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In this retrospective cohort study of patients presenting to a national direct-to-consumer medical practice, we found that provider geographic location is a stronger driver of antibiotic prescribing than patient location. Physicians in the Northeast and South are significantly more likely than physicians in the West to prescribe antibiotics for upper respiratory infection and bronchitis.
This study aimed to assess the impact of COVID-19 on presentations to an acute hospital with self-harm.
All presentations to University Hospital Galway with self-harm were assessed during the peak period of the coronavirus crisis in Ireland, over the 3 months from 1 March to 31 May 2020. These data were compared with presentations in the same months in the 3 years preceding (2017–2019). Data were obtained from the anonymised service database.
This study found that in 2020, the rate of presentation with self-harm dropped by 35% from March to April and rose by 104% from April to May, peaking from mid-May. When trends over a 4-year period were examined, there was a significantly higher lethality of attempt (p < 0.001), and significant differences in diagnosis (p = 0.031) in 2020 in comparison with the three previous years. The increased lethality of presentations remained significant after age and gender were controlled for (p = 0.036). There were also significant differences in the underlying psychiatric diagnoses (p = 0.018), notably with a significant increase in substance misuse disorders presenting during the 2020 study period.
COVID-19 showed a reduction in self-harm presentations initially, followed by a sharp increase in May 2020. If a period of economic instability follows as predicted, it is likely that this will further impact the mental health of the population, along with rates of self-harm and suicidal behaviours. There is a need for research into the longer-term effect of COVID-19 and lockdown restrictions, especially with respect to self-harm.
The Pennsylvania Longitudinal Study of Parents and Children Twin Registry was developed to capture a representative sample of multiple births and their parents in the state of Pennsylvania. The registry has two main efforts. The first began in 2012 through recruitment of adolescents in Pennsylvania schools. The second effort began in January 2019 in partnership with the Pennsylvania Department of Health to capture the birth cohort of twins born from 2007 to 2017. Study recruitment, sample demographics, focus and measures are provided, as well as future directions.
We conducted active surveillance of acute respiratory viral infections (ARIs) among residents and healthcare personnel (HCP) at a long-term care facility during the 2015–2016 respiratory illness season. ARIs were observed among both HCP and patients, highlighting the importance of including HCP in surveillance programs.
While assessing the environmental impact of nuclear power plants, researchers have focused their attention on radiocarbon (14C) owing to its high mobility in the environment and important radiological impact on human beings. The 10 MW high-temperature gas-cooled reactor (HTR-10) is the first pebble-bed gas-cooled test reactor in China that adopted helium as primary coolant and graphite spheres containing tristructural-isotropic (TRISO) coated particles as fuel elements. A series of experiments on the 14C source terms in HTR-10 was conducted: (1) measurement of the specific activity and distribution of typical nuclides in the irradiated graphite spheres from the core, (2) measurement of the activity concentration of 14C in the primary coolant, and (3) measurement of the amount of 14C discharged in the effluent from the stack. All experimental data on 14C available for HTR-10 were summarized and analyzed using theoretical calculations. A sensitivity study on the total porosity, open porosity, and percentage of closed pores that became open after irradiating the matrix graphite was performed to illustrate their effects on the activity concentration of 14C in the primary coolant and activity amount of 14C in various deduction routes.
Introduction: BACKGROUND: Recognition rates of delirium in older ED patients were reported between 13 to 25% in studies conducted in the U.S in the 1990's. Recently, there has been increased attention to delirium in Emergency Medicine, with the development of Geriatric curriculums in Canada specifically focused on delirium. However rates of delirium recognition have not been reassessed in Canadian ED's. OBJECTIVES: To assess the rate of delirium recognition by ED staff in a cohort of older ED patients assessed at a tertiary care Canadian ED. Methods: STUDY DESIGN: Prospective observational cohort study at a Canadian teaching ED. PARTICIPANTS: Eligible patients were aged ≥70 years and older who had stayed in the ED for a minimum of 4 hours. We excluded patients who were critically ill, visually impaired or otherwise unable to communicate. DATA COLLECTION: Trained research assistants approached clinical staff prior to approaching patients to confirm that patients were delirium free. They then assessed demographics, ED length of stay (LOS) and cognition using the validated Montreal Cognitive Assessment scale (MOCA), mini-mental status exam (MMSE), delirium index and Richardson Agitation Scale (RASS) at baseline. Delirium was assessed using the validated Confusion Assessment Method (CAM). We report descriptive statistics and 95% confidence intervals (CI) where appropriate. Results: We enrolled 203 patients of which 102 (50.3%) were female. Their mean age was 81.0 years, mean LOS was 16.3 hours, mean MOCA was 23.4 and mean MMSE was 26.7. RA's detected delirium using the CAM in 16/203 patients (7.9%, 95% CI 4.6 to 12.5%). Mean MOCA and MMSE for delirious patients was 13.4 and 18.3 and their mean DI was 6.4. All CAM positive patients were deemed to be delirium free by clinical staff. RA alerted clinical staff in all cases where patients had delirium, but 3/16 were discharged home (18.8%, 95% CI 4.1 to 45.7%). Conclusion: Our findings confirm previous low delirium recognition rates in a Canadian Tertiary ED. Future research should explore barriers and facilitators to recognizing delirium in the ED.
