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The most striking consequence of a heart attack is the loss of billions of heart muscle cells, alongside damage to the associated vasculature. The lost cardiovascular tissue is replaced by scar formation, which is non-functional and results in pathological remodelling of the heart and ultimately heart failure. It is, therefore, unsurprising that the heart regeneration field has centred efforts to generate new muscle and blood vessels through targeting cardiomyocyte proliferation and angiogenesis following injury. However, combined insights from embryological studies and regenerative models, alongside the adoption of -omics technology, highlight the extensive heterogeneity of cell types within the forming or re-forming heart and the significant crosstalk arising from non-muscle and non-vessel cells. In this review, we focus on the roles of fibroblasts, immune, conduction system, and nervous system cell populations during heart development and we consider the latest evidence supporting a function for these diverse lineages in contributing to regeneration following heart injury. We suggest that the emerging picture of neurologically, immunologically, and electrically coupled cell function calls for a wider-ranging combinatorial approach to heart regeneration.

BackgroundWe aimed to measure SARS-CoV-2 seroprevalence in a cohort of healthcare workers (HCWs) during the first UK wave of the COVID-19 pandemic, explore risk factors associated with infection, and investigate the impact of antibody titres on assay sensitivity.MethodsHCWs at Sheffield Teaching Hospitals NHS Foundation Trust (STH) were prospectively enrolled and sampled at two time points. SARS-CoV-2 antibodies were tested using an in-house assay for IgG and IgA reactivity against Spike and Nucleoprotein (sensitivity 99·47%, specificity 99·56%). Data were analysed using three statistical models: a seroprevalence model, an antibody kinetics model, and a heterogeneous sensitivity model.FindingsAs of 12th June 2020, 24·4% (n=311/1275) HCWs were seropositive. Of these, 39·2% (n=122/311) were asymptomatic. The highest adjusted seroprevalence was measured in HCWs on the Acute Medical Unit (41·1%, 95% CrI 30·0–52·9) and in Physiotherapists and Occupational Therapists (39·2%, 95% CrI 24·4–56·5). Older age groups showed overall higher median antibody titres. Further modelling suggests that, for a serological assay with an overall sensitivity of 80%, antibody titres may be markedly affected by differences in age, with sensitivity estimates of 89% in those over 60 years but 61% in those ≤30 years.InterpretationHCWs in acute medical units working closely with COVID-19 patients were at highest risk of infection, though whether these are infections acquired from patients or other staff is unknown. Current serological assays may underestimate seroprevalence in younger age groups if validated using sera from older and/or more symptomatic individuals.Research in contextEvidence before this studyWe searched PubMed for studies published up to March 6th 2021, using the terms “COVID”, “SARS-CoV-2”, “seroprevalence”, and “healthcare workers”, and in addition for articles of antibody titres in different age groups against coronaviruses using “coronavirus”, “SARS-CoV-2, “antibody”, “antibody tires”, “COVID” and “age”. We included studies that used serology to estimate prevalence in healthcare workers. SARS-CoV-2 seroprevalence has been shown to be greater in healthcare workers working on acute medical units or within domestic services. Antibody levels against seasonal coronaviruses, SARS-CoV and SARS-CoV-2 were found to be higher in older adults, and patients who were hospitalised.Added value of this studyIn this healthcare worker seroprevalence modelling study at a large NHS foundation trust, we confirm that those working on acute medical units, COVID-19 “Red Zones” and within domestic services are most likely to be seropositive. Furthermore, we show that physiotherapists and occupational therapists have an increased risk of COVID-19 infection. We also confirm that antibody titres are greater in older individuals, even in the context of non-hospitalised cases. Importantly, we demonstrate that this can result in age-specific sensitivity in serological assays, where lower antibody titres in younger individuals results in lower assay sensitivity.Implications of all the available evidenceThere are distinct occupational roles and locations in hospitals where the risk of COVID-19 infection to healthcare workers is greatest, and this knowledge should be used to prioritise infection prevention control and other measures to protect healthcare workers. Serological assays may have different sensitivity profiles across different age groups, especially if assay validation was undertaken using samples from older and/or hospitalised patients, who tend to have higher antibody titres. Future seroprevalence studies should consider adjusting for age-specific assay sensitivities to estimate true seroprevalence rates.Author Contributions

