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Growing emphasis on elementary STEM education has pushed elementary teachers to face curriculum changes that focus on standards with which they are largely unfamiliar (Smith, 2020; Trygstad et al., 2013). As a result, elementary students are not always exposed to STEM subjects or integration and miss out on opportunities to access and enjoy the hands-on, inquiry-driven activities that accompany them. This deficit disproportionally impacts high-need, urban districts that serve Black and Brown children and families, thus perpetuating inequities in STEM education and careers (Tate et al., 2012). To address these issues, we designed a Fellowship program that strengthened K-12 STEM teacher leadership in local, high-need, schools. In this paper, we take a closer look at how five elementary teachers took on STEM teacher leader identities and then sustained and strengthened those even as program supports reduced. We asked: How do elementary teachers develop and sustain STEM and leadership identities through participation in a Master Teacher Fellowship? Using positional identity and selfefficacy lenses, we interpreted focus group interviews, coursework, reflections, and Fellowship meeting notes. Findings suggest that elementary teachers developed their identities gradually--first, as they recognized themselves as STEM "teachers"; next, as they recognized themselves as STEM "leaders"; and then, as others recognized them as STEM teacher leaders and positioned them to enact change in their schools and to support their colleagues. Implications for teacher educators shed light on how elementary teachers can be best supported in increasing STEM learning for their students across grade levels to effect school change.

Abstract Background The online BeUpstanding™ program is an eight-week workplace-delivered intervention for desk-based workers to raise awareness of the benefits of sitting less and moving more and build a supportive culture for change. A workplace representative (the “champion”) delivers the program, which includes a workshop where teams collectively choose their sit less/move more strategies. A toolkit provides the champion with a step-by-step guide and associated resources to support program uptake, delivery, and evaluation. Here we report on the main findings from the Australian national implementation trial of BeUpstanding. Methods Recruitment (12/06/2019 to 30/09/2021) was supported by five policy and practice partners, with desk-based work teams from across Australia targeted. Effectiveness was measured via a single arm, repeated-measures trial. Data were collected via online surveys, toolkit analytics, and telephone calls with champions. The RE-AIM framework guided evaluation, with adoption/reach (number and characteristics); effectiveness (primary: self-reported workplace sitting time); implementation (completion of core components; costs); and, maintenance intentions reported here. Linear mixed models, correcting for cluster, were used for effectiveness, with reach, adoption, implementation, and maintenance outcomes described. Results Of the 1640 website users who signed-up to BeUpstanding during the recruitment period, 233 were eligible, 198 (85%) provided preliminary consent, and 118 (50.6%) champions consented and started the trial, with 94% (n = 111 champions) completing. Trial participation was from across Australia and across industries, and reached 2,761 staff, with 2,248 participating in the staff survey(s): 65% female; 64% university educated; 17% from a non-English speaking background. The program effectively changed workplace sitting (-38.5 [95%CI -46.0 to -28.7] minutes/8-hour workday) and all outcomes targeted by BeUpstanding (behaviours and culture), with small-to-moderate statistically-significant effects observed. All participating teams (n = 94) completed at least 5/7 core steps; 72.4% completed all seven. Most champions spent $0 (72%) or >$0-$5 (10%) per team member; most (67/70 96%) intended to continue or repeat the program. Conclusions BeUpstanding can be adopted and successfully implemented by a range of workplaces, reach a diversity of staff, and be effective at creating a supportive culture for teams of desk-based workers to sit less and move more. Learnings will inform optimisation of the program for longer-term sustainability. Trial registration ACTRN12617000682347.

The teacher certification process can be overwhelming for early-career educators. Negotiating teacher identity, completing fieldwork hours, and navigating institutional expectations can stress the most resilient teacher candidates. These pressures are further compounded as teacher certification assessments, such as the edTPA, introduce additional hurdles to achieving state licensure. This study approaches these obstacles by examining the stories of a diverse group of 14 early-career teachers as they reflect on completing edTPA and their current teaching practices. Through social constructivist perspectives and professional learning continuum framing, we interpreted narrative data to examine early-career teacher discussions of completing edTPA and developing pedagogical practices. These 14 teachers elucidated that the collaborative nature of their preparation program was integral to their completing the assessment, that the program approach to completing the portfolio assessment positioned them to think reflexively about their practice, and that the skills and tools used on edTPA remained useful to them throughout their early-career teaching. We suggest ways that preparation programs can interpret this teacher certification policy as an instructional touchpoint and can limit the gatekeeping capabilities of certification exams through collaboration, building capital, and supporting reflective portfolios. This work has implications for policymakers in teacher education and induction programs.

