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Preferentially Expressed Antigen in Melanoma (PRAME), a cancer-testis antigen, provides an ideal target for immunotherapy in acute myeloid leukemia (AML). We have shown expression of PRAME in a significant subset of childhood and adult AML and lack of expression in normal hematopoiesis. Although an intracellular antigen, we developed a novel approach to target PRAME using a chimeric antigen receptor (CAR) construct encoding a targeting domain based on T-cell receptor (TCR) mimic antibodies that target the peptide-HLA complex. We used the antibody sequence from a previously designed TCR mimic (mTCR) antibody, Pr20, that recognizes the PRAME ALY peptide in complex with HLA-A∗02 and verified expression of PRAME in AML cell lines and primary AML blasts. Using the Pr20 antibody sequence, we developed CAR T cells (PRAME mTCRCAR T) to be tested against primary samples from patients with AML and AML cell lines that express the PRAME antigen in the context of HLA-A2 expression. In contrast to appropriate controls, PRAME mTCRCAR T cells demonstrate target-specific and HLA-mediated in vitro activity in OCI-AML2 and THP-1 cell lines, HLA-A2 cell lines expressing the PRAME antigen, and against primary AML patient samples. In vivo cell-derived xenograft models treated with PRAME mTCRCAR T cells demonstrated potent leukemia clearance and improved survival compared with unmodified T-cell controls. Furthermore, the cytolytic activity of PRAME mTCRCAR T cells was enhanced by treating the target cells with interferon gamma, which increases PRAME antigen expression. These results demonstrate the feasibility and efficacy of targeting PRAME with novel PRAME mTCRCAR T cells.

Academic performance in preschool and early elementary grades has long been linked with child attention problems. There is empirical and theoretical support that this co-occurrence is attributable to longitudinal relations between attention and reading problems. However, the literature to date—coming primarily from psychology disciplines—has insufficiently explored the possibility that the relationship between attention problems and reading performance affects students differentially. Using data from the Early Childhood Longitudinal Study, this inquiry extends the current literature by examining whether initial scores and rates of change in the relationship between attention problems and later reading performance vary by child’s race, gender, and socioeconomic status (SES). Findings support the claim that attention and reading develop in a mutual process and reveal a complicated pattern of social and individual predictors of attention reading growth over time. Social work researchers can reframe and reinvestigate evidence derived from a psychological framing of the dual developmental processes of reading and attention within a broader understanding of the nested nature of child development within structures of oppression.

BACKGROUND: Active surveillance (AS) is recommended for low-risk and some intermediate-risk prostate cancer. Uptake and practice of AS vary significantly across different settings, as does the experience of surveillance-from which tests are offered, and to the levels of psychological support. OBJECTIVE: To explore the current best practice and determine the most important research priorities in AS for prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: A formal consensus process was followed, with an international expert panel of purposively sampled participants across a range of health care professionals and researchers, and those with lived experience of prostate cancer. Statements regarding the practice of AS and potential research priorities spanning the patient journey from surveillance to initiating treatment were developed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Panel members scored each statement on a Likert scale. The group median score and measure of consensus were presented to participants prior to discussion and rescoring at panel meetings. Current best practice and future research priorities were identified, agreed upon, and finally ranked by panel members. RESULTS AND LIMITATIONS: There was consensus agreement that best practice includes the use of high-quality magnetic resonance imaging (MRI), which allows digital rectal examination (DRE) to be omitted, that repeat standard biopsy can be omitted when MRI and prostate-specific antigen (PSA) kinetics are stable, and that changes in PSA or DRE should prompt MRI ± biopsy rather than immediate active treatment. The highest ranked research priority was a dynamic, risk-adjusted AS approach, reducing testing for those at the least risk of progression. Improving the tests used in surveillance, ensuring equity of access and experience across different patients and settings, and improving information and communication between and within clinicians and patients were also high priorities. Limitations include the use of a limited number of panel members for practical reasons. CONCLUSIONS: The current best practice in AS includes the use of high-quality MRI to avoid DRE and as the first assessment for changes in PSA, with omission of repeat standard biopsy when PSA and MRI are stable. Development of a robust, dynamic, risk-adapted approach to surveillance is the highest research priority in AS for prostate cancer. PATIENT SUMMARY: A diverse group of experts in active surveillance, including a broad range of health care professionals and researchers and those with lived experience of prostate cancer, agreed that best practice includes the use of high-quality magnetic resonance imaging, which can allow digital rectal examination and some biopsies to be omitted. The highest research priority in active surveillance research was identified as the development of a dynamic, risk-adjusted approach.

