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A nondestructive and rapid classification approach was developed for identifying aflatoxin-contaminated single peanut kernels using field-portable vibrational spectroscopy instruments (FT-IR and Raman). Single peanut kernels were either spiked with an aflatoxin solution (30 ppb–400 ppb) or hexane (control), and their spectra were collected via Raman and FT-IR. An uHPLC-MS/MS approach was used to verify the spiking accuracy via determining actual aflatoxin content on the surface of randomly selected peanut samples. Supervised classification using soft independent modeling of class analogies (SIMCA) showed better discrimination between aflatoxin-contaminated (30 ppb–400 ppb) and control peanuts with FT-IR compared with Raman, predicting the external validation samples with 100% accuracy. The accuracy, sensitivity, and specificity of SIMCA models generated with the portable FT-IR device outperformed the methods in other destructive studies reported in the literature, using a variety of vibrational spectroscopy benchtop systems. The discriminating power analysis showed that the bands corresponded to the C=C stretching vibrations of the ring structures of aflatoxins were most significant in explaining the variance in the model, which were also reported for Aspergillus-infected brown rice samples. Field-deployable vibrational spectroscopy devices can enable in situ identification of aflatoxin-contaminated peanuts to assure regulatory compliance as well as cost savings in the production of peanut products.

Many national, state, and institutional policies and initiatives advocate for change in higher education through structured forms of data use. The case study of "Old Main University" presented in this article shows how local reformers (n = 9) drew on data and data use tools provided by a long-term action research project implemented at the university to advance racial equity goals at their university. The case narrative utilizes practice theory, cultural historical activity theory (CHAT), and narrative inquiry to illustrate how administrative leaders and faculty at Old Main University coordinated their efforts in a sustained manner through two cycles of practitioner inquiry that was responsive to policy goals. The findings show that data use is productive to promote racial equity when data and data use protocols are used iteratively and in interaction among practitioners who use them to identify inequities rooted in their own practices. The findings support the conclusion that, to sustain change efforts as long-term (mesogenetic) projects, policy makers and local reformers should plan to iteratively redesign data tools, practices, and policies to institute changes in everyday (microgenetic) work practices. Such purposeful redesign holds potential to re-structure professional interactions, sustain motivation and organizational learning, and acculturate practitioners to equity as a standard of practice.

Objectives In recent years, ‘deaths of despair’ due to drugs, alcohol and suicide have contributed to rising mid-life mortality in the USA. We examine whether despair-related deaths and mid-life mortality trends are also changing in peer countries, the UK and Canada.Design Descriptive analysis of population mortality rates.Setting The USA, UK (and constituent nations England and Wales, Northern Ireland and Scotland) and Canada, 2001–2019.Participants Full population aged 35–64 years.Outcome measures We compared all-cause and ‘despair’-related mortality trends at mid-life across countries using publicly available mortality data, stratified by three age groups (35–44, 45–54 and 55–64 years) and by sex. We examined trends in all-cause mortality and mortality by causes categorised as (1) suicides, (2) alcohol-specific deaths and (3) drug-related deaths. We employ several descriptive approaches to visually inspect age, period and cohort trends in these causes of death.Results The USA and Scotland both saw large relative increases and high absolute levels of drug-related deaths. The rest of the UK and Canada saw relative increases but much lower absolute levels in comparison. Alcohol-specific deaths showed less consistent trends that did not track other ‘despair’ causes, with older groups in Scotland seeing steep declines over time. Suicide deaths trended slowly upward in most countries.Conclusions In the UK, Scotland has suffered increases in drug-related mortality comparable with the USA, while Canada and other UK constituent nations did not see dramatic increases. Alcohol-specific and suicide mortalities generally follow different patterns to drug-related deaths across countries and over time, questioning the utility of a cohesive ‘deaths of despair’ narrative.

IntroductionNatural products discovered from bacteria provide critically needed therapeutic leads for drug discovery, and myxobacteria are an established source for metabolites with unique chemical scaffolds and biological activities. Myxobacterial genomes accommodate an exceptional number and variety of biosynthetic gene clusters (BGCs) which encode for features involved in specialized metabolism.MethodsIn this study, we describe the collection, sequencing, and genome mining of 20 myxobacteria isolated from rhizospheric soil samples collected in North America.ResultsNine isolates were determined to be novel species of myxobacteria including representatives from the genera Archangium, Myxococcus, Nannocystis, Polyangium, Pyxidicoccus, Sorangium, and Stigmatella. Growth profiles, biochemical assays, and descriptions were provided for all proposed novel species. We assess the BGC content of all isolates and observe differences between Myxococcia and Polyangiia clusters.DiscussionContinued discovery and sequencing of novel myxobacteria from the environment provide BGCs for the genome mining pipeline. Utilizing complete or near-complete genome sequences, we compare the chromosomal organization of BGCs of related myxobacteria from various genera and suggest that the spatial proximity of hybrid, modular clusters contributes to the metabolic adaptability of myxobacteria.

