Clinician-targeted interventions to reduce antibiotic prescribing for acute respiratory infections in primary care:An overview of systematic reviews

This is the protocol for a review and there is no abstract. The objectives are as follows: To systematically review the literature and appraise the existing evidence from systematic reviews regarding the effects of interventions, aimed at changing clinician behaviour, to reduce antibiotic prescribing for ARIs in primary care

Statin initiation and acute kidney injury following elective cardiovascular surgery: a population cohort study in Denmark

OBJECTIVES: Acute kidney injury (AKI) is a serious complication of cardiac surgery. Statins may prevent post-surgical AKI, yet methodological concerns about existing studies raise questions about the magnitude of a protective effect. We sought to determine the effect of initiating a statin prior to elective cardiac surgery on post-surgical AKI in a regional Danish surgical cohort. METHODS: We identified adults who underwent cardiac surgery during 2006-11 using the Western Denmark Heart Registry. Presurgical medication use, pre- and post-surgical serum creatinine (sCr) measures, and other patient characteristics were obtained from Danish population-based registries. Post-surgical AKI was assessed using sCr measures within 5 days of surgery. The adjusted risk ratio (RR) of AKI and 95% confidence interval (CI) were estimated for patients who initiated a statin within 100 days prior to surgery compared with patients without prior statin use; long-term statin users were excluded to reduce healthy-user bias. Subanalyses were stratified by surgery type: coronary artery bypass grafting (CABG) and non-CABG surgeries. RESULTS: We identified 1929 CABG and 1775 non-CABG patients. AKI occurred in 25% of CABG and 28% of non-CABG surgeries, and in 29% of the non-users and 21% of the statin initiators. Half of CABG patients and 9% of non-CABG patients initiated a statin prior to surgery. The adjusted RRs for the effect of statin initiation on AKI were as follows: all surgeries combined, RR = 0.86 (95% CI: 0.74, 0.98); CABG, RR = 0.88 (0.74, 1.05); non-CABG RR = 0.87 (0.68, 1.11). CONCLUSIONS: Presurgical statin initiation is associated with a reduction in AKI risk after cardiac surgery

Perspectives on conservation impacts of the global primate trade

MFH and DRKN are grateful to Animal Protection Denmark and MFH to the Carlsberg Foundation (grant number CF21-0473). AMM thanks the Whitley Fund for Nature, The Rufford Small Grants, The International Primate Protection League, and Mr. Martin Stanley for their long-term financial support toward night monkey conservation.The global trade in nonhuman primates represents a substantial threat to ecosystem health, human health, and primate conservation worldwide. Most of the primate trade involves trade for pet-keeping, consumption, or biomedical experimentation. We present an overview of international primate trade through five case studies; each describes a different facet of this trade. We draw on published scientific literature, media outlets, and open access datasets, including the CITES Trade Database to build these case studies. Case study 1 describes the role of introduced island populations of Macaca and Chlorocebus in trade for biomedical experimentation; case study 2 covers the global health threats posed by the primate trade, including zoonotic disease transmission once animals enter the trade pipeline; case study 3 addresses the ways that changing patterns of primate trade, from local markets to online, have increased the demand for primates as pets; case study 4 recognizes the role that local environmental activism can play in mitigating trade; and case study 5 shows variation between global regions in their contribution to the primate trade. We recommend greater oversight of primate trade, especially domestic trade within primate range countries, and real-time reporting to CITES to accurately track primate trade. Effective conservation-focused regulations that can minimise the negative effects of primate trade must be tailored to specific regions and species and require transparency, careful regulation, field research, and an understanding of the magnitude of this trade.Peer reviewe

Properties and local environment of p-type dopants and photoluminescent rare-earths implanted into zon single-crystals