Abstract In this study, optical photothermal infrared (O-PTIR) spectroscopy combined with machine learning algorithms were used to evaluate 46 tissue cores of surgically resected cervical lymph nodes, some of which harboured oral squamous cell carcinoma nodal metastasis. The ratios obtained between O-PTIR chemical images at 1252 cm−1 and 1285 cm−1 were able to reveal morphological details from tissue samples that are comparable to the information achieved by a pathologist’s interpretation of optical microscopy of haematoxylin and eosin (H&E) stained samples. Additionally, when used as input data for a hybrid convolutional neural network (CNN) and random forest (RF) analyses, these yielded sensitivities, specificities and precision of 98.6 ± 0.3%, 92 ± 4% and 94 ± 5%, respectively, and an area under receiver operator characteristic (AUC) of 94 ± 2%. Our findings show the potential of O-PTIR technology as a tool to study cancer on tissue samples.

Objective: The role of selective decontamination with oral antibiotics (OABs) and mechanical bowel preparation (MBP) prior to elective colorectal surgery is still widely debated. The objective of this study was to compare the outcomes of selective decontamination with neomycin, metronidazole and MBP compared to those of decontamination with MBP alone or with no preparation. Methods: Selective decontamination with neomycin and metronidazole combined with bowel preparation was introduced prior to elective colorectal surgery as part of an enhanced recovery after surgery program at Westmead Hospital, a major Australian tertiary referral hospital, between June 2017 and January 2023. Comparisons between short-term outcomes of OAB + MBP and MBP/no preparation were made using prospectively collected data on length of stay (LOS), readmission, mortality within 30 days, anastomotic leakage (AL), surgical site infection (SSI), urinary tract infection, deep venous thrombosis and/or pulmonary embolism, pneumonia, and ileus. Follow-up was limited to hospital stays and subsequent presentations within the health district within thirty days of surgery. The Mann–Whitney U test was used to analyse continuous data, and the chi-square test was used for categorical data. Univariate and multivariate regression modelling was performed to identify risk factors associated with an increased likelihood of SSI and AL. Results: Patients with oral neomycin and metronidazole combined with bowel preparation had reduced superficial SSI (2.7% vs. 7.6%, p = 0.043) and overall complications (32.7% vs. 44.6%, p = 0.020), particularly Clavien–Dindo 1 complications (7.3% vs. 16.5%, p = 0.009). However, the differences in AL (2.7% vs. 4.5%, p = 0.369) and organ/space SSI (1.3% vs. 3.7%, p = 0.327) were not statistically significant. The median LOS (6 d vs. 6 d, p = 0.370) was not different between the groups. Conclusion: Selective decontamination with neomycin and metronidazole reduces the risk of SSIs and overall complications. There was a trend to toward a lower AL, but this difference was not statistically significant.

Parent engagement in early behavioral intervention is essential to achieving meaningful intervention outcomes. However, parents may experience multiple barriers to engagement. The Parent-coaching Assessment, Individualization, and Response to Stressors (PAIRS) was developed to help practitioners assess families' barriers and facilitators, individualize their intervention, and respond to stressors using a contextual, functional approach. An expert panel of Board Certified Behavior Analysts ® (BCBAs) evaluated the content validity of the PAIRS. Average scale values (S-CVI/Ave) were 0.92 for relevance, 0.85 for effectiveness, and 0.91 for appropriateness. The PAIRS was revised, and a follow-up evaluation was conducted to rate the tool's utility. This led to the final version of the PAIRS. Clinical implications and future directions are discussed.