BackgroundResearchers and policy-makers have highlighted that the potential for organized sports to promote health has been underexploited. Sports clubs have limited capacity to promote health due to their voluntary nature and have called for support from their national sports federations. The present article provides guidelines, based on the theoretical principles of health promoting sports clubs and an analysis of practical tools and proven strategies, to support national sports federations to invest in health promotion (HP).MethodsA qualitative iterative study was undertaken, based on five 2-h meetings of a group of 15 international researchers in HP in sports clubs. Notes and minutes from meetings, as well as shared outputs were analyzed based on the health promoting sports club framework.ResultsGuidelines developed for national sports federations to promote health includes a definition of a health promoting sports federation (HPSF), a description of how the settings-based approach to HP adapts to national sports federations, as well as practical applications of health promoting sports club’s intervention strategies. The analysis of existing tools also demonstrated that most tools are centered on a single dimension of health (social, mental, physical, spiritual or community), and often on a specific health topic. Furthermore, they do not cover HP as a continuous long-lasting process, but are generally short-term programs. The HPSF clarifies theoretical concepts, their practical implementation via case studies and outlines intervention components and tools useful for sports federations in their implementation of HP.ConclusionThe guidelines developed in this study are intended to facilitate national sports federations to acknowledge/understand, reinforce/underpin and foster current and further investment in HP.

BackgroundWe report a rare case of a 19-year-old female progressively affected by a peripheral arteriovenous malformation (pAVM), a midline cerebellar astrocytoma, and a brain arteriovenous malformation (bAVM).Case descriptionShe presented with a pulsatile mass on her left cheek, which was classified as a pAVM through angiography. Following treatment with embolization and surgical resection, she returned with enlargement of the mass and imaging incidentally identified a cerebellar astrocytoma. Suboccipital craniotomy, C1 laminectomy, and endoscopic third ventriculostomy were subsequently performed. She was later treated again for growth of her pAVM, and angiography revealed the presence of a left temporal bAVM, which was resected via a pterional craniotomy.ConclusionsPathological staining identified activation of mTOR and RAS/MAPK pathway in the patient's pAVM and bAVM tissue samples. Furthermore, genetic sequencing demonstrated an activating MAPK21 (K57N) mutation in the pAVM and a gain of distal chromosome 7q in the pilocytic astrocytoma. No germline mutation was identified to explain all pathologies. This case demonstrates the need for continued development and further integration of multi-disciplinary genetic, radiological, and neurological treatment teams to effectively care for such complex presentations.

BackgroundSleep disturbance is a core feature of post-traumatic stress disorder (PTSD). Given the relationship between sleep disturbance and PTSD, there has been a relative paucity of studies examining the potential therapeutic impact of using pharmacotherapy to target sleep disturbance in patients with PTSD. Eszopiclone (ESZ) is a non-benzodiazepine y-aminobutyric acid-A receptor agonist indicated for the treatment of sleep and may affect sleep in patients with PTSD.AimTo evaluate the efficacy of ESZ vs placebo (PBO) for patients with PTSD and insomnia.MethodsThe study was a 12-wk, double blind, randomized controlled trial with 3 mg of ESZ (n = 13) or PBO (n = 12).ResultsPatients in both arms experienced significant improvement in PTSD symptoms as assessed by the Clinician-Administered PTSD Scale for DSM-IV (CAPS): ESZ (t11 = -3.12, P = 0.005) and PBO (t11 = -3.5, P = 0.002) and by self-report with the Short PTSD Rating Interview (ESZ t11 = -3.38, P = 0.003 and PBO t11 = -4.48, P = 0.0005). There were no significant differences between treatments on the CAPS (t22 = -0.13, P = 0.70) or the Short PTSD Rating Interview (t22 = -0.58, P = 0.56). Similarly, both treated groups improved on sleep measures as assessed by the Pittsburgh Sleep Quality Index with PTSD Addendum (PSQI) and on total sleep time (TST) and sleep latency assessed by actigraphy with no significant differences between groups (PSQI t22 = -0.24, P = 0.81; total sleep time t10 = 0.13, P = 0.90 and sleep latency t10 = 0.68, P = 0.50). There was a significant correlation between improvement in sleep and overall improvement in PTSD as measured by change scores on the PSQI and CAPS, r(8) = 0.79, P = 0.01 for ESZ treated subjects, but not for those treated with PBO r(9) = 0.16, P = 0.69. Adverse events of ESZ were consistent with the known profile of the medication including dysgeusia (30%, mild), sedation (20%, mild) and headache (20%, moderate to severe).ConclusionResults do not support the hypothesis of a specific positive effect of ESZ compared to PBO for measures of PTSD and associated sleep disturbance.

Zika virus (ZIKV) infection of pregnant women is associated with congenital Zika syndrome (CZS) and no vaccine is available, although several are being tested in clinical trials. We tested the efficacy of ZIKV DNA vaccine VRC5283 in a rhesus macaque model of congenital ZIKV infection. Most animal vaccine experiments have a set pathogen exposure several weeks or months after vaccination. In the real world, people encounter pathogens years or decades after vaccination, or may be repeatedly exposed if the virus is endemic. To more accurately mimic how this vaccine would be used, we immunized macaques before conception and then exposed them repeatedly to ZIKV during early and mid-gestation. In comparison to unimmunized animals, vaccinated animals had a significant reduction in peak magnitude and duration of maternal viremia, early fetal loss, fetal infection, and placental and fetal brain pathology. Vaccine-induced neutralizing antibody titers on the day of first ZIKV exposure were negatively associated with the magnitude of maternal viremia, and the absence of prolonged viremia was associated with better fetal outcomes. These data support further clinical development of ZIKV vaccine strategies to protect against negative fetal outcomes.

