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Abstract Lung cancer remains the leading cause of cancer mortality, despite declining smoking rates. Previous lung cancer GWAS have identified numerous loci, but separating the genetic risks of lung cancer and smoking behavioral susceptibility remains challenging. Here, we perform multi-ancestry GWAS meta-analyses of lung cancer using the Million Veteran Program cohort (approximately 95% male cases) and a previous study of European-ancestry individuals, jointly comprising 42,102 cases and 181,270 controls, followed by replication in an independent cohort of 19,404 cases and 17,378 controls. We then carry out conditional meta-analyses on cigarettes per day and identify two novel, replicated loci, including the 19p13.11 pleiotropic cancer locus in squamous cell lung carcinoma. Overall, we report twelve novel risk loci for overall lung cancer, lung adenocarcinoma, and squamous cell lung carcinoma, nine of which are externally replicated. Finally, we perform PheWAS on polygenic risk scores for lung cancer, with and without conditioning on smoking. The unconditioned lung cancer polygenic risk score is associated with smoking status in controls, illustrating a reduced predictive utility in non-smokers. Additionally, our polygenic risk score demonstrates smoking-independent pleiotropy of lung cancer risk across neoplasms and metabolic traits.

Abstract Roaming is an unconventional type of molecular reaction where fragments, instead of immediately dissociating, remain weakly bound due to long-range Coulombic interactions. Due to its prevalence and ability to form new molecular compounds, roaming is fundamental to photochemical reactions in small molecules. However, the neutral character of the roaming fragment and its indeterminate trajectory make it difficult to identify experimentally. Here, we introduce an approach to image roaming, utilizing intense, femtosecond IR radiation combined with Coulomb explosion imaging to directly reconstruct the momentum vector of the neutral roaming H2, a precursor to $${{{{{{{{\rm{H}}}}}}}}_{3}}^{+}$$ H 3 + formation, in acetonitrile, CH3CN. This technique provides a kinematically complete picture of the underlying molecular dynamics and yields an unambiguous experimental signature of roaming. We corroborate these findings with quantum chemistry calculations, resolving this unique dissociative process.

Abstract Lassa virus (LASV) infection is expanding outside its traditionally endemic areas in West Africa, posing a pandemic biothreat. LASV-neutralizing antibodies, moreover, have proven difficult to elicit. To gain insight into LASV neutralization, here we develop a prefusion-stabilized LASV glycoprotein trimer (GPC), pan it against phage libraries comprising single-domain antibodies (nanobodies) from shark and camel, and identify one, D5, which neutralizes LASV. Cryo-EM analyses reveal D5 to recognize a cleavage-dependent site-of-vulnerability at the trimer apex. The recognized site appears specific to GPC intermediates, with protomers lacking full cleavage between GP1 and GP2 subunits. Guinea pig immunizations with the prefusion-stabilized cleavage-intermediate LASV GPC, first as trimer and then as a nanoparticle, induce neutralizing responses, targeting multiple epitopes including that of D5; we identify a neutralizing antibody (GP23) from the immunized guinea pigs. Collectively, our findings define a prefusion-stabilized GPC trimer, reveal an apex-situated site-of-vulnerability, and demonstrate elicitation of LASV-neutralizing responses by a cleavage-intermediate LASV trimer.

Abstract Fusion oncoproteins (FOs) arise from chromosomal translocations in ~17% of cancers and are often oncogenic drivers. Although some FOs can promote oncogenesis by undergoing liquid-liquid phase separation (LLPS) to form aberrant biomolecular condensates, the generality of this phenomenon is unknown. We explored this question by testing 166 FOs in HeLa cells and found that 58% formed condensates. The condensate-forming FOs displayed physicochemical features distinct from those of condensate-negative FOs and segregated into distinct feature-based groups that aligned with their sub-cellular localization and biological function. Using Machine Learning, we developed a predictor of FO condensation behavior, and discovered that 67% of ~3000 additional FOs likely form condensates, with 35% of those predicted to function by altering gene expression. 47% of the predicted condensate-negative FOs were associated with cell signaling functions, suggesting a functional dichotomy between condensate-positive and -negative FOs. Our Datasets and reagents are rich resources to interrogate FO condensation in the future.

Abstract Coronaviruses have been the causative agent of three epidemics and pandemics in the past two decades, including the ongoing COVID-19 pandemic. A broadly-neutralizing coronavirus therapeutic is desirable not only to prevent and treat COVID-19, but also to provide protection for high-risk populations against future emergent coronaviruses. As all coronaviruses use spike proteins on the viral surface to enter the host cells, and these spike proteins share sequence and structural homology, we set out to discover cross-reactive biologic agents targeting the spike protein to block viral entry. Through llama immunization campaigns, we have identified single domain antibodies (VHHs) that are cross-reactive against multiple emergent coronaviruses (SARS-CoV, SARS-CoV-2, and MERS). Importantly, a number of these antibodies show sub-nanomolar potency towards all SARS-like viruses including emergent CoV-2 variants. We identified nine distinct epitopes on the spike protein targeted by these VHHs. Further, by engineering VHHs targeting distinct, conserved epitopes into multi-valent formats, we significantly enhanced their neutralization potencies compared to the corresponding VHH cocktails. We believe this approach is ideally suited to address both emerging SARS-CoV-2 variants during the current pandemic as well as potential future pandemics caused by SARS-like coronaviruses.

Abstract Young people experiencing mental health conditions are vulnerable to poorer educational outcomes for many reasons, including: social exclusion, stigma, and limited in-school support. Using a near-complete New Zealand population administrative database, this prospective cohort study aimed to quantify differences in educational attainment (at ages 15–16 years) and school suspensions (over ages 13–16 years), between those with and without a prior mental health condition. The data included five student cohorts, each starting secondary school from 2013 to 2017 respectively (N = 272,901). Both internalising and externalising mental health conditions were examined. Overall, 6.8% had a mental health condition. Using adjusted modified Poisson regression analyses, those with prior mental health conditions exhibited lower rates of attainment (IRR 0.87, 95% CI 0.86–0.88) and higher rates of school suspensions (IRR 1.63, 95% CI 1.57–1.70) by age 15–16 years. Associations were stronger among those exhibiting behavioural conditions, compared to emotional conditions, in line with previous literature. These findings highlight the importance of support for young people experiencing mental health conditions at this crucial juncture in their educational pathway. While mental health conditions increase the likelihood of poorer educational outcomes, deleterious outcomes were not a necessary sequalae. In this study, most participants with mental health conditions had successful educational outcomes.

BackgroundChildhood and adolescent obesity are major, preventable public health concerns. Studies to date are inconclusive regarding an association between caesarean section (CS) delivery and offspring obesity, with fewer studies conducted in late adolescence. This study examined the association between CS delivery, with a specific focus on planned CS, and induction of labour and adolescent body mass index (BMI) and body fat percentage (BF%) at age 17 years.MethodsData on 8,880 mother-child pairs from the United Kingdom Millennium Cohort Study were analysed. The exposures were mode of delivery (normal vaginal delivery (VD) (reference), assisted VD, planned CS and emergency CS) and mode of delivery by induction of labour status. Crude and adjusted binary logistic regression and linear regression models were fitted examining BMI and BF% at age 17 years respectively, adjusting for several potential confounders.ResultsAdolescents born by CS did not have an elevated BMI or BF% compared to those born by normal VD. The fully adjusted results for overweight and obesity in children born by planned CS, compared to VD, were 1.05 (95% CI: 0.86-1.28) and 0.94 (95% CI: 0.72-1.23), respectively. The results were similar for the associations between CS and BF%, and between induction of labour and BMI.ConclusionOverall, this large longitudinal study did not support an association between CS or induction of labour and overweight, obesity or BF%. It is possible that previously reported associations are due to residual or unmeasured confounding and/or underlying indications for CS delivery.

