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Caring for children with acute illness is a challenge in limited-resource settings, especially when diagnostic imaging is limited or unavailable. We developed a training program in cardiac and lung point-of-care ultrasound (POCUS) for pediatric patients in eastern Uganda. Fourteen trainees including physicians, resident physicians and midlevels received training in cardiac and lung POCUS. Training included formal lectures, hands-on skills practice and individualized teaching sessions. Assessment included written knowledge assessment, direct observation and longitudinal image review. Blinded review of 237 consecutive ultrasound studies revealed satisfactory image quality (94.2% for lung and 93% for cardiac) and accurate image interpretation. Sensitivity and specificity of image interpretation were 0.93 (0.75-0.99) and 0.94 (0.78-0.99) for lung and 0.86 (0.71-0.95) and 0.94 (0.84-0.99) for cardiac compared with expert review. All trainees passed written knowledge assessments. After training, 100% of trainees reported that they would use POCUS in clinical activity and thought it would improve patient outcomes. Our training program indicated that trainees were able to perform high-quality cardiac and lung POCUS for pediatric patients with accurate interpretation. This builds a foundation for future studies addressing how POCUS can change outcomes for children in limited-resource settings.

Respiratory infection can be an immediate precursor to stroke and myocardial infarction. Influenza vaccination is associated with reduced risk of myocardial infarction and hospitalisation for cardiac disease, and influenza vaccination is strongly recommended for patients with heart disease. Evidence on whether the same protective association exists for stroke, and whether this potential effect is consistent across age and risk groups, is conflicting. We aimed to assess the risk of stroke after influenza vaccination in adults.We obtained administrative data from the Alberta Health Care Insurance Plan (which covers all residents of Alberta, Canada) beginning on Sept 30, 2009, or May 15 of the year in which residents were recorded as being 18 years of age. Individuals were censored at the earliest of three events: death, recorded outmigration, or Dec 31, 2018. The outcome of interest was any stroke event, comprising acute ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and transient ischaemic attack. We used Andersen-Gill Cox models to analyse the hazard of any stroke event for individuals with recent (lt;182 days) influenza vaccination compared with those without recent influenza vaccination, with adjustment for age, sex, anticoagulant use, atrial fibrillation, chronic obstructive pulmonary disease, diabetes, hypertension, income quintile, and rural or urban home location. Two-way interaction terms between each individual covariate and vaccination status were used to assess for effect modification by risk factor. The association between vaccination and risk of each type of stroke was also modelled, adjusting for baseline covariates.The study sample consisted of 4 141 209 adults (29 687 899 person-years of observation time) registered under the provincial health-care system between Sept 30, 2009, and Dec 31, 2018. 1 769 565 (42·73%) individuals received at least one vaccination during the study period, and 38 126 stroke events were recorded. Adjusted for demographics and comorbidities, recent influenza vaccination significantly reduced the hazard of stroke (hazard ratio 0·775 [95% CI 0·757-0·793]). This association persisted across all stroke types. We found effect modification by each covariate examined except for home location; however, vaccination was associated with a reduced risk of stroke overall across all ages and risk profiles with the exception of individuals without hypertension.The risk of stroke is reduced among people who have recently been vaccinated against influenza compared with those who have not. This association extended to the entire adult population and was not limited to individuals with a baseline high risk of stroke. Further studies in a variety of settings are needed to evaluate whether influenza vaccination could be used as a public health strategy to prevent stroke.None.

Objective Opioid use disorder (OUD) is a chronic relapsing disorder with a problematic pattern of opioid use, affecting nearly 27 million people worldwide. Machine learning (ML)-based prediction of OUD may lead to early detection and intervention. However, most ML prediction studies were not based on representative data sources and prospective validations, limiting their potential to predict future new cases. In the current study, we aimed to develop and prospectively validate an ML model that could predict individual OUD cases based on representative large-scale health data. Method We present an ensemble machine-learning model trained on a cross-linked Canadian administrative health data set from 2014 to 2018 ( n = 699,164), with validation of model-predicted OUD cases on a hold-out sample from 2014 to 2018 ( n = 174,791) and prospective prediction of OUD cases on a non-overlapping sample from 2019 ( n = 316,039). We used administrative records of OUD diagnosis for each subject based on International Classification of Diseases (ICD) codes. Results With 6409 OUD cases in 2019 (mean [SD], 45.34 [14.28], 3400 males), our model prospectively predicted OUD cases at a high accuracy (balanced accuracy, 86%, sensitivity, 93%; specificity 79%). In accord with prior findings, the top risk factors for OUD in this model were opioid use indicators and a history of other substance use disorders. Conclusion Our study presents an individualized prospective prediction of OUD cases by applying ML to large administrative health datasets. Such prospective predictions based on ML would be essential for potential future clinical applications in the early detection of OUD.

