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Background: Seasonality in human papillomavirus (HPV) vaccination could have a large impact on national cancer prevention efforts. We hypothesized that uptake of HPV vaccine and other adolescent vaccines in the United States would be highest in the summer.Methods: Data came from health care provider–verified vaccination records for 70,144 adolescents (ages 13–17 years) from the 2008 to 2012 versions of the National Immunization Survey-Teen. Using the Edwards method for testing annual trends, we examined seasonal patterns in the uptake of HPV and other recommended adolescent vaccines [tetanus, diphtheria, and pertussis (Tdap) booster and meningococcal vaccine]. HPV vaccine initiation (receipt of the first of the three-dose series) data were for female adolescents.Results: Uptake for HPV and other adolescent vaccines peaked in the summer across years and states (all P < 0.001). Uptake was five times as frequent at the peak as at the trough for HPV vaccine, and HPV vaccine initiation was highest in June, July, and August (percent of doses delivered in these months: 38.7%). The same pattern existed for Tdap booster and meningococcal vaccine. Concomitant (same-day) vaccination of HPV vaccine with other adolescent vaccines also demonstrated summer peaks each year nationally (all P < 0.001).Conclusion: Uptake of adolescent vaccines increased dramatically in summer months. These summer peaks are an important opportunity for interventions focused on concomitant vaccination.Impact: The potential cancer prevention impact of HPV vaccination programs could be increased, for example, by delivering messages about concomitant vaccination during the summer, when adolescents and their parents might be most open to them. Cancer Epidemiol Biomarkers Prev; 25(2); 274–81. ©2015 AACR.

Truncation mutations in cardiac myosin binding protein C (cMyBP-C) are common causes of hypertrophic cardiomyopathy (HCM). Heterozygous carriers present with classical HCM, while homozygous carriers present with early onset HCM that rapidly progress to heart failure. We used CRISPR-Cas9 to introduce heterozygous (cMyBP-C+/−) and homozygous (cMyBP-C−/−) frame-shift mutations into MYBPC3 in human iPSCs. Cardiomyocytes derived from these isogenic lines were used to generate cardiac micropatterns and engineered cardiac tissue constructs (ECTs) that were characterized for contractile function, Ca2+-handling, and Ca2+-sensitivity. While heterozygous frame shifts did not alter cMyBP-C protein levels in 2-D cardiomyocytes, cMyBP-C+/− ECTs were haploinsufficient. cMyBP-C−/− cardiac micropatterns produced increased strain with normal Ca2+-handling. After 2 wk of culture in ECT, contractile function was similar between the three genotypes; however, Ca2+-release was slower in the setting of reduced or absent cMyBP-C. At 6 wk in ECT culture, the Ca2+-handling abnormalities became more pronounced in both cMyBP-C+/− and cMyBP-C−/− ECTs, and force production became severely depressed in cMyBP-C−/− ECTs. RNA-seq analysis revealed enrichment of differentially expressed hypertrophic, sarcomeric, Ca2+-handling, and metabolic genes in cMyBP-C+/− and cMyBP-C−/− ECTs. Our data suggest a progressive phenotype caused by cMyBP-C haploinsufficiency and ablation that initially is hypercontractile, but progresses to hypocontractility with impaired relaxation. The severity of the phenotype correlates with the amount of cMyBP-C present, with more severe earlier phenotypes observed in cMyBP-C−/− than cMyBP-C+/− ECTs. We propose that while the primary effect of cMyBP-C haploinsufficiency or ablation may relate to myosin crossbridge orientation, the observed contractile phenotype is Ca2+-mediated.

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.

BACKGROUND: The prone transpsoas (PTP) approach for lateral lumbar interbody fusion (LLIF) is a relatively novel technique. Currently, little is known about its associated complications and early patient-reported outcomes. The aim of this study was to investigate the effect of LLIF performed via the PTP approach on sagittal radiographic parameters, patient-reported outcome measures (PROMs), and rates of complications. METHODS: A retrospective review was performed of 82 consecutive patients who underwent LLIF via a PTP technique. Lumbar lordosis (LL), segmental lordosis (SL), anterior disc height (ADH), and posterior disc height (PDH) were measured on preoperative, initial postoperative, and 3-month postoperative radiographs. PROMs including the Oswestry Disability Index (ODI); the visual analog scale (VAS); and pain portions of the EQ5D, VAS back, and VAS leg ratings were collected at the preoperative and subsequent postoperative visits. Length of hospital stay and postoperative complications related to the procedure were recorded. RESULTS: Significant improvements were seen at the initial (4.5° ± 8.6°, P < 0.001) and 3-month (4.4° ± 7.2°, P < 0.001) postoperative periods for LL, as well as SL (6.8° ± 4.8°, P < 0.001; 6.7° ± 4.4°, P < 0.001), ADH (8.0 mm ± 3.6, P < 0.001; 7.4 mm ± 3.6, P < 0.001), and PDH (3.3 mm ± 2.4, P < 0.001; 3.1 mm ± 2.5, P < 0.001). Significant improvements were seen at 3 months postoperatively for ODI (P < 0.001), EQ5D pain (P = 0.016), VAS leg (P < 0.001), and VAS back (P < 0.001). The average length of stay was 2.7 ± 4.5 days. The most common complications were ipsilateral thigh pain/numbness (45.1%), ipsilateral hip flexor weakness (39.0%), and contralateral thigh pain/numbness (14.6%). CONCLUSIONS: While early PROMs and correction of sagittal radiographic parameters show promising results for the PTP approach for LLIF, it is not without risks. CLINICAL RELEVANCE: PTP interbody fusion is an emerging technique that allows for simultaneous access to the anterior and posterior columns of the lumbar spine. This early case series demonstrates significant improvement in functional outcomes and lumbar lordosis with a safety profile comparable to other well-established techniques. LEVEL OF EVIDENCE: 3.

