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Abstract Hadron therapy is an advanced radiation modality for treating cancer, which currently uses protons and carbon ions. Hadrons allow for a highly conformal dose distribution to the tumour, minimising the detrimental side-effects due to radiation received by healthy tissues. Treatment with hadrons requires sub-millimetre spatial resolution and high dosimetric accuracy. This paper discusses the design, fabrication and performance tests of a detector based on Gas Electron Multipliers (GEM) coupled to a matrix of thin-film transistors (TFT), with an active area of 60 × 80 mm2 and 200 ppi resolution. The experimental results show that this novel detector is able to detect low-energy (40 kVp X-rays), high-energy (6 MeV) photons used in conventional radiation therapy and protons and carbon ions of clinical energies used in hadron therapy. The GEM-TFT is a compact, fully scalable, radiation-hard detector that measures secondary electrons produced by the GEMs with sub-millimetre spatial resolution and a linear response for proton currents from 18 pA to 0.7 nA. Correcting known detector defects may aid in future studies on dose uniformity, LET dependence, and different gas mixture evaluation, improving the accuracy of QA in radiotherapy.

Abstract In a population-based representative sample of adults residing in 22 communities in Botswana, a southern African country with high HIV prevalence, 1 in 4 individuals had high blood pressure. High blood pressure was less prevalent in adults with HIV than without HIV. Sixty percent of persons with high blood pressure had not previously been diagnosed. Among individuals with a prior diagnosis of high blood pressure who reported being prescribed anti-hypertension medications, almost half had elevated blood pressure, irrespective of HIV-status. One-third of adults in this setting (mainly men) declined free non-invasive blood pressure assessments in their households. In conclusion, our study highlights alarmingly high hypertension rates in the community, with low levels of awareness and control, emphasizing the urgent need for community level BP screening and active management to reach recommended targets.

Abstract Radio occultation (RO) by the Earth's atmosphere of the transmitted signals of the Global Navigation Satellite Systems' satellites has improved numerical weather prediction, has benefited atmospheric process studies, and benchmarked climate change by its strong traceability to the international definition of the second. Until now, research with RO has been isolated to the few centers that actually process the data and impracticable elsewhere because of limitations on data formats, organization and volume of the data, download bandwidth, and the lack of a database that can be queried before downloading data. We announce the availability of RO data in the Registry of Open Data of Amazon Web Services (AWS). RO data are freely available for download for the user and free to process and store for the manager of the repository. RO data as processed by the COSMIC Program Office at the University Corporation for Atmospheric Research, by the Radio Occultation Meteorology Satellite Application Facility (ROM SAF), by EUMETSAT, and by the NASA Jet Propulsion Laboratory are available beginning with calibrated (excess) phase, extending to bending angle and refractivity and to retrievals of pressure, temperature and water vapor. The same RO repository also contains a metadata database that permits simple querying, filtering, and download of data using a Python application programming interface provided by this same project. Four tutorial demonstrations are provided as jupyter notebooks to provide representative samples of code to perform common research activities with RO data, including database querying and analysis, inter‐center comparison of RO retrieval performance, and atmospheric process studies.

International concern for the human rights of Afghan women has spiked since the Taliban consolidated power in Afghanistan in fall 2021. Yet little is known about how to effectively advocate for women's human rights under this new context. We present findings from a random sample of all adult Afghan internet users' attitudes toward peace, security, gender, and human rights and find significant support for women's human rights as a national priority within Afghanistan, even when controlling for other priorities and even among many men and women aligned with the Taliban. Given that men now have much more political power in Afghan society to protect women's rights, we paid particular attention to men's attitudes toward women's human rights. Our evidence from an embedded survey experiment, building on earlier literature from other countries, demonstrates that fathers of eldest daughters are particularly likely to favor prioritizing women's rights when primed to think about the gender of their eldest children. Thus, the human rights and humanitarian community should spend more time and attention engaging with this demographic, and specifically creating marketing and advocacy strategies that encourage men to think about or act on behalf of their eldest daughters.

