Pseudomonas guariconensis Necrotizing Fasciitis, United Kingdom.

We describe a case of necrotizing fasciitis in the United Kingdom in which Pseudomonas guariconensis was isolated from multiple blood culture and tissue samples. The organism carried a Verona integron-encoded metallo-ß-lactamase gene and evidence of decreased susceptibility to ß-lactam antimicrobial agents. Clinicians should use caution when treating infection caused by this rare pathogen.

Identifying the public health needs of a UK probation cohort: a cross-sectional analysis.

BACKGROUND: The health needs of those under probation are likely high, but they have received very little public health attention. Limited evidence exists on the public health needs and interventions to support this cohort. METHODS: Surveys were completed by 257 people on probation as part of a local health needs assessment. Results were compared with the general population responses from the National Survey for Wales (2021-22). RESULTS: People on probation were 4.2 times more likely to self-report not-good general health (fair, bad or very bad) than the general population (adjusted Odds Ratio [aOR] 4.2, 95% Confidence Intervals [CI] 3.2-5.4). The odds of having a mental health condition were over eight times higher than the general population (aOR 8.8, 95% CI 6.8-11.4). Prevalence of smoking (52%), drug use (60%), attention-deficit hyperactivity disorder (21%), autism (4%) and dyslexia (15%) were all higher than the general population. General Practitioner usage and hospital stays were higher, but dentist or optician usage lower than the general population (P < 0.05). Emergency departments were accessed by 35%, with 9% frequenting them three or more times. CONCLUSIONS: People on probation have poorer self-reported health, higher prevalence of unhealthy behaviours and higher accessing of reactive health services than the general population.

Self-configuring nnU-Net for automatic delineation of the organs at risk and target in high-dose rate cervical brachytherapy, a low/middle-income country's experience.

BACKGROUND: The high-dose rate (HDR) brachytherapy treatment planning workflow for cervical cancer is a labor-intensive, time-consuming, and expertise-driven process. These issues are amplified in low/middle-income countries with large deficits in experienced healthcare professionals. Automation has the ability to substantially reduce bottlenecks in the planning process but often require a high level of expertise to develop. PURPOSE: To implement the out of the box self-configuring nnU-Net package for the auto-segmentation of the organs at risk (OARs) and high-risk CTV (HR CTV) for Ring-Tandem (R-T) HDR cervical brachytherapy treatment planning. METHODS: The computed tomography (CT) scans of 100 previously treated patients were used to train and test three different nnU-Net configurations (2D, 3DFR, and 3DCasc). The performance of the models was evaluated by calculating the Sørensen-dice similarity coefficient, Hausdorff distance (HD), 95th percentile Hausdorff distance, mean surface distance (MSD), and precision score for 20 test patients. The dosimetric accuracy between the manual and predicted contours was assessed by looking at the various dose volume histogram (DVH) parameters and volume differences. Three different radiation oncologists (ROs) scored the predicted bladder, rectum, and HR CTV contours generated by the best performing model. The manual contouring, prediction, and editing times were recorded. RESULTS: The mean DSC, HD, HD95, MSD and precision scores for our best performing model (3DFR) were 0.92/7.5 mm/3.0 mm/ 0.8 mm/0.91 for the bladder, 0.84/13.8 mm/5.3 mm/1.4 mm/0.84 for the rectum, and 0.81/8.5 mm/6.0 mm/2.2 mm/0.80 for the HR CTV. Mean dose differences (D2cc/90% ) and volume differences were 0.08 Gy/1.3 cm3 for the bladder, 0.02 Gy/0.7 cm3 for the rectum, and 0.33 Gy/1.5 cm3 for the HR CTV. On average, 65% of the generated contours were clinically acceptable, 33% requiring minor edits, 2% required major edits, and no contours were rejected. Average manual contouring time was 14.0 min, while the average prediction and editing times were 1.6 and 2.1 min, respectively. CONCLUSION: Our best performing model (3DFR) provided fast accurate auto generated OARs and HR CTV contours with a large clinical acceptance rate.

