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To describe an outbreak of bacteremia caused by vancomycin-sensitive Enterococcus faecalis (VSEfe).
An investigation by retrospective case control and molecular typing by whole-genome sequencing (WGS).
A tertiary-care neonatal unit in Melbourne, Australia.
Risk factors for 30 consecutive neonates with VSEfe bacteremia from June 2011 to December 2014 were analyzed using a case control study. Controls were neonates matched for gestational age, birth weight, and year of birth. Isolates were typed using WGS, and multilocus sequence typing (MLST) was determined.
Bacteremia for case patients occurred at a median time after delivery of 23.5 days (interquartile range, 14.9–35.8). Previous described risk factors for nosocomial bacteremia did not contribute to excess risk for VSEfe. WGS typing results designated 43% ST179 as well as 14 other sequence types, indicating a polyclonal outbreak. A multimodal intervention that included education, insertion checklists, guidelines on maintenance and access of central lines, adjustments to the late onset sepsis antibiotic treatment, and the introduction of diaper bags for disposal of soiled diapers after being handled inside the bed, led to termination of the outbreak.
Typing using WGS identified this outbreak as predominately nonclonal and therefore not due to cross transmission. A multimodal approach was then sought to reduce the incidence of VSEfe bacteremia.
Little information is available on the prevalence of Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 eating disorders in adolescence, and eating disorders remain unique in the DSM for not systematically including a criterion for clinical significance. This study aimed to provide the first prevalence report of the full suite of DSM-5 eating disorders in adolescence, and to examine the impact of applying a criterion for clinical significance.
In total, 5191 (participation rate: 70%) Australian adolescents completed a survey measuring 1-month prevalence of eating disorder symptoms for all criterial, ‘other specified’ and unspecified eating disorders, as well as health-related quality of life and psychological distress.
The point prevalence of any eating disorder was 22.2% (12.8% in boys, 32.9% in girls), and ‘other specified’ disorders (11.2%) were more common than full criterial disorders (6.2%). Probable bulimia nervosa and binge eating disorder, but not anorexia nervosa (AN), were more likely to be experienced by older adolescents. Most disorders were associated with an increased odds for being at a higher weight. The prevalence of eating disorders was reduced by 40% (to 13.6%) when a criterion for clinical significance was applied.
Eating disorders, particularly ‘other specified’ syndromes, are common in adolescence, and are experienced across age, weight, socioeconomic and migrant status. The merit of adding a criterion for clinical significance to the eating disorders, similar to other DSM-5 disorders, warrants consideration. At the least, screening tools should measure distress and impairment associated with eating disorder symptoms in order to capture adolescents in greatest need for intervention.
Jaswal & Akhtar provide several quotes ostensibly from people with autism but obtained via the discredited techniques of Facilitated Communication and the Rapid Prompting Method, and they do not acknowledge the use of these techniques. As a result, their argument is substantially less convincing than they assert, and the article lacks transparency.
To determine the impact of specialized treatments, relative to comparator treatments, upon the weight and psychological symptoms of anorexia nervosa (AN) at end-of-treatment (EOT) and follow-up.
Randomized controlled trials (RCTs) between January 1980 and December 2017 that reported the effects of at least two treatments on AN were screened. Weight and psychological symptoms were analyzed separately for each study. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed, and studies were assessed using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) criteria and Cochrane risk of bias tool.
We identified 35 eligible RCTs, comprising data from 2524 patients. Meta-analyses revealed a significant treatment effect on weight outcomes at EOT [g = 0.16, 95% CI (0.05–0.28), p = 0.006], but not at follow-up [g = 0.11, 95% CI (−0.04 to 0.27), p = 0.15]. There was no significant treatment effect on psychological outcomes at either EOT [g = −0.03, 95% CI (−0.14 to 0.08), p = 0.63], or follow-up [g = −0.001, 95% CI (−0.11 to 0.11), p = 0.98]. There was no strong evidence of publication bias or significant moderator effects for illness duration, mean age, year of publication, comparator group category, or risk of bias (all p values > 0.05).
Current specialized treatments are more adept than comparator interventions at imparting change in weight-based AN symptoms at EOT, but not at follow-up. Specialized treatments confer no advantage over comparator interventions in terms of psychological symptoms. Future precision treatment efforts require a specific focus on the psychological symptoms of AN.
