Quadrivalent influenza nanoparticle vaccines induce broad protection.

Influenza vaccines that confer broad and durable protection against diverse viral strains would have a major effect on global health, as they would lessen the need for annual vaccine reformulation and immunization1. Here we show that computationally designed, two-component nanoparticle immunogens2 induce potently neutralizing and broadly protective antibody responses against a wide variety of influenza viruses. The nanoparticle immunogens contain 20 haemagglutinin glycoprotein trimers in an ordered array, and their assembly in vitro enables the precisely controlled co-display of multiple distinct haemagglutinin proteins in defined ratios. Nanoparticle immunogens that co-display the four haemagglutinins of licensed quadrivalent influenza vaccines elicited antibody responses in several animal models against vaccine-matched strains that were equivalent to or better than commercial quadrivalent influenza vaccines, and simultaneously induced broadly protective antibody responses to heterologous viruses by targeting the subdominant yet conserved haemagglutinin stem. The combination of potent receptor-blocking and cross-reactive stem-directed antibodies induced by the nanoparticle immunogens makes them attractive candidates for a supraseasonal influenza vaccine candidate with the potential to replace conventional seasonal vaccines3.

Farmer decision making for hybrid maize seed purchases: Effects of brand loyalty, price discounts and product information.

CONTEXT: Each year public and private sector maize breeding programs in Kenya deliver high-yielding hybrids that are resistant to drought, pests, and diseases. Yet, most Kenyan maize farmers purchase older, well-known hybrids. While the 'varietal turnover' problem is well known, few solutions have emerged. OBJECTIVE: The potential for seed companies and retailers to influence farmers' product selection towards new products remains an open question. In-store marketing that induces farmers to experiment with new products may be a scalable and cost-effective way to advance seed systems development. METHODS: Our controlled field experiment with 600 farmers in Kenya comprised a mock agrodealer store stocked with locally available hybrids, where half the farmers who participated faced an out-of-stock situation for their preferred product. The influence of price promotions and product performance information on farmers' seed choice were assessed. RESULTS AND CONCLUSIONS: When a participant's preferred product was available, performance information and discounts had no effect on decisions. However, when the preferred product was unavailable, the treatments had limited effects on product selection. Prior experience and brand loyalty stood out as the strongest predictors of seed product selection. SIGNIFICANCE: Our work explored the potential for two interventions-information and price discounts-to influence farmers' product selection. While these interventions showed limited influence on selection, the study design provides a clear starting point for future related experiments. More public and private investments are required to generate timely, comparable, and reliable information on seed performance. The strong effect of brand loyalty favors larger-sized seed companies with sizable marketing budgets.

Supportive care interventions for men with urological cancers: a scoping review.

PURPOSE: To identify supportive care interventions for men with urological cancers. METHODS: Experimental studies conducted among men with any urological cancer were eligible for inclusion. Academic Search Complete, CINAHL Plus with Full Text, MEDLINE, APA PsycArticles, APA PsycInfo, Social Sciences Full Text (H.W. Wilson), SocINDEX with Full Text, ERIC, Google Scholar and ClinicalTrials.gov were searched on 6 December 2022. No database limits were applied. The included studies were methodologically appraised. A narrative synthesis of the results was conducted. RESULTS: Thirty studies were included with 10 categories of interventions identified. Over 300 outcomes were measured, and more than 100 instruments were used. Multicomponent interventions generally led to positive changes in physiological outcomes like body mass index, as well as exercise tolerance and quality of life. This change, however, was not sustained in the long term. Cognitive-behavioural interventions significantly improved psychological symptoms but seldom physical symptoms. Telephone and web-based interventions showed great promise in improving outcomes like depression, positive affect, negative affect, perceived stress, spiritual wellbeing and fatigue. Findings from physical activity/exercise-based interventions were promising for both, physical and psychological outcomes. Rehabilitative interventions were associated with significant improvements in quality of life, urinary symptoms and psychological symptoms, albeit in the short term. Mixed results were reported for nurse-led interventions, family-based interventions and nutritional interventions. CONCLUSION: All but one study focused exclusively on prostate cancer. The included studies were significantly heterogeneous. Multicomponent, cognitive-behavioural, telephone and web-based, physical activity/exercise-based and rehabilitative interventions showed great promise in improving various outcomes. This improvement, however, was often short-lived.

