably the most effective remedy for fully restoring competition. AAI’s macro-analysis of pharmaceutical mergers challenged by the FTC between 1994-2020 (to date) reveals that many drug makers engaged in serial mergers and/or repeatedly went to the till to purchase divestiture assets in other challenged mergers. Many of these firms were subsequently acquired by other pharmaceutical manufacturers, sometimes shortly after purchasing divestiture assets. The effect of the FTC’s policy has been the swapping of assets within a relatively small group of large and increasingly powerful firms. Just under 20% of all unique branded and generic firms that engaged in repeated mergers and acquisitions (M&A) and/or purchases of divestiture assets account for almost 45% of pharmaceutical assets “changing hands” from 1994-2020. Many of the very firms that were the most active in M&A, and as purchasers of divestiture assets, appear as defendants in private, state, and federal non-merger antitrust litigations and in federal criminal indictments. These accumulating lawsuits serve as powerful evidence that something has gone awry with merger policy in the pharmaceutical sector, leading to the exercise of market power by dominant firms and oligopolies. The FTC’s role in managing the allocation and ownership of important pharmaceutical assets through its extraordinary approach toward merger control has unduly involved it in shaping the industry. This resembles a form of “industrial planning” rather than antitrust law enforcement, which is designed to deter future anticompetitive conduct and relies on market forces to determine market structures. The FTC’s policy has also deprived the antitrust community and public of important transparency. Because no challenged merger between 1994-2020 was litigated in federal court, there is no judicial record detailing how highly concentrative mergers were likely to have survived a presumption of illegality. There is thus no way to evaluate claims that pharmaceutical mergers were likely to have delivered lower prices through claimed cost savings or consumer benefits due to improved quality and innovation. This White Paper begins with background on drug pricing and competition in the pharmaceutical supply chain. It then turns to the drug mergers themselves and the asset divestitures required in FTC consent orders. Next is an assessment of private, state, and federal antitrust cases against the companies involved in M&A and as buyers of divestiture assets. It concludes with policy recommendations on reframing competition policy in the pharmaceutical sector. The FTC, which has devoted considerable resources and expertise to understanding the pharmaceutical sector, should take the lead in reforming its own policy on merger control. Competition problems in pharmaceuticals now rise to the level a public policy concern, addressable only through a coordinated policy response, of which stronger antitrust enforcement and legislative reform should be central components. The imperative for wholesale change in the FTC’s merger policy in the pharmaceutical sector is more pressing than ever. Only robust competition among drug makers will result in the availability and affordability of drugs more generally, but also essential drug therapies and vaccines relating to the COVID-19 pandemic. more...
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- 2020
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28. Promoting colorectal cancer screening: A scoping review of screening interventions and resources
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Kelsey C. Stoltzfus, Jennifer L. Moss, Madyson L. Popalis, Kelsey M. Leach, and Marni E. Granzow
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Adult ,Program evaluation ,medicine.medical_specialty ,Epidemiology ,Colorectal cancer ,Psychological intervention ,Early detection ,Intervention effect ,01 natural sciences ,Article ,03 medical and health sciences ,0302 clinical medicine ,Surveys and Questionnaires ,Intervention (counseling) ,Humans ,Mass Screening ,Patient Navigation ,Medicine ,030212 general & internal medicine ,0101 mathematics ,Early Detection of Cancer ,business.industry ,010102 general mathematics ,Public Health, Environmental and Occupational Health ,Colonoscopy ,Evidence-based medicine ,medicine.disease ,Colorectal cancer screening ,Occult Blood ,Family medicine ,Colorectal Neoplasms ,business - Abstract
Background Early detection through screening can reduce colorectal cancer (CRC) mortality, but approximately 33% of adults aged 50–75 are not getting screened as recommended. Many interventions to increase CRC screening have been tested, but clinical and community organizations may be challenged in identifying the optimum programs and program materials to increase screening and ultimately reduce CRC mortality. Methods We conducted a scoping review to characterize existing, US-based interventions to improve CRC screening and to identify gaps in the literature. We used t-tests and correlations to analyze the relationship between project features and intervention effect sizes. Results The overall effect sizes were + 16% for changes in screening by any modality. The average effect sizes were greater for projects with more components, used patient navigation, and provided free/low-cost testing. Conclusion Interventions varied greatly in terms of follow-up time, test modality, and data sources. Organizations seeking to implement a program aimed at increasing CRC screening should consider both intervention components and relevant program materials. more...
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- 2021
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29. Iatrogenic Menopause After Treatment for Cervical Cancer
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S. Taneja, C. Kent, L. Robinson, Hilary McDermott, Fehmidah Munir, Esther L. Moss, P. Sarhanis, and N. Potdar
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Adult ,medicine.medical_specialty ,Hormone Replacement Therapy ,medicine.medical_treatment ,Iatrogenic Disease ,Population ,Psychological intervention ,Uterine Cervical Neoplasms ,03 medical and health sciences ,Surgical Menopause ,0302 clinical medicine ,Survivorship curve ,Humans ,Medicine ,Radiology, Nuclear Medicine and imaging ,education ,Intensive care medicine ,Cervical cancer ,education.field_of_study ,030219 obstetrics & reproductive medicine ,business.industry ,Hormone replacement therapy (menopause) ,Middle Aged ,Prognosis ,medicine.disease ,Premature ovarian failure ,Menopause ,Oncology ,030220 oncology & carcinogenesis ,Physical therapy ,Female ,business - Abstract
The ever-improving prognosis of women diagnosed with cervical cancer has meant that survivorship and treatment-related sequelae are being brought more into the spotlight in an attempt to try to reduce morbidity and improve women's long-term health. However, there are many issues surrounding an iatrogenic menopause in cervical cancer, a variety of potential management options and barriers to treatment. Women who have become menopausal under the age of 45 years as a result of cervical cancer are significantly less likely to start hormone replacement therapy (HRT) or continue it long term as compared with those who have undergone a surgical menopause for a benign reason. High profile media reports raising concerns about the safety of HRT use have left many women reluctant to consider HRT as a therapeutic option for menopausal symptoms and many are seeking to use complementary/alternative medicine, including non-pharmacological interventions, to alleviate symptoms. The benefits of HRT in this population have been shown to reduce these effects, although adherence to treatment regimens is a challenge due to poor compliance, which is in part due to the fear of a second malignancy. The development of non-HRT-based interventions to ameliorate menopausal symptoms and reduce the long-term health consequences are needed for women who choose not to take HRT. more...
