Engineering Customized Cell Sensing and Response Behaviors Using Synthetic Notch Receptors.

The Notch protein is one of the most mechanistically direct transmembrane receptors-the intracellular domain contains a transcriptional regulator that is released from the membrane when engagement of the cognate extracellular ligand induces intramembrane proteolysis. We find that chimeric forms of Notch, in which both the extracellular sensor module and the intracellular transcriptional module are replaced with heterologous protein domains, can serve as a general platform for generating novel cell-cell contact signaling pathways. Synthetic Notch (synNotch) pathways can drive user-defined functional responses in diverse mammalian cell types. Because individual synNotch pathways do not share common signaling intermediates, the pathways are functionally orthogonal. Thus, multiple synNotch receptors can be used in the same cell to achieve combinatorial integration of environmental cues, including Boolean response programs, multi-cellular signaling cascades, and self-organized cellular patterns. SynNotch receptors provide extraordinary flexibility in engineering cells with customized sensing/response behaviors to user-specified extracellular cues.

Oligodendrocyte-selective deletion of the eIF2α kinase Perk/Eif2ak3 limits functional recovery after spinal cord injury.

After spinal cord injury (SCI), re-establishing cellular homeostasis is critical to optimize functional recovery. Central to that response is PERK signaling, which ultimately initiates a pro-apoptotic response if cellular homeostasis cannot be restored. Oligodendrocyte (OL) loss and white matter damage drive functional consequences and determine recovery potential after thoracic contusive SCI. We examined acute (<48 h post-SCI) and chronic (6 weeks post-SCI) effects of conditionally deleting Perk from OLs prior to SCI. While Perk transcript is expressed in many types of cells in the adult spinal cord, its levels are disproportionately high in OL lineage cells. Deletion of OL-Perk prior to SCI resulted in: (1) enhanced acute phosphorylation of eIF2α, a major PERK substrate and the critical mediator of the integrated stress response (ISR), (2) enhanced acute expression of the downstream ISR genes Atf4, Ddit3/Chop, and Tnfrsf10b/Dr5, (3) reduced acute OL lineage-specific Olig2 mRNA, but not neuronal or astrocytic mRNAs, (4) chronically decreased OL content in the spared white matter at the injury epicenter, (5) impaired hindlimb locomotor recovery, and (6) reduced chronic epicenter white matter sparing. Cultured primary OL precursor cells with reduced PERK expression and activated ER stress response showed: (1) unaffected phosphorylation of eIF2α, (2) enhanced ISR gene induction, and (3) increased cytotoxicity. Therefore, OL-Perk deficiency exacerbates ISR signaling and potentiates white matter damage after SCI. The latter effect is likely mediated by increased loss of Perk-/- OLs.

In Situ Single-crystal X-ray Diffraction Studies of Physisorption and Chemisorption of SO2 within a Metal-Organic Framework and Its Competitive Adsorption with Water.

Living on an increasingly polluted planet, the removal of toxic pollutants such as sulfur dioxide (SO2) from the troposphere and power station flue gas is becoming more and more important. The CPO-27/MOF-74 family of metal-organic frameworks (MOFs) with their high densities of open metal sites is well suited for the selective adsorption of gases that, like SO2, bind well to metals and have been extensively researched both practically and through computer simulations. However, until now, focus has centered upon the binding of SO2 to the open metal sites in this MOF (called chemisorption, where the adsorbent-adsorbate interaction is through a chemical bond). The possibility of physisorption (where the adsorbent-adsorbate interaction is only through weak intermolecular forces) has not been identified experimentally. This work presents an in situ single-crystal X-ray diffraction (scXRD) study that identifies discrete adsorption sites within Ni-MOF-74/Ni-CPO-27, where SO2 is both chemisorbed and physisorbed while also probing competitive adsorption of SO2 of these sites when water is present. Further features of this site have been confirmed by variable SO2 pressure scXRD studies, DFT calculations, and IR studies.

Computerized adaptive test strategies for the matrix reasoning subtest of the Wechsler Adult Intelligence Scale, 4th Edition (WAIS-IV).

