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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.
Background: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a frequent cause of healthcare-associated infections (HAIs). The CDC Emerging Infections Program (EIP) conducted population and laboratory-based surveillance of CRPA in selected areas in 8 states from August 1, 2016, through July 31, 2018. We aimed to describe the molecular epidemiology and mechanisms of resistance of CRPA isolates collected through this surveillance. Methods: We defined a case as the first isolate of P. aeruginosa resistant to imipenem, meropenem, or doripenem from the lower respiratory tract, urine, wounds, or normally sterile sites identified from a resident of the EIP catchment area in a 30-day period; EIP sites submitted a systematic random sample of isolates to CDC for further characterization. Of 1,021 CRPA clinical isolates submitted, 707 have been sequenced to date using an Illumina MiSeq. Sequenced genomes were classified using the 7-gene multilocus sequence typing (MLST) scheme, and a core genome MLST (cgMLST) scheme was used to determine phylogeny. Antimicrobial resistance genes were identified using publicly available databases, and chromosomal mechanisms of carbapenem resistance were determined using previously validated genetic markers. Results: There were 189 sequence types (STs) among the 707 sequenced genomes (Fig. 1). The most frequently occurring were high-risk clones ST235 (8.5%) and ST298 (4.7%), which were found across all EIP sites. Carbapenemase genes were identified in 5 (<1%) isolates. Overall, 95.6% of the isolates had chromosomal mutations associated with carbapenem resistance: 93.2% had porinD-associated mutations that decrease membrane permeability to the drugs; 24.8% had mutations associated with overexpression of the multidrug efflux pump MexAB-OprM; and 22.9% had mutations associated with overexpression of the endogenous β-lactamase ampC. More than 1 such chromosomal resistance mutation type was present in 37.8% of the isolates. Conclusions: The diversity of the sequence types demonstrates that HAIs caused by CRPA can arise from a variety of strains and that high-risk clones are broadly disseminated across the EIP sites but are a minority of CRPA strains overall. Carbapenem resistance in P. aeruginosa was predominantly driven by chromosomal mutations rather than acquired mechanisms (ie, carbapenemases). The diversity of the CRPA isolates and the lack of carbapenemase genes suggest that this ubiquitous pathogen can readily evolve chromosomal resistance mechanisms, but unlike carbapenemases, these cannot be easily spread through horizontal transfer.
This study aimed to evaluate risk factors associated with shedding of pathogenic Leptospira species in urine at animal and herd levels. In total, 200 dairy farms were randomly selected from the DairyNZ database. Urine samples were taken from 20 lactating, clinically normal cows in each herd between January and April 2016 and tested by real-time polymerase chain reaction (PCR) using gyrB as the target gene. Overall, 26.5% of 200 farms had at least one PCR positive cow and 2.4% of 4000 cows were shedding Leptospira in the urine. Using a questionnaire, information about risk factors at cow and farm level was collected via face-to-face interviews with farm owners and managers. Animals on all but one farm had been vaccinated against Hardjo and Pomona and cows on 54 of 200 (27%) farms had also been vaccinated against Copenhageni in at least one age group (calves, heifers and cows). Associations found to be statistically significant in univariate analysis (at P < 0.2) were assessed by multivariable logistic regression. Factors associated with shedding included cattle age (Odds ratio (OR) 0.82, 95% CI 0.71–0.95), keeping sheep (OR 5.57, 95% confidence interval (CI) 1.46–21.25) or dogs (OR 1.45, 95% CI 1.07–1.97) and managing milking cows in a single as opposed to multiple groups (OR 0.45, 95% CI 0.20–0.99). We conclude that younger cattle were more likely to be shedding Leptospira than older cattle and that the presence of sheep and dogs was associated with an increased risk of shedding in cows. Larger herds were at higher risk of having Leptospira shedders. However, none of the environmental risk factors that were assessed (e.g. access to standing water, drinking-water source), or wildlife abundance on-farm, or pasture were associated with shedding, possibly due to low statistical power, given the low overall shedding rate.
Hyperspectral soft X-ray emission (SXE) and cathodoluminescence (CL) spectrometry have been used to investigate a carbonaceous-rich geological deposit to understand the crystallinity and morphology of the carbon and the associated quartz. Panchromatic CL maps show both the growth of the quartz and the evidence of recrystallization. A fitted CL map reveals the distribution of Ti4+ within the grains and shows subtle growth zoning, together with radiation halos from 238U decay. The sensitivity of the SXE spectrometer to carbon, together with the anisotropic X-ray emission from highly orientated pyrolytic graphite, has enabled the C Kα peak shape to be used to measure the crystal orientation of individual graphite regions. Mapping has revealed that most grains are predominantly of a single orientation, and a number of graphite grains have been investigated to demonstrate the application of this new SXE technique. A peak fitting approach to analyzing the SXE spectra was developed to project the C Kα 2pz and 2p(x+y) orbital components of the graphite. The shape of these two end-member components is comparable to those produced by electron density of states calculations. The angular sensitivity of the SXE spectrometer has been shown to be comparable to that of electron backscatter diffraction.