Background Prostate cancer (PCa) and its treatments can have a significant negative impact on the sexual health of survivors and couples, but few studies have specifically examined the impact of PCa-related sexual dysfunction on female partners of survivors. Aim Our objective was to perform a qualitative study to comprehensively characterize female partners’ perceptions of the implications of PCa on their sex lives, as well as partners’ sexual health concerns and unmet needs. Methods We conducted semi-structured telephone interviews about sexual health and unmet needs with female partners of PCa survivors recruited from multiple clinical locations and support groups for PCa caregivers from September 2021 to March 2022. Interviews were audio-recorded, transcribed verbatim, and independently coded. Participants were recruited until thematic saturation was achieved. Outcomes Outcomes of this study were female partner sexual health concerns and unmet needs. Results Among 12 participants, the median age was 65 (range 53 to 81) years, 9 were White, the median time since their partner’s PCa diagnosis was 2.25 years (range 11 months to 20 years), and a majority reported that their partner had undergone radical prostatectomy, radiation, and/or hormonal therapy. Major emergent themes pertained to the significant impact of age- and PCa-related sexual dysfunction on female sexual quality of life, the dyadic nature of sexual dysfunction and recovery, the role of the partner in coping with and adjusting to sexual dysfunction, difficulties communicating about sexual dysfunction in an intimate relationship, a lack of physician-led sexual health counseling and support, and the benefit of peer interactions and proactive information seeking in addressing unmet sexual health needs. Clinical Implications Future efforts should continue to explore the impact of PCa on partner sexual health and address unmet needs through sexual health education and support. Strengths and Limitations In this study, we identified female partners’ sexual health concerns both related to and independent of PCa survivor sexual health. Limitations include exclusion of male partners of survivors and potential responder bias, as partners who agreed to participate may have experienced more sexual health concerns. Conclusion We found that female partners experience PCa-related sexual dysfunction as a couple’s disease, grief due to age- and PCa-related sexual losses, and a lack of physician-led sexual health counseling and information. Our results highlight the importance of including partners of PCa survivors in the sexual recovery process and of developing sexual care programs to address partners’ unmet sexual health needs.

Prostate cancer (PCa) is a leading cause of death and partially heritable. Genetic risk prediction might be useful for strategies to reduce PCa mortality through early detection and prevention.To review evidence for genetic risk prediction for PCa.A collaborative literature review was conducted using PubMed and Google Scholar. Search terms included genetic, risk, prediction, and "prostate cancer". Articles addressing screening, early detection, or prevention were prioritized, as were studies involving diverse populations.Rare pathogenic mutations (RPMs), especially in DNA damage repair genes, increase PCa risk. RPMs in BRCA2 are most clearly deleterious, conferring 2-8.6 times higher risk of PCa and a higher risk of aggressive disease. Common genetic variants can be combined into genetic risk scores (GRSs). A high GRS (top 20-25% of the population) confers two to three times higher risk of PCa than average; a very high GRS (top 1-5%) confers six to eight times higher risk. GRSs are not specific for aggressive PCa, possibly due to methodological limitations and/or a field effect of an elevated risk for both low- and high-grade PCa. It is challenging to disentangle genetics from structural racism and social determinants of health to understand PCa racial disparities. GRSs are independently associated with a lethal PCa risk after accounting for family history and race/ancestry. Healthy lifestyle might partially mitigate the risk of lethal PCa.Genetic risk assessment is becoming more common; implementation studies are needed to understand the implications and to avoid exacerbating healthcare disparities. Men with a high genetic risk of PCa can reasonably be encouraged to adhere to a healthy lifestyle.Prostate cancer risk is inherited through rare mutations and through the combination of hundreds of common genetic markers. Some men with a high genetic risk (especially BRCA2 mutations) likely benefit from early screening for prostate cancer. The risk of lethal prostate cancer can be reduced through a healthy lifestyle.

Persons living with dementia (PLWD) are at increased risk for coronavirus disease 2019 (COVID-19) and poorer outcomes if they contract the disease. COVID-19 may also change and exacerbate usual stresses of family caregiving. The current qualitative descriptive study examined 14 family care partners' (FCPs) experiences and perspectives on how the COVID-19 pandemic impacted them, their care recipients, and their caregiving for their care recipients. Thematic analysis of interviews generated five themes: Cautious of COVID-19 Exposure , Challenges of Balancing COVID-19 Restrictions With Caregiv ing, Shared Loneliness , Functional Decline , and Communication Challenges With PLWD and Health Care Professionals (HCPs). FCPs are integral to the care of PLWD across care settings. The time is now to plan for changes in policy that will safely maintain FCPs' visitation with their care recipients with dementia and allow for partnering with HCPs to avoid the long-lasting negative effects on older adults' health and function. [ Journal of Gerontological Nursing, 49 (3), 27–33.]

To evaluate the longitudinal association between plant-based diet index (PDI) score and incident erectile dysfunction (ED).We conducted a prospective analysis of 21 942 men aged 40 to 75 years who were enrolled in the Health Professionals Follow-Up Study. ED was assessed with questionnaires every 4 years starting in 2000. Dietary data were collected via validated food frequency questionnaires completed every 4 years and were used to calculate total PDI scores, as well as healthy (hPDI) and unhealthy (uPDI) subscores. Multivariable Cox proportional hazards models were used to compute hazard ratios (HRs) for incident ED. All models were stratified by age (60, 60 to70, ≥70 years).Among men aged 60 to70 years, hPDI was inversely associated with incident ED. Those in the highest quintile of hPDI in that age group had an 18% lower risk of ED (HR 0.82, 95% confidence interval (CI) 0.73-0.91; P-trend0.001) compared to those in the lowest quintile. Conversely, uPDI was positively associated with ED in men aged60 years (HR 1.27, 95% CI 1.01-1.60; P-trend = 0.02).Encouraging a healthy plant-based diet may be an environmentally sustainable intervention for men interested in maintaining erectile function.

