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Multidrug-resistant organisms (MDROs) cause ~5%–10% of infections in hospitalized children, leading to an increased risk of death, prolonged hospitalization, and additional costs. Antibiotic exposure is considered a driving factor of MDRO acquisition; however, consensus regarding the impact of antibiotic factors, especially in children, is lacking. We conducted a systematic review to examine the relationship between antibiotic use and subsequent healthcare-associated infection or colonization with an MDRO in children.
Systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline.
We searched PubMed and Embase for all English, peer-reviewed original research studies published before September 2018. Included studies evaluated hospitalized children, antibiotic use as an exposure, and bacterial MDRO as an outcome.
Of the 535 studies initially identified, 29 met the inclusion criteria. Overall, a positive association was identified in most studies evaluating a specific antibiotic exposure (17 of 21, 81%), duration of antibiotics (9 of 12, 75%), and number of antibiotics received (2 of 3, 67%). Those studies that evaluated any antibiotic exposure had mixed results (5 of 10, 50%). Study sites, populations, and definitions of antibiotic use and MDROs varied widely.
Published studies evaluating this relationship are limited and are of mixed quality. Limitations include observation bias in recall of antibiotic exposure, variations in case definitions, and lack of evaluation of antibiotic dosing and appropriateness. Additional studies exploring the impact of antibiotic use and MDRO acquisition may be needed to develop effective antibiotic stewardship programs for hospitalized children.
Pelvic internal organs change in volume and position during radiotherapy. This may compromise the efficacy of treatment or worsen its toxicity. There may be limitations to fully correcting these changes using online image guidance; therefore, effective and consistent patient preparation and positioning remain important. This review aims to provide an overview of the extent of pelvic organ motion and strategies to manage this motion.
Methods and Materials:
Given the breadth of this topic, a systematic review was not undertaken. Instead, existing systematic reviews and individual high-quality studies addressing strategies to manage pelvic organ motion have been discussed. Suggested levels of evidence and grades of recommendation for each strategy have been applied.
Various strategies to manage rectal changes have been investigated including diet and laxatives, enemas and rectal emptying tubes and rectal displacement with endorectal balloons (ERBs) and rectal spacers. Bladder-filling protocols and bladder ultrasound have been used to try to standardise bladder volume. Positioning the patient supine, using a full bladder and positioning prone with or without a belly board, has been examined in an attempt to reduce the volume of irradiated small bowel. Some randomised trials have been performed, with evidence to support the use of ERBs, rectal spacers, bladder-filling protocols and the supine over prone position in prostate radiotherapy. However, there was a lack of consistent high-quality evidence that would be applicable to different disease sites within the pelvis. Many studies included small numbers of patients were non-randomised, used less conformal radiotherapy techniques or did not report clinical outcomes such as toxicity.
There is uncertainty as to the clinical benefit of many of the commonly adopted interventions to minimise pelvic organ motion. Given this and the limitations in online image guidance compensation, further investigation of adaptive radiotherapy strategies is required.
We apply two methods to estimate the 21-cm bispectrum from data taken within the Epoch of Reionisation (EoR) project of the Murchison Widefield Array (MWA). Using data acquired with the Phase II compact array allows a direct bispectrum estimate to be undertaken on the multiple redundantly spaced triangles of antenna tiles, as well as an estimate based on data gridded to the uv-plane. The direct and gridded bispectrum estimators are applied to 21 h of high-band (167–197 MHz; z = 6.2–7.5) data from the 2016 and 2017 observing seasons. Analytic predictions for the bispectrum bias and variance for point-source foregrounds are derived. We compare the output of these approaches, the foreground contribution to the signal, and future prospects for measuring the bispectra with redundant and non-redundant arrays. We find that some triangle configurations yield bispectrum estimates that are consistent with the expected noise level after 10 h, while equilateral configurations are strongly foreground-dominated. Careful choice of triangle configurations may be made to reduce foreground bias that hinders power spectrum estimators, and the 21-cm bispectrum may be accessible in less time than the 21-cm power spectrum for some wave modes, with detections in hundreds of hours.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
Background: Spinal muscular atrophy (SMA) is a children’s neuromuscular disorder. Although motor neuron loss is a major feature of the disease, we have identified fatty acid abnormalities in SMA patients and in preclinical animal models, suggesting metabolic perturbation is also an important component of SMA. Methods: Biochemical, histological, proteomic, and high resolution respirometry were used. Results: SMA patients are more susceptible to dyslipidemia than the average population as determined by a standard lipid profile in a cohort of 72 pediatric patients. As well, we observed a non-alcoholic liver disease phenotype in apreclinical mouse model. Denervation alone was not sufficient to induce liver steatosis, as a mouse model of ALS, did not develop fatty liver. Hyperglucagonemia in Smn2B/-mice could explain the hepatic steatosis by increasing plasma substrate availability via glycogen depletion and peripheral lipolysis. Proteomic analysis identified mitochondrion and lipid metabolism as major clusters. Alterations in mitochondrial function were revealed by high-resolution respirometry. Finally, low-fat diets led to increased survival in Smn2B/-mice. Conclusions: These results provide strong evidence for lipid metabolism defects in SMA. Further investigation will be required to establish the primary mechanism of these alterations and understand how they lead to additional co-morbidities in SMA patients.
