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1.  Transcriptionally active chromatin recruits homologous recombination at DNA double strand breaks 
While both Homologous recombination (HR) and Non Homologous End Joining (NHEJ) can repair DNA double Strand Breaks (DSB), the mechanisms by which one or other of these pathways is chosen remain unclear. Here we show that transcriptionally active chromatin is preferentially repaired by HR. Using chromatin immunoprecipitation-sequencing (ChIP-seq), to analyse repair of multiple DSBs induced throughout the human genome, we identify an “HR-prone” subset of DSBs that recruit the HR protein RAD51, undergo resection and rely on RAD51 for efficient repair. These DSBs are located in actively transcribed genes, and targeted to HR repair via the transcription-elongation associated histone mark, histone H3 lysine 36 trimethylation (H3K36me3). In agreement, depletion of SETD2, the main H3K36 tri-methyltransferase, severely impedes HR at such DSBs. Our study thereby demonstrates a primary role of the chromatin context, in which a break occurs, in DSB repair.
doi:10.1038/nsmb.2796
PMCID: PMC4300393  PMID: 24658350
DSB repair; NHEJ; HR; chromatin; transcription; ChIP-seq; H3K36me3
2.  Neighborhood Disparities in Prevalence of Childhood Obesity Among Low-Income Children Before and After Implementation of New York City Child Care Regulations 
Introduction
New York City Article 47 regulations, implemented in 2007, require licensed child care centers to improve the nutrition, physical activity, and television-viewing behaviors of enrolled children. To supplement an evaluation of the Article 47 regulations, we conducted an exploratory ecologic study to examine changes in childhood obesity prevalence among low-income preschool children enrolled in the Nutrition Program for Women, Infants, and Children (WIC) in New York City neighborhoods with or without a district public health office. We conducted the study 3 years before (from 2004 through 2006) and after (from 2008 through 2010) the implementation of the regulations in 2007.
Methods
We used an ecologic, time-trend analysis to compare 3-year cumulative obesity prevalence among WIC-enrolled preschool children during 2004 to 2006 and 2008 to 2010. Outcome data were obtained from the New York State component of the Centers for Disease Control and Prevention’s Pediatric Nutrition Surveillance System.
Results
Early childhood obesity prevalence declined in all study neighborhoods from 2004–2006 to 2008–2010. The greatest decline occurred in Manhattan high-risk neighborhoods where obesity prevalence decreased from 18.6% in 2004–2006 to 15.3% in 2008–2010. The results showed a narrowing of the gap in obesity prevalence between high-risk and low-risk neighborhoods in Manhattan and the Bronx, but not in Brooklyn.
Conclusion
The reductions in early childhood obesity prevalence in some high-risk and low-risk neighborhoods in New York City suggest that progress was made in reducing health disparities during the years just before and after implementation of the 2007 regulations. Future research should consider the built environment and markers of differential exposure to known interventions and policies related to childhood obesity prevention.
doi:10.5888/pcd11.140152
PMCID: PMC4208999  PMID: 25321632
3.  Scn3b knockout mice exhibit abnormal sino-atrial and cardiac conduction properties 
Aim
In contrast to extensive reports on the roles of Nav1.5 α-subunits, there have been few studies associating the β-subunits with cardiac arrhythmogenesis. We investigated the sino-atrial and conduction properties in the hearts of Scn3b−/− mice.
Methods
The following properties were compared in the hearts of wild-type (WT) and Scn3b−/− mice: (1) mRNA expression levels of Scn3b, Scn1b and Scn5a in atrial tissue. (2) Expression of the β3 protein in isolated cardiac myocytes. (3) Electrocardiographic recordings in intact anaesthetized preparations. (4) Bipolar electrogram recordings from the atria of spontaneously beating and electrically stimulated Langendorff-perfused hearts.