BackgroundThe objective of this study is to describe the use of targeted therapies for the treatment of advanced renal cell carcinoma (RCC) and overall survival (OS) among patients in clinical practice in the Veterans Health Administration (VHA).MethodsA retrospective cohort of 286 patients from 24 VHA Medical Centers diagnosed with advanced clear cell RCC between Fiscal Year (FY) 2010 and FY2014 was followed through September 30, 2016. Among patients who received targeted therapy, we described the medications taken, duration of therapy, and overall survival. We also assessed the effect of the first therapy received on overall survival using Cox Proportional Hazards models.ResultsThere were 66 patients who did not receive therapy for their advanced RCC. Of the 220 treated patients, the mean (sd) number of medications received was 1.9 (1.1). The medications most commonly used first were sunitinib (61.8%), pazopanib (17.3%), and temsirolimus (10.9%). The median duration of first-line therapy was 86 days (interquartile range [IQR] 42, 210). Median total duration of therapy was 159 days (IQR 58, 397). 62.3% of patients had ≥ 1 dose of therapy held or reduced, mainly due to an adverse drug event (ADE). Median survival from the start of treatment to death was 1.08 years (IQR 0.80, 1.31). Finally, receipt of temsirolimus vs sunitinib (HR 1.95 [95%CI 1.09,3.47]) as the first targeted therapy was independently associated with an increased hazard of death.ConclusionOur analysis of targeted therapies for advanced RCC in VHA suggests duration of treatment is shorter in a real-world setting than in clinical trials, and dose reductions and ADEs are more common.

Abstract Background Increases in serum gamma‐glutamyltransferase (GGT) activity have been reported in Thoroughbred (TB) racehorses and associated with maladaptation to training but the underlying etiology remains unknown. Hypothesis/Objectives Classify the etiology of high GGT syndrome in racing TBs by assessment of pancreatic enzymes, vitamin E concentrations, and both a candidate gene and whole genome association study. We hypothesized that a genetic variant resulting in antioxidant insufficiency or pancreatic dysfunction would be responsible for high GGT syndrome in TBs. Animals A total of 138 California racing TBs. Amylase: n = 31 affected (serum GGT activity ≥60 IU/L), n = 52 control (serum GGT activity

Abstract Background There has been a growing interest in the association between maternal levels of vitamin D during pregnancy and offspring autism. However, whether any associations reflect causal effects is still inconclusive. Methods We used data from a UK-based pregnancy cohort study (Avon Longitudinal Study of Parents and Children) comprising 7689 births between 1991 and 1992 with maternal blood vitamin D levels recorded during pregnancy and at least one recorded outcome measure, including autism diagnosis and autism-associated traits. The association between each outcome with seasonal and gestational age-adjusted maternal serum 25-hydroxyvitamin D during pregnancy was estimated using confounder-adjusted regression models. Multiple imputation was used to account for missing data, and restricted cubic splines were used to investigate nonlinear associations. Mendelian randomization was used to strengthen causal inference. Results No strong evidence of an association between maternal serum 25-hydroxyvitamin D during pregnancy and any offspring autism-associated outcome was found using multivariable regression analysis (autism diagnosis: adjusted OR = 0.98, 95% CI = 0.90–1.06), including with multiple imputation (autism diagnosis: adjusted OR = 0.99, 95% CI = 0.93–1.06), and no evidence of a causal effect was suggested by Mendelian randomization (autism diagnosis: causal OR = 1.08, 95% CI = 0.46–2.55). Some evidence of increased odds of autism-associated traits at lower levels of maternal serum 25-hydroxyvitamin D was found using spline analysis. Limitations Our study was potentially limited by low power, particularly for diagnosed autism cases as an outcome. The cohort may not have captured the extreme lows of the distribution of serum 25-hydroxyvitamin D, and our analyses may have been biased by residual confounding and missing data. Conclusions The present study found no strong evidence of a causal link between maternal vitamin D levels in pregnancy and offspring diagnosis or traits of autism.

With increased availability of disaggregated conflict event data for analysis, there are new and old concerns about bias. All data have biases, which we define as an inclination, prejudice, or directionality to information. In conflict data, there are often perceptions of damaging bias, and skepticism can emanate from several areas, including confidence in whether data collection procedures create systematic omissions, inflations, or misrepresentations. As curators and analysts of large, popular data projects, we are uniquely aware of biases that are present when collecting and using event data. We contend that it is necessary to advance an open and honest discussion about the responsibilities of all stakeholders in the data ecosystem – collectors, researchers, and those interpreting and applying findings – to thoughtfully and transparently reflect on those biases; use data in good faith; and acknowledge limitations. We therefore posit an agenda for data responsibility considering its collection and critical interpretation.