Objective Psoriasis is a chronic inflammatory skin disease that is thought to affect ∼2% of the global population. Psoriasis has been associated with ∼30% increased risk of developing type 2 diabetes (T2D), with numerous studies reporting that psoriasis is an independent risk-factor for T2D, separate from underlying obesity. Separately, studies of skin-specific transgenic mice have reported altered whole-body glucose homeostasis in these models. These studies imply a direct role for skin inflammation and dysfunction in mediating the onset of T2D in psoriasis patients, potentially via the endocrine effects of the skin secretome on key metabolic tissues. We used a combination of in vivo and ex vivo mouse models and ex vivo human imiquimod (IMQ) models to investigate the effects of psoriasis-mediated changes in the skin secretome on whole-body metabolic function. Methods To induce psoriatic skin inflammation, mice were topically administered 75 mg of 5% IMQ cream (or Vaseline control) to a shaved dorsal region for 4 consecutive days. On day 5, mice were fasted for glucose and insulin tolerance testing, or sacrificed in the fed state with blood and tissues collected for analysis. To determine effects of the skin secretome, mouse skin was collected at day 5 from IMQ mice and cultured for 24 h. Conditioned media (CM) was collected and used 1:1 with fresh media to treat mouse explant subcutaneous adipose tissue (sAT) and isolated pancreatic islets. For human CM experiments, human skin was exposed to 5% IMQ cream for 20 min, ex vivo, to induce a psoriatic phenotype, then cultured for 24 h. CM was collected, combined 1:1 with fresh media and used to treat human sAT ex vivo. Markers of tissue inflammation and metabolic function were determined by qPCR. Beta cell function in isolated islets was measured by dynamic insulin secretion. Beta-cell proliferation was determined by measurement of Ki67 immunofluorescence histochemistry and BrDU uptake, whilst islet apoptosis was assessed by caspase 3/7 activity. All data is expressed as mean ± SEM. Results Topical treatment with IMQ induced a psoriatic-like phenotype in mouse skin, evidenced by thickening, erythema and inflammation of the skin. Topical IMQ treatment induced inflammation and signs of metabolic dysfunction in sub-cutaneous and epidydimal adipose tissue, liver, skeletal muscle and gut tissue. However, consistent with islet compensation and a pre-diabetic phenotype, IMQ mice displayed improved glucose tolerance, increased insulin and c-peptide response to glucose, and increased beta cell proliferation. Treatment of sAT with psoriatic mouse or human skin-CM replicated the in vivo phenotype, leading to increased inflammation and metabolic dysfunction in mouse and human sAT. Treatment of pancreatic islets with psoriatic mouse skin-CM induced increases in beta-proliferation and apoptosis, thus partially replicating the in vivo phenotype. Conclusions Psoriasis-like skin inflammation induces a pre-diabetic phenotype, characterised by tissue inflammation and markers of metabolic dysfunction, together with islet compensation in mice. The in vivo phenotype is partially replicated by exposure of sAT and pancreatic islets to psoriatic-skin conditioned media. These results support the hypothesis that psoriatic skin inflammation, potentially via the endocrine actions of the skin secretome, may constitute a novel pathophysiological pathway mediating the development of T2D., Highlights • Topical IMQ treatment induced a psoriatic-like phenotype in mouse skin. • Skin IMQ treatment induced inflammation and signs of metabolic dysfunction in sub-cutaneous and epidydimal adipose tissue, liver, skeletal muscle and gut tissue. • Skin IMQ treatment induced islet compensation characterised by increased insulin and c-peptide response to glucose, and increased beta cell proliferation. • The in vivo IMQ mouse phenotype is partially replicated by exposure of sAT and pancreatic islets to psoriatic-skin conditioned media. • Psoriatic skin inflammation, potentially through the endocrine actions of the skin secretome, may constitute a novel pathophysiological pathway mediating the development of T2D.

Epidemiologic and syndromic surveillance metrics traditionally used by public health departments can be enhanced to better predict hospitalization for coronavirus disease (COVID-19). In Montgomery County, Maryland, measurements of oxygen saturation (SpO2) by pulse oximetry obtained by the emergency medical service (EMS) were added to these traditional metrics to enhance the public health picture for decision makers. During a 78-day period, the rolling 7-day average of the percentage of EMS patients with SpO2

