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Background: Automated testing instruments (ATIs) are commonly used by clinical microbiology laboratories to perform antimicrobial susceptibility testing (AST), whereas public health laboratories may use established reference methods such as broth microdilution (BMD). We investigated discrepancies in carbapenem minimum inhibitory concentrations (MICs) among Enterobacteriaceae tested by clinical laboratory ATIs and by reference BMD at the CDC. Methods: During 2016–2018, we conducted laboratory- and population-based surveillance for carbapenem-resistant Enterobacteriaceae (CRE) through the CDC Emerging Infections Program (EIP) sites (10 sites by 2018). We defined an incident case as the first isolation of Enterobacter spp (E. cloacae complex or E. aerogenes), Escherichia coli, Klebsiella pneumoniae, K. oxytoca, or K. variicola resistant to doripenem, ertapenem, imipenem, or meropenem from normally sterile sites or urine identified from a resident of the EIP catchment area in a 30-day period. Cases had isolates that were determined to be carbapenem-resistant by clinical laboratory ATI MICs (MicroScan, BD Phoenix, or VITEK 2) or by other methods, using current Clinical and Laboratory Standards Institute (CLSI) criteria. A convenience sample of these isolates was tested by reference BMD at the CDC according to CLSI guidelines. Results: Overall, 1,787 isolates from 112 clinical laboratories were tested by BMD at the CDC. Of these, clinical laboratory ATI MIC results were available for 1,638 (91.7%); 855 (52.2%) from 71 clinical laboratories did not confirm as CRE at the CDC. Nonconfirming isolates were tested on either a MicroScan (235 of 462; 50.9%), BD Phoenix (249 of 411; 60.6%), or VITEK 2 (371 of 765; 48.5%). Lack of confirmation was most common among E. coli (62.2% of E. coli isolates tested) and Enterobacter spp (61.4% of Enterobacter isolates tested) (Fig. 1A), and among isolates testing resistant to ertapenem by the clinical laboratory ATI (52.1%, Fig. 1B). Of the 1,388 isolates resistant to ertapenem in the clinical laboratory, 1,006 (72.5%) were resistant only to ertapenem. Of the 855 nonconfirming isolates, 638 (74.6%) were resistant only to ertapenem based on clinical laboratory ATI MICs. Conclusions: Nonconfirming isolates were widespread across laboratories and ATIs. Lack of confirmation was most common among E. coli and Enterobacter spp. Among nonconfirming isolates, most were resistant only to ertapenem. These findings may suggest that ATIs overcall resistance to ertapenem or that isolate transport and storage conditions affect ertapenem resistance. Further investigation into this lack of confirmation is needed, and CRE case identification in public health surveillance may need to account for this phenomenon.
To examine the impact of determinants of incident dementia in three different old age groups (75–79, 80–84, 85+years) in Germany.
Multicenter prospective AgeCoDe/AgeQualiDe cohort study with baseline and nine follow-up assessments at 1.5-year intervals.
Primary care medical record registry sample.
General practitioners’ (GPs) patients aged 75+years at baseline.
Conduction of standardized interviews including neuropsychological assessment and collection of GP information at each assessment wave. We used age-stratified competing risk regression models (accounting for the competing event of mortality) to assess determinants of incident dementia and age-stratified ordinary least square regressions to quantify the impact of identified determinants on the age at dementia onset.
Among 3027 dementia-free GP patients, n = 704 (23.3%) developed dementia during the 13-year study period. Worse cognitive performance and subjective memory decline with related worries at baseline, and the APOE ε4 allele were associated independently with increased dementia risk in all three old age groups. Worse cognitive performance at baseline was also associated with younger age at dementia onset in all three age groups. Other well-known determinants were associated with dementia risk and age at dementia onset only in some or in none of the three old age groups.
This study provides further evidence for the age-specific importance of determinants of incident dementia in old age. Such specifics have to be considered more strongly particularly with regard to potential approaches of early detection and prevention of dementia.
