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To describe the epidemiology of carbapenem-resistant Enterobacterales (CRE) bacteriuria and to determine whether urinary catheters increase the risk of subsequent CRE bacteremia.
Using active population- and laboratory-based surveillance we described a cohort of patients with incident CRE bacteriuria and identified risk factors for developing CRE bacteremia within 1 year.
The study was conducted among the 8 counties of Georgia Health District 3 (HD3) in Atlanta, Georgia.
Residents of HD3 with CRE first identified in urine between 2012 and 2017.
We identified 464 patients with CRE bacteriuria (mean yearly incidence, 1.96 cases per 100,000 population). Of 425 with chart review, most had a urinary catheter (56%), and many resided in long-term care facilities (48%), had a Charlson comorbidity index >3 (38%) or a decubitus ulcer (37%). 21 patients (5%) developed CRE bacteremia with the same organism within 1 year. Risk factors for subsequent bacteremia included presence of a urinary catheter (odds ratio [OR], 8.0; 95% confidence interval [CI], 1.8–34.9), central venous catheter (OR, 4.3; 95% CI, 1.7–10.6) or another indwelling device (OR, 4.3; 95% CI, 1.6–11.4), urine culture obtained as an inpatient (OR, 5.7; 95% CI, 1.3–25.9), and being in the ICU in the week prior to urine culture (OR, 2.9; 95% CI, 1.1–7.8). In a multivariable analysis, urinary catheter increased the risk of CRE bacteremia (OR, 5.3; 95% CI, 1.2–23.6).
In patients with CRE bacteriuria, urinary catheters increase the risk of CRE bacteremia. Future interventions should aim to reduce inappropriate insertion and early removal of urinary catheters.
Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
Background: Carbapenem-resistant Enterobacteriaceae (CRE) represent a significant antibiotic resistance threat, in part because carbapenemase genes can spread on mobile genetic elements. Here, we describe the molecular epidemiology and outcomes of patients with CRE bacteriuria from the same city in a nonoutbreak setting. Methods: The Georgia Emerging Infections Program performs active, population-based CRE surveillance in Atlanta. We studied a cohort of patients with CRE (resistant to all tested third-generation cephalosporins and ≥1 carbapenem, excluding ertapenem) first identified in urine, and not in a prior or simultaneous sterile site, between 2012 and 2015. Whole-genome sequencing (WGS) was performed on a convenience sample. We obtained epidemiologic and outcome data through chart review and Georgia Vital Statistics records (90-day mortality). Using WGS, we created a core-genome alignment-based phylogenetic tree of the Klebsiella pneumoniae isolates and calculated the SNP difference between each sample. Using SAS version 9.4 software, we performed the Fisher exact test and univariable odds ratios (OR) with 95% CI to compare patient isolates with and without a carbapenemase gene. Results: Among 81 patients included, the median age was 68 (IQR, 57–74) years, and most were female (58%), black (60%), and resided in a long-term care facility 4 days prior to culture isolation (53%). Organisms isolated were K. pneumoniae (84%), Escherichia coli (7%), Enterobacter cloacae (7%), and Klebsiella oxytoca (1%). WGS identified at least 1 β-lactamase gene in 91% of the isolates; 85% contained a carbapenemase gene, the most frequent of which was blaKPC-3 (94%). Patients with CRE containing a carbapenemase gene were more likely to be black (OR, 3.7; 95% CI, 1.0–13.8) and to have K. pneumoniae (OR, 8.9; 95% CI, 2.2–35.0). Using a core-genome alignment of 3,708 genes (~63% of the complete genome), we identified a median of 67 (IQR, 23–3,881) SNP differences between each K. pneumoniae isolate. A phylogenetic tree identified clustering around carbapenemase gene and multilocus sequence type (84% were ST 258) but not based on referring laboratory or county of residence (Fig. 1). Although 7% of patients developed an invasive CRE infection within 1 year and 21% died within 90 days, having a carbapenemase gene was not associated with these outcomes. Conclusions: Molecular sequencing of a convenience sample of CRE bacteriuria support K. pneumoniae ST258 harboring blaKPC-3 being distributed throughout the Atlanta area, across the healthcare continuum. Overall mortality was high in this population, but the presence of carbapenemase genes was not associated with worse outcomes.