OBJECTIVES/SPECIFIC AIMS: High on-treatment platelet reactivity (HTPR) with clopidogrel imparts an increased risk for ischemic events in adults with coronary artery disease. Although more potent antiplatelet agents are available, clopidogrel remains the most commonly used P2Y12 inhibitor in Puerto Rico. Platelet reactivity varies with ethnicity and is influenced by both clinical and genetic variables; however, no clopidogrel pharmacogenetic studies with Puerto Rican patients have been reported. Therefore, we sought to identify clinical and genetic determinants of on-treatment platelet reactivity in a cohort of Puerto Rican patients with cardiovascular disease. METHODS/STUDY POPULATION: We performed a retrospective study of 111 Puerto Rican patients on 75 mg/day maintenance dose of clopidogrel. Patients were allocated into 2 groups: Group I, without HTPR; and Group II, with HTPR. Clinical data was obtained from the medical record. Platelet function was measured ex vivo using the VerifyNow® P2Y12 assay and HTPR was defined as P2Y12 reaction units (PRU)≥230. Genotyping of CYP2C19, ABCB1, PON1, PY2R12, B4GALT2, CES1, and PEAR1 was performed using Taqman® Genotyping Assays. RESULTS/ANTICIPATED RESULTS: The mean PRU across the cohort was 203±61 PRU (range, 8–324), and 42 (38%) patients had HTPR. One in four individuals carried at least 1 copy of the CYP2C19*2 variant allele. Hematocrit and PON1 p.Q192R variant were inversely correlated with platelet reactivity (p<0.05). Multiple logistic regression showed that 27% of the total variation in PRU was explained by a history of diabetes mellitus, hematocrit, CYP2C19*2, and PON1 p.Q192R. Body mass index (OR=1.15; CI: 1.03–1.27), diabetes mellitus (OR=3.46; CI: 1.05–11.43), hematocrit (OR=0.75; CI: 0.65–0.87), and CYP2C19*2 (OR=4.44; CI: 1.21–16.20) were the only independent predictors of HTPR. DISCUSSION/SIGNIFICANCE OF IMPACT: In a representative sample of Puerto Rican patients with cardiovascular disease, diabetes mellitus, hematocrit, CYP2C19*2, and PON1 p.Q192R were associated with on-treatment platelet reactivity. These factors may identify a subset of patients at higher risk for adverse events on clopidogrel in the Hispanic population.
Making predictions about aliens is not an easy task. Most previous work has focused on extrapolating from empirical observations and mechanistic understanding of physics, chemistry and biology. Another approach is to utilize theory to make predictions that are not tied to details of Earth. Here we show how evolutionary theory can be used to make predictions about aliens. We argue that aliens will undergo natural selection – something that should not be taken for granted but that rests on firm theoretical grounds. Given aliens undergo natural selection we can say something about their evolution. In particular, we can say something about how complexity will arise in space. Complexity has increased on the Earth as a result of a handful of events, known as the major transitions in individuality. Major transitions occur when groups of individuals come together to form a new higher level of the individual, such as when single-celled organisms evolved into multicellular organisms. Both theory and empirical data suggest that extreme conditions are required for major transitions to occur. We suggest that major transitions are likely to be the route to complexity on other planets, and that we should expect them to have been favoured by similarly restrictive conditions. Thus, we can make specific predictions about the biological makeup of complex aliens.
Eating disorders, once thought to be largely confined to females, are
increasingly common in males. However, the presentation of disordered eating
among males is often distinct to that observed in females and this diversity
is not accommodated in current classification schemes. Here, we consider the
diagnostic and clinical challenges presented by these distinctive
Delirium is an acute, severe deterioration in mental functioning. Inattention is the core feature, yet there are few objective methods for assessing attentional deficits in delirium. We previously developed a novel, graded test for objectively detecting inattention in delirium, implemented on a computerized device (Edinburgh Delirium Test Box (EDTB)). Although the EDTB is effective, tests on universally available devices have potential for greater impact. Here we assessed feasibility and validity of the DelApp, a smartphone application based on the EDTB.