Results
Scn3b mRNA was expressed in the atria of WT but not Scn3b−/− hearts. This was in contrast to similar expression levels of Scn1b and Scn5a mRNA. Immunofluorescence experiments confirmed that the β3 protein was expressed in WT and absent in Scn3b−/− cardiac myocytes. Lead I electrocardiograms from Scn3b−/− mice showed slower heart rates, longer P wave durations and prolonged PR intervals than WT hearts. Spontaneously beating Langendorff-perfused Scn3b−/− hearts demonstrated both abnormal atrial electrophysiological properties and evidence of partial or complete dissociation of atrial and ventricular activity. Atrial burst pacing protocols induced atrial tachycardia and fibrillation in all Scn3b−/− but hardly any WT hearts. Scn3b−/− hearts also demonstrated significantly longer sinus node recovery times than WT hearts.
Conclusion
These findings demonstrate, for the first time, that a deficiency in Scn3b results in significant atrial electrophysiological and intracardiac conduction abnormalities, complementing the changes in ventricular electrophysiology reported on an earlier occasion.
doi:10.1111/j.1748-1716.2009.02048.x
PMCID: PMC3763209  PMID: 19796257
atrial arrhythmias; beta3; cardiac electrophysiology; Scn3b; sodium channel
4.  Transcription Elongation and Tissue-Specific Somatic CAG Instability 
PLoS Genetics  2012;8(11):e1003051.
The expansion of CAG/CTG repeats is responsible for many diseases, including Huntington's disease (HD) and myotonic dystrophy 1. CAG/CTG expansions are unstable in selective somatic tissues, which accelerates disease progression. The mechanisms underlying repeat instability are complex, and it remains unclear whether chromatin structure and/or transcription contribute to somatic CAG/CTG instability in vivo. To address these issues, we investigated the relationship between CAG instability, chromatin structure, and transcription at the HD locus using the R6/1 and R6/2 HD transgenic mouse lines. These mice express a similar transgene, albeit integrated at a different site, and recapitulate HD tissue-specific instability. We show that instability rates are increased in R6/2 tissues as compared to R6/1 matched-samples. High transgene expression levels and chromatin accessibility correlated with the increased CAG instability of R6/2 mice. Transgene mRNA and H3K4 trimethylation at the HD locus were increased, whereas H3K9 dimethylation was reduced in R6/2 tissues relative to R6/1 matched-tissues. However, the levels of transgene expression and these specific histone marks were similar in the striatum and cerebellum, two tissues showing very different CAG instability levels, irrespective of mouse line. Interestingly, the levels of elongating RNA Pol II at the HD locus, but not the initiating form of RNA Pol II, were tissue-specific and correlated with CAG instability levels. Similarly, H3K36 trimethylation, a mark associated with transcription elongation, was specifically increased at the HD locus in the striatum and not in the cerebellum. Together, our data support the view that transcription modulates somatic CAG instability in vivo. More specifically, our results suggest for the first time that transcription elongation is regulated in a tissue-dependent manner, contributing to tissue-selective CAG instability.
Author Summary
Several dominant genetic diseases, including Huntington's disease (HD) and myotonic dystrophy 1, are caused by the expansion of CAG/CTG repeats. These repeats are unstable in selective tissues. Repeat instability, resulting in the production of increasingly toxic mutant entities in the affected tissues, is proposed to accelerate disease progression. It is therefore essential to unravel the mechanisms contributing to tissue-selective somatic instability. In vitro and cell-based studies indicate that transcription is involved in CAG/CTG instability. However, the role of transcription in CAG/CTG instability in vivo has remained controversial, since mRNA tissue levels of CAG/CTG repeat-containing genes do not correlate with the tissue-specific pattern of instability. Moreover, it is unclear whether the transcriptional process would contribute per se to CAG/CTG instability or whether it is the increased chromatin accessibility associated with transcription that would promote instability. We addressed these issues using two HD transgenic mouse lines recapitulating HD tissue-specific instability. Our in vivo data indicate that high chromatin accessibility and transgene expression do not underlie tissue-selective CAG instability in HD, but suggest that the dynamics of transcription elongation is one mechanism contributing to this process.
doi:10.1371/journal.pgen.1003051
PMCID: PMC3510035  PMID: 23209427
5.  Feasibility of Increasing Childhood Outdoor Play and Decreasing Television Viewing Through a Family-Based Intervention in WIC, New York State, 2007-2008 
Preventing Chronic Disease  2011;8(3):A54.
