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Enteric illness outbreaks are complex events, therefore, outbreak investigators use many different hypothesis generation methods depending on the situation. This scoping review was conducted to describe methods used to generate a hypothesis during enteric illness outbreak investigations. The search included five databases and grey literature for articles published between 1 January 2000 and 2 May 2015. Relevance screening and article characterisation were conducted by two independent reviewers using pretested forms. There were 903 outbreaks that described hypothesis generation methods and 33 papers which focused on the evaluation of hypothesis generation methods. Common hypothesis generation methods described are analytic studies (64.8%), descriptive epidemiology (33.7%), food or environmental sampling (32.8%) and facility inspections (27.9%). The least common methods included the use of a single interviewer (0.4%) and investigation of outliers (0.4%). Most studies reported using two or more methods to generate hypotheses (81.2%), with 29.2% of studies reporting using four or more. The use of multiple different hypothesis generation methods both within and between outbreaks highlights the complexity of enteric illness outbreak investigations. Future research should examine the effectiveness of each method and the contexts for which each is most effective in efficiently leading to source identification.
We describe the case of an 11-month-old girl with a rare cerebellar glioblastoma driven by a NACC2-NTRK2 (Nucleus Accumbens Associated Protein 2-Neurotrophic Receptor Tyrosine Kinase 2) fusion. Initial workup of our case demonstrated homozygous CDKN2A deletion, but immunohistochemistry for other driver mutations, including IDH1 R132H, BRAF V600E, and H3F3A K27M were negative, and ATRX was retained. Tissue was subsequently submitted for personalized oncogenomic analysis, including whole genome and whole transcriptome sequencing, which demonstrated an activating NTRK2 fusion, as well as high PD-L1 expression, which was subsequently confirmed by immunohistochemistry. Furthermore, H3 and IDH demonstrated wildtype status. These findings suggested the possibility of treatment with either NTRK- or immune checkpoint- inhibitors through active clinical trials. Ultimately, the family pursued standard treatment that involved Head Start III chemotherapy and proton radiotherapy. Notably, at most recent follow upapproximately two years from initial diagnosis, the patient is in disease remission and thriving, suggesting favorable biology despite histologic malignancy. This case illustrates the value of personalized oncogenomics, as the molecular profiling revealed two actionable changes that would not have been apparent through routine diagnostics. NTRK fusions are known oncogenic drivers in a range of cancer types, but this is the first report of a NACC2-NTRK2 fusion in a glioblastoma.
This presentation will enable the learner to:
1.Explore the current molecular landscape of pediatric high grade gliomas
2.Recognize the value of personalized oncogenomic analysis, particularly in rare and/or aggressive tumors
3.Discuss the current status of NTRK inhibitor clinical trials
Two-dimensional particle-in-cell (PIC) simulations have been used to investigate the interaction between a laser pulse and a foil exposed to an external strong longitudinal magnetic field. Compared with that in the absence of the external magnetic field, the divergence of proton with the magnetic field in radiation pressure acceleration (RPA) regimes has improved remarkably due to the restriction of the electron transverse expansion. During the RPA process, the foil develops into a typical bubble-like shape resulting from the combined action of transversal ponderomotive force and instabilities. However, the foil prefers to be in a cone-like shape by using the magnetic field. The dependence of proton divergence on the strength of magnetic field has been studied, and an optimal magnetic field of nearly 60 kT is achieved in these simulations.
Copy number variations (CNVs), as an important source of genetic variation, can affect a wide range of phenotypes by diverse mechanisms. The somatostatin receptor 2 (SSTR2) gene plays important roles in cell proliferation and apoptosis. Recently, this gene was mapped to a CNV region, which encompasses quantitative trait loci of cattle economic traits including body weight, marbling score, etc. Therefore, SSTR2 CNV may exhibit phenotypic effects on cattle growth traits. In the current study, distribution of SSTR2 gene CNVs was investigated in six Chinese cattle breeds (XN, QC, NY, JA, LX and PN), and the results showed higher CNV polymorphisms in XN, QC and NY cattle. Next, association analysis between growth traits and SSTR2 CNV was performed for XN, QC and NY cattle. In NY, individuals with fewer copies showed better performance than those with more copies. Further, the effects of SSTR2 CNV on the SSTR2 mRNA level were also investigated, but revealed no significant correlation in either muscle or adipose tissue of adult NY cattle. The results suggested the potential for use of SSTR2 CNV as a marker for the molecular breeding of NY cattle.