The resource saving bias is a cognitive bias describing how resource savings from improvements of high-productivity units are overestimated compared to improvements of less productive units. Motivational reasoning describes how attitudes, here towards private/public health care, distort decisions based on numerical facts. Participants made a choice between two productivity increase options with the goal of saving doctor resources. The options described productivity increases in low-/high-productivity private/public emergency rooms. Jointly, the biases produced 78% incorrect decisions. The cognitive bias was stronger than the motivational bias. Verbal justifications of the decisions revealed elaborations of the problem beyond the information provided, biased integration of quantitative information, change of goal of decision, and motivational attitude biases. Most (83%) of the incorrect decisions were based on (incorrect) mathematical justifications illustrating the resource saving bias. Participants who had better scores on a cognitive test made poorer decisions. Women who gave qualitative justifications to a greater extent than men made more correct decision. After a first decision, participants were informed about the correct decision with a mathematical explanation. Only 6.3% of the participants corrected their decisions after information illustrating facts resistance. This could be explained by psychological sunk cost and coherence theories. Those who made the wrong choice remembered the facts of the problem better than those who made a correct choice.

Purpose Employees may feel overwhelmed with information privacy choices and have difficulties understanding what they are committing to in the digital workplace. This paper aims to analyze the role of different thinking styles for effort reduction, such as the use of intuition, when employees make decisions about the credibility and trustworthiness of workplace information privacy issues in Slovakia. While the General Data Protection Regulation sets precise requirements for valid consent, organizations are classified as data controllers and are subject to credibility judgments by their employees. Design/methodology/approach Data was collected from 230 employees in Slovakia using a survey questionnaire. Quantitative analysis using SPSS was conducted to describe employees thinking preferences when judging the credibility of information privacy in their organizations. Findings The survey participants revealed their perceived credibility and trust in personal data protection and thinking preferences. Unconscious thinking is the type of effort reduction often reported by participants, who perceive high credibility and trust in personal data protection. This study can help managers and data controllers in small- and medium-sized enterprises in reflecting about the way in which people use different thinking processes for decision-making about information privacy in their organizations. Research limitations/implications This study set out to explore how decision-making processes at the workplace relate to credibility of data practices. Focusing on the use of different types of intuition, the authors explored whether the preference for a specific decision-making style can explain the perceived credibility of data practices. The part of the workforce in the sample did not have a strict predisposition to use either intuitive or rational thinking. Practical implications The contribution provides scholars with an overview of the field of intuition, a field that is likely to grow given the challenges of digitalization for organizations, such as shitstorms, cyberattacks and whistleblowing. Originality/value The most well-known concepts from intuition research, e.g. the dual process theory, and practice are tested simultaneously, therewith contributing to the applied literature on domain-specific preferences for intuition and deliberation in decision-making.

Supplementary Data from Intratumoral Electroporation of Plasmid Encoded IL12 and Membrane-Anchored Anti-CD3 Increases Systemic Tumor Immunity

Supplementary Figure from Intratumoral Electroporation of Plasmid Encoded IL12 and Membrane-Anchored Anti-CD3 Increases Systemic Tumor Immunity

We reconstruct the phenotype of Balto, the heroic sled dog renowned for transporting diphtheria antitoxin to Nome, Alaska, in 1925, using evolutionary constraint estimates from the Zoonomia alignment of 240 mammals and 682 genomes from dogs and wolves of the 21st century. Balto shares just part of his diverse ancestry with the eponymous Siberian husky breed. Balto's genotype predicts a combination of coat features atypical for modern sled dog breeds, and a slightly smaller stature. He had enhanced starch digestion compared with Greenland sled dogs and a compendium of derived homozygous coding variants at constrained positions in genes connected to bone and skin development. We propose that Balto's population of origin, which was less inbred and genetically healthier than that of modern breeds, was adapted to the extreme environment of 1920s Alaska.