To determine the impact on preterm birth (PTB) of a history of large loop excision of the transformation zone (LLETZ)-alone compared with a history of previous preterm birth-alone (PPTB) or a history of both (LLETZ+PPTB). Secondary analyses were performed to evaluate the impact of antenatal interventions, depth of cervical excision, and patient risk factors on PTB rate in each cohort.A retrospective observational cohort study of women referred to a tertiary Antenatal Prematurity Prevention Clinic with a history of LLETZ, PPTB, or LLETZ+PPTB. Information was collated from routinely collected clinical data on patient demographics, previous obstetric history, LLETZ dimensions, antenatal investigations/interventions, and gestation at delivery.A total of 1231 women with singleton pregnancies were included, 543 with history of LLETZ-alone, 607 with a history of PPTB-alone and 81 with a history of LLETZ+PPTB. PTB rates were 8.8% in the LLETZ-alone group, which mirrored the PTB rate in the local background obstetric population (8.9%) compared with 28.7% in the PPTB-alone and 37.0% in the LLETZ+PPTB cohorts. PTB rates were higher in LLETZ cohorts treated with antenatal intervention (cervical cerclage or progesterone pessary) and there was no evidence of an effect of intervention on risk of PTB in post-excision patients with identified shortened mid-trimester cervical length. Logistic regression modeling identified PPTB as a strong predictor of recurrent PTB. Excision depth was correlated with gestation at delivery in the LLETZ-alone group (r = -0.183, p 0.01) although this only reached statistical significance at depths of 20 mm or more (odds ratio [OR] 3.40, 95% CI 1.04-1.11, p = 0.04). Depth of excision was not correlated with delivery gestation in the LLETZ+PPTB group (r = -0.031, p = 0.82).PPTB has a greater impact on subsequent PTB risk compared with depth of cervical excisional treatment. The value and nature of antenatal interventions should be investigated in the post-excision population.

Mortality from cervical and colorectal cancers can be reduced through routine screening, which can often be accessed through primary care. However, uptake of screening in the US remains suboptimal, with disparities observed across geographic characteristics, such as metropolitan status or level of racial residential segregation. Little is known about the interaction of metropolitan status and segregation in their relationship with cancer screening. We conducted a quantitative survey of 474 women aged 45–65 in central Pennsylvania. The survey collected county-level characteristics and participant-level demographics, beliefs, cancer screening barriers, and cervical and colorectal cancer screening. We used bivariate and multivariable logistic regression to analyze relationships between metropolitan status and segregation with screening. For cervical cancer screening, 82.8% of participants were up-to-date, which did not differ by county type in the final analysis. Higher healthcare trust, higher cancer fatalism, and reporting cost as a barrier were associated with cervical cancer screening. For colorectal cancer screening, 55.4% of participants were up-to-date, which differed by county type. In metropolitan counties, segregation was not associated with colorectal cancer screening, but in non-metropolitan counties, segregation was associated with greater colorectal cancer screening. The relationship between metropolitan status and being up-to-date with colorectal, but not cervical, cancer screening varied by segregation. Other important beliefs and barriers to screening varied by county type. This research can guide future cancer screening interventions in primary care settings in underserved communities.

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.