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- 2016
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30. Meta-analysis in zooarchaeology expands perspectives on Indigenous fisheries of the Northwest Coast of North America
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Iain McKechnie and Madonna L. Moss
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010506 paleontology ,Archeology ,Range (biology) ,Fishing ,Fisheries ,Historical ecology ,01 natural sciences ,Pacific hake ,Ichthyoarchaeology ,Northwest Coast ,Anchovy ,0601 history and archaeology ,14. Life underwater ,Zooarchaeology ,Archaeozoology ,0105 earth and related environmental sciences ,060102 archaeology ,biology ,Ecology ,Pacific herring ,06 humanities and the arts ,15. Life on land ,biology.organism_classification ,Pollock ,Fishery ,Meta-analysis - Abstract
Fisheries are of fundamental importance to Indigenous peoples of the Pacific Northwest of North America today and in the past but few archaeological analyses have documented geographic patterning in fisheries across the entire region. This paper adopts meta-analysis methods and GIS-based spatial visualizations to survey the single largest compilation of fine-screened zooarchaeological fisheries data reported to date, including 513,605 fish remains identified at 222 sites from Oregon to southeast Alaska. These systematically collected zooarchaeological data indicate the most ubiquitous and proportionally abundant fish taxa over the late Holocene and reveal previously undocumented spatial patterning, indicating where certain fish taxa are consistently found in high relative proportions. Rather than seeking to evaluate chronological and/or evolutionary change, this study explores the environmental and cultural basis for assessing variability in Indigenous fisheries over millennial time scales. Specifically, we observe Pacific herring and the Pacific salmons to be the two most ubiquitous and proportionally abundant fish taxa across the Northwest Coast followed by flatfishes, sculpins, rockfishes, greenlings, dogfish, and a host of other poorly known taxa that represent consistent fishing effort. We document geographic patterning in the abundance and ubiquity of a range of fish including greater abundance of salmons in northern portions of the study area and outline trends that could represent biogeographic ranges for northern anchovy, Pacific hake, and pollock, among others. We conclude that examining patterning in the ubiquity and rank-order abundance represented by archaeological fisheries data offers significant potential for linking regionally distinct cultural practices noted in the 18th and 19th centuries to much longer human and ecological histories over the Holocene. more...
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- 2016
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31. The historical ecology of Pacific herring: Tracing Alaska Native use of a forage fish
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Camilla Speller, Madonna L. Moss, Dongya Y. Yang, and Antonia T. Rodrigues
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010506 paleontology ,Archeology ,060102 archaeology ,biology ,Pleistocene ,Population size ,Pacific herring ,06 humanities and the arts ,biology.organism_classification ,01 natural sciences ,Archaeology ,Fishery ,Ancient DNA ,Geography ,Herring ,Forage fish ,0601 history and archaeology ,14. Life underwater ,Historical ecology ,Holocene ,0105 earth and related environmental sciences - Abstract
Long-term use of herring by Alaska Natives is not well-documented over space or through time, yet this information can illuminate pre-industrial patterns of herring abundance and distribution. Such information is important to understand the sustained relationships Alaska Native fishers and egg collectors have had with herring. Understanding the genetics of pre-industrial herring may also inform management of the fish and fisheries to insure their survival into the future. In this paper, we attempt a contextualized account of the long-term history of Alaska Native herring fisheries, bringing together archaeological, ethnographic, and ethnohistorical data. We tie these together as background for presenting the preliminary results of the NSF-funded project, The Archaeology of Herring: Reconstructing the Past to Redeem the Future (No. 1203868). We have now tested 84 herring bone samples from 17 archaeological sites in Alaska expanding beyond Speller et al. (2012), having tripled the earlier archaeological dataset. The oldest herring bones identified archaeologically in Alaska are dated to more than 10,000 cal BP. Early Holocene and Middle Holocene sites have also yielded herring bones, although most of the record dates to the last 2400 years. Preservation of genetic information is effectively complete for the last 2400 years, but achievable back to the terminal Pleistocene (68% success rate for samples between 10,500 and 2400 cal BP). This gives considerable confidence to the potential to expand the analyses and develop a richer pattern of biological variability. The resulting data show genetic continuity between archaeological and modern herring populations. The main technical challenge for the future is to extract adequate amounts of nuclear DNA from the ancient samples for identifying more informative DNA markers that can be used to more effectively reveal any population diversity and/or population size changes over time when compared to modern herring. more...
