Temporal Trends and Predictors of Antimicrobial Resistance Among \u3cem\u3eStaphylococcus\u3c/em\u3e spp. Isolated from Canine Specimens Submitted to a Diagnostic Laboratory

Background Resistance to commonly used antimicrobials is a growing concern in both human and veterinary medicine. Understanding the temporal changes in the burden of the problem and identifying its determinants is important for guiding control efforts. Therefore, the objective of this study was to investigate temporal patterns and predictors of antimicrobial resistance among Staphylococcus spp. isolated from canine specimens submitted to the University of Kentucky Veterinary Diagnostic Laboratory (UKVDL) between 1993 and 2009. Methods Retrospective data of 4,972 Staphylococcus isolates assessed for antimicrobial susceptibility using the disk diffusion method at the UKVDL between 1993 and 2009 were included in the study. Temporal trends were assessed for each antimicrobial using the Cochran-Armitage trend test. Logistic regression models were used to investigate predictors of antimicrobial resistance (AMR) and multidrug resistance (MDR). Results A total of 68.2% (3,388/4,972) Staphylococcus isolates were S. intermedius group (SIG), 18.2% (907/4,972) were coagulase-negative staphylococci (CoNS), 7.6% (375/4,972) were S. aureus, 5.8% (290/4,972) were S. hyicus, and S. schleiferi subsp. coagulans comprised 0.2% (12/4,972) of the isolates. The overall percentage of AMR and MDR were 77.2% and 25.6%, respectively. The highest levels of AMR were seen in CoNS (81.3%; 737/907), S. aureus (80.5%; 302/375), and SIG (77.6%; 2,629/3388). The lowest levels of AMR were observed in S. hyicus (57.9%; 168/290) and S. schleiferi subsp. coagulans (33.3%; 4/12). Overall, AMR and MDR showed significant (p \u3c 0.001) decreasing temporal trends. Significant temporal trends (both increasing and decreasing) were observed among 12 of the 16 antimicrobials covering 6 of the 9 drug classes assessed. Thus, significant increasing temporal trends in resistance were observed to β-lactams (p \u3c 0.001) (oxacillin, amoxicillin-clavulanate, cephalothin, and penicillin (p = 0.024)), aminoglycosides (p \u3c 0.001) (gentamicin, and neomycin), bacitracin (p \u3c 0.001), and enrofloxacin (p \u3c 0.001). In contrast, sulfonamide (p \u3c 0.001) (sulfadiazin) and tetracycline (p = 0.010) resistant isolates showed significant decreasing temporal trends in AMR. Staphylococcus spp., geographic region, and specimen source were significant predictors of both AMR and MDR. Conclusions Although not unexpected nor alarming, the high levels of AMR to a number of antimicrobial agents and the increasing temporal trends are concerning. Therefore, continued monitoring of AMR among Staphylococcus spp. is warranted. Future studies will need to identify local factors responsible for the observed geographic differences in risk of both AMR and MDR

The Economic Impact of Intensive Commodity Price Risk Management Education

Research shows that risk management, and in particular price risk management, has been a major concern for agricultural producers, and as such, has been the target area of a substantial amount of Extension education programming. Analysis of survey results indicate that the Master Marketer program, a 64-hour intensive training program that develops master volunteers who extend the education through marketing clubs, is a valuable Extension program helping producers to better-manage price and production risks. On average, graduates of the program have increased their net income by more than $33,000 annually

Temporal trends and predictors of antimicrobial resistance among Staphylococcus spp. isolated from canine specimens submitted to a diagnostic laboratory