Background: Evidence suggests that periodontal disease is associated with increased lung cancer risk, but whether periodontal pathogens are explanatory is unknown. We prospectively studied associations of prediagnostic circulating antibodies with oral bacteria and of periodontal bacteria in subgingival plaque with lung cancer. Methods: We included 4,263 cancer-free participants in the Atherosclerosis Risk in Communities study with previously measured serum IgG antibodies to 18 oral bacteria. In 1,287 participants for whom subgingival plaque was collected, counts for 8 periodontal bacteria were previously measured. Incident lung cancers (N = 118) were ascertained through 2015 (median follow-up = 17.5 years). We used Cox regression to estimate multivariable-adjusted associations, including for sums of antibodies to orange (C. rectus, F. nucleatum, P. intermedia, P. micra, and P. nigrescens) and red (P. gingivalis, T. forsythensis, and T. denticola) complex bacteria. Results: Orange complex bacteria antibodies were positively associated with lung cancer [per IQR hazard ratios (HR) = 1.15; 95% confidence intervals (CI), 1.02–1.29], which was stronger in men (HR = 1.27, 95% CI 1.08–1.49), and explained by P. intermedia and P. nigrescens (HR = 1.15; 95% CI, 1.04–1.26). Suggestive positive associations with lung cancer (N = 40) were observed for F. nucleatum, A. actinomycetemcomitans, and P. gingivalis counts. Significant positive associations were found for the count to antibody ratio for P. intermedia and P. gingivalis. Conclusions: We identified positive associations with lung cancer for oral bacteria, especially orange complex that are moderately pathogenic for periodontal disease. Impact: This prospective study supports the need for more research on periodontal bacteria in lung cancer etiology. If associations are supported, this may inform novel lung cancer prevention strategies.

Purpose Laparoscopy is used in many surgical specialties. Subjective reports have suggested that performing laparoscopic surgery in patients with a high body mass index (BMI) is leading to increased prevalence of musculoskeletal symptoms in surgeons. The aim of this study was to objectively quantify the impact on surgeon upper body kinematics and dynamic workload when performing simulated laparoscopy at different BMI levels. Methods Upper body kinematics and dynamic workload of novice, intermediate and expert surgeons were calculated based on measurements from inertial measurement units positioned on upper body segments. Varying thicknesses of foam were used to simulate patient BMIs of 20, 30, 40 and 50 kg/m2 during laparoscopic training. Results Significant increases in the jerkiness, angular speed and cumulative displacement of the head, torso and upper arms were found within all experience groups when subject to the 40 and 50 kg/m2 models. Novice surgeons were found to have less controlled kinematics and larger dynamic workloads compared to the more experienced surgeons. Conclusions Our findings indicate that performing laparoscopic surgery on a high BMI model worsens upper body motion efficiency and efficacy, and increases dynamic workload, producing conditions that are more physically demanding when compared to operating on a 20 kg/m2 model. These findings also suggest that the head, torso, and upper arm segments are especially affected by high BMI models and therefore exposure to patients with high BMIs may increase the risk of musculoskeletal injury when performing laparoscopic surgery.

We recruited women (primarily non-Hispanic White) from 14 rural, segregated counties in a Northeastern US state for an explanatory sequential study: 100 women (ages 50–65 years) completed a survey, and 16 women participated in focus groups. We sought to identify personal (e.g., healthcare mistrust) and environmental (e.g., travel time to healthcare providers) factors related to colorectal and cervical cancer screening. Quantitatively, 89% of participants were up-to-date for cervical screening, and 65% for colorectal screening. Factors interacted such that compounding barriers were associated with lower odds of screening (e.g., insurance status and healthcare mistrust: interaction p = .02 for cervical; interaction p = .05 for colorectal). Qualitatively, three themes emerged regarding barriers to screening: privacy concerns, logistical barriers, and lack of trust in adequacy of healthcare services. While cancer screening was common in rural, segregated counties, women who reported both environmental and personal barriers to screening had lower uptake. Future interventions to promote screening can target these barriers. Supplementary Information The online version contains supplementary material available at 10.1007/s13187-021-02069-0.

Purpose: Rates of loneliness and obesity have increased in recent decades. Loneliness and obesity independently have been found to be risk factors for negative physical and mental health outcomes. This study examined the rates and interrelationships of loneliness, body mass index (BMI), and health care utilization in a primary care setting. Methods: A cross-sectional survey of adult patients presenting for outpatient care at 7 family medicine clinical practices in Pennsylvania was conducted. Survey questions included self-reported measures of loneliness, height/weight, number of health care visits, and potential confounders (eg, sociodemographic variables, health status). Bivariate and multivariable linear regression models were used to analyze associations among loneliness, BMI, and health care utilization. Results: In all, 464 eligible patients returned surveys for an overall response rate of 26%. Mean (standard deviation) loneliness score was 4.2 (1.7), mean BMI was 30.4 (7.6), and mean number of visits in year prior was 2.7 (3.6). On bivariate analysis, BMI was positively associated with loneliness (effect estimate: 0.50; P = 0.03). On multivariable analysis, BMI was negatively associated with attending religious services and self-reported physical health and positively associated with self-reported mental health (P < 0.05 for all), but not associated with loneliness. While not associated with loneliness, health care utilization was negatively associated with Hispanic ethnicity, marital status, and self-reported physical health (P < 0.05 for all). Conclusions: Given the detrimental effects loneliness and obesity have on health outcomes, it might be prudent for health care providers to prioritize health concerns for their patients by assessing loneliness and counseling regarding associated risks, particularly in patients with obesity.