In recent years, concern has grown about the inappropriate application and interpretation of P values, especially the use of P

Viral encephalitis is a rare, yet severe neurological disorder. It poses a significant public health threat due to its high morbidity and mortality. Despite the disproportionate burden of the disease in impoverished African countries, the true extent of the problem remains elusive due to the scarcity of accurate diagnostic methods. The absence of timely and effective diagnostic tools, particularly Real-time Polymerase Chain Reaction, has led to misguided treatment, and an underestimation of the disease burden in Ghana. We conducted a prospective cross-sectional study to determine the viral aetiologies of encephalitis among patients presenting to a major referral hospital in Ghana from May 2019 and August 2022. The study aimed at providing a comprehensive information on the clinical epidemiology, and outcomes of viral encephalitis in Ghana. Clinical samples were collected from patients presenting with signs and symptoms of encephalitis and tested for viral agents using real-time polymerase chain reaction. We assessed the clinical epidemiology, risk factors and outcome of individuals using descriptive and logistic regression analysis. Seventy-seven (77) patients were enrolled unto the study. The participants frequently presented with fever (85.7%), seizures (80.5%), lethargy (64.9%) and headache (50.6%). Viruses were detected in 40.3% of the study participants in either cerebrospinal fluid, rectal or oral swab samples. The most frequently detected viruses were cytomegalovirus (48.4%), enteroviruses (38.7%) and HSV (29.0%). Twenty-one (27.3%) of the patients died while on hospital admission. Gender (OR = 5.70 (1.536-1.172), p = 0.01), and negative polymerase chain reaction test results were identified as significant factors associated with death. Antiviral treatment increased the chance of survival of viral encephalitis patients by 21.8%. Our results validate the crucial role of molecular tools as essential for the rapid diagnosis of viral encephalitis, enabling effective treatment and improved patient outcomes. This study contributes valuable epidemiological and clinical insight into viral encephalitis in Ghana.

There is a lack of standardisation in slide microscopy imaging data. Here the authors report Slim, an open-source, web-based slide microscopy viewer implementing the Digital Imaging and Communications in Medicine (DICOM) standard to achieve interoperability with a range of existing medical imaging systems.

IntroductionSeagrass meadows are among the most valuable ecosystems, providing numerous ecosystem services and functions. Despite its importance, there is a lack of knowledge about soil’s biogeochemical process variability, which can control microbiological communities. Thus, this study aimed to evaluate whether seagrass meadows in different geo-environments exhibit varying Fe and sulfate reduction intensities, shaping distinct archaea and bacteria communities.MethodsSoil samples were collected in seagrass meadows under contrasting climatic, geological, vegetational and hydrological settings along the Brazilian coast (e.g., Semiarid Coast - SC, Southeastern Granitic Coast – GC, and Southern Quaternary Coast - QC). The soils were characterized by particle size, pH, redox potential (Eh), total organic C and total N content, acid-volatile sulfides (AVS), and simultaneously extracted Fe. Furthermore, a solid-phase Fe fractionation was performed to characterize the decomposition pathways in these soils, and the shifts in the microbial community along this spatial variation were analyzed using denaturing gradient gel electrophoresis.ResultsThe studied soils presented a sandy texture (values ranging from 74 ± 11.8 to 80.5 ± 6.4%) caused by energetic hydrodynamic conditions. The pH values were circumneutral, while redox conditions presented significant distinction among the studied sites, ranging from anoxic to oxic (values ranging from -63 to +334 mV). The degree of pyritization (DOP) ranged from< 10% to values higher than 80%, highly influenced by rhizospheric oxidation, and higher AVS content was recorded for sites with lower DOP (i.e., GC and QC).DiscussionsThus, biogeochemical processes in the seagrass soils present a wide variation in response to the geo-environmental settings. Plants influence the soil’s geochemical and microbiological communities, retaining fine particles, promoting rhizosphere oxidation, and inducing anoxic conditions controlling the Fe and S forms. Moreover, the same plant species can result in distinct soil conditions and microbial communities due to geoenvironmental settings.

Seafloor pockmarks are abundant around Aotearoa New Zealand, occurring across a diverse range of tectonic, sedimentological and geomorphological settings. Globally, the formation and source of pockmarks is widely researched because they: 1) have potential links to subsurface hydrocarbon systems, 2) can provide important habitats for benthic organisms and 3) may be indications of fluid escape pathways or areas of sediment disturbance, which influence seafloor stability and could pose a risk to infrastructure. Pockmarks are widely associated with fluid release (such as gas or water) from subsurface reservoirs. However, the formation of pockmarks, the processes that shape and modify their morphology over time, and the relative timing of these events, remains enigmatic. Here, we compile the first national database of over 30,000 pockmarks around Aotearoa New Zealand, allowing us to begin to comprehend the dynamic processes that shape and affect pockmarks by exploring regional and inter-regional patterns in pockmark geometry and seabed characteristics. This compilation reveals several significant trends, including a distinct lack of correlation between active seafloor seeps and pockmarks, and a strong association of pockmarks with mud-rich seafloor substrate. Furthermore, we highlight key knowledge gaps that require further investigation moving forward, including a lack of constraint on the timing of pockmark formation, and limited modelling of the processes involved in their formation.

Abstract Microbially-induced calcium carbonate precipitation (MICP) is a bio-cementation process that can improve the engineering properties of granular soils through the precipitation of calcium carbonate (CaCO3) minerals on soil particle surfaces and contacts. The technology has advanced rapidly as an environmentally conscious soil improvement method, however, our understanding of the effect of changes in field-representative environmental conditions on the physical and chemical properties of resulting precipitates has remained limited. An improved understanding of the effect of subsurface geochemical and soil conditions on process reaction kinetics and the morphology and mineralogy of bio-cementation may be critical towards enabling successful field-scale deployment of the technology and improving our understanding of the long-term chemical permanence of bio-cemented soils in different environments. In this study, thirty-five batch experiments were performed to specifically investigate the influence of seawater ions and varying soil materials on the mineralogy, morphology, and reaction kinetics of ureolytic bio-cementation. During experiments, differences in reaction kinetics were quantified to identify conditions inhibiting CaCO3 precipitation and ureolysis. Following experiments, scanning electron microscopy, x-ray diffraction, and chemical composition analyses were employed to quantify differences in mineralogical compositions and material morphology. Ions present in seawater and variations in soil materials were shown to significantly influence ureolytic activity and precipitate mineralogy and morphology, however, calcite remained the predominant CaCO3 polymorph in all experiments with relative percentages exceeding 80% by mass in all precipitates.