Objectives To inform the design of a clinical trial of a targeted screening programme for relatives of individuals affected by thoracic aortic disease, we performed a consensus exercise as to the acceptability of screening, the optimal sequence and choice of tests, long-term patient management, and choice of trial design. Methods Working with the Aortic Dissection Awareness UK & Ireland patient association, we performed a Delphi exercise with clinical experts, patients, and carers, consisting of three rounds of consultation followed by a final multi-stakeholder face-to-face workshop. Results Thirty-five experts and 84 members of the public took part in the surveys, with 164 patients and clinicians attending the final workshop. There was substantial agreement on the need for a targeted screening pathway that would employ a combined approach (imaging + genetic testing). The target population would include the first- and second-degree adult (> 15 years) relatives, with no upper age limit of affected patients. Disagreement persisted about the screening process, sequence, personnel, the imaging method to adopt, computed tomography (CT) scan vs magnetic resonance imaging (MRI), and the specifics of a potential trial, including willingness to undergo randomisation, and measures of effectiveness and acceptability. Conclusion A Delphi process, initiated by patients, identified areas of uncertainty with respect to behaviour, process, and the design of a targeted screening programme for thoracic aortic disease that requires further research prior to any future trial.

To determine if additional children attending primary care clinics in moderate-altitude areas would screen positive for anemia if the hemoglobin cutoff were modified for altitude.This cross-sectional study evaluated children aged 11-19 months of age who had a screening hemoglobin conducted between January 2011 and December 2017 at 4 moderate-altitude (1726-2212 m) and 8 low-altitude (1-20 m) US military clinics. The primary outcome was anemia prevalence (hemoglobin11 g/dL) in moderate-altitude and low-altitude groups, before and after applying the current World Health Organization model for altitude-based hemoglobin modification. Groups were compared with prevalence ORs adjusted for age, sex, weight-for-length percentile, and parental military rank, and the false-negative proportion was calculated for children with anemia at moderate altitude.Before altitude modification, anemia prevalence was 4.4% in the moderate-altitude group (n = 1488) and 16.8% in the low-altitude group (n = 7090) (prevalence OR, 0.23; 95% CI, 0.17-0.29). After applying the World Health Organization model, anemia prevalence in the moderate-altitude group increased to 14.7% (prevalence OR, 0.82; 95% CI, 0.70-0.97). Nonapplication of the model at moderate altitude resulted in a false-negative proportion of 0.70 (95% CI, 0.63-0.76).Nonuse of the World Health Organization altitude-based modification model for hemoglobin may result in a large percentage of US children with anemia at moderate altitude screening falsely negative for anemia. Although ancestry disparities in altitude acclimatization may limit universal application of the current World Health Organization model, the existing standard of care may leave children at moderate altitude at risk for complications from iron deficiency anemia.

This chapter offers a concrete alternative to the language of vocation, examining how narratives shape a person’s self-perception. Human beings chart the future direction of their lives based on their construction of stories about themselves; moreover, these stories are woven together and interconnect in complex ways. Such self-constructed and self-referential narratives are best described using the word myth: we are always engaged in a process of myth-making as we explore the contours of our lives. This language, suggests the author, may help us to reshape the concept of vocation in a way that recognizes the dynamic nature of the self, clarifies matters of agency, and attends to the retrospective nature of the construction of the self. To illustrate these points, the author offers a number of his own “myths of self,” as well as references to self-constructed narratives in the Bhagavadgita and in other literary and cultural accounts.

The association of Hinduism with reincarnation is well-known, but this connection obscures a long tradition of ancestor worship. The ritual texts of the Vedic and later Hindu traditions describe in detail the procedure for several forms of ancestral rite. This paper outlines the development of the theological discourse on ancestor worship from its earliest expression to the formation of Classical Hinduism early in the Common Era and highlights the underlying theological, social, and practical concerns that shaped that discourse. The development that culminated in the theological construction of an enduring model of ancestor veneration, the śrāddha, revolves around two central tensions, between the solemn and domestic ritual traditions and between the ritual and renunciation traditions. The resolution of the first tension produces the śrāddha. The reactions to the second tension in the ritual literature shape the śrāddha, bringing it to its classical form, and generate the complex soteriology of later Hinduism.

The World Organisation for Animal Health (OIE) requested an International Standard anti-Brucella melitensis Serum (ISaBmS) to standardise diagnostic tests and reagents for sheep and goats. The agreed criteria were the highest dilution (in negative serum) of the standard which must give a positive result and the lowest dilution (in negative serum) which must simultaneously give a negative result. The two dilutions for each assay were, respectively: indirect enzyme-linked immunosorbent assay (iELISA) 1/64 and 1/750, competitive ELISA (cELISA) 1/8 and 1/300, fluorescent polarisation assay (FPA) 1/16 and 1/200, Rose Bengal test (RBT) 1/16 and 1/200. The OIE International Standard Serum (OIEISS) will remain the primary standard for the RBT; the ISaBmS is an additionalstandard. It was impossible to set criteria for the complement fixation test, therefore the OIEISS will remain the primary standard. The ISaBmS can be used to standardise iELISA, cELISA and FPA to diagnose sheep and goat brucellosis. This standard should facilitate harmonisation of tests used for brucellosis surveillance and international trade in these species.