Background Resistance to commonly used antimicrobials is a growing concern in both human and veterinary medicine. Understanding the temporal changes in the burden of the problem and identifying its determinants is important for guiding control efforts. Therefore, the objective of this study was to investigate temporal patterns and predictors of antimicrobial resistance among Staphylococcus spp. isolated from canine specimens submitted to the University of Kentucky Veterinary Diagnostic Laboratory (UKVDL) between 1993 and 2009. Methods Retrospective data of 4,972 Staphylococcus isolates assessed for antimicrobial susceptibility using the disk diffusion method at the UKVDL between 1993 and 2009 were included in the study. Temporal trends were assessed for each antimicrobial using the Cochran-Armitage trend test. Logistic regression models were used to investigate predictors of antimicrobial resistance (AMR) and multidrug resistance (MDR). Results A total of 68.2% (3,388/4,972) Staphylococcus isolates were S. intermedius group (SIG), 18.2% (907/4,972) were coagulase-negative staphylococci (CoNS), 7.6% (375/4,972) were S. aureus, 5.8% (290/4,972) were S. hyicus, and S. schleiferi subsp. coagulans comprised 0.2% (12/4,972) of the isolates. The overall percentage of AMR and MDR were 77.2% and 25.6%, respectively. The highest levels of AMR were seen in CoNS (81.3%; 737/907), S. aureus(80.5%; 302/375), and SIG (77.6%; 2,629/3388). The lowest levels of AMR were observed in S. hyicus (57.9%; 168/290) and S. schleiferi subsp. coagulans (33.3%; 4/12). Overall, AMR and MDR showed significant (p Conclusions Although not unexpected nor alarming, the high levels of AMR to a number of antimicrobial agents and the increasing temporal trends are concerning. Therefore, continued monitoring of AMR among Staphylococcus spp. is warranted. Future studies will need to identify local factors responsible for the observed geographic differences in risk of both AMR and MDR

Temporal trends and predictors of antimicrobial resistance among Staphylococcus spp. isolated from canine specimens submitted to a diagnostic laboratory

Background Resistance to commonly used antimicrobials is a growing concern in both human and veterinary medicine. Understanding the temporal changes in the burden of the problem and identifying its determinants is important for guiding control efforts. Therefore, the objective of this study was to investigate temporal patterns and predictors of antimicrobial resistance among Staphylococcus spp. isolated from canine specimens submitted to the University of Kentucky Veterinary Diagnostic Laboratory (UKVDL) between 1993 and 2009. Methods Retrospective data of 4,972 Staphylococcus isolates assessed for antimicrobial susceptibility using the disk diffusion method at the UKVDL between 1993 and 2009 were included in the study. Temporal trends were assessed for each antimicrobial using the Cochran-Armitage trend test. Logistic regression models were used to investigate predictors of antimicrobial resistance (AMR) and multidrug resistance (MDR). Results A total of 68.2% (3,388/4,972) Staphylococcus isolates were S. intermedius group (SIG), 18.2% (907/4,972) were coagulase-negative staphylococci (CoNS), 7.6% (375/4,972) were S. aureus, 5.8% (290/4,972) were S. hyicus, and S. schleiferi subsp. coagulans comprised 0.2% (12/4,972) of the isolates. The overall percentage of AMR and MDR were 77.2% and 25.6%, respectively. The highest levels of AMR were seen in CoNS (81.3%; 737/907), S. aureus(80.5%; 302/375), and SIG (77.6%; 2,629/3388). The lowest levels of AMR were observed in S. hyicus (57.9%; 168/290) and S. schleiferi subsp. coagulans (33.3%; 4/12). Overall, AMR and MDR showed significant (p\u3c0.001) decreasing temporal trends. Significant temporal trends (both increasing and decreasing) were observed among 12 of the 16 antimicrobials covering 6 of the 9 drug classes assessed. Thus, significant increasing temporal trends in resistance were observed to β-lactams (p\u3c0.001) (oxacillin, amoxicillin-clavulanate, cephalothin, and penicillin (p = 0.024)), aminoglycosides (p\u3c0.001) (gentamicin, and neomycin), bacitracin (p\u3c0.001), and enrofloxacin (p\u3c0.001). In contrast, sulfonamide (p\u3c0.001) (sulfadiazin) and tetracycline (p = 0.010) resistant isolates showed significant decreasing temporal trends in AMR. Staphylococcus spp., geographic region, and specimen source were significant predictors of both AMR and MDR. Conclusions Although not unexpected nor alarming, the high levels of AMR to a number of antimicrobial agents and the increasing temporal trends are concerning. Therefore, continued monitoring of AMR among Staphylococcus spp. is warranted. Future studies will need to identify local factors responsible for the observed geographic differences in risk of both AMR and MDR