Introduction
Active Families is a program developed to increase outdoor play and decrease television viewing among preschool-aged children enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). Our objective was to assess its feasibility and efficacy.
Methods
We implemented Active Families in a large WIC clinic in New York State for 1 year. To this end, we incorporated into WIC nutrition counseling sessions a community resource guide with maps showing recreational venues. Outcome measures were children's television viewing and time playing outdoors and parents' behaviors (television viewing, physical activity), self-efficacy to influence children's behaviors, and parenting practices specific to television viewing. We used a nonpaired pretest and posttest design to evaluate the intervention, drawing on comparison data from 3 matched WIC agencies.
Results
Compared with the children at baseline, the children at follow-up were more likely to watch television less than 2 hours per day and play outdoors for at least 60 minutes per day. Additionally, parents reported higher self-efficacy to limit children's television viewing and were more likely to meet physical activity recommendations and watch television less than 2 hours per day.
Conclusion
Results suggest that it is feasible to foster increased outdoor play and reduced television viewing among WIC-enrolled children by incorporating a community resource guide into WIC nutrition counseling sessions. Future research should test the intervention with a stronger evaluation design in multiple settings, with more diverse WIC populations, and by using more objective outcome measures of child behaviors.
PMCID: PMC3103559  PMID: 21477494
6.  Trends in Prevalence of Obesity and Overweight Among Children Enrolled in the New York State WIC Program, 2002–2007 
Public Health Reports  2010;125(2):218-224.
SYNOPSIS
Objective
We examined recent overweight and obesity trends in a multiethnic population of low-income preschool children.
Methods
We defined overweight as sex-specific body mass index (BMI)-for-age ≥85th and <95th percentile and obesity as sex-specific BMI-for-age ≥95th percentile, and calculated them using demographic data and randomly selected height and weight measurements that were recorded while 2- to <5-year-old children were enrolled in the New York State (NYS) Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) during 2002–2007.
Results
Obesity prevalence peaked at 16.7% in 2003, declined from 2003 through 2005, and stabilized at 14.7% through 2007. Among both boys and girls, the downward trend in annual prevalence of obesity was evident only among Hispanic children (22.8% boys and 20.9% girls in 2002 vs. 19.3% boys and 17.5% girls in 2007) and non-Hispanic black children (15.6% boys and 14.2% girls in 2002 vs. 13.6% boys and 12.4% girls in 2007). In contrast, the annual prevalence estimate for overweight showed an increasing trend from 2002 through 2007.
Conclusions
These results showed a slight decline in prevalence of childhood obesity and a continuing rise in prevalence of childhood overweight among children enrolled in the NYS WIC program during 2002–2007. Future research should investigate the extent to which the slight decline in childhood obesity prevalence may be attributable to population-based and high-risk obesity prevention efforts in NYS.
PMCID: PMC2821849  PMID: 20297748
8.  INFORMANT-BASED DEMENTIA SCREENING IN A POPULATION-BASED SAMPLE OF AFRICAN AMERICANS 
BACKGROUND
An informant-based screening tool for dementia may be useful in population-based studies of minority populations.
OBJECTIVE
Investigate the feasibility of screening for very mild dementia in a community sample of African Americans using an informant-based screening tool (AD8).
DESIGN
Cohort study
PARTICIPANTS
147 persons from the African American Health (AAH) project were screened for dementia; 61 of 93 who were invited had follow-up clinical assessments for dementia diagnosis.
MEASUREMENTS
The AD8, Mini-Mental State Examination (MMSE), Short Blessed Test (SBT), Brief Instrument for Dementia Detection (BIDD), and a neuropsychological battery were administered at visit 1. The Clinical Dementia Rating (CDR) was administered at visit 2 by clinicians blinded to visit 1 results; the presence of dementia was determined by a CDR greater than 0.