Summary: The COVID-19 pandemic continues to be a health crisis with major unmet medical needs. The early responses from airway epithelial cells, the first target of the virus regulating the progression toward severe disease, are not fully understood. Primary human air-liquid interface cultures representing the broncho-alveolar epithelia were used to study the kinetics and dynamics of SARS-CoV-2 variants infection. The infection measured by nucleoprotein expression, was a late event appearing between day 4–6 post infection for Wuhan-like virus. Other variants demonstrated increasingly accelerated timelines of infection. All variants triggered similar transcriptional signatures, an “early” inflammatory/immune signature preceding a “late” type I/III IFN, but differences in the quality and kinetics were found, consistent with the timing of nucleoprotein expression. Response to virus was spatially organized: CSF3 expression in basal cells and CCL20 in apical cells. Thus, SARS-CoV-2 virus triggers specific responses modulated over time to engage different arms of immune response.

ObjectiveThere is widespread agreement about the key role of hemoglobin for oxygen transport. Both observational and interventional studies have examined the relationship between hemoglobin levels and maximal oxygen uptake ([Formula: see text]) in humans. However, there exists considerable variability in the scientific literature regarding the potential relationship between hemoglobin and [Formula: see text]. Thus, we aimed to provide a comprehensive analysis of the diverse literature and examine the relationship between hemoglobin levels (hemoglobin concentration and mass) and [Formula: see text] (absolute and relative [Formula: see text]) among both observational and interventional studies.MethodsA systematic search was performed on December 6th, 2021. The study procedures and reporting of findings followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Article selection and data abstraction were performed in duplicate by two independent reviewers. Primary outcomes were hemoglobin levels and [Formula: see text] values (absolute and relative). For observational studies, meta-regression models were performed to examine the relationship between hemoglobin levels and [Formula: see text] values. For interventional studies, meta-analysis models were performed to determine the change in [Formula: see text] values (standard paired difference) associated with interventions designed to modify hemoglobin levels or [Formula: see text]. Meta-regression models were then performed to determine the relationship between a change in hemoglobin levels and the change in [Formula: see text] values.ResultsData from 384 studies (226 observational studies and 158 interventional studies) were examined. For observational data, there was a positive association between absolute [Formula: see text] and hemoglobin levels (hemoglobin concentration, hemoglobin mass, and hematocrit (PConclusionThese findings suggest that [Formula: see text] values are closely associated with hemoglobin levels among both observational and interventional studies. Although our findings suggest a lack of sex differences in these relationships, there were limited studies incorporating females or stratifying results by biological sex.

We present allele frequencies of pharmacogenomics relevant variants across multiple ancestry in a sample representative of the US population. We analyzed 658,582 individuals with genotype data and extracted pharmacogenomics relevant single nucleotide variant (SNV) alleles, human leukocyte antigens (HLA) 4-digit alleles and an important copy number variant (CNV), the full deletion/duplication of CYP2D6. We compiled distinct allele frequency tables for European, African American, Hispanic, and Asian ancestry individuals. In addition, we compiled allele frequencies based on local ancestry reconstruction in the African-American (2-way deconvolution) and Hispanic (3-way deconvolution) cohorts.

There have been over 621 million cases of COVID-19 worldwide with over 6.5 million deaths. Despite the high secondary attack rate of COVID-19 in shared households, some exposed individuals do not contract the virus. In addition, little is known about whether the occurrence of COVID-19 resistance differs among people by health characteristics as stored in the electronic health records (EHR). In this retrospective analysis, we develop a statistical model to predict COVID-19 resistance in 8,536 individuals with prior COVID-19 exposure using demographics, diagnostic codes, outpatient medication orders, and count of Elixhauser comorbidities in EHR data from the COVID-19 Precision Medicine Platform Registry. Cluster analyses identified 5 patterns of diagnostic codes that distinguished resistant from non-resistant patients in our study population. In addition, our models showed modest performance in predicting COVID-19 resistance (best performing model AUROC = 0.61). Monte Carlo simulations conducted indicated that the AUROC results are statistically significant (p < 0.001) for the testing set. We hope to validate the features found to be associated with resistance/non-resistance through more advanced association studies.

BackgroundGender discrimination among women healthcare workers (HCWs) negatively impacts job satisfaction, mental health, and career development; however, few studies have explored how experiences of gender discrimination change during times of health system strain. Thus, we conducted a survey study to characterize gender discrimination during a time of significant health system strain, i.e., the COVID-19 pandemic.MethodsWe used a convenience sampling approach by inviting department chairs of academic medical centers in the United States to forward our online survey to their staff in January 2021. The survey included one item assessing frequency of gender discrimination, and an open-ended question asking respondents to detail experiences of discrimination. The survey also included questions about social and work stressors, such as needing additional childcare support. We used ordinal logistic regression models to identify predictors of gender discrimination, and grounded theory to characterize themes that emerged from open-ended responses.ResultsAmong our sample of 716 women (mean age = 37.63 years, SD = 10.97), 521 (72.80%) were White, 102 (14.20%) Asian, 69 (9.60%) Black, 53 (7.4%) Latina, and 11 (1.50%) identified as another race. In an adjusted model that included demographic characteristics and social and work stressors as covariates, significant predictors of higher gender discrimination included younger age (OR = 0.98, 95%CI = 0.96, 0.99); greater support needs (OR = 1.26, 95%CI = 1.09,1.47); lower team cohesion (OR = 0.94, 95%CI = 0.91, 0.97); greater racial discrimination (OR = 1.07, 95%CI = 1.05,1.09); identifying as a physician (OR = 6.59, 95%CI = 3.95, 11.01), physician-in-training (i.e., residents and fellows; OR = 3.85, 95%CI = 2.27,6.52), or non-clinical worker (e.g., administrative assistants; OR = 3.08, 95%CI = 1.60,5.90), compared with nurses; and reporting the need for a lot more childcare support (OR = 1.84, 95%CI = 1.15, 2.97), compared with reporting no childcare support need. In their open-ended responses, women HCWs described seven themes: 1) belittlement by colleagues, 2) gendered workload distributions, 3) unequal opportunities for professional advancement, 4) expectations for communication, 5) objectification, 6) expectations of motherhood, and 7) mistreatment by patients.ConclusionsOur study underscores the severity of gender discrimination among women HCWs. Hospital systems should prioritize gender equity programs that improve workplace climate during and outside of times of health system strain.

Macrophages are a highly adaptive population of innate immune cells. Polarization with IFNγ and LPS into the ‘classically activated’ M1 macrophage enhances pro-inflammatory and microbicidal responses, important for eradicating bacteria such as Mycobacterium tuberculosis. By contrast, ‘alternatively activated’ M2 macrophages, polarized with IL-4, oppose bactericidal mechanisms and allow mycobacterial growth. These activation states are accompanied by distinct metabolic profiles, where M1 macrophages favor near exclusive use of glycolysis, whereas M2 macrophages up-regulate oxidative phosphorylation (OXPHOS). Here, we demonstrate that activation with IL-4 and IL-13 counterintuitively induces protective innate memory against mycobacterial challenge. In human and murine models, prior activation with IL-4/13 enhances pro-inflammatory cytokine secretion in response to a secondary stimulation with mycobacterial ligands. In our murine model, enhanced killing capacity is also demonstrated. Despite this switch in phenotype, IL-4/13 trained murine macrophages do not demonstrate M1-typical metabolism, instead retaining heightened use of OXPHOS. Moreover, inhibition of OXPHOS with oligomycin, 2-deoxy glucose or BPTES all impeded heightened pro-inflammatory cytokine responses from IL-4/13 trained macrophages. Lastly, this work identifies that IL-10 attenuates protective IL-4/13 training, impeding pro-inflammatory and bactericidal mechanisms. In summary, this work provides new and unexpected insight into alternative macrophage activation states in the context of mycobacterial infection.