An epidemiological investigation of COVID-19 outbreaks in a group of care homes in Wales, UK: a retrospective cohort study.

BACKGROUND: This study describes the epidemiology of COVID-19 outbreaks in four care homes in terms of spread, severity, presentation and interventions. METHODS: Participants were 100 residents and 102 staff from four co-located care homes in Wales. Data were collected from the homes and Public Health Wales, including demographics, presentations, test status and results, hospital admissions and deaths. Genomic sequencing of confirmed case samples was completed, where possible. Epi-curves, crude attack rates, a Kaplan-Meier survival curve and adjusted hazard ratios were calculated using R. RESULTS: About 14 confirmed and 43 possible resident cases, 23 confirmed and 47 possible staff cases occurred. Crude attack rates of possible and confirmed cases were 57% (residents) and 69% (staff). Genomic sequencing for 10 confirmed case PCR samples identified at least 5 different UK lineages of COVID-19.42 (42%) residents died, 23 (55%) with COVID-19 or suspected COVID-19 recorded on the death certificate. The hazard ratio for death amongst resident possible and confirmed cases compared to null cases, adjusting for age and sex, was 13.26 (95% CI 5.61-31.34). CONCLUSIONS: There were extensive outbreaks of COVID-19 in these homes with high crude attack rates and deaths. Universal testing and early isolation of residents are recommended.

Preventive Nail Care Among Diabetic Patients: A Quality Improvement Initiative.

PURPOSE: The purpose of this quality improvement initiative was to increase adherence to follow-up appointments in patients with diabetes mellitus for prevention of diabetic foot ulcers. PARTICIPANTS AND SETTING: The sample comprised 33 adults with diabetes mellitus being cared for at an outpatient wound care clinic affiliated with a large metropolitan hospital in the state of Mississippi, located in the Southern United States. APPROACH: This quality improvement approach used the Plan-Do-Study-Act method. Educational flyers and verbal instruction were provided to enhance adherence to preventive nail care and follow-up appointments. The goal for this quality improvement initiative was to increase adherence with preventive nail care and follow-up care. OUTCOMES: Participants were provided with educational flyers and verbal instruction that emphasized the importance of follow-up clinic appointments, which promoted increased attendance at follow-up appointments. The proportion of patients who did not attend follow-up appointments fell from 9.2% prior to the intervention to 5.8% after its introduction. IMPLICATIONS FOR PRACTICE: This quality improvement initiative positively impacted practice at a local wound care clinic in Mississippi resulting in a clinically relevant reduction in no-show follow-up visits when compared to the previous year.

Trade-Offs between Antibacterial Resistance and Fitness Cost in the Production of Metallo-ß-Lactamases by Enteric Bacteria Manifest as Sporadic Emergence of Carbapenem Resistance in a Clinical Setting.

Meropenem is a clinically important antibacterial reserved for treatment of multiresistant infections. In meropenem-resistant bacteria of the family Enterobacterales, NDM-1 is considerably more common than IMP-1, despite both metallo-ß-lactamases (MBLs) hydrolyzing meropenem with almost identical kinetics. We show that blaNDM-1 consistently confers meropenem resistance in wild-type Enterobacterales, but blaIMP-1 does not. The reason is higher blaNDM-1 expression because of its stronger promoter. However, the cost of meropenem resistance is reduced fitness of blaNDM-1-positive Enterobacterales. In parallel, from a clinical case, we identified multiple Enterobacter spp. isolates carrying a plasmid-encoded blaNDM-1 having a modified promoter region. This modification lowered MBL production to a level associated with zero fitness cost, but, consequently, the isolates were not meropenem resistant. However, we identified a Klebsiella pneumoniae isolate from this same clinical case carrying the same blaNDM-1 plasmid. This isolate was meropenem resistant despite low-level NDM-1 production because of a ramR mutation reducing envelope permeability. Overall, therefore, we show how the resistance/fitness trade-off for MBL carriage can be resolved. The result is sporadic emergence of meropenem resistance in a clinical setting.