This was a preliminary case-control study in hospital inpatients (aged 60–96 years) with delirium (N = 50), dementia (N = 52), or no cognitive impairment (N = 54) who performed the DelApp assessment, which comprises an arousal assessment followed by counting of lights presented serially. Delirium was assessed using the Confusion Assessment Method and Delirium Rating Scale-Revised-98 (DRS-R98), and cognition with conventional tests of attention (e.g. digit span) and the short Orientation-Memory-Concentration Test (OMCT).
DelApp scores (maximum score = 10) were lower in delirium (scores (median(IQR)): 6 (4–7)) compared to dementia (10 (9–10)) and control groups (10 (10–10), p-values < 0.001). Receiver operating characteristic (ROC) analyses revealed excellent accuracy of the DelApp for discriminating delirium from dementia (AUC = 0.93), and delirium from controls (AUC = 0.99, p-values < 0.001). DelApp and DRS-R98 severity scores were moderately well correlated (Kendall's tau = −0.60, p < 0.001). OMCT scores did not differ between delirium and dementia.
The DelApp test showed good performance, supporting the utility of objectively measuring attention in delirium assessment. This study provides evidence of the feasibility of using a smartphone test for attentional assessment in hospital inpatients with possible delirium, with potential applications in research and clinical practice.
We have been interested in the plasmonic properties of alternative conducting materials to metals, such as conducting oxides, and we have recently expanded our studies to include highly correlated oxides, such as vanadium dioxide (VO2) thin films. VO2 exhibits a metal-insulator transition (MIT) just above ambient temperature at ∼ 340K. Interestingly, this transition can be induced thermally, optically or applying electric fields. Across the MIT, the optical properties are completely modified over a broad frequency range. We will present our recent optical investigations on the photon induced transition studies on such films, as well as the surface plasmon resonance (SPR) modulation in nanopatterned Au gratings by the thermally induced MIT in VO2 thin films, addressing possibilities of ultrafast SPR modulation with VO2.
Molecular pathways underlying carcinogenesis: cell cycle
Shun J. Lee, Division of Hematology-Oncology, Department of Medicine, Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA,
Benjamin F. O’Connor, Division of Hematology-Oncology, Department of Medicine, Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA,
Scott A. Stuart, Division of Hematology-Oncology, Department of Medicine, Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA,
Jean Y. J. Wang, Division of Hematology-Oncology, Department of Medicine, Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA
Regulation of DNA-damage-induced apoptosis is important to oncology in two ways. First, the majority of carcinogens are genotoxins that cause DNA damage and the apoptotic response to carcinogens is an important tumor-suppression mechanism. Second, a number of mainstay cancer therapeutic agents are genotoxins and their efficacies can be influenced by the robustness of DNA-damage-induced apoptosis in tumor cells. This chapter focuses on a network of nuclear factors involved in the transmission of DNA-damage signals to the intrinsic apoptotic machinery. These nuclear factors include DNA-damage sensors, the PIKK-family of protein kinases that these sensors activate, and three downstream nuclear effectors, p53, Abl, and caspase-2 (Figure 39.1). We have chosen to focus on this collection of nuclear factors, which represent only a subset of the DNA-damage signaling pathways, to illustrate two major points: (i) DNA-damage-induced apoptosis is regulated by nuclear proteins that also regulate DNA repair and (ii) DNA damage signals can be independently transmitted by several downstream effectors, i.e. p53, Abl, and caspase-2, to activate intrinsic apoptosis.
DNA damage does not always activate apoptosis
The concept of a linear, hard-wired signaling pathway that links lesions in genomic DNA to the apoptosis machinery would predict that DNA damage should always lead to cell killing, but this is not the case. In cells that undergo DNA-damage-induced apoptosis, death is invariably a delayed response requiring hours of deliberation. Generally speaking, delayed responses to biological perturbations are those that involve the reprogramming of gene expression, which, by nature of the transcription and translation processes, requires time. As the reprogramming of gene expression is under the hierarchical control of a multitude of genetic and epigenetic factors, activation of DNA-damage-induced apoptotic response is highly dependent on the lineage and the developmental stage of a cell. In addition to apoptosis, DNA-damaged cells can choose to undergo premature senescence or adaptation, where cells resume proliferation despite the persistence of DNA lesions. The choice a cell makes among these delayed responses to DNA damage is determined by how a cell reprograms its gene expression.