Two solid state anaerobic digesters (SSADs), 15 L each, were set up for co-digestion of switchgrass with primary digestate of a liquid anaerobic digester (LAD) and the recirculating leachate. Both the LAD and two SSADs were operated at 50°C. The results showed that the bioreactors were not started up stably until day 16 and day 47 for reactors A and B, respectively. The supplement of LAD digestate or injection of sodium hydroxide (NaOH) into the recirculating leachate readily reinitiated the biogas production to normal daily high rates of the two individual SSADs, one on day 16 and the other on day 47. In contrast to reactor A, there was a longer lag phase for bioreactor B, however, it showed 46.2% [77.9 vs 53.3 L kg−1 volatile solid (VS)] more cumulative biogas yields, and higher reduction rate of total solid, VS, cellulose and hemicellulose of 29.5, 31, 40.6 and 15%, respectively, which was likely due to optimized pH and NaOH pretreated switchgrass during start-up period. Methane contents of biogas increased gradually and stabilized at 50% for both reactors, indicating a normal operation of anaerobic digestion lasted for at least 100 days. The determined parameters of digested residues met China organic fertilizer standard (NY 525-2012) except for high moisture and low total nutrient contents. Therefore, the product of SSAD has the potential value of organic fertilizer. It is concluded that the LAD digestate can be reused as inoculums by co-digestion with agricultural residues for biogas and organic fertilizer production in SSAD.
Rabies is one of the major public health problems in China, and the mortality rate of rabies remains the highest among all notifiable infectious diseases. A meta-analysis was conducted to investigate the post-exposure prophylaxis (PEP) vaccination rate and risk factors for human rabies in mainland China. The PubMed, Web of Science, Chinese National Knowledge Infrastructure, Chinese Science and Technology Periodical and Wanfang databases were searched for articles on rabies vaccination status (published between 2007 and 2017). In total, 10 174 human rabies cases from 136 studies were included in this meta-analysis. Approximately 97.2% (95% confidence interval (CI) 95.1–98.7%) of rabies cases occurred in rural areas and 72.6% (95% CI 70.0–75.1%) occurred in farmers. Overall, the vaccination rate in the reported human rabies cases was 15.4% (95% CI 13.7–17.4%). However, among vaccinated individuals, 85.5% (95% CI 79.8%–83.4%) did not complete the vaccination regimen. In a subgroup analysis, the PEP vaccination rate in the eastern region (18.8%, 95% CI 15.9–22.1%) was higher than that in the western region (13.3%, 95% CI 11.1–15.8%) and this rate decreased after 2007. Approximately 68.9% (95% CI 63.6–73.8%) of rabies cases experienced category-III exposures, but their PEP vaccination rate was 27.0% (95% CI 14.4–44.9%) and only 6.1% (95% CI 4.4–8.4%) received rabies immunoglobulin. Together, these results suggested that the PEP vaccination rate among human rabies cases was low in mainland China. Therefore, standardised treatment and vaccination programs of dog bites need to be further strengthened, particularly in rural areas.
Recent studies indicate that early postnatal period is a critical window for gut microbiota manipulation to optimise the immunity and body growth. This study investigated the effects of maternal faecal microbiota orally administered to neonatal piglets after birth on growth performance, selected microbial populations, intestinal permeability and the development of intestinal mucosal immune system. In total, 12 litters of crossbred newborn piglets were selected in this study. Litter size was standardised to 10 piglets. On day 1, 10 piglets in each litter were randomly allotted to the faecal microbiota transplantation (FMT) and control groups. Piglets in the FMT group were orally administrated with 2ml faecal suspension of their nursing sow per day from the age of 1 to 3 days; piglets in the control group were treated with the same dose of a placebo (0.1M potassium phosphate buffer containing 10% glycerol (vol/vol)) inoculant. The experiment lasted 21 days. On days 7, 14 and 21, plasma and faecal samples were collected for the analysis of growth-related hormones and cytokines in plasma and lipocalin-2, secretory immunoglobulin A (sIgA), selected microbiota and short-chain fatty acids (SCFAs) in faeces. Faecal microbiota transplantation increased the average daily gain of piglets during week 3 and the whole experiment period. Compared with the control group, the FMT group had increased concentrations of plasma growth hormone and IGF-1 on days 14 and 21. Faecal microbiota transplantation also reduced the incidence of diarrhoea during weeks 1 and 3 and plasma concentrations of zonulin, endotoxin and diamine oxidase activities in piglets on days 7 and 14. The populations of Lactobacillus spp. and Faecalibacterium prausnitzii and the concentrations of faecal and plasma acetate, butyrate and total SCFAs in FMT group were higher than those in the control group on day 21. Moreover, the FMT piglets have higher concentrations of plasma transforming growth factor-β and immunoglobulin G, and faecal sIgA than the control piglets on day 21. These findings indicate that early intervention with maternal faecal microbiota improves growth performance, decreases intestinal permeability, stimulates sIgA secretion, and modulates gut microbiota composition and metabolism in suckling piglets.