To investigate a Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak event involving multiple healthcare facilities in Riyadh, Saudi Arabia; to characterize transmission; and to explore infection control implications.
Cases presented in 4 healthcare facilities in Riyadh, Saudi Arabia: a tertiary-care hospital, a specialty pulmonary hospital, an outpatient clinic, and an outpatient dialysis unit.
Contact tracing and testing were performed following reports of cases at 2 hospitals. Laboratory results were confirmed by real-time reverse transcription polymerase chain reaction (rRT-PCR) and/or genome sequencing. We assessed exposures and determined seropositivity among available healthcare personnel (HCP) cases and HCP contacts of cases.
In total, 48 cases were identified, involving patients, HCP, and family members across 2 hospitals, an outpatient clinic, and a dialysis clinic. At each hospital, transmission was linked to a unique index case. Moreover, 4 cases were associated with superspreading events (any interaction where a case patient transmitted to ≥5 subsequent case patients). All 4 of these patients were severely ill, were initially not recognized as MERS-CoV cases, and subsequently died. Genomic sequences clustered separately, suggesting 2 distinct outbreaks. Overall, 4 (24%) of 17 HCP cases and 3 (3%) of 114 HCP contacts of cases were seropositive.
We describe 2 distinct healthcare-associated outbreaks, each initiated by a unique index case and characterized by multiple superspreading events. Delays in recognition and in subsequent implementation of control measures contributed to secondary transmission. Prompt contact tracing, repeated testing, HCP furloughing, and implementation of recommended transmission-based precautions for suspected cases ultimately halted transmission.
The goal of this study was to perform in situ electrochemical polymerization of poly(3,4-ethylenedioxythiophene) (PEDOT) in peripheral nerves to create a soft, precisely located injectable conductive polymer electrode for bi-directional communication. Intraneural PEDOT polymerization was performed to target both outer and inner fascicles via custom fabricated 3D printed cuff electrodes and monomer injection strategies using a combination electrode-cannula system. Electrochemistry, histology, and laser light sheet microscopy revealed the presence of PEDOT at specified locations inside of peripheral nerve. This work demonstrates the potential for using in situ PEDOT electrodeposition as an injectable electrode for recording and stimulation of peripheral nerves.
Prevalence of skin sores and scabies in remote Australian Aboriginal communities remains unacceptably high, with Group A Streptococcus (GAS) the dominant pathogen. We aim to better understand the drivers of GAS transmission using mathematical models. To estimate the force of infection, we quantified the age of first skin sores and scabies infection by pooling historical data from three studies conducted across five remote Aboriginal communities for children born between 2001 and 2005. We estimated the age of the first infection using the Kaplan–Meier estimator; parametric exponential mixture model; and Cox proportional hazards. For skin sores, the mean age of the first infection was approximately 10 months and the median was 7 months, with some heterogeneity in median observed by the community. For scabies, the mean age of the first infection was approximately 9 months and the median was 8 months, with significant heterogeneity by the community and an enhanced risk for children born between October and December. The young age of the first infection with skin sores and scabies reflects the high disease burden in these communities.
