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Introduction The empty pelvis syndrome is a significant source of morbidity following pelvic exenteration surgery. It remains poorly defined with research in this field being heterogeneous and of low quality. Furthermore, there has been minimal engagement with patient representatives following pelvic exenteration with respect to the empty pelvic syndrome. ‘PelvEx—Beating the empty pelvis syndrome’ aims to engage both patient representatives and healthcare professionals to achieve an international consensus on a core outcome set, pathophysiology and mitigation of the empty pelvis syndrome.Methods and analysis A modified-Delphi approach will be followed with a three-stage study design. First, statements will be longlisted using a recent systematic review, healthcare professional event, patient and public engagement, and Delphi piloting. Second, statements will be shortlisted using up to three rounds of online modified Delphi. Third, statements will be confirmed and instruments for measurable statements selected using a virtual patient-representative consensus meeting, and finally a face-to-face healthcare professional consensus meeting.Ethics and dissemination The University of Southampton Faculty of Medicine ethics committee has approved this protocol, which is registered as a study with the Core Outcome Measures in Effectiveness Trials Initiative. Publication of this study will increase the potential for comparative research to further understanding and prevent the empty pelvis syndrome.Trial registration number NCT05683795.

Objective: The empty pelvis syndrome (EPS) is common after pelvic exenteration (PE), causing fluid collections, bowel obstruction, perineal sinuses, and fistulas. The best approach to fill the pelvis to mitigate this remains controversial, and the impact of EPS on health-related quality of life (HrQoL) is unknown. This study is the first to begin to explore lived-experiences of EPS complications., Methods: Unstructured EPS virtual focus group meetings were conducted with a convenience sample of patients who underwent PE, as an extension of a modified-Delphi study. Interpretative phenomenological analysis was conducted on verbatim transcripts to generate group experiential themes., Results: Twelve patients (eight UK, one Dutch, and three Belgian) participated in four focus groups. Eight EPS complications were reported, (two pelvic collections, five chronic perineal sinuses, and one bowel obstruction). Group experiential themes were 'Out of Options', depicting patients forced to accept complications or limited survival; 'The New Normal', with EPS potentially delaying adaptation to post-PE HrQoL; 'Information Influencing Adaptation,' emphasising the significance of patients understanding EPS to cope with its effects; and 'Symptoms,' reporting manifestations of EPS, the resultant physical limitations, and an intangible feeling that patients lost part of themselves., Conclusions: EPS may influence patient decision-making, regret, adaptation, and information-seeking. It can cause a variety of unpleasant symptoms and physical limitations, which may include phantom phenomenon. This work supports ongoing purposeful HrQoL research to better define these themes., (© 2024 The Author(s). Psycho‐Oncology published by John Wiley & Sons Ltd.)

Quasi-3D plasmonic nanostructures are in high demand for their ability to manipulate and enhance light-matter interactions at subwavelength scales, making them promising building blocks for diverse nanophotonic devices. Despite their potential, the integration of these nanostructures with optical sensors and imaging systems on a large scale poses challenges. Here, a robust technique for the rapid, scalable, and seamless replication of quasi-3D plasmonic nanostructures is presented straight from their production wafers using a microbubble process. This approach not only simplifies the integration of quasi-3D plasmonic nanostructures into a wide range of standard and custom optical imaging devices and sensors but also significantly enhances their imaging and sensing performance beyond the limits of conventional methods. This study encompasses experimental, computational, and theoretical investigations, and it fully elucidates the operational mechanism. Additionally, it explores a versatile set of options for outfitting nanophotonic devices with custom-designed plasmonic nanostructures, thereby fulfilling specific operational criteria., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Objectives:  Efforts to reduce documentation burden (DocBurden) for all health professionals (HP) are aligned with national initiatives to improve clinician wellness and patient safety. Yet DocBurden has not been precisely defined, limiting national conversations and rigorous, reproducible, and meaningful measures. Increasing attention to DocBurden motivated this work to establish a standard definition of DocBurden, with the emergence of excessive DocBurden as a term., Methods:  We conducted a scoping review of DocBurden definitions and descriptions, searching six databases for scholarly, peer-reviewed, and gray literature sources, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extensions for Scoping Review guidance. For the concept clarification phase of work, we used the American Nursing Informatics Association's Six Domains of Burden Framework., Results:  A total of 153 articles were included based on a priori criteria. Most articles described a focus on DocBurden, but only 18% ( n  = 28) provided a definition. We define excessive DocBurden as the stress and unnecessarily heavy work an HP or health care team experiences when usability of documentation systems and documentation activities (i.e., generation, review, analysis, and synthesis of patient data) are not aligned in support of care delivery. A negative connotation was attached to burden without a neutral state in included sources, which does not align with dictionary definitions of burden., Conclusion:  Existing literature does not distinguish between a baseline or required task load to conduct patient care resulting from usability issues ( DocBurden ), and the unnecessarily heavy tasks and requirements that contribute to excessive DocBurden . Our definition of excessive DocBurden explicitly acknowledges this distinction, to support development of meaningful measures for understanding and intervening on excessive DocBurden locally, nationally, and internationally., Competing Interests: A.J.M. reports employment by JP Morgan Chase, with a role at the financial institution unrelated to her capacities associated with this research, and this work was performed on her own time. K.C. reports grant funding from National Institute of Nursing Research (NINR) and American Nursing Foundation, and a leadership role for AMIA (Board Member). J.J.C. reports professional duties at the University of Alabama at Birmingham. D.E.D. reports leadership roles on the Corporation for Corporation for National Research Initiatives (Board Member) and the International Academy for Health Sciences Informatics (Board Member). C.D. reports receiving training funding from National Library of Medicine T15 Training grant. K.J. reports grants from FDA Sentinel Program, NIH Pioneer Award, support for attending NIH and Robert Wood Johnson Foundation meetings, and leadership roles for American College of Medical Informatics (President), ex officio member of AMIA Board of Directors, and Robert Wood Johnson Foundation (Chair of National Advisory Committee for Amos Medical Faculty Development Program). J.A.M. reports serving on scientific advisory board for and holding shares in Augmedix. R.G.M. reports funding from the American Medical Association. S.C.R. reports grant funding from Agency for Healthcare Research and Quality, NINR, and a leadership role for AMIA (Chair of AMIA's 25 × 5 Task Force). V.T. reports a leadership role for AMIA (Board Member)., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: Large tissue defects following pelvic exenteration (PE) fill with fluid and small bowel, leading to the empty pelvis syndrome (EPS). EPS causes a constellation of complications including pelvic sepsis and reduced quality of life. EPS remains poorly defined and cannot be objectively measured. Pathophysiology of EPS is multifactorial, with increased pelvic dead space potentially important. This study aims to describe methodology to objectively measure volumetric changes relating to EPS., Methods: The true pelvis is defined by the pelvic inlet and outlet. Within the true pelvis there is physiological pelvic dead space (PDS) between the peritoneal reflection and the inlet. This dead space is increased following PE and is defined as the exenteration pelvic dead space (EPD). EPD may be reduced with pelvic filling and the volume of filling is defined as the pelvic filling volume (PFV). PDS, EPD, and PFV were measured intraoperatively using a bladder syringe, and Archimedes' water displacement principle., Results: A patient undergoing total infralevator PE had a PDS of 50 ml. A rectus flap rendered the pelvic outlet watertight. EPD was then measured as 540 ml. Therefore there was a 10.8-fold increase in true pelvis dead space. An omentoplasty was placed into the EPD, displacing 130 ml; therefore, PFV as a percentage of EPD was 24.1%., Conclusions: This is the first reported quantitative assessment of pathophysiological volumetric changes of pelvic dead space; these measurements may correlate to severity of EPS. PDS, EPD, and PFV should be amendable to assessment based on perioperative cross-sectional imaging, allowing for potential prediction of EPS-related outcomes., (© 2024. The Author(s).)