OBJECTIVE: Most neuropsychological tests were developed without the benefit of modern psychometric theory. We used item response theory (IRT) methods to determine whether a widely used test - the 26-item Matrix Reasoning subtest of the WAIS-IV - might be used more efficiently if it were administered using computerized adaptive testing (CAT). METHOD: Data on the Matrix Reasoning subtest from 2197 participants enrolled in the National Neuropsychology Network (NNN) were analyzed using a two-parameter logistic (2PL) IRT model. Simulated CAT results were generated to examine optimal short forms using fixed-length CATs of 3, 6, and 12 items and scores were compared to the original full subtest score. CAT models further explored how many items were needed to achieve a selected precision of measurement (standard error ≤ .40). RESULTS: The fixed-length CATs of 3, 6, and 12 items correlated well with full-length test results (with r = .90, .97 and .99, respectively). To achieve a standard error of .40 (approximate reliability = .84) only 3-7 items had to be administered for a large percentage of individuals. CONCLUSIONS: This proof-of-concept investigation suggests that the widely used Matrix Reasoning subtest of the WAIS-IV might be shortened by more than 70% in most examinees while maintaining acceptable measurement precision. If similar savings could be realized in other tests, the accessibility of neuropsychological assessment might be markedly enhanced, and more efficient time use could lead to broader subdomain assessment.

A dominance of Mu class glutathione transferases within the equine tapeworm Anoplocephala perfoliata.

The most common equine tapeworm, Anoplocephala perfoliata, has often been neglected amongst molecular investigations and has been faced with limited treatment options. However, the recent release of a transcriptome dataset has now provided opportunities for in-depth analysis of A. perfoliata protein expression. Here, global, and sub-proteomic approaches were utilized to provide a comprehensive characterization of the A. perfoliata soluble glutathione transferases (GST) (ApGST). Utilizing both bioinformatics and gel-based proteomics, GeLC and 2D-SDS PAGE, the A. perfoliata 'GST-ome' was observed to be dominated with Mu class GST representatives. In addition, both Sigma and Omega class GSTs were identified, albeit to a lesser extent and absent from affinity chromatography approaches. Moreover, 51 ApGSTs were localized across somatic (47 GSTs), extracellular vesicles (EVs) (Whole: 1 GST, Surface: 2 GSTs) and EV depleted excretory secretory product (ESP) (9 GSTs) proteomes. In related helminths, GSTs have shown promise as novel anthelmintic or vaccine targets for improved helminth control. Thus, provides potential targets for understanding A. perfoliata novel infection mechanisms, host­parasite relationships and anthelmintic treatments.

Publisher Correction: Adolescence and the next generation.

In Fig. 4a of this Analysis, owing to an error during the production process, the year in the header of the right column was '2016' rather than '2010'. In addition, in the HTML version of the Analysis, Table 1 was formatted incorrectly. These errors have been corrected online.

Adolescence and the next generation.

Adolescent growth and social development shape the early development of offspring from preconception through to the post-partum period through distinct processes in males and females. At a time of great change in the forces shaping adolescence, including the timing of parenthood, investments in today's adolescents, the largest cohort in human history, will yield great dividends for future generations.

Psychological Constructs From the Fear Avoidance Model and Beyond as Predictors for Persisting Symptoms After Concussion: An Integrative Review.

OBJECTIVES: To identify the range of evidence for relationships between psychological factors using the Fear Avoidance Model (FAM) as a guiding framework and relevant clinical outcomes in adult patients with persisting symptoms after concussion (PSaC), develop a comprehensive understanding of psychological factors that have been identified as predictors of clinical outcomes for PSaC, and contribute to the theoretical framework of the FAM for PSaC. DATA SOURCES: Six databases (CINAHL, Embase, PsycINFO, PubMed, SportDiscus, and Web of Science) were searched by a librarian for empirical and theoretical publications and experimental and quasi-experimental study designs. The literature search was not limited by publication date restrictions. Gray literature, with the exception of doctoral dissertations, was excluded. STUDY SELECTION: We included studies in the English language consisting of human participants aged ≥18 years. Articles must have included both outcomes pertaining to PSaC (≥3mo after injury) and psychological constructs. DATA EXTRACTION: One reviewer extracted data from the resulting studies using a standardized data extraction form designed for this review. Two reviewers independently assessed risk of bias using the Quality in Prognosis Studies tool. DATA SYNTHESIS: This review found numerous psychological constructs, some directly linked to the FAM, that have potential prognostic relationships with PSaC. However, research remains limited and some psychological factors central to FAM were only identified in a small number of studies (catastrophizing, cogniphobia, and avoidance), whereas other psychological factors were studied more extensively (anxiety and depression). CONCLUSIONS: There is the need for additional evidence, and this integrative review provides an adaptation of the FAM for PSaC to be used as a guiding preliminary framework for future research. Future research should aim to include psychological factors proposed in this modified FAM to fully understand PSaC.