Hospital red blood cell and platelet supply and utilization from March to December of the first year of the COVID-19 pandemic: The BEST collaborative study.

BACKGROUND: At the start of the coronavirus disease 2019 (COVID-19) pandemic, widespread blood shortages were anticipated. We sought to determine how hospital blood supply and blood utilization were affected by the first wave of COVID-19. STUDY DESIGN AND METHODS: Weekly red blood cell (RBC) and platelet (PLT) inventory, transfusion, and outdate data were collected from 13 institutions in the United States, Brazil, Canada, and Denmark from March 1st to December 31st of 2020 and 2019. Data from the sites were aligned based on each site's local first peak of COVID-19 cases, and data from 2020 (pandemic year) were compared with data from the corresponding period in 2019 (pre-pandemic baseline). RESULTS: RBC inventories were 3% lower in 2020 than in 2019 (680 vs. 704, p < .001) and 5% fewer RBCs were transfused per week compared to 2019 (477 vs. 501, p < .001). However, during the first COVID-19 peak, RBC and PLT inventories were higher than normal, as reflected by deviation from par, days on hand, and percent outdated. At this time, 16% fewer inpatient beds were occupied, and 43% fewer surgeries were performed compared to 2019 (p < .001). In contrast to 2019 when there was no correlation, there was, in 2020, significant negative correlations between RBC and PLT days on hand and both percentage occupancy of inpatient beds and percentage of surgeries performed. CONCLUSION: During the COVID-19 pandemic in 2020, RBC and PLT inventories remained adequate. During the first wave of cases, significant decreases in patient care activities were associated with excess RBC and PLT supplies and increased product outdating.

Patient reported factors influencing the decision-making process of men with localised prostate cancer when considering Active Surveillance-A systematic review and thematic synthesis.

OBJECTIVES: Outcomes for men with localised prostate cancer managed with Active Surveillance (AS) are similar to outcomes for men who have received Active Treatment. This review explore men's perceptions of the factors that influence their decision-making process when considering AS. METHOD: A systematic review of studies was conducted up to May 2021, including qualitative studies which explored the decision making of men with localised prostate cancer when considering AS. Evidence was analysed using thematic synthesis. RESULTS: Thirteen papers, including 426 men, met inclusion criteria and were analysed in the review. Approximately half of the men had chosen AS and half had chosen Active Treatment. The choice of AS was not a one-off decision but rather an ongoing behaviour. Four themes were identified and considered within a temporal model: pre-diagnosis representations of cancer and treatment; experience of testing and diagnosis; patient decision making; and emotional adjustment to AS. Key barriers and facilitators to men choosing AS were identified. In deciding whether or not to choose AS, men balanced a desire for quality of life against fear of cancer progression. CONCLUSIONS: Both cognitive representations and emotional arousal influence how men decided whether or not to opt for AS. Interventions tailored to elicit and address emotional appraisals of risk, and increase trust in AS protocols, may be of value in helping men to make decisions around treatment for localised prostate cancer.

Tranexamic acid for safer surgery: the time is now.

Tranexamic acid reduces surgical bleeding. Consistent with previous research, the POISE-3 (Peri-Operative Ischemic Evaluation-3) trial found that tranexamic acid reduces major bleeding by 25% and with a low probability of any increase in thromboembolic events. Wider tranexamic acid use will improve surgical safety, avoid unnecessary blood use, reduce the risk of transfusion transmitted infections, and save healthcare funds. 'Consideration of tranexamic acid use' should be included in the safe surgery checklist. We have the evidence, and we need to act on it.

Utility of pre-operative haemoglobin concentration to guide peri-operative blood tests for hip and knee arthroplasty: A decision curve analysis.

