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Introduction Peripheral intravenous catheters (PIVCs) are the most commonly used vascular access device in hospitalised patients. Yet PIVCs may be complicated by local or systemic infections leading to increased healthcare costs. Chlorhexidine gluconate (CHG)-impregnated dressings may help reduce PIVC-related infectious complications but have not yet been evaluated. We hypothesise an impregnated CHG transparent dressing, in comparison to standard polyurethane dressing, will be safe, effective and cost-effective in protecting against PIVC-related infectious complications and phlebitis.Methods and analysis The ProP trial is a multicentre, superiority, randomised clinical and cost-effectiveness trial with internal pilot, conducted across three centres in Australia and France. Patients (adults and children aged ≥6 years) requiring one PIVC for ≥48 hours are eligible. We will exclude patients with emergent PIVCs, known CHG allergy, skin injury at site of insertion or previous trial enrolment. Patients will be randomised to 3M Tegaderm Antimicrobial IV Advanced Securement dressing or standard care group. For the internal pilot, 300 patients will be enrolled to test protocol feasibility (eligibility, recruitment, retention, protocol fidelity, missing data and satisfaction of participants and staff), primary endpoint for internal pilot, assessed by independent data safety monitoring committee. Clinical outcomes will not be reviewed. Following feasibility assessment, the remaining 2624 (1312 per trial arm) patients will be enrolled following the same methods. The primary endpoint is a composite of catheter-related infectious complications and phlebitis. Recruitment began on 3 May 2023.Ethics and dissemination The protocol was approved by Ouest I ethic committee in France and by The Queensland Children’s Hospital Human Research Ethics Committee in Australia. The findings will be disseminated through presentation at scientific conferences and publication in peer-reviewed journals.Trial registration number NCT05741866.

Introduction Central venous access devices (CVADs) are commonly used for the treatment of paediatric cancer patients. Catheter locking is a routine intervention that prevents CVAD-associated adverse events, such as infection, occlusion and thrombosis. While laboratory and clinical data are promising, tetra-EDTA (T-EDTA) has yet to be rigorously evaluated or introduced in cancer care as a catheter lock.Methods and analysis This is a protocol for a two-arm, superiority type 1 hybrid effectiveness-implementation randomised controlled trial conducted at seven hospitals across Australia and New Zealand. Randomisation will be in a 3:2 ratio between the saline (heparinised saline and normal saline) and T-EDTA groups, with randomly varied blocks of size 10 or 20 and stratification by (1) healthcare facility; (2) CVAD type and (3) duration of dwell since insertion. Within the saline group, there will be a random allocation between normal and heparin saline. Participants can be re-recruited and randomised on insertion of a new CVAD. Primary outcome for effectiveness will be a composite of CVAD-associated bloodstream infections (CABSI), CVAD-associated thrombosis or CVAD occlusion during CVAD dwell or at removal. Secondary outcomes will include CABSI, CVAD-associated-thrombosis, CVAD failure, incidental asymptomatic CVAD-associated-thrombosis, other adverse events, health-related quality of life, healthcare costs and mortality. To achieve 90% power (alpha=0.05) for the primary outcome, data from 720 recruitments are required. A mixed-methods approach will be employed to explore implementation contexts from the perspective of clinicians and healthcare purchasers.Ethics and dissemination Ethics approval has been provided by Children’s Health Queensland Hospital and Health Service Human Research Ethics Committee (HREC) (HREC/22/QCHQ/81744) and the University of Queensland HREC (2022/HE000196) with subsequent governance approval at all sites. Informed consent is required from the substitute decision-maker or legal guardian prior to participation. In addition, consent may also be obtained from mature minors, depending on the legislative requirements of the study site. The primary trial and substudies will be written by the investigators and published in peer-reviewed journals. The findings will also be disseminated through local health and clinical trial networks by investigators and presented at conferences.Trial registration number ACTRN12622000499785.

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

Substantial progress has been made in understanding the neurocognitive underpinnings of learning math. Building on this work, it has been hypothesized that declarative and procedural memory, two domain-general learning and memory systems, play important roles in acquiring math skills. In a longitudinal study, we tested whether in fact declarative and procedural memory predict children's math skills during elementary school years. A sample of 109 children was tested across grades 2, 3 and 4. Linear mixed-effects regression and structural equation modeling revealed the following. First, learning in declarative but not procedural memory was associated with math skills within each grade. Second, declarative but not procedural memory in each grade was related to math skills in all later grades (e.g., declarative memory in grade 2 was related to math skills in grade 4). Sensitivity analyses showed that the pattern of results was robust, except for the longitudinal prediction of later math skills when accounting for stable inter-individual differences via the inclusion of random intercepts. Our findings highlight the foundational role of early domain-general learning and memory in children's acquisition of math.

Objetivo: analisar as vivências do diagnóstico de Doença Renal Crônica sob a ótica dos pacientes. Método: estudo qualitativo realizado por meio de entrevistas semiestruturadas realizadas junto aos pacientes atendidos em um serviço de hemodiálise; os dados foram submetidos à análise de Conteúdo de Bardin. Resultados: as vivências foram organizadas nas seguintes categorias significativas: Sentimentos vivenciados no momento do diagnóstico; Impactos do diagnóstico; Negação da doença; O paradoxo da gratidão e Enfrentamento da doença. Considerações finais: a vivência do diagnóstico da Doença Renal Crônica adquire uma perspectiva singular para cada paciente subsidiada por aspectos de ordem subjetiva, pelo suporte assistencial e familiar ao qual ele tem acesso.

