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We evaluated the relationship between local MRSA prevalence rates and antibiotic use across 122 VHA hospitals in 2016. Higher hospital-level MRSA prevalence was associated with significantly higher rates of antibiotic use, even after adjusting for case mix and stewardship strategies. Benchmarking anti-MRSA antibiotic use may need to adjust for MRSA prevalence.
Frowning expresses negative emotions like anger, fear, and sadness. According to the facial feedback hypothesis, suppression of frowning will also diminish the corresponding negative emotions. Hence, mood improvement has been observed in patients who underwent treatment of glabellar frown lines with botulinum neurotoxin. This observation suggests the possibility that the intervention may be employed for the management of psychiatric disorders associated with negative emotions. Preliminary data from an open case series indicate that the intervention might improve the symptoms of depression.
Aims & objectives
To test whether an onabotulinumtoxinA injection into the glabellar region is benefical as an adjunctive treatment of major depression within a clinical trial.
We used a randomized, double-blinded, placebo-controlled study design (n = 30; ClinicalTrials.gov, number, NCT00934687).
We show that a single onabotulinumtoxinA treatment shortly leads to a strong and sustained improvement in partly chronic major depression that did not respond sufficiently to previous treatment. As for the primary end-point, Hamilton Depression Rating Scale (HAM-D17) six weeks after treatment compared to baseline, scores of onabotulinumtoxinA recipients showed 37.9% (8.34 points) more improvement than those of placebo-treated participants (F = 12.30, p = 0.002, η2 = 0.31, d = 1.28).
Our findings support the concept that the facial musculature not only expresses, but also regulates, mood states. As it stands, treatment of glabellar frown lines with botulinum neurotoxin can be considered for depressed patients with the objective of inducing mood-lifting effects.
There is a lack of evidence for the efficacy of stimulant pharmacotherapy in patients with substance dependence and comorbid attention deficit hyperactivity disorder (ADHD).
The aim of the present trial was to test the efficacy and safety of 180 mg extended release methylphenidate for treating ADHD in patients with amphetamine dependence.
54 incarcerated men, mean age 42 years, meeting the DSM-IV criteria for amphetamine dependence and ADHD were randomized to methylphenidate or placebo in a 24-week randomized double-blind, placebo-controlled trial, with parallel groups design. The medication started within 14 days before release from prison and continued in outpatient care with twice weekly visits including once weekly cognitive behaviour therapy. The primary end point was relapse to any drug use measured by urine toxicology. Secondary endpoints included relapse to amphetamine use, retention to treatment, and change in selfrated ADHD symptoms.
The methylphenidate group had significantly fewer drug positive urines compared to the placebo group (95% CI -0.31 to -0.05, P=.034), fewer amphetamine positive urines, (95% CI -0.36 to -0.07, P=.019) and better retention to treatment (95% CI 15.64 to 78.58, P=.001). Compared to the placebo group, the methylphenidate group also significantly reduced their selfrated ADHD symptoms (95% CI -21.09 to -3.37, P=.008) during the 24-week treatment.
This is the first randomized clinical trial to demonstrate the efficacy of a stimulant treatment for substance dependent individuals with ADHD. The treatment with MPH led to reduction in drug use and a clinically relevant improvement of ADHD symptoms.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
In this cohort of Escherichia coli and Klebsiella spp hospital-onset bacteremia, isolated fluoroquinolone resistance had a larger relative impact on mortality than other phenotypic resistance patterns. This finding may support stewardship efforts targeting unnecessary fluoroquinolone use and increased attention from infection prevention and control departments.