With the 2004 reauthorization of the Individuals with Disabilities Education Improvement Act and No Child Left Behind, there has been an increasing emphasis on occupational therapy services that are provided across naturally occurring contexts and routines within the school settings. School-based occupational therapists are interested in maximizing students' achievement and want to know which models of therapeutic intervention are most effective for facilitating students' successful participation within their least restrictive environment. Thus, this critical appraisal of the topic (CAT) sought to answer the following question: For occupational therapists working in school system settings, is there evidence supporting the efficacy of a classroom-based collaborative approach versus a pull-out model of therapeutic intervention for facilitating students' participation in schools? After reviewing 10 articles (Level II-IV evidence), it appears that a collaborative approach to service delivery may be a...

We conducted a cross-sectional study on 255 cattle farms in England and Wales to identify risk factors for verocytotoxin-producing E. coli O157 (VTEC). Exposure variables were collected at the levels of the farm and of the group of young-stock within the farms. On each farm a group of young-stock (6–18 months of age) was sampled to establish VTEC status. In our multiple logistic regression, farm VTEC status was associated with access to springs (OR: 0.31, CI 95% : 0.12, 0.78) and assessing the wetness of the bedding material less frequently than daily (OR: 3.89 CI 95% : 1.5, 10.2). At group-level we found no associated risk factors for animals housed outdoors in fields. Significant for groups housed in pens were wet bedding (wet OR: 3.43, CI 95% : 1.3, 9.4; very wet OR: 4.24, CI 95% : 1.2, 14.6), number of animals in the group (10–15 OR: 2.72, CI 95% : 0.75, 9.9, 16–24, OR: 3.78, CI 95% : 1.2, 12.3; >25 OR: 3.78, CI 95% : 1.1, 12.7) and feeding straw (OR: 2.29, CI 95% : 1.2, 5.5).

hild maltreatment is a significant and preventable public health problem in North Carolina, and across the United States. It affects millions of children and their families each year in our country—often devastating children’s psychological and physical well-being, tearing families apart, and costing our society billions of dollars in services to respond to and treat child victims. In North Carolina alone, 113,557 children were assessed for child maltreatment in 2003-2004, and 27,310 were substantiated, or found to be “in need of services.” 1 For too many North Carolina children, maltreatment is fatal. In 2003, 30 children were killed by their parents or caretakers in our state as a result of being shaken, beaten, stabbed, poisoned, or drowned. 2 As alarming as these numbers are, they are likely the tip of the iceberg, as child maltreatment is significantly underreported and difficult to detect. For example, the CarolinaSAFE survey— an anonymous, random telephone survey of mothers of children (0-17 years old) in North and South Carolina—found that mothers self-reported physical abuse of their children (by either themselves or their husband or partner) at a rate more than 40 times higher and sexual abuse at a rate more than 15 times higher than rates found in official statistics. 3 Findings from this study and others suggest that the actual incidence of maltreatment may be much higher than official estimates. 4

Levels of T4 and tri-iodothyronine (T3), the activated hormone, correspond to thyroid function, but are also affected by changes in environment and physiological status (Suttle 2010). This paper reports serum and plasma T4 concentrations recorded in cattle and sheep in health monitoring and diagnostic projects. The Edinburgh University Dairy Herd Health and Productivity Service (DHHPS) surveyed plasma or serum samples from adult dairy cows throughout the UK, throughout their production cycles, for the assessment of nutritional status (Macrae and others 2006). The DHHPS laboratory found no difference between plasma and serum samples for T4 estimation (unpublished data). Samples numbering 3475, from October 1992 to September 1993, were obtained from animals' blood sampled on a routine basis to check nutritional status (‘routine’) where T4 status was not specifically requested. Samples numbering 3512, from October 1993 to September 2005, were tested for T4 at the request of the farmer, veterinary surgeon, or feed advisor (‘request’). The DHHPS T4 analysis was a competitive immunoassay using direct chemiluminescent technology (Bayer), employing a Bayer Operon analyser wet chemistry system. The Veterinary Laboratories Agency (VLA) analysed 1761 serum samples submitted from dairy and beef cattle and calves between January 2004 and October 2005, and 455 serum samples submitted from sheep between December 2000 and January 2006. Samples were submitted …

