Carbapenem Resistance in Klebsiella pneumoniae Not Detected by Automated Susceptibility Testing

Detecting β-lactamase–mediated carbapenem resistance among Klebsiella pneumoniae isolates and other Enterobacteriaceae is an emerging problem. In this study, 15 blaKPC-positive Klebsiella pneumoniae that showed discrepant results for imipenem and meropenem from 4 New York City hospitals were characterized by isoelectric focusing; broth microdilution (BMD); disk diffusion (DD); and MicroScan, Phoenix, Sensititre, VITEK, and VITEK 2 automated systems. All 15 isolates were either intermediate or resistant to imipenem and meropenem by BMD; 1 was susceptible to imipenem by DD. MicroScan and Phoenix reported 1 (6.7%) and 2 (13.3%) isolates, respectively, as imipenem susceptible. VITEK and VITEK 2 reported 10 (67%) and 5 (33%) isolates, respectively, as imipenem susceptible. By Sensititre, 13 (87%) isolates were susceptible to imipenem, and 12 (80%) were susceptible to meropenem. The VITEK 2 Advanced Expert System changed 2 imipenem MIC results from >16 μg/mL to <2 μg/mL but kept the interpretation as resistant. The recognition of carbapenem-resistant K. pneumoniae continues to challenge automated susceptibility systems

A cross-curricular physical activity intervention to combat cardiovascular disease risk factors in 11-14 year olds: 'Activity Knowledge Circuit'

Background: Cardiovascular disease is the leading cause of mortality worldwide. Risk factors associated with cardiovascular disease have been shown to track from childhood through to adulthood. Previous school-based physical activity interventions have demonstrated modest improvements to cardiovascular disease risk factors by implementing extra-curricular activities or improving current physical education curriculum. Few have attempted to increase physical activity in class-room taught curriculum subjects. This study will outline a school-based cross-curricular physical activity intervention to combat cardiovascular disease risk factors in 11-14 year old children. Method/Design: A South Wales Valley school of low socio-economic status has been selected to take part. Participants from year eight (12-13 years) are to be assigned to an intervention group, with maturation-matched participants from years seven (11-12 years) and nine (13-14 years) assigned to a control group. A cross-curricular physical activity intervention will be implemented to increase activity by two hours a week for 18 weeks. Participants will briskly walk 3200 m twice weekly during curriculum lessons (60 minutes duration). With the exception of physical education, all curriculum subjects will participate, with each subject delivering four intervention lessons. The intervention will be performed outdoors and on school premises. An indoor course of equal distance will be used during adverse weather conditions. Cardiovascular disease risk factors will be measured pre- and post-intervention for intervention and control groups. These will take place during physical education lessons and will include measures of stature, mass, waist, hip, and neck circumferences, together with skinfold measure's taken at four sites. Blood pressure will be measured, and fitness status assessed via the 20 m multi-stage fitness test. Questionnaires will be used to determine activity behaviour (physical activity questionnaire for adolescence), diet (seven day food diary) and maturation status. Fasting blood variables will include total cholesterol, lowdensity lipoprotein cholesterol, high density lipoprotein cholesterol, triglycerides, insulin, glucose, high-sensitivity C-reactive protein, interleukin-6, adiponectin, and fibrinogen. Motivational variables and psychological well-being will be assessed by questionnaire. Discussion: Our study may prove to be a cost effective strategy to increase school time physical activity to combat cardiovascular disease risk factors in children.</p

Crafting organization

The recent shift in attention away from organization studies as science has allowed for consideration of new ways of thinking about both organization and organizing and has led to several recent attempts to \u27bring down\u27 organizational theorizing. In this paper, we extend calls for organization to be represented as a creative process by considering organization as craft. Organizational craft, we argue, is attractive, accessible, malleable, reproducible, and marketable. It is also a tangible way of considering organization studies with irreverence. We draw on the hierarchy of distinctions among fine art, decorative art, and craft to suggest that understanding the organization of craft assists in complicating our understanding of marginality. We illustrate our argument by drawing on the case of a contemporary Australian craftworks and marketplace known initially as the Meat Market Craft Centre (\u27MMCC\u27) and then, until its recent closure, as Metro! &Dagger; Stella Minahan was a board member and then the Chief Executive Officer of the Metro! Craft Centre.<br /

Temporal, seasonal and weather effects on cycle volume: an ecological study

<p>Abstract</p> <p>Background</p> <p>Cycling has the potential to provide health, environmental and economic benefits but the level of cycling is very low in New Zealand and many other countries. Adverse weather is often cited as a reason why people do not cycle. This study investigated temporal and seasonal variability in cycle volume and its association with weather in Auckland, New Zealand's largest city.</p> <p>Methods</p> <p>Two datasets were used: automated cycle count data collected on Tamaki Drive in Auckland by using ZELT Inductive Loop Eco-counters and weather data (gust speed, rain, temperature, sunshine duration) available online from the National Climate Database. Analyses were undertaken using data collected over one year (1 January to 31 December 2009). Normalised cycle volumes were used in correlation and regression analyses to accommodate differences by hour of the day and day of the week and holiday.</p> <p>Results</p> <p>In 2009, 220,043 bicycles were recorded at the site. There were significant differences in mean hourly cycle volumes by hour of the day, day type and month of the year (<it>p </it>< 0.0001). All weather variables significantly influenced hourly and daily cycle volumes (<it>p </it>< 0.0001). The cycle volume increased by 3.2% (hourly) and 2.6% (daily) for 1°C increase in temperature but decreased by 10.6% (hourly) and 1.5% (daily) for 1 mm increase in rainfall and by 1.4% (hourly) and 0.9% (daily) for 1 km/h increase in gust speed. The volume was 26.2% higher in an hour with sunshine compared with no sunshine, and increased by 2.5% for one hour increase in sunshine each day.</p> <p>Conclusions</p> <p>There are temporal and seasonal variations in cycle volume in Auckland and weather significantly influences hour-to-hour and day-to-day variations in cycle volume. Our findings will help inform future cycling promotion activities in Auckland.</p

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

High-starch diets alter equine faecal microbiota and increase behavioural reactivity

Gut microbiota have been associated with health, disease and behaviour in several species and are an important link in gut-brain axis communication. Diet plays a key role in affecting the composition of gut microbiota. In horses, high-starch diets alter the hindgut microbiota. High-starch diets are also associated with increased behavioural reactivity in horses. These changes in microbiota and behaviour may be associated. This study compares the faecal microbiota and behaviour of 10 naïve ponies. A cross-over design was used with experimental groups fed high-starch (HS) or high-fibre (HF) diets. Results showed that ponies were more reactive and less settled when being fed the HS diet compared to the HF diet. Irrespective of diet, the bacterial profile was dominated by two main phyla, Firmicutes, closely followed by Bacteroidetes. However, at lower taxonomic levels multivariate analysis of 16S rRNA gene sequencing data showed diet affected faecal microbial community structure. The abundance of 85 OTUs differed significantly related to diet. Correlative relationships exist between dietary induced alterations to faecal microbiota and behaviour. Results demonstrate a clear link between diet, faecal microbial community composition and behaviour. Dietary induced alterations to gut microbiota play a role in affecting the behaviour of the host

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Biddle, Bruce J., Better Ideas: Expanding Funding for Educational Research, Educational Researcher, 25 (December, 1996), 12-14. *

Makes the case for funding educational research