Abstract Outcomes for patients with melanoma have improved over the past decade with the clinical development and approval of immunotherapies targeting immune checkpoint receptors such as programmed death-1 (PD-1), programmed death ligand 1 (PD-L1) or cytotoxic T lymphocyte antigen-4 (CTLA-4). Combinations of these checkpoint therapies with other agents are now being explored to improve outcomes and enhance benefit-risk profiles of treatment. Alternative inhibitory receptors have been identified that may be targeted for anti-tumor immune therapy, such as lymphocyte-activation gene-3 (LAG-3), as have several potential target oncogenes for molecularly targeted therapy, such as tyrosine kinase inhibitors. Unfortunately, many patients still progress and acquire resistance to immunotherapy and molecularly targeted therapies. To bypass resistance, combination treatment with immunotherapies and single or multiple TKIs have been shown to improve prognosis compared to monotherapy. The number of new combinations treatment under development for melanoma provides options for the number of patients to achieve a therapeutic benefit. Many diagnostic and prognostic assays have begun to show clinical applicability providing additional tools to optimize and individualize treatments. However, the question on the optimal algorithm of first- and later-line therapies and the search for biomarkers to guide these decisions are still under investigation. This year, the Melanoma Bridge Congress (Dec 1st–3rd, 2022, Naples, Italy) addressed the latest advances in melanoma research, focusing on themes of paramount importance for melanoma prevention, diagnosis and treatment. This included sessions dedicated to systems biology on immunotherapy, immunogenicity and gene expression profiling, biomarkers, and combination treatment strategies.

Rationale & Objective: Heart failure (HF) is an important cause of morbidity and mortality among individuals with chronic kidney disease (CKD). A large body of evidence from preclinical and clinical studies implicates excess levels of fibroblast growth factor 23 (FGF23) in HF pathogenesis in CKD. It remains unclear whether the relationship between elevated FGF23 levels and HF risk among individuals with CKD varies by HF subtype. Study Design: Prospective cohort study. Settings & Participants: A total of 3,502 participants were selected in the Chronic Renal Insufficiency Cohort study. Exposure: Baseline plasma FGF23. Outcomes: Incident HF by subtype and total rate of HF hospitalization. HF was categorized as HF with preserved ejection fraction (HFpEF, ejection fraction [EF] ≥ 50%), HF with reduced EF (HFrEF, EF

Background Preclinically, interleukin-15 (IL-15) monotherapy promotes antitumor immune responses, which are enhanced when IL-15 is used in combination with immune checkpoint inhibitors (ICIs). This first-in-human study investigated NIZ985, a recombinant heterodimer comprising physiologically active IL-15 and IL-15 receptor α, as monotherapy and in combination with spartalizumab, an anti-programmed cell death protein-1 (anti-PD-1) monoclonal antibody, in patients with advanced solid tumors.Methods This phase I/Ib study had two dose-escalation arms: single-agent NIZ985 administered subcutaneously thrice weekly (TIW, 2 weeks on/2 weeks off) or once weekly (QW, 3 weeks on/1 week off), and NIZ985 TIW or QW administered subcutaneously plus spartalizumab (400 mg intravenously every 4 weeks (Q4W)). The dose-expansion phase investigated NIZ985 1 µg/kg TIW/spartalizumab 400 mg Q4W in patients with anti-PD-1–sensitive or anti-PD-1–resistant tumor types stratified according to approved indications. The primary objectives were the safety, tolerability, and the maximum tolerated doses (MTDs) and/or recommended dose for expansion (RDE) of NIZ985 for the dose-expansion phase.Results As of February 17, 2020, 83 patients (median age: 63 years; range: 28–85) were treated in dose escalation (N=47; single-agent NIZ985: n=27; NIZ985/spartalizumab n=20) and dose expansion (N=36). No dose-limiting toxicities occurred nor was the MTD identified. The most common treatment-related adverse event (TRAE) was injection site reaction (primarily grades 1–2; single-agent NIZ985: 85% (23/27)); NIZ985/spartalizumab: 89% [50/56]). The most common grade 3–4 TRAE was decreased lymphocyte count (single-agent NIZ985: 7% [2/27]; NIZ985/spartalizumab: 5% [3/56]). The best overall response was stable disease in the single-agent arm (30% (8/27)) and partial response in the NIZ985/spartalizumab arm (5% [3/56]; melanoma, pancreatic cancer, gastric cancer). In dose expansion, the disease control rate was 45% (5/11) in the anti-PD-1–sensitive and 20% (5/25) in the anti-PD-1–resistant tumor type cohorts. Pharmacokinetic parameters were similar across arms. The transient increase in CD8+ T cell and natural killer cell proliferation and induction of several cytokines occurred in response to the single-agent and combination treatments.Conclusions NIZ985 was well tolerated in the single-agent and NIZ985/spartalizumab regimens. The RDE was established at 1 µg/kg TIW. Antitumor activity of the combination was observed against tumor types known to have a poor response to ICIs.Trial registration number NCT02452268.