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Purpose:Triple-negative breast cancer (TNBC) is an aggressive disease with limited therapeutic options. Antibodies targeting programmed cell death protein 1 (PD-1)/PD-1 ligand 1 (PD-L1) have entered the therapeutic landscape in TNBC, but only a minority of patients benefit. A way to reliably enhance immunogenicity, T-cell infiltration, and predict responsiveness is critically needed.Patients and Methods:Using mouse models of TNBC, we evaluate immune activation and tumor targeting of intratumoral IL12 plasmid followed by electroporation (tavokinogene telseplasmid; Tavo). We further present a single-arm, prospective clinical trial of Tavo monotherapy in patients with treatment refractory, advanced TNBC (OMS-I140). Finally, we expand these findings using publicly available breast cancer and melanoma datasets.Results:Single-cell RNA sequencing of murine tumors identified a CXCR3 gene signature (CXCR3-GS) following Tavo treatment associated with enhanced antigen presentation, T-cell infiltration and expansion, and PD-1/PD-L1 expression. Assessment of pretreatment and posttreatment tissue from patients confirms enrichment of this CXCR3-GS in tumors from patients that exhibited an enhancement of CD8+ T-cell infiltration following treatment. One patient, previously unresponsive to anti–PD-L1 therapy, but who exhibited an increased CXCR3-GS after Tavo treatment, went on to receive additional anti–PD-1 therapy as their immediate next treatment after OMS-I140, and demonstrated a significant clinical response.Conclusions:These data show a safe, effective intratumoral therapy that can enhance antigen presentation and recruit CD8 T cells, which are required for the antitumor efficacy. We identify a Tavo treatment-related gene signature associated with improved outcomes and conversion of nonresponsive tumors, potentially even beyond TNBC.

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Supplementary Figure Legends 1-5, Table Legend from Suppression of Integrin α3β1 in Breast Cancer Cells Reduces Cyclooxygenase-2 Gene Expression and Inhibits Tumorigenesis, Invasion, and Cross-Talk to Endothelial Cells

Supplementary Figure 2 from Suppression of Integrin α3β1 in Breast Cancer Cells Reduces Cyclooxygenase-2 Gene Expression and Inhibits Tumorigenesis, Invasion, and Cross-Talk to Endothelial Cells

Supplementary Figure 3 from Suppression of Integrin α3β1 in Breast Cancer Cells Reduces Cyclooxygenase-2 Gene Expression and Inhibits Tumorigenesis, Invasion, and Cross-Talk to Endothelial Cells

Supplementary Table 1 from Suppression of Integrin α3β1 in Breast Cancer Cells Reduces Cyclooxygenase-2 Gene Expression and Inhibits Tumorigenesis, Invasion, and Cross-Talk to Endothelial Cells

Supplementary Figure 5 from Suppression of Integrin α3β1 in Breast Cancer Cells Reduces Cyclooxygenase-2 Gene Expression and Inhibits Tumorigenesis, Invasion, and Cross-Talk to Endothelial Cells

Supplementary Figure 1 from Suppression of Integrin α3β1 in Breast Cancer Cells Reduces Cyclooxygenase-2 Gene Expression and Inhibits Tumorigenesis, Invasion, and Cross-Talk to Endothelial Cells

Supplementary Figure 4 from Suppression of Integrin α3β1 in Breast Cancer Cells Reduces Cyclooxygenase-2 Gene Expression and Inhibits Tumorigenesis, Invasion, and Cross-Talk to Endothelial Cells

Integrin receptors for cell adhesion to extracellular matrix have important roles in promoting tumor growth and progression. Integrin α3β1 is highly expressed in breast cancer cells in which it is thought to promote invasion and metastasis; however, its roles in regulating malignant tumor cell behavior remain unclear. In the current study, we used short-hairpin RNA (shRNA) to show that suppression of α3β1 in a human breast cancer cell line, MDA-MB-231, leads to decreased tumorigenicity, reduced invasiveness, and decreased production of factors that stimulate endothelial cell migration. Real-time PCR revealed that suppression of α3β1 caused a dramatic reduction in expression of the cyclooxygenase-2 (COX-2) gene, which is frequently overexpressed in breast cancers and has been exploited as a therapeutic target. Decreased COX-2 was accompanied by reduced prostaglandin E2 (PGE2), a major prostanoid produced downstream of COX-2 and an important effector of COX-2 signaling. shRNA-mediated suppression of COX-2 showed that it has a role in tumor cell invasion and cross-talk to endothelial cells. Furthermore, treatment with PGE2 restored these functions in α3β1-deficient MDA-MB-231 cells. These findings identify a role for α3β1 in regulating two properties of tumor cells that facilitate cancer progression: invasiveness and ability to stimulate endothelial cells. They also reveal a novel role for COX-2 as a downstream effector of α3β1 in tumor cells, thereby identifying α3β1 as a potential therapeutic target to inhibit breast cancer. Cancer Res; 70(15); 6359–67. ©2010 AACR.

