Homogeneity in Motor Competence Among Youths With Intellectual Disability With and Without Down Syndrome.

PURPOSE: To determine if there is a homogeneity of scores for youth with intellectual disability (ID) with and without Down syndrome (DS) in 19 test items of motor competence from the Bruininks-Oseretsky Test of Motor Proficiency-Second Edition (BOT-2). Homogeneity was defined as the means for each of the 19 test items scores by sex and the presence or absence of DS sharing the same population mean. METHOD: Participants were 622 youth with ID aged 6 to 21 years. Items for bilateral coordination, balance, and upper limb coordination were examined using the BOT-2. RESULTS: For all 19 BOT-2 items, means between youth with and without DS did not differ from the population mean. CONCLUSION: These results potentiate the development of expected BOT-2 motor competence scores for youth with ID independent of the presence of DS for clinical practice.

Molecular characterization of invasive and in situ squamous neoplasia of the vulva and implications for morphologic diagnosis and outcome.

Human papillomavirus (HPV)-independent vulvar squamous cell carcinoma (VSCC) is an aggressive clinical entity. Current diagnostic guidelines for premalignant lesions are ambiguous, and their molecular profile and progression events are still unclear. We selected 75 samples, from 40 patients, including 33 VSCC, 8 verrucous carcinomas (VC), 13 differentiated-type vulvar intraepithelial neoplasia (dVIN), 11 suspicious for dVIN (?dVIN), 6 differentiated exophytic vulvar intraepithelial lesions (DE-VIL), 2 vulvar acanthosis with altered differentiation (VAAD), and 2 usual-type vulvar intraepithelial neoplasia (uVIN/HSIL). Invasive and precursor lesions were matched in 29 cases. Clinical information, p16 immunohistochemistry, and mutation analysis were performed on all lesions. All dVIN, ?dVIN, DE-VIL, and VAAD were p16 negative, all uVIN/HSIL were p16 positive. In the HPV-independent group, mutations were identified in 6 genes: TP53 (n = 40), PIK3CA (n = 20), HRAS (n = 12), MET (n = 5), PTEN (n = 4), and BRAF (n = 1). TP53 mutations occurred in 73% (22/30) VSCC, 85% (11/13) dVIN, 70% (7/10) ?dVIN and no VC (0/8), DE-VIL (0/6) nor VAAD (0/2). Basal atypia was the only reliable feature of TP53 mutations. ?dVIN lesions that were non-acanthotic and atypical but obscured by inflammation, all harbored TP53 mutations. In lesions without TP53 mutations, PIK3CA (50% VC, 33% DE-VIL, 100% VAAD, 40% VSCC) and HRAS (63% VC, 33% DE-VIL, 0% VAAD, 20% VSCC) mutations were found. Mutational progression from in situ to invasive was seen (7/26, 27%) and usually involved TP53 (4/26, 15%). Cases with TP53 and PIK3CA co-mutations had the worse clinical outcomes (p < 0.001). We recommend testing for p53 in all HPV-independent lesions suspicious for dVIN, even in the presence of marked inflammation or non-acanthotic skin, particularly when close to a margin. VC, VAAD, and DE-VIL, were almost never mutated for TP53, but instead often harbored PIK3CA and HRAS mutations. In VSCC, combined TP53 and PIK3CA mutations may inform prognosis.

Comparing Motor Competence of Sex- and Age-Matched Youth With Intellectual Disability From Brazil and the United States.

Youth with intellectual disabilities (IDs) demonstrate below-criteria motor competence (MC) compared with typically developing (TD) youth. Whether differences in MC exist for youth with ID from different countries is unknown. This study examined the MC of youth with ID from Brazil (BR) and the United States (US) and compared it with norms for TD youth as established by the Bruininks-Oseretsky Test of Motor Proficiency (BOT-2). The authors measured 19 BOT-2 test items for bilateral coordination, balance, and upper limb coordination of 502 youth (BR = 252, US = 250) with ID (6-21 years). Raw scores were converted to %ceiling (percentile of highest expected scores). For all test items, no significant differences were seen between BR and US participants in %ceiling scores. Participants from both countries demonstrated equivalent to slightly below BOT-2 norms in 14 of the 19 test items, with lowest scores seen in contralateral synchronizing bilateral coordination, balancing on one leg, and ball handling.

Balance and Coordination Proficiency of Age-Matched Male and Female Children and Adolescents With Intellectual Disabilities.