Introduction: Prompt defibrillation is critical during paediatric cardiac arrest. The main objective of this systematic review was to determine the initial defibrillation energy dose for ventricular fibrillation (VF) or pulseless ventricular tachycardia (pVT) that is associated with sustained return of spontaneous circulation (ROSC) during paediatric cardiac arrest. Associations between initial defibrillation energy dose with any ROSC, survival and defibrillation-induced complications were also assessed. Methods: A systematic review was performed using four databases (Medline, Embase, Web of Science, Cochrane Library) (PROSPERO: CRD42016036734). Human studies (cohort studies or controlled trials) and animal model studies (controlled trials) of pediatric cardiac arrest involving assessment of external defibrillation energy dosing were considered. The primary outcome was sustained ROSC. Two researchers independently reviewed all the titles and abstracts of the retrieved citations, selected the studies and extracted the data using a standardized template. Risk of bias of human non-randomised studies were assessed using the ROBIN-I tool (formerly ACROBAT-NRSI) tool proposed by the Cochrane Collaboration group. Results: The search strategy identified 14,471 citations of which 232 manuscripts were reviewed. Ten human and 10 animal model studies met the inclusion criteria. Human studies were prospective (n = 6) or retrospective (n = 4) cohort studies and included between 11 and 266 patients (median = 46 patients). Sustained ROSC rates ranged from 0 to 61% (n = 7). No studies reported a statistically significant association between the initial defibrillation energy dose and the rate of sustained ROSC (n = 7) or survival (n = 6). No human studies reported defibrillation-induced complications. Meta-analysis was not considered appropriate due to clinical heterogeneity. The overall risk of bias was moderate. All animal studies were randomized controlled trials with 8 and 52 (median = 27) piglets. ROSC was frequently achieved (more than 85%) with energy dose ranging from 2 to 7 joules/kg (n = 7). The defibrillation threshold varied according to the body weight and appears to be higher in infant models. Conclusion: Defibrillation energy doses and thresholds varied according to the body weight and trended higher for infants. No definitive association between initial defibrillation doses and the outcomes of sustained ROSC or survival could be demonstrated.
Little is known about health-related quality of life in young children undergoing staged palliation for single-ventricle CHD. The aim of this study was to assess the impact of CHD on daily life in pre-schoolers with single-ventricle CHD and to identify determinants of health-related quality of life.
Prospective two-centre cohort study assessing health-related quality of life using the Preschool Paediatric Cardiac Quality of Life Inventory in 46 children at a mean age of 38 months and 3 weeks. Children with genetic anomalies were excluded. Scores were compared with reference data of children with biventricular CHD. Multiple linear regression analysis was used to identify determinants of health-related quality of life.
Health-related quality of life in pre-schoolers with single-ventricle CHD was comparable to children with biventricular CHD. Preterm birth and perioperative variables were significant predictors of low health-related quality of life. Notably, pre-Fontan brain MRI findings and neurodevelopmental status were not associated with health-related quality of life. Overall, perioperative variables explained 24% of the variability of the total health-related quality of life score.
Despite substantial health-related burden, pre-schoolers with single-ventricle CHD showed good health-related quality of life. Less-modifiable treatment-related risk factors and preterm birth had the highest impact on health-related quality of life. Long-term follow-up assessment of self-reported health-related quality of life is needed to identify patients with poorer health-related quality of life and to initiate supportive care.
A better understanding of the dynamics of different particulate organic matter (OM) pools in the coastal carbon budget is a key issue for quantifying the role of the coastal ocean in the global carbon cycle. To elucidate the benthic component of this carbon cycle at the land-sea interface, we investigated the carbon isotope signatures (δ13C and ∆14C) in the sediment pore waters dissolved inorganic carbon (DIC) in addition to the sediment OM to constrain the origin of the OM mineralized in sediments. The study site is located at the outlet of the Rhône River (Mediterranean Sea), which was chosen because this river is one of the most nuclearized rivers in Europe and nuclear 14C can serve as a tracer to follow the fate of the OM discharged by the river to the coastal sea. The ∆14C results found in the pore waters DIC show a general offset between buried and mineralized OM following a preferential mineralization model of young and fresh particles. For example, we found that the sediment OM has values with a mean ∆14C=–33‰ at sampling stations near the river mouth whereas enriched ∆14C values around +523‰ and +667‰ respectively were found for the pore waters DIC. This indicates complete mineralization of a riverine fraction of OM enriched in 14C in the river conduit during in-stream photosynthesis. In shelf sediments, the ∆14C of pore waters DIC is slightly enriched (+57‰) with sediment OM reaching –570‰. A mixing model shows that particles mineralized near the river mouth are certainly of riverine phytoplanktonic origin whereas OM mineralized on the shelf is of marine origin. This work highlights the fact that pore waters provide additional information compared to sediments alone and it seems essential to work on both pools to study the carbon budget in river prodelta.
It is now well accepted that exposure to adverse environmental conditions in utero can predispose a fetus to disease later in life. Using an avian model to study the programming of disease has a unique advantage as it allows isolation of the direct effects of adverse conditions on fetal physiology, without any confounding effects via the mother or placenta. However, experiments in avian models are limited by the lack of well-established surgical protocols for the adult bird, which we have established in this study. Surgery was performed on seven young adult Bovan Brown chickens (body weight 1617±214 g, mean±s.d.) in order to instrument them with femoral arterial and venous catheters and a femoral arterial flow probe. Isoflurane and lidocaine were both found to have depressive effects on chicken cardiovascular function. Optimised methods of anaesthesia, intraoperative monitoring, surgical approach, postoperative care, and experimentation are described. Chickens recovered rapidly from surgery without significant blood gas perturbation, and basal in vivo cardiovascular studies were performed following 5 days of recovery. These techniques allow detailed investigation of avian cardiometabolic function, permitting determination of the consequences in later life of direct environmental insults to fetal physiology, isolated from additional effects on maternal physiology and/or placental endocrinology.