Respiratory syncytial virus (RSV) is a major cause of acute respiratory infection (ARI), with high morbidity and mortality worldwide. RSV costing and burden estimates can highlight the potential benefits of future vaccination programs and are essential for economic evaluations.We aimed to determine RSV healthcare costs across age groups and the overall disease burden of medically attended RSV in Canada.We conducted a retrospective case-control study to estimate the attributable healthcare costs per RSV case in Alberta. We used two case definitions to capture diversity in case severity: laboratory-confirmed RSV and ARI attributable to RSV. Matching occurred on five criteria: (1) age, (2) urban/rural status, (3) sex, (4) prematurity and (5) Charlson Comorbidity Index score. We calculated the age-specific burden of medically attended RSV in Canada from 2010 to 2019 by multiplying the weekly age-specific incidence of medically attended ARI with the RSV positivity rate.Costs per laboratory-confirmed RSV case were (in Canadian dollars [CAD], year 2020 values) $CAD12,713 and 40,028 in the first 30 and 365 days following diagnosis, respectively, whereas a case of ARI potentially attributable to RSV cost $CAD316 and 915, in 30 and 365 days, respectively. Older (aged ≥ 65 years) and younger (aged 90 days) age groups had the highest case costs. The average medically attended RSV incidence rate across nine seasons was 1743 cases per 100,000 people per year.RSV is a common and expensive infection at the extremes of life, and the development of immunization programs targeting older and younger ages may be important for the reduction of RSV burden and cost.

[Image: see text] Antimicrobial drug resistance is a looming health crisis facing us in the modern era, and new drugs are urgently needed to combat this growing problem. Synthetic mimics of antimicrobial peptides have recently emerged as a promising class of compounds for the treatment of persistent microbial infections. In the current study, we investigate five cyclic N-alkylated amphiphilic 2,5-diketopiperazines against 15 different strains of bacteria and fungi, including drug-resistant clinical isolates. Several of the 2,5-diketopiperazines displayed activities similar or superior to antibiotics currently in clinical use, with activities coupled to both the cationic and hydrophobic substituents. All possible stereoisomers of the lead peptide were prepared, and the effects of stereochemistry and amphiphilicity were investigated via 1D and 2D NMR spectroscopy, solution dynamics, and membrane interaction modeling. Clear differences in solution structures and membrane interaction potentials explain the differences seen in the bioactivity and physicochemical properties of each stereoisomer.

Intratumoral delivery of plasmid IL12 via electroporation (IT-tavo-EP) induces localized expression of IL12 leading to regression of treated and distant tumors with durable responses and minimal toxicity. A key driver in amplifying this local therapy into a systemic response is the magnitude and composition of immune infiltrate in the treated tumor. While intratumoral IL12 typically increases the density of CD3+ tumor-infiltrating lymphocytes (TIL), this infiltrate is composed of a broad range of T-cell subsets, including activated tumor-specific T cells, less functional bystander T cells, as well as suppressive T regulatory cells. To encourage a more favorable on-treatment tumor microenvironment (TME), we explored combining this IL12 therapy with an intratumoral polyclonal T-cell stimulator membrane-anchored anti-CD3 to productively engage a diverse subset of lymphocytes including the nonreactive and suppressive T cells. This study highlighted that combined intratumoral electroporation of IL12 and membrane-anchored anti-CD3 plasmids can enhance cytokine production, T-cell cytotoxicity, and proliferation while limiting the suppressive capacity within the TME. These collective antitumor effects not only improve regression of treated tumors but drive systemic immunity with control of nontreated contralateral tumors in vivo. Moreover, combination of IL12 and anti-CD3 restored the function of TIL isolated from a patient with melanoma actively progressing on programmed cell death protein 1 (PD-1) checkpoint inhibitor therapy.Implications:This DNA-encodable polyclonal T-cell stimulator (membrane-anchored anti-CD3 plasmid) may represent a key addition to intratumoral IL12 therapies in the clinic.