The transradial approach (TRA) is an effective and safe alternative to transfemoral access for diagnostic neuroangiography and craniocervical interventions. While the technical aspects of supraclavicular intervention are well-described, there are little data on the TRA for thoracolumbar angiography and intervention. The authors describe the feasibility of the TRA for preoperative thoracic tumor embolization, emphasizing technique, device selection, navigation, and catheterization of thoracolumbar segmental arteries. This approach extends the benefits of TRA to spinal interventional neuroradiology.

Objective: We aimed to evaluate and compare the functional characteristics, safety profile and effectiveness of two commonly used ureteral access sheaths (UAS) during flexible ureteroscopy. Methods: After institutional review board approval, patients with proximal ureteral or kidney stones requiring flexible ureteroscopy and UAS were prospectively randomized to group I or group II according to the type of access sheath used. Primary outcome was incidence of intraoperative complications. Results: Eighty-eight patients were enrolled in the study, 44 patients in each group. Sheath size 12/14 FR was used in both cohorts. Median (IQR) stone size was 10 mm (7-13.5) and 10.5 mm (7.37-14) in group I and II respectively (p = 0.915). Nineteen and twenty patients, in group I and II respectively, were pre-stented. Subjective resistance with insertion of the UAS was observed in 9 and 11 patients in group I and II respectively (p = 0.61) while failed insertion was encountered in one patient in group I. Traxer grade 1 ureteral injury was noted in 5 and 6 patients in group I and II respectively while grade 3 injury was seen in 1 patient for both cohorts (p = 0.338). There was less resistance for UAS placement in pre-stented patients (p = 0.0202) but without significant difference in ureteric injury incidence (p = 0.175). Emergency department visits were encountered in 7 (group I) and 5 patients (group II) (p = 0.534). Conclusions: The studied UASs were comparable regarding safety and efficacy in the current study. Pre-stented and dilated ureters had less resistance to insertion although this was not reflected on incidence of ureteric injury.

Lead (Pb) toxicity is a major health problem and bone is the major reservoir. Lead is detrimental to bone, affects bone remodeling and is associated with elderly fractures. Osteocalcin (OC) affects bone remodeling, improves fracture resistance and decreases with age and in some diseases. The effect of lead in osteocalcin depleted bone is unknown and of interest. We compared bone mineral properties of control and Pb exposed (from 2 to 6 months) femora from female adult C57BL6 OC+/+ and OC−/− mice using Fourier Transform Infrared Imaging (FTIRI), Micro-computed tomography (uCT), bone biomechanical measurements and serum turnover markers (P1NP, CTX). Lead significantly increased turnover in OC+/+ and in OC−/− bones producing increased total volume, area and marrow area/total area with decreased BV/TV compared to controls. The increased turnover decreased mineral/matrix vs. Oc+/+ and increased mineral/matrix and crystallinity vs. OC−/−. PbOC−/− had increased bone formation, cross-sectional area (Imin) and decreased collagen maturity compared OC−/− and PbOC+/+. Imbalanced turnover in PbOC−/− confirmed the role of osteocalcin as a coupler of formation and resorption. Bone strength and stiffness were reduced in OC−/− and PbOC−/− due to reduced material properties vs. OC+/+ and PbOC+/+ respectively. The PbOC−/− bones had increased area to compensate for weaker material properties but were not proportionally stronger for increased size. However, at low lead levels osteocalcin plays the major role in bone strength suggesting increased fracture risk in low Pb2+ exposed elderly could be due to reduced osteocalcin as well. Years of low lead exposure or higher blood lead levels may have an additional effect on bone strength.

Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor, known for its poor prognosis and high recurrence rate. Current standard of care includes surgical resection followed by combined radiotherapy and chemotherapy. Although immunotherapies have yielded promising results in hematological malignancies, their successful application in GBM remains limited due to a host of immunosuppressive factors unique to GBM. As a result of these roadblocks, research efforts have focused on utilizing combinatorial immunotherapies that target networks of immune processes in GBM with promising results in both preclinical and clinical trials, although limitations in overcoming the immunosuppressive factors within GBM remain. In this review, we aim to discuss the intrinsic and adaptive immune resistance unique to GBM and to summarize the current evidence and outcomes of engineered and non-engineered treatments targeted at overcoming GBM resistance to immunotherapy. Additionally, we aim to highlight the most promising strategies of targeted GBM immunotherapy combinatorial treatments and the insights that may directly improve the current patient prognosis and clinical care.