OBJECTIVE: Assess the prognostic value of pre-operative haemoglobin concentration (Hb) for identifying patients who develop severe post-operative anaemia or require blood transfusion following primary total hip or knee, or unicompartmental knee arthroplasty (THA, TKA, UKA). BACKGROUND: Pre-operative group and save (G&S), and post-operative Hb measurement may be unnecessary for many patients undergoing hip and knee arthroplasty provided individuals at greatest risk of severe post-operative anaemia can be identified. METHODS AND MATERIALS: Patients undergoing THA, TKA, or UKA between 2011 and 2018 were included. Outcomes were post-operative Hb below 70 and 80 g/L, and peri-operative blood transfusion. Logistic regression assessed the association between pre-operative Hb and each outcome. Decision curve analysis compared strategies for selecting patients for G&S and post-operative Hb measurement. RESULTS: 10 015 THA, TKA and UKA procedures were performed in 8582 patients. The incidence of blood transfusion (4.5%) decreased during the study. Using procedure specific Hb thresholds to select patients for pre-operative G&S and post-operative Hb testing had a greater net benefit than selecting all patients, no patients, or patients with pre-operative anaemia. CONCLUSIONS: Pre-operative G&S and post-operative Hb measurement may not be indicated for UKA or TKA when adopting restrictive transfusion thresholds, provided clinicians accept a 0.1% risk of patients developing severe undiagnosed post-operative anaemia (Hb < 70 g/L). The decision to perform these blood tests for THA patients should be based on local institutional data and selection of acceptable risk thresholds.

Anxiety, resilience and local conditions: A cross-cultural investigation in the time of Covid-19.

The spread of Covid-19 is a worldwide phenomenon, unprecedented in modern times. Differences among countries in such matters are of interest as they provide a unique window to understand human behaviour and culture. The aim of this study is to examine cross-cultural differences in state anxiety, and any moderating role of resilience and social contact. Participants from three countries were recruited: Ireland (n = 449), Italy (n = 324) and Spain (n = 471). While these countries share many characteristics, it was anticipated that their experiences might differ because of pronounced differences in governmental measures and the local severity and history of the pandemic at the time of data collection. Results indicated that: (a) Resilience was negatively related to state anxiety both bivariately and multivariately; (b) number of hours outside per week did not predict state anxiety but was negatively correlated with fear of contagious diseases in the essential workers from the Irish sample; (c) national measures had a moderating role in the relationship between resilience and state anxiety; and (d) social contact, in terms of numbers of written, audio or visual interactions, was not a statistically significant predictor of state anxiety. These results may help to understand the adverse impact on mental health.

A Systematic Review of Barriers and Facilitators to Implementing Assisted Dying: A Qualitative Evidence Synthesis of Professionals' Perspectives.

Assisted dying is a divisive topic and draws both lamenting and approving commentary from political, medical, legal, and philosophical domains. This systematic review and qualitative evidence synthesis aims to identify the factors that healthcare professionals experience when working within assisted dying frameworks. PRISMA guidelines for systematic reviews were followed. Search results yielded 15,426 papers with 39 papers meeting inclusion criteria for this review. Remaining papers were subjected to critical appraisal and a thematic synthesis. Eight themes fell under the domain of 'barrier' and represented different personal and professional factors that hinder professionals from delivering assisted dying healthcare. Five themes came under the domain of 'facilitators' and represent factors that contribute to the smooth implementation and delivery of assisted dying services. Health professionals experience a range of factors that both impede and propel delivery of assisted dying frameworks.

Migration, labor and women's empowerment: Evidence from an agricultural value chain in Bangladesh.