As the commercial use of seaweed for natural product extraction calls for abundant, uniform biomass, this study focused on the production and the variability of the harvested biomass of valuable compounds produced by a commercially relevant red algal species, Asparagopsis armata. Its tetrasporophyte stage was retrieved from two Irish localities and grown for over 2 years in indoor cultures at 13 °C and 17 °C, and bromoform, mycosporine-like amino acids and phycobiliprotein contents were monitored over time. Growth rates at different temperatures were specific to isolates, and one isolate failed to grow at 17 °C. All compounds of interest were detected by the end of the 2-year cultivation period, and most of them were produced at an exponential rate at 13 °C but not at the higher temperature. At 13 °C, bromoform reached concentrations of 10.00 ± 0.55 mg g−1, total mycosporine-like amino acids of 2.65 ± 0.10 mg g−1, phycoerythrin of 11.46 ± 0.35 mg g−1 and phycocyanin of 72.13 ± 1.74 mg g−1 in Irish isolates. The observed variability in compound content was statistically significant but not large enough to impede commercial utilization. Bromoform content in cultivated samples was almost 6-fold higher than in field-collected samples though natural bromoform variability remains to be elucidated. Our findings suggest that the tetrasporophytic phase of A. armata is a suitable candidate for indoor cultivation; abundant and homogeneous biomass composition can be obtained which can be further optimized by growth temperature.

The effectiveness of current assessment tools for cervical fracture are mixed with respect to elderly patients. We aim to examine utility of history and physical exam to assess for cervical fracture for elderly patients suffering a ground-level fall.Retrospective cohort from a tertiary-care ED for patients ≥65 years, including dementia, after ground-level fall. Logistic regression was used to examine predictability of various clinical factors. Neurologic deficits were considered a hard sign for imaging and were not assessed.Of 1035 patient encounters analyzed, 683 had CT cervical-spine (C-spine) imaging (66.0%) and 16 (1.5%) had cervical fracture. C-spine tenderness (OR 4.7, 95% CI 1.5-14.1), neck pain (OR 10.5, 95% CI 3.4-32.5), altered mental status (AMS) (OR 5.1, 95% CI 1.7-15.6), and external trauma above the clavicles (ETC) (OR 3.8, 95% CI 1.2-12.3) predicted cervical fracture. C-spine tenderness and neck pain were collinear and run-in separate models. Dementia (OR 0.2, 95% CI 0.4-0.9) did not predict cervical fracture in this population. A combination of ETC, C-spine tenderness, and AMS had a sensitivity = 100% and specificity = 40.0% for detection of cervical fracture. ETC was found in all but two fractures requiring intervention with negative predictive value = 99.3%.Clinical assessment for elderly patients without neurologic signs, together with the absence of ETC, cervical tenderness, and AMS may be reliable in ruling out cervical fracture after a ground-level fall, including patients with history of dementia. Fractures requiring intervention were rare in patients without ETC. However, findings are retrospective and prospective validation is required.

ObjectiveWe assessed coronavirus disease 2019 (COVID-19) vaccine uptake among individuals with immune-mediated inflammatory diseases (IMIDs) and the Ontario general population.MethodsWe studied all residents aged ≥ 16 years who were alive and enrolled in the Ontario Health Insurance Plan as of December 14, 2020, when vaccination commenced (n = 12,435,914). Individuals with rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), psoriasis (PsO), and inflammatory bowel disease (IBD) were identified using established disease-specific case definitions applied to health administrative data. Vaccination status was extracted from the provincial COVaxON registry. Weekly cumulative proportions of first and second doses up until October 3, 2021, were expressed as the vaccinated percentage of each disease group, compared to the general Ontario population, and stratified by age.ResultsBy October 3, 2021, the cumulative percentage with at least 1 dose was 82.1% for the general population, 88.9% for those with RA, 87.4% for AS, 90.6% for PsA, 87.3% for PsO, and 87.0% for IBD. There was also a higher total cumulative percentage with 2 doses among IMIDs (83.8–88.2%) vs the general population (77.9%). The difference was also evident when stratifying by age. Individuals with IMIDs in the youngest age group initially had earlier uptake than the general population but remain the lowest age group with 2 doses (70.6% in the general population vs. 73.7–79.2% across IMID groups).ConclusionWhile implementation of COVID-19 vaccination programs has differed globally, these Canadian estimates are the first to reassuringly show higher COVID-19 vaccine uptake among individuals with IMIDs.