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- 2016
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32. Colposcopists’ experiences of HPV Test of Cure for the follow up of cervical intra-epithelial neoplasia
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Charles W.E. Redman, Esther L. Moss, Susan M. Sherman, and Philippa Pearmain
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medicine.medical_specialty ,Patient anxiety ,Uterine Cervical Neoplasms ,Alphapapillomavirus ,Cervical intraepithelial neoplasia ,03 medical and health sciences ,0302 clinical medicine ,Surveys and Questionnaires ,medicine ,Humans ,030212 general & internal medicine ,Hpv test ,Gynecology ,Response rate (survey) ,Colposcopy ,030219 obstetrics & reproductive medicine ,Cervical screening ,medicine.diagnostic_test ,business.industry ,Obstetrics ,HPV Positive ,Papillomavirus Infections ,Obstetrics and Gynecology ,Uterine Cervical Dysplasia ,medicine.disease ,R1 ,Reproductive Medicine ,Practice Guidelines as Topic ,Anxiety ,Female ,medicine.symptom ,business - Abstract
Objective To survey lead colposcopists in England to explore their views on the recently introduced HPV Test of Cure (TOC) following treatment for cervical intra-epithelial neoplasia (CIN) and to determine the extent to which it has impacted their clinical practice and affected their patients. Methods An online survey was sent to lead colposcopists across England. Questions were asked focusing on the clinicians’ confidence in the ability of TOC to guide follow up in various clinical scenarios and how the implementation of TOC had changed patient management. Results There was a 50% (N = 88) response rate. 90% of respondents indicated they were happy with the new procedure. In the follow-up questions, 20% indicated they were uncomfortable with the procedure when it was applied to women who were CIN2+ with incomplete excision at the endocervical margin. Open-ended questions elicited positive aspects of TOC including reduced follow-up, increased reassurance for patients and clinicians and a faster return to the call–recall system. Negative observations included concerns around HPV positive cases, possible false negatives and anxiety in those women who were originally subject to the pre-TOC guidelines and were now returned to call–recall “earlier” than originally indicated to them. 11% of respondents also indicated they work around the new guidelines to some extent. Conclusion Although clinicians are on the whole positive towards the introduction of TOC, concerns were raised which centre primarily around those patients with CIN2+ combined with positive endocervical margins, issues related to HPV positive cases and the possibility of a false negative HPV result. The possibility of patient anxiety due to return to routine screening earlier than originally expected was also identified as a concern. more...
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- 2016
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33. Domestic dogs and wild canids on the Northwest Coast of North America: Animal husbandry in a region without agriculture?
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Iain McKechnie, Susan Crockford, and Madonna L. Moss
- Subjects
010506 paleontology ,Archeology ,History ,060102 archaeology ,Osteology ,biology ,business.industry ,Ecology ,Archaeological record ,Human Factors and Ergonomics ,06 humanities and the arts ,15. Life on land ,biology.organism_classification ,01 natural sciences ,Canis ,Geography ,Abundance (ecology) ,0601 history and archaeology ,Mammal ,Livestock ,business ,Domestication ,Relative species abundance ,0105 earth and related environmental sciences - Abstract
Domestic dogs (Canis familiaris) occur in the archaeological record throughout North America but few zooarchaeological studies have examined the extent of wild and domestic canids using multi-site observations across regions. Here, we present a meta-analysis of 172,310 mammal specimens identified from 210 archaeological sites along the Northwest Coast focusing on canid abundance, distribution, and osteological identifications. We show that canids have a ubiquitous geographic distribution and a high relative abundance in particular Northwest Coast sub-regions and that species-level identifications are overwhelmingly of domestic dogs in contrast to ~1% of non-domestic canids (wolf, coyote, and fox). Along with geochemical and genetic data, these zooarchaeological observations indicate a variety of roles for dogs including hunting, companionship, and wool production in a region lacking terrestrial agriculture and domestic livestock. We suggest the frequently applied taxonomic status of ‘indeterminate canid’ underestimates the extent to which domestic dogs played key roles in regional economies and cultural practices. Increased attention to resolving taxonomic ambiguity of canids through improving comparative collections and osteometric datasets will help clarify the non-conventional domestication pathways practiced by Northwest Coast peoples. more...
- Published
- 2020
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34. The Record of Weak U.S. Merger Enforcement in Big Tech
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Diana L. Moss
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White paper ,Market economy ,Multinational corporation ,Dominance (economics) ,Business ,Business model ,Policy analysis ,Market value ,Enforcement ,Organic growth - Abstract
The term “Big Tech” is often used to describe the five largest multinational online service or computer hardware and software companies: Amazon, Apple, Facebook, Google, and Microsoft. These companies hold five of the top six slots, by market value, for publicly traded firms. The growth of Big Tech over the past three decades is a function of numerous forces. These range from economic phenomena such as network effects and winner-take-all markets, organic growth resulting from innovative business models and technologies, to expansion through a series of acquisitions of smaller, potential, or nascent rivals. While Big Tech has undoubtedly produced benefits, significant concerns have coalesced around it. The growth of Big Tech has created controversy over the companies’ role in our society and raised a suite of competition issues that are attracting attention from Congress and enforcers. These include effects on innovation and market entry; incentives to compete on price and non-price dimensions of competition such as privacy; and the potential for artificial intelligence-driven algorithmic pricing to facilitate coordinated conduct. The debate over the size and alleged dominance of Big Tech companies has promoted wideranging proposals to use the antitrust laws to break them up. But few of these proposals are driven by a methodological, fact-based analysis. Such analysis would explore the strategic competitive abilities and incentives that are specific to different Big Tech business models, how the companies compete in a variety of individual markets and clusters of related markets, and how alleged conduct potentially runs afoul of the U.S. antitrust laws. Breakup proposals therefore “put the cart before the horse” and fail to provide needed support for more vigorous antitrust enforcement and beneficial reform proposals. This American Antitrust Institute (AAI) White Paper offers a fact-based analysis of one important component of a broader assessment of the competitive issues surrounding Big Tech. It focuses on Big Tech’s acquisition of over 720 smaller, potential, and nascent rivals over almost the last three decades. As is typical of M&A activity, only a portion of these transactions were reportable to the U.S. antitrust agencies under the Hart Scott Rodino Act (HSR) federal premerger reporting requirements.8 A closer look at enforcement data for one major Big Tech industry category reveals that while the U.S. Department of Justice (DOJ) and Federal Trade Commission (FTC) appear to have subjected a higher than average number of transactions to more extensive agency investigation, only one deal has been challenged in federal court. It does not come as a surprise therefore that the record of U.S. merger enforcement in an important Big Tech industry category is far lower than the record across all sectors, as defined by the rate of merger challenges in federal court. This statistic warrants further inquiry. This White Paper does not investigate whether serial acquisitions by Big Tech companies have created dominance in certain markets, or if they engage in conduct that violates the antitrust laws. Those questions should be the subject of appropriately framed merger retrospectives and antitrust agency inquiries, including the DOJ’s reported investigation into Google. Rather, the analysis herein explores the various reasons why enforcement might be weaker in Big Tech and the policy implications raised by those explanations. The AAI has provided independent, in-depth legal, economic, and policy analysis of antitrust and competition issues for over 20 years. The organization has been outspoken on the issue of competition in the tech sector through its research, education, and advocacy agenda and initiatives. This White Paper begins with an empirical review of the acquisition history of Big Tech and the U.S. antitrust agencies’ limited record of merger enforcement in a major industry area in which many Big Tech firms operate. It then unpacks the limited merger enforcement record and examines why it can and should be invigorated. more...