The impact of the COVID-19 pandemic on 397 631 elective dental admissions among the under-25s in England: a retrospective study.

BACKGROUND: COVID-19 caused widespread disruptions to health services worldwide, including reductions in elective surgery. Tooth extractions are among the most common reasons for elective surgery among children and young people (CYP). It is unclear how COVID-19 affected elective dental surgeries in hospitals over multiple pandemic waves at a national level. METHODS: Elective dental tooth extraction admissions were selected using Hospital Episode Statistics. Admission trends for the first 14 pandemic months were compared with the previous five years and results were stratified by age (under-11s, 11-16s, 17-24s). RESULTS: The most socioeconomically deprived CYP comprised the largest proportion of elective dental tooth extraction admissions. In April 2020, admissions dropped by >95%. In absolute terms, the biggest reduction was in April (11-16s: -1339 admissions, 95% CI -1411 to -1267; 17-24s: -1600, -1678 to -1521) and May 2020 (under-11s: -2857, -2962 to -2752). Admissions differed by socioeconomic deprivation for the under-11s (P < 0.0001), driven by fewer admissions than expected by the most deprived and more by the most affluent during the pandemic. CONCLUSION: Elective tooth extractions dropped most in April 2020, remaining below pre-pandemic levels throughout the study. Despite being the most likely to be admitted, the most deprived under-11s had the largest reductions in admissions relative to other groups.

Effect of vitamin E-enhanced highly cross-linked polyethylene on wear rate and particle debris in anatomic total shoulder arthroplasty: a biomechanical comparison to ultrahigh-molecular-weight polyethylene.

BACKGROUND: Particle-induced osteolysis resulting from polyethylene wear remains a source of implant failure in anatomic total shoulder designs. Modern polyethylene components are irradiated in an oxygen-free environment to induce cross-linking, but reducing the resulting free radicals with melting or heat annealing can compromise the component's mechanical properties. Vitamin E has been introduced as an adjuvant to thermal treatments. Anatomic shoulder arthroplasty models with a ceramic head component have demonstrated that vitamin E-enhanced polyethylene show improved wear compared with highly cross-linked polyethylene (HXLPE). This study aimed to assess the biomechanical wear properties and particle size characteristics of a novel vitamin E-enhanced highly cross-linked polyethylene (VEXPE) glenoid compared to a conventional ultrahigh-molecular-weight polyethylene (UHMWPE) glenoid against a cobalt chromium molybdenum (CoCrMo) head component. METHODS: Biomechanical wear testing was performed to compare the VEXPE glenoid to UHMWPE glenoid with regard to pristine polyethylene wear and abrasive endurance against a polished CoCrMo alloy humeral head in an anatomic shoulder wear-simulation model. Cumulative mass loss (milligrams) was recorded, and wear rate calculated (milligrams per megacycle [Mc]). Under pristine wear conditions, particle analysis was performed, and functional biologic activity (FBA) was calculated to estimate particle debris osteolytic potential. In addition, 95% confidence intervals for all testing conditions were calculated. RESULTS: The average pristine wear rate was statistically significantly lower for the VEXPE glenoid compared with the HXLPE glenoid (0.81 ± 0.64 mg/Mc vs. 7.00 ± 0.45 mg/Mc) (P < .05). Under abrasive wear conditions, the VEXPE glenoid had a statistically significant lower average wear rate compared with the UHMWPE glenoid comparator device (18.93 ± 5.80 mg/Mc vs. 40.47 ± 2.63 mg/Mc) (P < .05). The VEXPE glenoid demonstrated a statistically significant improvement in FBA compared with the HXLPE glenoid (0.21 ± 0.21 vs. 1.54 ± 0.49 (P < .05). CONCLUSIONS: A new anatomic glenoid component with VEXPE demonstrated significantly improved pristine and abrasive wear properties with lower osteolytic particle debris potential compared with a conventional UHMWPE glenoid component. Vitamin E-enhanced polyethylene shows early promise in shoulder arthroplasty components. Long-term clinical and radiographic investigation needs to be performed to verify if these biomechanical wear properties translate to diminished long-term wear, osteolysis, and loosening.