Low-density, highly porous graphene/graphene oxide (GO) based-foams have shown high performance in energy absorption applications, even under high compressive deformations. In general, foams are very effective as energy dissipative materials and have been widely used in many areas such as automotive, aerospace and biomedical industries. In the case of graphene-based foams, the good mechanical properties are mainly attributed to the intrinsic graphene and/or GO electronic and mechanical properties. Despite the attractive physical properties of graphene/GO based-foams, their structural and thermal stabilities are still a problem for some applications. For instance, they are easily degraded when placed in flowing solutions, either by the collapsing of their layers or just by structural disintegration into small pieces. Recently, a new and scalable synthetic approach to produce low-density 3D macroscopic GO structure interconnected with polydimethylsiloxane (PDMS) polymeric chains (pGO) was proposed. A controlled amount of PDMS is infused into the freeze-dried foam resulting into a very rigid structure with improved mechanical properties, such as tensile plasticity and toughness. The PDMS wets the graphene oxide sheets and acts like a glue bonding PDMS and GO sheets. In order to obtain further insights on mechanisms behind the enhanced mechanical pGO response we carried out fully atomistic molecular dynamics (MD) simulations. Based on MD results, we build up a structural model that can explain the experimentally observed mechanical behavior.
The ability to interface electronic materials with the peripheral nervous system is required for stimulation and monitoring of neural signals. Thus, the design and engineering of robust neural interfaces that maintain material-tissue contact in the presence of material or tissue micromotion offer the potential to conduct novel measurements and develop future therapies that require chronic interface with the peripheral nervous system. However, such remains an open challenge given the constraints of existing materials sets and manufacturing approaches for design and fabrication of neural interfaces. Here, we investigated the potential to leverage a rapid prototyping approach for the design and fabrication of nerve cuffs that contain supporting features to mechanically stabilize the interaction between cuff electrodes and peripheral nerve. A hybrid 3D printing and robotic-embedding (i.e., pick-and-place) system was used to design and fabricate silicone nerve cuffs (800 µm diameter) containing conforming platinum (Pt) electrodes. We demonstrate that the electrical impedance of the cuff electrodes can be reduced by deposition of the conducting polymer poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) on cuff electrodes via a post-processing electropolymerization technique. The computer-aided design and manufacturing approach was also used to design and integrate supporting features to the cuff that mechanically stabilize the interface between the cuff electrodes and the peripheral nerve. Both ‘self-locking’ and suture-assisted locking mechanisms are demonstrated based on the principle of making geometric alterations to the cuff opening via 3D printing. Ultimately, this work shows 3D printing offers considerable opportunity to integrate supporting features, and potentially even novel electronic materials, into nerve cuffs that can support the design and engineering of next generation neural interfaces.
This study aims to investigate the climate–malaria associations in nine cities selected from malaria high-risk areas in China. Daily reports of malaria cases in Anhui, Henan, and Yunnan Provinces for 2005–2012 were obtained from the Chinese Center for Disease Control and Prevention. Generalized estimating equation models were used to quantify the city-specific climate–malaria associations. Multivariate random-effects meta-regression analyses were used to pool the city-specific effects. An inverted-U-shaped curve relationship was observed between temperatures, average relative humidity, and malaria. A 1 °C increase of maximum temperature (Tmax) resulted in 6·7% (95% CI 4·6–8·8%) to 15·8% (95% CI 14·1–17·4%) increase of malaria, with corresponding lags ranging from 7 to 45 days. For minimum temperature (Tmin), the effect estimates peaked at lag 0 to 40 days, ranging from 5·3% (95% CI 4·4–6·2%) to 17·9% (95% CI 15·6–20·1%). Malaria is more sensitive to Tmin in cool climates and Tmax in warm climates. The duration of lag effect in a cool climate zone is longer than that in a warm climate zone. Lagged effects did not vanish after an epidemic season but waned gradually in the following 2–3 warm seasons. A warming climate may potentially increase the risk of malaria resurgence in China.
This study was conducted to evaluate the effect of a 12-h light, 12-h dark (12L : 12D) photoperiod of green light during day 1 to day 18 of incubation time, on embryo growth, hormone concentration and the hatch process. In the test group, monochromatic light was provided by a total of 204 green light-emitting diodes (522 nm) mounted in a frame which was placed above the top tray of eggs to give even spread of illumination. No light–dark cycle was used in the control group. Four batches of eggs (n=300/group per batch) from fertile Ross 308 broiler breeders were used in this experiment. The beak length and crown–rump length of embryos incubated under green light were significantly longer than that of control embryos at day 10 and day 12, respectively (P<0.01). Furthermore, green light-exposed embryos had a longer third toe length compared with control embryos at day 10, day 14 and day 17 (P=0.02). At group level (n=4 batches), light stimulation had no effect on chick weight and quality at take-off, the initiation of hatch and hatch window. However, the individual hatching time of the light exposure focal chicks (n=33) was 3.4 h earlier (P=0.49) than the control focal chicks (n=36) probably due to the change in melatonin rhythm of the light group. The results of this study indicate that green light accelerates embryo development and alters hatch-related hormones (thyroid and corticosterone), which may result in earlier hatching.