The Endosomal Sorting Complexes Required for Transport (ESCRT) machinery mediates the membrane fission step that completes cytokinetic abscission and separates dividing cells. Filaments composed of ESCRT-III subunits constrict membranes of the intercellular bridge midbody to the abscission point. These filaments also bind and recruit cofactors whose activities help execute abscission and/or delay abscission timing in response to mitotic errors via the NoCut/Abscission checkpoint. We previously showed that the ESCRT-III subunit IST1 binds the cysteine protease Calpain-7 (CAPN7) and that CAPN7 is required for both efficient abscission and NoCut checkpoint maintenance (Wenzel et al., 2022). Here, we report biochemical and crystallographic studies showing that the tandem microtubule-interacting and trafficking (MIT) domains of CAPN7 bind simultaneously to two distinct IST1 MIT interaction motifs. Structure-guided point mutations in either CAPN7 MIT domain disrupted IST1 binding in vitro and in cells, and depletion/rescue experiments showed that the CAPN7-IST1 interaction is required for (1) CAPN7 recruitment to midbodies, (2) efficient abscission, and (3) NoCut checkpoint arrest. CAPN7 proteolytic activity is also required for abscission and checkpoint maintenance. Hence, IST1 recruits CAPN7 to midbodies, where its proteolytic activity is required to regulate and complete abscission.

Vascular calcification (VC) is concomitant with atherosclerosis, yet it remains uncertain why rupture-prone high-risk plaques do not typically show extensive calcification. Intraplaque hemorrhage (IPH) deposits erythrocyte-derived cholesterol, enlarging the necrotic core and promoting high-risk plaque development. Pro-atherogenic CD163+ alternative macrophages engulf hemoglobin:haptoglobin (HH) complexes at IPH sites. However, their role in VC has never been examined to our knowledge. Here we show, in human arteries, the distribution of CD163+ macrophages correlated inversely with VC. In vitro experiments using vascular smooth muscle cells (VSMCs) cultured with HH-exposed human macrophage — M(Hb) — supernatant reduced calcification, while arteries from ApoE–/– CD163–/– mice showed greater VC. M(Hb) supernatant–exposed VSMCs showed activated NF-κB, while blocking NF-κB attenuated the anticalcific effect of M(Hb) on VSMCs. CD163+ macrophages altered VC through NF-κB–induced transcription of hyaluronan synthase (HAS), an enzyme that catalyzes the formation of the extracellular matrix glycosaminoglycan, hyaluronan, within VSMCs. M(Hb) supernatants enhanced HAS production in VSMCs, while knocking down HAS attenuated its anticalcific effect. NF-κB blockade in ApoE–/– mice reduced hyaluronan and increased VC. In human arteries, hyaluronan and HAS were increased in areas of CD163+ macrophage presence. Our findings highlight an important mechanism by which CD163+ macrophages inhibit VC through NF-κB–induced HAS augmentation and thus promote the high-risk plaque development.

Correlation does not imply causation, but this does not necessarily stop people from drawing causal inferences from correlational statements. We show that people do in fact infer causality from statements of association, under minimal conditions. In Study 1, participants interpreted statements of the form "X is associated with Y" to imply that Y causes X. In Studies 2 and 3, participants interpreted statements of the form "X is associated with an increased risk of Y" to imply that X causes Y. Thus, even the most orthodox correlational language can give rise to causal inferences.

Objectives Tocilizumab showed trends for improving skin fibrosis and prevented progression of lung fibrosis in systemic sclerosis (SSc) in randomised controlled clinical trials. We aimed to assess safety and effectiveness of tocilizumab in a real-life setting using the European Scleroderma Trial and Research (EUSTAR) database.Methods Patients with SSc fulfilling the American College of Rheumatology (ACR)/EULAR 2013 classification criteria, with baseline and follow-up visits at 12±3 months, receiving tocilizumab or standard of care as the control group, were selected. Propensity score matching was applied. Primary endpoints were the modified Rodnan skin score (mRSS) and FVC at 12±3 months compared between the groups. Secondary endpoints were the percentage of progressive/regressive patients for skin and lung at 12±3 months.Results Ninety-three patients with SSc treated with tocilizumab and 3180 patients with SSc with standard of care fulfilled the inclusion criteria. Comparison between groups did not show significant differences, but favoured tocilizumab across all predefined primary and secondary endpoints: mRSS was lower in the tocilizumab group (difference −1.0, 95% CI −3.7 to 1.8, p=0.48). Similarly, FVC % predicted was higher in the tocilizumab group (difference 1.5 (−6.1 to 9.1), p=0.70). The percentage of progressive/regressive patients favoured tocilizumab over controls. These results were robust regarding the sensitivity analyses. Safety analysis confirmed previously reported adverse event profiles.Conclusion Although this large, observational, controlled, real-life EUSTAR study did not show significant effectiveness of tocilizumab on skin and lung fibrosis, the consistency of direction of all predefined endpoints generates hypothesis for potential effectiveness in a broader SSc population.