RESULTS
465 individuals from the AAH cohort were sent a letter describing the study and, among this group, 252 individuals were contacted by phone to request participation in this study. 6% (14 / 252) of participants contacted by phone were unable to identify an informant (required for the AD8). 150 individuals agreed by phone to participate of which 2% (n=3) did not have an informant available at the time of participation. The AD8 alone was effective at discriminating between CDR 0 and CDR 0.5 (area under the curve = .847; p <.001; 95% confidence interval 0.73-0.96).
CONCLUSIONS
A brief informant-based instrument, the AD8, has high sensitivity and specificity for distinguishing CDR 0 from CDR 0.5 in the community. Informant availability may not be a barrier to using the AD8 in an African American community sample; however, further study in larger samples with a higher response rate, different community settings (e.g., community clinics), and among older age groups (e.g., age 75+) is warranted to confirm this.
PMCID: PMC2763355  PMID: 19484913
African Americans; Dementia; Screening
9.  Necrotising soft tissue infection following mastectomy 
Necrotising fasciitis is a rare but rapidly progressive soft tissue disease which can lead to extensive necrosis, systemic sepsis and death. Including this case, only 7 other cases have been reported in the world literature with only 2 others affecting the patient post mastectomy.
This 59 year old Caucasian lady presented with severe soft tissue infection soon after mastectomy, which was successfully treated with a combination of debridement, triangulation, VAC© dressing and skin grafting.
Necrotising soft tissue infections following mastectomy are rapidly progressive and potentially extremely serious. It is essential that a high index of clinical suspicion is maintained together with prompt aggressive treatment in a multidisciplinary environment to prevent worsening physical and psychological sequelae.
doi:10.1093/jscr/2010.1.4
PMCID: PMC3649077  PMID: 24945507
10.  Twelve-month mental disorders in South Africa: prevalence, service use and demographic correlates in the population-based South African Stress and Health Study 
Psychological medicine  2007;38(2):211-220.
Background
South Africa’s history and current social conditions suggest that mental disorders are likely to be a major contributor to disease burden, but there has been no national study using standardized assessment tools.
Method
The South African Stress and Health Study was a nationally representative in-person psychiatric epidemiological survey of 4351 adults (aged ≥18 years) that was conducted as part of the WHO World Mental Health (WMH) Survey Initiative between January 2002 and June 2004. Twelve-month prevalence and severity of DSM-IV disorders, treatment, and sociodemographic correlates were assessed with Version 3.0 of the WHO Composite International Diagnostic Interview (CIDI 3.0).
Results
The 12-month prevalence of any DSM-IV/CIDI disorder was 16.5%, with 26.2% of respondents with disorder classified as severe cases and an additional 31.1% as moderately severe cases. The most common disorders were agoraphobia (4.8 %), major depressive disorder (4.9%) and alcohol abuse or dependence (4.5 %). Twenty-eight percent of adults with a severe or moderately severe disorder received treatment compared to 24.4% of mild cases. Some 13.8% of persons with no disorder received treatment. Treatment was mostly provided by the general medical sector with few people receiving treatment from mental health providers.
Conclusions
Psychiatric disorders are much higher in South Africa than in Nigeria and there is a high level of unmet need among persons with severe and moderately severe disorders.
doi:10.1017/S0033291707001420
PMCID: PMC2718686  PMID: 17903333
Mental disorders; mental health services; South Africa
11.  A second locus for Aicardi‐Goutières syndrome at chromosome 13q14–21 
Journal of Medical Genetics  2005;43(5):444-450.
Background
Aicardi‐Goutières syndrome (AGS) is an autosomal recessive, early onset encephalopathy characterised by calcification of the basal ganglia, chronic cerebrospinal fluid lymphocytosis, and negative serological investigations for common prenatal infections. AGS may result from a perturbation of interferon α metabolism. The disorder is genetically heterogeneous with approximately 50% of families mapping to the first known locus at 3p21 (AGS1).
Methods
A genome‐wide scan was performed in 10 families with a clinical diagnosis of AGS in whom linkage to AGS1 had been excluded. Higher density genotyping in regions of interest was also undertaken using the 10 mapping pedigrees and seven additional AGS families.