Breastfeeding may reduce obesity risk, but this association could be confounded by breastfeeding families’ characteristics. We investigated if body composition differs at birth among infants who were either exclusively breast- or formula-fed. We hypothesized the two groups would differ in body composition, even at birth, prior to their post-natal feeding experience. Healthy primiparous carrying singleton pregnancy were recruited at 15 weeks’ gestation. PEA POD® measured body composition within 72 hours of delivery and infant feeding was prospectively captured. Out of the 1,152 infants recruited, 117 (10.2%) and 239 (20.7%) went on to be either exclusively breast- or formula-fed, respectively. Breastfed infants were heavier at birth, but their percentage fat mass (FM) was lower than that of exclusively formula-fed infants (covariate adjusted β = −1.91 percentage points of FM; 95% CI −2.82 to −1.01). Differences in intra-uterine exposures, irrespective of early diet, may partly explain an infant’s obesity risk.
Methane is the second most important anthropogenically produced greenhouse gas, and radiocarbon (14C) analysis is extremely valuable in identifying its age and source in the environment. At the NERC Radiocarbon Facility (East Kilbride, UK) we have developed expertise in analysis of methane 14C concentration and methodological approaches to field sampling over the past 20 years. This has opened a wide range of applications, which have mainly focused on (1) the age and source of methane emitted by peatlands and organic soils (e.g. to quantify the release of ancient carbon), (2) the source of aquatic emissions of methane, and (3) the age of methane generated by amenity and illegal landfill. Many of these scientifically important applications involve challenging sampling and measurement considerations, which our development program has continually aimed to overcome. Here, we describe our current methods, and recent improvements to aid field collection of samples in remote locations. We present the results of tests which (1) show the effectiveness of our methods to remove contaminants, especially CO2, (2) quantify the 14C background contribution, and (3) demonstrate the reliability of metal gas storage canisters for sample storage.
There is substantial evidence that many depressed individuals experience impaired executive functioning. Understanding the causes of executive dysfunction in depression is clinically important because cognitive impairment is a substantial contributor to functional impairment. This study investigated whether elevated levels of an inflammatory cytokine [interleukin-6 (IL-6)] and/or higher body mass index (BMI) concurrently and/or prospectively accounted for the relationship between depressive symptoms and impaired executive functioning in adolescents.
A diverse, community sample of adolescents (N = 288; mean age = 16.33; 51.4% female; 59.0% African-American) completed assessments of height and weight, IL-6, depressive symptoms, and self-report/behavioral measures of executive functioning (selective attention, switching attention) and future orientation annually over 3 years. Adolescents experiencing acute illness or medical conditions that affect inflammation were excluded from analyses. Path analysis within a structural equation modeling framework simultaneously examined the concurrent and prospective relationships between BMI, IL-6, depressive symptoms, and the measures of cognitive functioning across three timepoints.
Across all timepoints, higher BMI was prospectively associated with higher levels of IL-6 and depressive symptoms, while higher levels of IL-6 were associated with worse performance on three behavioral and self-report measures of cognitive functioning. Higher depressive symptoms also were prospectively associated with elevated IL-6 and both higher depressive symptoms and a higher BMI predicted worse future executive functioning via increased IL-6.
More severe depressive symptoms and increased BMI may disrupt executive functioning via elevated IL-6.
We reconstruct the provenance of aluminosilicate sediment deposited in Ulleung Basin, Japan Sea, over the last 12 Ma at Site U1430 drilled during Integrated Ocean Drilling Program Expedition 346. Using multivariate partitioning techniques (Q-mode factor analysis, multiple linear regressions) applied to the major, trace and rare earth element composition of the bulk sediment, we identify and quantify four aluminosilicate components (Taklimakan, Gobi, Chinese Loess and Korean Peninsula), and model their mass accumulation rates. Each of these end-members, or materials from these regions, were present in the top-performing models in all tests. Material from the Taklimakan Desert (50–60 % of aluminosilicate contribution) is the most abundant end-member through time, while Chinese Loess and Gobi Desert components increase in contribution and flux in the Plio-Pleistocene. A Korean Peninsula component is lowest in abundance when present, and its occurrence reflects the opening of the Tsushima Strait at c. 3 Ma. Variation in dust source regions appears to track step-wise Asian aridification influenced by Cenozoic global cooling and periods of uplift of the Tibetan Plateau. During early stages of the evolution of the East Asian Monsoon, the Taklimakan Desert was the major source of dust to the Pacific. Continued uplift of the Tibetan Plateau may have influenced the increase in aeolian supply from the Gobi Desert and Chinese Loess Plateau into the Pleistocene. Consistent with existing records from the Pacific Ocean, these observations of aeolian fluxes provide more detail and specificity regarding the evolution of different Asian source regions through the latest Cenozoic.
