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The smr and qacA/B genes in Staphylococcus aureus confer tolerance to antiseptics and are associated with nosocomial acquisition of infection and underlying medical conditions. Such antiseptic tolerance (AT) genes have also been reported in coagulase-negative staphylococci (CoNS) and enterococci, however, few data are available regarding their prevalence. We sought to describe the frequency of AT genes among bloodstream isolates of S. aureus, CoNS and enterococci at Texas Children’s Hospital (TCH).
Banked CoNS, S. aureus and enterococci isolated from blood cultures collected bewteen October 1, 2016, and October 1, 2017, were obtained from the TCH clinical microbiology laboratory. All isolates underwent polymerase chain reaction (PCR) assay for the qacA/B and smr genes. Medical records were reviewed for all cases.
In total, 103 CoNS, 19 Enterococcus spp, and 119 S. aureus isolates were included in the study, and 80.6% of the CoNS possessed at least 1 AT gene compared to 37% of S. aureus and 43.8% of E. faecalis isolates (P < .001). Among CoNS bloodstream isolates, the presence of either AT gene was strongly associated with nosocomial infection (P < .001). The AT genes in S. aureus were associated with nosocomial infection (P = .025) as well as the diagnosis of central-line–associated bloodstream infection (CLABSI; P = .04) and recent hospitalizations (P < .001). We found no correlation with genotypic AT in E. faecalis and any clinical variable we examined.
Antiseptic tolerance is common among bloodstream staphylococci and E. faecalis isolates at TCH. Among CoNS, the presence of AT genes is strongly correlated with nosocomial acquisition of infection, consistent with previous studies in S. aureus. These data suggest that the healthcare environment contributes to AT among staphylococci.
OBJECTIVES/SPECIFIC AIMS: Oncostreams represent a novel growth pattern of GBM. In this study we uncovered the cellular and molecular mechanism that regulates the oncostreams function in GBM growth and invasion. METHODS/STUDY POPULATION: We studied oncostreams organization and function using genetically engineered mouse gliomas models (GEMM), mouse primary patient derived GBM model and human glioma biopsies. We evaluated the molecular landscape of oncostreams by laser capture microdissection (LCM) followed by RNA-Sequencing and bioinformatics analysis. RESULTS/ANTICIPATED RESULTS: Oncostreams are multicellular structures of 10-20 cells wide and 2-400 μm long. They are distributed throughout the tumors in mouse and human GBM. Oncostreams are heterogeneous structures positive for GFAP, Nestin, Olig2 and Iba1 cells and negative for Neurofilament. Using GEMM we found a negative correlation between oncostream density and animal survival. Moreover, examination of patient’s glioma biopsies evidenced that oncostreams are present in high grade but no in low grade gliomas. This suggests that oncostreams may play a role in tumor malignancy. Our data also indicated that oncostreams aid local invasion of normal brain. Transcriptome analysis of oncostreams revealed 43 differentially expressed (DE) genes. Functional enrichment analysis of DE genes showed that “collagen catabolic processes”, “positive regulation of cell migration”, and “extracellular matrix organization” were the most over-represented GO biological process. Network analysis indicated that Col1a1, ACTA2, MMP9 and MMP10 are primary target genes. These genes were also overexpressed in more malignant tumors (WT-IDH) compared to the less malignant (IDH1- R132H) tumors. Confocal time lapse imagining of 3D tumor slices demonstrated that oncostreams display a collective motion pattern within gliomas that has not been seen before. DISCUSSION/SIGNIFICANCE OF IMPACT: In summary, oncostreams are anatomically and molecularly distinctive, regulate glioma growth and invasion, display collective motion and are regulated by the extracellular matrix. We propose oncostreams as novel pathological markers valuable for diagnosis, prognosis and designing therapeutics for GBM patients.
Multiple studies have demonstrated that daily chlorhexidine gluconate (CHG) bathing is associated with a significant reduction in infections caused by gram-positive pathogens. However, there are limited data on the effectiveness of daily CHG bathing on gram-negative infections. The aim of this study was to determine whether daily CHG bathing is effective in reducing the rate of gram-negative infections in adult intensive care unit (ICU) patients.