Many studies demonstrate that marriage protects against risky alcohol use and moderates genetic influences on alcohol outcomes; however, previous work has not considered these effects from a developmental perspective or in high-risk individuals. These represent important gaps, as it cannot be assumed that marriage has uniform effects across development or in high-risk samples. We took a longitudinal developmental approach to examine whether marital status was associated with heavy episodic drinking (HED), and whether marital status moderated polygenic influences on HED. Our sample included 937 individuals (53.25% female) from the Collaborative Study on the Genetics of Alcoholism who reported their HED and marital status biennially between the ages of 21 and 25. Polygenic risk scores (PRS) were derived from a genome-wide association study of alcohol consumption. Marital status was not associated with HED; however, we observed pathogenic gene-by-environment effects that changed across young adulthood. Among those who married young (age 21), individuals with higher PRS reported more HED; however, these effects decayed over time. The same pattern was found in supplementary analyses using parental history of alcohol use disorder as the index of genetic liability. Our findings indicate that early marriage may exacerbate risk for those with higher polygenic load.
World War II sparked cultural and material transformations to American food and agriculture. Indeed, even before the United States formally entered the war in December 1941, American farmers played a critical role in supplying its Allies with foodstuffs. The war recast farming as an act of national security, for the animals and plants raised on American farms were critical to the war effort. Some wartime changes were short-lived. But others, such as the movement of farm laborers to industrial work in the West and North, and the technological developments facilitated by war-funded research, would have long-lasting effects. The war induced demand for farm crops and created labor shortages that required farmers to make new choices about how they tilled soil and which technologies they used to do it. Further, the higher farm prices farmers earned during the war years made it possible for them to invest in new technologies. By familiarizing farmers with new crops and technologies, the effects of World War II on the nation’s rural environment were profound, and they unfolded for decades after the Axis powers surrendered.
UK Biobank is a well-characterised cohort of over 500 000 participants including genetics, environmental data and imaging. An online mental health questionnaire was designed for UK Biobank participants to expand its potential.
Describe the development, implementation and results of this questionnaire.
An expert working group designed the questionnaire, using established measures where possible, and consulting a patient group. Operational criteria were agreed for defining likely disorder and risk states, including lifetime depression, mania/hypomania, generalised anxiety disorder, unusual experiences and self-harm, and current post-traumatic stress and hazardous/harmful alcohol use.
A total of 157 366 completed online questionnaires were available by August 2017. Participants were aged 45–82 (53% were ≥65 years) and 57% women. Comparison of self-reported diagnosed mental disorder with a contemporary study shows a similar prevalence, despite respondents being of higher average socioeconomic status. Lifetime depression was a common finding, with 24% (37 434) of participants meeting criteria and current hazardous/harmful alcohol use criteria were met by 21% (32 602), whereas other criteria were met by less than 8% of the participants. There was extensive comorbidity among the syndromes. Mental disorders were associated with a high neuroticism score, adverse life events and long-term illness; addiction and bipolar affective disorder in particular were associated with measures of deprivation.
The UK Biobank questionnaire represents a very large mental health survey in itself, and the results presented here show high face validity, although caution is needed because of selection bias. Built into UK Biobank, these data intersect with other health data to offer unparalleled potential for crosscutting biomedical research involving mental health.
Major depressive disorder and neuroticism (Neu) share a large genetic basis. We sought to determine whether this shared basis could be decomposed to identify genetic factors that are specific to depression.
We analysed summary statistics from genome-wide association studies (GWAS) of depression (from the Psychiatric Genomics Consortium, 23andMe and UK Biobank) and compared them with GWAS of Neu (from UK Biobank). First, we used a pairwise GWAS analysis to classify variants as associated with only depression, with only Neu or with both. Second, we estimated partial genetic correlations to test whether the depression's genetic link with other phenotypes was explained by shared overlap with Neu.
We found evidence that most genomic regions (25/37) associated with depression are likely to be shared with Neu. The overlapping common genetic variance of depression and Neu was genetically correlated primarily with psychiatric disorders. We found that the genetic contributions to depression, that were not shared with Neu, were positively correlated with metabolic phenotypes and cardiovascular disease, and negatively correlated with the personality trait conscientiousness. After removing shared genetic overlap with Neu, depression still had a specific association with schizophrenia, bipolar disorder, coronary artery disease and age of first birth. Independent of depression, Neu had specific genetic correlates in ulcerative colitis, pubertal growth, anorexia and education.
Our findings demonstrate that, while genetic risk factors for depression are largely shared with Neu, there are also non-Neu-related features of depression that may be useful for further patient or phenotypic stratification.
The Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) cohort study of the Canadian Consortium on Neurodegeneration in Aging (CCNA) is a national initiative to catalyze research on dementia, set up to support the research agendas of CCNA teams. This cross-country longitudinal cohort of 2310 deeply phenotyped subjects with various forms of dementia and mild memory loss or concerns, along with cognitively intact elderly subjects, will test hypotheses generated by these teams.
The COMPASS-ND protocol, initial grant proposal for funding, fifth semi-annual CCNA Progress Report submitted to the Canadian Institutes of Health Research December 2017, and other documents supplemented by modifications made and lessons learned after implementation were used by the authors to create the description of the study provided here.
The CCNA COMPASS-ND cohort includes participants from across Canada with various cognitive conditions associated with or at risk of neurodegenerative diseases. They will undergo a wide range of experimental, clinical, imaging, and genetic investigation to specifically address the causes, diagnosis, treatment, and prevention of these conditions in the aging population. Data derived from clinical and cognitive assessments, biospecimens, brain imaging, genetics, and brain donations will be used to test hypotheses generated by CCNA research teams and other Canadian researchers. The study is the most comprehensive and ambitious Canadian study of dementia. Initial data posting occurred in 2018, with the full cohort to be accrued by 2020.
Availability of data from the COMPASS-ND study will provide a major stimulus for dementia research in Canada in the coming years.
Breakthrough Listen is a 10-yr initiative to search for signatures of technologies created by extraterrestrial civilisations at radio and optical wavelengths. Here, we detail the digital data recording system deployed for Breakthrough Listen observations at the 64-m aperture CSIRO Parkes Telescope in New South Wales, Australia. The recording system currently implements two modes: a dual-polarisation, 1.125-GHz bandwidth mode for single-beam observations, and a 26-input, 308-MHz bandwidth mode for the 21-cm multibeam receiver. The system is also designed to support a 3-GHz single-beam mode for the forthcoming Parkes ultra-wideband feed. In this paper, we present details of the system architecture, provide an overview of hardware and software, and present initial performance results.
UK Biobank is a well-characterised cohort of over 500 000 participants that offers unique opportunities to investigate multiple diseases and risk factors.
An online mental health questionnaire completed by UK Biobank participants was expected to expand the potential for research into mental disorders.
An expert working group designed the questionnaire, using established measures where possible, and consulting with a patient group regarding acceptability. Case definitions were defined using operational criteria for lifetime depression, mania, anxiety disorder, psychotic-like experiences and self-harm, as well as current post-traumatic stress and alcohol use disorders.
157 366 completed online questionnaires were available by August 2017. Comparison of self-reported diagnosed mental disorder with a contemporary study shows a similar prevalence, despite respondents being of higher average socioeconomic status than the general population across a range of indicators. Thirty-five per cent (55 750) of participants had at least one defined syndrome, of which lifetime depression was the most common at 24% (37 434). There was extensive comorbidity among the syndromes. Mental disorders were associated with high neuroticism score, adverse life events and long-term illness; addiction and bipolar affective disorder in particular were associated with measures of deprivation.
The questionnaire represents a very large mental health survey in itself, and the results presented here show high face validity, although caution is needed owing to selection bias. Built into UK Biobank, these data intersect with other health data to offer unparalleled potential for crosscutting biomedical research involving mental health.
Declaration of interest
G.B. received grants from the National Institute for Health Research during the study; and support from Illumina Ltd. and the European Commission outside the submitted work. B.C. received grants from the Scottish Executive Chief Scientist Office and from The Dr Mortimer and Theresa Sackler Foundation during the study. C.S. received grants from the Medical Research Council and Wellcome Trust during the study, and is the Chief Scientist for UK Biobank. M.H. received grants from the Innovative Medicines Initiative via the RADAR-CNS programme and personal fees as an expert witness outside the submitted work.
We present a snapshot of our ongoing investigation of molecular clouds in Clump 2 located in the Galactic Bar region at a projected distance of ~400pc from the Galactic Center. We show that the analysis of the Clump 2 molecular clouds is complicated because of many fore- and background clouds in the line of sight. Of all clouds, IGGC 22 is the most interesting one, showing very high dust column densities, significant high-J CO emission, and, potentially harbors star formations as eluded to by the detection of [OIII] emission.