Associations among Trauma Exposure, Post-Traumatic Stress Symptoms and Alcohol Use in Black/African American Treatment-Seeking Adults.

OBJECTIVE: Black/African American (AA) individuals are a group at risk for co-occurring posttraumatic stress disorder (PTSD) symptoms and alcohol use due to unique cultural and system-level barriers. Although associations between trauma exposure, PTSD symptoms, and alcohol use are well established across various populations, Black/AA individuals are underrepresented in this literature, and related findings in this population are inconclusive. Thus, the goal of this study was to examine the associations among trauma exposure, PTSD symptoms, and alcohol use in a sample of treatment-seeking, Black/AA adults. We hypothesized that trauma exposure and alcohol use would be positively associated and that this relationship would be mediated by PTSD symptoms. METHODS: This study conducted secondary analysis of screening data from a PTSD and alcohol use disorder clinical trial. Participants were 96 Black/AA adults (57.3% male; 2.0% Hispanic; M age = 44.73, SD = 11.83) who were seeking treatment for alcohol use and endorsed trauma exposure. Associations between trauma exposure, PTSD symptom severity, and quantity and frequency of alcohol use were tested using bivariate correlations and linear regressions. Hypothesized indirect effects were tested using IBM SPSS Statistics Version 27 PROCESS model 4 with bootstrapping. RESULTS: Findings illustrated a significant positive association between trauma exposure and PTSD symptoms and between PTSD symptoms and drinks per typical drinking day. PTSD symptoms were not significantly associated with number of drinking days. Tests of indirect effects were significant for trauma exposure on drinks per typical drinking day through PTSD symptoms. CONCLUSIONS: Results from the test of indirect effects suggest that among Black/AA adults with heavy alcohol use and trauma exposure, trauma exposure is associated with PTSD symptoms, which in turn is associated with quantity of alcohol use. These findings are consistent with research conducted with White/mixed groups and align with tenets of the self-medication model of PTSD-AUD comorbidity. These findings support current practices that highlight the importance of screening for and addressing PTSD and alcohol use in individuals exposed to trauma. Findings from this paper provide initial data on understudied relationships in an underserved sample and several suggestions are made to generate future research and improve clinical care for Black/AA adults. CLINICAL TRIALS REGISTRY NAME: Pharmacogenetic Treatment With Anti-Glutaminergic Agents for Comorbid PTSD & AUD; ClinicalTrials.gov Identifier: NCT02884908.

Childhood attention-deficit hyperactivity disorder: socioeconomic inequalities in symptoms, impact, diagnosis and medication.

BACKGROUND: Children from disadvantaged backgrounds are at greater risk of attention-deficit hyperactivity disorder (ADHD)-related symptoms, being diagnosed with ADHD, and being prescribed ADHD medications. We aimed to examine how inequalities manifest across the 'patient journey', from perceptions of impacts of ADHD symptoms on daily life, to the propensity to seek and receive a diagnosis and treatment. METHODS: We investigated four 'stages': (1) symptoms, (2) caregiver perception of impact, (3) diagnosis and (4) medication, in two data sets: UK Millennium Cohort Study (MCS, analytic n ~ 9,000), with relevant (parent-reported) information on all four stages (until 14 years); and a population-wide 'administrative cohort', which includes symptoms (child health checks) and prescriptions (dispensing records), born in Scotland, 2010-2012 (analytic n ~ 100,000), until ~6 years. We described inequalities according to maternal occupational status, with percentages and relative indices of inequality (RII). RESULTS: The prevalence of ADHD symptoms and medication receipt was considerably higher in the least compared to the most advantaged children in the administrative cohort (RIIs of 5.9 [5.5-6.4] and 8.1 [4.2-15.6]) and the MCS (3.08 [2.68-3.55], 3.75 [2.21-6.36]). MCS analyses highlighted complexities between these two stages, however, those from least advantaged backgrounds, with ADHD symptoms, were the least likely to perceive impacts on daily life (15.7% vs. average 19.5%) and to progress from diagnosis to medication (44.1% vs. average 72.5%). CONCLUSIONS: Despite large inequalities in ADHD symptoms and medication, parents from the least advantaged backgrounds were less likely to report impacts of ADHD symptoms on daily life, and their children were less likely to have received medication postdiagnosis, highlighting how patient journeys differed according to socioeconomic circumstances.