Introduction: Chronic cancer-related pain from locally recurrent infiltrative cancers within the bony confines of the pelvis is a devastating and hard to manage condition that can be refractory to many conventional pain management methods. Spinal cord stimulation (SCS) is an evolving and safe method of pain management and can be trialled in a quick and well-tolerated operation under local anaesthesia. To date, this has not been reported in the setting of locally recurrent inoperable pelvic cancers., Case Description: In the present study, we report two cases of patients with severe back and lower limb pain resulting from recurrent anal and rectal cancers involving the right lumbar and sacral nerve roots as well as the bony sacrum, which severely affected quality of life and daily functioning., Discussion: Following successful SCS, effective pain relief was observed., Conclusion: SCS could represent an effective supplementary or alternative technique to conventional pain management in this challenging group of patients, especially if other available methods have been exhausted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Salem, West, West, Yano, Fernandes, Vajramani and Mirnezami.)

Ten cases of small intestinal tympany with or without volvulus were documented in Central American river turtles ( Dermatemys mawii ). These turtles were under managed care at the Philadelphia Zoo in Philadelphia, PA, USA, with one case followed after transfer to a different institution. The primary clinical presentation was abnormal buoyancy in nearly all cases (9/10) and anorexia in two cases (2/10). Five of 10 turtles with suspected or radiographically confirmed small intestinal tympany recovered (5/10), whereas five cases (5/ 10) resulted in death or euthanasia. In all fatal cases (5/5), small intestinal volvulus was identified at gross necropsy, with concurrent colonic volvulus identified in 2/5 cases. Other notable necropsy findings were hepatic lipidosis (3/5) and thrombosis of intestinal or renal vasculature (2/5). In all fatal cases (5/5), there was short (1 to 2 days) clinical progression from abnormal buoyancy to death or euthanasia. In the majority of cases (6/10), an abrupt change in diet, notably the overfeeding of fresh fruit or excessive amounts of mulberry ( Morus spp.) browse, or ingestion of indigestible foreign material, occurred prior to presentation. Temporary suboptimal environmental temperatures were suspected prior to the onset of clinical signs in 4/10 cases. Optimal husbandry conditions including nutrition and environmental temperature appear vital to preventing this condition. Recognition of early clinical signs of this condition, such as abnormal buoyancy and anorexia, and environmental correction or medical therapy, may prevent fatality and result in a better outcome in these cases.

Over the last century, outbreaks and pandemics have occurred with disturbing regularity, necessitating advance preparation and large-scale, coordinated response. Here, we developed a machine learning predictive model of disease severity and length of hospitalization for COVID-19, which can be utilized as a platform for future unknown viral outbreaks. We combined untargeted metabolomics on plasma data obtained from COVID-19 patients (n = 111) during hospitalization and healthy controls (n = 342), clinical and comorbidity data (n = 508) to build this patient triage platform, which consists of three parts: (i) the clinical decision tree, which amongst other biomarkers showed that patients with increased eosinophils have worse disease prognosis and can serve as a new potential biomarker with high accuracy (AUC = 0.974), (ii) the estimation of patient hospitalization length with ± 5 days error (R 2  = 0.9765) and (iii) the prediction of the disease severity and the need of patient transfer to the intensive care unit. We report a significant decrease in serotonin levels in patients who needed positive airway pressure oxygen and/or were intubated. Furthermore, 5-hydroxy tryptophan, allantoin, and glucuronic acid metabolites were increased in COVID-19 patients and collectively they can serve as biomarkers to predict disease progression. The ability to quickly identify which patients will develop life-threatening illness would allow the efficient allocation of medical resources and implementation of the most effective medical interventions. We would advocate that the same approach could be utilized in future viral outbreaks to help hospitals triage patients more effectively and improve patient outcomes while optimizing healthcare resources., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Child growth failure, as indicated by low height-for-age z-scores (HAZ), is an important metric of health, social inequality, and food insecurity. Understanding the environmental pathways to this outcome can provide insight into how to prevent it. While other studies have examined the environmental determinants of HAZ, there is no agreed upon best-practices approach to measure the environmental context of this outcome. From this literature, we derive a large set of potential environmental predictors and specifications including temperature and precipitation levels, anomalies, and counts as well as vegetation anomalies and trends, which we include using linear, nonlinear, and interactive specifications. We compare these measures and specifications using four rounds of DHS survey data from Burkina Faso and a large set of fixed effects regression models, focusing on exposures from the time of conception through the second year of life and relying on joint hypothesis tests and goodness-of-fit measures to determine which approach best explains HAZ. Our analysis reveals that nonlinear and interactive transformations of climate anomalies, as opposed to climate levels or vegetation indices, provide the best explanation of child growth failure. These results underline the complex and nonlinear pathways through which climate change affects child health and should motivate climate-health researchers to more broadly adopt measures and specifications that capture these pathways., Competing Interests: Statements and Declarations: The authors have no financial or non-financial interests to disclose.