This study investigated the prevalence of perfectionism among young female competitive Irish dancers and examined the relationships between perfectionistic tendencies and coping strategies used when experiencing injury. Sixty-eight female dancers (Mean age: 14 ± 2.3 years) completed the Child-Adolescent Perfectionism Scale and the Ways of Coping Questionnaire and provided a record of injuries incurred during their championship careers. Participants reported 189 injuries, mostly involving the lower extremities. Seventy-nine percent of dancers reported perfectionistic tendencies (mixed perfectionism 40%, pure self-oriented perfectionism 29%, pure socially prescribed perfectionism 10%), and most frequently adopted "planful problem-solving," "seeking social support," "distancing," and "self-controlling" strategies to cope with injury. Perfectionism and two coping strategies were found to be significantly related (p = 0.03); "planful problem-solving" was typically used "quite a bit or a great deal" by the mixed perfectionism group, but only "somewhat" by the non-perfectionism group, whereas "confrontive coping" was typically not used by the non-perfectionism group but was used "somewhat" by the mixed perfectionism group. Given the presence of such a large degree of perfectionism and the simultaneous employment of problem- and emotion-focused strategies when coping with injuries, it is suggested that medical practitioners acknowledge such tendencies when supporting their dancers in order to reduce the likelihood of negative psychological impact.

BACKGROUND Peri-operative variables associated with prolonged Intensive Care Unit (ICU) admission following cytoreductive surgery for ovarian cancer were investigated. PATIENTS AND METHODS A retrospective review was carried out of patients admitted to the ICU following cytoreductive surgery for ovarian cancer in a single tertiary referral centre from 2015-2019. Patients were categorized according to length of ICU stay (

PURPOSE. Self-sampling tests may be used to overcome barriers to screening that are more prevalent in rural populations compared to urban populations. This study aims to qualitatively examine the attitudes towards established and novel self-sampling tests for cervical and colorectal cancer among women, comparing themes from rural versus urban areas. METHODS. We recruited women (ages 45-65) from 28 counties in Pennsylvania. Four focus groups were conducted with women from metropolitan counties, and 7 focus groups were conducted with women from non-metropolitan counties. A brief survey was conducted prior to the focus group regarding general health and willingness to complete self-sampling tests for cervical and colorectal cancer. FINDINGS. We identified three themes about the potential for self-sampling for cancer screening: advantages and disadvantages of self-sampling compared to traditional testing, impact of self-sampling on patient interactions with their health care providers/clinics, and implications for improving/worsening access to quality health care services. We detected differences in responses from rural versus urban participants in the potential impact of self-sampling for cancer screening. CONCLUSIONS. There are several barriers and facilitators at the individual, interpersonal, and organizational levels that influence the feasibility of implementing self-sampling for cancer screening in routine clinical practice. Rural participants face unique barriers to cancer screening across all levels. These findings can be used to guide interventions aimed at increasing the use of self-sampling methods.

Chicken ovalbumin (cOVA) has been studied for decades primarily due to the robust genetic and molecular resources that are available for experimental investigations. cOVA is a member of the serpin superfamily of proteins that function as protease inhibitors, although cOVA does not exhibit this activity. As a serpin, cOVA possesses a protease-sensitive reactive center loop that lies adjacent to the OVA 323–339 CD4+ T-cell epitope. We took advantage of the previously described single-substitution variant, OVA R339T, which can undergo the dramatic structural transition observed in serpins, to study how changes in loop size and protein stability influence the processing and presentation of the OVA 323–339 epitope. We observed that the OVA R339T loop insertion increases the stability and protease resistance, resulting in the reduced presentation of the OVA 323–339 epitope in vitro. These findings have implications for the design of more effective vaccines for the treatment of infectious diseases and cancer as well as the development of more robust CD4+ T-cell epitope prediction tools.

Purpose The purpose of this study was to utilise the intervention mapping (IM) protocol as a framework with which to develop an intervention underpinned by relevant behaviour change theory to promote physical activity (PA) following treatment for cervical cancer. Methods The six steps of the IM protocol were followed. A qualitative semi-structured interview study and a rapid review of the literature were conducted along with the development of a logic model of the problem and a logic model of change to inform intervention development. Results An intervention was developed which aims to increase PA levels following treatment for cervical cancer, tailored to address key findings from the IM needs assessment. These include embedding behavioural and social strategies that help participants to overcome perceived barriers to PA participation; goal setting strategies to gradually increase PA levels with a view of reaching relevant PA guidelines for cancer survivors and feedback to encourage self-assessment of well-being and PA capability. Conclusion This study maps the development of a novel PA intervention for those who have been treated for cervical cancer. The use of a systematic development framework was necessary as little insight exists regarding PA preferences after treatment for cervical cancer. Implications for Cancer Survivors PA behaviour is associated with positive physical and psychological health outcomes for cancer survivors. Optimising targeted promotion of PA behaviour following treatment for cervical cancer may result in an enhanced survivorship experience through increased PA behaviour and improved quality of life (QOL).