BackgroundThe declaration of COVID-19 as a pandemic on March 11 2020, by the World Health Organisation prompted the need for a sustained and a rapid international response. In a swift response, the Government of Ghana, in partnership with Zipline company, launched the use of Unmanned Automated Vehicles (UAV) to transport suspected samples from selected districts to two foremost testing centres in the country. Here, we present the experiences of employing this technology and its impact on the transport time to the second largest testing centre, the Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR) in Kumasi, Ghana.MethodsSwab samples collected from suspected COVID-19 patients were transported to the Zipline office by health workers. Information on the samples were sent to laboratory personnel located at KCCR through a WhatsApp platform to get them ready to receive the suspected COVID-19 samples while Zipline repackaged samples and transported them via drone. Time of take-off was reported as well as time of drop-off.ResultsA total of 2537 COVID-19 suspected samples were received via drone transport from 10 districts between April 2020 to June 2021 in 440 deliveries. Ejura-Sekyedumase District Health Directorate delivered the highest number of samples (765; 30%). The farthest district to use the drone was Pru East, located 270 km away from KCCR in Kumasi and 173 km to the Zipline office in Mampong. Here, significantly, it took on the average 39 minutes for drones to deliver samples compared to 117 minutes spent in transporting samples by road (pConclusionThe use of drones for sample transport during the COVID-19 pandemic significantly reduced the travel time taken for samples to be transported by road to the testing site. This has enhanced innovative measures to fight the pandemic using technology.

The restoration of the once abundant Cisco (Coregonus artedi) is a management interest across the Laurentian Great Lakes. To inform the restoration, we (1) described historical distributions of Cisco and (2) explored whether non-indigenous Rainbow Smelt (Osmerus mordax) and Alewife (Alosa pseudoharengus) played a role in the decline of Cisco populations across the upper Great Lakes (i.e., Lakes Superior, Michigan, and Huron). Our source data were collected from fishery-independent surveys conducted by the U.S. Fish and Wildlife Service's research vessel R/V Cisco in 1952-1962. By analyzing data collected by gill-net surveys, we confirmed the importance of embayment and shallow-water habitats to Cisco. We found that Cisco was abundant in Whitefish Bay and Keweenaw Bay, Lake Superior, and in Green Bay, Lake Michigan, but we also found a sign of Cisco extirpation in Saginaw Bay, Lake Huron. Our results also showed that Ciscoes generally stayed in waters 150 m in bottom depth) in summer and fall in Lake Michigan, although we cannot exclude the possibility that these Ciscoes had hybridized with the other Coregonus species. By comparing complementary data collected from bottom-trawl surveys, we concluded that the spatiotemporal overlap between Rainbow Smelt and Cisco likely occurred across the upper Great Lakes throughout 1952-1962. These data were consistent with the hypothesis that Rainbow Smelt played a role in the decline of Cisco populations across the upper Great Lakes in the period. We also found that the spatiotemporal overlap between Alewife and Cisco likely occurred only in Saginaw Bay in fall 1956 and in Lake Michigan after 1960. Thus, any potential recovery of Cisco after the 1950s could have been inhibited by Alewife in Lakes Michigan and Huron.

BackgroundNeutralizing monoclonal antibody (mAb) treatment for COVID-19 prevents hospitalization and death but is underused, especially in racial/ethnic minority and rural populations. Reasons for underuse and inequity may include community member lack of awareness or healthcare access barriers, among others. This study assessed mAbs community awareness and opportunities for improving equitable mAb access.MethodsA concurrent mixed methods study including surveys and focus groups with adults with high-risk conditions or their proxy decision-makers. Surveys and focus group guides addressed diffusion of innovation theory factors. Descriptive statistics and Fisher's exact method was used to report and compare survey findings by race and ethnicity. Rapid qualitative methods were used for focus group analysis.ResultsSurveys from 515 individuals (460 English, 54 Spanish, 1 Amharic), and 8 focus groups (6 English, 2 Spanish) with 69 participants, completed June 2021 to January 2022. Most survey respondents (75%) had heard little or nothing about mAbs, but 95% would consider getting mAb treatment. Hispanic/Latino and Non-Hispanic People of Color (POC) reported less awareness, greater concern about intravenous infusions, and less trust in mAb safety and effectiveness than White, Non-Hispanic respondents. Focus group themes included little awareness but high interest in mAb treatment and concerns about cost and access barriers such as lacking established sources of care and travel from rural communities. Focus groups revealed preferences for broad-reaching but tailored messaging strategies using multiple media and trusted community leaders.ConclusionsDespite unfamiliarity with mAb treatment, most respondents were open to receiving mAbs or recommending mAbs to others. While mAb messaging should have broad reach "to everyone everywhere," racial and geographic disparities in awareness and trust about mAbs underscore need for tailored messaging to promote equitable access. Care processes should address patient-level barriers like transportation, insurance, or primary care access. COVID-19 treatment dissemination strategies should promote health equity.

IntroductionFamily-level psychosocial factors appear to play a critical role in mediating the intergenerational transmission of trauma; however, no review article has quantitatively synthesized causal mechanisms across a diversity of trauma types. This study aims to systematically consolidate the epidemiological research on family-level psychosocial mediators and moderators to ultimately produce causal diagram(s) of the intergenerational transmission of trauma.MethodsWe will identify epidemiological peer-reviewed publications, dissertations, and conference abstracts that measure the impact of at least one psychosocial family-level factor mediating or moderating the relationship between parental trauma exposure and a child mental health outcome. English, French, Kinyarwanda, and Spanish articles will be eligible. We will search MEDLINE, PsycINFO, PTSDpubs, Scopus, and ProQuest Dissertations and Theses and will conduct forward citation chaining of included documents. Two reviewers will perform screening independently. We will extract reported mediators, moderators, and relevant study characteristics for included studies. Findings will be presented using narrative syntheses, descriptive analyses, mediation meta-analyses, moderating meta-analyses, and causal diagram(s), where possible. We will perform a risk of bias assessment and will assess for publication bias.DiscussionThe development of evidence-based causal diagram(s) would provide more detailed understanding of the paths by which the psychological impacts of trauma can be transmitted intergenerationally at the family-level. This review could provide evidence to better support interventions that interrupt the cycle of intergenerational trauma.Trial registrationSystematic review registration: PROSPERO registration ID #CRD42021251053.