In spite of evidence of increasing prevalence of substance use disorders (SUDs) among women, there is little information on gender differences in SUD treatment use. Nationally representative survey data were used to compare specialized SUD treatment among women and men with past-year DSM-5 SUD diagnoses (N = 5,789, 42.8% women). An estimated 10.7% of women and 9.9% of men (p = 0.45) received SUD treatment. Those who received treatment among both men and women had more problems than others. Five variables were independently associated with receipt of past-year treatment in both women and men and while five others were independently associated with receipt of treatment for only one gender. Interaction analysis, however, revealed no statistically significant gender differences in any correlate of treatment receipt. Although men were more likely to have SUDs than women, there were no significant differences by gender in rates or correlates of service use., (© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Fundamental to the synthesis of enantioenriched chiral molecules is the ability to assign absolute configuration at each stereogenic center, and to determine the enantiomeric excess for each compound. While determination of enantiomeric excess and absolute configuration is often considered routine in many facets of asymmetric synthesis, the same determinations for enantioisotopomers remains a formidable challenge. Here, we report the first highly enantioselective metal-catalyzed synthesis of enantioisotopomers that are chiral by virtue of deuterium substitution along with the first general spectroscopic technique for assignment of the absolute configuration and quantitative determination of the enantiomeric excess of isotopically chiral molecules. Chiral tag rotational spectroscopy uses noncovalent chiral derivatization, which eliminates the possibility of racemization during derivatization, to perform the chiral analysis without the need of reference samples of the enantioisotopomer., (© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Objectives: The aim of this study was to determine the incidence of and risk factors for both gastrointestinal (GI) incisional dehiscence and mortality in a large cohort of cats undergoing GI surgery. We hypothesized that cats with preoperative septic peritonitis (PSP), systemic inflammatory response syndrome (SIRS) or sepsis would have higher GI dehiscence and mortality rates than unaffected cats., Methods: A medical records search identified cats with surgically created, full-thickness incisions into their stomach, small intestines or large intestines. Preoperative data, including signalment, clinical signs, comorbidities, surgical history, current medications, presenting physical examination findings, complete blood counts and serum biochemistry values, were collected. It was determined whether or not cats had PSP, SIRS or sepsis at admission. Intraoperative data, final diagnosis and postoperative variables such as vital parameters, bloodwork and (if applicable) the development of GI dehiscence or mortality were noted. Postoperative follow-up of at least 10 days was obtained in survivors., Results: In total, 126 cats were included. One cat developed GI dehiscence following complete resection of a jejunal adenocarcinoma. Twenty-three cats (18.2%) died within 10 days of surgery. Cats with PSP ( P = 0.0462) or that developed hypothermia 25-72 h postoperatively ( P = 0.0055) had higher odds of mortality in multivariate analysis. Cats with PSP had 6.7-times higher odds of mortality than cats not diagnosed with PSP., Conclusions and Relevance: In cats receiving GI surgery, the incidence of GI incisional dehiscence was <1%. Cats with PSP had a higher likelihood of mortality. SIRS was a common finding in cats with septic peritonitis, but was not associated with mortality. Postoperative mortality during the home recovery period might be significant in cats. Future studies evaluating postoperative mortality in cats should consider extending the research period beyond the date of discharge.

Introduction: Haemorrhage is the major cause of early mortality following traumatic injury. Patients suffering from non-compressible torso haemorrhage are more likely to suffer early death. Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) can be effective in initial resuscitation; however, establishing swift arterial access is challenging, particularly in a severe shock. This is made more difficult by anatomical variability of the femoral vessels., Methods: The femoral vessels were characterised in 81 cadaveric lower limbs, measuring specifically the distance from the inferior border of the inguinal ligament to the distal part of the origin of the profunda femoris artery (PFA), and from the distal part of the origin of the PFA to where the femoral vein lies posterior to and is completely overlapped by the femoral artery., Results: The femoral vein lay deep to the femoral artery at a mean distance of 105 mm from the inferior border of the inguinal ligament. The PFA arose from the femoral artery at a mean distance of 51.1 mm from the inguinal ligament. From the results, it is predicted that the PFA originates from the common femoral artery approximately 24 mm from the inguinal ligament, and the femoral vein is completely overlapped by the femoral artery by 67.7 mm distal from the inguinal ligament, in 95% of subjects., Conclusions: Based on the results, proposed is an 'optimal access window' of up to 24 mm inferior to the inguinal ligament for common femoral arterial catheterisation for pre-hospital REBOA, or more simply within one finger breadth., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Declining grazing lands threaten the livelihoods of Fulɓe herders in Burkina Faso and other parts of Africa. I used GIS to spatially represent ethnographic narratives about land use and land cover changes. In a place where maps were unavailable or treated as closely held community secrets, I used participatory mapping to offer participants the opportunity to control the process and resulting maps. Our project sought to understand environmental challenges from a fine-grained emic perspective using high-resolution satellite imagery and focus groups. I reflect on challenges of conducting fieldwork in one's home country, which made it easier to build relationships and interact with officials. At the same time, however, I faced the intersecting challenges of "being an outsider and a woman" as I interacted with Fulɓe men and that of being "too educated" in interacting with women.

Introduction: The lungs have three main fissures: the right oblique fissure (ROF), right horizontal fissure (RHF), and left oblique fissure (LOF). These can be complete, incomplete or absent; quantifying the degree of completeness of these fissures is novel. Standard textbooks often refer to the fissures as complete, but awareness of variation is essential in thoracic surgery., Materials and Methods: Fissures in 81 pairs of cadaveric lungs were classified. Oblique fissures were measured from lung hila posteriorly to the lung hila anteriorly; and the RHF measured from the ROF to the anteromedial lung edge. The degree of completeness of fissures was expressed as a percentage of the total projected length were they to be complete. The frequency and location of accessory fissures was noted., Results: LOF were complete in 66/81 (81.5%), incomplete in 13/81 (16.0%) and absent in 2/81 (2.47%); ROF were complete in 52/81 (64.2%), incomplete in 29/81 (35.8%) and never absent; RHF were more variable, complete in 18/81 (22.2%), incomplete in 54/81 (66.7%) and absent in 9/81 (11.1%). LOF and ROF were on average 97.1% and 91.6% complete, respectively, being deficient posteriorly at the lung hila. The RHF on average 69.4% complete, being deficient anteromedially. There were accessory fissures in 10 left and 19 right lungs., Conclusions: This study provides a projection of the anatomy thoracic surgeons may encounter at operation, in particular the variable RHF. This knowledge is essential for optimal outcomes in both benign and oncological procedures influenced by the fissures., (© 2020 The Authors. Clinical Anatomy published by Wiley Periodicals LLC on behalf of American Association of Clinical Anatomists.)