In 1919 Charlotte Hawkins Brown, founder of the Palmer Memorial Institute, wrote the novella, Mammy: An Appeal to the Heart of the South as a persuasive appeal to white Southern women in Greensboro...

The case of Southern regionalism shows both the problems with current treatments of regionalism—illustrative of the problem of colonialist perspectives more generally—and the path forward. That path forward involves rethinking whose ancestors count as members of a place, the issue of whose voices are centered, memory and trauma, and counterpublics. The authors advise (1) embracing the field’s interest in local identities and identity movements—therefore, interrogating rhetoric as symbol systems carried in intergenerational, relational identity; (2) pushing further against colonialism, as the world is more layered by global systems of trauma and memory; and (3) admitting that nation-building rhetoric is an imperfect paradigm compared to resistive counterpublic discourse.

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.

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The Burdett Trust for Nursing Background The COVID-19 pandemic affected health care systems profoundly. Inherited cardiac condition (ICC) specialist nurses were redeployed to intensive care or acute settings which either left services with no nurse or a single nurse manning a normally busy service (Bueser 2020). An exponential rise in patients reaching out to patient support charities was seen (Charity Today 2020) and at the peak of the pandemic, nurses based at an ICC charity dealt with 599 inquiries which was a 328% increase in activity. The toll on the mental health of nurses during the pandemic is well documented and programmes have been suggested to address this which includes peer support and psychological support by clinical psychologists Purpose The aim was to develop and strengthen collaborations between ICC specialist nurses in a tertiary hospital and those working in the community charity sector; and provide peer and psychological support to enable consistent high quality patient care. Methods The project was based on Wenger’s (1999) Communities of Practice (COP) framework model of situational learning, collaboration among peers, working to a common purpose. To develop the counselling aspect, a psychotherapist led a scoping exercise with the group. The 4Rs Skilled Helper Programme (SHP) of reflective learning, supervision and continuing professional development was then adapted as a bespoke programme - combining 30 hours of formal counselling, communication and reflective learning skills with equal attention to the normative, formative and restorative components of support and development needed to ensure practitioner health and wellbeing and the safety and quality of patient care Results Nine ICC nurses from a tertiary hospital and 3 from the charity sector participated in the project. Nine nurses undertook the tailored 4RS SHP course, adapting Egan's 3 stage problem-solving, decision-making and opportunity development framework as the vehicle for personalised, psychosocial, time-sensitive decision-making and informed consent for patients, and for the identification of support and development strategies that represent the 'best fit' for both clients and practitioners in their particular social and organisational circumstances. Counselling supervision is ongoing on a whole group, team and individual basis and provides opportunities to discuss collaborations, gain support for challenging clinical cases and work situations; and promoting psychological well-being. Conclusions The COP established through this project alongside the development of a bespoke counselling course and psychological supervision is an exemplar of how nurses can be empowered to continue to provide excellent care despite challenging circumstances. The 4RS SHP course also specifically addresses the competency needs for ICC nurses as move towards a genomics-driven, personalised health care delivery model.

Birds have been an integral part of traditional Yup’ik lifeways in the Yukon–Kuskokwim Delta, southwest Alaska, both economically and symbolically. From a subsistence point of view, the rich ethnographic record for the region highlights the importance of this resource as a critical seasonal food and a source of raw materials for clothing and tools. Little is known of bird exploitation in precontact Yup’ik society, however, as a result of limited archaeological research in the region, which thus constrains our ability to understand subsistence strategies prior to Euro-American contact. Recent excavations at the Nunalleq site (sixteenth to seventeenth century AD) have yielded a well-preserved avian assemblage that provides the opportunity to explore the use of birds during the late prehistoric period in the region. In this paper, we present the results of our preliminary zooarchaeological and technological analyses of this material. These new data demonstrate that a relatively wide range of taxa were harvested by precontact Yupiit, reflecting their multiple uses of birds. People not only exploited birds for their meat but also targeted specific taxa for the qualities of their skins for making parkas, their feathers as adornments or for fletching arrows, and their bones for making needles and other tools. Though this study shows a certain degree of continuity between precontact and historic Yup’ik subsistence practices, it also highlights a gradual decline in the non-dietary use of birds and the gradual increase in the intake of birds primarily targeted as sources of food in more recent times., Les oiseaux ont été une partie intégrante des modes de vie traditionnels yup’ik dans le Delta du Yukon-Kuskokwim et le sud-ouest de l’Alaska, autant économiquement que symboliquement. Du point de vue de la subsistance, les riches données ethnographiques pour la région montrent l’importance de cette ressource comme un aliment critique saisonnier et une source de matériaux bruts pour la fabrication de vêtements et d’outils. L’exploitation aviaire dans la société yup’ik precontact est cependant peu connue en raison du manque de recherches archéologiques dans la région, ce qui limite notre aptitude à comprendre les stratégies de subsistance avant le contact euro-américain. Des fouilles récentes sur le site de Nunalleq (XVIe-XVIIe siècles après J.C.) ont mis au jour un assemblage aviaire bien préservé procurant l’opportunité d’explorer l’utilisation des oiseaux pendant la période préhistorique tardive dans la région. Dans cet article, nous présentons les résultats de nos analyses archéozoologique et technique préliminaires de ce matériel. Ces nouvelles données indiquent qu’une relativement grande variété d’oiseaux était exploitée par les Yupiit precontacts, reflétant ainsi l’usage diversifié qu’ils en faisaient. Les oiseaux étaient non seulement exploités pour leur viande mais certains taxons étaient également chassés pour la qualité de leurs peaux dans la fabrication de parkas, de leurs plumes comme parure ou pour l’empennage de flèches, ainsi que de leurs os pour la production d’aiguilles et autres outils. Bien que cette étude montre un certain degré de continuité entre les pratiques de subsistance des Yupiit précontact et historiques, elle souligne un déclin graduel dans l’utilisation non-carnée des oiseaux et une croissance progressive, plus récemment, de l’exploitation d’espèces principalement chassées pour la consommation.