Loss of Atrx Affects Trophoblast Development and the Pattern of X-Inactivation in Extraembryonic Tissues

ATRX is an X-encoded member of the SNF2 family of ATPase/helicase proteins thought to regulate gene expression by modifying chromatin at target loci. Mutations in ATRX provided the first example of a human genetic disease associated with defects in such proteins. To better understand the role of ATRX in development and the associated abnormalities in the ATR-X (alpha thalassemia mental retardation, X-linked) syndrome, we conditionally inactivated the homolog in mice, Atrx, at the 8- to 16-cell stage of development. The protein, Atrx, was ubiquitously expressed, and male embryos null for Atrx implanted and gastrulated normally but did not survive beyond 9.5 days postcoitus due to a defect in formation of the extraembryonic trophoblast, one of the first terminally differentiated lineages in the developing embryo. Carrier female mice that inherit a maternal null allele should be affected, since the paternal X chromosome is normally inactivated in extraembryonic tissues. Surprisingly, however, some carrier females established a normal placenta and appeared to escape the usual pattern of imprinted X-inactivation in these tissues. Together these findings demonstrate an unexpected, specific, and essential role for Atrx in the development of the murine trophoblast and present an example of escape from imprinted X chromosome inactivation

Manipulating the Mouse Genome to Engineer Precise Functional Syntenic Replacements with Human Sequence

SummaryWe have devised a strategy (called recombinase-mediated genomic replacement, RMGR) to allow the replacement of large segments (>100 kb) of the mouse genome with the equivalent human syntenic region. The technique involves modifying a mouse ES cell chromosome and a human BAC by inserting heterotypic lox sites to flank the proposed exchange interval and then using Cre recombinase to achieve segmental exchange. We have demonstrated the feasibility of this approach by replacing the mouse α globin regulatory domain with the human syntenic region and generating homozygous mice that produce only human α globin chains. Furthermore, modified ES cells can be used iteratively for functional studies, and here, as an example, we have used RMGR to produce an accurate mouse model of human α thalassemia. RMGR has general applicability and will overcome limitations inherent in current transgenic technology when studying the expression of human genes and modeling human genetic diseases

Inflammation, insulin resistance, and diabetes-mendelian randomization using CRP haplotypes points upstream

Background Raised C-reactive protein (CRP) is a risk factor for type 2 diabetes. According to the Mendelian randomization method, the association is likely to be causal if genetic variants that affect CRP level are associated with markers of diabetes development and diabetes. Our objective was to examine the nature of the association between CRP phenotype and diabetes development using CRP haplotypes as instrumental variables. Methods and Findings We genotyped three tagging SNPs (CRP + 2302G > A; CRP + 1444T > C; CRP + 4899T > G) in the CRP gene and measured serum CRP in 5,274 men and women at mean ages 49 and 61 y (Whitehall II Study). Homeostasis model assessment-insulin resistance (HOMA-IR) and hemoglobin A1c (HbA1c) were measured at age 61 y. Diabetes was ascertained by glucose tolerance test and self-report. Common major haplotypes were strongly associated with serum CRP levels, but unrelated to obesity, blood pressure, and socioeconomic position, which may confound the association between CRP and diabetes risk. Serum CRP was associated with these potential confounding factors. After adjustment for age and sex, baseline serum CRP was associated with incident diabetes (hazard ratio = 1.39 [95% confidence interval 1.29-1.51], HOMA-IR, and HbA1c, but the associations were considerably attenuated on adjustment for potential confounding factors. In contrast, CRP haplotypes were not associated with HOMA-IR or HbA1c (p=0.52-0.92). The associations of CRP with HOMA-IR and HbA1c were all null when examined using instrumental variables analysis, with genetic variants as the instrument for serum CRP. Instrumental variables estimates differed from the directly observed associations (p=0.007-0.11). Pooled analysis of CRP haplotypes and diabetes in Whitehall II and Northwick Park Heart Study II produced null findings (p=0.25-0.88). Analyses based on the Wellcome Trust Case Control Consortium (1,923 diabetes cases, 2,932 controls) using three SNPs in tight linkage disequilibrium with our tagging SNPs also demonstrated null associations. Conclusions Observed associations between serum CRP and insulin resistance, glycemia, and diabetes are likely to be noncausal. Inflammation may play a causal role via upstream effectors rather than the downstream marker CRP