Vaccination coverage among children in kindergarten varies across the country and within states. We surveyed a convenience sample of kindergarten school nurses to investigate self-reported vaccination-related activities conducted at schools nationwide. The majority of the 1,435 kindergarten school nurses responding reported that their schools communicate with parents and guardians of undervaccinated students by phone (96%), postal mail (67%), newsletters (61%), and e-mail (59%). Most respondents reported documenting vaccination coverage in electronic systems (85%) and sharing coverage reports with health departments (69%). A total of 41% of school nurses worked with external partners for vaccination efforts, the most common support received from partners being vaccine administration (38%) and providing materials/vaccines (21%). School nurses also reported that 95% of kindergartners were up to date for all vaccines. School-based vaccination-related activities are essential to sustaining high levels of vaccination coverage for the protection of children at schools and in the broader community.

Abstract U.S.-based research suggests conservatism is linked with less concern about contracting coronavirus and less preventative behaviors to avoid infection. Here, we investigate whether these tendencies are partly attributable to distrust in scientific information, and evaluate whether they generalize outside the U.S., using public data and recruited representative samples across three studies (N total = 34,710). In Studies 1 and 2, we examine these relationships in the U.S., yielding converging evidence for a sequential indirect effect of conservatism on compliance through scientific (dis)trust and infection concern. In Study 3, we compare these relationships across 19 distinct countries. Although the relationships between trust in scientific information about the coronavirus, concern about coronavirus infection, and compliance are consistent cross-nationally, the relationships between conservatism and trust in scientific information are not. These relationships are strongest in North America. Consequently, the indirect effects observed in Studies 1–2 only replicate in North America (the U.S. and Canada) and in Indonesia. Study 3 also found parallel direct and indirect effects on support for lockdown restrictions. These associations suggest not only that relationships between conservatism and compliance are not universal, but localized to particular countries where conservatism is more strongly related to trust in scientific information about the coronavirus pandemic.

On June 17, 2024, the Food and Drug Administration approved 21-valent pneumococcal conjugate vaccine (PCV) (PCV21; CAPVAXIVE; Merck Sharp & Dohme, LLC) for adults aged >18 years. PCV21 does not contain certain serotypes that are included in other licensed pneumococcal vaccines but adds eight new serotypes. The Advisory Committee on Immunization Practices (ACIP) recommends use of a PCV for all adults aged ≥65 years, as well as adults aged 19--64 years with certain risk conditions for pneumococcal disease if they have not received a PCV or whose vaccination history is unknown. Previously, options included either 20-valent PCV (PCV20; Prevnar20; Wyeth Pharmaceuticals, Inc.) alone or a 15-valent PCV (PCV15; VAXNEUVANCE; Merck Sharp & Dohme, LLC) in series with 23-valent pneumococcal polysaccharide vaccine (PPSV23; Pneumovax23; Merck Sharp & Dohme, LLC). Additional recommendations for use of PCV20 exist for adults who started their pneumococcal vaccination series with 13-valent PCV (PCV13; Prevnar13; Wyeth Pharmaceuticals, Inc.). The ACIP Pneumococcal Vaccines Work Group employed the Evidence to Recommendations framework to guide its deliberations on PCV21 vaccination among U.S. adults. On June 27, 2024, ACIP recommended a single dose ofPCV21 as an option for adults aged >19 years for whom PCV is currently recommended. Indications for PCV have not changed from previous recommendations. This report summarizes evidence considered for these recommendations and provides clinical guidance for use of PCV21. [ABSTRACT FROM AUTHOR]

Imitating each other is a central element of human nature and everyday life. Modelling – setting an example to others – and imitation – when the modelled behaviour is copied – are just as fundamental to learning as to maintaining and transmitting culture. Yet, the moral connotations of modelling and imitation are not well understood. Building on and extending the theoretical framework of vicarious responsibility, we investigate the imitated model's responsibility and the psychological processes underlying blame attribution to the model for their imitators’ behaviour. We argue that people understand that imitating a wrongdoing renders it potentially more consequential and that people account for these additional consequences in their appraisals of the original, modelled wrongdoing. Moreover, we hypothesized that models would be blamed for their imitators’ harmful behaviour to the extent that the observers copied the model's action. Five studies (Ntotal = 945) utilizing various contexts from animal mistreatment to online bullying, three of them preregistered, provide consistent support for our hypotheses and show that models are blamed for their imitators’ behaviour, that is, for setting a bad example for others. Extending present theories of vicarious responsibility, we demonstrate that shared group membership is not always a necessary requirement for vicarious blame attributions. [ABSTRACT FROM AUTHOR]