Atopic dermatitis is a chronic condition where epidermal barrier dysfunction and cytokine production by infiltrating immune cells exacerbate skin inflammation and damage. A total lipid extract from Macrocystis pyrifera, a brown seaweed, was previously reported to suppress inflammatory responses in monocytes. Here, treatment of human HaCaT keratinocytes with M. pyrifera lipids inhibited tumour necrosis factor (TNF)-α induced TNF receptor-associated factor 2 and monocyte chemoattractant protein (MCP)-1 protein production. HaCaT cells stimulated with TNF-α, interleukin (IL)-4, and IL-13 showed loss of claudin-1 tight junctions, but little improvement was observed following lipid pre-treatment. Three-dimensional cultures of HaCaT cells differentiated at the air–liquid interface showed increased MCP-1 production, loss of claudin-1 tight junctions, and trans-epidermal leakage with TNF-α, IL-4, and IL-13 stimulation, with all parameters reduced by lipid pre-treatment. These findings suggest that M. pyrifera lipids have anti-inflammatory and barrier-protective effects on keratinocytes, which may be beneficial for the treatment of atopic dermatitis or other skin conditions.

Introduction: The aim of this study was to address and enhance our ability to study the clinical outcome of limb salvage (LS), a commonly referenced but ill-defined clinical care pathway, by developing a data-driven approach for the identification of LS cases using existing medical code data to identify characteristic diagnoses and procedures, and to use that information to describe a cohort of US Service members (SMs) for further study. Methods: Diagnosis code families and inpatient procedure codes were compiled and analyzed to identify medical codes that are disparately associated with a LS surrogate population of SMs who underwent secondary amputation within a broader cohort of 3390 SMs with lower extremity trauma (AIS > 1). Subsequently, the identified codes were used to define a cohort of all SMs who underwent lower extremity LS which was compared with the opinion of a panel of military trauma surgeons. Results: The data-driven approach identified a population of n = 2018 SMs who underwent LS, representing 59.5% of the combat-related lower extremity (LE) trauma population. Validation analysis revealed 70% agreement between the data-driven approach and gold standard SME panel for the test cases studied. The Kappa statistic (κ = 0.55) indicates a moderate agreement between the data-driven approach and the expert opinion of the SME panel. The sensitivity and specificity were identified as 55.6% (expert range of 51.8–66.7%) and 87% (expert range of 73.9–91.3%), respectively. Conclusions: This approach for identifying LS cases can be utilized to enable future high-throughput retrospective analyses for studying both short- and long-term outcomes of this underserved patient population.

ObjectivePreoperative embolization of brain arteriovenous malformations (AVMs) is performed to facilitate resection, although its impact on surgical performance has not been clearly defined. The authors tested for associations between embolization and surgical performance metrics.MethodsThe authors analyzed AVM cases resected by one neurosurgeon from 2006 to 2017. They tested whether cases with and without embolization differed from one another with respect to patient and AVM characteristics using t-tests for continuous variables and Fisher's exact tests for categorical variables. They used simple and multivariable regression models to test whether surgical outcomes (blood loss, resection time, surgical clip usage, and modified Rankin Scale [mRS] score) were associated with embolization. Additional regression analyses integrated the peak arterial afferent contrast normalized for the size of the region of interest (Cmax/ROI) into models as an additional predictor.ResultsThe authors included 319 patients, of whom 151 (47%) had preoperative embolization. Embolized AVMs tended to be larger (38% with diameter > 3 cm vs 19%, p = 0.001), less likely to have hemorrhaged (48% vs 63%, p = 0.013), or be diffuse (19% vs 29%, p = 0.045). Embolized AVMs were more likely to have both superficial and deep venous drainage and less likely to have exclusively deep drainage (32% vs 17% and 12% vs 23%, respectively; p = 0.002). In multivariable analysis, embolization was not a significant predictor of blood loss or mRS score changes, but did predict longer operating times (+29 minutes, 95% CI 2-56 minutes; p = 0.034) and increased clip usage (OR 2.61, 95% CI 1.45-4.71; p = 0.001). Cmax/ROI was not a significant predictor, although cases with large Cmax/ROI tended to have longer procedure times (+25 minutes per doubling of Cmax/ROI, 95% CI 0-50 minutes; p = 0.051).ConclusionsIn this series, preoperative embolization was associated with longer median resection times and had no association with intraoperative blood loss or mRS score changes.

Closed depressions are scale-invariant landforms that are the most distinctive and characteristic landform in karst terrains at the millimetre-to-kilometre scales. The purpose of this paper is twofold. The first is to raise awareness of the geoheritage and geoeducational asset provided by closed depressions in a high-relief karst massif with the objective of promoting geotourism in the Sierra de las Nieves National Park in Southern Spain, which was declared a national park in 2021. The second is to propose a general, sound methodological approach to achieve the first purpose that can be applied to other national parks and geoparks with karst terrains. This paper identifies the factors that generate geodiversity in closed depressions in karst and, although dissolution is the primary generator in the high relief karst massif analysed, five distinctive types of natural, closed depressions have been recognized and described together with particular cases that deserve consideration. A sixth type of closed depression comprises anthropic closed depressions. Lithology and tectonics are the two main geological factors that determine the different types of natural closed depressions. Closed depressions add value to the geomorphological and hydrogeological diversity of karst terrains, and they can be used at various levels both off-site and on-site for preparing exhibits at a visitor or interpretation centre; as a story resource for guided field tours; and for identifying geosites of special interest for geological itineraries. Generating interpretation methods is an important component of transferring scientific knowledge of, and interest in, karst landscapes to the various types of visitors to the recently declared Sierra de las Nieves National Park in Andalusia, Southern Spain. In addition, an extensive inventory of closed depressions can be used for their identification, mapping, conservation, protection, and management. Such an inventory, which can be obtained efficiently from high spatial resolution digital elevation models, also contributes to the promotion and dissemination of geomorphological science to the general public.