BackgroundDuring the COVID-19 pandemic people were asked to keep interpersonal distance, wash their hands and avoid gatherings of people. But, do people understand how much a change of the distance to a virus infected person means for the exposure to that person’s virus? To answer this question, we studied how people perceive virus exposure from an infected person at different distances and lengths of a conversation.MethodAn online questionnaire was distributed to 101 participants drawn from the general US population. Participants judged perceived virus exposure at different interpersonal distances to an infected person in a face to face conversation of different lengths of time. A model based on empirical and theoretical studies of dispersion of particles in the air was used to estimate a person’s objective virus exposure during different times and distances from a virus source. The model and empirical data show that exposure changes with the square of the distance and linearly with time.ResultsA majority (78%) of the participants underestimated the effects on virus exposure following a change of interpersonal distance. The dominating bias was assuming that exposure varies linearly with distance. To illustrate, an approach to a virus source from 6 to 2 feet was judged to give a 3 times higher exposure but, objectively it is 9 times. By way of contrast, perceptions of exposure as a function of the duration of a conversation were unbiased. The COVID-19 pandemic caused by the SARS-CoV2 virus is likely to be followed by other pandemics also caused by airborne Corona or other viruses. Therefore, the results are important for administrators when designing risk communications to the general public and workers in the health care sector about social distancing and infection risks.ConclusionsPeople quite drastically underestimate the increase in virus exposure following an approach to a virus infected person. They also overestimate exposure after a move away from an infected person. For public health reasons, the correct function connecting distance with virus exposure should be communicated to the general public to avoid deliberate violations of recommended interpersonal distances.

This study sought to examine differences in measures of intense periods of physical performance during competitive match-play, between one-match (1 match weeks) and two-match microcycles (2 match week). 1, 3 and 5 min "peak" and mean averages for total distance (TD), high-speed running (HSR) and metabolic power (MP) were analysed for each 15 min period of match-play. Linear mixed models were employed to examine the differences in dependent variables for each method of measurement between the 1 and 2 game microcycles. No differences were reported for "peak" values for all epoch lengths, however, results revealed significantly reduced "average" values, during periods of fixture congestion, for 1, 3 and 5 min epochs for average TD, and 3 min epochs for average HSR towards the end of the match (75-90 min split). There was, however, a trend for the opposite response to occur in the 60-75-min period. The current data suggests that players potentially display altered pacing strategies during periods of fixture congestion, with these observed responses being dependent on sampling method and epoch length.

The sponge derived 2,5-diketopiperazine metabolite barettin is a potent antifouling compound effective against the settlement and metamorphosis of barnacles. Simplified derivatives of barettin have previously been shown to display similar inhibitory properties. The synthetic derivative benzo[g]dipodazine has been reported to display significantly improved antifouling properties in comparison with the native barettin with inhibitory activities as low a 0.034 µM reported against barnacle cyprid settlement. In the current study we report the antifouling activity of 29 synthetic analogs designed and inspired by the potent antifouling effect seen for benzo[g]dipodazine. The library contains mainly not only dipodazine derivatives but also disubstituted diketopiperazines and compounds incorporating alternative heterocyclic cores such as hydantoin, creatinine, and rhodanine. Several of the prepared compounds inhibit the settlement of Amphibalanus improvisus cyprids at low micromolar concentrations, in parity with the natural barettin. While several highly active compounds were prepared by incorporating the benzo[g]indole as hydrophobic substituent, the remarkable antifouling effect reported for benzo[g]dipodazine was not observed when evaluated in our study.

Marine biofouling is a problem that plagues all maritime industries at vast economic and environmental cost. Previous and current methods to prevent biofouling have employed the use of heavy metals and other toxic or highly persistent chemicals, and these methods are now coming under immense regulatory pressure. Recent studies have illustrated the potential of nature-inspired tetrasubstituted 2,5-diketopiperazines (2,5-DKPs) as eco-friendly marine biocides for biofouling control. These highly active symmetrically substituted 2,5-DKPs can be generated by combining structural motifs from cationic innate defence peptides and natural marine antifoulants. A balance between a threshold hydrophobic contribution and sufficient cationic charge has been established as key for bioactivity, and our current study further increases understanding of the antifouling mechanism by investigating the effect of both regio- and stereochemistry. Novel synthetic routes for the generation of unsymmetrical 2,5-DKPs were developed and a library of nine compounds was prepared. The compounds were screened against a series of four model macrofouling organisms (