Limited phylogenetic overlap between fluoroquinolone-resistant Escherichia coli isolated on dairy farms and those causing bacteriuria in humans living in the same geographical region.

BACKGROUND: Our primary aim was to test whether cattle-associated fluoroquinolone-resistant (FQ-R) Escherichia coli found on dairy farms are closely phylogenetically related to those causing bacteriuria in humans living in the same 50 × 50 km geographical region suggestive of farm-human sharing. Another aim was to identify risk factors for the presence of FQ-R E. coli on dairy farms. METHODS: FQ-R E. coli were isolated during 2017-18 from 42 dairy farms and from community urine samples. Forty-two cattle and 489 human urinary isolates were subjected to WGS, allowing phylogenetic comparisons. Risk factors were identified using a Bayesian regularization approach. RESULTS: Of 489 FQ-R human isolates, 255 were also third-generation-cephalosporin-resistant, with strong genetic linkage between aac(6')Ib-cr and blaCTX-M-15. We identified possible farm-human sharing for pairs of ST744 and ST162 isolates, but minimal core genome SNP distances were larger between farm-human pairs of ST744 and ST162 isolates (71 and 63 SNPs, respectively) than between pairs of isolates from different farms (7 and 3 SNPs, respectively). Total farm fluoroquinolone use showed a positive association with the odds of isolating FQ-R E. coli, while total dry cow therapy use showed a negative association. CONCLUSIONS: This work suggests that FQ-R E. coli found on dairy farms have a limited impact on community bacteriuria within the local human population. Reducing fluoroquinolone use may reduce the on-farm prevalence of FQ-R E. coli and this reduction may be greater when dry cow therapy is targeted to the ecology of resistant E. coli on the farm.

One-Year Retrospective Review of Psychiatric Consultations in Lassa Fever, Southern Nigeria.

We conducted a retrospective review of psychiatric consultations for hospitalized patients with Lassa fever in southern Nigeria. Ten (8.8%) of 113 patients had psychiatric consultations. Delirium was the most common psychiatric manifestation complicating Lassa fever. Findings suggest that psychiatric intervention could improve overall outcomes of Lassa fever.

Conductivity Induced by High-Field Terahertz Waves in Dielectric Material.

An intense, subpicosecond, relativistic electron beam traversing a dielectric-lined waveguide generates very large amplitude electric fields at terahertz (THz) frequencies through the wakefield mechanism. In recent work employing this technique to accelerate charged particles, the generation of high-power, narrow-band THz radiation was demonstrated. The radiated waves contain fields with measured amplitude exceeding 2 GV/m, orders of magnitude greater than those available by other THz generation techniques at a narrow bandwidth. For fields approaching the GV/m level, a strong damping has been observed in SiO_{2}. This wave attenuation with an onset near 850 MV/m is consistent with changes to the conductivity of the dielectric lining and is characterized by a distinctive latching mechanism that is reversible on longer timescales. We describe the detailed measurements that serve to clarify the underlying physical mechanisms leading to strong field-induced damping of THz radiation (hω=1.59 meV, f=0.38 THz) in SiO_{2}, a bulk, wide band-gap (8.9 eV) dielectric.

Acute management of cellulitis: A review.

Cellulitis is an acute localised skin infection, usually accompanied by symptoms such as fever and rigors, nausea, and vomiting. It most commonly affects the lower limbs, although it can involve any part of the skin. It presents as area of redness and inflammation of the skin, with associated pain and swelling.

Prediction of Fluoroquinolone Susceptibility Directly from Whole-Genome Sequence Data by Using Liquid Chromatography-Tandem Mass Spectrometry To Identify Mutant Genotypes.