Characterization of microtubule-associated protein tau isoforms and Alzheimer's disease-like pathology in normal sheep (Ovis aries): relevance to their potential as a model of Alzheimer's disease.

Alzheimer's disease is a chronic neurodegenerative disease that accounts for up to 80% of all dementias. Characterised by deteriorations of memory and cognitive function, the key neuropathological features are accumulations of ß-amyloid and hyperphosphorylated tau, as 'plaques' and 'tangles', respectively. Despite extensive study, however, the exact mechanism underlying aggregate formation in Alzheimer's disease remains elusive, as does the contribution of these aggregates to disease progression. Importantly, a recent evaluation of current Alzheimer's disease animal models suggested that rodent models are not able to fully recapitulate the pathological intricacies of the disease as it occurs in humans. Therefore, increasing attention is being paid to species that might make good alternatives to rodents for studying the molecular pathology of Alzheimer's disease. The sheep (Ovis aries) is one such species, although to date, there have been few molecular studies relating to Alzheimer's disease in sheep. Here, we investigated the Alzheimer's disease relevant histopathological characteristics of 22 sheep, using anti-ß-amyloid (Abcam 12267 and mOC64) and phosphorylation specific anti-tau (AT8 and S396) antibodies. We identified numerous intraneuronal aggregates of both ß-amyloid and tau that are consistent with early Alzheimer's disease-like pathology. We confirmed the expression of two 3-repeat (1N3R, 2N3R) and two 4-repeat (1N4R, 2N4R) tau isoforms in the ovine brain, which result from the alternative splicing of two tau exons. Finally, we investigated the phosphorylation status of the serine396 residue in 30 sheep, and report that the phosphorylation of this residue begins in sheep aged as young as 2 years. Together, these data show that sheep exhibit naturally occurring ß-amyloid and tau pathologies, that reflect those that occur in the early stages of Alzheimer's disease. This is an important step towards the validation of the sheep as a feasible large animal species in which to model Alzheimer's disease.

Predicting the in vitro dissolution rate constant of mineral wool fibers from fiber composition.

OBJECTIVE: We developed predictive formulae for the in vitro dissolution rate constant kdis of acid-soluble synthetic vitreous fibers (SVF), paralleling our earlier work with glass wools, which are typically more soluble at neutral pH. Developing simple models for predicting the kdis of a fiber can allow prediction of in vivo behavior, aid fiber developers, and potentially reduce in vivo testing. METHODS: The kdis of several acid-soluble SVF were determined using high simulant fluid flow/fiber surface area (F/A) conditions via a single-fiber measurement system. Four fluids were employed, varying in base composition and citrate levels. Equations predicting the kdis were derived from fiber chemistry and dissolution measurements for two of the fluids. RESULTS: Testing of several fibers showed a ∼10× increase in the kdis when citrate was included in the simulant solution. Data from tests with Stefaniak's citrate-free Phagoloysosmal Simulant Fluid (PSF) yielded kdis values aligned with expectations from in vivo results, unlike results from citrate-containing modified Gamble's solution. Predictive equations relating fiber chemistry to kdis showed reasonable agreement between the measured and predicted values. CONCLUSIONS: Citrate inclusion in the solution under high F/A conditions significantly increased the measured kdis. This resulted in more biorelevant data being obtained using the PSF fluid with the high F/A method used. The developed predictive equations, sufficient for fiber development work, require refinement before a recommending their use in place of in vivo biopersistence testing. Significant fit improvements are possible through additional measurements under these experimental conditions.

This needs to be a journey that we're actually on together'-the introduction of integrated care systems for children and young people in England: a qualitative study of the views of local system stakeholders during winter 2021/22.