Significance Hypertrophic cardiomyopathy (HCM) is a common genetic heart disease and a leading cause of sudden cardiac death in young adults. HCM has been linked to mutations in genes encoding sarcomeric proteins, but how different mutations can result in a similar clinical phenotype is unknown. Analysis of surgical heart tissue samples from HCM patients with severe outflow track obstruction using high-resolution mass spectrometry–based top-down proteomics revealed a common pattern of altered sarcomeric proteoforms across HCM tissues compared to non-failing donor heart tissues. Our data suggest that common pathways are associated with clinical phenotypes in patients diagnosed with obstructive HCM, opening the door for the development of interventions that target the HCM phenotype rather than the individual sarcomeric gene mutation., Hypertrophic cardiomyopathy (HCM) is the most common heritable heart disease. Although the genetic cause of HCM has been linked to mutations in genes encoding sarcomeric proteins, the ability to predict clinical outcomes based on specific mutations in HCM patients is limited. Moreover, how mutations in different sarcomeric proteins can result in highly similar clinical phenotypes remains unknown. Posttranslational modifications (PTMs) and alternative splicing regulate the function of sarcomeric proteins; hence, it is critical to study HCM at the level of proteoforms to gain insights into the mechanisms underlying HCM. Herein, we employed high-resolution mass spectrometry–based top-down proteomics to comprehensively characterize sarcomeric proteoforms in septal myectomy tissues from HCM patients exhibiting severe outflow track obstruction (n = 16) compared to nonfailing donor hearts (n = 16). We observed a complex landscape of sarcomeric proteoforms arising from combinatorial PTMs, alternative splicing, and genetic variation in HCM. A coordinated decrease of phosphorylation in important myofilament and Z-disk proteins with a linear correlation suggests PTM cross-talk in the sarcomere and dysregulation of protein kinase A pathways in HCM. Strikingly, we discovered that the sarcomeric proteoform alterations in the myocardium of HCM patients undergoing septal myectomy were remarkably consistent, regardless of the underlying HCM-causing mutations. This study suggests that the manifestation of severe HCM coalesces at the proteoform level despite distinct genotype, which underscores the importance of molecular characterization of HCM phenotype and presents an opportunity to identify broad-spectrum treatments to mitigate the most severe manifestations of this genetically heterogenous disease.

The Antitrust Revolution remains the only comprehensive framework for understanding major developments in antitrust through the economic case study device. In putting the debate over the role of economics in modern antitrust at center stage, The Antitrust Revolution identifies the broader themes that have emerged in antitrust enforcement over the last four decades. This article explores The Antitrust Revolution as a “microcosm” of antitrust, and valuable pedagogical tool, by unpacking the coeditors’ approach to case selection across seven editions. The analysis highlights how The Antitrust Revolution has, in retrospect, identified with remarkable accuracy the major developments and conflicts in antitrust law and economics over a critical period of time in U.S. history.

Background Traumatic rotatory subluxation of the atlantoaxial joint is a rare but potentially life-threatening injury in adults. While acute cases have been shown to be managed successfully with closed reduction, chronic injuries in skeletally mature patients have rarely been reported. Methods We present management of a 64-year-old female who presents 2.5 years after a traumatic cervical injury with neck pain and torticollis. Imaging revealed rotatory subluxation of C1–C2 without cord impingement. A focused appraisal of the reported literature was also performed. Results Successful reduction was achieved with halo cervical traction, followed by definitive treatment with atlantoaxial arthrodesis. Conclusions Cases of fixed, chronic C1–C2 rotatory subluxation after traumatic etiology may be amenable to closed reduction with skeletal traction and fusion. Level of Evidence 4. Clinical Relevance Chronic, post-traumatic atlantoaxial rotatory subluxation in the adult population is extremely rare, without a well-described treatment algorithm. The purpose of this case report is to highlight the reduction and fixation of someone with this injury.