As a substantial portion of the rural labor force migrates to urban areas, it is commonly assumed that women could take over traditionally male tasks in agricultural production, with potentially empowering outcomes for women. We study how changes in the supply of labor may influence female labor participation and empowerment outcomes. Using a detailed panel dataset on jute producers in the delta region of Bangladesh, we test whether out-migration of household members and perceived labor shortages are associated with the share of household and hired labor performed by women, and women's empowerment. When a household experiences reduced household or hired labor supply, we observe a relatively larger use of female household labor, but a reduced share of female hired labor. We also find that reduced labor supply is not associated with significant reductions in gender wage gaps, or enhanced women's empowerment. These findings suggest that given existing gender norms, male and female labor are not perfect substitutes for one another, and as a result, male outmigration is not associated with improved outcomes for women in cash crop production in the short run. Our results demonstrate a need for better understanding of the role of gender in rural labor markets, particularly in contexts of rapid urbanization.

Practical guidance for the management of adults with immune thrombocytopenia during the COVID-19 pandemic.

This document aims to provide practical guidance for the assessment and management of patients with thrombocytopenia, with a particular focus on immune thrombocytopenia (ITP), during the COVID-19 pandemic. The intention is to support clinicians and, although recommendations have been provided, it is not a formal guideline. Nor is there sufficient evidence base to conclude that alternative approaches to treatment are incorrect. Instead, it is a consensus written by clinicians with an interest in ITP or coagulation disorders and reviewed by members of the UK ITP forum.

Diagnosis and management of acute lower gastrointestinal bleeding: guidelines from the British Society of Gastroenterology.

This is the first UK national guideline to concentrate on acute lower gastrointestinal bleeding (LGIB) and has been commissioned by the Clinical Services and Standards Committee of the British Society of Gastroenterology (BSG). The Guidelines Development Group consisted of representatives from the BSG Endoscopy Committee, the Association of Coloproctology of Great Britain and Ireland, the British Society of Interventional Radiology, the Royal College of Radiologists, NHS Blood and Transplant and a patient representative. A systematic search of the literature was undertaken and the quality of evidence and grading of recommendations appraised according to the GRADE(Grading of Recommendations Assessment, Development and Evaluation) methodology. These guidelines focus on the diagnosis and management of acute LGIB in adults, including methods of risk assessment and interventions to diagnose and treat bleeding (colonoscopy, computed tomography, mesenteric angiography, endoscopic therapy, embolisation and surgery). Recommendations are included on the management of patients who develop LGIB while receiving anticoagulants (including direct oral anticoagulants) or antiplatelet drugs. The appropriate use of blood transfusion is also discussed, including haemoglobin triggers and targets.

Rebleeding and Mortality After Lower Gastrointestinal Bleeding in Patients Taking Antiplatelets or Anticoagulants.

BACKGROUND & AIMS: Patients who develop lower gastrointestinal bleeding (LGIB) while receiving anticoagulants or anti-platelets have increased severity of bleeding and risk of rebleeding. We compared outcomes of patients receiving antiplatelets, anticoagulants, or direct oral anticoagulants (DOACs) who develop LGIB, as well as the effects of withholding these drugs on their course of bleeding. METHODS: We performed a retrospective study of 2528 consecutive adult patients with LGIB at 143 hospitals in the United Kingdom, from September through December 2015; 917 were taking anticoagulant or antiplatelet drugs and 1218 were taking neither (unexposed). We collected data on demographic features of patients, interventions or medications, outcomes, laboratory test results, and patient readmission until patient death, discharge, or 28 days after admission (whichever came first). Rebleeding was defined as additional transfusion requirements and/or a decrease in hematocrit ≥20% after 24 hrs of clinical stability. Multivariate regression was used to examine the relationship between drug class on presentation with LGIB and rebleeding, mortality, and cardiovascular events. Rates of rebleeding and cardiovascular complications in patients who had these drugs withheld were also analyzed. RESULTS: Patients receiving antiplatelets, but not those receiving warfarin (n = 232) or DOACs (n = 102), had a higher risk of in-hospital rebleeding (monotherapy hazard ratio [HR], 3.57; 95% CI, 1.13-11.28; n = 504 and dual antiplatelet therapy hazard ratio, 5.3; 95% CI, 1.56-18.54; n = 79) compared with the unexposed group. This risk was not lower in patients who received antiplatelets and had the drug withheld for fewer than 5 days, compared to those who continued the drug throughout admission (HR, 0.98; 95% CI, 0.45-2.17) No differences were observed in risk-adjusted mortality or readmission with further bleeding for patients receiving antiplatelets, DOACs, or warfarin. Cardiovascular events were too few to allow meaningful comparison. CONCLUSIONS: In patients with LGIB, antiplatelet drugs, but not warfarin or DOACs, are associated with an increased risk of rebleeding. Withholding antiplatelets during admission does not lead to reduction in rebleeding.