In this article we present results from transect walks and participatory mapping done in Burkina Faso. Since the Sahelian drought of the 1970s, researchers have continued to depict the Sahelian region of West Africa as an environment experiencing severe degradation; a narrative that persists over time. Recently, however, analyses of satellite imagery have identified remarkable patterns of greening across the Sahel. The causes of this greening are hotly debated. Through this project we aim to inform these debates with on-the-ground perceptions of local farmers and pastoralists. The transect walk method is a community-based process that collects information on the land-use/land-cover (LULC) features across villages. Transects help triangulate data by combining high-resolution satellite imagery, firsthand observations, and local experiences of ecological processes. We describe the methodology behind transects and discuss how they contextualize an otherwise removed process of environmental analysis. We also describe the challenges that arise throughout the fieldwork process.

Septicemia from bloodstream infections (BSI) is the second largest cause of inpatient mortality and the single most expensive condition for US hospitals to manage. There has been an explosive development of commercial diagnostic systems to accelerate the identification and antimicrobial susceptibility testing (AST) of causative pathogens. Despite adoption of advanced technologies like matrix-assisted laser desorption imaging-time-of-flight mass spectrometry and multiplex polymerase chain reaction for rapid identification, clinical impact has been variable, in part due to the persistent need for conventional AST as well as prescriber understanding of these rapidly evolving platforms. Newer technologies are expanding on rapid detection of genotypic determinants of resistance, but only recently has rapid phenotypic AST been available. Yet, improved outcomes with rapid diagnostic platforms are still most evident in conjunction with active antimicrobial stewardship. This review will outline key advancements in rapid diagnostics for BSI and the role of antimicrobial stewardship in this new era., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Competing Interests: Competing interests: None declared.

The 2019-2020 pandemic Coronavirus Disease 2019 (COVID-19) has inundated hospital systems globally, as they prepare to accommodate surge of patients requiring advanced levels of care. Pandemic preparedness has not been this urgently and widely needed in the last several decades. According to epidemiologic predictions, the peak of this pandemic has still not been reached, and hospitals everywhere need to ensure readiness to care for more patients than they usually do, and safety for healthcare workers who strive to save lives. We share our hospital-wide rapid preparedness and response to COVID-19 to help provide information to other healthcare systems globally.

Sahelian West Africa is a region that suffers from high population densities, frequent severe droughts, and enormous pressure on natural resources. Because of these challenges, it is the place where the term "desertification" was originally coined. Recently, however, experts have identified large zones of "greening" where the amount of vegetation exceeds what one would expect based on rainfall alone. This pattern is well documented, but its mechanisms remain poorly understood. This research employs participatory mapping linked with high-resolution satellite imagery to better understand the human role behind regional vegetation trends. Through a case study of three communities in northern Burkina Faso, this paper presents a pilot methodology for explicitly mapping perceived areas of both land degradation and rehabilitation. Combining participatory mapping exercises with standard image classification techniques allows areas of land degradation and rehabilitation to be precisely located and their extents measured for individual communities and their surrounding terroirs . Results of the spatial analysis show that the relative proportion of greening and browning varies among communities. In the case of Sakou, nearly 60 percent of its terroir is degraded. While in another, Kouka, this is 48 percent. This method also elicits perspectives of Burkinabè agro-pastoralists on the local land-use practices driving these twin environmental processes. Altogether, this case study demonstrates the analytical power of integrating ethnography and high-resolution satellite imagery to provide a bottom-up perspective on social-ecological dynamics.

The resettlement of herders in pastoral zones is often criticized for hindering pastoral mobility, which is essential to survival. We integrate narratives of conflict and environmental change with maps to demonstrate the complementarity between pastoral mobility - porous borders- and border demarcation - rigid borders. We use evidence from the Sondré-Est Pastoral Zone in southern Burkina Faso, where herders were voluntarily resettled near agricultural villages following the droughts of the 1970s. Over time, however, farmers encroached on the borders of the pastoral zone and surrounding grazing areas declined. This increased land-use disputes. Tensions were exacerbated by the fact that these communities kept maps as community secrets. We re-created the administrative boundaries of the pastoral zone to map land-use/land-cover changes and conflict hot spots. The maps show that conflicts happened along porous borders where agricultural fields encroached. Herders called for a clear demarcation of the border of the pastoral zone to preserve exclusive access to resources within it. Simultaneously, they also wanted to maintain shared access to other resources outside the pastoral zone. The herders' desire for both border clarity and some form of flexibility underlines the complementary between both processes, especially in times of resource scarcity and land-use conflict. The mystery around the maps helps sustain ambiguity that is key for pursuing both goals.

Case Presentation: An 80-year-old man was admitted to our hospital with 24 hours of epigastric pain. The pain was described as sharp, episodic, nonradiating, and without an identifiable provoking factor. Associated symptoms included nausea and nonbloody vomiting. He denied dyspnea, angina, fevers, chills, dysphagia, diarrhea, melena, or hematochezia. He had taken less than 2 g of acetaminophen earlier in the day without symptomatic relief. He had a 30-pack-year smoking history but quit over 25 years ago. He did not drink alcohol or use illicit drugs. He had a medical history of end-stage renal disease, for which he had undergone hemodialysis; hypertension; metastatic prostate cancer, for which he had received androgen deprivation therapy; and abdominal aortic aneurysm. His surgical history included a remote endovascular repair of the abdominal aortic aneurysm. His medications included amlodipine, losartan, carvedilol, sevelamer, and leuprolide., (Copyright © 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Urinary incontinence is a common and distressing condition which interferes with everyday life. Patients frequently experience discomfort related to urine leakage and the subsequent need to use absorbent pads. Since the continence mechanism is primarily maintained by a proper function of pelvic floor muscles (PFM), many treatment methods focused on strengthening of the PFM have been introduced in the past. The aim of this study was to evaluate the safety and efficacy of a high-intensity focused electromagnetic technology (HIFEM) for treatment of urinary incontinence with emphasis on effects on prospective patients' quality of life., Study Design/materials and Methods: The study followed an institutional review board approved protocol. A total of 75 women (55.45 ± 12.80 years, 1.85 ± 1.28 deliveries) who showed symptoms of stress, urge, or mixed urinary incontinence were enrolled. They received six HIFEM treatments (2 per week) in duration of 28 minutes. Outcomes were evaluated after the sixth treatment and at the 3-month follow-up. The primary outcome was to assess changes in urinary incontinence by the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) and changes in the number of absorbent pads used per day. The secondary outcome was subjective evaluation of the therapy and self-reported changes in quality of life. The statistical analysis was conducted by paired T-test and Pearson correlation coefficient ( α = 0.05)., Results: After the sixth session, 61 out of 75 patients (81.33%) reported significant reduction of their symptoms. The average improvement of 49.93% in ICIQ-SF score was observed after the sixth treatment, which further increased to 64.42% at the follow-up (both P < 0.001). Individually, the highest level of improvement was reached in patients suffering from mixed urinary incontinence (69.90%). The reduction of absorbent pads averaged 43.80% after the sixth treatment and 53.68% at 3 months (both P < 0.001), while almost 70% of patients (30 out of 43) reported decreased number of used pads. At the follow-up, a highly significant medium correlation (r = 0.53, P < 0.001) was found between the ICIQ-SF score improvement and the reduction in pad usage. A substantial decrease in the frequency of urine leakage triggers was documented. Patients reported no pain, downtime or adverse events, and also reported additional beneficial effects of the therapy such as increased sexual desire and better urination control., Conclusions: This study demonstrated that HIFEM technology is able to safely and effectively treat a wide range of patients suffering from urinary incontinence. After six treatments, an improvement in ICIQ-SF score and reduction in absorbent pads usage was observed. Based on subjective evaluation, these changes positively influenced quality of life. © 2019 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc., (© 2019 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.)