Recent developments allowed generating multiple high-quality 'omics' data that could increase the predictive performance of genomic prediction for phenotypes and genetic merit in animals and plants. Here, we have assessed the performance of parametric and nonparametric models that leverage transcriptomics in genomic prediction for 13 complex traits recorded in 478 animals from an outbred mouse population. Parametric models were implemented using the best linear unbiased prediction, while nonparametric models were implemented using the gradient boosting machine algorithm. We also propose a new model named GTCBLUP that aims to remove between-omics-layer covariance from predictors, whereas its counterpart GTBLUP does not do that. While gradient boosting machine models captured more phenotypic variation, their predictive performance did not exceed the best linear unbiased prediction models for most traits. Models leveraging gene transcripts captured higher proportions of the phenotypic variance for almost all traits when these were measured closer to the moment of measuring gene transcripts in the liver. In most cases, the combination of layers was not able to outperform the best single-omics models to predict phenotypes. Using only gene transcripts, the gradient boosting machine model was able to outperform best linear unbiased prediction for most traits except body weight, but the same pattern was not observed when using both single nucleotide polymorphism genotypes and gene transcripts. Although the GTCBLUP model was not able to produce the most accurate phenotypic predictions, it showed the highest accuracies for breeding values for 9 out of 13 traits. We recommend using the GTBLUP model for prediction of phenotypes and using the GTCBLUP for prediction of breeding values.

In 2021, the National Institutes of Health Advisory Committee to the Director (ACD) announced recommendations to improve the reproducibility of biomedical research using animals. In response, The Jackson Laboratory faculty and institutional leaders identified key strategies to further address this important issue. Taking inspiration from the evolution of clinical trials over recent decades in response to similar challenges, we identified opportunities for improvement, including establishment of common standards, use of genetically diverse populations, requirement for robust study design with appropriate statistical methods, and improvement in public databases to facilitate meta-analyses. In this Perspective, we share our response to ACD recommendations, with a specific focus on mouse models, with the aim of promoting continued active dialogue among researchers, using any animal system, worldwide. Such discussion will help to inform the biomedical community about these recommendations and further support their much-needed implementation.

We see a collection of colours. Different shades, tones, textures. They form a rhythmic whole, they seem to move together, talk to one another . . . This is Amsterdam, seen through the colours of r...

Functioning healthcare systems provide emergency medical care. Disparities exist in accessibility and availability of emergency care in low- and middle-income countries. We present a descriptive epidemiologic analysis of Emergency Department (ED) usage in a rural, indigenous Guatemalan population. San Lucas Tolimán is situated in central Guatemala. Hospital Parroquial de San Lucas offers emergency care to San Lucas Tolimán and surrounding villages. All ED visits between January 1st, 2016 and December 31st 2018 were recorded and analyzed. During the study period, 12,229 patient encounters occurred. Almost all patients identified as indigenous. Children comprised 43% of visits. Medical issues represented a majority (83%) of complaints. Respiratory (40%) and gastrointestinal disease (26%) were frequent presenting complaints. Almost all visits (83%) occurred during the day and evening hours. Trauma/surgical complaints were slightly more frequent at night. 93% of patients were discharged, while the rest were admitted or transferred. These data contribute to understanding of disease burden and emergency care needs and capacity in rural areas of low- and middle-income countries. This information may be used to inform local policy decisions, identify research priorities, and create training topics for local health care providers in Guatemala and other countries in this region.