This paper presents latest thinking from the Institute and Faculty of Actuaries’ Model Risk Working Party and follows on from their Phase I work, Model Risk: Daring to Open the Black Box. This is a more practical paper and presents the contributors’ experiences of model risk gained from a wide range of financial and non-financial organisations with suggestions for good practice and proven methods to reduce model risk. After a recap of the Phase I work, examples of model risk communication are given covering communication: to the Board; to the regulator; and to external stakeholders. We present a practical framework for model risk management and quantification with examples of the key actors, processes and cultural challenge. Lessons learned are then presented from other industries that make extensive use of models and include the weather forecasting, software and aerospace industries. Finally, a series of case studies in practical model risk management and mitigation are presented from the contributors’ own experiences covering primarily financial services.
We studied the imprints that feedback from Active Galactic Nuclei (AGN) leaves on the intracluster plasma during the assembly history of galaxy clusters. To this purpose we used state-of-the-art cosmological hydrodynamical simulations based on an updated version of the Tree-PM SPH GADGET-3 code, comparing three sets of simulations with different prescriptions for the physics of baryons (including AGN and/or stellar feedback). We explore the effect of these different physics, in particular AGN feedback, on IntraCluster medium (ICM) properties observed via Sunyaev-Zel’dovich (SZ) effect using an extended set of galaxy clusters (~100 clusters with M500 masses above 5 × 1013M⊙/h). Some of the main findings are that the scaling relation between the integrated SZ flux and the galaxy cluster total mass is in good accordance with several observed samples, especially for massive clusters, and does not show any clear redshift evolution, with the slope of the relation close to the theoretical one in the AGN feedback case. As for the scatter of this relation, we obtain a mild dependence on the cluster dynamical state.
A serosurvey of 349 military working horses and 231 military working dogs was conducted in ten sites in Morocco in 2012. This survey revealed a high level of exposure of these animals to flaviviruses: seroprevalence rates of 60% in horses and of 62% in dogs were observed using a competitive West Nile virus (WNV) enzyme-linked immunosorbent assay (cELISA). Seroneutralization test results showed that the majority of cELISA-positive results were due to exposure to WNV. Further assays conducted in vaccinated horses with a DIVA (Differentiating Infected from Vaccinated Animals) test indicated that anti-WNV antibodies had been stimulated through WNV natural infection. Moreover, in both species, seroneutralization tests suggested an exposure to Usutu virus (USUV). Data analysis did not show any significant difference of cELISA seropositivity risk between horses and dogs. Dogs may thus represent an interesting alternative to equines for the serological surveillance of WNV or USUV circulation, especially in areas where equine vaccination precludes passive surveillance (based on the detection of West Nile fever cases) in horses.
With the increasing use of complex quantitative models in applications throughout the financial world, model risk has become a major concern. Such risk is generated by the potential inaccuracy and inappropriate use of models in business applications, which can lead to substantial financial losses and reputational damage. In this paper, we deal with the management and measurement of model risk. First, a model risk framework is developed, adapting concepts such as risk appetite, monitoring, and mitigation to the particular case of model risk. The usefulness of such a framework for preventing losses associated with model risk is demonstrated through case studies. Second, we investigate the ways in which different ways of using and perceiving models within an organisation both lead to different model risks. We identify four distinct model cultures and argue that in conditions of deep model uncertainty, each of those cultures makes a valuable contribution to model risk governance. Thus, the space of legitimate challenges to models is expanded, such that, in addition to a technical critique, operational and commercial concerns are also addressed. Third, we discuss through the examples of proxy modelling, longevity risk, and investment advice, common methods and challenges for quantifying model risk. Difficulties arise in mapping model errors to actual financial impact. In the case of irreducible model uncertainty, it is necessary to employ a variety of measurement approaches, based on statistical inference, fitting multiple models, and stress and scenario analysis.