Results
Our results demonstrate significant linkage to a second AGS locus (AGS2) at chromosome 13q14–21 with a maximum multipoint heterogeneity logarithm of the odds (LOD) score of 5.75 at D13S768. The AGS2 locus lies within a 4.7 cM region as defined by a 1 LOD‐unit support interval.
Conclusions
We have identified a second AGS disease locus and at least one further locus. As in a number of other conditions, genetic heterogeneity represents a significant obstacle to gene identification in AGS. The localisation of AGS2 represents an important step in this process.
doi:10.1136/jmg.2005.031880
PMCID: PMC2649012  PMID: 15908569
AGS2; Aicardi‐Goutières syndrome; interferon α; intracranial calcification; 13q14–21
12.  The genome of the simian and human malaria parasite Plasmodium knowlesi 
Nature  2008;455(7214):799-803.
Plasmodium knowlesi is an intracellular malaria parasite whose natural vertebrate host is Macaca fascicularis (the ‘kra’ monkey); however, it is now increasingly recognized as a significant cause of human malaria, particularly in southeast Asia1,2. Plasmodium knowlesi was the first malaria parasite species in which antigenic variation was demonstrated3, and it has a close phylogenetic relationship to Plasmodium vivax​4, the second most important species of human malaria parasite (reviewed in ref. 4). Despite their relatedness, there are important phenotypic differences between them, such as host blood cell preference, absence of a dormant liver stage or ‘hypnozoite’ in P. knowlesi, and length of the asexual cycle (reviewed in ref. 4). Here we present an analysis of the P. knowlesi (H strain, Pk1(A+) clone5) nuclear genome sequence. This is the first monkey malaria parasite genome to be described, and it provides an opportunity for comparison with the recently completed P. vivax genome4 and other sequenced Plasmodium genomes6-8. In contrast to other Plasmodium genomes, putative variant antigen families are dispersed throughout the genome and are associated with intrachromosomal telomere repeats. One of these families, the KIRs9, contains sequences that collectively match over one-half of the host CD99 extracellular domain, which may represent an unusual form of molecular mimicry.
doi:10.1038/nature07306
PMCID: PMC2656934  PMID: 18843368
13.  A Novel Size-Selective Airborne Particle Size Fractionating Instrument for Health Risk Evaluation 
Annals of Occupational Hygiene  2009;53(3):225-237.
Health risks associated with the inhalation of airborne particles are known to be influenced by particle size. Studies have shown that certain nanoparticles, with diameters <100 nm, have increased toxicity relative to larger particles of the same substance. A reliable, size-resolving sampler able to collect a wide range of particle sizes, including particles with sizes in the nanometre range, would be beneficial in investigating health risks associated with the inhalation of airborne particles. A review of current aerosol samplers used for size-resolved collection of airborne particles highlighted a number of limitations. These could be overcome by combining an inertial deposition impactor with a diffusion collector in a single device. Verified theories of diffusion and inertial deposition suggested an optimal design and operational regime. The instrument was designed for analysing mass distribution functions. Calibration was carried out using a number of recognized techniques. The sampler was tested in the field by collecting size-resolved samples of lead containing aerosols present at workplaces in factories producing crystal glass. The mass deposited on each screen proved sufficient to be detected and measured by an appropriate analytical technique. Mass concentration distribution functions of lead were produced. The nanofraction of lead in air varied from 10 to 70% by weight of total lead.
doi:10.1093/annhyg/mep002
PMCID: PMC2662094  PMID: 19279163
Brownian diffusion; humidity; inertial deposition; nanoparticles; size-resolved chemical composition; PM10
14.  GPRC6A Null Mice Exhibit Osteopenia, Feminization and Metabolic Syndrome 
PLoS ONE  2008;3(12):e3858.
Background
GPRC6A is a widely expressed orphan G-protein coupled receptor that senses extracellular amino acids, osteocalcin and divalent cations in vitro. The physiological functions of GPRC6A are unknown.