Health insurance registries, which capture insurance coverage and demographic information for entire populations, are a critical component of population health surveillance and research when using administrative data. Lack of standardization of registry information across Canada's provinces and territories could affect the comparability of surveillance measures. We assessed the contents of health insurance registries across Canada to describe the populations covered and document registry similarities and differences.A survey about the data and population identifiers in health insurance registries was developed by the study team and representatives from the Public Health Agency of Canada. The survey was completed by key informants from most provinces and territories and then descriptively analyzed.Responses were received from all provinces; partial responses were received from the Northwest Territories. Demographic information in health insurance registries, such as primary address, date of birth and sex, were captured in all jurisdictions. Data captured on familial relationships, ethnicity and socioeconomic status varied among jurisdictions, as did start and end dates of coverage and frequency of registry updates. Identifiers for specific populations, such as First Nations individuals, were captured in some, but not all jurisdictions.Health insurance registries are a rich source of information about the insured populations of the provinces and territories. However, data heterogeneity may affect who is included and excluded in population surveillance estimates produced using administrative health data. Development of a harmonized data framework could support timely and comparable population health research and surveillance results from multi-jurisdiction studies.Les registres d’assurance-maladie, qui recueillent des renseignements sur la couverture et certaines caractéristiques des individus à l’échelle de larges populations, sont précieux pour la surveillance de la santé de la population et de la recherche fondée sur l’utilisation de données administratives. Le fait que les données des registres des provinces et des territoires du Canada ne soient pas normalisées est susceptible de nuire à la comparabilité des mesures de surveillance. Nous avons évalué le contenu des registres d’assurance-maladie au Canada afin de décrire les populations couvertes et de relever les similitudes et les différences entre les registres.L’équipe de l’étude et des représentants de l’Agence de la santé publique du Canada ont élaboré une enquête sur les caractéristiques individuelles et les données sur la population recueillies dans les registres d’assurance-maladie. Les réponses des informateurs clés des provinces et territoires qui ont répondu à l’enquête ont été analysées de façon descriptive.Toutes les provinces ont répondu à l’enquête et les Territoires du Nord-Ouest ont fourni des réponses partielles. Certaines caractéristiques individuelles figurant dans les registres d’assurance-maladie (l’adresse principale, la date de naissance et le sexe) sont saisies dans toutes les provinces et tous les territoires. Les données disponibles sur les liens de parenté, l’origine ethnique et le statut socioéconomique sont variables selon les provinces et territoires, tout comme les dates de début et de fin de couverture et la fréquence de mise à jour du registre. L’information sur des populations particulières, comme les membres des Premières Nations, est saisie dans certaines provinces et certains territoires seulement.Les registres d’assurance-maladie constituent une riche source d’information sur les populations assurées des provinces et des territoires. Cependant, l’hétérogénéité des données peut avoir un impact sur les personnes incluses et exclues dans les estimations de surveillance de la population produites à partir de données administratives sur la santé. L’élaboration d’un cadre de données harmonisé favoriserait l’obtention de résultats comparables et à jour en matière de recherche et de surveillance de la santé de la population dans le cadre d’études intergouvernementales.All reporting Canadian health insurance registries contain data going back to at least 1996. The earliest year of available data was 1968, in Saskatchewan. Some features of registry data, such as change in coverage, primary address, date of birth and sex, were consistent across all reporting jurisdictions. Other features, such as family unit identifiers, socioeconomic status and population identifiers, varied across reporting jurisdictions. Differences in Canadian health insurance registries present opportunities for studies that compare the populations covered by provincial/territorial health insurance plans. Creation of a harmonized data framework would benefit national surveillance initiatives and multi-jurisdiction studies.Tous les registres canadiens de déclaration de l’assurance-maladie contiennent des données remontant au moins à 1996. La première année pour laquelle des données sont disponibles est 1968, en Saskatchewan. Certaines données fournies par le registre, comme la modification de la couverture, l’adresse principale, la date de naissance et le sexe des individus, sont uniformes dans toutes les administrations déclarantes. D’autres caractéristiques, telles que l’information sur les relations familiales, le statut socioéconomique et d’autres données sur les individus, sont variables. Les différences entre les registres d’assurance-maladie canadiens permettent d’effectuer des comparaisons entre les populations couvertes par les régimes d’assurance-maladie provinciaux et territoriaux. La création d’un cadre de données harmonisé serait, quant à elle, utile aux stratégies de surveillance nationales et aux études intergouvernementales.

Iron deficiency anaemia (IDA) and anaemia of chronic disease (ACD) are common causes of anaemia with similar clinical and laboratory features. IDA is caused by low iron stores while ACD is due to iron-restricted erythropoiesis occurring in inflammatory states. Differential diagnosis requires analysis of multiple biochemical and haematological parameters. IDA can occur simultaneously to ACD (mixed aetiology). It is essential that true iron deficiency is identified, as these patients will require iron therapy. This preliminary study investigated whether hepcidin, the master regulator of iron homeostasis, in conjunction with reticulocyte haemoglobin equivalent (RetHe) has the potential to differentiate IDA from ACD, and to exclude IDA in patients with mixed aetiology.Hepcidin concentration (measured using a commercially available ELISA method), RetHe, and iron parameters along with C-reactive protein (CRP) were analysed in 77 Gastroenterology patients with anaemia in a secondary care setting.Receiver operator characteristic (ROC) analysis showed that hepcidin at an optimal cut-off concentration of6ng/ml could identify IDA with a sensitivity and specificity of 88.9% and 90.6% respectively and could distinguish ACD from IDA with both a sensitivity and specificity of 100% at a cut-off of46ng/ml. Identifying true IDA in mixed aetiology patients could be achieved by RetHe analysis and applying an optimal cut-off of30pg.Hepcidin, in conjunction with RetHe, offers a new simplified diagnostic pathway for differential diagnosis of IDA and ACD, thereby reducing the diagnostic turnaround time and allowing appropriate treatment of patients with a true iron deficiency.

This study will explore current smokers who are non-vapers perception of e-cigarettes. This studly will look at how these perceptions differ after viewing different public information campaigns on the benefits of e-cigarettes over smoking.