Male youth (8-18 years) with intellectual disability (ID) demonstrate motor proficiency below age-related competence capacities for typically developing youth. Whether below-criteria motor proficiency also exists for females with ID is not known. The purpose of this study was to determine if sex-specific differences exist in motor proficiency for youth with ID. The Bruininks-Oseretsky Test of Motor Proficiency was used to measure motor proficiency: six items for upper limb coordination, seven items for balance, and six items for bilateral coordination. One hundred and seventy-two (172) males and 85 females with ID but without Down syndrome were divided into five age groups for comparative purposes: 8-10, 11-12, 13-14, 15-16, and 17-21 years. Males scored sufficiently higher than females to suggest that sex data should not be combined to established Bruininks-Oseretsky Test of Motor Proficiency standards for upper limb coordination, balance, and bilateral coordination subtests.

RNA-Seq Analysis of Gene Expression, Viral Pathogen, and B-Cell/T-Cell Receptor Signatures in Complex Chronic Disease.

Background: Chronic fatigue syndrome (CFS) remains poorly understood. Although infections are speculated to trigger the syndrome, a specific infectious agent and underlying pathophysiological mechanism remain elusive. In a previous study, we described similar clinical phenotypes in CFS patients and alternatively diagnosed chronic Lyme syndrome (ADCLS) patients­individuals diagnosed with Lyme disease by testing from private Lyme specialty laboratories but who test negative by reference 2-tiered serologic analysis. Methods: Here, we performed blinded RNA-seq analysis of whole blood collected from 25 adults diagnosed with CFS and 13 ADCLS patients, comparing these cases to 25 matched controls and 11 patients with well-controlled systemic lupus erythematosus (SLE). Samples were collected at patient enrollment and not during acute symptom flares. RNA-seq data were used to study host gene expression, B-cell/T-cell receptor profiles (BCR/TCR), and potential viral infections. Results: No differentially expressed genes (DEGs) were found to be significant when CFS or ADCLS cases were compared to controls. Forty-two DEGs were found when SLE cases were compared to controls, consistent with activation of interferon signaling pathways associated with SLE disease. BCR/TCR repertoire analysis did not show significant differences between CFS and controls or ADCLS and controls. Finally, viral sequences corresponding to anelloviruses, human pegivirus 1, herpesviruses, and papillomaviruses were detected in RNA-seq data, but proportions were similar (P = .73) across all genus-level taxonomic categories. Conclusions: Our observations do not support a theory of transcriptionally mediated immune cell dysregulation in CFS and ADCLS, at least outside of periods of acute symptom flares.

Balance and Coordination Capacities of Male Children and Adolescents With Intellectual Disability.

Children and adolescents with intellectual disability (ID) exhibit a mixture of cognitive, motor, and psychosocial limitation. Identifying specific inadequacies in motor proficiency in youth with ID would improve therapeutic management to enhance functional capacity and health-related physical activity. The purpose of this study was to initiate descriptive data collection of gross motor skills of youth with ID and compare those skills with competency norms. The Bruininks-Oseretsky Test of Motor Proficiency (BOT-2) was used to measure 6 items for balance (BAL), 5 items for upper limb coordination (ULC), and 6 items for bilateral coordination (BLC) of 123 males (ages 8-18) with ID but without Down syndrome. The authors performed 2,840 assessments (10-32 for each item); 944, 985, and 913 for BAL, ULC, and BLC, respectively. Mean scores for all age groups for BAL, ULC, and BLC were consistently below BOT-2 criteria. Overall motor skills of males with ID are below the competence expected for children and adolescents without disabilities.

Genomic Analysis of a Serotype 5 Streptococcus pneumoniae Outbreak in British Columbia, Canada, 2005-2009.

Background. Streptococcus pneumoniae can cause a wide spectrum of disease, including invasive pneumococcal disease (IPD). From 2005 to 2009 an outbreak of IPD occurred in Western Canada, caused by a S. pneumoniae strain with multilocus sequence type (MLST) 289 and serotype 5. We sought to investigate the incidence of IPD due to this S. pneumoniae strain and to characterize the outbreak in British Columbia using whole-genome sequencing. Methods. IPD was defined according to Public Health Agency of Canada guidelines. Two isolates representing the beginning and end of the outbreak were whole-genome sequenced. The sequences were analyzed for single nucleotide variants (SNVs) and putative genomic islands. Results. The peak of the outbreak in British Columbia was in 2006, when 57% of invasive S. pneumoniae isolates were serotype 5. Comparison of two whole-genome sequenced strains showed only 10 SNVs between them. A 15.5 kb genomic island was identified in outbreak strains, allowing the design of a PCR assay to track the spread of the outbreak strain. Discussion. We show that the serotype 5 MLST 289 strain contains a distinguishing genomic island, which remained genetically consistent over time. Whole-genome sequencing holds great promise for real-time characterization of outbreaks in the future and may allow responses tailored to characteristics identified in the genome.