BACKGROUND: Integrated care has become a central feature of health system reform worldwide. In England, Integrated Care Systems (ICS) are intended to improve integration across public health, the National Health Service (NHS), education and social care. By April 2021, England had been divided into 42 geographical areas, each tasked with developing local ICS provision. However, it was not clear how ICSs would address the specific needs of children and young people (CYP). This study elicited the views of senior professional stakeholders in the first year of the ICS national roll out, to learn how integrated care for CYP was being implemented within the ICSs and future plans for service provision. METHODS: A qualitative analysis of in-depth interviews with stakeholders, including healthcare professionals, NHS managers and local authority leaders (n = 25) selected from a diverse sample of ICSs (n = 7) across England, conducted during winter 2021/22. Reflexive thematic analysis involving a collaborative coding approach was used to analyse interview transcripts. RESULTS: Four themes were identified, indicating challenges and opportunities for ICSs in relation to the health of CYP: 1) Best start in life (a more holistic approach to health afforded by integrated care); 2) Local and national contexts (tensions between local and national settings and priorities); 3) Funding and planning (instituting innovative, long-term plans using limited existing CYP funding streams); 4) Organisational complexities (integrating the work of diverse organisations). CONCLUSIONS: The views of stakeholders, provided at the beginning of the journey towards developing local ICS CYP provision, revealed a common aspiration to change focus from provision of acute, largely adult-orientated services towards one with a broader, population health remit, including prevention and early intervention. This would be delivered by integration of a range of local services, including health, education, housing and social care, to set CYP on a life-long path towards improved health and wellbeing. Yet there was an awareness that change would take place over time within existing national policy and funding frameworks, and would require overcoming organisational barriers through further developing local collaborations and partnerships. As ICSs mature, the experiences of stakeholders should continue to be canvassed to identify practical lessons for successful CYP integrated care.

Causes of death and pathogen prevalence in bottlenose dolphins Tursiops truncatus stranded in Alabama, USA, between 2015 and 2020, following the Deepwater Horizon oil spill.

Between 2010 and 2014, an unusual mortality event (UME) involving bottlenose dolphins Tursiops truncatus occurred in the northern Gulf of Mexico, associated with the Deepwater Horizon oil spill (DWHOS). Cause of death (COD) patterns in bottlenose dolphins since then have not been analyzed, and baseline prevalence data for Brucella ceti and cetacean morbillivirus, 2 pathogens previously reported in this region, are lacking. We analyzed records from bottlenose dolphins stranded in Alabama from 2015 to 2020 with necropsy and histological findings to determine COD (n = 108). This period included another UME in 2019 associated with prolonged freshwater exposure. A subset of individuals that stranded during this period were selected for molecular testing for Brucella spp. and Morbillivirus spp. Causes of death for all age classes were grouped into 6 categories, including (1) human interaction, (2) infectious disease, (3) noninfectious disease (prolonged freshwater exposure and degenerative), (4) trauma, (5) multifactorial, and (6) unknown. Two additional categories unique to perinates included fetal distress and in utero pneumonia. Human interaction was the most common primary COD (19.4%) followed closely by infectious disease (17.6%) and noninfectious disease (freshwater exposure; 13.9%). Brucella was detected in 18.4% of the 98 animals tested, but morbillivirus was not detected in any of the 66 animals tested. Brucella was detected in some moderately to severely decomposed carcasses, indicating that it may be beneficial to test a broad condition range of stranded animals. This study provides valuable information on COD in bottlenose dolphins in Alabama following the DWHOS and is the first to examine baseline prevalence of 2 common pathogens in stranded animals from this region.

Extracellular Vesicles in Microbes, Pathogens, and Infectious Diseases.

Extracellular vesicles (EVs) are nanosized lipid bilayer particles that are produced by all kinds of organisms, including both pathogenic and non-pathogenic archaea, bacteria, fungi, and parasites [...].

Learning outcomes in primary school children with emotional problems: a prospective cohort study.