Fluoroquinolone resistance in Gram-negative bacteria is multifactorial, involving target site mutations, reductions in fluoroquinolone entry due to reduced porin production, increased fluoroquinolone efflux, enzymes that modify fluoroquinolones, and Qnr, a DNA mimic that protects the drug target from fluoroquinolone binding. Here we report a comprehensive analysis, using transformation and in vitro mutant selection, of the relative importance of each of these mechanisms for fluoroquinolone nonsusceptibility using Klebsiella pneumoniae as a model system. Our improved biological understanding was then used to generate 47 rules that can predict fluoroquinolone susceptibility in K. pneumoniae clinical isolates. Key to the success of this predictive process was the use of liquid chromatography-tandem mass spectrometry to measure the abundance of proteins in extracts of cultured bacteria, identifying which sequence variants seen in the whole-genome sequence data were functionally important in the context of fluoroquinolone susceptibility.

Experimental Characterization of Electron-Beam-Driven Wakefield Modes in a Dielectric-Woodpile Cartesian Symmetric Structure.

Photonic structures operating in the terahertz (THz) spectral region enable the essential characteristics of confinement, modal control, and electric field shielding for very high gradient accelerators based on wakefields in dielectrics. We report here an experimental investigation of THz wakefield modes in a three-dimensional photonic woodpile structure. Selective control in exciting or suppressing of wakefield modes with a nonzero transverse wave vector is demonstrated by using drive beams of varying transverse ellipticity. Additionally, we show that the wakefield spectrum is insensitive to the offset position of strongly elliptical beams. These results are consistent with analytic theory and three-dimensional simulations and illustrate a key advantage of wakefield systems with Cartesian symmetry: the suppression of transverse wakes by elliptical beams.

Multiple sclerosis: long-term outcomes in ethnic minorities. Analysis of a UK population-based registry.

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) is most frequent in Caucasian populations. However, studies of MS in other ethnic groups may offer unique insights into genetic and environmental influences on the disease, and data on long-term outcomes in these patients is limited. In this work clinical features and time to disability milestones were investigated in ethnic minority (EM) patients with MS in a UK population and comparisons were made to a Caucasian cohort from the same region. METHODS: In all, 1949 MS patients (1866 Caucasian, 83 EM) were identified from a regional disease registry. Cox proportional hazards regression was used to analyse the time to Expanded Disability Status Scale (EDSS) 3.0, 4.0 and 6.0. RESULTS: Ethnic minority patients were younger at disease onset (28.6 years vs. 32.8 years, P = 0.001), and primary progressive MS was less common (EM 4.8%, Caucasian 11.6%, P = 0.03). After correction for clinical variables, ethnicity was associated with time to EDSS 3.0 [EM: hazard ratio (HR) 1.75, P < 0.0001] and 4.0 (HR 1.46, P = 0.03), but not 6.0 (HR 1.5, P = 0.05). CONCLUSIONS: Ethnic minority patients reach early levels of fixed disability more rapidly than Caucasian patients, but this effect diminishes at later stages of the disease. This has implications for clinical management of these patients.

Clinical research training and capacity building for prevention and control of non-communicable diseases: A programme in India.

BACKGROUND.: Non-communicable diseases (NCDs)-a term which includes diabetes, cardiovascular disease, cancers, chronic respiratory diseases, and mental illness-are now the major cause of death in India and pose healthcare and economic challenges. There is an urgent need for enhanced clinical research training and capacity building for NCD prevention and control in India. METHODS.: We describe a multi-pronged approach funded in part by the US National Institutes of Health Fogarty International Center, which was initiated in 2001, to train Indian present and future scientists/doctors in NCD prevention and control. The approaches used were annual national seminars, intensive training courses, in-house workshops, short-term training sessions in the USA and monthly video conferences. RESULTS.: During 2001-2016, a total of 3650 undergraduate, postgraduate and faculty from medical colleges and institutes from almost all states in India and several neighbouring countries participated in seminars and other capacity-building workshops held at the Madras Diabetes Research Foundation, Chennai and at six other medical colleges; 883 delegates participated in the in-house workshops, 463 in the intensive interactive sessions; 244 in workshops on advanced techniques in genomics; and 37 in short-term training sessions held in the USA. CONCLUSION.: Through this unique capacity-building programme, more than 5000 individuals representing faculty and students from various medical colleges and research institutes across, and beyond, India, underwent training in the prevention and control of NCDs.