Our objective was to identify predictors of severe acute respiratory infection in hospitalised patients and understand the impact of vaccination and neuraminidase inhibitor administration on severe influenza. We analysed data from a study evaluating influenza vaccine effectiveness in two Michigan hospitals during the 2014–2015 and 2015–2016 influenza seasons. Adults admitted to the hospital with an acute respiratory infection were eligible. Through patient interview and medical record review, we evaluated potential risk factors for severe disease, defined as ICU admission, 30-day readmission, and hospital length of stay (LOS). Two hundred sixteen of 1119 participants had PCR-confirmed influenza. Frailty score, Charlson score and tertile of prior-year healthcare visits were associated with LOS. Charlson score >2 (OR 1.5 (1.0–2.3)) was associated with ICU admission. Highest tertile of prior-year visits (OR 0.3 (0.2–0.7)) was associated with decreased ICU admission. Increasing tertile of visits (OR 1.5 (1.2–1.8)) was associated with 30-day readmission. Frailty and prior-year healthcare visits were associated with 30-day readmission among influenza-positive participants. Neuraminidase inhibitors were associated with decreased LOS among vaccinated participants with influenza A (HR 1.6 (1.0–2.4)). Overall, frailty and lack of prior-year healthcare visits were predictors of disease severity. Neuraminidase inhibitors were associated with reduced severity among vaccine recipients.
Dengue is the fastest spreading mosquito-transmitted disease in the world. In China, Guangzhou City is believed to be the most important epicenter of dengue outbreaks although the transmission patterns are still poorly understood. We developed an autoregressive integrated moving average model incorporating external regressors to examine the association between the monthly number of locally acquired dengue infections and imported cases, mosquito densities, temperature and precipitation in Guangzhou. In multivariate analysis, imported cases and minimum temperature (both at lag 0) were both associated with the number of locally acquired infections (P < 0.05). This multivariate model performed best, featuring the lowest fitting root mean squared error (RMSE) (0.7520), AIC (393.7854) and test RMSE (0.6445), as well as the best effect in model validation for testing outbreak with a sensitivity of 1.0000, a specificity of 0.7368 and a consistency rate of 0.7917. Our findings suggest that imported cases and minimum temperature are two key determinants of dengue local transmission in Guangzhou. The modelling method can be used to predict dengue transmission in non-endemic countries and to inform dengue prevention and control strategies.
Introduction: Survival from cardiac arrest has been linked to the quality of resuscitation care. Unfortunately, healthcare providers frequently underperform in these critical scenarios, with a well-documented deterioration in skills weeks to months following advanced life support courses. Improving initial training and preventing decay in knowledge and skills are a priority in resuscitation education. The spacing effect has repeatedly been shown to have an impact on learning and retention. Despite its potential advantages, the spacing effect has seldom been applied to organized education training or complex motor skill learning where it has the potential to make a significant impact. The purpose of this study was to determine if a resuscitation course taught in a spaced format compared to the usual massed instruction results in improved retention of procedural skills. Methods: EMS providers (Paramedics and Emergency Medical Technicians (EMT)) were block randomized to receive a Pediatric Advanced Life Support (PALS) course in either a spaced format (four 210-minute weekly sessions) or a massed format (two sequential 7-hour days). Blinded observers used expert-developed 4-point global rating scales to assess video recordings of each learner performing various resuscitation skills before, after and 3-months following course completion. Primary outcomes were performance on infant bag-valve-mask ventilation (BVMV), intraosseous (IO) insertion, infant intubation, infant and adult chest compressions. Results: Forty-eight of 50 participants completed the study protocol (26 spaced and 22 massed). There was no significant difference between the two groups on testing before and immediately after the course. 3-months following course completion participants in the spaced cohort scored higher overall for BVMV (2.2 ± 0.13 versus 1.8 ± 0.14, p=0.012) without statistically significant difference in scores for IO insertion (3.0 ± 0.13 versus 2.7± 0.13, p= 0.052), intubation (2.7± 0.13 versus 2.5 ± 0.14, p=0.249), infant compressions (2.5± 0.28 versus 2.5± 0.31, p=0.831) and adult compressions (2.3± 0.24 versus 2.2± 0.26, p=0.728) Conclusion: Procedural skills taught in a spaced format result in at least as good learning as the traditional massed format; more complex skills taught in a spaced format may result in better long term retention when compared to traditional massed training as there was a clear difference in BVMV and trend toward a difference in IO insertion.