To assess the impact of a newly developed Central-Line Insertion Site Assessment (CLISA) score on the incidence of local inflammation or infection for CLABSI prevention.
A pre- and postintervention, quasi-experimental quality improvement study.
Setting and participants:
Adult inpatients with central venous catheters (CVCs) hospitalized in an intensive care unit or oncology ward at a large academic medical center.
We evaluated CLISA score impact on insertion site inflammation and infection (CLISA score of 2 or 3) incidence in the baseline period (June 2014–January 2015) and the intervention period (April 2015–October 2017) using interrupted times series and generalized linear mixed-effects multivariable analyses. These were run separately for days-to-line removal from identification of a CLISA score of 2 or 3. CLISA score interrater reliability and photo quiz results were evaluated.
Among 6,957 CVCs assessed 40,846 times, percentage of lines with CLISA score of 2 or 3 in the baseline and intervention periods decreased by 78.2% (from 22.0% to 4.7%), with a significant immediate decrease in the time-series analysis (P < .001). According to the multivariable regression, the intervention was associated with lower percentage of lines with a CLISA score of 2 or 3, after adjusting for age, gender, CVC body location, and hospital unit (odds ratio, 0.15; 95% confidence interval, 0.06–0.34; P < .001). According to the multivariate regression, days to removal of lines with CLISA score of 2 or 3 was 3.19 days faster after the intervention (P < .001). Also, line dwell time decreased 37.1% from a mean of 14 days (standard deviation [SD], 10.6) to 8.8 days (SD, 9.0) (P < .001). Device utilization ratios decreased 9% from 0.64 (SD, 0.08) to 0.58 (SD, 0.06) (P = .039).
The CLISA score creates a common language for assessing line infection risk and successfully promotes high compliance with best practices in timely line removal.
Declining mortality following invasive pneumococcal disease (IPD) has been observed concurrent with a reduced incidence due to effective pneumococcal conjugate vaccines. However, with IPD now increasing due to serotype replacement, we undertook a statistical analysis to estimate the trend in all-cause 30-day case fatality rate (CFR) in the North East of England (NEE) following IPD. Clinical, microbiological and demographic data were obtained for all laboratory-confirmed IPD cases (April 2006–March 2016) and the adjusted association between CFR and epidemiological year estimated using logistic regression. Of the 2510 episodes of IPD included in the analysis, 486 died within 30 days of IPD (CFR 19%). Increasing age, male sex, a diagnosis of septicaemia, being in ⩾1 clinical risk groups, alcohol abuse and individual serotypes were independently associated with increased CFR. A significant decline in CFR over time was observed following adjustment for these significant predictors (adjusted odds ratio 0.93, 95% confidence interval 0.89–0.98; P = 0.003). A small but significant decline in 30-day all-cause CFR following IPD has been observed in the NEE. Nonetheless, certain population groups remain at increased risk of dying following IPD. Despite the introduction of effective vaccines, further strategies to reduce the ongoing burden of mortality from IPD are needed.
Filamentary structures can form within the beam of protons accelerated during the interaction of an intense laser pulse with an ultrathin foil target. Such behaviour is shown to be dependent upon the formation time of quasi-static magnetic field structures throughout the target volume and the extent of the rear surface proton expansion over the same period. This is observed via both numerical and experimental investigations. By controlling the intensity profile of the laser drive, via the use of two temporally separated pulses, both the initial rear surface proton expansion and magnetic field formation time can be varied, resulting in modification to the degree of filamentary structure present within the laser-driven proton beam.
Antineuronal antibodies are associated with psychosis, although their clinical significance in first episode of psychosis (FEP) is undetermined.
To examine all patients admitted for treatment of FEP for antineuronal antibodies and describe clinical presentations and treatment outcomes in those who were antibody positive.
Individuals admitted for FEP to six mental health units in Queensland, Australia, were prospectively tested for serum antineuronal antibodies. Antibody-positive patients were referred for neurological and immunological assessment and therapy.
Of 113 consenting participants, six had antineuronal antibodies (anti-N-methyl-D-aspartate receptor antibodies [n = 4], voltage-gated potassium channel antibodies [n = 1] and antibodies against uncharacterised antigen [n = 1]). Five received immunotherapy, which prompted resolution of psychosis in four.
A small subgroup of patients admitted to hospital with FEP have antineuronal antibodies detectable in serum and are responsive to immunotherapy. Early diagnosis and treatment is critical to optimise recovery.