In this article, we explore how playing with dominoes not only requires students to count but also to subitize when constructing number and operations.

Conventional word problems can't help students build mathematical modeling skills. on their own. But they can be leveraged! We examined how middle and high school students made sense of word problems and offer strategies to question and extend word problems to promote mathematical reasoning.

Purpose: To determine the utility of running-only and rugby-specific, in-season sprint interval interventions in professional rugby league players. Methods: Thirty-one professional academy rugby players were assigned to a rugby-specific (SITr/s, n = 16) or running-only (SITr, n = 15) sprint interval training group. Measures of speed, power, change of direction ability, prone Yo-Yo Intermittent Recovery Test (Yo-Yo IR1) performance, and heart rate recovery were taken before and after the 2-week intervention as were submaximal responses to the prone Yo-Yo IR1. Internal, external, and perceptual responses were collected during SITr/s and SITr, with well-being and neuromuscular function assessed before each session. Results: Despite contrasting (possible to most likely) internal, external, and perceptual responses to the SIT interventions, possible to most likely within-group improvements in physical characteristics, heart rate recovery, and submaximal responses to the prone Yo-Yo IR1 were observed after both interventions. Between-group analysis favored the SITr/s intervention (trivial to moderate) for changes in 10-m sprint time, countermovement jump, change of direction, and medicine ball throw as well as submaximal (280–440 m) high metabolic power, PlayerLoad™, and acceleration distance during the prone Yo-Yo IR1. Overall changes in well-being or neuromuscular function were unclear. Conclusions: Two weeks of SITr/s and SITr were effective for improving physical characteristics, heart rate recovery, and submaximal responses to the prone Yo-Yo IR1, with no clear change in well-being and neuromuscular function. Between-group analysis favored the SITr/s group, suggesting that the inclusion of sport-specific actions should be considered for in-season conditioning of rugby league players.

Background Populations of closely related microbial strains can be simultaneously present in bacterial communities such as the human gut microbiome. We recently developed a de novo genome assembly approach that uses read cloud sequencing to provide more complete microbial genome drafts, enabling precise differentiation and tracking of strain-level dynamics across metagenomic samples. In this case study, we present a proof-of-concept using read cloud sequencing to describe bacterial strain diversity in the gut microbiome of one hematopoietic cell transplantation patient over a 2-month time course and highlight temporal strain variation of gut microbes during therapy. The treatment was accompanied by diet changes and administration of multiple immunosuppressants and antimicrobials. Methods We conducted short-read and read cloud metagenomic sequencing of DNA extracted from four longitudinal stool samples collected during the course of treatment of one hematopoietic cell transplantation (HCT) patient. After applying read cloud metagenomic assembly to discover strain-level sequence variants in these complex microbiome samples, we performed metatranscriptomic analysis to investigate differential expression of antibiotic resistance genes. Finally, we validated predictions from the genomic and metatranscriptomic findings through in vitro antibiotic susceptibility testing and whole genome sequencing of isolates derived from the patient stool samples. Results During the 56-day longitudinal time course that was studied, the patient’s microbiome was profoundly disrupted and eventually dominated by Bacteroides caccae. Comparative analysis of B. caccae genomes obtained using read cloud sequencing together with metagenomic RNA sequencing allowed us to identify differences in substrain populations over time. Based on this, we predicted that particular mobile element integrations likely resulted in increased antibiotic resistance, which we further supported using in vitro antibiotic susceptibility testing. Conclusions We find read cloud assembly to be useful in identifying key structural genomic strain variants within a metagenomic sample. These strains have fluctuating relative abundance over relatively short time periods in human microbiomes. We also find specific structural genomic variations that are associated with increased antibiotic resistance over the course of clinical treatment.

The maritime fur trade caused the extirpation of sea otters from southeast Alaska. In the 1960s, sea otters were reintroduced, and their numbers have increased. Now, sea otters are competing with people for what have become commercially important invertebrates. After having been absent for more than a century, the reentry of this keystone species has unsettled people. Although some communities perceive sea otters as a threat to their livelihoods, others view their return as restoration of the marine ecosystem. The federal Marine Mammal Protection Act authorizes any Alaska Native to harvest sea otters for subsistence provided that the harvest is not wasteful. Some people are seeking to define “traditional” Tlingit use of sea otters as not only using their pelts but consuming them as food, but some Tlingit maintain they never ate sea otters. This project analyzes the largest precontact archaeological assemblage of sea otter bones in southeast Alaska, with the benefit of insights gained from observing a Tlingit hunter skin a sea otter to infer that Tlingit ancestors hunted sea otters primarily for pelts. The extent to which other Indigenous peoples of the North Pacific consumed sea otters as food deserves investigation, especially as sea otters recolonize their historic range.