Background: Unplanned readmissions following elective total hip (THA) and knee (TKA) arthroplasty as a result of surgical complications likely have different quality improvement targets and cost implications than those for nonsurgical readmissions. We compared payments, timing, and location of unplanned readmissions with Center for Medicare and Medicaid Services (CMS)-defined surgical complications to readmissions without such complications., Methods: We performed a retrospective analysis on unplanned readmissions within 90 days of discharge following elective primary THA/TKA among Medicare patients discharged between April 2013 and March 2016. We categorized unplanned readmissions into groups with and without CMS-defined complications. We compared the location, timing, and payments for unplanned readmissions between both readmission categories., Results: Among THA (N = 23,231) and TKA (N = 43,655) patients with unplanned 90-day readmissions, 27.1% (n = 6307) and 16.4% (n = 7173) had CMS-defined surgical complications, respectively. These readmissions with surgical complications were most commonly at the hospital of index procedure (THA: 84%; TKA: 80%) and within 30 days postdischarge (THA: 73%; TKA: 77%). In comparison, it was significantly less likely for patients without CMS-defined surgical complications to be rehospitalized at the index hospital (THA: 63%; TKA: 63%; P < .001) or within 30 days of discharge (THA: 58%; TKA: 59%; P < .001). Generally, payments associated with 90-day readmissions were higher for THA and TKA patients with CMS-defined complications than without (P < .001 for all)., Conclusion: Readmissions associated with surgical complications following THA and TKA are more likely to occur at the hospital of index surgery, within 30 days of discharge, and cost more than readmissions without CMS-defined surgical complications, yet they account for only 1 in 5 readmissions., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A 37-year-old woman presented with an incarcerated hernia at a previous umbilical laparoscopic port site. This was found to contain an ischaemic appendix, which was managed successfully with open appendicectomy and a mesh repair. Previous imaging from a year prior to these events demonstrated a degree of intestinal malrotation with the caecal pole lying just under the umbilicus. Finding the appendix within an incisional port site is very rare, for this to occur at the umbilicus is unique.

Background: Little information exists on red blood cell (RBC) alloimmunization in healthy US blood donors, despite the potential significance for donors themselves, blood recipients, and the blood center., Study Design and Methods: Donor/donation data were sourced from the Recipient Epidemiology and Donor Evaluation Study-III, which contains information from four US blood centers during 2012 through 2016. Multivariable logistic regression was used to assess prevalence of positive antibody screen by donor demographics, blood type, parity, and transfusion history., Results: More than 2 million units were collected from 632,378 donors, with 0.51% of donations antibody screen positive and 0.77% of donors having at least one positive antibody screen. The most common antibody specificities were D (26.4%), E (23.8%), and K (21.6%). Regression analysis indicated that increasing age, female sex, D-negative status, and history of transfusion and pregnancy were positively associated with a positive antibody screen. Prior transfusion history was most strongly associated with a positive antibody screen, with donors reporting a prior transfusion having a higher adjusted odds ratio (3.9) of having a positive antibody screen compared to donors reporting prior pregnancy (adjusted odds ratio, 2.0). Though transfusion was a more potent immune stimulus for RBC alloantibody formation than pregnancy, the sheer number of previously pregnant donors contributed to pregnancy being a risk factor for the majority of clinically significant RBC alloantibodies detected in females., Conclusion: These findings on prevalence of and risk factors for RBC antibodies may have implications for future medical care of donors and for operations at blood centers., (© 2018 AABB.)

Background and Aims: Cannabis is one of the most commonly used substances among adolescents and young adults. Earlier age at cannabis initiation is linked to adverse life outcomes, including multi-substance use and dependence. This study estimated the heritability of age at first cannabis use and identified associations with genetic variants., Methods: A twin-based heritability analysis using 8055 twins from three cohorts was performed. We then carried out a genome-wide association meta-analysis of age at first cannabis use in a discovery sample of 24 953 individuals from nine European, North American and Australian cohorts, and a replication sample of 3735 individuals., Results: The twin-based heritability for age at first cannabis use was 38% [95% confidence interval (CI) = 19-60%]. Shared and unique environmental factors explained 39% (95% CI = 20-56%) and 22% (95% CI = 16-29%). The genome-wide association meta-analysis identified five single nucleotide polymorphisms (SNPs) on chromosome 16 within the calcium-transporting ATPase gene (ATP2C2) at P < 5E-08. All five SNPs are in high linkage disequilibrium (LD) (r 2  > 0.8), with the strongest association at the intronic variant rs1574587 (P = 4.09E-09). Gene-based tests of association identified the ATP2C2 gene on 16q24.1 (P = 1.33e-06). Although the five SNPs and ATP2C2 did not replicate, ATP2C2 has been associated with cocaine dependence in a previous study. ATP2B2, which is a member of the same calcium signalling pathway, has been associated previously with opioid dependence. SNP-based heritability for age at first cannabis use was non-significant., Conclusion: Age at cannabis initiation appears to be moderately heritable in western countries, and individual differences in onset can be explained by separate but correlated genetic liabilities. The significant association between age of initiation and ATP2C2 is consistent with the role of calcium signalling mechanisms in substance use disorders., (© 2018 Society for the Study of Addiction.)

Competing Interests: Competing interests: None declared.