Currently, the systematics, biology and epidemiology of piscine Cryptosporidium species are poorly understood. Here, we compared Sanger ‒ and next-generation ‒ sequencing (NGS), of piscine Cryptosporidium, at the 18S rRNA and actin genes. The hosts comprised 11 ornamental fish species, spanning four orders and eight families. The objectives were: to (i) confirm the rich genetic diversity of the parasite and the high frequency of mixed infections; and (ii) explore the potential of NGS in the presence of complex genetic mixtures. By Sanger sequencing, four main genotypes were obtained at the actin locus, while for the 18S locus, seven genotypes were identified. At both loci, NGS revealed frequent mixed infections, consisting of one highly dominant variant plus substantially rarer genotypes. Both sequencing methods detected novel Cryptosporidium genotypes at both loci, including a novel and highly abundant actin genotype that was identified by both Sanger sequencing and NGS. Importantly, this genotype accounted for 68·9% of all NGS reads from all samples (249 585/362 372). The present study confirms that aquarium fish can harbour a large and unexplored Cryptosporidium genetic diversity. Although commonly used in molecular parasitology studies, nested PCR prevents quantitative comparisons and thwarts the advantages of NGS, when this latter approach is used to investigate multiple infections.
In a previous study we investigated three-scalar mixing in a turbulent coaxial jet (Cai et al.J. Fluid Mech., vol. 685, 2011, pp. 495–531). In this flow a centre jet and a co-flow are separated by an annular flow; therefore, the resulting mixing process approximates that in a turbulent non-premixed flame. In the present study, we investigate the effects of the velocity and length scale ratios of the annular flow to the centre jet, which determine the relative mean shear rates between the streams and the degree of separation between the centre jet and the co-flow, respectively. Simultaneous planar laser-induced fluorescence and Rayleigh scattering are employed to obtain the mass fractions of the centre jet scalar (acetone-doped air) and the annular flow scalar (ethylene). The results show that varying the velocity ratio and the annulus width modifies the scalar fields through mean-flow advection, turbulent transport and small-scale mixing. While the evolution of the mean scalar profiles is dominated by the mean-flow advection, the shape of the joint probability density function (JPDF) was found to be largely determined by the turbulent transport and molecular diffusion. Increasing the velocity ratio results in stronger turbulent transport, making the initial scalar evolution faster. However, further downstream the evolution is delayed due to slower small-scale mixing. The JPDF for the higher velocity ratio cases is bimodal at some locations while it is always unimodal for the lower velocity ratio cases. Increasing the annulus width delays the progression of mixing, and makes the effects of the velocity ratio more pronounced. For all cases the diffusion velocity streamlines in the scalar space representing the effects of molecular diffusion generally converge quickly to a curved manifold, whose curvature is reduced as mixing progresses. The curvature of the manifold increases significantly with the velocity and length scale ratios. Predicting the observed mixing path along the manifold as well as its dependence on the velocity and length scale ratios presents a challenge for mixing models. The results in the present study have implications for understanding and modelling multiscalar mixing in turbulent reactive flows.
Bacillary dysentery continues to be a major health issue in developing countries and ambient temperature is a possible environmental determinant. However, evidence about the risk of bacillary dysentery attributable to ambient temperature under climate change scenarios is scarce. We examined the attributable fraction (AF) of temperature-related bacillary dysentery in urban and rural Hefei, China during 2006–2012 and projected its shifting pattern under climate change scenarios using a distributed lag non-linear model. The risk of bacillary dysentery increased with the temperature rise above a threshold (18·4 °C), and the temperature effects appeared to be acute. The proportion of bacillary dysentery attributable to hot temperatures was 18·74% (95 empirical confidence interval (eCI): 8·36–27·44%). Apparent difference of AF was observed between urban and rural areas, with AF varying from 26·87% (95% eCI 16·21–36·68%) in urban area to −1·90% (95 eCI −25·03 to 16·05%) in rural area. Under the climate change scenarios alone (1–4 °C rise), the AF from extreme hot temperatures (>31·2 °C) would rise greatly accompanied by the relatively stable AF from moderate hot temperatures (18·4–31·2 °C). If climate change proceeds, urban area may be more likely to suffer from rapidly increasing burden of disease from extreme hot temperatures in the absence of effective mitigation and adaptation strategies.