Introduction Testosterone replacement therapy (TRT) remains a commonly utilized treatment for men with testosterone deficiency (TD). Despite the recent FDA approval of new oral TRT medications, concerns remain regarding their efficacy and safety, and prescription rates for these medications have decreased compared to those for TD medications with other routes of administration. Objective In this study we sought to investigate the efficacy and safety of oral testosterone undecanoate (oTU), a new oral TRT medication. Methods A comprehensive review of the literature was performed using the Medline, EMBASE, and Cochrane Library databases; 1269 articles were identified, with 44 articles included in the final review and 12 used to perform meta-analyses to investigate the change in serum total testosterone (TT) and risk of adverse effects following oral testosterone undecanoate (oTU) use. Articles were also reviewed to investigate the reported effects of oTU on body composition, liver function, hematologic assays, lipid profiles, hormone assays, prostate growth, hypertension, and symptoms of TD. Results Across placebo-controlled randomized trials, there was no significant increase in TT for those receiving oTU vs placebo (mean difference, −0.26 [95% CI, −1.26 to 0.73]). On subanalysis, when eugonadal participants received oTU, a significant decrease in TT was demonstrated (mean difference −0.86 [95% CI, −1.28 to 0.43]). When participants who were hypogonadal at baseline received oTU, a significant increase in TT compared to placebo was seen (mean difference 1.25 [95% CI, 0.22-2.29]). There was no significant risk of adverse effects (RR, −0.03 [95% CI, −0.08 to 0.03]) or serious adverse effects (RR, 0.15 [95% CI, −0.66 to 0.96]) in the oTU groups compared to placebo. Conclusion oTU was found to be well tolerated in hypogonadal patients, resulting in improved testosterone levels, height velocity, and sexual symptoms, without significant hepatotoxicity, prostatic enlargement, or worsening hypertension. There was no consensus regarding the effect of oTU on lean and fat mass percentages, hematologic assays, lipid profiles, mood, and general well-being.

BackgroundInformation regarding the Medicaid coverage of artificial urinary sphincter (AUS) and male suburethral slings (MS) placement in the United States (US) is not readily available. In this manuscript, we seek to elucidate the state-by-state Medicaid coverage of these two procedures in the US.MethodsState Medicaid websites were utilized to access publicly available physician fee schedules for the calendar year 2020. Fee schedules were searched for current procedural terminology (CPT) codes. CPT codes representing insertion of tandem cuff, insertion of AUS, removal of AUS, removal and replacement AUS, sling operation for correction of male stress urinary incontinence (SUI), and removal or revision of sling for male SUI were utilized. Data were recorded by the procedure for each device, including the coverage status and physician fees.ResultsOf the 50 US states analyzed, 49 publish publicly accessible physician fee schedules. All 49 of these states reported coverage for removal with and without revision of the AUS, and 48 states reported coverage for insertion of an AUS, and insertion of a tandem cuff. The median reimbursement for each AUS related procedure was $624.00 ($181.84-$10,960.90) for tandem cuff, $665.54 ($199.89-$11,949.86) for AUS insertion, $528.03 ($146.90-$1,893.12) for AUS removal, and $630.29 ($208.55-$11,586.74) for AUS revision. All 49 states reported coverage for placement of MS, and 48 states reported coverage for removal or revision of MS. The median reimbursement was $652.57 ($198.00-$5,237.35) for MS placement and $554.47 ($104.27-$2,288.93) for MS revision.ConclusionsAUS and MS procedures in the Medicaid population are covered by nearly all states. Therefore, surgical treatment of SUI may be offered to Medicaid patients in most states without reimbursement concerns.

The Seraph® 100 Microbind® Affinity Blood Filter (Seraph® 100) is a hemoperfusion device designed to adsorb bacteria, viruses, and toxins when added to extracorporeal circuits. The FDA granted emergency use authorization in adults, but this device had never been utilized in children. A 17-year-old patient with asthma presented with respiratory distress due to COVID-19. His course was complicated by respiratory failure, rhabdomyolysis, and stage 3 AKI requiring initiation of continuous kidney replacement therapy (CKRT) on ICU day 3. The Seraph® 100 filter was added on ICU day 4. He was treated with 3 filters from ICU day 4 to 8. On ICU day 8, he was extubated and CKRT discontinued. He required no further kidney replacement therapy but did not have laboratory work post-discharge. In conclusion, this adolescent patient with COVID-19 and AKI requiring CKRT tolerated treatment with the Seraph® 100 Microbind® Affinity Blood Filter without significant adverse events.

Introduction Prostate cancer is the second leading cause of cancer deaths among men in the United States and harms Black men disproportionately. Most US men are uninformed about many key facts important to make an informed decision about prostate cancer. Most experts agree that it is important for men to learn about these problems as early as possible in their lifetime. Objectives To compare the effect of a community health worker (CHW)-led educational session with a physician-led educational session that counsels Black men about the risks and benefits of prostate-specific antigen (PSA) screening. Methods One hundred eighteen Black men recruited in 8 community-based settings attended a prostate cancer screening education session led by either a CHW or a physician. Participants completed surveys before and after the session to assess knowledge, decisional conflict, and perceptions about the intervention. Both arms used a decision aid that explains the benefits, risks, and controversies of PSA screening and decision coaching. Results There was no significant difference in decisional conflict change by group: 24.31 physician led versus 30.64 CHW led (P=.31). The CHW-led group showed significantly greater improvement on knowledge after intervention, change (SD): 2.6 (2.81) versus 5.1 (3.19), P Conclusions CHW-led interventions can effectively assist Black men with complex health decision-making in community-based settings. This approach may improve prostate cancer knowledge and equally minimize decisional conflict compared with a physician-led intervention.