- Published
- 2019
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- View/download PDF
35. The nutritional value of Pacific herring: An ancient cultural keystone species on the Northwest Coast of North America
- Author
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Madonna L. Moss
- Subjects
0106 biological sciences ,chemistry.chemical_classification ,Archeology ,060101 anthropology ,Ecology ,Pacific herring ,06 humanities and the arts ,Clupea ,Biology ,biology.organism_classification ,01 natural sciences ,Eicosapentaenoic acid ,Optimal foraging theory ,010601 ecology ,Fishery ,Herring ,chemistry ,0601 history and archaeology ,Ecosystem ,14. Life underwater ,Keystone species ,Essential nutrient - Abstract
The perspective of nutritional ecology produces a more comprehensive understanding of the dietary, economic, and socio-cultural importance of Pacific herring (Clupea pallasii) to Northwest Coast societies and Alaska Natives than do models derived from optimal foraging theory. The food value of herring meat, eggs, and oil are found to rank highly not just in calories or protein, but especially in healthy omega-3 fatty acids. Herring provides large amounts of EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) in addition to iron, zinc, copper, and selenium. In coastal Alaska and along the Northwest Coast, herring was/is one of a vast array of traditional foods in a diverse diet. Herring apparently played different dietary roles in different cultural settings; in some areas it was a seasonal feast food, while in others its products were processed into forms that could be consumed throughout the annual cycle. Herring provided essential nutrients that affected human health, growth, and development, and likely facilitated demographic expansion. Paired with the indigenous and scientific knowledge of how herring function within North Pacific ecosystems, we can better appreciate the role of herring as a cultural keystone species. more...
- Published
- 2016
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36. Male adolescent fertility preservation
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Jared L. Moss, Robert E. Brannigan, Andrew Choi, and Mary Kate Keeter
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Male ,Program evaluation ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,media_common.quotation_subject ,Fertility ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Neoplasms ,medicine ,Humans ,Survivors ,Fertility preservation ,Program Development ,Young adult ,Spermatogenesis ,Intensive care medicine ,Infertility, Male ,media_common ,Cryopreservation ,030219 obstetrics & reproductive medicine ,business.industry ,Puberty ,Age Factors ,Fertility Preservation ,Obstetrics and Gynecology ,Cancer ,medicine.disease ,Surgery ,Radiation therapy ,Adolescent fertility ,Reproductive Medicine ,030220 oncology & carcinogenesis ,Professional association ,business ,Program Evaluation ,Semen Preservation - Abstract
Until the 1960s, few adolescents and young adults (AYAs) survived their initial cancer diagnoses. Now, ∼12,400 AYA patients are diagnosed with cancer each year, and almost 80% will now achieve a long-term cure. This dramatic improvement in survival is primarily due to multimodal treatments and combined chemotherapeutic regimens. Unfortunately, the increase in survival is often accompanied by treatment-related toxicities due to chemotherapy, radiation therapy, and surgical procedures. Despite guidelines published by the American Society of Clinical Oncology and numerous other professional organizations, high percentages of male AYA oncology patients are not properly counseled regarding their fertility preservation options before cancer treatment. Although administering fertility preservation care to adolescent males can be challenging in many ways, numerous studies show that this care can be delivered with high degrees of success and high levels of patient and parent satisfaction. The key to this success at many institutions has been the implementation of formalized integrated fertility preservation programs with infrastructure geared toward the delivery of comprehensive expedited care. more...
- Published
- 2016
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37. Physician communication about adolescent vaccination: How is human papillomavirus vaccine different?