Metacognition is the capacity to evaluate and control one’s own cognitive processes. Metacognition operates over a range of cognitive domains, such as perception and memory, but the neurocognitive architecture supporting this ability remains controversial. Is metacognition enabled by a common, domain-general resource that is recruited to evaluate performance on a variety of tasks? Or is metacognition reliant on domain-specific modules? This article reviews recent literature on the domain-generality of human metacognition, drawing on evidence from individual differences and neuroimaging. A meta-analysis of behavioral studies found that perceptual metacognitive ability was correlated across different sensory modalities, but found no correlation between metacognition of perception and memory. However, evidence for domain-generality from behavioral data may suffer from a lack of power to identify correlations across model parameters indexing metacognitive efficiency. Neuroimaging data provide a complementary perspective on the domain-generality of metacognition, revealing co-existence of neural signatures that are common and distinct across tasks. We suggest that such an architecture may be appropriate for “tagging” generic feelings of confidence with domain-specific information, in turn forming the basis for priors about self-ability and modulation of higher-order behavioral control.
With the increase in long-term survival of post-transplant children, there is a paradigm shift in the emphasis of post-transplant care. We describe de novo cardiovascular abnormalities, which occurred in otherwise asymptomatic paediatric liver transplant recipients, who received liver allografts between 1991 and 2014 at the National University Hospital, Singapore, detected during routine post-transplant monitoring. A total of 96 paediatric liver transplants were performed in 90 children. After transplant, 7/90 (7.8%) recipients were identified with new-onset aortopathy. Glycogen storage disease type I (42.9% versus 2.4%; p<0.001) and recipient Epstein-Barr virus seropositivity (85.7 versus 31.0%, p=0.004) were significant risk factors for aortopathy on univariate analysis. On multivariate analysis, only glycogen storage disease type I remained as the significant risk factor (odds ratio 51.3 [95% confidence intervals: 1.1–2498.1, p=0.047]). Liver transplant is a double-edged sword that reverses certain cardiopulmonary complications of end-stage liver disease but may induce de novo structural cardiac injury in the form of aortic dilation.
The Teotihuacan Mapping Project (TMP) provided vast quantities of invaluable data to our understanding of this famous ancient city. The ‘Documenting, Disseminating, and Archiving Data from the Teotihuacan Mapping Project’ aims to analyse, re-examine and ultimately coalesce TMP data for entry into The Digital Archaeological Record.
We previously found that guar gum (GG) and chickpea flour (CPF) added to flatbread wheat flour lowered postprandial blood glucose (PPG) and insulin responses dose dependently. However, rates of glucose influx cannot be determined from PPG, which integrates rates of influx, tissue disposal and hepatic glucose production. The objective was to quantify rates of glucose influx and related fluxes as contributors to changes in PPG with GG and CPF additions to wheat-based flatbreads. In a randomised cross-over design, twelve healthy males consumed each of three different 13C-enriched meals: control flatbreads (C), or C incorporating 15 % CPF with either 2 % (GG2) or 4 % (GG4) GG. A dual isotope technique was used to determine the time to reach 50 % absorption of exogenous glucose (T50 %abs, primary objective), rate of appearance of exogenous glucose (RaE), rate of appearance of total glucose (RaT), endogenous glucose production (EGP) and rate of disappearance of total glucose (RdT). Additional exploratory outcomes included PPG, insulin, glucose-dependent insulinotropic peptide and glucagon-like peptide 1, which were additionally measured over 4 h. Compared with C, GG2 and GG4 had no significant effect on T50 %abs. However, GG4 significantly reduced 4-h AUC values for RaE, RaT, RdT and EGP, by 11, 14, 14 and 64 %, respectively, whereas GG2 showed minor effects. Effect sizes over 2 and 4 h were similar except for significantly greater reduction in EGP for GG4 at 2 h. In conclusion, a soluble fibre mix added to flatbreads only slightly reduced rates of glucose influx, but more substantially affected rates of postprandial disposal and hepatic glucose production.