The 12 related human ESCRT-III proteins form filaments that constrict membranes and mediate fission, including during cytokinetic abscission. The C-terminal tails of polymerized ESCRT-III subunits also bind proteins that contain Microtubule-Interacting and Trafficking (MIT) domains. MIT domains can interact with ESCRT-III tails in many different ways to create a complex binding code that is used to recruit essential cofactors to sites of ESCRT activity. Here, we have comprehensively and quantitatively mapped the interactions between all known ESCRT-III tails and 19 recombinant human MIT domains. We measured 228 pairwise interactions, quantified 60 positive interactions, and discovered 18 previously unreported interactions. We also report the crystal structure of the SPASTIN MIT domain in complex with the IST1 C-terminal tail. Three MIT enzymes were studied in detail and shown to: (1) localize to cytokinetic midbody membrane bridges through interactions with their specific ESCRT-III binding partners (SPASTIN-IST1, KATNA1-CHMP3, and CAPN7-IST1), (2) function in abscission (SPASTIN, KATNA1, and CAPN7), and (3) function in the ‘NoCut’ abscission checkpoint (SPASTIN and CAPN7). Our studies define the human MIT-ESCRT-III interactome, identify new factors and activities required for cytokinetic abscission and its regulation, and provide a platform for analyzing ESCRT-III and MIT cofactor interactions in all ESCRT-mediated processes.

Abstract T-cell-redirecting bispecific antibodies have emerged as a new class of therapeutic agents designed to simultaneously bind to T cells via CD3 and to tumor cells via tumor-cell-specific antigens (TSA), inducing T-cell-mediated killing of tumor cells. The promising preclinical and clinical efficacy of TSAxCD3 antibodies is often accompanied by toxicities such as cytokine release syndrome due to T-cell activation. How the efficacy and toxicity profile of the TSAxCD3 bispecific antibodies depends on the binding affinity to CD3 remains unclear. Here, we evaluate bispecific antibodies that were engineered to have a range of CD3 affinities, while retaining the same binding affinity for the selected tumor antigen. These agents were tested for their ability to kill tumor cells in vitro, and their biodistribution, serum half-life, and anti-tumor activity in vivo. Remarkably, by altering the binding affinity for CD3 alone, we can generate bispecific antibodies that maintain potent killing of TSA + tumor cells but display differential patterns of cytokine release, pharmacokinetics, and biodistribution. Therefore, tuning CD3 affinity is a promising method to improve the therapeutic index of T-cell-engaging bispecific antibodies.

Abstract Treatment of cancers in the lung remains a critical challenge in the clinic for which gene therapy could offer valuable options. We describe an effective approach through systemic injection of engineered polymer/DNA nanoparticles that mediate tumor-specific expression of a therapeutic gene, under the control of the cancer-selective progression elevated gene 3 (PEG-3) promoter, to treat tumors in the lungs of diseased mice. A clinically tested, untargeted, polyethylenimine carrier was selected to aid rapid transition to clinical studies, and a CpG-free plasmid backbone and coding sequences were used to reduce inflammation. Intravenous administration of nanoparticles expressing murine single-chain interleukin 12, under the control of PEG-3 promoter, significantly improved the survival of mice in both an orthotopic and a metastatic model of lung cancer with no marked symptoms of systemic toxicity. These outcomes achieved using clinically relevant nanoparticle components raises the promise of translation to human therapy.

Abstract Humans recognize individual faces regardless of variation in the facial view. The view-tuned face neurons in the inferior temporal (IT) cortex are regarded as the neural substrate for view-invariant face recognition. This study approximated visual features encoded by these neurons as combinations of local orientations and colors, originated from natural image fragments. The resultant features reproduced the preference of these neurons to particular facial views. We also found that faces of one identity were separable from the faces of other identities in a space where each axis represented one of these features. These results suggested that view-invariant face representation was established by combining view sensitive visual features. The face representation with these features suggested that, with respect to view-invariant face representation, the seemingly complex and deeply layered ventral visual pathway can be approximated via a shallow network, comprised of layers of low-level processing for local orientations and colors (V1/V2-level) and the layers which detect particular sets of low-level elements derived from natural image fragments (IT-level).

Abstract Investigating historical anthropogenic impacts on faunal communities is key to understanding present patterns of biodiversity and holds important implications for conservation biology. While several studies have demonstrated the human role in the extinction of large herbivores, effective methods to study human interference on large carnivores in the past are limited by the small number of carnivoran remains in the paleozoological record. Here, we integrate a systematic paleozoological survey of biogenic cave assemblages with the archaeological and paleoenvironmental records of the Judean Desert, to reveal historical changes in the large carnivore community. Our results show a late Holocene (~ 3400 years ago) faunal reassembly characterized by the diminishment of the dominant large carnivoran, the Arabian leopard (Panthera pardus sbsp. nimr), and the spread of the Syrian striped hyena (Hyaena hyaena sbsp. syriaca). We suggest that increased hunting pressure in combination with regional aridification were responsible for the decrease in the number of leopards, while the introduction of domestic animals and settlement refuse brought new scavenging opportunities for hyenas. The recent extirpation of leopards from the region has been a final note to the Holocene human impact on the ecosystem.

Background In COVID-19 patients, lung ultrasound is superior to chest radiograph and has good agreement with computerized tomography to diagnose lung pathologies. Most lung ultrasound protocols published to date are complex and time-consuming. We describe a new illustrative Point-of-care ultrasound Lung Injury Score (PLIS) to help guide the care of patients with COVID-19 and assess if the PLIS would be able to predict COVID-19 patients’ clinical course. Methods This retrospective study describing the novel PLIS was conducted in a large tertiary-level hospital. COVID-19 patients were included if they required any form of respiratory support and had at least one PLIS study during hospitalization. Data collected included PLIS on admission, demographics, Sequential Organ Failure Assessment (SOFA) scores, and patient outcomes. The primary outcome was the need for intensive care unit (ICU) admission. Results A total of 109 patients and 293 PLIS studies were included in our analysis. The mean age was 60.9, and overall mortality was 18.3%. Median PLIS score was 5.0 (3.0–6.0) vs. 2.0 (1.0–3.0) in ICU and non-ICU patients respectively (pConclusions The PLIS for COVID-19 patients is simple and associated with SOFA score, ICU admission, and in-hospital mortality. Further studies are needed to demonstrate whether the PLIS can improve outcomes and become an integral part of the management of COVID-19 patients.