Presented here is a report on the development of practical techniques for laboratory spectroscopy in the 5 to 150 A wavelength region as may be applied, for example, to light element and surface state analysis, high temperature plasma diagnostics and to the design and calibration of x-ray astronomy measurements.
This article considers the relationship between moral philosophy and constitutional theory through a detailed examination of the work of Jeremy Waldron—an unavoidable voice in contemporary constitutionalist debate. Through a rigorous, original and holistic deconstruction of his work and its philosophical implications, I argue that Waldron’s engagement with core philosophy within his constitutional scholarship is wholly problematic, containing a number of ambiguities and apparent inconsistencies. These issues, I suggest, may stem from an at times rather casual treatment of the realist/anti-realist issue of core philosophy, perhaps owing something to his view that it is in fact safely irrelevant to his constitutional pursuits. In any case, this view, I argue, is misguided, and the problems which result are real: they not only create issues of theoretical consistency and clarity; they put Waldron’s constitutional theory in danger. Like all good tales, I suggest there are lessons to be learned from this: one must think, and think carefully, about the philosophical background of one’s work, and take care in setting this out in a clear, thorough and coherent way—the stakes are too high not to. With this in mind, this article also lays some groundwork for a path into constitutional theory firmly grounded in my own anti-realist moral scepticism.
This article is concerned with the accountability of the civil advocate for results obtained for a client. It distinguishes the criminal trial by arguing that for effective implementation the adversary system, as it is commonly understood, requires that the professional advocates be equally competent and equally adversary and that because it does not meet these criteria, the criminal trial cannot be looked to as a model either of the adversary system or of the behavior of advocates in the civil trial. Rules of behavior for the civil litigator should be drawn with the primary objective of ascertaining truth. Moreover, the civil litigator cannot claim immunity from moral accountability by reference to the lawyer's role; he or she is personally accountable for an immoral result obtained for a client. Seeking to avoid this accountability all lawyers might reject an immoral but lawful cause, so that persons with such causes would be deprived of professional representation. The conflict between the lawyer's personal morality and the social value of professional assistance is resolved by reference to a formula for assigning counsel similar to those in Mathews v. Eldridge and Lassiter v. Department of Social Services. The author analyzes the moral dilemma of a lawyer who is so assigned and proposes a solution.
The American Bar Association's Commission on Evaluation of Professional Standards has proposed the replacement of the existing Code of Professional Responsibility with its Model Rules of Professional Conduct. The public discussion of the Model Rules has focused largely on specific provisions, such as the proposed requirement that lawyers disclose clients' confidences in some circumstances and the exhortation that all lawyers engage in pro bono activity. Another proposed change, however, would at least on its face seem to be more significant for the future of the bar's professional standards and its self-concept than for the resolution of particular professional dilemmas. That change is the proposed elimination of about half the current Code of Professional Responsibility: those provisions included under the rubric “Ethical Considerations.”
The value of the nosological distinction between non-affective and affective psychosis has frequently been challenged. We aimed to investigate the transdiagnostic dimensional structure and associated characteristics of psychopathology at First Episode Psychosis (FEP). Regardless of diagnostic categories, we expected that positive symptoms occurred more frequently in ethnic minority groups and in more densely populated environments, and that negative symptoms were associated with indices of neurodevelopmental impairment.
This study included 2182 FEP individuals recruited across six countries, as part of the EUropean network of national schizophrenia networks studying Gene–Environment Interactions (EU-GEI) study. Symptom ratings were analysed using multidimensional item response modelling in Mplus to estimate five theory-based models of psychosis. We used multiple regression models to examine demographic and context factors associated with symptom dimensions.
A bifactor model, composed of one general factor and five specific dimensions of positive, negative, disorganization, manic and depressive symptoms, best-represented associations among ratings of psychotic symptoms. Positive symptoms were more common in ethnic minority groups. Urbanicity was associated with a higher score on the general factor. Men presented with more negative and less depressive symptoms than women. Early age-at-first-contact with psychiatric services was associated with higher scores on negative, disorganized, and manic symptom dimensions.
Our results suggest that the bifactor model of psychopathology holds across diagnostic categories of non-affective and affective psychosis at FEP, and demographic and context determinants map onto general and specific symptom dimensions. These findings have implications for tailoring symptom-specific treatments and inform research into the mood-psychosis spectrum.
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.