Men's information-seeking behavior regarding cancer risk and screening: A meta-narrative systematic review.

OBJECTIVE: Preventive strategies are known to reduce cancer risk and incidence and improve prognosis. Men seldom seek medical information about cancer prevention and risk reduction. The aim of this meta-narrative systematic review was to critically appraise evidence from qualitative, quantitative, and mixed-methods studies that explored men's information-seeking behaviors in relation to cancer prevention and risk reduction. METHODS: MEDLINE, CINAHL Plus with Full Text, PsycINFO, PsycARTICLES, Psychology and Behavioral Sciences Collection, Education Full Text, and ERIC were systematically searched for studies published in English between January 1, 2006 and May 30, 2016. A total of 4117 titles were identified; of which, 31 studies were included (21 qualitative studies, 9 quantitative studies, and 1 mixed-methods study). The methodological quality of the studies was appraised by using different tools. RESULTS: Most studies focused on screening for prostate (n = 18) and colorectal cancer (n = 7). Most men were passive information-gatherers rather than active information-seekers. Key sources of information included the Internet for active information-seekers and health care professionals for passive information-gatherers. Barriers to information-seeking included information overload, embarrassment, and fear. Low literacy and health literacy levels were addressed in 3 studies and were identified as impediments to active information-seeking. Facilitators to information-seeking included family support, media, celebrity endorsements, and targeted information. CONCLUSIONS: Men's information-seeking behavior regarding cancer risk reduction, prevention, and screening is influenced by several factors. This necessitates targeted interventions aimed at raising awareness of cancer prevention and screening, while accounting for men's informational needs, preferred learning strategies, and literacy levels.

A simple post mortem room angiography method for the investigation of traumatic basal subarachnoid hemorrhage.

Identifying the site of vascular bleeding in fatal cases of traumatic basal subarachnoid hemorrhage (TBSAH) is important, but can be very difficult to achieve when there is extensive blood clot in the posterior cranial fossa. Post mortem angiography in these circumstances has been reported previously but with mixed results, and is rarely used in current practice within the United Kingdom. We have developed a simple and effective post mortem angiography method, using fluoroscopy and clear modern contrast medium, suitable for use in the autopsy room. Contrast medium was injected through an angiographic catheter positioned (with water filled balloon) in the extracranial vertebral artery (ECVA) just behind the clavicle, whilst the base of the skull and upper cervical spine area was visualized by fluoroscopy following digital subtraction of the bony images. The procedure was developed over a series of 8 TBSAH cases and using unfixed cadaveric specimens. A clear leak point was identified in 3 cases and the likely site indicated in a further fatality (all with tears subsequently confirmed by histology). In 4 cases, the bleeding point was not identified by angiography. In 7 deaths, the anatomy of the upper cervical loops and intracranial course of the vertebral arteries were well delineated by angiography and several small loop segments were documented. In 1 case, with severe degenerative vascular disease, extracranial vessel wall trauma and luminal thrombosis, angiography was unsuccessful above the level of the first cervical (C1) vertebra. Injecting contrast through the internal carotid artery, just above the bifurcation, was also shown to visualize the anterior cerebral circulation well. This method is likely to identify the main site of vascular tearing in about 50% of cases of TBSAH and to delineate the important anatomy of the vessels, prior to dissection of the upper neck and posterior fossa, thus minimizing handling artefacts and guiding the histological sampling of the vessels.