Central line-associated bloodstream infections (CLABSIs) in intensive care units (ICUs) result in poor clinical outcomes and increased costs. Although frequently regarded as preventable, infection risk may be influenced by non-modifiable factors. The objectives of this study were to evaluate organisational factors associated with CLABSI in Victorian ICUs to determine the nature and relative contribution of modifiable and non-modifiable risk factors. Data captured by the Australian and New Zealand Intensive Care Society regarding ICU-admitted patients and resources were linked to CLABSI surveillance data collated by the Victorian Healthcare Associated Infection Surveillance System between 1 January 2010 and 31 December 2013. Accepted CLABSI surveillance methods were applied and hospital/patient characteristics were classified as ‘modifiable’ and ‘non-modifiable’, enabling longitudinal Poisson regression modelling of CLABSI risk. In total, 26 ICUs were studied. Annual CLABSI rates were 1·72, 1·37, 1·00 and 0·93/1000 CVC days for 2010–2013. Of non-modifiable factors, the number of non-invasively ventilated patients standardised to total ICU bed days was found to be independently associated with infection (RR 1·07; 95% CI 1·01–1·13; P = 0·030). Modelling of modifiable risk factors demonstrated the existence of a policy for mandatory ultrasound guidance for central venous catheter (CVC) localisation (RR 0·51; 95% CI 0·37–0·70; P < 0·001) and increased number of sessional specialist full-time equivalents (RR 0·52; 95% CI 0·29–0·93; P = 0·027) to be independently associated with protection against infection. Modifiable factors associated with reduced CLABSI risk include ultrasound guidance for CVC localisation and increased availability of sessional medical specialists.
The East Asian–Australasian flyway contains some of the most threatened habitats in the world, with at least 155 waterbird species reliant on the tidal habitats it comprises. The black-faced spoonbill (Platalea minor) is an iconic endangered species distributed across the coast of East Asia. Its population suffered a severe decline into the 1990s, but extensive monitoring and conservation interventions have aided a substantial recovery of the species. We used a population viability analysis based on data collected over the past two decades in conjunction with species distribution models to project spatially explicit models of population change for the next 35 years. Over nearly all scenarios of habitat loss and climate change, the global spoonbill population was projected to increase in the short-term due to low population numbers likely well below current population carrying capacities. However, climate change and habitat loss together threaten the recovery of the spoonbill population such that, by 2050, population declines are apparent as a consequence of these cumulative impacts. These threats are also cryptic and represent a challenge to the conservation of species recovering from anthropogenic impacts; observed population increases can hide large reductions in habitat suitability that threaten the long-term viability of species.
Australia's National Immunisation Program (NIP) provides free influenza vaccination for children at high risk of severe influenza; a pilot-funded programme for vaccine in all children aged 6 months to <5 years in one of eight states, has seen poor vaccine impact, related to recent vaccine safety concerns. This retrospective review examined influenza hospitalizations in children aged <16 years from three seasons (2011–2013) at two paediatric hospitals on opposite sides of the country. Comparisons of this cohort were made with state-based data on influenza-coded hospitalizations and national immunization register data on population-level immunization coverage. Of 740 hospitalizations, the majority were aged <5 years (476/740, 64%), and a substantial proportion (57%) involved healthy children, not currently funded for influenza vaccine. Intensive care unit admission occurred in 8·5%, and 1·5% of all children developed encephalitis. Use of antiviral therapy was uncommon (20·5%) and decreasing. Of those hospitalized, only 5·0% of at-risk children, who are currently eligible for free vaccine, and 0·7% of healthy children were vaccinated prior to hospitalization. This was consistent with low population-wide estimates of influenza vaccine uptake. It highlights the need to examine alternative strategies, such as universally funded paediatric influenza vaccination, to address disease burden in Australian children.
There are two marine species in the genus Ozobranchus. Ozobranchus branchiatus mainly parasitizes green turtles and O. margoi parasitizes most turtle species. We used sequences for the mitochondrial cytochrome c oxidase subunit I gene (COI sequence analysis), along with morphological diagnosis, to compare the population genetic structures of O. branchiatus and O. margoi collected near Taiwan to those of their populations in the Atlantic. The results provide estimates of the genetic divergence between these leeches in the two regions. Ozobranchus branchiatus had a greater pairwise distance within Taiwan (0.0031–0.0141) than O. margoi (no differences). Phylogenetic tree analysis identified one O. branchiatus clade and one O. margoi clade in Taiwan. The better environmental adaptability and lower host specificity of O. margoi might result in lower genetic divergence among populations.