Despite the significance of red blood cell (RBC) alloimmunization, the lack of standardized registries in the US has prevented the completion of large studies. Data from 3·5 years of the Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) recipient database, containing information from 12 hospitals, were studied. A RBC alloantibody responder had an antibody identified at any point during the study, and a non-responder had a negative antibody screen at least 15 days post-RBC transfusion. Demographics, blood type, ICD9/10 codes, and other potential correlates were evaluated. Of 319 177 (2·07%) screened patients, 6597 had a total of 8892 clinically significant RBC alloantibodies identified, with 75% being in the Rh or Kell families. Alloimmunization was more common in females (2·38%) than males (1·68%), and in RhD negative (2·82%) than RhD positive (1·94%) patients. Age, sex, RhD status and race were associated with being a responder, and certain diagnoses (including sickle cell disease or trait, systemic lupus erythematosus, rheumatoid arthritis and myelodysplastic syndrome) were more common among responders than non-responders. Data collected in this multi-centre recipient database provide the largest RBC alloimmunized patient cohort studied in the US, with previously known demographic and disease associations of responder status confirmed, and new associations identified., (© 2018 John Wiley & Sons Ltd.)

Objectives: The effectiveness and costs associated with addition of pharmacist-led group medical visits to standard care for patients with Type-2 Diabetes Mellitus (T2DM) is unknown., Methods: Randomized-controlled-trial in three US Veteran Health Administration (VHA) Hospitals, where 250 patients with T2DM, HbA1c >7% and either hypertension, active smoking or hyperlipidemia were randomized to either (1) addition of pharmacist-led group-medical-visits or (2) standard care alone for 13 months. Group (4-6 patients) visits consisted of 2-hour, education and comprehensive medication management sessions once weekly for 4 weeks, followed by quarterly visits. Change from baseline in cardiovascular risk estimated by the UKPDS-risk-score, health-related quality-of-life (SF36v) and institutional healthcare costs were compared between study arms., Results: After 13 months, both groups had similar and significant improvements from baseline in UKPDS-risk-score (-0.02 ±0.09 and -0.04 ±0.09, group visit and standard care respectively, adjusted p<0.05 for both); however, there was no significant difference between the study arms (adjusted p = 0.45). There were no significant differences on improvement from baseline in A1c, systolic-blood-pressure, and LDL as well as health-related quality-of-life measures between the study arms. Compared to 13 months prior, the increase in per-person outpatient expenditure from baseline was significantly lower in the group visit versus the standard care arm, both during the study intervention period and at 13-months after study interventions. The overall VHA healthcare costs/person were comparable between the study arms during the study period (p = 0.15); then decreased by 6% for the group visit but increased by 13% for the standard care arm 13 months post-study (p<0.01)., Conclusions: Addition of pharmacist-led group medical visits in T2DM achieved similar improvements from baseline in cardiovascular risk factors than usual care, but with reduction in the healthcare costs in the group visit arm 13 months after completion compared to the steady rise in cost for the usual care arm., Trial Registration: NCT00554671 ClinicalTrials.gov.

The United States is in the midst of a prescription opioid epidemic, with the number of yearly opioid-related overdose deaths increasing almost fourfold since 2000 1 . To more effectively prevent unintentional opioid overdoses, the medical profession requires robust surveillance tools that can effectively identify at-risk patients. Drug-related aberrant behaviors observed in the clinical context may be important indicators of patients at risk for or actively abusing opioids. In this paper, we describe a natural language processing (NLP) method for automatic surveillance of aberrant behavior in medical notes relying only on the text of the notes. This allows for a robust and generalizable system that can be used for high volume analysis of electronic medical records for potential predictors of opioid abuse.

Background: The carotid sinus (CS) is a dilatation in the carotid bifurcation usually at the origin of proximal internal carotid artery (ICA). It contains baroreceptors which influence blood pressure. Variations in the location of the CS are of importance as atheromatous plaque commonly forms in this area and procedures such as carotid endarterectomy are performed to reduce the risk of stroke. Inadvertent stimulation of the CS baroreceptors during interventions can have profound effects on the patient's haemodynamic status both intra- and postoperatively, causing serious complications. The aim of this study is to determine the inter- and intra-individual variations in the location of the CS., Materials and Methods: Eighty-two carotid arteries were dissected bilaterally from 41 cadavers. The locations of the CS were noted and divided into four potential sites., Results: The commonest site is the origin of the ICA (74.3%), but the CS can also be found in the distal part of the common carotid artery (CCA) inferior to the bifurcation (17.1%); at the bifurcation involving the distal CCA and origins of both the external carotid artery (ECA) and ICA (7.32%); and at the origin of the ECA (1.22%). In individual cadavers, the CS was located at the origin of the ICA in 97.6% on at least one side. The sites of the CS were asymmetrical in 34.1%., Conclusions: Clinicians performing carotid interventions should be aware of these anatomical variations to avoid inadvertent stimulation of the CS which can cause profound bradycardia and hypotension.

When cash cropping leads to agricultural and livelihood changes in the Global South, concern about food security is common among policy makers. This is indeed the case in the Sikasso region of Mali, where many have suggested that the ubiquitous cash crop cotton is a cause of the unexpectedly high rates of malnutrition in the region. Using household and forest surveys, we found little evidence that cotton cultivation is associated with malnutrition or decreased food security at a household level, but we did find evidence of a coassociation between cotton cultivation, loss of natural capital, and malnutrition at the village level.

This piece describes the approach by which even a small CADD (Computer-Aided Drug Design) group with limited resources and limited time can achieve substantial success given short budgets and the compressed, urgent environment of a biotech. Some comparisons are made with CADD operations in big pharma.

Historically, the Sahel of West Africa has been considered synonymous with desertification. In recent decades, however, satellite images reveal patterns of enhanced vegetation termed the "greening of the Sahel." This greening is well-documented but its mechanisms remain poorly understood. The Sahel is also a region emerging from a thirty-year period of reduced rainfall in which several severe droughts occurred. As a response to droughts and land degradation, farmers have rehabilitated thousands of hectares of degraded soils by constructing low barriers of rock through widespread soil and water conservation (SWC) development projects. Remote sensing analyses suggest that these extensive soil conservation projects may explain greening in northern Burkina Faso. This study combines ethnographic fieldwork with the analysis of Geographic Information System (GIS) and remote sensing (RS) data to test whether SWC investments contribute to greening. Ethnographic data reveals a tension between the perceptions of rural producers who feel that their SWC efforts contribute to greening and those of state officials who contend that SWC has only local impacts and that the regional landscape continues to degrade. Our analysis of GIS and RS data suggest that both perspectives are valid but contingent on particular spatial and temporal scale used for analysis., Competing Interests: Conflict of Interest The authors declare they have no conflict of interest.