Assessing the Congregate Disaster Shelter: Using Shelter Facility Assessment Data for Evaluating Potential Hazards to Occupants During Disasters.

Disaster shelter assessments are environmental health assessments conducted during disaster situations to evaluate the living environment of shelters for hygiene, sanitation, and safety conditions. We conducted a secondary data analysis of shelter assessment records available (n = 108) on ice storms, floods, and tornado events from 1 state jurisdiction. Descriptive statistics were used to analyze results of environmental health deficiencies found in the facilities. The greater numbers of environmental health deficiencies were associated with sanitation (26%), facility physical issues (19%), and food areas (17%). Most deficiencies were reported following ice storms, tornadoes, and flood events. This report describes the first analysis of environmental health deficiencies found in disaster shelters across a spectrum of disaster events. Although the number of records analyzed for this project was small and results may not be generalizable, this new insight into the living environment in shelter facilities offers the first analysis of deficiencies of the shelter operation and living environment that have great potential to affect the safety and health of shelter occupants.

Effect of BMI and fat mass on HIV disease progression in HIV-infected, antiretroviral treatment-naïve adults in Botswana.

An obesity paradox has been proposed in many conditions including HIV. Studies conducted to investigate obesity and its effect on HIV disease progression have been inconclusive and are lacking for African settings. This study investigated the relationship between overweight/obesity (BMI≥25 kg/m2) and HIV disease progression in HIV+ asymptomatic adults not on antiretroviral treatment (ART) in Botswana over 18 months. A cohort study in asymptomatic, ART-naïve, HIV+ adults included 217 participants, 139 with BMI of 18·0-24·9 kg/m2 and seventy-eight participants with BMI≥25 kg/m2. The primary outcome was time to event (≥25 % decrease in cluster of differentiation 4 (CD4) cell count) during 18 months of follow-up; secondary outcomes were time to event of CD4 cell count<250 cells/µl and AIDS-defining conditions. Proportional survival hazard models were used to compare hazard ratios (HR) on time to events of HIV disease progression over 18 months. Higher baseline BMI was associated with significantly lower risk of an AIDS-defining condition during the follow-up (HR 0·218; 95 % CI 0·068, 0·701; P=0·011). Higher fat mass at baseline was also significantly associated with decreased risk of AIDS-defining conditions during the follow-up (HR 0·855; 95 % CI 0·741, 0·987; P=0·033) and the combined outcome of having CD4 cell count≤250/µl and AIDS-defining conditions, whichever occurred earlier (HR 0·918; 95 % CI 0·847, 0·994; P=0·036). All models were adjusted for covariates. Higher BMI and fat mass among the HIV-infected, ART-naïve participants were associated with slower disease progression. Mechanistic research is needed to evaluate the association between BMI, fat mass and HIV disease progression.

Prospective association of polycystic ovary syndrome with coronary artery calcification and carotid-intima-media thickness: the Coronary Artery Risk Development in Young Adults Women's study.