The objective of the present study was to investigate live weight (LW) gain, urinary nitrogen (UN) excretion and urination behaviour of dairy heifers grazing pasture, chicory and plantain in autumn and spring. The study comprised a 35-day autumn trial (with a 7-day acclimation period) and a 28-days spring trial (with a 7-day acclimation period). For each trial, 56 Friesian × Jersey heifers were blocked into five dietary treatments balanced for their LW and breeding worth (i.e. genetic merit of a cow for production and reproduction): 1·00 perennial ryegrass–white clover pasture (PA); 1·00 chicory (CH); 1·00 plantain (PL); 0·50 pasture + 0·50 chicory (PA + CH); and 0·50 pasture + 0·50 plantain (PA + PL). A fresh allocation of the herbage was offered every 3 days with allowance calculated according to feed requirement for maintenance plus gain of 1·0 kg LW/day. In both trials, LW gain was lower on CH than other treatments. In the spring trial, UN concentration and UN excretion were lower in CH and PL than other treatments. In autumn, a higher urination frequency was observed over the first 6 h after forage allocation in CH and PA + CH than other treatments. Data from the present study indicate that feeding CH alone limited heifer LW gain. However, heifers grazing swards containing chicory (CH and PA + CH) and plantain (PL and PA + PL) had the potential to lower nitrous oxide emissions and nitrate leaching from soil compared with heifers grazing PA, by reducing N loading in urine patches.
This paper investigates the rupture problem of a thin micropolar liquid film under a magnetic field on a horizontal plate, using long-wave perturbation to resolve nonlinear evolution equations with a free film interface. The governing equation is resolved using a finite difference method as part of an initial value problem for spatial periodic boundary conditions. The effect of a micropolar liquid under a magnetic field on the nonlinear rupture mechanism is studied in terms of the micropolar parameter, R, the Hartmann constant, m and the initial disturbance amplitude, H0. Modeling results indicate that the R, m and H0 parameters strongly affect the film flow. Enhancing the micropolar and magnetic effects is found to delay the rupture time. In addition, the results show that the film rupture time increases as the values of initial disturbance magnitude decrease. The micropolar and magnetic parameters indeed play a significant role in the film flow on a horizontal plate. Moreover, the optimum conditions can be found to alter stability of the film flow by controlling the applied magnetic field.
Overwhelming post-splenectomy infection (OPSI) is a serious complication of asplenia and is associated with encapsulated organisms, most commonly Streptococcus pneumoniae, but also Haemophilus influenzae and Neisseria meningitidis. We aimed to estimate the risk of infection in this patient group. We reviewed data collected by the Victorian Spleen Registry in Australia. On registration, all patients are asked about significant infections requiring admission to hospital for intravenous antibiotics; those requiring admission to ICU were defined as OPSI. In the 3274 asplenic patients registered 492 patients reported at least one episode of infection. There were 47 episodes of OPSI requiring intensive care (incidence rate 1·11/1000 patient-years). The risk of OPSI was highest in older patients, and there were no statistically significant differences in incidence by reason for splenectomy except for a higher rate in patients with medical hyposplenia. This study reinforces that post-splenectomy infection is a clinically significant but uncommon complication, and that fulminant infection requiring intensive care is a minority of all infections.
The present study investigated alteration of brain resting-state activity induced by antidepressant treatment and attempted to investigate whether treatment efficacy can be predicted at an early stage of pharmacological treatment.
Forty-eight first-episode medication-free patients diagnosed with major depression received treatment with escitalopram. Resting-state functional magnetic resonance imaging was administered prior to treatment, 5 h after the first dose, during the course of pharmacological treatment (week 4) and at endpoint (week 8). Resting-state activity was evaluated in the course of the 8-week treatment and in relation to clinical improvement.
Escitalopram dynamically modified resting-state activity in depression during the treatment. After 5 h the antidepressant induced a significant decrease in the signal in the occipital cortex and an increase in the dorsolateral and dorsomedial prefrontal cortices and middle cingulate cortex. Furthermore, while remitters demonstrated more obvious changes following treatment, these were more modest in non-responders suggesting possible tonic and dynamic differences in the serotonergic system. Changes after 5 h in the caudate, occipital and temporal cortices were the best predictor of clinical remission at endpoint.
This study revealed the possibility of using the measurement of resting-state neural changes a few hours after acute administration of antidepressant to identify individuals likely to remit after a few weeks of treatment.