BackgroundWidespread use of at-home rapid COVID-19 antigen tests has been proposed as an important public health intervention to interrupt chains of transmission. Antigen tests may be preferred over PCR because they provide on-demand results for relatively low cost and can identify people when they are most likely to be infectious, particularly when used daily. Yet the extent to which a frequent antigen testing intervention will result in a positive public health impact for COVID-19 will depend on high acceptability and high adherence to such regimens.MethodsWe conducted a mixed-methods study assessing acceptability of and adherence to a daily at-home mobile-app connected rapid antigen testing regimen among employees of a US-based media company. Acceptability was assessed across seven domains of the Theoretical Framework of Acceptability.ResultsAmong 31 study participants, acceptability of the daily testing intervention was generally high, with participants reporting high perceived effectiveness, intervention coherence, and self-efficacy; positive affective attitude; acceptable degree of burden and opportunity cost; and assessing the intervention as ethical. 71% reported a preference to test daily using an at-home antigen test than weekly employment-based PCR. Mean adherence to the 21-day testing regimen was 88% with 43% of participants achieving 100% adherence, 48% testing at least every other day, and 10% testing less than every other day.ConclusionsDespite overall high acceptability and adherence, we identified three implementation challenges that must be addressed for frequent serial testing for COVID-19 to be implemented at scale and have a positive public health impact. First, users need guidance on how and when to adapt testing frequencies to different epidemiological conditions. Second, users and institutions need guidelines for how to safely store and share test results. Third, implementation of serial testing strategies must prioritize health equity and protect those most vulnerable to COVID-19.

Seismic oceanography generally makes use of multi-channel seismic reflection data sourced by air gun arrays and long hydrophone streamers to image oceanographic water masses and processes—often piggybacking on surveys that target deeper geological features below the seafloor. However, due to the acquisition methods employed, shallow (upper 200 m or so) regions of the ocean can be poorly imaged with this technique, and resolution is often lower than desirable for imaging fine-structure within the water column. In 2012, we collected a set of higher-resolution seismic lines off the southeast coast of New Zealand, with a generator-injector airgun source and hydrophone streamer configuration designed to improve images of shallower water masses and their boundaries. The seismic lines were acquired with coincident expendable bathythermograph deployments which provides direct ties between physical oceanographic data and seismic data, allowing for definitive identification of the Subtropical Front and associated water masses in the subsurface. Repeat acquisition along the same transect shows significant temporal variability on the scale of hours, illustrating the highly dynamic nature of this important ocean boundary. Comparisons to conventional low-frequency seismic data in the same location show the value of high-resolution acquisition methods in imaging the near-surface of the ocean and allowing subsurface features to be linked to their expressions at the surface.

Summary: T cell exhaustion and dysfunction are hallmarks of severe COVID-19. To gain insights into the pathways underlying these alterations, we performed a comprehensive transcriptome analysis of peripheral-blood-mononuclear-cells (PBMCs), spleen, lung, kidney, liver, and heart obtained at autopsy from COVID-19 patients and matched controls, using the nCounter CAR-T-Characterization panel. We found substantial gene alterations in COVID-19-impacted organs, especially the lung where altered TCR repertoires are noted. Reduced TCR repertoires are also observed in PBMCs of severe COVID-19 patients. ENTPD1/CD39, an ectoenzyme defining exhausted T-cells, is upregulated in the lung, liver, spleen, and PBMCs of severe COVID-19 patients where expression positively correlates with markers of vasculopathy. Heightened ENTPD1/CD39 is paralleled by elevations in STAT-3 and HIF-1α transcription factors; and by markedly reduced CD39-antisense-RNA, a long-noncoding-RNA negatively regulating ENTPD1/CD39 at the post-transcriptional level. Limited TCR repertoire and aberrant regulation of ENTPD1/CD39 could have permissive roles in COVID-19 progression and indicate potential therapeutic targets to reverse disease.

We evaluated annual and regional variation in the dietary niche of Pygoscelis penguins including the sea ice-obligate Adélie penguin (Pygoscelis adeliae), and sea ice-intolerant chinstrap (Pygoscelis antarcticus) and gentoo (Pygoscelis papua) penguins, three species that nest throughout the western Antarctic Peninsula (AP) to test the sea ice trophic interaction hypothesis, which posits that penguin breeding populations with divergent trends, i.e., declining or increasing, are reliant on differing food webs. Our study relies on values of naturally occurring carbon (13C/12C, δ13C) and nitrogen (15N/14N, δ15N) stable isotopes as integrated proxies of penguin food webs measured over three years at three different breeding colonies. At Anvers Island in the north, where reductions in sea ice and changes in breeding population trends among sympatric sea ice-obligate (Adélie) and sea ice-intolerant (chinstrap and gentoo) penguins have been most notable, our analyses show that all three species of Pygoscelis penguins became more similar isotopically over the reproductive period. By late chick-rearing at Anvers Island, crèched chicks at 5-weeks-old for all species occupied similar trophic positions. Isotopic mixing models indicated that the proportions of prey provisioned by adult penguins to 5-week-old chicks at Anvers Island were generally similar across species within years, consisting primarily of Antarctic krill (Euphausia superba). Crèched Adélie chicks had higher δ13C and δ15N values at Avian and Charcot Islands, southern breeding colonies where sea ice is more prominent and populations of Adélie penguins have increased or remain stable. Trophic position increased with latitude, while the proportions of prey provisioned by Adélie penguin adults to chicks at southern breeding colonies included species typical of high Antarctic marine food webs, especially crystal krill (Euphausia crystallorophias). A Bayesian metric for dietary niche width, standard ellipse area (SEA-B), indicated that Pygoscelis penguins with greater population changes in the north had more variability in dietary niche width than stable populations further south. Our results lend insight on marine food web drivers of Pygoscelis penguin reproduction at the regional scale and question the long-standing paradigm that Antarctic krill are the only food web component critical to penguin reproductive survival in this region of the Southern Ocean.

A cost-benefit analysis (CBA) is described for a novel wave energy converters (WEC) design based on a marine hybrid bio-structure—a combination of macroalgae, shellfish or other species on a built frame. The Bio-Oscillator design utilises a hard “skeleton” (e.g., carbon fibre, wood) on which biological organisms (e.g., shellfish, large macroalgae) are grown. As waves pass by, the load generated by the oscillating drag and inertia is transferred through mooring lines to power takeoff technology. This novel approach essentially reverses the typical marine engineering view that “bio-fouling is bad” and instead leverages off the added-drag of biological growth on structures. The approach results in a structure that is largely biodegradable, naturally self-replicating and synergistic with the background environment, self-de-risking in terms of failure impact and can leverage off its own form to enhance energy capture beyond a conventional design. This reduces impact while connecting with conventional marine industries such as aquaculture. A CBA examines the economic pros and cons of this approach, focusing on installation and material costs, along with benefits from synergistic production. The analysis suggests that in addition to typical wave energy obstacles (e.g., cable length, capture width, and power take off) the benefits (biodegradability, harvestability, and carbon reduction) of replacing much of the mass of the structure with living biological material can be included.

Summary: The efficacy of ALVAC-based HIV and SIV vaccines in humans and macaques correlates with antibodies to envelope variable region 2 (V2). We show here that vaccine-induced antibodies to SIV variable region 1 (V1) inhibit anti-V2 antibody-mediated cytotoxicity and reverse their ability to block V2 peptide interaction with the α4β7 integrin. SIV vaccines engineered to delete V1 and favor an α helix, rather than a β sheet V2 conformation, induced V2-specific ADCC correlating with decreased risk of SIV acquisition. Removal of V1 from the HIV-1 clade A/E A244 envelope resulted in decreased binding to antibodies recognizing V2 in the β sheet conformation. Thus, deletion of V1 in HIV envelope immunogens may improve antibody responses to V2 virus vulnerability sites and increase the efficacy of HIV vaccine candidates.