Most of the previous studies attempted to disentangle the relationship between disability and depressive symptoms were limited to observation periods of only few years. Moreover, evidence is missing regarding the complex co-occurrence of disability and depressive symptoms in old age in Germany. In order to close the research gap, we aimed at disentangling the complex co-occurrence of disability and depressive symptoms in old age in Germany over a longer time frame.
Based on data from a representative survey of the German general population aged 75 years and older, the course of disability as well as depressive symptoms was observed every 1.5 years over six waves. While disability was quantified by the Lawton and Brody Instrumental Activities of Daily Living scale, the Geriatric Depression Scale was used to measure depressive symptoms. Taking into account the complex co-occurrence of depressive symptoms and disability, a panel vector autoregressive model was used. By taking the first differences, unobserved heterogeneity was taken into account.
In the total sample and in both sexes, we revealed a robust positive association between an initial change in depressive symptoms and subsequent changes in disability. No robust association between an initial change in disability and a subsequent change in depressive symptoms was detected.
Our findings highlight the importance of changes in depressive symptoms for future changes in disability in old age.
Bipolar disorder is a highly heritable polygenic disorder. Recent
enrichment analyses suggest that there may be true risk variants for
bipolar disorder in the expression quantitative trait loci (eQTL) in the
We sought to assess the impact of eQTL variants on bipolar disorder risk
by combining data from both bipolar disorder genome-wide association
studies (GWAS) and brain eQTL.
To detect single nucleotide polymorphisms (SNPs) that influence
expression levels of genes associated with bipolar disorder, we jointly
analysed data from a bipolar disorder GWAS (7481 cases and 9250 controls)
and a genome-wide brain (cortical) eQTL (193 healthy controls) using a
Bayesian statistical method, with independent follow-up replications. The
identified risk SNP was then further tested for association with
hippocampal volume (n = 5775) and cognitive performance
(n = 342) among healthy individuals.
Integrative analysis revealed a significant association between a brain
eQTL rs6088662 on chromosome 20q11.22 and bipolar disorder (log Bayes
factor = 5.48; bipolar disorder P =
5.85×10–5). Follow-up studies across multiple independent
samples confirmed the association of the risk SNP (rs6088662) with gene
expression and bipolar disorder susceptibility (P =
3.54×10–8). Further exploratory analysis revealed that
rs6088662 is also associated with hippocampal volume and cognitive
performance in healthy individuals.
Our findings suggest that 20q11.22 is likely a risk region for bipolar
disorder; they also highlight the informative value of integrating
functional annotation of genetic variants for gene expression in
advancing our understanding of the biological basis underlying complex
disorders, such as bipolar disorder.
Consumption of carbohydrate-containing foods leads to transient postprandial rises in blood glucose concentrations that vary between food types. Higher postprandial glycaemic exposures have particularly been implicated in the development of chronic cardiometabolic diseases. Reducing such diet-related exposures may be beneficial not only for diabetic patients but also for the general population. A variety of markers have been used to track different aspects of glycaemic exposures, with most of the relevant knowledge derived from diabetic patients. The assessment of glycaemic exposures among the non-diabetic population may require other, more sensitive markers. The present report summarises key messages of presentations and related discussions from a workshop organised by Unilever intended to consider currently applied markers of glycaemic exposure. The particular focus of the meeting was to identify the potential applicability of glycaemic exposure markers for studying dietary effects in the non-diabetic population. Workshop participants concluded that markers of glycaemic exposures are sparsely used in intervention studies among non-diabetic populations. Continuous glucose monitoring remains the optimal approach to directly assess glycaemic exposure. Markers of glycaemic exposure such as glycated Hb, fructosamine, glycated albumin, 1,5-anhydroglucitol and advanced glycation end products can be preferred dependent on the aspect of interest (period of exposure and glucose variability). For all the markers of glycaemia, the responsiveness to interventions will probably be smaller among the non-diabetic than among the diabetic population. Further validation and acceptance of existing glycaemic exposure markers applied among the non-diabetic population would aid food innovation and better design of dietary interventions targeting glycaemic exposure.