Methods/Principal Findings
In this study, we created and characterized the phenotype of GPRC6A−/− mice. We observed complex metabolic abnormalities in GPRC6A−/− mice involving multiple organ systems that express GPRC6A, including bone, kidney, testes, and liver. GPRC6A−/− mice exhibited hepatic steatosis, hyperglycemia, glucose intolerance, and insulin resistance. In addition, we observed high expression of GPRC6A in Leydig cells in the testis. Ablation of GPRC6A resulted in feminization of male GPRC6A−/− mice in association with decreased lean body mass, increased fat mass, increased circulating levels of estradiol, and reduced levels of testosterone. GPRC6A was also highly expressed in kidney proximal and distal tubules, and GPRC6A−/− mice exhibited increments in urine Ca/Cr and PO4/Cr ratios as well as low molecular weight proteinuria. Finally, GPRC6A−/− mice exhibited a decrease in bone mineral density (BMD) in association with impaired mineralization of bone.
Conclusions/Significance
GPRC6A−/− mice have a metabolic syndrome characterized by defective osteoblast-mediated bone mineralization, abnormal renal handling of calcium and phosphorus, fatty liver, glucose intolerance and disordered steroidogenesis. These findings suggest the overall function of GPRC6A may be to coordinate the anabolic responses of multiple tissues through the sensing of extracellular amino acids, osteocalcin and divalent cations.
doi:10.1371/journal.pone.0003858
PMCID: PMC2585477  PMID: 19050760
16.  Physiological upper limits of ventricular cavity size in highly trained adolescent athletes 
Heart  2005;91(4):495-499.
Objectives: To define physiological upper limits of left ventricular (LV) cavity size in trained adolescent athletes.
Design: Cross sectional echocardiographic study.
Setting: British national sports training grounds and Olympic Medical Institute.
Subjects: 900 elite adolescent athletes (77% boys) aged 15.7 (1.2) years participating in ball, racket, and endurance sports and 250 healthy controls matched for age, sex, and size.
Main outcome measures: LV end diastolic cavity size.
Results: Compared with controls, athletes had a larger LV cavity (50.8 (3.7) v 47.9 (3.5) mm), a difference of 6%. The LV cavity was > 54 mm in 18% athletes, whereas none of the controls had an LV cavity > 54 mm. The LV cavity exceeded predicted sizes in 117 (13%) athletes. Among the athletes with LV dilatation, 78% were boys, LV size ranged from 52–60 mm, and left atrial diameter and LV wall thickness were enlarged. Systolic and diastolic function were normal. None of the athletes in the study had an LV cavity size > 60 mm. LV cavity size correlated with age, sex, heart rate, and body surface area.
Conclusion: Highly trained junior athletes usually have only modest increases in LV cavity size. A proportion of trained adolescent athletes have LV cavity size exceeding predicted values but, in absolute terms, LV cavity rarely exceeds 60 mm as in patients with dilated cardiomyopathy. In highly trained adolescent athletes with an LV cavity size > 60 mm and any impairment of systolic or diastolic function, the diagnosis of dilated cardiomyopathy should be considered.
doi:10.1136/hrt.2004.035121
PMCID: PMC1768829  PMID: 15772210
adolescent; elite athlete; athlete’s heart; cardiomyopathy; ventricular cavity dilatation
17.  Identification of a Novel Extracellular Cation-sensing G-protein-coupled Receptor* 
The Journal of biological chemistry  2005;280(48):40201-40209.