A pilot study by 6 Clinical and Translational Science Awards (CTSAs) explored how bibliometrics can be used to assess research influence.
Evaluators from 6 institutions shared data on publications (4202 total) they supported, and conducted a combined analysis with state-of-the-art tools. This paper presents selected results based on the tools from 2 widely used vendors for bibliometrics: Thomson Reuters and Elsevier.
Both vendors located a high percentage of publications within their proprietary databases (>90%) and provided similar but not equivalent bibliometrics for estimating productivity (number of publications) and influence (citation rates, percentage of papers in the top 10% of citations, observed citations relative to expected citations). A recently available bibliometric from the National Institutes of Health Office of Portfolio Analysis, examined after the initial analysis, showed tremendous potential for use in the CTSA context.
Despite challenges in making cross-CTSA comparisons, bibliometrics can enhance our understanding of the value of CTSA-supported clinical and translational research.
Brain Metastases (BM) represent a leading cause of cancer mortality. While metastatic lesions contain subclones derived from their primary lesion, their functional characterization has been limited by a paucity of preclinical models accurately recapitulating the stages of metastasis. This work describes the isolation of a unique subset of metastatic stem-like cells from primary human patient samples of BM, termed brain metastasis initiating cells (BMICs). Utilizing these BMICs we have established a novel patient-derived xenograft (PDX) model of BM that recapitulates the entire metastatic cascade, from primary tumor initiation to micro-metastasis and macro-metastasis formation in the brain. We then comprehensively interrogated human BM to identify genetic regulators of BMICs using in vitro and in vivo RNA interference screens, and validated hits using both our novel PDX model as well as primary clinical BM specimens. We identified SPOCK1 and TWIST2 as novel BMIC regulators, where in our model SPOCK1 regulated BMIC self-renewal and tumor initiation, and TWIST2 specifically regulated cell migration from lung to brain. A prospective cohort of primary lung cancer specimens was used to establish that SPOCK1 and TWIST2 were only expressed in patients who ultimately developed BM, thus establishing both clinical and functional utility for these gene products. This work offers the first comprehensive preclinical model of human brain metastasis for further characterization of therapeutic targets, identification of predictive biomarkers, and subsequent prophylactic treatment of patients most likely to develop BM. By blocking this process, metastatic lung cancer would effectively become a localized, more manageable disease.
Declines in populations of the Critically Endangered Spoon-billed Sandpiper Calidris pygmaeus have been rapid, with the breeding population now perhaps numbering fewer than 120 pairs. The reasons for this decline remain unresolved. Whilst there is evidence that hunting in wintering areas is an important factor, loss of suitable habitat on passage and wintering areas is also of concern. While some key sites for the species are already documented, many of their wintering locations are described here for the first time. Their wintering range primarily stretches from Bangladesh to China. Comprehensive surveys of potential Spoon-billed Sandpiper wintering sites from 2005 to 2013 showed a wide distribution with three key concentrations in Myanmar and Bangladesh, but also regular sites in China, Vietnam and Thailand. The identification of all important non-breeding sites remains of high priority for the conservation of the species. Here, we present the results of field surveys of wintering Spoon-billed Sandpipers that took place in six countries between 2005 and 2013 and present species distribution models which map the potential wintering areas. These include known and currently unrecognised wintering locations. Our maximum entropy model did not identify any new extensive candidate areas within the winter distribution, suggesting that most key sites are already known, but it did identify small sites on the coast of eastern Bangladesh, western Myanmar, and the Guangxi and Guangdong regions of China that may merit further investigation. As no extensive areas of new potential habitat were identified, we suggest that the priorities for the conservation of this species are habitat protection in important wintering and passage areas and reducing hunting pressure on birds at these sites.
Impetigo is common in remote Indigenous children of northern Australia, with the primary driver in this context being Streptococcus pyogenes [or group A Streptococcus (GAS)]. To reduce the high burden of impetigo, the transmission dynamics of GAS must be more clearly elucidated. We performed whole genome sequencing on 31 GAS isolates collected in a single community from children in 11 households with ⩾2 GAS-infected children. We aimed to determine whether transmission was occurring principally within households or across the community. The 31 isolates were represented by nine multilocus sequence types and isolates within each sequence type differed from one another by only 0–3 single nucleotide polymorphisms. There was evidence of extensive transmission both within households and across the community. Our findings suggest that strategies to reduce the burden of impetigo in this setting will need to extend beyond individual households, and incorporate multi-faceted, community-wide approaches.