Day-roost selection by Lasiurine tree bats during winter and their response to dormant season fires is unknown in the southeastern United States where dormant season burning is widely applied. Although fires historically were predominantly growing season, they now occur in the dormant season in this part of the Coastal Plain to support a myriad of stewardship activities, including habitat management for game species. To examine the response of bats to landscape condition and the application of prescribed fire, in the winter of 2019, we mist-netted and affixed radio-transmitters to 16 Lasiurine bats, primarily Seminole bats (Lasiurus seminolus) at Camp Blanding Joint Training Center in northern Florida. We then located day-roost sites to describe roost attributes. For five Seminole bats, one eastern red bat (Lasiurus borealis), and one hoary bat (Lasiurus cinereus), we applied prescribed burns in the roost area to observe bat response in real-time. Generally, Seminole bats selected day-roosts in mesic forest stands with high mean fire return intervals. At the roost tree scale, Seminole day-roosts tended to be larger, taller and in higher canopy dominance classes than surrounding trees. Seminole bats roosted in longleaf (Pinus palustris), slash (Pinus elliotii) and loblolly pine (Pinus taeda) more than expected based on availability, whereas sweetbay (Magnolia virginiana), water oak (Quercus nigra) and turkey oak (Quercus laevis), were roosted in less than expected based on availability. Of the seven roosts subjected to prescribed burns, only one male Seminole bat and one male eastern red bat evacuated during or immediately following burning. In both cases, these bats had day-roosted at heights lower than the majority of other day-roosts observed during our study. Our results suggest Seminole bats choose winter day-roosts that both maximize solar exposure and minimize risks associated with fire. Nonetheless, because selected day-roosts largely were fire-dependent or tolerant tree species, application of fire does need to periodically occur to promote recruitment and retention of suitable roost sites.

Although combination BRAF and MEK inhibitors are highly effective for the 40-50% of cutaneous metastatic melanomas harboring BRAFV600 mutations, targeted agents have been ineffective for BRAFV600wild-type (wt) metastatic melanomas. The SU2C Genomics-Enabled Medicine for Melanoma Trial utilized a Simon two-stage optimal design to assess whether comprehensive genomic profiling improves selection of molecular-based therapies for BRAFV600wt metastatic melanoma patients who had progressed on standard-of-care therapy, which may include immunotherapy. Of the response-evaluable patients, binimetinib was selected for 20 patients randomized to the genomics-enabled arm, and nine were treated on the alternate treatment arm. Response rates for 27 patients treated with targeted recommendations included one (4%) partial response, 18 (67%) with stable disease, and eight (30%) with progressive disease. Post-trial genomic and protein pathway activation mapping identified additional drug classes that may be considered for future studies. Our results highlight the complexity and heterogeneity of metastatic melanomas, as well as how the lack of response in this trial may be associated with limitations including monotherapy drug selection and the dearth of available single and combination molecularly-driven therapies to treat BRAFV600wt metastatic melanomas.

Objectives: Patient preference studies are increasingly used to inform decision-making during the medical product lifecycle but are rarely used to inform early stages of drug development. The primary aim of this study is to quantify treatment preferences of patients with neuromuscular disorders, which represent serious and debilitating conditions with limited or no treatment options available. Methods: This quantitative patient preferences study was designed as an online survey, with a cross-over design. This study will target two different diseases from the neuromuscular disorders disease group, myotonic dystrophy type 1 (DM1) and mitochondrial myopathies (MM). Despite having different physio-pathological pathways both DM1 and MM manifest in a clinically similar manner and may benefit from similar treatment options. The sample will be stratified into three subgroups: two patient groups differentiated by age of symptom onset and one caregivers group. Each subgroup will be randomly assigned to complete two of three different preference elicitation methods at two different time points: Q-methodology survey, discrete choice experiment, and best-worst scaling type 2, allowing cross-comparisons of the results across each study time within participants and within elicitation methods. Additional variables such as sociodemographic, clinical and health literacy will be collected to enable analysis of potential heterogeneity. Ethics and Dissemination: This study protocol has undergone ethical review and approval by the Newcastle University R&D Ethics Committee (Ref: 15169/2018). All participants will be invited to give electronic informed consent to take part in the study prior accessing the online survey. All electronic data will be anonymised prior analysis. This study is part of the Patient Preferences in Benefit-Risk Assessments during the Drug Life Cycle (IMI-PREFER) project, a public-private collaborative research project aiming to develop expert and evidence-based recommendations on how and when patient preferences can be assessed and used to inform medical product decision making.

Individual growth rates are intrinsically related to survival and lifetime reproductive success and hence, are key determinants of population growth. Efforts to quantify age-size relationships are hampered by difficulties in aging individuals in wild populations. In addition, species with complex life-histories often show distinct shifts in growth that cannot be readily accommodated by traditional modelling techniques. Amphibians are often characterized by rapid larval growth, cessation of growth prior to metamorphosis, and resumption of growth in the adult stage. Compounding issues of non-linear growth, amphibian monitoring programs typically sample larval and adult populations using dissimilar methods. Here we present the first multistage growth model that combines disparate data collected across life-history stages. We model the growth of the endangered Reticulated Flatwoods Salamander, Ambystoma bishopi, in a Bayesian framework, that accounts for unknown ages, individual heterogeneity, and reconciles dip-net and drift fence sampling designs. Flatwoods salamanders achieve 60% of growth in the first 3 months of life but can survive for up to 13 years as a terrestrial adult. We find evidence for marked variability in growth rate, the timing and age at metamorphosis, and maximum size, within populations. Average size of metamorphs in a given year appeared strongly dependent on hydroperiod, and differed by >10mm across years with successful recruitment. In contrast, variation in the sizes of emerging metamorphs appeared relatively constant across years. An understanding of growth will contribute to the development of population viability analyses for flatwoods salamanders, will guide management actions, and will ultimately aid the recovery of the species. Our model formulation has broad applicability to amphibians, and likely any stage-structured organism in which homogenous data cannot be collected across life-stages. The tendency to ignore stage-structure or omit non-conforming data in growth analyses can no longer be afforded given the high stakes of management decisions, particularly for endangered or at-risk populations.

BackgroundGlobal cases of COVID-19 continue to rise, causing havoc to several economies. So far, Ghana has recorded 48,643 confirmed cases with 320 associated deaths. Although summaries of data are usually provided by the Ministry of Health, detailed epidemiological profile of cases are limited. This study sought to describe the socio-demographic features, pattern of COVID-19 spread and the viral load dynamics among subjects residing in northern, middle and part of the southern belt of Ghana.MethodsThis was a cross-sectional retrospective study that reviewed records of samples collected from February to July, 2020. Respiratory specimens such as sputum, deep-cough saliva and nasopharyngeal swabs were collected from suspected COVID-19 subjects in 12 regions of Ghana for laboratory analysis and confirmation by real-time reverse transcription polymerase chain reaction (RT-PCR).ResultsA total of 72,434 samples were collected during the review period, with majority of the sampled individuals being females (37,464; 51.9%). The prevalence of SARS-CoV-2 identified in the study population was 13.2% [95%CI: 12.9, 13.4). Males were mostly infected (4,897; 51.5%) compared to females. Individuals between the ages 21-30 years recorded the highest number of infections (3,144, 33.4%). Symptomatic subjects had higher viral loads (1479.7 copies/μl; IQR = 40.6-178919) than asymptomatic subjects (49.9; IQR = 5.5-3641.6). There was significant association between gender or age and infection with SARS-CoV-2 (pConclusionThis study has described the epidemiological profile of COVID-19 cases in northern, middle and part of the southern belt of Ghana, with males and younger individuals at greater risk of contracting the disease. Health professionals should be conscious of individuals presenting with anosmia since this was seen as the strongest predictor of virus infection.

