Investigation of a Cluster of Sequence Type 22 Methicillin-Resistant Staphylococcus aureus Transmission in a Community Setting.

BACKGROUND: Whole-genome sequencing (WGS) has typically been used to confirm or refute hospital/ward outbreaks of methicillin-resistant Staphylococcus aureus (MRSA) identified through routine practice. However, appropriately targeted WGS strategies that identify routinely "undetectable" transmission remain the ultimate aim. METHODS: WGS of MRSA isolates sent to a regional microbiological laboratory was performed as part of a 12-month prospective observational study. Phylogenetic analyses identified a genetically related cluster of E-MRSA15 isolated from patients registered to the same general practice (GP) surgery. This led to an investigation to identify epidemiological links, find additional cases, and determine potential for ongoing transmission. RESULTS: We identified 15 MRSA-positive individuals with 27 highly related MRSA isolates who were linked to the GP surgery, 2 of whom died with MRSA bacteremia. Of the 13 cases that were further investigated, 11 had attended a leg ulcer/podiatry clinic. Cases lacked epidemiological links to hospitals, suggesting that transmission occurred elsewhere. Environmental and staff screening at the GP surgery did not identify an ongoing source of infection. CONCLUSIONS: Surveillance in the United Kingdom shows that the proportion of MRSA bacteremias apportioned to hospitals is decreasing, suggesting the need for greater focus on the detection of MRSA outbreaks and transmission in the community. This case study confirms that the typically nosocomial lineage (E-MRSA15) can transmit within community settings. Our study exemplifies the continued importance of WGS in detecting outbreaks, including those which may be missed by routine practice, and suggests that universal WGS of bacteremia isolates may help detect outbreaks in low-surveillance settings

Genome-wide determinants of mortality and motor progression in Parkinson’s disease

There are 90 independent genome-wide significant genetic risk variants for Parkinson’s disease (PD) but currently only five nominated loci for PD progression. The biology of PD progression is likely to be of central importance in defining mechanisms that can be used to develop new treatments. We studied 6766 PD patients, over 15,340 visits with a mean follow-up of between 4.2 and 15.7 years and carried out genome-wide survival studies for time to a motor progression endpoint, defined by reaching Hoehn and Yahr stage 3 or greater, and death (mortality). There was a robust effect of the APOE ε4 allele on mortality in PD. We also identified a locus within the TBXAS1 gene encoding thromboxane A synthase 1 associated with mortality in PD. We also report 4 independent loci associated with motor progression in or near MORN1, ASNS, PDE5A, and XPO1. Only the non-Gaucher disease causing GBA1 PD risk variant E326K, of the known PD risk variants, was associated with mortality in PD. Further work is needed to understand the links between these genomic variants and the underlying disease biology. However, these may represent new candidates for disease modification in PD

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

Analysis of DNM3 and VAMP4 as genetic modifiers of LRRK2 Parkinson's disease.

The LRRK2 gene has rare (p.G2019S) and common risk variants for Parkinson's disease (PD). DNM3 has previously been reported as a genetic modifier of the age at onset in PD patients carrying the LRRK2 p.G2019S mutation. We analyzed this effect in a new cohort of LRRK2 p.G2019S heterozygotes (n = 724) and meta-analyzed our data with previously published data (n = 754). VAMP4 is in close proximity to DNM3, and was associated with PD in a recent study, so it is possible that variants in this gene may be important. We also analyzed the effect of VAMP4 rs11578699 on LRRK2 penetrance. Our analysis of DNM3 in previously unpublished data does not show an effect on age at onset in LRRK2 p.G2019S carriers; however, the inter-study heterogeneity may indicate ethnic or population-specific effects of DNM3. There was no evidence for linkage disequilibrium between DNM3 and VAMP4. Analysis of sporadic patients stratified by the risk variant LRRK2 rs10878226 indicates a possible interaction between common variation in LRRK2 and VAMP4 in disease risk

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

Understanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics

Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

AbstractUnderstanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.</jats:p

Investigation of a Cluster of Sequence Type 22 Methicillin-Resistant Staphylococcus aureus Transmission in a Community Setting.