The Molonglo Observatory Synthesis Telescope (MOST) is an 18000 m2 radio telescope located 40 km from Canberra, Australia. Its operating band (820–851 MHz) is partly allocated to telecommunications, making radio astronomy challenging. We describe how the deployment of new digital receivers, Field Programmable Gate Array-based filterbanks, and server-class computers equipped with 43 Graphics Processing Units, has transformed the telescope into a versatile new instrument (UTMOST) for studying the radio sky on millisecond timescales. UTMOST has 10 times the bandwidth and double the field of view compared to the MOST, and voltage record and playback capability has facilitated rapid implementaton of many new observing modes, most of which operate commensally. UTMOST can simultaneously excise interference, make maps, coherently dedisperse pulsars, and perform real-time searches of coherent fan-beams for dispersed single pulses. UTMOST operates as a robotic facility, deciding how to efficiently target pulsars and how long to stay on source via real-time pulsar folding, while searching for single pulse events. Regular timing of over 300 pulsars has yielded seven pulsar glitches and three Fast Radio Bursts during commissioning. UTMOST demonstrates that if sufficient signal processing is applied to voltage streams, innovative science remains possible even in hostile radio frequency environments.
The class of radio transients called Fast Radio Bursts (FRBs) encompasses enigmatic single pulses, each unique in its own way, hindering a consensus for their origin. The key to demystifying FRBs lies in discovering many of them in order to identity commonalities – and in real time, in order to find potential counterparts at other wavelengths. The recently upgraded UTMOST in Australia, is undergoing a backend transformation to rise as a fast transient detection machine. The first interferometric detections of FRBs with UTMOST, place their origin beyond the near-field region of the telescope thus ruling out local sources of interference as a possible origin. We have localised these bursts to much better than the ones discovered at the Parkes radio telescope and have plans to upgrade UTMOST to be capable of much better localisation still.
The study purpose was to provide evidence of validity for the Primary Health Care Engagement (PHCE) Scale, based on exploratory factor analysis and reliability findings from a large national survey of regulated nurses residing and working in rural and remote Canadian communities.
There are currently no published provider-level instruments to adequately assess delivery of community-based primary health care, relevant to ongoing primary health care (PHC) reform strategies across Canada and elsewhere. The PHCE Scale reflects a contemporary approach that emphasizes community-oriented and community-based elements of PHC delivery.
Data from the pan-Canadian Nursing Practice in Rural and Remote Canada II (RRNII) survey were used to conduct an exploratory factor analysis and evaluate the internal consistency reliability of the final PHCE Scale.
The RRNII survey sample included 1587 registered nurses, nurse practitioners, licensed practical nurses, and registered psychiatric nurses residing and working in rural and remote Canada. Exploratory factor analysis identified an eight-factor structure across 28 items overall, and good internal consistency reliability was indicated by an α estimate of 0.89 for the final scale. The final 28-item PHCE Scale includes three of four elements in a contemporary approach to PHC (accessibility/availability, community participation, and intersectoral team) and most community-oriented/based elements of PHC (interdisciplinary collaboration, person-centred, continuity, population orientation, and quality improvement). We recommend additional psychometric testing in a range of health care providers and settings, as the PHCE Scale shows promise as a tool for health care planners and researchers to test interventions and track progress in primary health care reform.
To achieve their conservation goals individuals, communities and organizations need to acquire a diversity of skills, knowledge and information (i.e. capacity). Despite current efforts to build and maintain appropriate levels of conservation capacity, it has been recognized that there will need to be a significant scaling-up of these activities in sub-Saharan Africa. This is because of the rapid increase in the number and extent of environmental problems in the region. We present a range of socio-economic contexts relevant to four key areas of African conservation capacity building: protected area management, community engagement, effective leadership, and professional e-learning. Under these core themes, 39 specific recommendations are presented. These were derived from multi-stakeholder workshop discussions at an international conference held in Nairobi, Kenya, in 2015. At the meeting 185 delegates (practitioners, scientists, community groups and government agencies) represented 105 organizations from 24 African nations and eight non-African nations. The 39 recommendations constituted six broad types of suggested action: (1) the development of new methods, (2) the provision of capacity building resources (e.g. information or data), (3) the communication of ideas or examples of successful initiatives, (4) the implementation of new research or gap analyses, (5) the establishment of new structures within and between organizations, and (6) the development of new partnerships. A number of cross-cutting issues also emerged from the discussions: the need for a greater sense of urgency in developing capacity building activities; the need to develop novel capacity building methodologies; and the need to move away from one-size-fits-all approaches.