The discovery of two ultraviolet (UV)-bright galaxy candidates at z ∼ 13, HD1 and HD2, laid the foundation for a new race to study the early Universe. Previous investigations suggested that they are powered either by a supermassive black hole or by an extreme, transient burst of star formation. Given their uncertain nature, we investigate whether these sources could be lensed by a hitherto undetected, faint foreground galaxy. We find that at the current limiting magnitude with which HD1 and HD2 were imaged, there is only a $7.39{{\ \rm per\ cent}}$ probability they are strongly lensed by spherical deflectors and that the hypothetical lensing galaxy was too faint to be detected. Meanwhile, with the limiting magnitudes of the Hubble Space Telescope (HST) and JWST, the theoretical probability would drop precipitously to 0.058 and $0.0012{{\ \rm per\ cent}}$, respectively. We further find it unlikely that the luminosities of both sources can be accounted for by lensing that produces a single, resolved image with sufficiently high magnification. Alternatively, in the unlikely event that their brightness results from lensing by an elliptical isothermal galaxy, there is a $30.9 {{\ \rm per\ cent}}$ probability that the lensing galaxy is too faint to be observable at the current limiting magnitude. Future HST (JWST) imaging will drop this probability to $0.245 {{\ \rm per\ cent}}$ ($0.0025 {{\ \rm per\ cent}}$). In summary, while deep imaging with HST and JWST is required to discard the lensing hypothesis entirely, it is unlikely that the exceptional luminosity of the two z ∼ 13 sources can be accounted for by gravitational lensing.

Background: It is uncertain if medical masks offer similar protection against COVID-19 compared with N95 respirators. Objective: To determine whether medical masks are noninferior to N95 respirators to prevent COVID-19 in health care workers providing routine care. Design: Multicenter, randomized, noninferiority trial. (ClinicalTrials.gov: NCT04296643). Setting: 29 health care facilities in Canada, Israel, Pakistan, and Egypt from 4 May 2020 to 29 March 2022. Participants: 1009 health care workers who provided direct care to patients with suspected or confirmed COVID-19. Intervention: Use of medical masks versus fit-tested N95 respirators for 10 weeks, plus universal masking, which was the policy implemented at each site. Measurements: The primary outcome was confirmed COVID-19 on reverse transcriptase polymerase chain reaction (RT-PCR) test. Results: In the intention-to-treat analysis, RT-PCR–confirmed COVID-19 occurred in 52 of 497 (10.46%) participants in the medical mask group versus 47 of 507 (9.27%) in the N95 respirator group (hazard ratio [HR], 1.14 [95% CI, 0.77 to 1.69]). An unplanned subgroup analysis by country found that in the medical mask group versus the N95 respirator group RT-PCR–confirmed COVID-19 occurred in 8 of 131 (6.11%) versus 3 of 135 (2.22%) in Canada (HR, 2.83 [CI, 0.75 to 10.72]), 6 of 17 (35.29%) versus 4 of 17 (23.53%) in Israel (HR, 1.54 [CI, 0.43 to 5.49]), 3 of 92 (3.26%) versus 2 of 94 (2.13%) in Pakistan (HR, 1.50 [CI, 0.25 to 8.98]), and 35 of 257 (13.62%) versus 38 of 261 (14.56%) in Egypt (HR, 0.95 [CI, 0.60 to 1.50]). There were 47 (10.8%) adverse events related to the intervention reported in the medical mask group and 59 (13.6%) in the N95 respirator group. Limitation: Potential acquisition of SARS-CoV-2 through household and community exposure, heterogeneity between countries, uncertainty in the estimates of effect, differences in self-reported adherence, differences in baseline antibodies, and between-country differences in circulating variants and vaccination. Conclusion: Among health care workers who provided routine care to patients with COVID-19, the overall estimates rule out a doubling in hazard of RT-PCR–confirmed COVID-19 for medical masks when compared with HRs of RT-PCR–confirmed COVID-19 for N95 respirators. The subgroup results varied by country, and the overall estimates may not be applicable to individual countries because of treatment effect heterogeneity. Primary Funding Source: Canadian Institutes of Health Research, World Health Organization, and Juravinski Research Institute.