Lyme Disease Diagnosed by Alternative Methods: A Phenotype Similar to That of Chronic Fatigue Syndrome.

BACKGROUND: A subset of patients reporting a diagnosis of Lyme disease can be described as having alternatively diagnosed chronic Lyme syndrome (ADCLS), in which diagnosis is based on laboratory results from a nonreference Lyme specialty laboratory using in-house criteria. Patients with ADCLS report symptoms similar to those reported by patients with chronic fatigue syndrome (CFS). METHODS: We performed a case-control study comparing patients with ADCLS and CFS to each other and to both healthy controls and controls with systemic lupus erythematosus (SLE). Subjects completed a history, physical exam, screening laboratory tests, 7 functional scales, reference serology for Lyme disease using Centers for Disease Control and Prevention criteria, reference serology for other tick-associated pathogens, and cytokine expression studies. RESULTS: The study enrolled 13 patients with ADCLS (12 of whom were diagnosed by 1 alternative US laboratory), 25 patients with CFS, 25 matched healthy controls, and 11 SLE controls. Baseline clinical data and functional scales indicate significant disability among ADCLS and CFS patients and many important differences between these groups and controls, but no significant differences between each other. No ADCLS patient was confirmed as having positive Lyme serology by reference laboratory testing, and there was no difference in distribution of positive serology for other tick-transmitted pathogens or cytokine expression across the groups. CONCLUSIONS: In British Columbia, a setting with low Lyme disease incidence, ADCLS patients have a similar phenotype to that of CFS patients. Disagreement between alternative and reference laboratory Lyme testing results in this setting is most likely explained by false-positive results from the alternative laboratory.

Submaximal exercise testing with near-infrared spectroscopy in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients compared to healthy controls: a case-control study.

BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating illness. Symptoms include profound fatigue and distinctive post-exertional malaise (PEM). We asked whether a submaximal exercise test would prove useful for identifying different patterns of tissue oxygen utilization in individuals with ME/CFS versus healthy subjects. Such a test has potential to aid with ME/CFS diagnosis, or to characterize patients' illness. METHODS: A case-control study of 16 patients with ME/CFS compared to 16 healthy controls completing a 3-min handgrip protocol was performed. Response was measured using near-infrared spectroscopy, resulting in measurements of oxygenated (O2Hb) and deoxygenated hemoglobin (HHb) over wrist extensors and flexors. Changes in O2Hb (delta (d)O2Hb) and HHb (dHHb) absorbance between the first and last contraction were calculated, as were the force-time product of all contractions, measured as tension-time index (TTI), and ratings of perceived exertion (RPE). RESULTS: Individuals with ME/CFS demonstrated smaller dO2Hb and dHHb than controls. However, after adjusting for TTI and change in total hemoglobin (delta (d)tHb), differences in dO2Hb and dHHb were reduced, with large overlapping variances. RPE was significantly higher for cases than controls, particularly at rest. CONCLUSIONS: Relative to controls, participants with ME/CFS demonstrated higher RPE, lower TTI, and reduced dO2Hb and dHHb during repetitive handgrip exercise, although considerable variance was observed. With further study, submaximal exercise testing may prove useful for stratifying patients with a lower propensity for inducing PEM, and have the ability to establish baseline intensities for exercise prescription.

Evolutionary dynamics of Staphylococcus aureus during progression from carriage to disease.