Insulating silicon dioxide (SiO2) films can be produced by hydrolysis of metal alkoxide tetraethylorthosilicate (TEOS) in the presence of an acid catalyst in supercritical fluid CO2 (sc-CO2). In this study, SiO2 films are formed on different substrates using TEOS as a source of silicon, and acetic acid (HAc) as a catalyst. Water required for the hydrolysis reaction is from in situ generation of esterification and condensation reactions involving HAc and the alcohol produced. The acid catalyzed deposition reaction actually starts at room temperature but produces decent films in sc-CO2 at moderately high temperatures (e.g. 50 °C). Supercritical fluid CO2 is known to have near zero surface tension and provides an ideal medium for fabrication of SiO2 films. Formation of SiO2 films via hydrolysis reaction in sc-CO2 is more rapid compared to the traditional hydrolysis reaction at room temperature. In general, metal alkoxide hydrolysis reactions carried out in a closed sc-CO2 system is not affected by moisture in air compared with traditional open-air hydrolysis systems. Using sc-CO2 as a reaction medium can eliminate undesirable organic solvents utilized in traditional alkoxide hydrolysis reactions.
X-ray diffraction (XRD) and electron diffraction (ED) measurements demonstrated that the SiO2 films produced are amorphous. Energy dispersive spectroscopy (EDS), attenuated total reflectance-Fourier transform infrared (ATR-FTIR) and X-ray photoelectron (XPS) spectroscopy show elemental compositions of the films formed on the substrate surfaces to be SiO2. Film thickness formation by controlling the amount of the catalyst is discussed.
Disorders of intellectual development: comorbidity and complications
Marc Woodbury-Smith, Associate Professor and CIHR Clinician- Scientist, Departments of Psychiatry & Behavioural Neurosciences,
Howard Ring, University Lecturer, Department of Psychiatry, University of Cambridge, UK
Epilepsy is a common, often chronic neuropsychiatric disorder that sits firmly between the disciplines of neurology and psychiatry. A detailed lexicon has evolved to capture the phenomenology of seizures, and there is increasing understanding of the complex relationship between seizures and associated psychological and behavioural manifestations, as well as frank psychiatric comorbidity. This has facilitated their earlier management. Moreover, research has continued to make significant progress in identifying genetic and metabolic factors that contribute to the aetiology of epilepsy.
Epilepsy is notably more prevalent among individuals with disorders of intellectual development (DID). Disproportionate severity in all the neuropsychiatric characteristics of epilepsy, compounded by unique challenges in diagnosis and management, occur in this population. In this chapter, those aspects of epilepsy that are most relevant to this population will be discussed.
Epilepsy is a common neuropsychiatric disorder characterised by episodic disturbances of consciousness, sensorimotor function, behaviour and emotion resulting from paroxysmal abnormalities of the electrical activity of the brain. While the seizure itself is described by the symptomatic disturbance, the term ‘epilepsy’ is used when seizures become recurrent, more specifically when there are two unprovoked seizures more than 24 hours apart. The prevalence of epilepsy in the general population is 0.5–1.0% (Banerjee et al, 2009), and the lifetime prevalence is 1.5–5.0%. Among those with DID, however, this prevalence is increased severalfold. For example, among those with severe DID (IQ<50), a prevalence of 30% has been reported, and even among those with milder DID (IQ≥50), the prevalence is still relatively high, at 15% or more (Hannah & Brodie, 1998; Lhatoo & Sander, 2001; McGrother et al, 2006). The risk appears to be higher among those with additional neurological diagnoses, such as cerebral palsy (Singhi et al, 2003), and among those with autism spectrum disorder (ASD) (Spence & Schneider, 2009). As will be discussed below, the prevalence is also higher in association with particular genetic intellectual disability syndromes. Also of note is that the prevalence of the psychological, behavioural and psychiatric manifestations associated with epilepsy are more frequent among those with DID.
Gaia's Radial Velocity Spectrometer (RVS) has been operating in routine phase for over one year since initial commissioning. RVS continues to work well but the higher than expected levels of straylight reduce the limiting magnitude. The end-of-mission radial-velocity (RV) performance requirement for G2V stars was 15 km s−1 at V = 16.5 mag. Instead, 15 km s−1 precision is achieved at 15 < V < 16 mag, consistent with simulations that predict a loss of 1.4 mag. Simulations also suggest that changes to Gaia's onboard software could recover ~0.14 mag of this loss. Consequently Gaia's onboard software was upgraded in April 2015. The status of this new commissioning period is presented, as well as the latest scientific performance of the on-ground processing of RVS spectra. We illustrate the implications of the RVS limiting magnitude on Gaia's view of the Milky Way's halo in 6D using the Gaia Universe Model Snapshot (GUMS).