In a post-pandemic world, school absence is an ever-increasing concern for governments, school leaders, and local authorities worldwide. School absence is associated with poor academic outcomes and long-term illness (physical and mental). Absenteeism increases the risk of financial difficulties in adulthood and involvement in the criminal justice system. As a result, the upstream costs to already overstretched public services are crippling. In England, all children are judged by teachers on their “school readiness” over their first year of formal education. We hypothesised that early childhood problems (i.e., not school ready) might be an antecedent of absenteeism. We tested this by investigating the pre-pandemic association between school readiness and persistent absenteeism using a population-linked dataset. Analyses included 62,598 children aged 5-13 years from the Connected Bradford database (spanning academic years 2012/13-2019/20). Special educational needs (SEN) status, English as an Additional Language status, socioeconomic status, sex, and ethnicity were covariates significantly associated with persistent absenteeism. Children who were not “school ready” had increased odds of being persistently absent later in their education journey after controlling for these covariates. School readiness was associated with even greater odds of being persistently absent over two or more years. These findings show: (i) the potential of using existing administrative data to identify children at risk of disengagement from the education system; (ii) absenteeism reflects stark structural inequities. As the rates of absence is still rising, schools can use these data to flag the children who may benefit from early intervention to keep them engaged in school.

Ethyl carbamate (EC) is a process contaminant found in fermented foods and alcoholic beverages. Metabolic conversion of ethyl carbamate generates vinyl carbamate (VC), a carcinogenic metabolite. EC, as a Group 2A probable human carcinogen, and the more potent VC, are known to cause tumors in rodents. However, their effects on the kidney are unknown and were explored here. Female A/J inbred mice received an intraperitoneal injection of vehicle or VC. Beginning 5 weeks after VC injection, mice showed signs of moribund state. Mouse necropsies revealed renal glomerular injury that histopathologically recapitulated human membranoproliferative glomerulonephritis (MPGN), as evidenced by light microscopy, immunostaining for immunoglobulins and complements, and electron microscopy. To determine the molecular pathomechanisms, a post-hoc analysis was performed on a publicly available RNA-Seq transcriptome of kidneys from control rats and rats treated with fermented wine containing high concentrations of EC. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the differentially expressed genes revealed that the complement and coagulation cascades were a top predicted biological process involved. Furthermore, pathway-based data integration and visualization revealed that key regulators of complement activation were altered by high EC treatment. Among these, complement factors (CF) D and H, critical positive and negative regulators of the alternative pathway, respectively, were most affected, with CFD induced by 3.49-fold and CFH repressed by 5.9-fold, underscoring a hyperactive alternative pathway. Consistently, exposure of primary glomerular endothelial cells to EC or VC resulted in induction of CFD and repression of CFH, accompanied by increased fixation of C3 and C5b9. This effect seems to be mediated by Ras, one of the top genes that interact with both EC and VC, as identified by analyzing the chemical-gene/protein interactions database. Indeed, EC or VC-elicited complement activation was associated with activation of Ras signaling, but was abolished by the Ras inhibitor farnesyl thiosalicylic acid. Collectively, our findings suggest that VC, a metabolite of EC, induces glomerular injury in mice akin to human MPGN, possibly via perturbing the expression of complement regulators, resulting in an effect that favors activation of the alternative complement pathway.

OBJECTIVES:. Anemia has been associated with an increased risk of both cardiac arrest and stroke, frequent complications of COVID-19. The effect of hemoglobin level at ICU admission on a composite outcome of cardiac arrest or stroke in an international cohort of COVID-19 patients was investigated. DESIGN:. Retrospective analysis of prospectively collected database. SETTING:. A registry of COVID-19 patients admitted to ICUs at over 370 international sites was reviewed for patients diagnosed with cardiac arrest or stroke up to 30 days after ICU admission. Anemia was defined as: normal (hemoglobin ≥ 12.0 g/dL for women, ≥ 13.5 g/dL for men), mild (hemoglobin 10.0–11.9 g/dL for women, 10.0–13.4 g/dL for men), moderate (hemoglobin ≥ 8.0 and < 10.0 g/dL for women and men), and severe (hemoglobin < 8.0 g/dL for women and men). PATIENTS:. Patients older than 18 years with acute COVID-19 infection in the ICU. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. Of 6926 patients (median age = 59 yr, male = 65%), 760 patients (11.0%) experienced stroke (2.0%) and/or cardiac arrest (9.4%). Cardiac arrest or stroke was more common in patients with low hemoglobin, occurring in 12.8% of patients with normal hemoglobin, 13.3% of patients with mild anemia, and 16.7% of patients with moderate/severe anemia. Time to stroke or cardiac arrest by anemia status was analyzed using Cox proportional hazards regression with death as a competing risk. Covariates selected through clinical knowledge were age, sex, comorbidities (diabetes, hypertension, obesity, and cardiac or neurologic conditions), pandemic era, country income, mechanical ventilation, and extracorporeal membrane oxygenation. Moderate/severe anemia was associated with a higher risk of cardiac arrest or stroke (hazard ratio, 1.32; 95% CI, 1.05–1.67). CONCLUSIONS:. In an international registry of ICU patients with COVID-19, moderate/severe anemia was associated with increased hazard of cardiac arrest or stroke.