Introduction Sphincterotomy and balloon/basket trawl at ERCP is the standard treatment to clear stones from the common bile duct. The BSG in 2014 published a key performance indicator of >75% stone clearance during first ERCP. Balloon sphincteroplasty as an adjunct to sphincterotomy can increase stone clearance. The aim of this study is to review the success/safety for balloon sphincteroplasty compared to sphincterotomy alone. Methods Retrospective study between 1st April 2010–2014 in a large district general hospital of all ERCPs documenting a common bile duct stone. Electronic records were analysed with the following exclusion criteria: anticoagulants, biliary leak, unchecked cardiac device or incomplete follow up. Balloon sphincteroplasty was always performed after a sphincterotomy, using a Boston Scientific CRE wire guided balloon with a maximal diameter dilation that corresponded to the patient’s mid common bile duct diameter (8–15 mm). Results Total study population was 390 patients. Stone clearance with initial sphincterotomy alone and balloon/basket trawl was successful in 70% (n = 274) patients. 116 patients underwent additional balloon sphincteroplasty with a success rate of 85.5% (n = 100). The remaining patients underwent mechanical lithotripsy (n = 15) or tertiary care referral (n = 1). Therefore, sphincterotomy +/- balloon sphincteroplasty achieved stone clearance in 96% (n = 374) of patients. No statistically significant diferences were observed for complication rates when comparing sphincterotomy alone to balloon sphincteroplasty. Actual complication rates for sphincterotomy alone/balloon sphincteroplasty were: overall 5%/5.2%; pancreatitis 1%/2.6%; cholangitis 3%/3%; bleeding 3%/0% perforation 0%/0%. Conclusion Balloon sphincteroplasty is an effective and safe adjunct in patients who do not achieve bile duct stone clearance with sphincterotomy and balloon/basket trawl alone, allowing clearance rates to exceed current guideline recommendations. Reference 1 Wilkinson, et al. BSG ERCP – the way forward, A standards framework. 2014. http://www.bsg.org.uk Disclosure of Interest None Declared

The associations between three major categories of the neurohistological diagnoses and the epidemiological data were examined in unconfirmed cases of clinically suspect bovine spongiform encephalopathy (BSE). The diagnostic categories were focal spongiosis of white matter (37 cases), encephalic listeriosis (13 cases) and no significant lesions (78 cases). An additional control category of 200 confirmed cases of BSE were included for comparison. Epidemiological variables were the frequencies of specific clinical signs, the season of clinical onset, the age, the duration of the clinical signs and the geographical origin of the cases. Discriminant analysis was used to assess the contribution of these variables to the distinction between the diagnostic categories. The analyses characterised the cases of listeriosis by their shortest clinical duration, the greater prevalences of certain clinical signs and their occurrence mainly in winter and spring, consistent with current understanding of the disease. Cases of focal spongiosis, a lesion of unknown significance, but potentially with a metabolic causation, were tentatively separable from cases with no significant lesions by their winter onset. The results also confirmed that among the categories, the cases of BSE had the longest clinical duration. Despite their statistical significance, the findings do not have sufficient predictive power to be of value in making clinical decisions.

Following the initial diagnosis of chronic copper poisoning (CCP), the copper (Cu) status of a British dairy herd was investigated. Eight fatal cases of CCP were identified over a 17-month period, from December 1999 to May 2001, involving seven Jersey cows and one Holstein-Friesian; seven cows were dry when CCP occurred. Case diagnostic criteria were necrotising hepatopathy associated with abnormally high liver and kidney Cu concentrations. Analysis of the ration for the high-yielding Jersey cow group revealed about 50 mg Cu/kg dry matter intake (DMI). Risk factors predisposing to fatal CCP were Jersey breed, previous high yield, first two weeks of the dry period and moderately high dietary Cu (greater than 40 mg Cu/kg DMI).

In this paper I bring the history of the Hindu traditions of śrāddha and the traditions surrounding Gayā to bear on the history of Gayā and Bodhgayā in order to answer a simple question: Why did the Buddha go to Bodhgayā to achieve enlightenment? The first half of my paper briefly address the textual history of śrāddha in the Brahmanical sources from the earliest domestic ritual manuals, the Gṛhyasūtras, to the dharma and Epic literature, where its centrality to the Gayā pilgrimage is commonly accepted. I then examine the Buddhist texts from the same time frame that evidence the practice of śrāddha, highlighting the conceptions of ancestor worship shared by both Brahmanical and Buddhist sources. In the second half of my paper I synthesize the history of śrāddha and the evidence of the Hindu conception of Gayā and the Buddhist descriptions of Gayā and Uruvelā to describe Gayā during the life of the Buddha and reflect upon why the Buddha is said to have gone there to achieve enlightenment. In the end I hope to expand the context within which we study Bodhgayā, problematizing it to some degree, in order to understand why this place attracted the Buddha.