- Author
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Jennifer L. Moss, Noel T. Brewer, Melissa B. Gilkey, Parth D. Shah, Tamera Coyne-Beasley, and Megan E. Hall
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Male ,Parents ,medicine.medical_specialty ,Adolescent ,Attitude of Health Personnel ,Epidemiology ,Meningococcal Vaccines ,Context (language use) ,Meningococcal vaccine ,Diphtheria-Tetanus-acellular Pertussis Vaccines ,Article ,Papillomavirus Vaccines ,Surveys and Questionnaires ,Humans ,Medicine ,Practice Patterns, Physicians' ,Health communication ,Immunization Schedule ,Gynecology ,business.industry ,Tetanus ,Communication ,Diphtheria ,Public Health, Environmental and Occupational Health ,virus diseases ,medicine.disease ,United States ,Family medicine ,Female ,business ,Adolescent health - Abstract
Low human papillomavirus (HPV) vaccination coverage stands in stark contrast to our success in delivering other adolescent vaccines. To identify opportunities for improving physicians' recommendations for HPV vaccination, we sought to understand how the communication context surrounding adolescent vaccination varies by vaccine type.A national sample of 776 U.S. physicians (53% pediatricians, 47% family medicine physicians) completed our online survey in 2014. We assessed physicians' perceptions and communication practices related to recommending adolescent vaccines for 11- and 12-year-old patients.About three-quarters of physicians (73%) reported recommending HPV vaccine as highly important for patients, ages 11-12. More physicians recommended tetanus, diphtheria, and acellular pertussis (Tdap) (95%) and meningococcal vaccines (87%, both p0.001) as highly important for this age group. Only 13% of physicians perceived HPV vaccine as being highly important to parents, which was far fewer than perceived parental support for Tdap (74%) and meningococcal vaccines (62%, both p0.001). Physicians reported that discussing HPV vaccine took almost twice as long as discussing Tdap. Among physicians with a preferred order for discussing adolescent vaccines, most (70%) discussed HPV vaccine last.Our findings suggest that primary care physicians perceived HPV vaccine discussions to be burdensome, requiring more time and engendering less parental support than other adolescent vaccines. Perhaps for this reason, physicians in our national study recommended HPV vaccine less strongly than other adolescent vaccines, and often chose to discuss it last. Communication strategies are needed to support physicians in recommending HPV vaccine with greater confidence and efficiency. more...
- Published
- 2015
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38. Measurement and modelling of the ingestion bioaccessibility of polyaromatic hydrocarbons in soils
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Gareth Wills, Victoria L. Moss-Hayes, Alexander W. Kim, Joanna Wragg, Claire L. Richardson, Christopher H. Vane, Heather Harrison, C. Paul Nathanail, Russell Thomas, and Mark Cave
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Total organic carbon ,chemistry.chemical_classification ,Soil test ,Chemistry ,Iron oxide ,Soil Science ,Polycyclic aromatic hydrocarbon ,Plant Science ,body regions ,Partition coefficient ,chemistry.chemical_compound ,Environmental chemistry ,Soil water ,Carbonate ,Diffuse reflection ,General Environmental Science - Abstract
Total and human ingestion bioaccessible polycyclic aromatic hydrocarbon fractions of individual polycyclic aromatic hydrocarbons were determined (representative of a combination of the saliva, gastric and upper intestine compartments) on 26 soil samples from 3 gasworks sites and from a domestic garden. A Random Forest model using the Infra-red spectra of the soils and the PAH properties successfully predicted the bioaccessibility of PAHs in the soils. The Near Infra-red and Mid Infra-red diffuse reflection spectra of the soils were subjected to a mixture resolution algorithm. Comparison with spectra of known minerals tentatively identified carbonate, silica, clay and iron oxide components in the Mid Infra-red spectra. Multiple linear regression analysis suggested that three Mid Infra-red components were associated with the organic carbon. Principal Component Analysis of polycyclic aromatic hydrocarbon properties identified three components associated with the hydrophobicity, the aliphatic nature and the vapour phase partition coefficient of the polycyclic aromatic hydrocarbons. more...
- Published
- 2015
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39. The Role of cMyBP-C in Regulating the Frank-Starling Relationship
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Daniel P. Fitzsimons, Timothy A. Hacker, Laurin M. Hanft, Richard L. Moss, and Kerry S. McDonald
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Frank–Starling law of the heart ,Biophysics ,Biology ,Cell biology - Published
- 2020
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40. Validity of the Perception Neuron inertial motion capture system for upper body motion analysis
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Steph Forrester, Jianjia Ma, Massimiliano Zecca, Stephen Ward, Esther L. Moss, and Ryan Sers
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Motion analysis ,Computer science ,business.industry ,Shoulders ,Applied Mathematics ,media_common.quotation_subject ,020208 electrical & electronic engineering ,010401 analytical chemistry ,02 engineering and technology ,Kinematics ,Condensed Matter Physics ,01 natural sciences ,Motion capture ,Motion (physics) ,0104 chemical sciences ,Perception ,0202 electrical engineering, electronic engineering, information engineering ,Computer vision ,Artificial intelligence ,Electrical and Electronic Engineering ,business ,Range of motion ,Instrumentation ,Functional movement ,media_common - Abstract
The commercially available Perception Neuron motion capture (Mo-Cap) system is a cost effective and easy to use option for motion analysis. However, the accuracy of this system in a practical setting is unknown and needs to be evaluated if it is to be considered for applications that require a specific level of measurement precision. Therefore, the validity of the Mo-Cap system for estimating postural angular kinematics of the upper body was assessed. Upper body motion was evaluated through three-dimensional analysis of functional movements performed by the neck, thorax and shoulders. Range of motion (RoM) estimates were compared to Vicon using Bland-Altman analysis. Systematic biases in neutral to peak RoM differences were all ≤4.5° and random biases ≤±4.5° except for neck extension where the values were larger. The present findings suggest that the Mo-Cap system is a valid method for assessing the majority of upper body ROM to within 5°. more...