Bacteria of the Borrelia burgdorferi sensu lato complex are the causative agents of Lyme borreliosis (LB). Even if the conventional diagnosis of LB does not rely on the species itself, an accurate species identification within the complex will provide a deepened epidemiological scenario, a better diagnosis leading to a more targeted therapeutic approach, as well as promote the general public’s awareness. A comparative genomics approach based on the 210 Borrelia spp. genomes available in 2019 were used to set up three species-specific PCR protocols, able to detect and provide species typing of Borrelia afzelii, Borrelia burgdorferi sensu stricto (s.s.) and Borrelia garinii, the three most common and important human pathogenic Lyme Borrelia species in Europe. The species-specificity of these protocols was confirmed on previously identified B. afzelii, B. burgdorferi s.s. and B. garinii specimens detected in Ixodes ricinus samples. In addition, the protocols were validated on 120 DNA samples from ticks collected in Sweden, showing 88% accuracy, 100% precision, 72% sensitivity and 100% specificity. The proposed approach represents an innovative tool in epidemiological studies focused on B. burgdorferi s.l. occurrence in ticks, and future studies could suggest its helpfulness in routine diagnostic tests for health care.

The abscission checkpoint regulates the ESCRT membrane fission machinery and thereby delays cytokinetic abscission to protect genomic integrity in response to residual mitotic errors. The checkpoint is maintained by Aurora B kinase, which phosphorylates multiple targets, including CHMP4C, a regulatory ESCRT-III subunit necessary for this checkpoint. We now report the discovery that cytoplasmic abscission checkpoint bodies (ACBs) containing phospho-Aurora B and tri-phospho-CHMP4C develop during an active checkpoint. ACBs are derived from mitotic interchromatin granules, transient mitotic structures whose components are housed in splicing-related nuclear speckles during interphase. ACB formation requires CHMP4C, and the ESCRT factor ALIX also contributes. ACB formation is conserved across cell types and under multiple circumstances that activate the checkpoint. Finally, ACBs retain a population of ALIX, and their presence correlates with delayed abscission and delayed recruitment of ALIX to the midbody where it would normally promote abscission. Thus, a cytoplasmic mechanism helps regulate midbody machinery to delay abscission.

Introduction Young people in contact with the youth justice system are more likely to present with complex ongoing needs than young people in the general population. To address this, the Framework for Integrated Care (SECURE STAIRS) is being implemented in the Children and Young People's Secure Estate: a ‘whole systems’ approach to support secure settings to develop trauma-informed and relationally based environments, supporting staff to provide consistent, therapeutic care. This paper aims to present the protocol for a national cohort study examining the impact and implementation of this cultural transformation programme.Methods and analysis A mixed-methods realist evaluation will be conducted. Data collection will take place between August 2018 and December 2020. Eighteen sites will collect routine service activity data and questionnaires completed by young people, parents/guardians and staff. Semi-structured interviews and non-participant observations will be conducted across five qualitative focus sites with young people and staff. An economic evaluation will examine value for money. The results will be triangulated at the analysis stage to gain an in-depth understanding of experiences.Ethics and dissemination Ethical approval was granted by the Health Research Authority, Her Majesty’s Prison and Probation Service and UCL Ethics Committee. Findings will be disseminated via project reports, site feedback, peer-reviewed journal publications and conference presentations.

Introduction Peripherally inserted central catheters (PICCs) are vital for the delivery of medical therapies, but up to 30% of PICCs are associated with complications such as deep vein thrombosis or infection. The integration of antimicrobial and hydrophobic catheter materials, and pressure-activated valves, into polyurethane PICCs are innovations designed to prevent infective and/or thrombotic complications.Methods and analysis A multicentre, parallel group, superiority randomised controlled trial with two experimental arms ((1) hydrophobic PICC (with pressure-activated valve); (2) chlorhexidine gluconate-impregnated PICC (with external clamp)) and one control group ((3) conventional polyurethane PICC (with external clamp)). Recruitment of 1098 adult and paediatric patients will take place over 2 years at three tertiary-referral hospitals in Queensland, Australia. Patients are eligible for inclusion if their PICC is to be inserted for medical treatment, with a vascular size sufficient to support a 4-Fr PICC or larger, and with informed consent. The primary outcome is PICC failure, a composite of thrombotic (venous thrombosis, breakage and occlusion) and infective complications (PICC-associated bloodstream infection and local infection). Secondary outcomes include: all-cause PICC complication; thrombotic complications; infective complications; adverse events (local or systemic reaction); PICC dwell time; patient/parent satisfaction; and healthcare costs. Differences between both intervention groups and the control group will be compared using Cox proportional hazards regression. Effect estimates will be presented as HRs with corresponding 95% CI.Ethics and dissemination Ethical approval from Queensland Health (HREC/QCHQ/48682) and Griffith University (Ref. No. 2019/094). Results will be published.Trial registration number ACTRN12619000022167.