BACKGROUND: Academic difficulties are common in adolescents with mental health problems. Although earlier childhood emotional problems, characterised by heightened anxiety and depressive symptoms are common forerunners to adolescent mental health problems, the degree to which mental health problems in childhood may contribute independently to academic difficulties has been little explored. METHODS: Data were drawn from a prospective cohort study of students in Melbourne, Australia (N = 1239). Data were linked with a standardised national assessment of academic performance at baseline (9 years) and wave three (11 years). Depressive and anxiety symptoms were assessed at baseline and wave two (10 years). Regression analyses estimated the association between emotional problems (9 and/or 10 years) and academic performance at 11 years, adjusting for baseline academic performance, sex, age and socioeconomic status, and hyperactivity/inattention symptoms. RESULTS: Students with depressive symptoms at 9 years of age had lost nearly 4 months of numeracy learning two years later after controlling for baseline academic performance and confounders. Results were similar for anxiety symptoms. Regardless of when depressive symptoms occurred there were consistent associations with poorer numeracy performance at 11 years. The association of depressive symptoms with reading performance was weaker than for numeracy if they were present at wave two. Persistent anxiety symptoms across two waves led to nearly a 4 month loss of numeracy learning at 11 years, but the difference was not meaningful for reading. Findings were similar when including hyperactivity/inattention symptoms. CONCLUSIONS: Childhood anxiety and depression are not only forerunners of later mental health problems but predict academic achievement. Partnerships between education and health systems have the potential to not only improve childhood emotional problems but also improve learning.

Fasciola hepatica Cathepsin L Zymogens: Immuno-Proteomic Evidence for Highly Immunogenic Zymogen-Specific Conformational Epitopes to Support Diagnostics Development.

Fasciola hepatica, the common liver fluke and causative agent of zoonotic fasciolosis, impacts on food security with global economic losses of over $3.2 BN per annum through deterioration of animal health, productivity losses, and livestock death and is also re-emerging as a foodborne human disease. Cathepsin proteases present a major vaccine and diagnostic target of the F. hepatica excretory/secretory (ES) proteome, but utilization in diagnostics of the highly antigenic zymogen stage of these proteins is surprisingly yet to be fully exploited. Following an immuno-proteomic investigation of recombinant and native procathepsins ((r)FhpCL1), including mass spectrometric analyses (DOI: 10.6019/PXD030293), and using counterpart polyclonal antibodies to a recombinant mutant procathepsin L (anti-rFhΔpCL1), we have confirmed recombinant and native cathepsin L zymogens contain conserved, highly antigenic epitopes that are conformationally dependent. Furthermore, using diagnostic platforms, including pilot serum and fecal antigen capture enzyme-linked immunosorbent assay (ELISA) tests, the diagnostic capacities of cathepsin L zymogens were assessed and validated, offering promising efficacy as markers of infection and for monitoring treatment efficacy.

Professionalism of Admitting and Consulting Services and Trauma Patient Outcomes.

OBJECTIVE: To determine whether trauma patients managed by an admitting or consulting service with a high proportion of physicians exhibiting patterns of unprofessional behaviors are at greater risk of complications or death. SUMMARY BACKGROUND DATA: Trauma care requires high-functioning interdisciplinary teams where professionalism, particularly modeling respect and communicating effectively, is essential. METHODS: This retrospective cohort study used data from 9 level I trauma centers that participated in a national trauma registry linked with data from a national database of unsolicited patient complaints. The cohort included trauma patients admitted January 1, 2012 through December 31, 2017. The exposure of interest was care by 1 or more high-risk services, defined as teams with a greater proportion of physicians with high numbers of patient complaints. The study outcome was death or complications within 30 days. RESULTS: Among the 71,046 patients in the cohort, 9553 (13.4%) experienced the primary outcome of complications or death, including 1875 of 16,107 patients (11.6%) with 0 high-risk services, 3788 of 28,085 patients (13.5%) with 1 high-risk service, and 3890 of 26,854 patients (14.5%) with 2+ highrisk services (P < 0.001). In logistic regression models adjusting for relevant patient, injury, and site characteristics, patients who received care from 1 or more high-risk services were at 24.1% (95% confidence interval 17.2% to 31.3%; P < 0.001) greater risk of experiencing the primary study outcome. CONCLUSIONS: Trauma patients who received care from at least 1 service with a high proportion of physicians modeling unprofessional behavior were at an increased risk of death or complications.