The C family G-protein-coupled receptors contain members that sense amino acid and extracellular cations, of which calcium-sensing receptor (CASR) is the prototypic extracellular calcium-sensing receptor. Some cells, such as osteoblasts in bone, retain responsiveness to extracellular calcium in CASR-deficient mice, consistent with the existence of another calcium-sensing receptor. We examined the calcium-sensing properties of GPRC6A, a newly identified member of this family. Alignment of GPRC6A with CASR revealed conservation of both calcium and calcimimetic binding sites. In addition, calcium, magnesium, strontium, aluminum, gadolinium, and the calcimimetic NPS 568 resulted in a dose-dependent stimulation of GPRC6A overexpressed in human embryonic kidney cells 293 cells. Also, osteocalcin, a calcium-binding protein highly expressed in bone, dose-dependently stimulated GPRC6A activity in the presence of calcium but inhibited the calcium-dependent activation of CASR. Coexpression of β-arrestins 1 and 2, regulators of G-protein signaling RGS2 or RGS4, the RhoA inhibitor C3 toxin, the dominant negative Gαq-(305–359) minigene, and pretreatment with pertussis toxin inhibited activation of GPRC6A by extracellular cations. Reverse transcription-PCR analyses showed that mouse GPRC6A is widely expressed in mouse tissues, including bone, calvaria, and the osteoblastic cell line MC3T3-E1. These data suggest that in addition to sensing amino acids, GPRC6A is a cation-, calcimimetic-, and osteocalcin-sensing receptor and a candidate for mediating extracellular calcium-sensing responses in osteoblasts and possibly other tissues.
doi:10.1074/jbc.M505186200
PMCID: PMC1435382  PMID: 16199532
18.  L-carnitine in cyclical vomiting syndrome 
doi:10.1136/adc.2003.047183
PMCID: PMC1719739  PMID: 15557068
19.  Cardiac troponins 
Journal of Clinical Pathology  2004;57(10):1025-1026.
doi:10.1136/jcp.2003.015420
PMCID: PMC1770452  PMID: 15452153
cardiac troponins; myocardial infarction; ischaemic heart disease; diagnosis
20.  Genetic Diversity among Botulinum Neurotoxin-Producing Clostridial Strains▿  
Journal of Bacteriology  2006;189(3):818-832.
Clostridium botulinum is a taxonomic designation for many diverse anaerobic spore-forming rod-shaped bacteria that have the common property of producing botulinum neurotoxins (BoNTs). The BoNTs are exoneurotoxins that can cause severe paralysis and death in humans and other animal species. A collection of 174 C. botulinum strains was examined by amplified fragment length polymorphism (AFLP) analysis and by sequencing of the 16S rRNA gene and BoNT genes to examine the genetic diversity within this species. This collection contained representatives of each of the seven different serotypes of botulinum neurotoxins (BoNT/A to BoNT/G). Analysis of the16S rRNA gene sequences confirmed previous identifications of at least four distinct genomic backgrounds (groups I to IV), each of which has independently acquired one or more BoNT genes through horizontal gene transfer. AFLP analysis provided higher resolution and could be used to further subdivide the four groups into subgroups. Sequencing of the BoNT genes from multiple strains of serotypes A, B, and E confirmed significant sequence variation within each serotype. Four distinct lineages within each of the BoNT A and B serotypes and five distinct lineages of serotype E strains were identified. The nucleotide sequences of the seven toxin genes of the serotypes were compared and showed various degrees of interrelatedness and recombination, as was previously noted for the nontoxic nonhemagglutinin gene, which is linked to the BoNT gene. These analyses contribute to the understanding of the evolution and phylogeny within this species and assist in the development of improved diagnostics and therapeutics for the treatment of botulism.
doi:10.1128/JB.01180-06
PMCID: PMC1797315  PMID: 17114256
22.  Measuring the fate of plant diversity: towards a foundation for future monitoring and opportunities for urgent action 
Vascular plants are often considered to be among the better known large groups of organisms, but gaps in the available baseline data are extensive, and recent estimates of total known (described) seed plant species range from 200 000 to 422 000. Of these, global assessments of conservation status using International Union for the Conservation of Nature (IUCN) categories and criteria are available for only approximately 10 000 species. In response to recommendations from the Conference of the Parties to the Convention on Biological Diversity to develop biodiversity indicators based on changes in the status of threatened species, and trends in the abundance and distribution of selected species, we examine how existing data, in combination with limited new data collection, can be used to maximum effect. We argue that future work should produce Red List Indices based on a representative subset of plant species so that the limited resources currently available are directed towards redressing taxonomic and geographical biases apparent in existing datasets. Sampling the data held in the world's major herbaria, in combination with Geographical Information Systems techniques, can produce preliminary conservation assessments and help to direct selective survey work using existing field networks to verify distributions and gather population data. Such data can also be used to backcast threats and potential distributions through time. We outline an approach that could result in: (i) preliminary assessments of the conservation status of tens of thousands of species not previously assessed, (ii) significant enhancements in the coverage and representation of plant species on the IUCN Red List, and (iii) repeat and/or retrospective assessments for a significant proportion of these. This would result in more robust Sampled Red List Indices that can be defended as more representative of plant diversity as a whole; and eventually, comprehensive assessments at species level for one or more major families of angiosperms. The combined results would allow scientifically defensible generalizations about the current status of plant diversity by 2010 as well as tentative comments on trends. Together with other efforts already underway, this approach would establish a firmer basis for ongoing monitoring of the status of plant diversity beyond 2010 and a basis for comparison with the trend data available for vertebrates.