We searched MEDLINE and 3 other databases for original studies comparing daily bathing with and without CHG. Two investigators extracted data independently on baseline characteristics, study design, form and concentration of CHG, incidence, and outcomes related to gram-negative infections. Data were combined using a random-effects model and pooled relative risk ratios (RRs), and 95% confidence intervals (CIs) were derived.
In total, 15 studies (n = 34,895 patients) met inclusion criteria. Daily CHG bathing was not significantly associated with a lower risk of gram-negative infections compared with controls (RR, 0.89; 95% CI, 0.73–1.08; P = .24). Subgroup analysis demonstrated that daily CHG bathing was not effective for reducing the risk of gram-negative infections caused by Acinetobacter, Escherichia coli, Klebsiella, Enterobacter, or Pseudomonas spp.
The use of daily CHG bathing was not associated with a lower risk of gram-negative infections. Further, better designed trials with adequate power and with gram-negative infections as the primary end point are needed.
To systematically review studies from Irish prisons that estimate the prevalence of major mental illness, alcohol and substance misuse, and homelessness at the time of committal.
Healthcare databases were searched for studies quantifying the point prevalence for each outcome of interest. Searches were augmented by scanning of bibliographies and searches of governmental and non-governmental websites. Proportional meta-analyses were completed for each outcome.
We found eight, six and five studies quantifying the point prevalence of major mental illness, substance misuse, and homelessness respectively. Considerable heterogeneity was found for each subgroup (except psychosis where substantial heterogeneity was observed) and random effects models were used to calculate pooled percentages. The pooled percentage for psychotic disorder was 3.6% [95% confidence interval (CI) 3.0–4.2%], for affective disorder 4.3% (95% CI 2.1–7.1%), for alcohol use disorder 28.3% (95% CI 19.9–37.4%), for substance use disorder 50.9% (95% CI 37.6–64.2%) and for those who were homeless on committal 17.4% (95% CI 8.7–28.4%).
Estimates for the prevalence of psychotic illness and substance abuse amongst Irish prisoners are in keeping with international estimates of morbidity in prisons, whilst those for affective disorders are lower. The prevalence of homelessness in committal to Irish prisons is higher than some international estimates. Rates for psychoses, alcohol and substance misuse as well as homelessness in Irish prisons are significantly higher than the general population prevalence of these vulnerabilities. A need for service development is discussed.
Non-axisymmetric endwalls in turbine stages have shown to be a robust method to improve the performance of turbines in both power generation and aero-derivative applications. Non-axisymmetric endwalls target the control of secondary flows and are designed using detailed computational fluid dynamics coupled with a variety of optimisation algorithms and utilising a number of objective functions according to the engine company or researcher's preference. These numerical predictions are often backed up by detailed measurements in linear and annular cascades and later proven in full-scale engine tests. Relatively little literature is available describing their performance in rotating test rigs or at conditions other than design, apart from that of the authors. This study comprehensively revisits the low-speed, model turbines used in the earlier study, replacing all of the 5-hole probe data with more accurate results and additional hot-film measurements. These results together with computational fluid dynamics solutions are used to show the success of the method across a large incidence range and to compare to earlier cascade results for a similar endwall and blade profile to establish the usefulness of cascade testing in this application. In addition, a comparison to two other off-design studies is made. Results indicate that the endwalls successfully improve the rotor total isentropic efficiency at all test conditions and that the improvement increases with increased turning in the blade row, from 0.5% to 1.8% across the incidence range. The results also compare well to the estimation of isentropic efficiency improvement that can be drawn from the cascade testing which stands at 1.55%.