Abstract Background PRAETORIAN is the first randomized controlled trial that demonstrated the noninferiority of subcutaneous ICD (S‐ICD) in comparison with transvenous ICD (TV‐ICD). We retrospectively reviewed electronic records of patients with ICD implanted over the past 6 years, with the primary objective to compare our real‐world single tertiary center experience with the randomized data from the PRAETORIAN study. Methods Seventy S‐ICD patients were compared with 197 TV‐ICD patients, from July 2014 to June 2020 retrospectively, over a median period of 1304 days (296–2451 days). Primary composite endpoints included inappropriate shocks and device‐related malfunctions. Results Patients with S‐ICD implantation were younger than those who received TV‐ICD (mean, 49.7 years vs 63.9 years, p

Introduction: Substance use disorders (SUDs) and addictive behaviours are growing problems which negatively impact health and wellbeing. Occupational therapy can support recovery by facilitating engagement in everyday activities that promote health. To date, the inclusion of occupational therapy in addiction recovery is limited and the evidence base for occupation-focused interventions is lacking. This study explores the impact of an occupational therapy-led intervention on self-reported occupational performance and occupational balance issues for people living with SUDs within an inpatient addiction service. Methodology: A quantitative pre and post-test study was implemented. The Canadian Personal Recovery Outcome Measure (C-PROM) was the sole outcome measure. The C-PROM is a self-report measure which aims to measure personal views of recovery based on rating activity engagement. The cohort of participants were recruited from referrals into 2 inpatient addiction recovery treatment programmes using purposive sampling. Descriptive statistics were run, and a Wilcoxon Signed Rank Test was used to analyse pre and post-test scoring. Results: Sixteen participants (9 male and 7 female) completed the intervention and outcome measure. The majority of participants (31.3%, n = 5) were between 45 and 54 years old. 25% of the sample (n = 4) were in the 35 to 44 age bracket while 18.8% (n = 3) were aged 55 to 64. The majority of participants (68.8%, n = 11) reported substance misuse as their main healthcare concern. The mean score on the C-PROM was significantly higher after participants received the intervention when compared with baseline scoring. Conclusion: Following engagement with an occupational therapist-led intervention participants reported increased engagement in activities and occupational performance. Participants also reported improved occupational balance and increased awareness of personal recovery needs. Further research is required to explore the effectiveness of this intervention in larger samples and to explore the transferability and sustainability of skills post discharge.

Summary: To disseminate through the body, Zika virus (ZIKV) is thought to exploit the mobility of myeloid cells, in particular monocytes and dendritic cells. However, the timing and mechanisms underlying shuttling of the virus by immune cells remains unclear. To understand the early steps in ZIKV transit from the skin, at different time points, we spatially mapped ZIKV infection in lymph nodes (LNs), an intermediary site en route to the blood. Contrary to prevailing hypotheses, migratory immune cells are not required for the virus to reach the LNs or blood. Instead, ZIKV rapidly infects a subset of sessile CD169+ macrophages in the LNs, which release the virus to infect downstream LNs. Infection of CD169+ macrophages alone is sufficient to initiate viremia. Overall, our experiments indicate that macrophages that reside in the LNs contribute to initial ZIKV spread. These studies enhance our understanding of ZIKV dissemination and identify another anatomical site for potential antiviral intervention.

Background Poor immune function is associated with increased risk for a number of age-related diseases, however, little is known about the impact of early life trauma on immune function in late-life. Methods Using nationally representative data from the Health and Retirement Study (n = 5,823), we examined the association between experiencing parental/caregiver death or separation before age 16 and four indicators of immune function in late-life: C-reactive Protein (CRP), Interleukin-6 (IL-6), soluble Tumor Necrosis Factor (sTNFR), and Immunoglobulin G (IgG) response to cytomegalovirus (CMV). We also examined racial/ethnic differences. Findings Individuals that identified as racial/ethnic minorities were more likely to experience parental/caregiver loss and parental separation in early life compared to Non-Hispanic Whites, and had poorer immune function in late-life. We found consistent associations between experiencing parental/caregiver loss and separation and poor immune function measured by CMV IgG levels and IL-6 across all racial/ethnic subgroups. For example, among Non-Hispanic Blacks, those that experienced parental/caregiver death before age 16 had a 26% increase in CMV IgG antibodies in late-life (β = 1.26; 95% CI: 1.17, 1.34) compared to a 3% increase in CMV antibodies among Non-Hispanic Whites (β = 1.03; 95% CI: 0.99, 1.07) controlling for age, gender, and parental education. Interpretation Our results suggest a durable association between experiencing early life trauma and immune health in late-life, and that structural forces may shape the ways in which these relationships unfold over the life course.