The Next Generation Transit Survey (NGTS) is a new ground-based survey for transiting exoplanets. Our primary goal is to find the first statistically-significant sample of Neptunes and super-Earths that are bright enough for radial velocity confirmation. By measuring precise masses and radii we will constrain the bulk composition and internal structure of planets that span the transition between the gas giants and terrestrial planets. Our brightest exoplanets will also be suitable for atmospheric characterisation with large facilities such as the VLT, JWST and the E-ELT. NGTS construction began in June 2013, and the survey is due to commence in 2014.
Tuberculosis (TB) in livestock, caused by Mycobacterium bovis, persists in many countries. In the UK and Ireland, efforts to control TB through culling of badgers (Meles meles), the principal wildlife host, have failed and there is significant interest in vaccination of badgers as an alternative or complementary strategy. Using a simulation model, we show that where TB is self-contained within the badger population and there are no external sources of infection, limited-duration vaccination at a high level of efficacy can reduce or even eradicate TB from the badger population. However, where sources of external infection persist, benefits in TB reduction in badgers can only be achieved by ongoing, annual vaccination. Vaccination is likely to be most effective as part of an integrated disease management strategy incorporating a number of different approaches across the entire host community.
Plant sugars are often considered as primary feeding stimuli, conditioning host plant acceptance by herbivorous insects. Of the nine sugars identified from methanolic extracts of seven grass species, only turanose, a sucrose isomer, was negatively correlated with the survival and growth of the noctuid larva of cereal stemborer, Busseola fusca. Sucrose was the most abundant sugar, although it did not vary significantly in concentration among the plant species studied. Using Styrofoam™ cylinders impregnated with increasing concentrations of turanose or sucrose, the two sugars had opposing effects: turanose appeared phagodeterrent while sucrose was phagostimulatory. Electrophysiological studies indicated that B. fusca larvae were able to detect both sugars via their styloconic sensilla located on the mouthparts. The findings indicate that, whereas sucrose is a feeding stimulant and positively influences food choice by B. fusca larvae, turanose negatively contributes to larval food choice. The balance in concentrations of both sugars, however, somehow influences the overall host plant choice made by the larvae. This can partly explain host plant suitability and choice by this caterpillar pest in the field.
Background: Patient involvement is widely acknowledged to be a valuable component in health technology assessment (HTA) and healthcare decision making. However, quantitative approaches to ascertain patients' preferences for treatment endpoints are not yet established. The objective of this study is to introduce the analytic hierarchy process (AHP) as a preference elicitation method in HTA. Based on a systematic literature review on the use of AHP in health care in 2009, the German Institute for Quality and Efficiency in Health Care (IQWiG) initiated an AHP study related to its HTA work in 2010.
Methods: The AHP study included two AHP workshops, one with twelve patients and one with seven healthcare professionals. In these workshops, both patients and professionals rated their preferences with respect to the importance of different endpoints of antidepressant treatment by a pairwise comparison of individual endpoints. These comparisons were performed and evaluated by the AHP method and relative weights were generated for each endpoint.
Results: The AHP study indicates that AHP is a well-structured technique whose cognitive demands were well handled by patients and professionals. The two groups rated some of the included endpoints of antidepressant treatment differently. For both groups, however, the same six of the eleven endpoints analyzed accounted for more than 80 percent of the total weight.
Conclusions: AHP can be used in HTA to give a quantitative dimension to patients' preferences for treatment endpoints. Preference elicitation could provide important information at various stages of HTA and challenge opinions on the importance of endpoints.