Whole-genome sequencing offers new insights into the evolution of bacterial pathogens and the etiology of bacterial disease. Staphylococcus aureus is a major cause of bacteria-associated mortality and invasive disease and is carried asymptomatically by 27% of adults. Eighty percent of bacteremias match the carried strain. However, the role of evolutionary change in the pathogen during the progression from carriage to disease is incompletely understood. Here we use high-throughput genome sequencing to discover the genetic changes that accompany the transition from nasal carriage to fatal bloodstream infection in an individual colonized with methicillin-sensitive S. aureus. We found a single, cohesive population exhibiting a repertoire of 30 single-nucleotide polymorphisms and four insertion/deletion variants. Mutations accumulated at a steady rate over a 13-mo period, except for a cluster of mutations preceding the transition to disease. Although bloodstream bacteria differed by just eight mutations from the original nasally carried bacteria, half of those mutations caused truncation of proteins, including a premature stop codon in an AraC-family transcriptional regulator that has been implicated in pathogenicity. Comparison with evolution in two asymptomatic carriers supported the conclusion that clusters of protein-truncating mutations are highly unusual. Our results demonstrate that bacterial diversity in vivo is limited but nonetheless detectable by whole-genome sequencing, enabling the study of evolutionary dynamics within the host. Regulatory or structural changes that occur during carriage may be functionally important for pathogenesis; therefore identifying those changes is a crucial step in understanding the biological causes of invasive bacterial disease.

Measuring joint hypermobility using the Beighton scale in children with intellectual disability.

PURPOSE: To determine the feasibility and reliability of using the 9-point Beighton Hypermobility Score (9-BHS) with youth with intellectual disabilities using a least to most prompting technique. METHOD: One hundred one youth (5-18 years old) enrolled in the study. Two separate evaluations, separated by 3 to 4 weeks, were performed on 25 participants. RESULTS: Ninety assented to the test, and 85 performed all 9-BHS maneuvers. Scores were not significantly different for age and gender, but participants with Down syndrome had significantly higher scores. Test-retest scores showed 80% to 90% agreement (n = 25). Cohen kappa ranged from moderate (0.41-0.60) to perfect (1.0) for the 9 maneuvers, and an ICC of 0.88 was found for total scores. CONCLUSION: The results demonstrate that the use of the 9-BHS in youth with intellectual disabilities in the manner described is feasible and reliable.

Prevalence of Staphylococcus aureus protein A (spa) mutants in the community and hospitals in Oxfordshire.

BACKGROUND: Staphylococcal protein A (spa) is an important virulence factor which enables Staphylococcus aureus to evade host immune responses. Genotypes known as "spa-types", based on highly variable Xr region sequences of the spa-gene, are frequently used to classify strains. A weakness of current spa-typing primers is that rearrangements in the IgG-binding region of the gene cause 1-2% of strains to be designated as "non-typeable". RESULTS: We developed an improved primer which enabled sequencing of all strains, containing any type of genetic rearrangement, in a large study among community carriers and hospital inpatients in Oxfordshire, UK (6110 isolates). We identified eight novel spa-gene variants, plus one previously described. Three of these rearrangements would be designated "non-typeable" using current spa-typing methods; they occurred in 1.8% (72/3905) asymptomatically carried and 0.6% (14/2205) inpatient S. aureus strains. Some individuals were simultaneously colonized by both formerly non-typeable and typeable strains; previously such patients would have been identified as carrying only currently typeable strains, underestimating mixed carriage prevalence and diversity. Formerly non-typeable strains were found in more spa-types associated with multilocus sequence type ST398 (35%), common among livestock, compared to other groups with any non-typeable strains (1-4%), suggesting particular spa-types may have been under-represented in previous human studies. CONCLUSIONS: This improved method allows us to spa-type previously non-typeable strains with rearrangements in the spa-gene and to resolve cases of mixed colonization with deletions in one or more strains, thus accounting for hidden diversity of S. aureus in both community and hospital environments.

Development and Delphi consensus validation of the Medication-Related Fall screening and scoring tool.

BACKGROUND: Falls are a significant public health problem and constitute a major cause of injuries and mortality. Risk factors for falls are multifactorial and include medication use. AIM: To develop and investigate the content validity of the Medication-Related fall (MRF) screening and scoring tool. METHOD: The MRF tool was developed from clinical practice guidelines addressing medication-related problems, and additional medications identified by specialist pharmacists across a region of the United Kingdom (Northern Ireland). Medication classes were categorised according to their 'potential to cause falls' as: high-risk (three points), moderate-risk (two points) or low-risk (one point). The overall medication-related falls risk for the patient was determined by summing the scores for all medications. The MRF was validated using Delphi consensus methodology, whereby three iterative rounds of surveys were conducted using SurveyMonkey®. Twenty-two experts from 10 countries determined their agreement with the falls risk associated with each medication on a 5-point Likert scale. Only medications with at least 75% of respondents agreeing or strongly agreeing were retained in the next round. RESULTS: Consensus was reached for 19 medications/medication classes to be included in the final version of the MRF tool; ten were classified as high-risk, eight as moderate-risk and one as low-risk. CONCLUSION: The MRF tool is simple and has the potential to be integrated into medicines optimisation to reduce falls risk and negative fall-related outcomes. The score from the MRF tool can be used as a clinical parameter to assess the need for medication review and clinical interventions.