BackgroundThe benefits of real-time continuous glucose monitoring (RT-CGM) are well established for patients with type 1 diabetes (T1D) and patients with insulin-treated type 2 diabetes (T2D). However, the usage and effectiveness of RT-CGM in the context of non–insulin-treated T2D has not been well studied. ObjectiveWe aimed to assess glycemic metrics and rates of RT-CGM feature utilization in users with T1D and non–insulin-treated T2D. MethodsWe retrospectively analyzed data from 33,685 US-based users of an RT-CGM system (Dexcom G6; Dexcom, Inc) who self-identified as having either T1D (n=26,706) or T2D and not using insulin (n=6979). Data included glucose concentrations, alarm settings, feature usage, and event logs. ResultsThe T1D cohort had lower proportions of glucose values in the 70 mg/dl to 180 mg/dl range than the T2D cohort (52.1% vs 70.8%, respectively), with more values indicating hypoglycemia or hyperglycemia and higher glycemic variability. Discretionary alarms were enabled by a large majority in both cohorts. The data sharing feature was used by 38.7% (10,327/26,706) of those with T1D and 10.4% (727/6979) of those with T2D, and the mean number of followers was higher in the T1D cohort. Large proportions of patients with T1D or T2D enabled and customized their glucose alerts. Retrospective analysis features were used by the majority in both cohorts (T1D: 15,783/26,706, 59.1%; T2D: 3751/6979, 53.8%). ConclusionsSimilar to patients with T1D, patients with non–insulin-treated T2D used RT-CGM system features, suggesting beneficial, routine engagement with data by patients and others involved in their care. Motivated patients with diabetes could benefit from RT-CGM coverage.

The precision of temporal multisensory integration is associated with specific aspects of physical functioning in ageing, including gait speed and incidents of falling. However, it is unknown if such an association exists between multisensory integration and grip strength, an important index of frailty and brain health and predictor of disease and mortality in older adults. Here, we investigated whether temporal multisensory integration is associated with longitudinal (eight-year) grip strength trajectories in a large sample of 2,061 older adults (mean age = 64.42 years, SD = 7.20; 52% female) drawn from The Irish Longitudinal Study on Ageing (TILDA). Grip strength (kg) for the dominant hand was assessed with a hand-held dynamometer across four testing waves. Longitudinal k-means clustering was applied to these data separately for sex (male, female) and age group (50–64, 65–74, 75+ years). At wave 3, older adults participated in the Sound Induced Flash Illusion (SIFI), a measure of the precision of temporal audio-visual integration, which included three audio-visual stimulus onset asynchronies (SOAs): 70, 150 and 230 ms. Results showed that older adults with a relatively lower (i.e., weaker) grip strength were more susceptible to the SIFI at the longer SOAs compared to those with a relatively higher (i.e., stronger) grip strength (p

Background: Intellectual disability (ID) describes a neurodevelopmental condition involving impaired cognitive and functional ability. Here, we describe a multisource variable of ID using data from the Avon Longitudinal Study of Parents and Children (ALSPAC). Methods: The multisource indicator variable for ID was derived from i) IQ scores less than 70 measured at age 8 and at age 15, ii) free text fields from parent reported questionnaires, iii) school reported provision of educational services for individuals with a statement of special educational needs for cognitive impairments, iv) from relevant READ codes contained in GP records, iv) international classification of disease diagnoses contained in electronic hospital records and hospital episode statistics and v) recorded interactions with mental health services for ID contained within the mental health services data set. A case of ID was identified if two or more sources indicated ID. A second indicator, labelled as “probable ID”, was created by relaxing the cut off in IQ scores to be less than 85. An indicator variable for known causes of ID was also created to aid in aetiological studies where ID with a known cause may need to be excluded. Results: 158 of 14,370 participants (1.10%) were indicated as having ID by two or more sources and 449 (3.12%) were indicated as having probable ID when the criteria for IQ scores was relaxed to less than 85. There were 476 participants (3.31%) with 1 or fewer sources of available information on ID; these participants had their multisource variable set to missing. The number of cases of ID with known cause was 31 (0.22% of the cohort, 19.6% of those with ID). Conclusions: The multisource variable of ID can be used in future analyses on ID in ALSPAC children.

Variation in the electrical conductivity (EC) of water can reveal environmental disturbance and natural dynamics, including factors such as anthropogenic salinization. Broader application of open source (OS) EC sensors could provide an inexpensive method to measure water quality. While studies show that other water quality parameters can be robustly measured with sensors, a similar effort is needed to evaluate the performance of OS EC sensors. To address this need, we evaluated the accuracy (mean error, %) and precision (sample standard deviation) of OS EC sensors in the laboratory via comparison to EC calibration standards using three different OS and OS/commercial-hybrid (OS/C) EC sensors and data logger configurations and two commercial (C) EC sensors and data logger configurations. We also evaluated the effect of cable length (7.5 m and 30 m) and sensor calibration on OS sensor accuracy and precision. We found a significant difference between OS sensor mean accuracy (3.08%) and all other sensors combined (9.23%). Our study also found that EC sensor precision decreased across all sensor configurations with increasing calibration standard EC. There was also a significant difference between OS sensor mean precision (2.85 μS/cm) and the mean precision of all other sensors combined (9.12 μS/cm). Cable length did not affect OS sensor precision. Furthermore, our results suggest that future research should include evaluating how performance is impacted by combining OS sensors with commercial data loggers as this study found significantly decreased performance in OS/commercial-hybrid sensor configurations. To increase confidence in the reliability of OS sensor data, more studies such as ours are needed to further quantify OS sensor performance in terms of accuracy and precision across different settings and OS sensor and data collection platform configurations.