This article presents reflections from 12 experts on "language learners strategy" (LLS) research. They were asked to offer their reflections in one of their domains of expertise, linking research into LLS with successful language learning and use practices. In essence, they were called upon to provide a review of recent scholarship by identifying areas where results of research had already led to the enhancement of learner strategy use, as well as to describe ongoing and future research efforts intended to enhance the strategy domain. The LLS areas dealt with include theory building, the dynamics of delivering "strategy instruction" (SI), meta-analyses of SI, learner diversity, SI for young language learners, SI for fine-tuning the comprehension and production of academic-level, grammar strategies at the macro and micro levels, lessons learned from many years of LLS research in Greece, the past and future roles of technology aimed at enhancing language learning, and applications of LLS in content instruction. This review is intended to provide the field with an updated statement as to where we have been, where we are now, and where we need to go. Ideally, it will provide ideas for future studies.

Abstract Background Genetic variants that severely alter protein products (e.g. nonsense, frameshift) are often associated with disease. For some genes, these predicted loss-of-function variants (pLoFs) are observed throughout the gene, whilst in others, they occur only at specific locations. We hypothesised that, for genes linked with monogenic diseases that display incomplete penetrance, pLoF variants present in apparently unaffected individuals may be limited to regions where pLoFs are tolerated. To test this, we investigated whether pLoF location could explain instances of incomplete penetrance of variants expected to be pathogenic for Mendelian conditions. Methods We used exome sequence data in 454,773 individuals in the UK Biobank (UKB) to investigate the locations of pLoFs in a population cohort. We counted numbers of unique pLoF, missense, and synonymous variants in UKB in each quintile of the coding sequence (CDS) of all protein-coding genes and clustered the variants using Gaussian mixture models. We limited the analyses to genes with ≥ 5 variants of each type (16,473 genes). We compared the locations of pLoFs in UKB with all theoretically possible pLoFs in a transcript, and pathogenic pLoFs from ClinVar, and performed simulations to estimate the false-positive rate of non-uniformly distributed variants. Results For most genes, all variant classes fell into clusters representing broadly uniform variant distributions, but genes in which haploinsufficiency causes developmental disorders were less likely to have uniform pLoF distribution than other genes (P < 2.2 × 10−6). We identified a number of genes, including ARID1B and GATA6, where pLoF variants in the first quarter of the CDS were rescued by the presence of an alternative translation start site and should not be reported as pathogenic. For other genes, such as ODC1, pLoFs were located approximately uniformly across the gene, but pathogenic pLoFs were clustered only at the end, consistent with a gain-of-function disease mechanism. Conclusions Our results suggest the potential benefits of localised constraint metrics and that the location of pLoF variants should be considered when interpreting variants.

Abstract Focal adhesions (FAs) connect inner workings of cell to the extracellular matrix to control cell adhesion, migration and mechanosensing. Previous studies demonstrated that FAs contain three vertical layers, which connect extracellular matrix to the cytoskeleton. By using super-resolution iPALM microscopy, we identify two additional nanoscale layers within FAs, specified by actin filaments bound to tropomyosin isoforms Tpm1.6 and Tpm3.2. The Tpm1.6-actin filaments, beneath the previously identified α-actinin cross-linked actin filaments, appear critical for adhesion maturation and controlled cell motility, whereas the adjacent Tpm3.2-actin filament layer beneath seems to facilitate adhesion disassembly. Mechanistically, Tpm3.2 stabilizes ACF-7/MACF1 and KANK-family proteins at adhesions, and hence targets microtubule plus-ends to FAs to catalyse their disassembly. Tpm3.2 depletion leads to disorganized microtubule network, abnormally stable FAs, and defects in tail retraction during migration. Thus, FAs are composed of distinct actin filament layers, and each may have specific roles in coupling adhesions to the cytoskeleton, or in controlling adhesion dynamics.