Confirmatory Factor Analysis for the Multidimensional Scale of Perceived Social Support in a Sample of Early Retirees Enrolled in University Programs.

OBJECTIVE: The aims of this study were twofold-first, to use confirmatory factor analysis (CFA) to help assess which of the previously identified factor structures (identified through exploratory factor analysis) best fits a Spanish-language version of the Multidimensional Scale of Perceived Social Support (MSPSS), and second, to validate the MSPSS (and its subscales) for use among early retirees. METHODS: The psychometric properties of the MPSS were analyzed in a sample of 991 Spanish early retirees enrolled in university programs. Participants had an average age of 62.7 years (SD = 5.89). An exploratory factor analysis and second-order confirmatory factor analysis were developed to identify the factorial solution and the best model fit. RESULTS: The three factors identified were MSPSS significant others, MSPSS friends, and MSPSS family. Regarding reliability and validity, internal consistency indices were above .92 and the correlation between perceived social support subscales and measures of satisfaction with life in retirement were significantly positive. CONCLUSION: The Spanish language version of the MSPSS demonstrates acceptable psychometric properties in relation to internal structure and reliability, and all but one of the goodness-of-fit indices emerging from the CFA also supported this factor structure. The practical implications of the scale in different populations and the problems in relation to the three-factor solution and the index values obtained are discussed.

Changes in blood center red blood cell distributions in the era of patient blood management: the trends for collection (TFC) study.

BACKGROUND: As patient blood management becomes more widespread, fewer red blood cell (RBC) units have been transfused. This multinational study evaluated changes in blood center RBC distributions. STUDY DESIGN AND METHODS: Data on number and ABO and D groups of RBC distributions were obtained from several large American blood centers and national or provincial blood services (NPBS) from fiscal year (FY) 2010 through FY2014. Due to relatively larger numbers of distributions and differences in ABO and D groups between the Japanese Red Cross and the other NPBS, Japanese data were not included in distributions calculations. RESULTS: Data from seven American blood centers and eight NPBS were obtained. Overall, at both the American and the seven NPBS that were analyzed, there were declines in the number of RBC distributions between FY2010 and FY2014, 16.9 and 8.0%, respectively. The number of O- RBC distributions decreased by 9.0% at American blood centers but the proportion of RBC distributions that were O- increased by 9.3% during this time. The NPBS had 1.6% increase in O- RBC distributions and 10.5% increase in the proportion of O- distributions. The proportion of O+ distributions increased slightly over time at American centers (2.9%) while decreasing slightly (1.1%) at NPBS despite reductions in the absolute numbers of O+ distributions. Overall there was 2.6% decrease in the proportion of B+ and AB+ RBCs distributed and 13.6% absolute reduction in the number of these units distributed. CONCLUSION: Although overall RBC distributions have decreased over time, the proportion of O units has increased substantially.

Lymphocyte-specific compensation for XLF/cernunnos end-joining functions in V(D)J recombination.

Mutations in XLF/Cernunnos (XLF) cause lymphocytopenia in humans, and various studies suggest an XLF role in classical nonhomologous end joining (C-NHEJ). We now find that XLF-deficient mouse embryonic fibroblasts are ionizing radiation (IR) sensitive and severely impaired for ability to support V(D)J recombination. Yet mature lymphocyte numbers in XLF-deficient mice are only modestly decreased. Moreover, XLF-deficient pro-B lines, while IR-sensitive, perform V(D)J recombination at nearly wild-type levels. Correspondingly, XLF/p53-double-deficient mice are not markedly prone to the pro-B lymphomas that occur in previously characterized C-NHEJ/p53-deficient mice; however, like other C-NHEJ/p53-deficient mice, they still develop medulloblastomas. Despite nearly normal V(D)J recombination in developing B cells, XLF-deficient mature B cells are moderately defective for immunoglobulin heavy-chain class switch recombination. Together, our results implicate XLF as a C-NHEJ factor but also indicate that developing mouse lymphocytes harbor cell-type-specific factors/pathways that compensate for the absence of XLF function during V(D)J recombination.