Circulating tumour mutation detection in triple-negative breast cancer as an adjunct to tissue response assessment.

Circulating tumour DNA (ctDNA) detection via liquid biopsy is an emerging alternative to tissue biopsy, but its potential in treatment response monitoring and prognosis in triple negative breast cancer (TNBC) is not yet well understood. Here we determined the prevalence of actionable mutations detectable in ctDNA using a clinically validated cancer gene panel assay in patients with TNBC, without recurrence at the time of study entry. Sequencing of plasma DNA and validation of variants from 130 TNBC patients collected within 7 months of primary treatment completion revealed that 7.7% had detectable residual disease with a hotspot panel. Among neoadjuvant treated patients, we observed a trend where patients with incomplete pathologic response and positive ctDNA within 7 months of treatment completion were at much higher risk of reduced progression free survival. We propose that a high risk subset of early TNBC patients treated in neoadjuvant therapy protocols may be identifiable by combining tissue response and sensitive ctDNA detection.

Dentists as oral physicians: the overlooked primary health care resource.

The United States is currently experiencing a primary care shortage. One solution to improving health care is to increase the utilization of existing health care providers, particularly dentists, an opportunity that has been largely ignored. By employing mid-level providers for less complex procedures to deliver more accessible dental care at lower cost, dentists can redistribute tasks to their office workforce. They can then serve as oral physicians who can provide limited preventive primary care, including screening for chronic diseases, while continuing to oversee all dental care, whether provided by dentists or non-dentists. Thus, they could improve the health of the US population as well as increase access to dental care at lower cost, while partially alleviating the primary care shortage by filling a need for the screening aspects of primary care.

Temperature dependent performance of Schmidt-Boelter heat flux sensors.

The total heat flux sensors for NASA's Mars Entry, Descent, and Landing Instrumentation 2 (MEDLI2) sensor suite on the Mars 2020 vehicle and the Low-Earth Orbit Flight Test of an Inflatable Decelerator (LOFTID) technology demonstration mission are passively cooled Schmidt-Boelter gauges. The output of these sensors has been experimentally demonstrated to be dependent on the temperature of the sensing element. The experimental results are shown to align with a model that assumes temperature-dependent material properties, specifically the Seebeck coefficient. The MEDLI2 and LOFTID flight total heat flux sensors did not undergo a full thermal calibration prior to being installed on the flight vehicles since the temperature dependence was unknown ahead of time. Additionally, the material properties are not known due to the designs being proprietary. For these reasons, an approximate correction factor was derived. The applicability and associated uncertainty of this temperature-dependent correction factor are presented. The error that would be introduced into the measurement if temperature effects were not accounted for would be as high as 9.5% and 16% for the MEDLI2 and LOFTID total heat flux sensors, respectively. As a best practice for future flight missions and ground-based applications that employ similar passively cooled heat flux sensors, it is recommended to individually calibrate each sensor across all applicable use temperatures to account for sensor-to-sensor variations and minimize measurement uncertainty.

Heterogeneity in Longitudinal Healthcare Utilisation by Older Adults: A Latent Transition Analysis of the Irish Longitudinal Study on Ageing.

BACKGROUND: Older adults likely exhibit considerable differences in healthcare need and usage. Identifying differences in healthcare utilisation both between and within individuals over time may support future service development. OBJECTIVES: To characterise temporal changes in healthcare utilisation among a nationally representative sample of community-dwelling older adults. METHODS: A latent transition analysis of the first three waves of The Irish Longitudinal Study on Ageing (TILDA) (N = 6128) was conducted. RESULTS: Three latent classes of healthcare utilisation were identified, 'primary care only'; 'primary care and outpatient visits' and 'multiple utilisation'. The classes were invariant across all three waves. Transition probabilities indicated dynamic changes over time, particularly for the 'primary care and outpatient visits' and 'multiple utilisation' statuses. DISCUSSION: Older adults exhibit temporal changes in healthcare utilisation which may reflect changes in healthcare need and disease progression. Further research is required to identify the factors which influence movement between healthcare utilisation patterns.