Diarrhea in mink kits is a major cause of disease and mortality in the mink production. The etiology remains unknown in most outbreaks due to a lack of diagnostic assays. In the current study we present an RT-qPCR method to detect mink astrovirus in fecal samples from mink kits with diarrhea. All sampled animals were classified based on age and patoanatomical evaluation as having pre-weaning diarrhea, diarrhea in the growth period or as having no macroscopic signs of diarrhea. Fecal samples were analyzed for MiAstV with RT-qPCR, next generation sequencing and electron microscopy in parallel. Mink astrovirus was detected with RT-qPCR in 92 out of 203 samples. This detection was confirmed by next generation sequencing in a high proportion of samples (22/27), and by visualization of astrovirus particles with EM in some of the samples. Mink astrovirus was highly prevalent (68%) among kits in the outbreaks of pre-weaning diarrhea, in particular outbreaks from May, while less prevalent in outbreaks in June. Mink astrovirus was detected in outbreaks of diarrhea in the growth period, though in a much lesser extent than in the pre-weaning period. The role of mink astrovirus in the diarrhea disease complex of mink remain to be investigated, and for that purpose this sensitive and robust RT-qPCR can be a valuable tool in the future.

Introduction: Despite the extraordinary amount of time physicians spend communicating with patients, dedicated education strategies on this topic are lacking. The objective of this study was to develop a multimodal curriculum including direct patient feedback and assess whether it improves communication skills as measured by the Communication Assessment Tool (CAT) in fourth-year medical students during an emergency medicine (EM) clerkship. Methods: This was a prospective, randomized trial of fourth-year students in an EM clerkship at an academic medical center from 2016–2017. We developed a multimodal curriculum to teach communication skills consisting of 1) an asynchronous video on communication skills, and 2) direct patient feedback from the CAT, a 15-question tool with validity evidence in the emergency department setting. The intervention group received the curriculum at the clerkship midpoint. The control group received the curriculum at the clerkship’s end. We calculated proportions and odds ratios (OR) of students achieving maximum CAT score in the first and second half of the clerkship. Results: A total of 64 students were enrolled: 37 in the control group and 27 in the intervention group. The percentage of students achieving the maximum CAT score was similar between groups during the first half (OR 0.70, p = 0.15). Following the intervention, students in the intervention group achieved a maximum score more often than the control group (OR 1.65, p = 0.008). Conclusion: Students exposed to the curriculum early had higher patient ratings on communication compared to the control group. A multimodal curriculum involving direct patient feedback may be an effective means of teaching communication skills.

The structure of the interview day affects applicant interactions with faculty and residents, which can influence the applicant’s rank list decision. We aimed to determine if there was a difference in matched residents between those interviewing on a day on which didactics were held and had increased resident and faculty presence (didactic day) versus an interview day with less availability for applicant interactions with residents and faculty (non-didactic day). This was a retrospective study reviewing interview dates of matched residents from 2009-2015. Forty-two (61.8%) matched residents interviewed on a didactic day with increased faculty and resident presence versus 26 (38.2%) on a non-didactic interview day with less availability for applicant interactions (p = 0.04). There is an association between interviewing on a didactic day with increased faculty and resident presence and matching in our program.

Over the last two decades, much of the recent efforts dedicated to the Levantine Middle Paleolithic has concentrated on the role of open-air sites in the settlement system in the region. Here focus on the site of 'Ein Qashish as a cases study. Located in present-day northern Israel, the area of this site is estimated to have been >1300 m2, of which ca. 670 were excavated. The site is located at the confluence of the Qishon stream with a small tributary running off the eastern flanks of the Mt. Carmel. At the area of this confluence, water channels and alluvial deposits created a dynamic depositional environment. Four Archaeological Units were identified in a 4.5-m thick stratigraphic sequence were dated by Optically Stimulated Luminescence (OSL) to between-71 and 54 ka, and probably shorter time span-~70-~60 ka. Here we present the diverse material culture remains from the site (lithics, including refitted sequences; modified limestone pieces; molluscs; faunal remains) against their changing paleogeographic backdrop. Skeletal evidence suggests that these remains were associated with Neanderthals. The large-scale repeated accumulation of late Middle Paleolithic remains in the same place on the landscape provides a unique opportunity to address questions of occupation duration and intensity in open-air sites. We find that each occupation was of ephemeral nature, yet presents a range of activities, suggesting that the locale has been used as a generalized residential site rather than specialized task-specific ones. This role of 'Ein Qashish did not change through time, suggesting that during the late Middle Paleolithic settlement system in this part of the southern Levant were stable.

People spend much of their time in imaginary worlds, and have beliefs about the events that are likely in those worlds, and the laws that govern them. Such beliefs are likely affected by people's intuitive theories of the real world. In three studies, people judged the effort required to cast spells that cause physical violations. People ranked the actions of spells congruently with intuitive physics. For example, people judge that it requires more effort to conjure up a frog than to levitate it one foot off the ground. A second study manipulated the target and extent of the spells, and demonstrated with a continuous measure that people are sensitive to this manipulation even between participants. A pre-registered third study replicated the results of Study 2. These results suggest that people's intuitive theories partly account for how they think about imaginary worlds.