Accurate models of X-ray absorption and re-emission in partly stripped ions are necessary to calculate the structure of stars, the performance of hohlraums for inertial confinement fusion and many other systems in high-energy-density plasma physics. Despite theoretical progress, a persistent discrepancy exists with recent experiments at the Sandia Z facility studying iron in conditions characteristic of the solar radiative–convective transition region. The increased iron opacity measured at Z could help resolve a longstanding issue with the standard solar model, but requires a radical departure for opacity theory. To replicate the Z measurements, an opacity experiment has been designed for the National Facility (NIF). The design uses established techniques scaled to NIF. A laser-heated hohlraum will produce X-ray-heated uniform iron plasmas in local thermodynamic equilibrium (LTE) at temperatures
eV and electron densities
. The iron will be probed using continuum X-rays emitted in a
diameter source from a 2 mm diameter polystyrene (CH) capsule implosion. In this design,
of the NIF beams deliver 500 kJ to the
mm diameter hohlraum, and the remaining
directly drive the CH capsule with 200 kJ. Calculations indicate this capsule backlighter should outshine the iron sample, delivering a point-projection transmission opacity measurement to a time-integrated X-ray spectrometer viewing down the hohlraum axis. Preliminary experiments to develop the backlighter and hohlraum are underway, informing simulated measurements to guide the final design.
We describe the performance of the Boolardy Engineering Test Array, the prototype for the Australian Square Kilometre Array Pathfinder telescope. Boolardy Engineering Test Array is the first aperture synthesis radio telescope to use phased array feed technology, giving it the ability to electronically form up to nine dual-polarisation beams. We report the methods developed for forming and measuring the beams, and the adaptations that have been made to the traditional calibration and imaging procedures in order to allow BETA to function as a multi-beam aperture synthesis telescope. We describe the commissioning of the instrument and present details of Boolardy Engineering Test Array’s performance: sensitivity, beam characteristics, polarimetric properties, and image quality. We summarise the astronomical science that it has produced and draw lessons from operating Boolardy Engineering Test Array that will be relevant to the commissioning and operation of the final Australian Square Kilometre Array Path telescope.
Skin and soft tissue infections (SSTIs) due to Staphylococcus aureus have become increasingly common in the outpatient setting; however, risk factors for differentiating methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) SSTIs are needed to better inform antibiotic treatment decisions. We performed a case-case-control study within 14 primary-care clinics in South Texas from 2007 to 2015. Overall, 325 patients [S. aureus SSTI cases (case group 1, n = 175); MRSA SSTI cases (case group 2, n = 115); MSSA SSTI cases (case group 3, n = 60); uninfected control group (control, n = 150)] were evaluated. Each case group was compared to the control group, and then qualitatively contrasted to identify unique risk factors associated with S. aureus, MRSA, and MSSA SSTIs. Overall, prior SSTIs [adjusted odds ratio (aOR) 7·60, 95% confidence interval (CI) 3·31–17·45], male gender (aOR 1·74, 95% CI 1·06–2·85), and absence of healthcare occupation status (aOR 0·14, 95% CI 0·03–0·68) were independently associated with S. aureus SSTIs. The only unique risk factor for community-associated (CA)-MRSA SSTIs was a high body weight (⩾110 kg) (aOR 2·03, 95% CI 1·01–4·09).
Many adults with autism spectrum disorder (ASD) remain undiagnosed. Specialist assessment clinics enable the detection of these cases, but such services are often overstretched. It has been proposed that unnecessary referrals to these services could be reduced by prioritizing individuals who score highly on the Autism-Spectrum Quotient (AQ), a self-report questionnaire measure of autistic traits. However, the ability of the AQ to predict who will go on to receive a diagnosis of ASD in adults is unclear.
We studied 476 adults, seen consecutively at a national ASD diagnostic referral service for suspected ASD. We tested AQ scores as predictors of ASD diagnosis made by expert clinicians according to International Classification of Diseases (ICD)-10 criteria, informed by the Autism Diagnostic Observation Schedule-Generic (ADOS-G) and Autism Diagnostic Interview-Revised (ADI-R) assessments.
Of the participants, 73% received a clinical diagnosis of ASD. Self-report AQ scores did not significantly predict receipt of a diagnosis. While AQ scores provided high sensitivity of 0.77 [95% confidence interval (CI) 0.72–0.82] and positive predictive value of 0.76 (95% CI 0.70–0.80), the specificity of 0.29 (95% CI 0.20–0.38) and negative predictive value of 0.36 (95% CI 0.22–0.40) were low. Thus, 64% of those who scored below the AQ cut-off were ‘false negatives’ who did in fact have ASD. Co-morbidity data revealed that generalized anxiety disorder may ‘mimic’ ASD and inflate AQ scores, leading to false positives.
The AQ's utility for screening referrals was limited in this sample. Recommendations supporting the AQ's role in the assessment of adult ASD, e.g. UK NICE guidelines, may need to be reconsidered.