To understand increasing rates of hepatitis C virus (HCV) infection in Tennessee, we conducted testing, risk factor analysis and a nested case–control study among persons who use drugs. During June–October 2016, HCV testing with risk factor assessment was conducted in sexually transmitted disease clinics, family planning clinics and an addiction treatment facility in eastern Tennessee; data were analysed by using multivariable logistic regression. A nested case–control study was conducted to assess drug-using risks and behaviours among persons who reported intranasal or injection drug use (IDU). Of 4753 persons tested, 397 (8.4%) were HCV-antibody positive. HCV infection was significantly associated with a history of both intranasal and IDU (adjusted odds ratio (aOR) 35.4, 95% confidence interval (CI) 24.1–51.9), IDU alone (aOR 52.7, CI 25.3–109.9), intranasal drug use alone (aOR 2.6, CI 1.8–3.9) and incarceration (aOR 2.7, CI 2.0–3.8). By 4 October 2016, 574 persons with a reported history of drug use; 63 (11%) were interviewed further. Of 31 persons who used both intranasal and injection drugs, 26 (84%) reported previous intranasal drug use, occurring 1–18 years (median 5.5 years) before their first IDU. Our findings provide evidence that reported IDU, intranasal drug use and incarceration are independent indicators of risk for past or present HCV infection in the study population.
Supranutritional supplementation of cattle with vitamin E has improved the colour and lipid stability of beef. Grass-fed cattle have muscle vitamin E concentrations which are 2 to 3 times greater than unsupplemented concentrate-fed cattle (Lanari et al., 2002) but also have higher concentrations of the highly oxidisable long chain n-3 polyunsaturated fatty acids (Nuernberg et al., 2005). The objective was to compare the oxidative stability of grass-with concentrate-fed beef, both minced and intact, and to determine if supplemental vitamin E can increase the oxidative stability of such beef in high oxygen packaging.
Hunger strikes in a custodial setting are complex to manage clinically, with associated legal and ethical complexities. Hunger strikes in Irish prisons have received, and are likely to continue to be the focus of, considerable media attention. Whilst there is an internationally accepted consensus ethical position, there is limited legal guidance available for psychiatrists to draw upon in such cases. In this paper, we review recent case-law and discuss the legal considerations in the management of prisoners on hunger strike.
The effects of shape and thickness of a tin surface layer and of the energy of a 170 ps neodymium:yttrium-aluminum-garnet laser pulse on the conversion efficiency (CE) into extreme ultraviolet emission in the 13.5 nm region is investigated. Whereas a CE of up to 1.16% into the 2% reflection band of multilayer Mo/Si optics was measured for a bulk Sn target at a laser energy of 25 mJ, significant CE enhancement up to 1.49% is demonstrated for a 200-nm-thick Sn layer on a microstructured porous alumina substrate.
We sought to identify and review published studies that discuss the ethical considerations, from a physician’s perspective, of managing a hunger strike in a prison setting.
A database search was conducted to identify relevant publications. We included case studies, case series, guidelines and review articles published over a 20-year period. Non-English language publications were translated.
The review found 23 papers from 12 jurisdictions published in five languages suitable for inclusion.
Key themes from included publications are identified and summarised in the context of accepted guidelines from the World Medical Association. Whilst there seems to be an overall consensus favouring autonomy over beneficence, tensions along this fine balance are magnified in jurisdictions where legislation leads to a dual loyalty conflict for the physician.
The use of hedging with commodity futures markets to reduce the price risk in corn production is examined. Both intra-year and inter-year risk are evaluated with different hedging strategies. Strategies involve no hedge, hedge and hold, controlled hedge placement and hold, and in and out hedging. Both technical and forecasting criteria are used to place hedges in the more active strategies. Substantial risk reduction is possible, often without a reduction in price received. Considerable basis risk diminishes the risk reducing properties of a hedge and hold strategy.
The aim of this paper is to review the Australian and international literature on social and emotional issues affecting children in kinship foster care and to examine stresses experienced by kinship foster carers.
There is a growing trend of kinship foster care as an alternative form of care for children in Australia and overseas which is attributed to factors such as child abuse, parental incapacity, parental incarceration, and parental substance misuse. The ideology supporting the use of kinship care is that it is in the child’s best interests because it helps them to maintain ties with their family of origin.