Introduction The diagnostic yield of endobiliary brush cytology remains inadequate, with published rates ranging from 30–57%. 1 The Infinity TM cytology brush (US Endoscopy, Ohio, USA) aims to improve detection rates by using a combination of stiffer outer bristles to create a tissue defect, and softer inner bristles to capture abraded material. 2 Furthermore, gaps between the bristle segments help capture more tissue in each brush and the brush also has a dedicated catheter that can be flushed/aspirated to retrieve additional cells. We aim to determine whether introducing this new brush could result in an improved diagnostic yield. Method In November 2013, our endoscopy department switched from using a standard cytology brush (Combo Cath TM Rx Cytology Brush, Boston Scientific, Massachusetts, USA) to the Infinity TM cytology brush. Our electronic endoscopy system was retrospectively analysed between April 2010 and December 2014. All patients with pancreatic cancer or cholangiocarcinoma who had brush cytology taken at endoscopic retrograde cholangio-pancreatography were included. A diagnosis of cancer was made by the upper gastrointestinal cancer multidisciplinary team using radiological, histological and/or cytological findings. Patients subsequently found to have benign disease were excluded from the analysis. All strictures were brushed with a minimum of 10 passes, with the addition of bile aspiration when the Infinity TM cytology brush was used. A positive cytological sample was defined as containing either malignant or dysplastic cells. A negative cytology result only contained benign and/or inflammatory cells. All samples were independently reviewed by a consultant histopathologist blinded to the procedure. Group differences were analysed by the Fisher–s exact test. Results Conclusion Our initial experience shows that the use of the Infinity™ cytology brush does not increase diagnostic yield. Further trials of this cytology brush at other centres are required to determine whether our findings are reproducible. Disclosure of interest None Declared. References Larghi A, Waxman I. Differentiating benign from malignant idiopathic biliary strictures: are we there yet? Gastrointest Endosc. 2007 Jul;66(1):97-9 Infinity ERCP sampling device international specification sheet. Available on 27 February 2015 at http://www.usendoscopy.com/∼/media/Files/Documents/Spec-Sheet-International/cytology_INTL_spec_sheet_760893B.pdf

A study of randomly selected dairy farms in England and Wales was made between October 1999 and February 2001 to estimate the prevalence and incidence of Salmonella serovars. The farms were enrolled through five milk-buying companies, which represented 63 per cent of the dairy farms in England and Wales, and they were sampled on up to four occasions (449 farms at visit 1, 272 farms at visit 2, 251 farms at visit 3 and 243 farms at visit 4). In total, 19,296 samples of pooled faecal pats and slurry were collected. The farm-specific prevalence of all serovars of Salmonella ranged from 12.1 per cent (95 per cent confidence interval [CI] 8.2 to 16.0 per cent) to 24.7 per cent (95 per cent CI 19.4 to 30.1 per cent) at each visit. The most common serovars identified were Salmonella Dublin (3.7 to 6.6 per cent farm-specific prevalence at each visit), Salmonella Agama (1.8 to 7.6 per cent) and Salmonella Typhimurium (2.6 to 4.1 per cent) The prevalence varied by region and month of sampling and increased in late summer. The incidence rate of all serovars of Salmonella was 0.43 (95 per cent CI 0.34 to 0.54) cases per farm-year at risk. There was no significant difference between the incidence rates of the common serovars S Typhimurium (0.07), S Dublin (0.06) and S Agama (0.13). A total of 29 Salmonella serovars were isolated. Few of the isolates were resistant to the 16 antimicrobial agents tested, except the isolates of S Typhimurium dt104, of which 67.9 per cent were resistant to at least five of them.