Membranous nephropathy (MN) continues to be a leading cause of nephrotic syndrome in non-diabetic adults. As a unique subtype in the serology-based classification of MN, thrombospondin type 1 domain containing 7A (THSD7A)-associated MN has attracted increasing interest, because, unlike other autoantigens, THSD7A is also expressed in preclinical species, facilitating the study of its role in MN. A heterologous mouse model of THSD7A-associated MN was previously established using a proprietary in-house antibody that was unfortunately not available to the research community. Here, we developed a mouse model of THSD7A-associated MN by administering a commercially available antibody targeting the most N-terminal part of THSD7A. Our model was characterized by heavy proteinuria and pathological features of human MN without sex differences. Complement depletion with cobra venom factor only partially attenuated proteinuria and glomerular injury in this model, entailing that complement-independent pathomechanisms also contribute. Consistently, in vitro in primary podocytes, exposure to the anti-THSD7A antibody caused evident podocytopathic changes, including disruption of actin cytoskeleton integrity, podocyte hypermobility, oxidative stress, and apoptotic cell death. These signs of podocytopathy were preserved, albeit to a lesser extent, after complement inactivation, indicating autonomous podocyte injury. Furthermore, as the first FDA-approved treatment for primary MN, adrenocorticotropic hormone therapy with repository corticotropin injection (Purified Cortrophin Gel®) appeared to be beneficial and significantly attenuated proteinuria and glomerular injury, suggesting that this model may be useful for developing novel treatments or understanding the pathogenesis of MN. Collectively, our model, based on the use of a commercially available anti-THSD7A antibody, will be an important tool for MN research.

Post-pandemic school absence is an increasing concern for governments worldwide. Absence is associated with poor academic outcomes and long-term illness (physical and mental). Absenteeism increases the risk of financial difficulties in adulthood and involvement in the criminal justice system. We hypothesized that early childhood problems might be an antecedent of absenteeism. We tested this hypothesis by investigating the pre-pandemic association between school readiness and persistent absenteeism using a population-linked dataset. Analyses included 62,598 children aged 5–13 years from the Connected Bradford database (spanning academic years 2012/13 to 2019/20). Special educational needs status, English as an Additional Language status, socioeconomic status, sex and ethnicity were covariates significantly associated with persistent absenteeism. Children who were not ‘school ready’ had increased odds of being persistently absent later in their education journey after controlling for these covariates. School readiness was associated with even greater odds of being persistently absent over two or more years. These findings show (i) the seeds of absenteeism are sown early in childhood; (ii) absenteeism shows the hallmark of structural inequities; and (iii) the potential of ‘school readiness’ measures to identify children at risk of long-term disengagement from the education system.

Objective To estimate the cost-effectiveness of craniotomy, compared with decompressive craniectomy (DC) in UK patients undergoing evacuation of acute subdural haematoma (ASDH).Design Economic evaluation undertaken using health resource use and outcome data from the 12-month multicentre, pragmatic, parallel-group, randomised, Randomised Evaluation of Surgery with Craniectomy for Patients Undergoing Evacuation-ASDH trial.Setting UK secondary care.Participants 248 UK patients undergoing surgery for traumatic ASDH were randomised to craniotomy (N=126) or DC (N=122).Interventions Surgical evacuation via craniotomy (bone flap replaced) or DC (bone flap left out with a view to replace later: cranioplasty surgery).Main outcome measures In the base-case analysis, costs were estimated from a National Health Service and Personal Social Services perspective. Outcomes were assessed via the quality-adjusted life-years (QALY) derived from the EuroQoL 5-Dimension 5-Level questionnaire (cost-utility analysis) and the Extended Glasgow Outcome Scale (GOSE) (cost-effectiveness analysis). Multiple imputation and regression analyses were conducted to estimate the mean incremental cost and effect of craniotomy compared with DC. The most cost-effective option was selected, irrespective of the level of statistical significance as is argued by economists.Results In the cost-utility analysis, the mean incremental cost of craniotomy compared with DC was estimated to be −£5520 (95% CI −£18 060 to £7020) with a mean QALY gain of 0.093 (95% CI 0.029 to 0.156). In the cost-effectiveness analysis, the mean incremental cost was estimated to be −£4536 (95% CI −£17 374 to £8301) with an OR of 1.682 (95% CI 0.995 to 2.842) for a favourable outcome on the GOSE.Conclusions In a UK population with traumatic ASDH, craniotomy was estimated to be cost-effective compared with DC: craniotomy was estimated to have a lower mean cost, higher mean QALY gain and higher probability of a more favourable outcome on the GOSE (though not all estimated differences between the two approaches were statistically significant).Ethics Ethical approval for the trial was obtained from the North West—Haydock Research Ethics Committee in the UK on 17 July 2014 (14/NW/1076).Trial registration number ISRCTN87370545.