A comprehensive search of the literature on kinship care was undertaken and articles addressing social and emotional issues of children in kinship care or their carers were selected for critical review.
The literature suggests that children placed with kinship foster carers suffer from a range of social and emotional issues and these may impact on outcomes in adulthood. The existing literature does not, however, adequately differentiate the impacts of kinship care itself from the children’s pre-existing difficulties and there is a paucity of literature comparing kinship care outcomes with outcomes for children who have experienced other forms of out-of-home care. Common factors experienced by kinship foster carers that can make it challenging for them to deal with children’s issues are economic disadvantage, stress, health issues and lack of resources.
In conclusion, this review supports the arguments for assessment and interventions for children in kinship foster care; and support, parent training and interventions for kinship carers. Longitudinal studies are needed in this area.
Prisoners have an exceptional risk of suicide. Cognitive–behavioural therapy for suicidal behaviour has been shown to offer considerable potential, but has yet to be formally evaluated within prisons. This study investigated the feasibility of delivering and evaluating a novel, manualized cognitive–behavioural suicide prevention (CBSP) therapy for suicidal male prisoners.
A pilot randomized controlled trial of CBSP in addition to treatment as usual (CBSP; n = 31) compared with treatment as usual (TAU; n = 31) alone was conducted in a male prison in England. The primary outcome was self-injurious behaviour occurring within the past 6 months. Secondary outcomes were dimensions of suicidal ideation, psychiatric symptomatology, personality dysfunction and psychological determinants of suicide, including depression and hopelessness. The trial was prospectively registered (number ISRCTN59909209).
Relative to TAU, participants receiving CBSP therapy achieved a significantly greater reduction in suicidal behaviours with a moderate treatment effect [Cohen's d = −0.72, 95% confidence interval −1.71 to 0.09; baseline mean TAU: 1.39 (s.d. = 3.28) v. CBSP: 1.06 (s.d. = 2.10), 6 months mean TAU: 1.48 (s.d. = 3.23) v. CBSP: 0.58 (s.d. = 1.52)]. Significant improvements were achieved on measures of psychiatric symptomatology and personality dysfunction. Improvements on psychological determinants of suicide were non-significant. More than half of the participants in the CBSP group achieved a clinically significant recovery by the end of therapy, compared with a quarter of the TAU group.
The delivery and evaluation of CBSP therapy within a prison is feasible. CBSP therapy offers significant promise in the prevention of prison suicide and an adequately powered randomized controlled trial is warranted.
The quality of the therapeutic alliance (TA) has been invoked to explain the equal effectiveness of different psychotherapies, but prior research is correlational, and does not address the possibility that individuals who form good alliances may have good outcomes without therapy.
We evaluated the causal effect of TA using instrumental variable (structural equation) modelling on data from a three-arm, randomized controlled trial of 308 people in an acute first or second episode of a non-affective psychosis. The trial compared cognitive behavioural therapy (CBT) over 6 weeks plus routine care (RC) v. supportive counselling (SC) plus RC v. RC alone. We examined the effect of TA, as measured by the client-rated CALPAS, on the primary trial 18-month outcome of symptom severity (PANSS), which was assessed blind to treatment allocation.
Both adjunctive CBT and SC improved 18-month outcomes, compared to RC. We showed that, for both psychological treatments, improving TA improves symptomatic outcome. With a good TA, attending more sessions causes a significantly better outcome on PANSS total score [effect size −2.91, 95% confidence interval (CI) −0.90 to −4.91]. With a poor TA, attending more sessions is detrimental (effect size +7.74, 95% CI +1.03 to +14.45).
This is the first ever demonstration that TA has a causal effect on symptomatic outcome of a psychological treatment, and that poor TA is actively detrimental. These effects may extend to other therapeutic modalities and disorders.