Sea salt aerosols play an important role in the radiation budget and atmospheric composition over the Arctic, where the climate is rapidly changing. Previous observational studies have shown that Arctic sea ice leads are an important source of sea salt aerosols, and modeling efforts have also proposed blowing snow sublimation as a source. In this study, size-resolved atmospheric particle number concentrations and chemical composition were measured at the Arctic coastal tundra site of Utqiaġvik, Alaska, during spring (3 April–7 May 2016). Blowing snow conditions were observed during 25 % of the 5-week study period and were overpredicted by a commonly used blowing snow parameterization based solely on wind speed and temperature. Throughout the study, open leads were present locally. During periods when blowing snow was observed, significant increases in the number concentrations of 0.01–0.06 µm particles (factor of 6, on average) and 0.06–0.3 µm particles (67 %, on average) and a significant decrease (82 %, on average) in 1–4 µm particles were observed compared to low wind speed periods. These size distribution changes were likely caused by the generation of ultrafine particles from leads and/or blowing snow, with scavenging of supermicron particles by blowing snow. At elevated wind speeds, both submicron and supermicron sodium and chloride mass concentrations were enhanced, consistent with wind-dependent local sea salt aerosol production. At moderate wind speeds below the threshold for blowing snow as well as during observed blowing snow, individual sea spray aerosol particles were measured. These individual salt particles were enriched in calcium relative to sodium in seawater due to the binding of this divalent cation with organic matter in the sea surface microlayer and subsequent enrichment during seawater bubble bursting. The chemical composition of the surface snowpack also showed contributions from sea spray aerosol deposition. Overall, these results show the contribution of sea spray aerosol production from leads on both aerosols and the surface snowpack. Therefore, if blowing snow sublimation contributed to the observed sea salt aerosol, the snow being sublimated would have been impacted by sea spray aerosol deposition rather than upward brine migration through the snowpack. Sea spray aerosol production from leads is expected to increase, with thinning and fracturing of sea ice in the rapidly warming Arctic.

Influenza increases the risk of cardiovascular events and deaths. We aimed to see whether influenza vaccination reduces death and vascular events in patients with heart failure.We did a pragmatic, randomised, double-blind, placebo-controlled trial in 30 centres (mostly hospitals affliated with universities or a research institute) in ten countries in Asia, the Middle East, and Africa (7 in India, 4 in Philippines, 4 in Nigeria, 6 in China, 1 in Zambia, 2 in Mozambique, 3 in Saudi Arabia, 1 in Kenya, 1 in Uganda, and 1 in Zambia). Participants (aged ≥18 years; 52·1% female; not disaggregated by race or ethnicity) with heart failure (New York Heart Association class II, III, or IV) were randomly assigned (1:1) by a centralised web-based system with block randomisation stratified by site, to receive 0·5 ml intramuscularly once a year for up to 3 years of either inactivated standard dose influenza vaccine or placebo (saline). We excluded people who had received influenza vaccine in 2 of the previous 3 years, and those likely to require valve repair or replacement. Those who administered assigned treatments were not masked and had no further role in the study. Investigators, study coordinators, outcome adjudicators, and participants were masked to group assignment. The first of two co-primary outcomes was a first-event composite for cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke, and the second was a recurrent-events composite for cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and hospitalisation for heart failure. Outcomes were assessed every 6 months in the intention-to-treat population. Secondary outcomes were all-cause death, cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, all-cause hospitalisation, hospitalisation for heart failure, and pneumonia, both overall and during periods of peak influenza exposure. This study is registered with ClinicalTrials.gov, NCT02762851.Between June 2, 2015, and Nov 21, 2021, we enrolled 5129 participants and randomly assigned (1:1) 2560 (50·0%) to influenza vaccine and 2569 (50·0%) to placebo. The first co-primary outcome occurred in 380 (14·8%) of 2560 participants in the vaccine group and 410 (16·0%) of 2569 participants in the placebo group (hazard ratio [HR] 0·93 [95% CI 0·81-1·07]; p=0·30). The second co-primary outcome occurred in 754 (29·5%) of 2560 participants in the vaccine group and 819 (31·9%) of 2569 participants in the placebo group; HR 0·92 [95% CI 0·84-1·02]; p=0·12). The secondary outcomes of all-cause hospitalisations (HR 0·84 [95% CI 0·74-0·97]; p=0·013) and pneumonia (HR 0·58 [0·42-0·80]; p=0·0006) were significantly reduced in the vaccine group compared with in the placebo group but there was no significant difference between groups for all-cause death, cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and hospitalisation for heart failure. In a prespecified analysis, in which events were limited to periods of peak influenza circulation, the first co-primary outcome, and the secondary outcomes of all-cause death, cardiovasular death, and pneumonia were significantly lower in the vaccinated group than in the placebo group, whereas the second co-primary outcome and the secondary outcomes of non-fatal myocardial infarction, non-fatal stroke, all-cause hospitalisation, and hospitalisation for heart failure were not significantly lower.Although the prespecified co-primary outcomes during the entire period of observation were not statistically significant, the reduction during the peak influenza circulating period suggests that there is likely to be a clinical benefit of giving influenza vaccine, given the clear reduction in pneumonia, a moderate reduction in hospitalisations, and a reduction in cardiovascular events and deaths during periods of peak circulation of influenza. Taken in conjunction with previous trials and the observational studies, the collective data suggest benefit.UK Joint Global Health Trials Scheme and Canadian Institutes for Health Research Foundation.