Abstract Background Classification of rare missense variants remains an ongoing challenge in genomic medicine. Evidence of pathogenicity is often sparse, and decisions about how to weigh different evidence classes may be subjective. We used a Bayesian variant classification framework to investigate the performance of variant co-localisation, missense constraint, and aggregating data across paralogous protein domains (“meta-domains”). Methods We constructed a database of all possible coding single nucleotide variants in the human genome and used PFam predictions to annotate structurally-equivalent positions across protein domains. We counted the number of pathogenic and benign missense variants at these equivalent positions in the ClinVar database, calculated a regional constraint score for each meta-domain, and assessed this approach versus existing missense constraint metrics for classifying variant pathogenicity and benignity. Results Alternative pathogenic missense variants at the same amino acid position in the same protein provide strong evidence of pathogenicity (positive likelihood ratio, LR+ = 85). Additionally, clinically annotated pathogenic or benign missense variants at equivalent positions in different proteins can provide moderate evidence of pathogenicity (LR+ = 7) or benignity (LR+ = 5), respectively. Applying these approaches sequentially (through PM5) increases sensitivity for classifying pathogenic missense variants from 27 to 41%. Missense constraint can also provide strong evidence of pathogenicity for some variants, but its absence provides no evidence of benignity. Conclusions We propose using structurally equivalent positions across related protein domains from different genes to augment evidence for variant co-localisation when classifying novel missense variants. Additionally, we advocate adopting a numerical evidence-based approach to integrating diverse data in variant interpretation.

Extensive research exists on students who are the first in their families to pursue post-secondary education, i.e. first-generation college students. But what about first-generation students who pursue careers in education? This study highlights the experiences of first-generation college students, then graduate students, turned teachers and may shed light on how teacher preparation programs could improve persistence among first-generation college and graduate students and support this population as they embark on careers in K-12 settings. First-generation college students who become teachers frequently share demographic characteristics with students in high-need schools, i.e., many are of low socioeconomic status and/or are people of color. Thus, these teachers may help to fill a critical need as they may be more likely to persist as teachers in high-need schools, which are typically hardest to staff and have high turnover.

Supporting social competence in early childhood is associated with the development of friendships, positive outcomes across developmental domains, and preventing challenges in later life. However, within social skills interventions to improve social competence, identifying and selecting target social skills that are likely to be functional within a child's environment represent a complex challenge. In the current research, descriptive analysis was employed within the preschool context, to identify the common, functional social skills that typically developing children engage in, within naturally occurring social exchanges. Environmental variables possibly correlated with social behavior within the preschool context were analyzed. An analysis of the social antecedents and consequences for social behavior was also conducted. Specific social behaviors that are likely to be functional and developmentally appropriate within the preschool context were identified. Analyses of factors are discussed in terms of recommendations for developing social skills interventions for early educational settings.

IntroductionInfective Endocarditis (IE) is a rare, life-threatening infection of the endocardium with multisystem effects. Culprit microorganisms derived from different niches circulate through the bloodstream and attach to the endocardium, particularly the heart valves. This study aimed to investigate culprit microorganisms among a cross-sectional cohort of IE patients, their associated factors, and to explore the potential relationship to the oral microbiome.MethodsIn this observational study, we undertook a cross-sectional analysis of 392 medical records from patients diagnosed with IE. The primary outcome of this study was to analyse the association between the IE culprit microorganisms and the underlying anatomical types of IE (native valve (NVE), prosthetic valve (PVE), or cardiac device-related (CDE)). Secondary outcomes encompassed a comparative analysis of additional factors, including: the treatment approaches for IE, and the categorisation of blood cultures, extending to both genus and species levels. Additionally, we cross-referenced and compared the species-level identification of IE bacteraemia outcome measures with data from the expanded Human Oral Microbiome Database (eHOMD).ResultsA culprit microorganism was identified in 299 (76.28%) case participants. Staphylococcal infections were the most common (p