Microbial genomes can be assembled from short-read sequencing data, but the assembly contiguity of these metagenome-assembled genomes is constrained by repeat elements. Correct assignment of genomic positions of repeats is crucial for understanding the effect of genome structure on genome function. We applied nanopore sequencing and our workflow, named Lathe, which incorporates long-read assembly and short-read error correction, to assemble closed bacterial genomes from complex microbiomes. We validated our approach with a synthetic mixture of 12 bacterial species. Seven genomes were completely assembled into single contigs and three genomes were assembled into four or fewer contigs. Next, we used our methods to analyze metagenomics data from 13 human stool samples. We assembled 20 circular genomes, including genomes of Prevotella copri and a candidate Cibiobacter sp. Despite the decreased nucleotide accuracy compared with alternative sequencing and assembly approaches, our methods improved assembly contiguity, allowing for investigation of the role of repeat elements in microbial function and adaptation., Nanopore-metagenomics workflow enables assembly of complete, closed bacterial genomes from human stool samples.

Objective The CMS mandated hospital price transparency reporting on January 1, 2021 aiming to empower patients, enhance market competition, and curtail healthcare costs in the US. We aimed to characterize variability in hospital pricing reported by 1982 hospitals on six standard procedures (including abdominal ultrasound, diagnostic colonoscopy, kidney function blood test panel, knee arthroscopic cartilage removal, magnetic resonance imaging scan of brain, and pelvis computed tomography scan with contrast), with a particular focus on variations in pricing by insurance plan type. Results We found substantial heterogeneity across insurance plan types. The minimum number of prices reported was 18,679 for knee arthroscopic cartilage removal (reported by 908 hospitals, average = 21 prices/hospital), while the maximum number of prices reported was 44,921 for abdominal ultrasound (reported by 1861 hospitals, average = 24 prices/hospital). In general, reported hospital pricing was highest for the list price, followed by cash price and prices negotiated with commercial insurance plans. Government insurance, including Medicare, Medicaid and Veterans/Tricare plans, had much lower prices. However, prices were very heterogeneous with substantial overlaps between pricing for all plan types. The coefficients of variation for all procedures exceeded 100%, ranging from 106% for knee arthroscopic cartilage removal to 397% for kidney function blood test panel.

Loss or damage to the mandible caused by trauma, treatment of oral malignancies, and other diseases is treated using bone-grafting techniques that suffer from numerous shortcomings and contraindications. Zebrafish naturally heal large injuries to mandibular bone, offering an opportunity to understand how to boost intrinsic healing potential. Using a novel her6:mCherry Notch reporter, we show that canonical Notch signaling is induced during the initial stages of cartilage callus formation in both mesenchymal cells and chondrocytes following surgical mandibulectomy. We also show that modulation of Notch signaling during the initial post-operative period results in lasting changes to regenerate bone quantity one month later. Pharmacological inhibition of Notch signaling reduces the size of the cartilage callus and delays its conversion into bone, resulting in non-union. Conversely, conditional transgenic activation of Notch signaling accelerates conversion of the cartilage callus into bone, improving bone healing. Given the conserved functions of this pathway in bone repair across vertebrates, we propose that targeted activation of Notch signaling during the early phases of bone healing in mammals may both augment the size of the initial callus and boost its ossification into reparative bone.

Background Most persistent poverty counties are rural and contain high concentrations of racial minorities. Cancer mortality across persistent poverty, rurality, and race is understudied. Methods We gathered data on race and cancer deaths (all sites, lung and bronchus, colorectal, liver and intrahepatic bile duct, oropharyngeal, breast and cervical [females], and prostate [males]) from the National Death Index (1990-1992; 2014-2018). We linked these data to county characteristics: 1) persistent poverty or not; and 2) rural or urban. We calculated absolute (range difference [RD]) and relative (range ratio [RR]) disparities for each cancer mortality outcome across persistent poverty, rurality, race, and time. Results The 1990-1992 RD for all sites combined indicated persistent poverty counties had 12.73 (95% confidence interval [CI] = 11.37 to 14.09) excess deaths per 100 000 people per year compared with nonpersistent poverty counties; the 2014-2018 RD was 10.99 (95% CI = 10.22 to 11.77). Similarly, the 1990-1992 RR for all sites indicated mortality rates in persistent poverty counties were 1.06 (95% CI = 1.05 to 1.07) times as high as nonpersistent poverty counties; the 2014-2018 RR was 1.07 (95% CI = 1.07 to 1.08). Between 1990-1992 and 2014-2018, absolute and relative disparities by persistent poverty widened for colorectal and breast cancers; however, for remaining outcomes, trends in disparities were stable or mixed. The highest mortality rates were observed among African American or Black residents of rural, persistent poverty counties for all sites, colorectal, oropharyngeal, breast, cervical, and prostate cancers. Conclusions Mortality disparities by persistent poverty endured over time for most cancer outcomes, particularly for racial minorities in rural, persistent poverty counties. Multisector interventions are needed to improve cancer outcomes.