Tese de doutoramento em Física, apresentada à Universidade de Lisboa através da Faculdade de Ciências, 2008This thesis presents an experimental study of the local environment of P-type and Rare-Earth dopants implanted in ZnO single-crystals (SCs). Various nuclear and bulk property techniques were combined in the following evaluations: Implantation damage annealing Implantation damage annealing was evaluated in ZnO SCs implanted with Fe, Sr and Ca. P-type dopants Cu and Ag implanted ZnO SCs were studied revealing that the solubility of Cu in substituting Zn is considerably higher than that of Ag. These results are discussed within the scope of the ZnO p-type doping problematic with these elements. Experimental proofs of the As anti-site behavior in ZnO were for the first time attained, i.e., the majority of As atoms are substitutional at the Zn site (SZn), possibly surrounded by two Zn vacancies (VZn). This reinforces the theoretical prediction that As acts as an acceptor in ZnO via the AsZn-2VZn complex formation. The co-doping of ZnO SC with In (donor) and As (acceptor) was addressed. The most striking result is the possible In-As pair formation. Two configurations are proposed for this pair , both with In and As at SZn. A purely In-related defect is also identified. These are preliminary experiments that can serve as guidelines for future and deeper studies. Rare-earths (RE) RE lattice site location, RE surface segregation and optical activation were investigated in Er and Tm implanted ZnO SCs, as a function of annealing temperature, implantation doses and implantation conditions. RE surface segregation and lattice recovery occur for high annealing temperatures, being more pronounced in the low dose implanted crystals. The RE-O clusters formation is suggested for the higher dose implanted samples. Er and Tm optical activation occurs at different annealing temperatures depending on the implantation doses, suggesting that the RE-related emission is associated with defects/impurities in the RE close vicinity that change with the annealings

Use of the prognostic biomarker suPAR in the emergency department improves risk stratification but has no effect on mortality:a cluster-randomized clinical trial (TRIAGE III)

Abstract Background Risk stratification of patients in the emergency department can be strengthened using prognostic biomarkers, but the impact on patient prognosis is unknown. The aim of the TRIAGE III trial was to investigate whether the introduction of the prognostic and nonspecific biomarker: soluble urokinase plasminogen activator receptor (suPAR) for risk stratification in the emergency department reduces mortality in acutely admitted patients. Methods The TRIAGE III trial was a cluster-randomized interventional trial conducted at emergency departments in the Capitol Region of Denmark. Eligible hospitals were required to have an emergency department with an intake of acute medical and surgical patients and no previous access to suPAR measurement. Three emergency departments were randomized; one withdrew shortly after the trial began. The inclusion period was from January through June of 2016 consisting of twelve cluster-periods of 3-weeks alternating between intervention and control and a subsequent follow-up of ten months. Patients were allocated to the intervention if they arrived in interventional periods, where suPAR measurement was routinely analysed at arrival. In the control periods suPAR measurement was not performed. The main outcome was all-cause mortality 10 months after arrival of the last patient in the inclusion period. Secondary outcomes included 30-day mortality. Results The trial enrolled a consecutive cohort of 16,801 acutely admitted patients; all were included in the analyses. The intervention group consisted of 6 cluster periods with 8900 patients and the control group consisted of 6 cluster periods with 7901 patients. After a median follow-up of 362 days, death occurred in 1241 patients (13.9%) in the intervention group and in 1126 patients (14.3%) in the control group. The weighted Cox model found a hazard ratio of 0.97 (95% confidence interval, 0.89 to 1.07; p = 0.57). Analysis of all subgroups and of 30-day all-cause mortality showed similar results. Conclusions The TRIAGE III trial found no effect of introducing the nonspecific and prognostic biomarker suPAR in emergency departments on short- or long-term all-cause mortality among acutely admitted patients. Further research is required to evaluate how prognostic biomarkers can be implemented in routine clinical practice. Trial registration clinicaltrials.gov, NCT02643459. Registered 31 December 2015

C. elegans rrf-1 Mutations Maintain RNAi Efficiency in the Soma in Addition to the Germline

Gene inactivation through RNA interference (RNAi) has proven to be a valuable tool for studying gene function in C. elegans. When combined with tissue-specific gene inactivation methods, RNAi has the potential to shed light on the function of a gene in distinct tissues. In this study we characterized C. elegans rrf-1 mutants to determine their ability to process RNAi in various tissues. These mutants have been widely used in RNAi studies to assess the function of genes specifically in the C. elegans germline. Upon closer analysis, we found that two rrf-1 mutants carrying different loss-of-function alleles were capable of processing RNAi targeting several somatically expressed genes. Specifically, we observed that the intestine was able to process RNAi triggers efficiently, whereas cells in the hypodermis showed partial susceptibility to RNAi in rrf-1 mutants. Other somatic tissues in rrf-1 mutants, such as the muscles and the somatic gonad, appeared resistant to RNAi. In addition to these observations, we found that the rrf-1(pk1417) mutation induced the expression of several transgenic arrays, including the FOXO transcription factor DAF-16. Unexpectedly, rrf-1(pk1417) mutants showed increased endogenous expression of the DAF-16 target gene sod-3; however, the lifespan and thermo-tolerance of rrf-1(pk1417) mutants were similar to those of wild-type animals. In sum, these data show that rrf-1 mutants display several phenotypes not previously appreciated, including broader tissue-specific RNAi-processing capabilities, and our results underscore the need for careful characterization of tissue-specific RNAi tools