Abstract Background Estimation of prognosis of oral squamous cell carcinoma (OSCC) is inaccurate prior to surgery, only being effected following subsequent pathological analysis of the primary tumour and excised lymph nodes. Consequently, a proportion of patients are overtreated, with an increase in morbidity, or undertreated, with inadequate margins and risk of recurrence. We hypothesise that it is possible to accurately characterise clinical outcomes from infrared spectra arising from diagnostic biopsies. In this first step, we correlate survival with IR spectra derived from the primary tumour. Methods Infrared spectra were collected from tumour tissue from 29 patients with OSCC and subject to classification modelling. Results The model had a median AUROC of 0.89 with regard to prognosis, a median specificity of 0.83, and a hazard ratio of 6.29 in univariate Cox proportional hazard modelling. Conclusion The data suggest that FTIR spectra may be a useful early biomarker of prognosis in OSCC.

ABSTRACTCancer patients are at risk for severe coronavirus disease 2019 (COVID-19) outcomes due to impaired immune responses. However, the immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is inadequately characterized in this population. We hypothesized that cancer vs non-cancer individuals would mount less robust humoral and/or cellular vaccine-induced immune SARS-CoV-2 responses. Receptor binding domain (RBD) and SARS-CoV-2 spike protein antibody levels and T-cell responses were assessed in immunocompetent individuals with no underlying disorders (n = 479) and immunocompromised individuals (n = 115). All 594 individuals were vaccinated and of varying COVID-19 statuses (i.e., not known to have been infected, previously infected, or “Long-COVID”). Among immunocompromised individuals, 59% (n = 68) had an underlying hematologic malignancy; of those, 46% (n = 31) of individuals received cancer treatment 1,000 U/mL), and of these, 60% (n = 281) and 44% (n = 41), respectively, also had elevated T-cell responses. Composite T-cell responses were higher in individuals previously infected with SARS-CoV-2 or those diagnosed with Long-COVID compared to uninfected individuals. T-cell responses varied between immunocompetent vs carcinoma (n = 12) cohorts (P < 0.01) but not in immunocompetent vs hematologic malignancy cohorts. Most SARS-CoV-2 vaccinated individuals mounted robust cellular and/or humoral responses, though higher immunogenicity was observed among the immunocompetent compared to cancer populations. The study suggests B-cell targeted therapies suppress antibody responses, but not T-cell responses, to SARS-CoV-2 vaccination. Thus, vaccination continues to be an effective way to induce humoral and cellular immune responses as a likely key preventive measure against infection and/or subsequent more severe adverse outcomes.IMPORTANCEThe study was prompted by a desire to better assess the immune status of patients among our cancer host cohort, one of the largest in the New York metropolitan region. Hackensack Meridian Health is the largest healthcare system in New Jersey and cared for more than 75,000 coronavirus disease 2019 patients in its hospitals. The John Theurer Cancer Center sees more than 35,000 new cancer patients a year and performs more than 500 hematopoietic stem cell transplants. As a result, the work was undertaken to assess the effectiveness of vaccination in inducing humoral and cellular responses within this demographic.

Background Adolescence and transition into adulthood are periods shaping life-long mental health, cardiometabolic risk, and inequalities. However, they are poorly studied and understood. By extending and expanding the Born in Bradford (BiB) cohort study through this period using innovative, co-produced approaches to collect and analyse data, we aim to understand better the interplay of factors that influence health and wellbeing, and inform/evaluate interventions to improve them and reduce inequalities. Protocol BiB Age of Wonder (AoW) is a large, whole city cohort that will capture the contemporary lived experience amongst multi-ethnic adolescents progressing into young adulthood. We will collect repeated data from existing BiB participants and their peers (N~30,000 adolescents). The protocol for the first phase of the quantitative methods, involving survey measurements and health assessments in mainstream secondary schools is described here. We describe the co-production behind these methods, and lessons learned from the first year of data collection.