- Published
- 2020
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41. HCM-related W792R and T1075fs mutations of cMyBP-C accelerate cross-bridge cycling kinetics in murine skinned myocardium
- Author
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Richard L. Moss, Jasmine Giles, Daniel P. Fitzsimons, and Jitandrakumar R. Patel
- Subjects
Chemistry ,Kinetics ,Biophysics ,Cross bridge cycling ,Cardiology and Cardiovascular Medicine ,Molecular Biology - Published
- 2018
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42. Novel Regulatory Elements within Myofilaments of Vertebrate Striated Muscles—Who Knew
- Author
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Richard L. Moss
- Subjects
0301 basic medicine ,Myofilament ,biology ,New and Notable ,Chemistry ,Biophysics ,Vertebrate ,Molecular Machhines, Motors, and Nanoscale Biophysics ,macromolecular substances ,Anatomy ,Striated Muscles ,Muscle, Striated ,Actin Cytoskeleton ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Myofibrils ,biology.animal ,Vertebrates ,Animals ,Muscle, Skeletal ,030217 neurology & neurosurgery - Abstract
Myofilament extensibility is a key structural parameter for interpreting myosin cross-bridge kinetics in striated muscle. Previous studies reported much higher thick-filament extensibility at low tension than the better-known and commonly used values at high tension, but in interpreting mechanical studies of muscle, a single value for thick-filament extensibility has usually been assumed. Here, we established the complete thick-filament force-extension curve from actively contracting, intact vertebrate skeletal muscle. To access a wide range of tetanic forces, the myosin inhibitor blebbistatin was used to induce low tetanic forces in addition to the higher tensions obtained from tetanic contractions of the untreated muscle. We show that the force/extensibility curve of the thick filament is nonlinear, so assuming a single value for thick-filament extensibility at all force levels is not justified. We also show that independent of whether tension is generated passively by sarcomere stretch or actively by cross-bridges, the thick-filament extensibility is nonlinear. Myosin head periodicity, however, only changes when active tension is generated under calcium-activated conditions. The nonlinear thick-filament force-extension curve in skeletal muscle, therefore, reflects a purely passive response to either titin-based force or actomyosin-based force, and it does not include a thick-filament activation mechanism. In contrast, the transition of myosin head periodicity to an active configuration appears to only occur in response to increased active force when calcium is present. more...
- Published
- 2018
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43. PSU30 EQUITY OF ACCESS TO MINIMAL INVASIVE SURGERY FOR WOMEN WITH ENDOMETRIAL CANCER
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Gareth Morgan, Panos Sarhanis, Thomas Ind, Esther L. Moss, and Antony P. Martin
- Subjects
medicine.medical_specialty ,Obstetrics ,business.industry ,Health Policy ,Endometrial cancer ,Public Health, Environmental and Occupational Health ,Equity (finance) ,medicine ,Minimal invasive surgery ,business ,medicine.disease - Published
- 2019
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44. A design-based predictive model for lithium-ion capacitors
- Author
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Wanjun Cao, D. G. Moye, Simon Y. Foo, Xujie Chen, and Pedro L. Moss
- Subjects
Physics ,Work (thermodynamics) ,Renewable Energy, Sustainability and the Environment ,Nuclear engineering ,Energy Engineering and Power Technology ,Charge (physics) ,02 engineering and technology ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,Capacitance ,Energy storage ,0104 chemical sciences ,law.invention ,Capacitor ,State of charge ,law ,Equivalent circuit ,Electrical and Electronic Engineering ,Physical and Theoretical Chemistry ,0210 nano-technology ,Voltage - Abstract
Recent years have seen substantial developments of lithium-ion capacitor (LIC) technology. However, there has been little research in physics-based models to predict the performance of LICs. Existing models have focused upon cell degradation over time or equivalent circuit models to describe laboratory work. Experimentalists have determined that LICs' energy storage capabilities are inversely proportional to their charge or discharge current. This study developed a physics-based model in Simulink to predict this relationship as a function of a LIC's constituent materials' properties, charge current, and their effects upon the LIC's internal temperature in accordance with the Butler-Volmer equation. The Butler-Volmer temperature increase and the LIC's exchange current in turn affected the capacitance of the LIC. Once these relationships were understood, the model was able to predict energy storage as a function of charge power. Additionally, the model was able to estimate LIC voltage and therefore state of charge. This is the first known physics-based model to predict an LIC's energy storage as a function of its charge current. more...
- Published
- 2019
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45. Gas-phase structures of phosphopeptide ions: A difficult case
- Author
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K. Gulyuz, Nick C. Polfer, František Tureček, Jonathan P. Williams, Jeffery Mark Brown, Ioannis Pikalov, Keith Richardson, Matthew F. Bush, Christopher L. Moss, and Robert Pepin
- Subjects
Chemistry ,Anharmonicity ,Electronic structure ,Condensed Matter Physics ,Normal mode ,Absorption band ,Ab initio quantum chemistry methods ,Density functional theory ,Physical and Theoretical Chemistry ,Atomic physics ,Spectroscopy ,Instrumentation ,Conformational isomerism - Abstract
The goal of this paper was to investigate gas-phase structures of conformers of doubly charged phosphopeptide ions (ApSAAR + 2H) 2+ and (AApSAR + 2H) 2+ using traveling-wave and drift-tube ion mobility and IR action spectroscopy measurements in combination with molecular dynamics and electronic structure calculations. Lowest free-energy conformers were identified by extensive search of the conformational space with combined molecular dynamics, semi-empirical, density functional theory and perturbational Moller–Plesset ab initio calculations. The low-energy conformers had collisional cross sections that were compatible with the experimental data but did not allow the conformers to be distinguished. IR absorption spectra that were calculated by density functional theory for harmonic normal modes showed several intense bands that were absent in the experimental action spectrum. Agreement with experiment was improved upon implementing second-order anharmonic corrections to the calculated vibrational frequencies. Several factors affecting the action spectra are discussed such as effects of mode anharmonicity on the absorption band intensities, the magnitude of frequency shifts in anharmonic corrections, as well as non-linear effects in multiple-photon absorption that may suppress the detection of strongly H-bonded modes in these measurements. more...