Lower birth weight and increased body fat at school age in children prenatally exposed to modern pesticides: a prospective study

Background: Endocrine disrupting chemicals have been hypothesized to play a role in the obesity epidemic. Long-term effects of prenatal exposure to non-persistent pesticides on body composition have so far not been investigated. The purpose of this study was to assess possible effects of prenatal exposure to currently used pesticides on children's growth, endocrine and reproductive function. Methods: In a prospective study of 247 children born by women working in greenhouses in early pregnancy, 168 were categorized as prenatally exposed to pesticides. At three months (n = 203) and at 6 to11 years of age (n = 177) the children underwent a clinical examination and blood sampling for analysis of IGF-I, IGFBP3 and thyroid hormones. Body fat percentage at age 6 to11 years was calculated from skin fold measurements. Pesticide related associations were tested by linear multiple regression analysis, adjusting for relevant confounders. Results: Compared to unexposed children birth weight and weight for gestational age were lower in the highly exposed children: -173 g (-322; -23), -4.8% (-9.0; -0.7) and medium exposed children: -139 g (-272; -6), -3.6% (-7.2; -0.0). Exposed (medium and highly together) children had significantly larger increase in BMI Z-score (0.55 SD (95% CI: 0.1; 1.0) from birth to school age) and highly exposed children had 15.8% (0.2; 34.6) larger skin folds and higher body fat percentage compared to unexposed. If prenatally exposed to both pesticides and maternal smoking (any amount), the sum of four skin folds was 46.9% (95% CI: 8.1; 99.5) and body fat percentage 29.1% (95% CI: 3.0; 61.4) higher. There were subtle associations between exposure and TSH Z-score -0.66(-1.287; -0.022) and IGF-I Z-score (girls: -0.62(-1.0; -0.22), boys: 0.38(-0.03; 0.79)), but not IGFBP3. Conclusions: Occupational exposure to currently used pesticides may have adverse effects in spite of the added protection offered to pregnant women. Maternal exposure to combinations of modern, non-persistent pesticides during early pregnancy was associated with affected growth, both prenatally and postnatally. We found a biphasic association with lower weight at birth followed by increased body fat accumulation from birth to school age. We cannot rule out some residual confounding due to differences in social class, although this was adjusted for. Associations were stronger in highly exposed than in medium exposed children, and effects on body fat content at school age was potentiated by maternal smoking in pregnancy

Bioinformatics-Driven Identification and Examination of Candidate Genes for Non-Alcoholic Fatty Liver Disease

ObjectiveCandidate genes for non-alcoholic fatty liver disease (NAFLD) identified by a bioinformatics approach were examined for variant associations to quantitative traits of NAFLD-related phenotypes.Research Design and MethodsBy integrating public database text mining, trans-organism protein-protein interaction transferal, and information on liver protein expression a protein-protein interaction network was constructed and from this a smaller isolated interactome was identified. Five genes from this interactome were selected for genetic analysis. Twenty-one tag single-nucleotide polymorphisms (SNPs) which captured all common variation in these genes were genotyped in 10,196 Danes, and analyzed for association with NAFLD-related quantitative traits, type 2 diabetes (T2D), central obesity, and WHO-defined metabolic syndrome (MetS).Results273 genes were included in the protein-protein interaction analysis and EHHADH, ECHS1, HADHA, HADHB, and ACADL were selected for further examination. A total of 10 nominal statistical significant associations (P<0.05) to quantitative metabolic traits were identified. Also, the case-control study showed associations between variation in the five genes and T2D, central obesity, and MetS, respectively. Bonferroni adjustments for multiple testing negated all associations.ConclusionsUsing a bioinformatics approach we identified five candidate genes for NAFLD. However, we failed to provide evidence of associations with major effects between SNPs in these five genes and NAFLD-related quantitative traits, T2D, central obesity, and MetS