Hematopoietic stem cell transplantation is a well known treatment of hematologic malignancies wherein nascent stem cells provide a regenerating marrow and immunotherapy against the tumor. The progeny of hematopoietic stem cells also populate a wide spectrum of tissues, including the brain, as bone marrow derived macrophages similar to microglial cells. We developed a sensitive and novel combined IHC and XY FISH assay to detect, quantify and characterize donor cells in the cerebral cortex of 19 female allogeneic stem cell transplant patients. We show that the number of male donor cells ranged from 0.14-3.0% of total cells or 1.2-25% of microglial cells. Using tyramide based fluorescent IHC we found at least 80% of the donor cells express the microglial marker Iba1 consistent with being bone marrow derived macrophages. The percentage of donor cells was related to pretransplant conditioning; donor cells from radiation based myeloablative cases averaged 8.1% of microglial cells, while those from non-myeloablative cases averaged only 1.3%. The number of donor cells in patients conditioned with Busulfan or Treosulfan based myeloablation were similar to TBI based conditioning; donor cells averaged 6.8% of microglial cells. Notably, patients who received multiple transplants and those with the longest post-transplant survival had the highest level of donor engraftment, with donor cells averaging 16.3% of microglial cells. Our work represents the largest study characterizing bone marrow-derived macrophages in post-transplant patients. The efficiency of engraftment observed in our study warrants future research on microglial replacement as a therapeutic option for disorders of the central nervous system.Key PointsWe developed a sensitive Iba1 IHC and XY FISH co-stain assay to detect bone marrow derived donor cells in the brain of HSCT patients.Donor cells in the CNS express Iba1 and average 8% of microglia after myeloablative HSCT; double transplants increase engraftment up to 25%.

The risk of a catastrophic or existential disaster for our civilization is increasing this century. A significant motivation for a near-term space settlement is the opportunity to safeguard civilization in the event of a planetary-scale disaster. A catastrophic event could destroy the significant cultural, scientific, and technological progress on Earth. However, early space settlements can preserve records of human activity by maintaining a backup data storage system. The backup can also store information about the events leading up to the disaster. The system would improve the ability of early space settlers to recover our civilization after collapse. We show that advances in laser communications and data storage enable the development of a data storage system on the lunar surface with a sufficient uplink data rate and storage capacity to preserve valuable information about the achievements of our civilization and the chronology of the disaster., 12 pages, 2 figures; accepted for publication in the journal "Signals" (2022)

Background Patients with prostate cancer suffer significant sexual dysfunction after treatment which negatively affects them and their partners psychologically, and strain their relationships. Aim We convened an international panel with the aim of developing guidelines that will inform clinicians, patients and partners about the impact of prostate cancer therapies (PCT) on patients’ and partners’ sexual health, their relationships, and about biopsychosocial rehabilitation in prostate cancer (PC) survivorship. Methods The guidelines panel included international expert researchers and clinicians, and a guideline methodologist. A systematic review of the literature, using the Ovid MEDLINE, Scopus, CINAHL, PsychINFO, LGBT Life, and Embase databases was conducted (1995–2022) according to the Cochrane Handbook for Systematic Reviews of Interventions. Study selection was based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Each statement was assigned an evidence strength (A-C) and a recommendation level (strong, moderate, conditional) based on benefit/risk assessment. Data synthesis included meta-analyses of studies deemed of sufficient quality (3), using A Measurement Tool to Assess Systematic Reviews (AMSTAR). Outcomes Guidelines for sexual health care for patients with prostate cancer were developed, based on available evidence and the expertise of the international panel. Results The guidelines account for patients’ cultural, ethnic, and racial diversity. They attend to the unique needs of individuals with diverse sexual orientations and gender identities. The guidelines are based on literature review, a theoretical model of sexual recovery after PCT, and 6 principles that promote clinician-initiated discussion of realistic expectations of sexual outcomes and mitigation of sexual side-effects through biopsychosocial rehabilitation. Forty-seven statements address the psychosexual, relationship, and functional domains in addition to statements on lifestyle modification, assessment, provider education, and systemic challenges to providing sexual health care in PC survivorship. Clinical Implications The guidelines provide clinicians with a comprehensive approach to sexual health care for patients with prostate cancer. Strengths & Limitations The strength of the study is the comprehensive evaluation of existing evidence on sexual dysfunction and rehabilitation in prostate cancer that can, along with available expert knowledge, best undergird clinical practice. Limitation is the variation in the evidence supporting interventions and the lack of research on issues facing patients with prostate cancer in low and middle-income countries. Conclusion The guidelines document the distressing sexual sequelae of PCT, provide evidence-based recommendations for sexual rehabilitation and outline areas for future research.

Satellite observations from Clouds and the Earth’s Radiant Energy System (CERES) radiometers have produced over two decades of world-class data documenting time–space variations in Earth’s top-of-atmosphere (TOA) radiation budget. In addition to energy exchanges among Earth and space, climate studies require accurate information on radiant energy exchanges at the surface and within the atmosphere. The CERES Cloud Radiative Swath (CRS) data product extends the standard Single Scanner Footprint (SSF) data product by calculating a suite of radiative fluxes from the surface to TOA at the instantaneous CERES footprint scale using the NASA Langley Fu–Liou radiative transfer model. Here, we describe the CRS flux algorithm and evaluate its performance against a network of ground-based measurements and CERES TOA observations. CRS all-sky downwelling broadband fluxes show significant improvements in surface validation statistics relative to the parameterized fluxes on the SSF product, including a ∼30%–40% (∼20%) reduction in SW↓ (LW↓) root-mean-square error (RMSΔ), improved correlation coefficients, and the lowest SW↓ bias over most surface types. RMSΔ and correlation statistics improve over five different surface types under both overcast and clear-sky conditions. The global mean computed TOA outgoing LW radiation (OLR) remains within −2) of CERES observations, while the global mean reflected SW radiation (RSW) is excessive by ∼3.5% (∼9 W m−2) owing to cloudy-sky computation errors. As we highlight using data from two remote field campaigns, the CRS data product provides many benefits for studies requiring advanced surface radiative fluxes.