Introduction: Emergency physicians (EP) experience high rates of workplace violence, the risks of which increase with the presence of weapons. Up to 25% of trauma patients brought to the emergency department (ED) have been found to carry weapons. Given these risks, we conducted an educational needs assessment to characterize EPs’ knowledge of firearms, frequency of encountering firearms in the ED, and level of confidence with safely removing firearms from patient care settings. Methods: This was a survey study of attending and resident EPs at two academic and four community hospitals in the Midwest and Northeast. A 26-item questionnaire was emailed to all EPs at the six institutions. Questions pertained to EPs’ knowledge of firearms, experience with handling firearms, and exposure to firearms while at work. We calculated response proportions and p-values. Results: Of 243 recipients who received the survey, 149 (61.3%) completed it. Thirty-three respondents (22.0%) reported encountering firearms in the workplace, 91 (60.7%) reported never handling firearms, and 25 (16.7%) reported handling firearms at least once per year. Thirty-six respondents (24.0%) reported formal firearms training, and 63 (42.3%) reported no firearms training. There were no significant regional differences regarding firearms training or exposure. Residents from the Northeast were more likely to be moderately confident that they could safely handle a firearm prior to law enforcement involvement (p=0.043), while residents from the Midwest were more likely to be not at all confident (p=0.018). Conclusion: The majority of surveyed attending and resident EPs reported little experience with handling firearms. Among resident EPs, there was a regional difference in confidence in handling firearms prior to law enforcement involvement. Given the realities of workplace violence and the frequency with which firearms are encountered in the ED, further investigation is needed to evaluate provider competence in safely handling them. EPs may benefit from training on this topic.

To identify factors that regulate gut microbiota density and the impact of varied microbiota density on health, we assayed this fundamental ecosystem property in fecal samples across mammals, human disease, and therapeutic interventions. Physiologic features of the host (carrying capacity) and the fitness of the gut microbiota shape microbiota density. Therapeutic manipulation of microbiota density in mice altered host metabolic and immune homeostasis. In humans, gut microbiota density was reduced in Crohn’s disease, ulcerative colitis, and ileal pouch-anal anastomosis. The gut microbiota in recurrent Clostridium difficile infection had lower density and reduced fitness that were restored by fecal microbiota transplantation. Understanding the interplay between microbiota and disease in terms of microbiota density, host carrying capacity, and microbiota fitness provide new insights into microbiome structure and microbiome targeted therapeutics.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).

Tomato spotted wilt virus (TSWV; species Tomato spotted wilt orthotospovirus; genus Orthotospovirus; family Tospoviridae) is a thrips-transmitted virus that can cause substantial economic losses to many crops, including tomato (Solanum lycopersicum). Since 2005, TSWV emerged as an economically important virus of processing tomatoes in the Central Valley of California, in part due to increased populations of the primary thrips vector, western flower thrips (WFT; Frankliniella occidentalis). To develop an understanding of the epidemiology of TSWV in this region, population densities of WFT and incidence of TSWV were monitored in California’s processing tomato transplant-producing greenhouses and associated open fields from 2007 to 2013. Thrips were monitored with yellow sticky cards and in tomato flowers, whereas TSWV incidence was assessed with indicator plants and field surveys for virus symptoms. All thrips identified from processing tomato fields were WFT, and females were three-fold more abundant on sticky cards than males. Symptoms of TSWV infection were observed in all monitored processing tomato fields. Incidences of TSWV ranged from 1 to 20%, with highest incidence found in late-planted fields. There was no single primary inoculum source, and inoculum sources for thrips/TSWV varied depending on the production region. These results allowed us to develop a model for TSWV infection of processing tomatoes in the Central Valley of California. The model predicts that low levels of primary TSWV inoculum are amplified in early-planted tomatoes and other susceptible crops leading to highest levels of infection in later-planted fields, especially those with high thrips populations. Based upon these findings, an integrated pest management (IPM) strategy for TSWV in processing tomatoes in California was devised. This IPM strategy focuses on strategic field placement (identification of high-risk situations), planting TSWV- and thrips-free transplants, planting resistant varieties, monitoring for TSWV symptoms and thrips, roguing infected plants, thrips management targeting early generations, extensive sanitation after harvest, and strategic cropping to avoid overlap with winter bridge crops.

Apolipoprotein E (APOE) genotype is believed to play a role in the onset of dementia, though less is known about its relationship with non-pathogenic age-related cognitive decline. We assessed whether APOE was a risk factor for cognitive decline among older Taiwanese adults using nationally representative data. General cognition was measured longitudinally over eleven years; domain-specific cognitive assessments of working memory, declarative learning and three aspects of attention (executive function, alerting, and orientation) were performed once. Having at least one risky APOE allele was associated with more rapid longitudinal cognitive decline compared to those with no risky alleles. Some evidence from the cross-sectional analysis of domain-specific cognitive assessments suggested that APOE genotype may be more closely associated with working memory and declarative learning than with attention. Most genetic studies of cognition include only populations of European descent; extension is crucial. This study confirmed the association between APOE genotype and the rate of cognitive decline in a predominantly Han Chinese population. Additional studies on diverse populations are warranted.

Pre-weaning diarrhea (PWD) in mink kits is a common multifactorial syndrome on commercial mink farms. Several potential pathogens such as astroviruses, caliciviruses, Escherichia coli and Staphylococcus delphini have been studied, but the etiology of the syndrome seems complex. In pooled samples from 38 diarrheic and 42 non-diarrheic litters, each comprising of intestinal contents from 2-3 mink kits from the same litter, the bacterial populations were studied using Illumina Next Generation Sequencing technology and targeted 16S amplicon sequencing. In addition, we used deep sequencing to determine and compare the viral intestinal content in 31 healthy non-diarrheic and 30 diarrheic pooled samples (2-3 mink kits from the same litter per pool). The results showed high variations in composition of the bacterial species between the pools. Enterococci, staphylococci and streptococci dominated in both diarrheic and non-diarrheic pools. However, enterococci accounted for 70% of the reads in the diarrheic group compared to 50% in the non-diarrheic group and this increase was at the expense of staphylococci and streptococci which together accounted for 45% and 17% of the reads in the non-diarrheic and diarrheic group, respectively. Moreover, in the diarrheic pools there were more reads assigned to Clostridia, Escherichia-Shigella and Enterobacter compared to the non-diarrheic pools. The taxonomically categorized sequences from the virome showed that the most prevalent viruses in all pools were caliciviruses and mamastroviruses (almost exclusively type 10). However, the numbers of reads assigned to caliciviruses were almost 3 times higher in the diarrheic pools compared the non-diarrheic pools and Sapporo-like caliciviruses were more abundant than the Norwalk-like caliciviruses. The results from this study have contributed to the insight into the changes in the intestinal microbiota associated with the PWD syndrome of mink.