- Published
- 2013
- Full Text
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46. European Federation of Colposcopy quality standards Delphi consultation
- Author
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Karl Ulrich Petry, Marc Arbyn, Pekka Nieminen, Esther L. Moss, Charles W.E. Redman, Simon Leeson, and Elizabeth Dollery
- Subjects
medicine.medical_specialty ,media_common.quotation_subject ,03 medical and health sciences ,0302 clinical medicine ,Documentation ,medicine ,Humans ,Medical physics ,Quality (business) ,Quality Indicators, Health Care ,computer.programming_language ,media_common ,Gynecology ,Colposcopy ,030219 obstetrics & reproductive medicine ,medicine.diagnostic_test ,business.industry ,Obstetrics and Gynecology ,3. Good health ,Europe ,Reproductive Medicine ,Target level ,030220 oncology & carcinogenesis ,Abnormal cervical cytology ,Female ,Performance indicator ,business ,computer ,Quality assurance ,Delphi - Abstract
Objective Optimization of colposcopy practice requires a program of quality assurance including the monitoring of performance indicators. The European Federation of Colposcopy (EFC) aimed to identify a list of quality indicators for colposcopic practice, which are relevant, reproducible and practical across all of the member countries. Study design A five-round Delphi consultation was conducted in 30 full, 5 associate and 4 potential member countries in order to determine a core list of quality indicators including optimal target ranges. Results Six indicators were selected from a list of 37 proposed standards. Two further rounds of consultation were conducted to determine expert opinion on the target level for each of the standards. The six indicators identified and corresponding targets were: documentation of whether or not the squamocolumnar junction has been seen (100%); colposcopy prior to treatment for abnormal cervical cytology (100%); percentage of excisional treatments/conizations to contain cervical intra-epithelial neoplasia grade two or worse (≥85%); percentage of excised lesions/conizations with clear margins (≥80%); and two indicators concerned the number of cases to be colposcoped per year: ≥50 low-grade/minor and ≥50 high-grade/major cytological abnormalities. Conclusions A Delphi consultation identified six EFC quality indicators. These are a first step in an international attempt to optimize colposcopy practice throughout Europe. The current targets are based on expert opinion and may need adaptation in the future. Data are needed from European colposcopy settings to determine whether the indicators are achievable practice-based benchmarks and will help in improving and fine tuning the list of performance indicators and targets. more...
- Published
- 2013
- Full Text
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47. Effect of rejuvenation hormones on spermatogenesis
- Author
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Lindsey E. Crosnoe, Edward D. Kim, and Jared L. Moss
- Subjects
Male ,Aging ,endocrine system ,medicine.medical_specialty ,Hormone Replacement Therapy ,Population ,Human chorionic gonadotropin ,Anabolic Agents ,Pregnancy ,Internal medicine ,medicine ,Humans ,Rejuvenation ,Hormone replacement therapy ,Aromatase ,Spermatogenesis ,education ,Testosterone ,Azoospermia ,education.field_of_study ,biology ,Age Factors ,Pregnancy Outcome ,Obstetrics and Gynecology ,medicine.disease ,Hormones ,Semen Analysis ,Fertility ,Endocrinology ,Reproductive Medicine ,Androgens ,biology.protein ,Female ,Hormone - Abstract
Objective To review the current literature for the effect of hormones used in rejuvenation clinics on the maintenance of spermatogenesis. Design Review of published literature. Setting Not applicable. Patient(s) Men who have undergone exogenous testosterone (T) and/or anabolic androgenic steroid (AAS) therapies. Intervention(s) None. Main Outcome Measure(s) Semen analysis, pregnancy outcomes, and time to recovery of spermatogenesis. Result(s) Exogenous testosterone and anabolic androgenic steroids suppress intratesticular testosterone production, which may lead to azoospermia or severe oligozoospermia. Therapies that protect spermatogenesis involve human chorionic gonadotropin (hCG) therapy and selective estrogen receptor modulators (SERMs). The studies examining the effect of human growth hormone (HGH) on infertile men are uncontrolled and unconvincing, but they do not appear to negatively impact spermatogenesis. At present, routine use of aromatase inhibitors is not recommended based on a lack of long-term data. Conclusion(s) The use of hormones for rejuvenation is increasing with the aging of the Baby Boomer population. Men desiring children at a later age may be unaware of the side-effect profile of hormones used at rejuvenation centers. Testosterone and anabolic androgenic steroids have well-established detrimental effects on spermatogenesis, but recovery may be possible with cessation. Clomiphene citrate, human growth hormone (HGH)/insulin-like growth factor-1 (IGF-1), human chorionic gonadotropin (hCG), and aromatase inhibitors do not appear to have significant negative effects on sperm production, but quality data are lacking. more...
- Published
- 2013
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48. Correlating ETD fragment ion intensities with peptide ion conformational and electronic structure
- Author
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Christopher L. Moss, Thomas W. Chung, and František Tureček
- Subjects
Protonation ,Condensed Matter Physics ,Tautomer ,Electron-transfer dissociation ,chemistry.chemical_compound ,Crystallography ,chemistry ,Computational chemistry ,Zwitterion ,Side chain ,Density functional theory ,Physical and Theoretical Chemistry ,Instrumentation ,Conformational isomerism ,Spectroscopy ,Bond cleavage - Abstract
Amino acid residues affect the formation of backbone fragments upon electron transfer dissociation of doubly charged peptide ions of the AAXAR type. Peptide ions having non-polar residues (X = A, V, L, M, W) undergo backbone dissociations near the protonated N- and C-termini, forming mainly z 1 and z 4 fragment ions. Polar residues (X = H, D) prefer backbone dissociations occurring next to the polar residue, forming z 2 and z 3 fragment ions. Computational analysis, combining molecular dynamics, semi-empirical, density functional theory, and Moller–Plesset theory of precursor ion conformational space, identified the thermodynamically most stable tautomers and conformers for (AAVAR + 2H) 2+ , (AAHAR + 2H) 2+ , and (AADAR + 2H) 2+ precursor ions. Analysis of electronic states and potential energy surfaces for charge-reduced cation-radicals was used to interpret the ETD fragmentations. Electron attachment to (AAVAR + 2H) 2+ and (AAHAR + 2H) 2+ forms zwitterionic tautomers of charge-reduced cation-radicals as local energy minima in the ground electronic state. These are dynamically unstable with respect to exothermic ammonium proton migration forming aminoketyl intermediates. Direct N C α bond cleavage in the zwitterion requires an energy barrier which makes it noncompetitive with the proton migration. This bears on the long-standing chicken-and-egg problem of the ExD dissociation mechanisms according to the Utah–Washington model. Migration of a proton from a proximate neutral amide group was found to form a dynamically unstable enolimidate intermediate that cannot undergo N C α bond cleavage according to the Murrell–Laidler rule of reaction dynamics. According to electronic structure analysis in a conformationally defined peptide ion, the non-polar side chain in charge-reduced (AAVAR + 2H) + has only a spectator role in isomerizations and backbone dissociations. This casts doubt on the “hydrophobic” effect of amino acid residues on electron-based fragmentations proposed previously. more...