OBJECTIVE: To study the independent associations of polycystic ovary syndrome (PCOS), and its 2 components, hyperandrogenism and anovulation, with coronary artery calcification (CAC) and carotid artery intima-media thickness (IMT). APPROACH AND RESULTS: At the year 20 of the Coronary Artery Risk Development in Young Adults (CARDIA) study, a population-based multicenter cohort of young adults, women (mean age, 45 years) with information on menses and hirsutism in their twenties were assessed for CAC (n=982) and IMT (n=988). We defined PCOS as women who had both irregular menses and hyperandrogenism (n=55); isolated oligomenorrhea (n=103) as women who only had irregular menses; and isolated hyperandrogenism (n=156) as women who had either hirsutism or increased testosterone levels. Logistic regressions and general linear models were used to estimate the associations between components of PCOS and subclinical CVD. The prevalence of CAC was 10.3% overall. Women with PCOS had a multivariable adjusted odds ratio of 2.70 (95% confidence interval, 1.31-5.60) for CAC. Women with either isolated oligomenorrhea or isolated hyperandrogenism had no increased risk of CAC when compared with unexposed women. Women with PCOS had significantly increased bulb and internal carotid-IMT measurements; however, no significant differences were noted in bulb or internal carotid artery IMT among women with either isolated oligomenorrhea or isolated hyperandrogenism when compared with unexposed women. There were no differences in common carotid-IMT among the 4 study groups. CONCLUSIONS: In this study, women with PCOS, manifested as both anovulation and hyperandrogenism, but not women with one of these manifestations alone, were at increased risk for the development of subclinical CVD.

Physically active lessons as physical activity and educational interventions: a systematic review of methods and results.

OBJECTIVE: Physically active lessons aim to increase children's physical activity whilst maintaining academic time. This systematic review aimed to investigate the methods used in such interventions and their effects on physical activity and educational outcomes. METHODS: In March 2014; PubMed, Web of Science, PsycINFO and ERIC electronic databases were searched. Inclusion criteria were: 1. Classroom lessons containing both PA and educational elements; 2. intervention studies featuring a control group or within-subjects baseline measurement period; 3. any age-group; and 4. English language. Studies assessing physically active lessons within complex interventions were excluded. Data were extracted onto a standardised form. Risk of bias was assessed using the Effective Public Health Practice Project (EPHPP) tool. RESULTS: Eleven studies were identified: five examined physical activity outcomes only, three examined educational outcomes only and three examined both physical activity and educational outcomes. All studies found improved physical activity following physically active lessons: either in the whole intervention group or in specific demographics. Educational outcomes either significantly improved or were no different compared to inactive teaching. Studies ranged from low to high risk of bias. CONCLUSIONS: Encouraging evidence of improved physical activity and educational outcomes following physically active lessons is provided. However, too few studies exist to draw firm conclusions. Future high-quality studies with longer intervention periods are warranted.

Genome-wide joint meta-analysis of SNP and SNP-by-smoking interaction identifies novel loci for pulmonary function.

Genome-wide association studies have identified numerous genetic loci for spirometic measures of pulmonary function, forced expiratory volume in one second (FEV(1)), and its ratio to forced vital capacity (FEV(1)/FVC). Given that cigarette smoking adversely affects pulmonary function, we conducted genome-wide joint meta-analyses (JMA) of single nucleotide polymorphism (SNP) and SNP-by-smoking (ever-smoking or pack-years) associations on FEV(1) and FEV(1)/FVC across 19 studies (total N = 50,047). We identified three novel loci not previously associated with pulmonary function. SNPs in or near DNER (smallest P(JMA = )5.00×10(-11)), HLA-DQB1 and HLA-DQA2 (smallest P(JMA = )4.35×10(-9)), and KCNJ2 and SOX9 (smallest P(JMA = )1.28×10(-8)) were associated with FEV(1)/FVC or FEV(1) in meta-analysis models including SNP main effects, smoking main effects, and SNP-by-smoking (ever-smoking or pack-years) interaction. The HLA region has been widely implicated for autoimmune and lung phenotypes, unlike the other novel loci, which have not been widely implicated. We evaluated DNER, KCNJ2, and SOX9 and found them to be expressed in human lung tissue. DNER and SOX9 further showed evidence of differential expression in human airway epithelium in smokers compared to non-smokers. Our findings demonstrated that joint testing of SNP and SNP-by-environment interaction identified novel loci associated with complex traits that are missed when considering only the genetic main effects.