Nowadays, notothenioids are the teleostean group that dominates marine Antarctic waters. However, during the Mesozoic a diverse ichthyofauna inhabited the sea that surrounded Antarctic. We present the preliminary results of the last two Argentinian Antarctic field expedition to the Late Jurassic of Antactic Peninsula (Longing Gape) and Cretaceous-Paleogene of Seymour (=Marambio) Island. The fish material recovered is extremely abundant and their further detailed study may provide significant clues into the taxonomy and paleobiogeography of the mesozoic antactic ichthyofaunas.

La nanotecnología tendría un increíble potencial de aplicación en el sector alimentario a lo largo de la cadena alimentaria priorizando los requerimientos del consumidor. Tiene la capacidadde proveer nuevas formas de control y estructurado de alimentos con mayor funcionalidad y valor. En este trabajo se explican brevemente los principales conceptos de la nanotecnología y la implicancia que tiene la reducción de tamaño en sus propiedades. Se describen los principales nanoobjetos de uso potencial en alimentos y se ofrece una visión global de diferentes estudios llevados a cabo y sus aplicaciones en la industria alimentaria.

Sport participation has been shown to be associated with health and social benefits. However, there are persisting inequities and barriers to sport participation that can prevent children and young people with diverse backgrounds and abilities from accessing these benefits. This mixed methods study investigated how diversity is understood, experienced and managed in junior sport. The study combined in-depth interviews (n = 101), surveys (n = 450) and observations over a three-year period. The results revealed that a focus on performance and competitiveness negatively affected junior sports clubs' commitment to diversity and inclusive participation. Gender and a range of attitudes about diversity were also strongly related. On average, we found that those who identified as men were more likely to support a pro-performance stance, be homophobic, endorse stricter gender roles, and endorse violence as a natural masculine trait. In addition, those who identified as men were less likely to hold pro-disability attitudes. These findings suggest that the participation-performance tension and gender affect to what extent, and how, sports clubs engage children and young people with diverse backgrounds and abilities.

Archival tissues represent a rich resource for clinical genomic studies, particularly when coupled with comprehensive medical records. Use of these in next generation sequencing (NGS) is a priority. Nine formalin-fixed paraffin-embedded (FFPE) DNA extraction methods were evaluated using twelve FFPE samples of varying tissue types. Quality assessment included total yield, percent dsDNA, fragment analysis and multiplex PCR. After assessment, three tissue types from four FFPE DNA methods were selected for NGS downstream evaluation, targeted and whole exome sequencing. In addition, two low input library protocols were evaluated for WES. Analysis revealed average coverage across the target regions for WES was ~20-30X for all four FFPE DNA extraction methods. For the targeted panels, the highest molecular tag coverage was obtained with the Kingfisher FFPE extraction method. The genotype concordance was 99% for the commonly called variant positions between all four extraction methods with the targeted PCR NGS panel and 96% with WES. Assessing quality of extracted DNA aids in selecting the optimal NGS approach, and the choice of both DNA extraction and library preparation approaches can impact the performance of archival tissue in NGS.

Our aim was to develop a widely available educational program in which students conducted authentic research that met the expectations of both the scientific and educational communities. This paper describes the development and implementation of a citizen science project based on DNA barcoding of reptile specimens obtained from the Museums Victoria frozen tissue collection. The student program was run by the Gene Technology Access Centre (GTAC) and was delivered as a "one day plus one lesson" format incorporating a one-day wet laboratory workshop followed by a single lesson at school utilising online bioinformatics tools. The project leveraged the complementary resources and expertise of the research and educational partners to generate robust scientific data that could be analysed with confidence, meet the requirements of the Victorian state education curriculum, and provide participating students with an enhanced learning experience. During two 1-week stints in 2013 and 2014, 406 students mentored by 44 postgraduate university students participated in the project. Students worked mainly in pairs to process ~200 tissue samples cut from 53 curated reptile specimens representing 17 species. A total of 27 novel Cytochrome Oxidase subunit 1 (CO1) sequences were ultimately generated for 8 south-east Australian reptile species of the families Scincidae and Agamidae.

This article describes the UniversAAL platform, an open platform intended to facilitate the development, distribution, and deployment of technological solutions for Ambient assisted living (AAL). The platform is intended to benefit end users (i.e., assisted persons, their families, and caregivers), authorities with responsibility for AAL, and organizations involved in the development and deployment of AAL services. It consists of an extensive set of resources (some are software and some are models/architectures) aimed at these different groups. The resources are classified into three main groups: runtime support, development support, and community support. The article presents the benefits that can be expected from the widespread adoption of the platform. The article also describes progress on prototype implementations of some of the software resources, and the results of initial evaluations of the platform. The work is partially based on results from earlier European Union-funded research projects in the area.

Determination of qubit initialisation and measurement fidelity is important for the overall performance of a quantum computer. However, the method by which it is calculated in semiconductor qubits varies between experiments. In this paper we present a full theoretical analysis of electronic single-shot readout and describe critical parameters to achieve high fidelity readout. In particular, we derive a model for energy selective state readout based on a charge detector response and examine how to optimise the fidelity by choosing correct experimental parameters. Although we focus on single electron spin readout, the theory presented can be applied to other electronic readout techniques in semiconductors that use a reservoir.

Climate change may constrain future electricity supply adequacy by reducing electric transmission capacity and increasing electricity demand. The carrying capacity of electric power cables decreases as ambient air temperatures rise; similarly, during the summer peak period, electricity loads typically increase with hotter air temperatures due to increased air conditioning usage. As atmospheric carbon concentrations increase, higher ambient air temperatures may strain power infrastructure by simultaneously reducing transmission capacity and increasing peak electricity load. We estimate the impacts of rising ambient air temperatures on electric transmission ampacity and peak per-capita electricity load for 121 planning areas in the United States using downscaled global climate model projections. Together, these planning areas account for roughly 80% of current peak summertime load. We estimate climate-attributable capacity reductions to transmission lines by constructing thermal models of representative conductors, then forcing these models with future temperature projections to determine the percent change in rated ampacity. Next, we assess the impact of climate change on electricity load by using historical relationships between ambient temperature and utility-scale summertime peak load to estimate the extent to which climate change will incur additional peak load increases. We find that by mid-century (2040–2060), increases in ambient air temperature may reduce average summertime transmission capacity by 1.9%–5.8% relative to the 1990–2010 reference period. At the same time, peak per-capita summertime loads may rise by 4.2%–15% on average due to increases in ambient air temperature. In the absence of energy efficiency gains, demand-side management programs and transmission infrastructure upgrades, these load increases have the potential to upset current assumptions about future electricity supply adequacy.