This study examined development of emotional support competence within close friendships across adolescence. A sample of 184 adolescents (53% girls, 47% boys; 58% White, 29% Black, 14% other identity groups) participated in seven waves of multimethod assessments with their best friends and romantic partners from age 13 to 24. Latent change score models identified coupled predictions over time from emotional support competence to increasing friendship quality and decreasing support received from friends. Friend-rated emotional support competence in adolescence predicted supportiveness in adult romantic relationships, over and above supportiveness in adolescent romantic relationships. Teen friendships may set the stage for developing emotional support capacities that progress across time and relationships into adulthood.

Zika virus (ZIKV) infections occurred in epidemic form in the Americas in 2014–2016, with some of the earliest isolates in the region coming from Haiti. We isolated ZIKV from 20 children with acute undifferentiated febrile illness who were part of a cohort of children seen at a school clinic in the Gressier region of Haiti. The virus was also isolated from three pools of Aedes aegypti mosquitoes collected at the same location. On phylogenetic analysis, three distinct ZIKV clades were identified. Strains from all three clades were present in Haiti in 2014, making them among the earliest isolates identified in the Western Hemisphere. Strains from all three clades were also isolated in 2016, indicative of their persistence across the time period of the epidemic. Mosquito isolates were collected in 2016 and included representatives from two of the three clades; in one instance, ZIKV was isolated from a pool of male mosquitoes, suggestive of vertical transmission of the virus. The identification of multiple ZIKV clades in Haiti at the beginning of the epidemic suggests that Haiti served as a nidus for transmission within the Caribbean.

Staphylococcus aureus bacteremia (SAB) is a common infection worldwide. We compared SAB mortality in low- and middle-income countries (LMIC) versus high-income countries (HIC) in a meta-analysis.We searched MEDLINE, Embase, and Cochrane Database of Systematic Reviews from 1991-2021 and included observational, single-country studies on patients with positive blood cultures for S. aureus. The main outcome was the proportion of patients with SAB who died in the hospital. A generalized linear mixed random-effects model was used to pool estimates, and a meta-regression was used to adjust for study-level characteristics.A total of 332 studies involving 517,671 patients in 39 countries were included. No study was conducted in a low-income country. Only 33 (10%) studies were performed in middle-income countries (MIC), which described 6,216 patients. The pooled in-hospital mortality was 32.4% (95% confidence interval [CI] 27.2%-38.2%, TIn SAB studies, LMIC are poorly represented. In-hospital mortality was significantly higher in MIC than in HIC. Research should be conducted in LMIC to characterize differences in care processes driving the mortality gap.

Humans can produce "express" (∼100 ms) arm muscle responses that are inflexibly locked in time and space to visual target presentations, consistent with subcortical visuomotor transformations via the tecto-reticulo-spinal pathway. These express visuomotor responses are sensitive to explicit cue-driven expectations, but it is unclear at what stage of sensory-to-motor transformation such modulation occurs. Here, we recorded electromyographic activity from shoulder muscles as participants reached toward one of four virtual targets whose physical location was partially predictable from a symbolic cue. In an experiment in which targets could be veridically reached, express responses were inclusive of the biomechanical requirements for reaching the cued locations and not systematically modulated by cue validity. In a second experiment, movements were restricted to the horizontal plane so that the participants could perform only rightward or leftward reaches, irrespective of target position on the vertical axis. Express muscle responses were almost identical for targets that were validly cued in the horizontal direction, regardless of cue validity in the vertical dimension. Together, these findings suggest that the cue-induced enhancements of express responses are dominated by effects at the level of motor plans and not solely via facilitation of early visuospatial target processing. Notably, direct corticotectal and corticoreticular projections exist that are well-placed to modulate prestimulus motor preparation state in subcortical circuits. Our results could reflect a neural mechanism by which contextually relevant motor responses to compatible visual inputs are rapidly released via subcortical circuits that are sufficiently along the sensory-to-motor continuum.

The use of social media continues to increase in health care and academia. Health care practice, particularly the oncologic field, is constantly changing because of new knowledge, evidence-based research, clinical trials, and government policies. Therefore, oncology trainees and professionals continue to strive to stay up-to-date with practice guidelines, research, and skills. Although social media as an educational and professional development tool is no longer completely new to medicine and has been embraced, it is still under-researched in terms of various outcomes. Social media plays several key roles in professional development and academic advancement. We reviewed the literature to evaluate how social media can be used for professional development and academic promotion of oncology professionals.