Health and wellbeing amongst older people research in Northamptonshire

The Ageing Research Centre of the University of Northampton (2014-current), in collaboration with the East Midlands Research into Ageing Network (EMRAN) is pleased to compile this brochure on research activity associated with older people across the county of Northamptonshire. This provides a comprehensive overview of activity that is relevant and of value to practice, identifying research outcomes that have real significance to age-related health and wellbeing. The brochure provides a summary of research activity over the last five years from academic, clinical and professional colleagues and demonstrates cross sector networks of collaboration around the common agenda of aging. Such collaboration will enhance the capacity of research understanding across the county and provide information and support for the needs of older people, their families and carers. The translation of research outcomes into practice is essential if we are to promote wellness, independence and healthy aging within the county and beyond and I would like to thank all contributors for their commitment and hard work in the production of this brochure

Are symptoms of insomnia in primary care associated with subsequent onset of dementia? A matched retrospective case-control study

Objective: There is evidence from neuroimaging studies of an association between insomnia and early dementia biomarkers, but observational studies have so far failed to show a clear association between insomnia and the later development of dementia. We investigated the association between dementia diagnosis and recording of insomnia symptoms 5-10 years earlier in primary care. Method: A case-control study using data from the Clinical Practice Research Datalink. 15,209 cases with dementia (either Alzheimer's, vascular, mixed or non-specific subtypes) at least 65 years old at time of diagnosis, were matched with the same number of controls on year of birth and gender. We ascertained the presence of insomnia symptoms during a five-year period starting 10 years before the index date. Odds ratios for developing dementia were estimated using logistic regression after controlling for hypnotic exposure and physical and mental health comorbidities. Results: The adjusted odds ratio for dementia in those with previous insomnia was 1.34 (95% CI = 1.20-1.50). Conclusion: There is an association between dementia and previous insomnia. It may be possible to incorporate insomnia into predictive tools for dementia

A pragmatic cluster randomised trial evaluating three implementation interventions

Background Implementation research is concerned with bridging the gap between evidence and practice through the study of methods to promote the uptake of research into routine practice. Good quality evidence has been summarised into guideline recommendations to show that peri-operative fasting times could be considerably shorter than patients currently experience. The objective of this trial was to evaluate the effectiveness of three strategies for the implementation of recommendations about peri-operative fasting. Methods A pragmatic cluster randomised trial underpinned by the PARIHS framework was conducted during 2006 to 2009 with a national sample of UK hospitals using time series with mixed methods process evaluation and cost analysis. Hospitals were randomised to one of three interventions: standard dissemination (SD) of a guideline package, SD plus a web-based resource championed by an opinion leader, and SD plus plan-do-study-act (PDSA). The primary outcome was duration of fluid fast prior to induction of anaesthesia. Secondary outcomes included duration of food fast, patients' experiences, and stakeholders' experiences of implementation, including influences. ANOVA was used to test differences over time and interventions. Results Nineteen acute NHS hospitals participated. Across timepoints, 3,505 duration of fasting observations were recorded. No significant effect of the interventions was observed for either fluid or food fasting times. The effect size was 0.33 for the web-based intervention compared to SD alone for the change in fluid fasting and was 0.12 for PDSA compared to SD alone. The process evaluation showed different types of impact, including changes to practices, policies, and attitudes. A rich picture of the implementation challenges emerged, including inter-professional tensions and a lack of clarity for decision-making authority and responsibility. Conclusions This was a large, complex study and one of the first national randomised controlled trials conducted within acute care in implementation research. The evidence base for fasting practice was accepted by those participating in this study and the messages from it simple; however, implementation and practical challenges influenced the interventions' impact. A set of conditions for implementation emerges from the findings of this study, which are presented as theoretically transferable propositions that have international relevance. Trial registration ISRCTN18046709 - Peri-operative Implementation Study Evaluation (POISE