Background: Whole-genome sequencing (WGS) has typically been used to confirm or refute hospital/ward outbreaks of methicillin-resistant Staphylococcus aureus (MRSA) identified through routine practice. However, appropriately targeted WGS strategies that identify routinely "undetectable" transmission remain the ultimate aim. Methods: WGS of MRSA isolates sent to a regional microbiological laboratory was performed as part of a 12-month prospective observational study. Phylogenetic analyses identified a genetically related cluster of E-MRSA15 isolated from patients registered to the same general practice (GP) surgery. This led to an investigation to identify epidemiological links, find additional cases, and determine potential for ongoing transmission. Results: We identified 15 MRSA-positive individuals with 27 highly related MRSA isolates who were linked to the GP surgery, 2 of whom died with MRSA bacteremia. Of the 13 cases that were further investigated, 11 had attended a leg ulcer/podiatry clinic. Cases lacked epidemiological links to hospitals, suggesting that transmission occurred elsewhere. Environmental and staff screening at the GP surgery did not identify an ongoing source of infection. Conclusions: Surveillance in the United Kingdom shows that the proportion of MRSA bacteremias apportioned to hospitals is decreasing, suggesting the need for greater focus on the detection of MRSA outbreaks and transmission in the community. This case study confirms that the typically nosocomial lineage (E-MRSA15) can transmit within community settings. Our study exemplifies the continued importance of WGS in detecting outbreaks, including those which may be missed by routine practice, and suggests that universal WGS of bacteremia isolates may help detect outbreaks in low-surveillance settings

Leucine rich repeat kinase 2 (LRRK2) GLY2019SER mutation is absent in a second cohort of Nigerian Africans with Parkinson disease.

To date the LRRK2 p.G2019S mutation remains the most common genetic cause of Parkinson disease (PD) worldwide. It accounts for up to 6% of familial and approximately 1.5% of sporadic cases. LRRK2 has a kinase enzymatic domain which provides an attractive potential target for drug therapies and LRRK2 kinase inhibitors are in development. Prevalence of the p.G2019S has a variable ethnic and geographic distribution, the highest reported among Ashkenazi Jews (30% in patients with familial PD, 14% in sporadic PD, 2.0% in controls) and North African Berbers (37% in patients with familial PD, 41% in sporadic PD, and 1% in controls). Little is known about the frequency of the LRRK2 p.G2019S among populations in sub-Saharan Africa. Our group and others previously reported that the p.G2019S is absent in a small cohort of Nigerian PD patients and controls. Here we used Kompetitive Allele Specific PCR (KASP) assay to screen for the p.G2019S in a larger cohort of Black African PD patients (n = 126) and healthy controls (n = 54) from Nigeria. Our analysis confirmed that all patients and controls are negative for the p.G2019S mutation. This report provides further evidence that the LRRK2 p.G2019S is not implicated in PD in black populations from Nigeria and support the notion that p.G2019S mutation originated after the early human dispersal from sub-Saharan Africa. Further studies using larger cohorts and advance sequencing technology are required to underpin the genetic causes of PD in this region

Ratnieks et al. Data reliability in citizen science (data sets)

Two data sets analyzed in Experiments 1 and 2, respectively, from the paper of Ratnieks et al., Data reliability in citizen science: learning curve and the effects of training method, volunteer background and experience on identification accuracy of insects visiting ivy flowers. Methods in Ecology and Evolution. Both data sets are in the form of Tab-delimited text files. The variables included are as follows: Experiment 1: (each row represents one test of one participant, where participants were tested only once) Training = training method (pamphlet only, pamphlet + slide show, pamphlet + direct training) Degree = study degree of participants, biology-related (B) or not (N) Experience = prior experience of participants (Y/N) Experiment 2: (each participant was tested three times) Participant = unique participant id TestNo = test number (first, second or third) AdMat = type of additional training material (video or stills) Both datasets: Other variables present the proportion of insects identified correctly by each participant on each test. HB - honey bees SOCW - social wasps HBMHOV - honey bee-mimicking hover flies WMHOV - wasp-mimicking hover flies OTHFLY - non-syrphid flies IVYBEE - ivy bees BB - bumble bees BF - butterflies MO - moths ALL - all insects combine