Effects of cloud diurnal cycle on top-of-atmosphere (TOA) and surface regional monthly mean irradiances, climatological mean, and anomalies are analyzed using CERES derived TOA irradiances and surface irradiances computed with MODIS derived cloud properties. Cloud properties derived from Terra and Aqua MODIS are sufficient to capture cloud diurnal cycle to compute regional monthly mean surface irradiances. While missing cloud diurnal cycle leads to a biased TOA and surface regional irradiances for regions with a strong cloud diurnal cycle, monthly regional TOA and surface anomalies derived from one sun-synchronous orbit agrees well with those derived from two sun-synchronous orbits. Based on these results, the algorithm to produce Edition 4.2 CERES EBAF product is developed. Regional TOA and surface climatological means derived from one sun-synchronous orbit are adjusted to match corresponding climatological means derived from Terra+Aqua observations. This climatological adjustment approach is used to merge the Terra only period to the Terra+Aqua period and to extend the Terra and Aqua record by merging NOAA20 observations. Two additional differences of Edition 4.2 EBAF algorithm to compute surface irradiances compared to the earlier version are: 1) no geostationary satellite derived cloud properties are used and 2) temperature and humidity from MERRA-2 instead of GEOIS-5.4.1 are used. Once surface monthly regional mean irradiances are compared with surface observations, the agreement is equivalent to the agreement with the earlier version. However, because surface irradiances are not affected by geostationary satellite artifacts, regional surface irradiance anomaly time series is significantly improved, especially for longwave irradiances., The 28th IUGG General Assembly (IUGG2023) (Berlin 2023)

We study the recent Physical Review Letter [1] which presents a new mechanism for black hole evaporation through a spatially dependent temperature. This new temperature is comparable to the Hawking result near the black hole, but is very small far away, and therefore could be a small correction. Here we apply the proposed reasoning to the case of de Sitter space, finding that it over predicts the de Sitter temperature of a minimally coupled scalar by factor of $\approx 4.3$ and therefore cannot be ignored in any limit. This indicates an inconsistency in the proposed formalism., 2 pages, 1 figure, in double column format

This thesis explores the genetic architecture of malting quality within the Virginia Tech barley breeding program, and discusses implications for imposing selection on complex traits that are difficult to phenotype. Malting quality measures are destructive, and can not be performed before selection must be made for advancement of breeding lines in winter barley. A growing body of evidence suggests that malt quality is influenced by malting regime, growing environment, line genotype, and the interactions between them. We aim to better understand the genetic effect on malt quality in two manners: first, as it relates to the genetic architecture regulating malt quality parameters, and second the relationship between genetic growth patterns to end-use malting traits. This study included two years of breeding trial data of two and six-row winter malt barley across two locations. Results of a genome-wide association scan and genomic prediction of malt quality traits indicated that they are largely quantitative traits with complex inheritance. Previous studies have identified quantitative trait loci and genes regulating malt quality traits in markedly different germplasm. Heritability of traits ranged from 0.27 to 0.72, while mean predictive abilities ranged from 0.45 to 0.74. Thus, selection on genomic estimated breeding values (gEBVs) should perform similarly to selection on single phenotypic observations of quality, but can be done within the same season. This indicates that genomic selection may be a viable method to accelerate genetic improvement of malting quality traits. The use of gEBVs requires that lines be genotyped with genome-wide markers, somewhat limiting the number of candidate individuals. Selection on growth and development traits genetically correlated with quality measures could allow for selection among a much greater number of candidates if high-throughput phenotypes can be collected on many ungenotyped indivduals. Growth and development was quantified by the near-infrared vegetation index (NDVI) extracted from aerial images captured from multiple time points throughout the growing season. Estimates of genetic correlation identified time points throughout the season when quality traits are related to growth and development. We demonstrated that aerial imagery can discern growth patterns in barley and suggest ways it can be incorporated into the breeding pipeline. Master of Science Malt barley (Hordeum vulgare) is the preferred source of fermentable sugar used to brew beer. Currently, the majority of malt barley used in the United States is grown in the upper mid-west or imported from Europe. The east coast could become a producing region if high quality, disease resistant varieties were available to growers. The Virginia Tech small grains breeding program began breeding locally adapted malt barley in 2010. This project aims to improve the breeding process by incorporating information from genomic sequencing, malt quality and aerial imagery. Malt barley differs from that used for animal feed or human food because specific quantities of starches, proteins, and enzymes are necessary in the brewing process. The quantity of these molecules are determined through lab analysis and determine the grain's suitability for particular brewing styles. This analysis is timeconsuming and costly because it involves a three-step process of malting the grain, brewing with the malt, and analyzing the wort. The wort is the liquid sugar solution which is produced by heating the malt with water to a high temperature in a process called 'mashing'. Lab quality analysis for the thousands of lines evaluated in a breeding program in any given year is unfeasible. However, by understanding the genetic regulation of malt quality traits, breeders can employ techniques like genomic selection to improve these traits in a shorter amount of time. Additionally, this work identifies relationships between growth and quality. The grain is the result of the plant's growth throughout the entirety of the season. Measuring growth repeatedly through time was previously difficult until the advent of aerial imagery. Images captured from drones have been used to quantify growth in a variety of plants, but is not extensively done in malt barley. Relating growth to quality will help breeders understand genetic patterns of growth and development which may be advantageous in the production of high quality malt barley.

We consider a cross-silo federated learning (FL) setting where a machine learning model with a fully connected first layer is trained between different clients and a central server using FedAvg, and where the aggregation step can be performed with secure aggregation (SA). We present SRATTA an attack relying only on aggregated models which, under realistic assumptions, (i) recovers data samples from the different clients, and (ii) groups data samples coming from the same client together. While sample recovery has already been explored in an FL setting, the ability to group samples per client, despite the use of SA, is novel. This poses a significant unforeseen security threat to FL and effectively breaks SA. We show that SRATTA is both theoretically grounded and can be used in practice on realistic models and datasets. We also propose counter-measures, and claim that clients should play an active role to guarantee their privacy during training., Accepted to ICML2023