This study describes the first large-scale serosurvey on West Nile virus (WNV) conducted in the equine population in Pakistan. Sera were collected from 449 equids from two provinces of Pakistan during 2012–2013. Equine serum samples were screened using a commercial ELISA kit detecting antibodies against WNV and related flaviviruses. ELISA-positive samples were further investigated using virus-specific microneutralization tests (MNTs) to identify infections with Japanese encephalitis virus (JEV), WNV and tick-borne encephalitis virus (TBEV). Anti-WNV antibodies were detected in 292 samples by ELISA (seroprevalence 65·0%) and WNV infections were confirmed in 249 animals by MNT. However, there was no animal found infected by JEV or TBEV. The detection of WNV-seropositive equines in Pakistan strongly suggests a widespread circulation of WNV in Pakistan.
This study aimed to evaluate in vitro and in vivo trypanocidal activity of free and nanoencapsulated curcumin against Trypanosoma evansi. In vitro efficacy of free curcumin (CURC) and curcumin-loaded in lipid-core nanocapsules (C-LNCs) was evaluated to verify their lethal effect on T. evansi. To perform the in vivo tests, T. evansi-infected animals were treated with CURC (10 and 100 mg kg−1, intraperitoneally [i.p.]) and C-LNCs (10 mg kg−1, i.p.) during 6 days, with the results showing that these treatments significantly attenuated the parasitaemia. Infected untreated rats showed protein peroxidation and an increase of nitrites/nitrates, whereas animals treated with curcumin showed a reduction on these variables. As a result, the activity of antioxidant enzymes (superoxide dismutase and catalase) differs between groups (P<0·05). Infected animals and treated with CURC exhibited a reduction in the levels of alanine aminotransferase and creatinine, when compared with the positive control group. The use of curcumin in vitro resulted in a better parasitaemia control, an antioxidant activity and a protective effect on liver and kidney functions of T. evansi-infected adult male Wistar rats.
We carried out an extensive photometric and spectroscopic investigation of the SPB binary, HD 25558 (see Fig. 1 for the time and geographic distribution of the observations). The ~2000 spectra obtained at 13 observatories during 5 observing seasons, the ground-based multi-colour light curves and the photometric data from the MOST satellite revealed that this object is a double-lined spectroscopic binary with a very long orbital period of about 9 years. We determined the physical parameters of the components, and have found that both lie within the SPB instability strip. Accordingly, both components show line-profile variations consistent with stellar pulsations. Altogether, 11 independent frequencies and one harmonic frequency were identified in the data. The observational data do not allow the inference of a reliable orbital solution, thus, disentangling cannot be performed on the spectra. Since the lines of the two components are never completely separated, the analysis is very complicated. Nevertheless, pixel-by-pixel variability analysis of the cross-correlated line profiles was successful, and we were able to attribute all the frequencies to the primary or secondary component. Spectroscopic and photometric mode-identification was also performed for several of these frequencies of both binary components. The spectroscopic mode-identification results suggest that the inclination and rotation of the two components are rather different. While the primary is a slow rotator with ~6 d rotation period, seen at ~60° inclination, the secondary rotates fast with ~1.2 d rotation period, and is seen at ~20° inclination. Our spectropolarimetric measurements revealed that the secondary component has a magnetic field with at least a few hundred Gauss strength, while no magnetic field was detected in the primary.
The detailed analysis and results of this study will be published elsewhere.
In the lead-up to the Square Kilometre Array (SKA) project, several next-generation radio telescopes and upgrades are already being built around the world. These include APERTIF (The Netherlands), ASKAP (Australia), e-MERLIN (UK), VLA (USA), e-EVN (based in Europe), LOFAR (The Netherlands), MeerKAT (South Africa), and the Murchison Widefield Array. Each of these new instruments has different strengths, and coordination of surveys between them can help maximise the science from each of them. A radio continuum survey is being planned on each of them with the primary science objective of understanding the formation and evolution of galaxies over cosmic time, and the cosmological parameters and large-scale structures which drive it. In pursuit of this objective, the different teams are developing a variety of new techniques, and refining existing ones. To achieve these exciting scientific goals, many technical challenges must be addressed by the survey instruments. Given the limited resources of the global radio-astronomical community, it is essential that we pool our skills and knowledge. We do not have sufficient resources to enjoy the luxury of re-inventing wheels. We face significant challenges in calibration, imaging, source extraction and measurement, classification and cross-identification, redshift determination, stacking, and data-intensive research. As these instruments extend the observational parameters, we will face further unexpected challenges in calibration, imaging, and interpretation. If we are to realise the full scientific potential of these expensive instruments, it is essential that we devote enough resources and careful study to understanding the instrumental effects and how they will affect the data. We have established an SKA Radio Continuum Survey working group, whose prime role is to maximise science from these instruments by ensuring we share resources and expertise across the projects. Here we describe these projects, their science goals, and the technical challenges which are being addressed to maximise the science return.