Despite a large body of research on response properties of neurons in the inferior temporal (IT) cortex, studies to date have not yet produced quantitative feature descriptions that can predict responses to arbitrary objects. This deficit in the research prevents a thorough understanding of object representation in the IT cortex. Here we propose a fragment-based approach for finding quantitative feature descriptions of face neurons in the IT cortex. The development of the proposed method was driven by the assumption that it is possible to recover features from a set of natural image fragments if the set is sufficiently large. To find the feature from the set, we compared object responses predicted from each fragment and responses of neurons to these objects, and search for the fragment that revealed the highest correlation with neural object responses. Prediction of object responses of each fragment was made by normalizing Euclidian distance between the fragment and each object to 0 to 1 such that the smaller distance gives the higher value. The distance was calculated at the space where images were transformed to a local orientation space by a Gabor filter and a local max operation. The method allowed us to find features with a correlation coefficient between predicted and neural responses of 0.68 on average (number of object stimuli, 104) from among 560,000 feature candidates, reliably explaining differential responses among faces as well as a general preference for faces over to non-face objects. Furthermore, predicted responses of the resulting features to novel object images were significantly correlated with neural responses to these images. Identification of features comprising specific, moderately complex combinations of local orientations and colors enabled us to predict responses to upright and inverted faces, which provided a possible mechanism of face inversion effects. (292/300).

Tomatoes (Solanum lycopersicum L.) have been bred to exude higher amounts or different types of the specialized plant metabolites, acylsugars, from type IV trichomes. Acylsugars are known to deter several herbivorous insect pests, including the western flower thrips (WFT), Frankliniella occidentalis (Pergande); however, all previous studies investigated the effect of acylsugars on leaves, or acylsugar extracts obtained from leaves. In spite of the WFT predilection for flowers, there is a gap in knowledge about flower defenses against thrips damage. This is especially important in light of their capacity to acquire and inoculate viruses in the genus Orthotospovirus, such as Tomato spotted wilt orthotospovirus (TSWV), in flowers. Therefore, we turned our attention to assessing thrips oviposition differences on flowers of 14 entries, including 8 interspecific hybrids, 5 tomato lines bred for specific acylsugar-related characteristics (type IV trichome densities, acylsugar amount, sugar moiety and fatty acid profile), and a fresh market tomato hybrid, Mt. Spring, which only produces trace amounts of acylsugars. Our results show that the density of the acylsugar droplet bearing type IV trichomes is greatest on sepals, relative to other flower structures, and accordingly, WFT avoids oviposition on sepals in favor of trichome-sparse petals. In concordance with past studies, acylsugar amount was the most important acylsugar-related characteristic suppressing WFT oviposition. Certain acylsugar fatty acids, specifically i-C5, i-C9 and i-C11, were also significantly associated with changes in WFT oviposition. These results support continued breeding efforts to increase acylsugar amounts and explore modifications of fatty acid profile and their roles in deterring thrips oviposition. The finding that acylsugar production occurs and reduces thrips oviposition in tomato flowers will be important in efforts to use acylsugar-mediated resistance to reduce incidence of orthotospoviruses such as TSWV in tomato by deterring virus transmission and development of thrips vector populations in the crop.

Peripheral intravascular cannula/catheter (PIVC) insertion is a common invasive procedure, but PIVC failure before the end of therapy is unacceptably high. As PIVC failure disrupts treatment and reinsertion can be distressing for the patient, prevention of PIVC failure is an important patient outcome. Consumer participation in PIVC care to prevent failure is an untapped resource. This study aimed to understand consumers' PIVC experience; establish aspects of PIVC insertion and care relevant to them; and to compare experiences of adult consumers to adult carers of a child. An international, web-based, cross-sectional survey was distributed via social media inviting adult consumers and adult carers of a child under 18 years who had experienced having a PIVC in the last five years (one survey each for adults and adult carers) to complete a 10-item survey. As such, sampling bias is a limitation and results should be carefully considered in light of this. There were 712 respondents from 25 countries, mainly female (87.1%) and adults (80%). A little over 50% of adults described insertion as moderately painful or worse, with level of insertion difficulty (0-10 scale) identified as moderate (median 4, IQR 1, 7). Adult carers reported significantly more pain during insertion and insertion difficulty (both p < 0.001). Rates of first insertion attempt failure were higher in children compared with adults (89/139 [64%] vs 221/554 [40%]; p < 0.001), and 23% of children required ≥ 4 attempts, compared with 9% of adults (p < 0.0001). Three themes from open-ended question emerged: Significance of safe and consistent PIVC care; Importance of staff training and competence; and Value of communication. The PIVC experience can be painful, stressful and frustrating for consumers. Priorities for clinicians and policy makers should include use of pain relief as standard practice to reduce the pain associated with PIVC insertion and developing strategies to increase first PIVC insertion attempt success particularly for children and older consumers.