Comprehensive human amniotic fluid metagenomics supports the sterile womb hypothesis.

As metagenomic approaches for detecting infectious agents have improved, each tissue that was once thought to be sterile has been found to harbor a variety of microorganisms. Controversy still exists over the status of amniotic fluid, which is part of an immunologically privileged zone that is required to prevent maternal immune system rejection of the fetus. Due to this privilege, the exclusion of microbes has been proposed to be mandatory, leading to the sterile womb hypothesis. Since nucleic acid yields from amniotic fluid are very low, contaminating nucleic acid found in water, reagents and the laboratory environment frequently confound attempts to address this hypothesis. Here we present metagenomic criteria for microorganism detection and a metagenomic method able to be performed with small volumes of starting material, while controlling for exogenous contamination, to circumvent these and other pitfalls. We use this method to show that human mid-gestational amniotic fluid has no detectable virome or microbiome, supporting the sterile womb hypothesis.

Histologic and Genotypic Characterization of Lung Cancer in the Inuit Population of the Eastern Canadian Arctic.

Inuit are the Indigenous Arctic peoples and residents of the Canadian territory of Nunavut who have the highest global rate of lung cancer. Given lung cancer's mortality, histological and genomic characterization was undertaken to better understand the disease biology. We retrospectively studied all Inuit cases from Nunavut's Qikiqtani (Baffin) region, referred to the Ottawa Hospital Cancer Center between 2001 and 2011. Demographics were compiled from medical records and tumor samples underwent pathologic/histologic confirmation. Tumors were analyzed by next generation sequencing (NGS) with a cancer hotspot mutation panel. Of 98 patients, the median age was 66 years and 61% were male. Tobacco use was reported in 87%, and 69% had a history of lung disease (tuberculosis or other). Histological types were: non-small cell lung carcinoma (NSCLC), 81%; small cell lung carcinoma, 16%. Squamous cell carcinoma (SCC) represented 65% of NSCLC. NGS on 55 samples demonstrated mutation rates similar to public lung cancer datasets. In SCC, the STK11 F354L mutation was observed at higher frequency than previously reported. This is the first study to characterize the histologic/genomic profiles of lung cancer in this population. A high incidence of SCC, and an elevated rate of STK11 mutations distinguishes this group from the North American population.

Antimicrobial resistance determinants are associated with Staphylococcus aureus bacteraemia and adaptation to the healthcare environment: a bacterial genome-wide association study.

Staphylococcus aureus is a major bacterial pathogen in humans, and a dominant cause of severe bloodstream infections. Globally, antimicrobial resistance (AMR) in S. aureus remains challenging. While human risk factors for infection have been defined, contradictory evidence exists for the role of bacterial genomic variation in S. aureus disease. To investigate the contribution of bacterial lineage and genomic variation to the development of bloodstream infection, we undertook a genome-wide association study comparing bacteria from 1017 individuals with bacteraemia to 984 adults with asymptomatic S. aureus nasal carriage. Within 984 carriage isolates, we also compared healthcare-associated (HA) carriage with community-associated (CA) carriage. All major global lineages were represented in both bacteraemia and carriage, with no evidence for different infection rates. However, kmers tagging trimethoprim resistance-conferring mutation F99Y in dfrB were significantly associated with bacteraemia-vs-carriage (P=10-8.9-10-9.3). Pooling variation within genes, bacteraemia-vs-carriage was associated with the presence of mecA (HMP=10-5.3) as well as the presence of SCCmec (HMP=10-4.4). Among S. aureus carriers, no lineages were associated with HA-vs-CA carriage. However, we found a novel signal of HA-vs-CA carriage in the foldase protein prsA, where kmers representing conserved sequence allele were associated with CA carriage (P=10-7.1-10-19.4), while in gyrA, a ciprofloxacin resistance-conferring mutation, L84S, was associated with HA carriage (P=10-7.2). In an extensive study of S. aureus bacteraemia and nasal carriage in the UK, we found strong evidence that all S. aureus lineages are equally capable of causing bloodstream infection, and of being carried in the healthcare environment. Genomic variation in the foldase protein prsA is a novel genomic marker of healthcare origin in S. aureus but was not associated with bacteraemia. AMR determinants were associated with both bacteraemia and healthcare-associated carriage, suggesting that AMR increases the propensity not only to survive in healthcare environments, but also to cause invasive disease.