In March 2021, Serbia made the unprecedented announcement to offer free Covid‐19 vaccination to citizens of Bosnia and Herzegovina, and notably to Bosniaks, against whom three decades earlier Serbia had waged a bloody war. How was this policy appraised and, most importantly, did the policy appraisal impact reconciliation? We report here the results of a longitudinal investigation amid a representative sample of Bosniak youth (N = 450). Results suggest that a positive appraisal of this actual, state‐level policy, predicted improvement on a series of intergroup reconciliation indicators (e.g., trust in the out‐group, forgiveness for past violence, hope for future relationship), particularly so amid those who are strongly attached to their Bosniak in‐group. [ABSTRACT FROM AUTHOR]

International concern for the human rights of Afghan women has spiked since the Taliban consolidated power in Afghanistan in fall 2021. Yet little is known about how to effectively advocate for women's human rights under this new context. We present findings from a random sample of all adult Afghan internet users' attitudes toward peace, security, gender, and human rights and find significant support for women's human rights as a national priority within Afghanistan, even when controlling for other priorities and even among many men and women aligned with the Taliban. Given that men now have much more political power in Afghan society to protect women's rights, we paid particular attention to men's attitudes toward women's human rights. Our evidence from an embedded survey experiment, building on earlier literature from other countries, demonstrates that fathers of eldest daughters are particularly likely to favor prioritizing women's rights when primed to think about the gender of their eldest children. Thus, the human rights and humanitarian community should spend more time and attention engaging with this demographic, and specifically creating marketing and advocacy strategies that encourage men to think about or act on behalf of their eldest daughters. [ABSTRACT FROM AUTHOR]

Abstract Background The external validity of the randomized controlled trial (RCT) refers to the extent to which the results of the RCT apply to the relevant, non-trial population and is impacted by its eligibility criteria, its organization, and its delivery of the intervention. Here, we compared the outcomes of mortality and hospitalization between an RCT and a cohort study that concurrently enrolled HIV-exposed uninfected (HEU) newborns in Botswana. Methods The Mpepu Study (the RCT) was a clinical trial which determined that co-trimoxazole (CTX) provided no survival benefit for HEUs, allowing both arms of the RCT to be used. The Maikaelelo study (the cohort study) was a prospective observational study that enrolled HEU newborns with telephone follow-up and no in-person visits. Rates of death and hospitalization in the pooled population, were modeled using cox-proportional hazards models for time to death or time to first hospitalization, with study setting (RCT vs. cohort study) as an independent variable. The causal effect of study setting on morbidity and mortality was obtained through a treatment effects approach. Results In total, 4,010 infants were included; 1,306 were enrolled into the cohort study and 2,704 were enrolled into the RCT. No significant differences in mortality were observed between the two study settings (HR: 1.28, 95% CI: 0.76, 2.13), but RCT participants had a lower risk of hospitalization (HR: 0.72, 95% CI: 0.58, 0.89) that decreased with age. However, RCT participants had a higher risk of hospitalization within the first six months of life. The causal risk difference in hospitalizations attributable to the RCT setting was -0.03 (95% CI: -0.05, -0.01). Conclusions Children in an RCT with rigorous application of national standard of care guidelines experienced a significantly lower risk of hospitalization than children participating in a cohort study that did not alter clinical care. Future research is needed to further investigate outcome disparities when real-world results fail to mirror those achieved in a clinical trial. Trial registration The Mpepu Trial was funded by the U.S. National Institutes of Health (No. NCT01229761) and the Maikaelelo Study was funded primarily by the U.S. Centers for Disease Control and Prevention (32AI007433-21).

The Advisory Committee on Immunization Practices (ACIP) recommends recombinant zoster vaccine (RZV) to prevent against herpes zoster (HZ) and related complications in immunocompetent adults ≥50 y and immunocompromised adults ≥19 y. In 2019, a statistical safety signal for Guillain-Barré syndrome (GBS) following RZV was identified using data from the Vaccine Safety Datalink (VSD). Subsequently, the U.S. Food and Drug Administration (FDA), the Centers for Disease Control and Prevention (CDC), and collaborators undertook additional analyses using Centers for Medicare & Medicaid Services (CMS) Medicare data to further investigate the potential risk of GBS following RZV. Concurrently, epidemiologic data suggested a potentially elevated risk of GBS following HZ in U.S. adults. Using data from these sources and a published simulation model, this study evaluated the health benefits and risks associated with vaccinating immunocompetent adults ≥50 y with RZV compared to no vaccination. In the base case analysis, RZV vaccination averted 43,000–63,000 cases of HZ, including GBS complications, per million vaccinated per 10-y age cohort compared to 3–6 additional cases of GBS projected following RZV per million vaccinated in the same population. This analysis highlights the projected health benefits of RZV vaccination compared to the relatively low potential risk of GBS following RZV.