After being vaccinated against rabies some cats and dogs fail to show an antibody titre adequate to meet the requirements of the UK Pet Travel Scheme. To investigate this problem, the data derived from 16,073 serum samples submitted to the Veterinary Laboratories Agency for serological testing between 1999 and 2002, 1002 samples submitted to BioBest during March and April 2001, and 1264 samples associated with one make of vaccine submitted to BioBest between June 2001 and January 2003, were analysed. The probability of antibody titre failing to reach at least 0.5 iu/ml was analysed by logistic regression as a function of the choice of vaccine, the interval between vaccination and sampling, the sex and age of the animal, and its country of origin. In dogs, all these factors, except sex, had highly significant (P

ContextNontypeable Haemophilus influenzae strains form part of the normal flora of the human upper respiratory tract but are also implicated in a wide range of diseases. Infections caused by nontypeable H influenzae are major health and socioeconomic burdens. No single bacterial trait has been associated with disease as opposed to colonization.ObjectivesTo compare IgA1 protease activity in nontypeable H influenzae strains isolated from patients with symptomatic Haemophilus infection (sputum, cerebrospinal fluid, blood, or normally sterile tissue) vs strains from throat swabs of asymptomatic carriers and to compare iga gene carriage and variability in nontypeable H influenzae strains.Design and SettingRetrospective study of 63 strains (44 clinical and 19 carriage) collected between 1991 and 2000 and maintained at the Public Health Laboratory, Gwynedd General Hospital, Bangor, Wales.Main Outcome MeasuresLevels of IgA1 protease activity produced by carriage strains and clinical isolates from symptomatic patients; the determination of the size and sequence of a variable region of the iga gene.ResultsBacterial IgA1 protease activity was significantly higher (P

The single intradermal comparative cervical tuberculin (SICCT) test is the primary test used for surveillance for bovine tuberculosis (bTB) in cattle in Great Britain (GB). The tuberculin used can, with other factors, influence test accuracy. In this analysis, the detection of infected cattle in GB 2005-2009 was compared between SICCT tests using tuberculins manufacturered by different manufacturers. Higher rates of reactors (adjusted rate 209 vs 186 per 100,000 tests, P = 0.003) and herd bTB incidents (adjusted total breakdown rate 5.1 vs 4.5 per 100 herd-years at risk, P < 0.001) were detected using tuberculin manufactured at Weybridge compared with Lelystad. However, confirmation of infection in reactors by postmortem evidence was higher with Lelystad tuberculin (adjusted percent 44.1 vs 47.1, P = 0.018). The findings, overall, suggest slightly higher test sensitivity and lower test specificity associated with Weybridge tuberculin compared with Lelystad. Assuming effective adjustment for confounding, the overall impact of tuberculin manufacturing source (2007-2009), was calculated to range somewhere between 315 false positive breakdowns, and 1086 bTB breakdowns missed (624 confirmed) as a result of using Weybridge and Lelystad tuberculin, respectively. However, animals that tested negative to the SICCT were not slaughtered at the time of the tests, so definitive conclusions are not possible.

Introduction and Objectives Ward based NIV is proven treatment in AECOPD with type II respiratory failure with pH 7.25– 7.35.(1) Increasingly this modality is being used out with the trial evidence. The RCP audit of real world practise showed concerning results: failure or delay to deliver NIV and increaced mortality in NIV-treated patients compared to equally severe patients managed without NIV (26% vs 14%).(2) In light of these factors we reviewed our NIV use across our hospital. Did our local service need improvement? Methods We audited 4 months of emergency department admissiond in late 2011 to 2012, ward based NIV care in February-March 2011 and February-March 2012 using the BTS audit tool and critical care admissions for AECOPD from January 2010 to Decemeber 2011. Emergency Department NIV was only considered in 78% of possible patients and only given in 37%. Significant delays were seen in starting NIV; median 357 minutes (range 138–1366). Ward-based NIV In 2011 overall mortality was 33%, however patients with pH 7.25–7.35 mortality was 11%, matching the landmark trial outcomes.(1) If pH was

Background New and emerging diseases of livestock may impact animal welfare, trade and public health. Early detection of outbreaks can reduce the impact of these diseases by triggering control measures that limit the number of cases that occur. The aim of this study was to investigate whether prospective spatiotemporal methods could be used to identify outbreaks of new and emerging diseases in scanning surveillance data. SaTScan was used to identify clusters of unusually high levels of submissions where a diagnosis could not be reached (DNR) using different probability models and baselines. The clusters detected were subjected to a further selection process to reduce the number of false positives and a more detailed epidemiological analysis to ascertain whether they were likely to represent real outbreaks. Results 187,925 submissions of clinical material from cattle were made to the Regional Laboratory of the Veterinary Laboratories Agency (VLA) between 2002 and 2007, and the results were stored on the VLA FarmFile database. 16,925 of these were classified as DNRs and included in the analyses. Variation in the number and proportion of DNRs was found between syndromes and regions, so a spatiotemporal analysis for each DNR syndrome was done. Six clusters were identified using the Bernoulli model after applying selection criteria (e.g. size of cluster). The further epidemiological analysis revealed that one of the systemic clusters could plausibly have been due to Johne's disease. The remainder were either due to misclassification or not consistent with a single diagnosis. Conclusions Our analyses have demonstrated that spatiotemporal methods can be used to detect clusters of new or emerging diseases, identify clusters of known diseases that may not have been diagnosed and identify misclassification in the data, and highlighted the impact of data quality on the ability to detect outbreaks. Spatiotemporal methods should be used alongside current temporal methods for analysis of scanning surveillance data. These statistical analyses should be followed by further investigation of possible outbreaks to determine whether cases have common features suggesting that these are likely to represent real outbreaks, or whether issues with the collection or processing of information have resulted in false positives.