Background: In this study, 82 forearms from 41 cadavers were dissected to establish the incidence of variant additional radial wrist extensors. Three variants have been described in the literature: extensor carpi radialis intermedius (ECRI), extensor carpi radialis accessorius (ECRA) and extensor carpi radialis tertius (ECRT)., Materials and Methods: Of the 41 cadavers studied, 5/41 (12%) had an additional radial wrist extensor. Of these 5 individuals, 2 had bilateral additional muscles and 3 were unilateral. Of the 82 forearms, 7/82 (9%) had additional radial wrist extensors., Results: We found 4 examples of ECRI and 3 examples of ECRA. We did not find any examples of ECRT. One specimen of ECRA had an atypical, previously undescribed, course., Conclusions: These accessory muscles are of clinical relevance, as they may be a contributing factor in tennis elbow and nerve entrapment, or cause diagnostic confusion, especially in ultrasound scans. However, they may also be used for tendon transfer. Of the 7 muscles found in the current study, 3 would have been suitable for such procedures.

Integrating information from existing research, qualitative ethnographic interviews, and participant observation, we designed a field experiment that introduces idiosyncratic environmental risk and a voluntary sharing decision into a standard public goods game. Conducted with subsistence resource users in rural villages on the Kamchatka Peninsula in Northeast Siberia, we find evidence consistent with a model of indirect reciprocity and local social norms of helping the needy. When participants are allowed to develop reputations in the experiments, as is the case in most small-scale societies, we find that sharing is increasingly directed toward individuals experiencing hardship, good reputations increase aid, and the pooling of resources through voluntary sharing becomes more effective. We also find high levels of voluntary sharing without a strong commitment device; however, this form of cooperation does not increase contributions to the public good. Our results are consistent with previous experiments and theoretical models, suggesting strategic risks tied to rewards, punishments, and reputations are important. However, unlike studies that focus solely on strategic risks, we find the effects of rewards, punishments, and reputations are altered by the presence of environmental factors. Unexpected changes in resource abundance increase interdependence and may alter the costs and benefits of cooperation, relative to defection. We suggest environmental factors that increase interdependence are critically important to consider when developing and testing theories of cooperation.

Cannabis is the most widely produced and consumed illicit psychoactive substance worldwide. Occasional cannabis use can progress to frequent use, abuse and dependence with all known adverse physical, psychological and social consequences. Individual differences in cannabis initiation are heritable (40-48%). The International Cannabis Consortium was established with the aim to identify genetic risk variants of cannabis use. We conducted a meta-analysis of genome-wide association data of 13 cohorts (N=32 330) and four replication samples (N=5627). In addition, we performed a gene-based test of association, estimated single-nucleotide polymorphism (SNP)-based heritability and explored the genetic correlation between lifetime cannabis use and cigarette use using LD score regression. No individual SNPs reached genome-wide significance. Nonetheless, gene-based tests identified four genes significantly associated with lifetime cannabis use: NCAM1, CADM2, SCOC and KCNT2. Previous studies reported associations of NCAM1 with cigarette smoking and other substance use, and those of CADM2 with body mass index, processing speed and autism disorders, which are phenotypes previously reported to be associated with cannabis use. Furthermore, we showed that, combined across the genome, all common SNPs explained 13-20% (P<0.001) of the liability of lifetime cannabis use. Finally, there was a strong genetic correlation (rg=0.83; P=1.85 × 10(-8)) between lifetime cannabis use and lifetime cigarette smoking implying that the SNP effect sizes of the two traits are highly correlated. This is the largest meta-analysis of cannabis GWA studies to date, revealing important new insights into the genetic pathways of lifetime cannabis use. Future functional studies should explore the impact of the identified genes on the biological mechanisms of cannabis use.

Sub-Saharan Africa is often portrayed as a region of chronic hunger, conflict, and poverty. The country of Burkina Faso is a bright spot on the continent where government agencies, NGOs, and development organizations have progressively improved food security to the point where citizens often state, "famines of the past could never happen again." This study evaluates such claims by looking at food security trends over the last 18 years using ethnographic participatory fieldwork and grain price data. Community members have invested in numerous soil and water conservation (SWC) measures that buffer their crops from droughts and agro-climatic variability. There is also a national famine early warning system in place and improved infrastructure that helps the government and NGOs efficiently provide food assistance in times of need. Thus, fewer households are affected when droughts occur due to these adaptations and food insecurity is not as severe or widespread as in the past. Local grain prices are, however, rising and becoming more closely linked to world food markets. Just as most households are becoming more food secure, those who are dependent on grain purchases are becoming more food insecure.

Human Adenovirus (Ad) is a non-enveloped, icosahedral virus with a linear, double-stranded DNA genome. The Ad IVa2 protein is involved in multiple viral processes including viral late gene transcription and virus assembly. Previous studies have shown that IVa2 loads additional viral proteins onto conserved DNA elements within the Ad genome to regulate these viral processes. IVa2 also possesses strong non-specific DNA binding activity, and it is likely it uses this activity to recruit proteins to the conserved DNA elements. Here we have investigated the non-specific DNA binding activity of IVa2 using nitrocellulose/DEAE filter binding and sedimentation equilibrium techniques. We have analyzed our data using the McGhee and Von Hippel approach [1], and find that IVa2 binds with strong, positive nearest-neighbor cooperativity. In addition, we describe how to apply the McGhee and von Hippel approach to directly analyze sedimentation equilibrium data using non-linear least-squares methods. We discuss the implications of these results with respect to current virus assembly mechanisms., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Clergy and religious leaders are facing a wide variety of sexual needs and concerns within their faith communities. Conflicts over sexual issues are growing across the entire spectrum of religious denominations, and clerics remain ill prepared to deal with them. As religious communities work to remain influential in public policy debates, clergy and the institutions that train them need to be properly prepared for twenty-first century challenges that impact sexuality and religion. Clergy are often the first point of contact for sexual problems and concerns of their faith community members-complex issues centered on morals, spirituality, and ethics. Yet, there still exists a significant lack of sexual curricula in the programs that are educating our future religious leaders. The resulting paucity of knowledge leaves these leaders unprepared to address the needs and concerns of their congregants. However, with accurate, relevant human sexuality curricula integrated into theological formation programs, future leaders will be equipped to competently serve their constituencies. This paper provides a rationale for the need for such training, an overview of the faith- and theology-based history of a pilot training project, and a description of how the Christian faith and the social sciences intersect in a training pilot project's impetus and process.