OBJECTIVE:Bed rest or activity restriction is a common obstetrical practice, despite a paucity of data to support its efficacy. The aim of this study was to determine whether physical activity, as assessed by a smart band activity tracker, is associated with preterm birth in pregnant women at high risk for preterm delivery. METHODS:This was a pilot prospective cohort study including pregnant women at high risk for preterm delivery between 24 and 32 weeks-of-gestation. Physical activity level was assessed by smart band activity. Patients with sonographic short cervical length (≤ 20 mm) were asked to wear the smart band activity tracker continuously for at least one week, including one weekend. Both physicians and patients were blinded to the data stored in the smart band activity tracker. No specific recommendations were given to participants as to the level or intensity of physical activity. The primary outcome was the rate of preterm birth (< 37 weeks-of-gestation). Secondary outcomes included the rate of delivery before 34 weeks of gestation and neonatal outcome. Parametric and nonparametric statistics were used for analysis. RESULTS:Study population included 49 pregnant women: 37 women (75.7%) delivered preterm and 12 (24.5%) delivered at or after 37 weeks-of-gestation. The median steps per day was significantly lower in patients who delivered preterm (3576, IQR: 2478-4775 vs. 4554, IQR: 3632-6337, p = 0.02). Regression analysis revealed that the median number of steps per day was independently inversely associated with preterm birth, after adjustment for maternal age, body mass index, gestational age at recruitment, cervical length, cervical dilatation and plurality. CONCLUSION:This pilot study represents the first quantitative assessment of the association between physical activity and preterm birth. The results of this pilot study do not support the efficacy of decreased physical activity in the prevention of preterm birth in patients with sonographic short cervical length.

Introduction: Chest pain is a common emergency department (ED) presentation accounting for 8–10 million visits per year in the United States. Physician-level factors such as risk tolerance are predictive of admission rates. The recent advent of accelerated diagnostic pathways and ED observation units may have an impact in reducing variation in admission rates on the individual physician level. Methods: We conducted a single-institution retrospective observational study of ED patients with a diagnosis of chest pain as determined by diagnostic code from our hospital administrative database. We included ED visits from 2012 and 2013. Patients with an elevated troponin or an electrocardiogram (ECG) demonstrating an ST elevation myocardial infarction were excluded. Patients were divided into two groups: “admission” (this included observation and inpatients) and “discharged.” We stratified physicians by age, gender, residency location, and years since medical school. We controlled for patient- and hospital-related factors including age, gender, race, insurance status, daily ED volume, and lab values. Results: Of 4,577 patients with documented dispositions, 3,252 (70.9%) were either admitted to the hospital or into observation (in an ED observation unit or in the hospital), while 1,333 (29.1%) were discharged. Median number of patients per physician was 132 (interquartile range 89–172). Average admission rate was 73.7±9.5% ranging from 54% to 96%. Of the 3,252 admissions, 2,638 (81.1%) were to observation. There was significant variation in the admission rate at the individual physician level with adjusted odds ratio ranging from 0.42 to 5.8 as compared to the average admission. Among physicians’ characteristics, years elapsed since finishing medical school demonstrated a trend towards association with a higher admission probability. Conclusion: There is substantial variation among physicians in the management of patients presenting with chest pain, with physician experience playing a role.

We examined learning and retention in nonverbal and verbal declarative memory in Hungarian children with (n = 21) and without (n = 21) SLI. Recognition memory was tested both 10 minutes and one day after encoding. On nonverbal items, only the children with SLI improved overnight, with no resulting group differences in performance. In the verbal domain, the children with SLI consistently showed worse performance than the typically-developing children, but the two groups showed similar overnight changes. The findings suggest the possibility of spared or even enhanced declarative memory consolidation in SLI.

BACKGROUND:Randomized controlled trials evaluate the effectiveness of interventions for central venous access devices, however, high complication rates remain. Scoping reviews map the available evidence and demonstrate evidence deficiencies to focus ongoing research priorities. METHOD:A scoping review (January 2006-December 2015) of randomized controlled trials evaluating the effectiveness of interventions to improve central venous access device outcomes; including peripherally inserted central catheters, non-tunneled, tunneled and totally implanted venous access catheters. MeSH terms were used to undertake a systematic search with data extracted by two independent researchers, using a standardized data extraction form. RESULTS:In total, 178 trials were included (78 non-tunneled [44%]; 40 peripherally inserted central catheters [22%]; 20 totally implanted [11%]; 12 tunneled [6%]; 6 non-specified [3%]; and 22 combined device trials [12%]). There were 119 trials (68%) involving adult participants only, with 18 (9%) pediatric and 20 (11%) neonatal trials. Insertion-related themes existed in 38% of trials (67 RCTs), 35 RCTs (20%) related to post-insertion patency, with fewer trials on infection prevention (15 RCTs, 8%), education (14RCTs, 8%), and dressing and securement (12 RCTs, 7%). There were 46 different study outcomes reported, with the most common being infection outcomes (161 outcomes; 37%), with divergent definitions used for catheter-related bloodstream and other infections. CONCLUSION:More high quality randomized trials across central venous access device management are necessary, especially in dressing and securement and patency. These can be encouraged by having more studies with multidisciplinary team involvement and consumer engagement. Additionally, there were extensive gaps within population sub-groups, particularly in tunneled devices, and in pediatrics and neonates. Finally, outcome definitions need to be unified for results to be meaningful and comparable across studies.