RADIO-ACTIVITY, the property of radium that led to its isolation more than thirty years ago, is the characteristic that makes it of value in the treatment of disease. Tyler2 gives the following brief history of the investigation: “The way to the discovery of radium was opened in 1895 by Roentgen, who found that the glow from a Crookes tube contained penetrating rays, which he called x-rays. Prof. Henri Becquerel, while investigating the effect of various phosphorescent substances, found that uranium salts produced photographic impressions even when enveloped with opaque substances. To Marie Sklodouska, a young Polish student, who later became Madame Curie, Prof. Becquerel delegated the task of learning how and why uranium possessed power to emit these peculiar rays, which he had proved to be electrical in character. Madame Curie, examining by electrical methods the radio-activity of a large number of minerals containing uranium and thorium, discovered that some specimens of pitchblende had about four time...

THE importance attached to the silicosis problem may be thought of as due to three chief causes: (1) Silica occurs extensively in Nature and is widely used in industry, resulting in the exposure of a large percentage of the industrial population; (2) once silicosis is well established, there is no known treatment capable of restoring normal respiratory function, and in advanced cases there is a definite tendency for them to grow progressively worse, regardless of the measures taken for their relief; (3) individuals suffering from silicosis are particularly susceptible to tuberculosis, so that prevention of silicosis should materially reduce the general morbidity and mortality rates due to pulmonary tuberculosis. It is an axiomatic principle that accurate knowledge concerning the etiology of any disease is a prerequisite to its effectual prevention, diagnosis, and treatment. A certain amount of general information relative to the pathology resulting from the inhalation of dusts has been in existence since ...

"In recent years," wrote Sir George Newman,1"we have learned that public health is not only a matter of the postponing of mortality and the prevention of sickness, but of the positive side of health—the increase of vitality, capacity, and efficiency of the human body. Our aim is not only to oppose diseases but to advance and develop physical fitness and well being. To secure this end, we must have regard to the whole life of man —his heredity and upbringing, his work and rest, his food, his habits, his environment. We must pay attention not only to his actual ailments and diseases, but to the conditions making for a maximum degree of personal health. Thus it comes about that a new relation is found to exist between occupation and health. In a word, the health of the industrial worker forms an integral and inseparable part of the health

Industrial hygiene has been defined as that branch of preventive medicine which has to do with the protection of health of the industrial population. It is much broader than the consideration of specific occupational diseases. Occupational disease is a difficult term to define, for, in addition to the medical difficulties in determining the relationship between the associated industry and the disease, the difficulties are further increased by the fact that occupational diseases are often legally defined, and these legal definitions vary from state to state or from country to country. Many states have schedules of occupational diseases, and no other diseases can be considered as occupational in that particular state. In the Act on Occupational Diseases, recently passed in Illinois, it is stated: "In this Act the term 'occupational disease' means the disease arising out of and in the course of the employment. Ordinary diseases of life to which the

Serious or measurable damage from exposure to benzene or any gas or vapor, obviously, can be Prevented if the concentration of the contaminant and duration of exposure are so controlled that the amount absorbed is insufficient to produce damage. Unfortunatelyrocedures and information necessary for such control are frequently inadequate or completely lacking. As knowledge and understanding of the phenomena that accompany exposure to a gas or vapor increase, the possibility of more perfect control of the industrial disease hazards also increases. The commonly used procedures for the control of chronic benzene poisoning are examination of the blood, particularly for evidence of anemia and leuko-leukopenia,penia,nation of the amount of benzene in the atmosphere. The Bureau of Mines has recently developed a microco 1 1imetricas many desirable featuresustrial hygiene surveys. Owing to the fact that as little as 0.001 mg. of benzene can be detected, the method is also valuable fore determination