BackgroundThe COVID-19 pandemic was accompanied by an "infodemic"-an overwhelming excess of accurate, inaccurate, and uncertain information. The social media-based science communication campaign Dear Pandemic was established to address the COVID-19 infodemic, in part by soliciting submissions from readers to an online question box. Our study characterized the information needs of Dear Pandemic's readers by identifying themes and longitudinal trends among question box submissions.MethodsWe conducted a retrospective analysis of questions submitted from August 24, 2020, to August 24, 2021. We used Latent Dirichlet Allocation topic modeling to identify 25 topics among the submissions, then used thematic analysis to interpret the topics based on their top words and submissions. We used t-Distributed Stochastic Neighbor Embedding to visualize the relationship between topics, and we used generalized additive models to describe trends in topic prevalence over time.ResultsWe analyzed 3839 submissions, 90% from United States-based readers. We classified the 25 topics into 6 overarching themes: 'Scientific and Medical Basis of COVID-19,' 'COVID-19 Vaccine,' 'COVID-19 Mitigation Strategies,' 'Society and Institutions,' 'Family and Personal Relationships,' and 'Navigating the COVID-19 Infodemic.' Trends in topics about viral variants, vaccination, COVID-19 mitigation strategies, and children aligned with the news cycle and reflected the anticipation of future events. Over time, vaccine-related submissions became increasingly related to those surrounding social interaction.ConclusionsQuestion box submissions represented distinct themes that varied in prominence over time. Dear Pandemic's readers sought information that would not only clarify novel scientific concepts, but would also be timely and practical to their personal lives. Our question box format and topic modeling approach offers science communicators a robust methodology for tracking, understanding, and responding to the information needs of online audiences.

Introduction: Point-of care-ultrasound (POCUS) has become ubiquitous in emergency medicine practice for the management of emergent pathophysiology. There is growing interest in its potential as a diagnostic tool in the prehospital setting. Few studies have examined the feasibility or efficacy of curricula targeted at teaching POCUS to prehospital personnel. Our objective in this study was to investigate a curriculum for the extended focused assessment with sonography in trauma (eFAST) exam in helicopter emergency medical services (HEMS) crews. Methods: This was a pre/post intervention study of HEMS personnel at a tertiary care center. Subjects were administered a pre-intervention written test and an observed structured clinical evaluation (OSCE). Subsequently, they participated in an educational intervention intended to impart proficiency in performing the eFAST. Subjects underwent post-intervention written exams and OSCEs. We analyzed pre- and post-intervention test performance along with the number and quality of practice ultrasound examinations achieved. Results: Sixteen subjects were enrolled (62.5% male, mean age 44.1). After undergoing the intervention, the mean written test score increased 22.1% (t=3.41; P

We introduce a simple extension to the CBDX model to project cohort mortality rates to extreme old age. The proposed approach fits a polynomial to a sample of age effects, uses the fitted polynomial to project the age effects to ages beyond the sample age range, then splices the sample and projected age effects, and uses the spliced age effects to obtain mortality rates for the higher ages. The proposed approach can be used to value financial instruments such as life annuities that depend on projections of extreme old age mortality rates.

This paper investigates the relationship between rainfall, groundwater and Gravity Recovery and Climate Experiment (GRACE) data to generate regional-scale estimates of terrestrial water storage variations in the Andalucía region of southern Spain. These estimates can provide information on groundwater depletion (caused by periods of low rainfall or droughts) and groundwater recovery. The spatial distribution of groundwater bodies in southern Spain is complex and current in situ groundwater monitoring methods are deficient, particularly in terms of obtaining representative samples and in implementing and maintaining groundwater monitoring networks. The alternative approach proposed here is to investigate the relationship between precipitation time series and changes in the terrestrial water storage estimated from GRACE observations. The results were validated against the estimated fluctuation in regional groundwater. The maximum correlation between the mean groundwater level and the GRACE observations is 0.69 and this occurs at a lag of one month because the variation in gravity is immediate, but rainfall water requires around one month to travel across the vadose zone before it reaches the groundwater table. Using graphical methods of accumulated deviations from the mean, we show that, in general, groundwater storage follows the smooth, multi-year trends of terrestrial water storage but with less short-term trends; the same is true of rainfall, for which the local trends are more pronounced. There is hysteresis-like behaviour in the variations in terrestrial water storage and in the variations of groundwater. In practical terms, this study shows that, despite the abnormal dryness of the Iberian Peninsula during the 2004–2010 drought, the depleted groundwater storage in Andalucía recovered almost to its pre-drought level by 2016. In addition, groundwater storage and terrestrial water storage show very similar trends but with a delay in the groundwater trend.