Pharmacokinetic and metabolism aspects of AMG 222 interaction with target enzyme, dipeptidylpeptidase IV (DPPIV) were investigated. Inhibition of recombinant human DPPIV by AMG 222 was measured. IC(50) decreased as preincubation time increased. k(off), k(on) and K(d) were measured. Dilution assay indicated a long dissociation half-life (730 min) relative to DPPIV inhibitor vildagliptin. AMG 222 is a slow-on, tight-binding, slowly reversible inhibitor of DPPIV. Amide and acid metabolites arising from hydrolysis of AMG 222's cyano group were formed slowly by rhDPPIV, but not by microsomes or S9. The amide metabolite was converted to the acid metabolite by rhDPPIV, but not by an active site mutant. These metabolites of AMG 222 are formed by target-mediated metabolism of the cyano group, similar to vildagliptin. Human plasma protein binding of [(14)C]AMG 222 was saturable and concentration-dependent. After 30 min, [(14)C]AMG 222 was 80.8% bound at 1 nM and binding decreased to 29.4% above 100 nM. The plasma DPPIV concentration (4.1 nM) and human plasma AMG 222 concentrations that inhibit DPPIV, occurred in the range of concentration-dependent binding. Target-mediated drug disposition influences AMG 222 pharmacokinetics, similar to DPPIV inhibitor, linagliptin.

We study a new class of chaotic systems with dynamical localization, where gain or loss mechanisms break the Hermiticity, while allowing for parity-time (PT) symmetry. For a value gamma{PT} of the gain or loss parameter the spectrum undergoes a spontaneous phase transition from real (exact phase) to complex values (broken phase). We develop a one parameter scaling theory for gamma{PT}, and show that chaos assists the exact PT phase. Our results have applications to the design of optical elements with PT symmetry.

We study the Loschmidt echo F(t) for a class of dynamical systems showing critical chaos. Using a kicked rotor with singular potential as a prototype model, we found that the classical echo shows a gap (initial drop) 1-F&#95;{g} , where F&#95;{g} scales as F&#95;{g}(alpha,,eta)=f&#95;{cl}(chi&#95;{cl} identical witheta;{3-alpha}/) ; alpha is the order of singularity of the potential, eta is the spread of the initial phase-space density, and is the perturbation strength. Instead, the quantum echo gap is insensitive to alpha , described by a scaling law F&#95;{g}=f&#95;{q}(chi&#95;{q}=eta;{2}/) which can be captured by a random matrix theory modeling of critical systems. We trace this quantum-classical discrepancy to strong diffraction effects that dominate the dynamics.

Tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) selectively induces apoptosis in transformed cells. Normal cells and certain tumor cells can evade Apo2L/TRAIL induced cell death, but the determinants of Apo2L/TRAIL sensitivity are poorly understood. To better understand the factors that contribute to Apo2L/TRAIL resistance, we characterized two colon carcinoma lines with pronounced differences in Apo2L/TRAIL sensitivity. Colo205 cells are highly sensitive to Apo2L/TRAIL whereas Colo320 cells are unresponsive. Components of the DISC (death inducing signaling complex) could be immunoprecipitated from both cell lines in response to Apo2L/TRAIL. Sensitizing agents including a proteasome inhibitor conferred Apo2L/TRAIL sensitivity in Colo320 cells, indicating that the apoptotic machinery was intact and functional. We specifically suppressed the expression of Bcl-2, FLIP or XIAP in Colo320 cells. Downregulation of either FLIP or XIAP but not Bcl-2 restored sensitivity of Colo320 cells to Apo2L/TRAIL. Moreover, stable knockdown of XIAP expression in Colo320 subcutaneous tumors resulted in suppression of tumor growth and sensitivity to Apo2L/TRAIL in vivo. Our results indicate that only a specific subset of anti-apoptotic proteins can confer resistance to Apo2L/TRAIL in Colo320 cells. Elucidation of the factors that contribute to Apo2L/TRAIL resistance in tumor cells may provide insight into combination therapies with Apo2L/TRAIL in a clinical setting.

In vitro experimental models designed to study the effects of hypoxia and ischemia typically employ oxygen-depleted media and/or hypoxic chambers. These approaches, however, allow for metabolites to diffuse away into a large volume and may not replicate the high local concentrations that occur in ischemic myocardium in vivo. We describe herein a novel and simple method for creating regional hypoxic and ischemic conditions in neonatal rat cardiac myocyte monolayers. This method consists of creating a localized diffusion barrier by placing a glass coverslip over a portion of the monolayer. The coverslip restricts covered myocytes to a thin film of media while leaving uncovered myocytes free to access the surrounding bulk media volume. Myocytes under the coverslip undergo marked morphology changes over time as assessed by video microscopy. Fluorescence microscopy shows that these changes are accompanied by alterations in mitochondrial membrane potential and plasma membrane dynamics and eventually result in myocyte death. We also show that the metabolic activity of myocytes drives cell necrosis under the coverslip. In addition, the intracellular pH of synchronously contracting myocytes under the coverslip drops rapidly, which further implicates metabolic activity in regulating cell death under the coverslip. In contrast with existing models of hypoxia/ischemia, this technique provides a simple and effective way to create hypoxic/ischemic conditions in vitro. Moreover, we conclude that myocyte death is hastened by the combination of hypoxia, metabolites, and acidosis and is facilitated by a reduction in media volume, which may better represent ischemic conditions in vivo.

The results of this study indicate that the experience of sexual harassment among nursing professionals may be more widespread than previously reported. With only one percent of respondents reporting ¿quid pro quo¿ harassment, the vast majority of harassment fell into the ¿hostile environment¿ category where the victim's perceptions are all important. Health care administrators should be cautioned that harassment and discrimination are evolving and expanding areas of the law, necessitating current knowledge of the standards for actionable conduct. To lower the risk of liability from claims of both victims and the accused, harassment and discrimination policies should be aggressive, proactive, fair, and thorough.

Daphnia pulicaria from three different populations were observed to express within-population variation in habitat-choice behavior in field assays. Individuals from different habitats (i.e., lake depths) were isolated and cultured as clonal lines under standard conditions. Habitat choices by clonal descendants were then estimated in the field, using replicate experimental columns. There was significant heritable and ontogenetic variation in habitat choice, but the heritable effect was small relative to the phenotypic variation of the original isolates. In a second set of experiments, D. pulicaria that were acclimatized to different habitats showed a strong tendency to choose the habitat to which they had been acclimatized. These data suggest that a given genotype can use a wide range of habitats, given appropriate acclimatization. Although genetic variation is significant, we hypothesize that natural selection on correlated ecological traits is more likely to maintain patterns of genotypic segregation among habitats in Daphnia., (© 1994 The Society for the Study of Evolution.)