As concern for the environment increases, so does the desire to reduce emissions and improve fuel efficiency. One avenue being investigated in the aerospace industry is the reduction in losses in a gas turbine engine through endwall contouring, which has shown some promise in improving efficiency. The current investigation was aimed at investigating the unsteady effects downstream of a rotor with a non-axisymmetric endwall contour originally designed for a cascade.
Previous investigations (numerical and experimental) have shown that the endwall contour improved the turbine efficiency by reducing the cross passage secondary flows. The contour however had a detrimental effect on the tip flow. The current investigation found that there were negligible unsteady differences between the annular and contoured rotor, with the average comparing well to the steady state results. It was also found that the effects at the tip were due to the experimental blades untwisting during operation.
We describe a laboratory plasma physics experiment at Los Alamos National Laboratory that uses two merging supersonic plasma jets formed and launched by pulsed-power-driven railguns. The jets can be formed using any atomic species or mixture available in a compressed-gas bottle and have the following nominal initial parameters at the railgun nozzle exit: ne ≈ ni ~ 1016 cm−3, Te ≈ Ti ≈ 1.4 eV, Vjet ≈ 30–100 km/s, mean charge
≈ 1, sonic Mach number Ms ≡ Vjet/Cs > 10, jet diameter = 5 cm, and jet length ≈20 cm. Experiments to date have focused on the study of merging-jet dynamics and the shocks that form as a result of the interaction, in both collisional and collisionless regimes with respect to the inter-jet classical ion mean free path, and with and without an applied magnetic field. However, many other studies are also possible, as discussed in this paper.
Persecutory delusions are a key psychotic experience. A reasoning style known as ‘jumping to conclusions’ (JTC) – limited information gathering before reaching certainty in decision making – has been identified as a contributory factor in the occurrence of delusions. The cognitive processes that underpin JTC need to be determined in order to develop effective interventions for delusions. In the current study two alternative perspectives were tested: that JTC partially results from impairment in information-processing capabilities and that JTC is a motivated strategy to avoid uncertainty.
A group of 123 patients with persistent persecutory delusions completed assessments of JTC (the 60:40 beads task), IQ, working memory, intolerance of uncertainty, and psychiatric symptoms. Patients showing JTC were compared with patients not showing JTC.
A total of 30 (24%) patients with delusions showed JTC. There were no differences between patients who did and did not jump to conclusions in overall psychopathology. Patients who jumped to conclusions had poorer working memory performance, lower IQ, lower intolerance of uncertainty and lower levels of worry. Working memory and worry independently predicted the presence of JTC.
Hasty decision making in patients with delusions may partly arise from difficulties in keeping information in mind. Interventions for JTC are likely to benefit from addressing working memory performance, while in vivo techniques for patients with delusions will benefit from limiting the demands on working memory. The study provides little evidence for a contribution to JTC from top-down motivational beliefs about uncertainty.
For people with psychosis, contact with informal caregivers is an important source of social support, associated with recovery, and with better outcomes following individual cognitive therapy (CBTp). In this study, we tested whether increased flexibility in delusional thinking, an established predictor of positive outcome following CBTp, was a possible mechanism underlying this effect.
219 participants with delusions (mean age 38 years; 71% male; 75% White) were grouped according to the presence of a caregiver (37% with a caregiver) and caregiver level of expressed emotion (High/Low EE, 64% Low). Delusional belief flexibility was compared between groups, controlling for interpersonal functioning, severity of psychotic symptoms, and other hypothesised outcome predictors.
Participants with caregivers were nearly three times more likely than those without to show flexibility (OR = 2.7, 95% CI 1.5 to 5.0, p = 0.001), and five times more likely if the caregiving relationship was Low EE (OR = 5.0, 95% CI 2.0–13.0, p = 0.001). ORs remained consistent irrespective of controlling for interpersonal functioning and other predictors of outcome.
This is the first evidence that having supportive caregiving relationships is associated with a specific cognitive attribute in people with psychosis, suggesting a potential cognitive mechanism by which outcomes following CBTp, and perhaps more generally, are improved by social support.