The long term scaling prospects for solid-state quantum computing architectures relies heavily on the ability to simply and reliably measure and control the coherent electron interaction strength, known as the tunnel coupling, t _c . Here, we describe a method to extract the t _c between two quantum dots (QDs) utilising their different tunnel rates to a reservoir. We demonstrate the technique on a few donor triple QD tunnel coupled to a nearby single-electron transistor (SET) in silicon. The device was patterned using scanning tunneling microscopy-hydrogen lithography allowing for a direct measurement of the tunnel coupling for a given inter-dot distance. We extract ${t}_{{\rm{c}}}=5.5\pm 1.8\;{\rm{GHz}}$ and ${t}_{{\rm{c}}}=2.2\pm 1.3\;{\rm{GHz}}$ between each of the nearest-neighbour QDs which are separated by 14.5 nm and 14.0 nm, respectively. The technique allows for an accurate measurement of t _c for nanoscale devices even when it is smaller than the electron temperature and is an ideal characterisation tool for multi-dot systems with a charge sensor.

We describe a parametric frequency conversion scheme for trapped charged particles, which enables a coherent interface between atomic and solid-state quantum systems. The scheme uses geometric nonlinearities of the potential of coupling electrodes near a trapped particle, and can be implemented using standard charged-particle traps. Our scheme does not rely on actively driven solid-state devices, and is hence largely immune to noise in such devices. We present a toolbox which can be used to build electron-based quantum information processing platforms, as well as quantum hybrid platforms using trapped electrons and superconducting electronics.

A long-established area of scientific excellence in Europe, solid state chemistry has emerged in the US in the past two decades as a field experiencing rapid growth and development. At its core, it is an interdisciplinary melding of chemistry, physics, engineering, and materials science, as it focuses on the design, synthesis and structural characterization of new chemical compounds and characterization of their physical properties. As a consequence of this inherently interdisciplinary character, the solid state chemistry community is highly open to the influx of new ideas and directions. The inclusionary character of the field’s culture has been a significant factor in its continuing growth and vitality.This report presents an elaboration of discussions held during an NSF-sponsored workshop on Future Directions in Solid State Chemistry, held on the UC Davis Campus in October 2001. That workshop was the second of a series of workshops planned in this topical area. The first, held at NSF headquarters in Arlington, Virginia, in January of 1998, was designed to address the core of the field, describing how it has developed in the US and worldwide in the past decade, and how the members of the community saw the central thrusts of research and education in solid state chemistry proceeding in the next several years. A report was published on that workshop (J.M. Honig, chair, “Proceedings of the Workshop on the Present Status and Future Developments of Solid State Chemistry and Materials”, Arlington, VA, January 15–16, 1998) describing the state of the field and recommendations for future development of the core discipline.In the spirit of continuing to expand the scope of the solid state chemistry community into new areas of scientific inquiry, the workshop elaborated in this document was designed to address the interfaces between our field and fields where we thought there would be significant opportunity for the development of new scientific advancements through increased interaction. The 7 topic areas, described in detail in this report, ranged from those with established ties to solid state chemistry such as Earth and planetary sciences, and energy storage and conversion, to those such as condensed matter physics, where the connections are in their infancy, to biology, where the opportunities for connections are largely unexplored. Exciting ties to materials chemistry were explored in discussions on molecular materials and nanoscale science, and a session on the importance of improving the ties between solid state chemists and experts in characterization at national experimental facilities was included. The full report elaborates these ideas extensively. [Copyright &y& Elsevier]

Abstract Each year, more than 40,000 people undergo mitral valve (MV) repair surgery domestically to treat regurgitation caused by myocardial infarction (MI). Although continual MV tissue remodelling following repair is believed to be a major contributor to regurgitation recurrence, the effects of the post-MI state on MV remodelling remain poorly understood. This lack of understanding limits our ability to predict the remodelling of the MV both post-MI and post-surgery to facilitate surgical planning. As a necessary first step, the present study was undertaken to noninvasively quantify the effects of MI on MV remodelling in terms of leaflet geometry and deformation. MI was induced in eight adult Dorset sheep, and real-time three-dimensional echocardiographic (rt-3DE) scans were collected pre-MI as well as at 0, 4, and 8 weeks post-MI. A previously validated image-based morphing pipeline was used to register corresponding open- and closed-state scans and extract local in-plane strains throughout the leaflet surface at systole. We determined that MI induced permanent changes in leaflet dimensions in the diastolic configuration, which increased with time to 4 weeks, then stabilised. MI substantially affected the systolic shape of the MV, and the range of stretch experienced by the MV leaflet at peak systole was substantially reduced when referred to the current time-point. Interestingly, when we referred the leaflet strains to the pre-MI configuration, the systolic strains remained very similar throughout the post-MI period. Overall, we observed that post-MI ventricular remodeling induced permanent changes in the MV leaflet shape. This predominantly affected the MV’s diastolic configuration, leading in turn to a significant decrease in the range of stretch experienced by the leaflet when referenced to the current diastolic configuration. These findings are consistent with our previous work that demonstrated increased plastic (i.e. non-recoverable) leaflet deformations post-MI, that was completely accounted for by the associated changes in collagen fiber structure. Moreover, we demonstrated through noninvasive methods that the state of the MV leaflet can elucidate the progression and extent of MV adaptation following MI and is thus highly relevant to the design of current and novel patient specific minimally invasive surgical repair strategies.

Abstract Respiratory epithelium in the conducting airways of the human body is one of the primary targets of SARS-CoV-2 infection, however, there is a paucity of studies describing the association between COVID-19 and physical characteristics of the conducting airways. To better understand the pathophysiology of COVID-19 on the size of larger conducting airways, we determined the luminal area of the central airways in patients with a history of COVID-19 compared to a height-matched cohort of controls using a case–control study design. Using three-dimensional reconstruction from low-dose high-resolution computed tomography, we retrospectively assessed airway luminal cross-sectional area in 114 patients with COVID-19 (66 females, 48 males) and 114 healthy, sex- and height-matched controls (66 females, 48 males). People with a history of smoking, cardiopulmonary disease, or a body mass index greater than 40 kg·m−2 were excluded. Luminal areas of seven conducting airways were analyzed, including trachea, left and right main bronchus, intermediate bronchus, left and right upper lobe, and left lower lobe. For the central conducting airways, luminal area was ~ 15% greater patients with COVID-19 compared to matched controls (p

Abstract The broadly neutralizing antibody (bNAb) CAP256-VRC26.25 has exceptional potency against HIV-1 and has been considered for clinical use. During the characterization and production of this bNAb, we observed several unusual features. First, the antibody appeared to adhere to pipette tips, requiring tips to be changed during serial dilution to accurately measure potency. Second, during production scale-up, proteolytic cleavage was discovered to target an extended heavy chain loop, which was attributed to a protease in spent medium from 2-week culture. To enable large scale production, we altered the site of cleavage via a single amino acid change, K100mA. The resultant antibody retained potency and breadth while avoiding protease cleavage. We also added the half-life extending mutation LS, which improved the in vivo persistence in animal models, but did not impact neutralization activity; we observed the same preservation of neutralization for bNAbs VRC01, N6, and PGDM1400 with LS on a 208-virus panel. The final engineered antibody, CAP256V2LS, retained the extraordinary neutralization potency of the parental antibody, had a favorable pharmacokinetic profile in animal models, and was negative in in vitro assessment of autoreactivity. CAP256V2LS has the requisite potency, developability and suitability for scale-up, allowing its advancement as a clinical candidate.