- Published
- 2012
- Full Text
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49. Myosin binding protein-C phosphorylation is the principal mediator of protein kinase A effects on thick filament structure in myocardium
- Author
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Richard L. Moss, Jitandrakumar R. Patel, Mohamed Abdalla, Thomas C. Irving, Peter P. Chen, Carl W. Tong, Daniel P. Fitzsimons, Brett A. Colson, and Tanya Bekyarova
- Subjects
inorganic chemicals ,Myofilament ,Heart Ventricles ,Mice, Transgenic ,macromolecular substances ,Biology ,environment and public health ,Article ,Ventricular Function, Left ,Dephosphorylation ,Mice ,X-Ray Diffraction ,Troponin I ,Myosin ,Animals ,Phosphorylation ,Protein kinase A ,Molecular Biology ,Ultrasonography ,Myocardium ,Stroke Volume ,Actin cytoskeleton ,Cyclic AMP-Dependent Protein Kinases ,Molecular biology ,Actin Cytoskeleton ,enzymes and coenzymes (carbohydrates) ,Amino Acid Substitution ,Biophysics ,bacteria ,Carrier Proteins ,Cardiology and Cardiovascular Medicine ,Protein Processing, Post-Translational ,PRKCE - Abstract
Phosphorylation of cardiac myosin binding protein-C (cMyBP-C) is a regulator of pump function in healthy hearts. However, the mechanisms of regulation by cAMP-dependent protein kinase (PKA)-mediated cMyBP-C phosphorylation have not been completely dissociated from other myofilament substrates for PKA, especially cardiac troponin I (cTnI). We have used synchrotron X-ray diffraction in skinned trabeculae to elucidate the roles of cMyBP-C and cTnI phosphorylation in myocardial inotropy and lusitropy. Myocardium in this study was isolated from four transgenic mouse lines in which the phosphorylation state of either cMyBP-C or cTnI was constitutively altered by site-specific mutagenesis. Analysis of peak intensities in X-ray diffraction patterns from trabeculae showed that cross-bridges are displaced similarly from the thick filament and toward actin (1) when both cMyBP-C and cTnI are phosphorylated, (2) when only cMyBP-C is phosphorylated, and (3) when cMyBP-C phosphorylation is mimicked by replacement with negative charge in its PKA sites. These findings suggest that phosphorylation of cMyBP-C relieves a constraint on cross-bridges, thereby increasing the proximity of myosin to binding sites on actin. Measurements of Ca(2+)-activated force in myocardium defined distinct molecular effects due to phosphorylation of cMyBP-C or co-phosphorylation with cTnI. Echocardiography revealed that mimicking the charge of cMyBP-C phosphorylation protects hearts from hypertrophy and systolic dysfunction that develops with constitutive dephosphorylation or genetic ablation, underscoring the importance of cMyBP-C phosphorylation for proper pump function. more...
- Published
- 2012
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50. Protonation sites in peptide dications and cation-radicals containing β-amino acid residues
- Author
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Christopher L. Moss and František Tureček
- Subjects
Chemistry ,Hydrogen bond ,Solvation ,Protonation ,Condensed Matter Physics ,Photochemistry ,Tautomer ,Transition state ,Dication ,Crystallography ,chemistry.chemical_compound ,Fragmentation (mass spectrometry) ,Amide ,Physical and Theoretical Chemistry ,Instrumentation ,Spectroscopy - Abstract
Protonation sites in a model pentapeptide Ala-Ala-βAb-Ala-Ala, where βAb was β-aminobutyric acid, were studied by ab initio and density functional theory calculations. Gas-phase dication tautomers protonated at the N-terminus and amide oxygens were found to be substantially more stable than tautomers protonated at amide nitrogens. This order of ion stability did not change upon solvation with methanol. Conformational analysis of dication tautomers indicated similar degrees of internal solvation by hydrogen bonding in amide O- and N-protonated ions in the gas phase. Because of the low stability of amide N-protonated tautomers, their formation by electrospray of non-basic peptides is highly unlikely. Computational analysis of Ala-Ala-βAb-Ala-Ala cation-radicals indicated substantially lower transition-state energies for N Cα bond dissociations at Ala residues than for the N Cβ bond dissociation at βAb. The formation of β-radicals as z fragments was found to require a high threshold energy. Cleavage of the CO NH2 bond leading to b and y fragments was hampered by a high-energy transition state for the formation of an N-protonated cation-radical intermediate as well as by a high threshold energy for the fragment formation. The calculated energies for transition states and dissociation thresholds explain the less efficient N Cβ bond dissociation upon electron capture or transfer in peptide ions containing β-amino acid residues. more...
- Published
- 2012
- Full Text
- View/download PDF
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