doi:10.1098/rstb.2004.1596
PMCID: PMC1569457  PMID: 15814350
global biodiversity; species richness; conservation assessments; extinction risk; IUCN Red List; Living Planet Index
23.  Acute effects of winter air pollution on respiratory function in schoolchildren in southern England 
Aim: To investigate the acute health effects of winter outdoor air pollution (nitrogen dioxide (NO2), ozone (O3), sulphur dioxide (SO2), sulphate (SO42-) ,and particles (PM10)) on schoolchildren in an area of southern England where levels of SO2 had been reported to be high.
Methods: A total of 179 children, aged 7–13, from three schools (two urban and one rural location), were included. Peak expiratory flow rate (PEFR) and presence or absence of upper respiratory infections were recorded on 63 school days from 1 November 1996 to 14 February 1997. Air pollution and meteorological data were taken from monitors at each school site. The analysis regressed daily PEFR on pollutant level adjusting for confounders and serial correlation and calculated a weighted pooled estimate of effect overall for each pollutant. In addition, large decrements in PEFR were analysed as a binary outcome. Same day, lag 1, lag 2, and a five day average of pollutant levels were used.
Results: There were no clear effects of any pollutant on mean PEFR. In addition, we analysed large PEFR decrements (a binary outcome), observing consistent negative associations with NO2, SO42-, and PM10, although few lag/pollutant combinations were significant: odds ratios (95% CI) for five day average effect: NO2 24 h average 1.043 (1.000 to 1.089), SO42- 1.090 (0.898 to 1.322), PM10 1.037 (0.992 to 1.084). The observed effects of PM10 (only) were stronger in wheezy children (1.114 (1.057 to 1.174)). There were no consistent negative associations between large decrements and ozone or SO2 .
Conclusions: There is no strong evidence for acute effects of winter outdoor air pollution on mean PEFR overall in this area, but there is evidence for negative effects on large PEFR decrements.
doi:10.1136/oem.60.2.82
PMCID: PMC1740463  PMID: 12554833
24.  An audit of first aid qualifications and knowledge among team officials in two English youth football leagues: a preliminary study 
Objectives: To determine if youth football officials responsible for dealing with injuries have appropriate first aid qualifications and knowledge?
Methods: Information was collected from two youth football leagues by questionnaire. First aiders were asked to provide details of their qualifications and their response from a list of alternatives to an injury scenario.
Results: Fifty two of 86 respondents did not have a current first aid qualification. Only 12% and 38% respectively gave the correct response to the injury scenarios "player choking" and "player unconscious". Health and injury records for the players were kept by 40% and 19% of teams. Written parental consent to emergency treatment was obtained by 30%.
Conclusion: This preliminary study shows an obligation on teams who do not possess a qualified first aider to evaluate their legal and moral responsibilities to their players. The Football Association and Health and Safety Executive should produce a list of recommended equipment, facilities, and first aid qualified personnel to which teams should have access at games and training sessions. Providers of first aid training should reassess their teaching of the management of the choking and unconscious casualty.
doi:10.1136/bjsm.36.4.295
PMCID: PMC1724527  PMID: 12145121
25.  An Innovative Approach to Enhancing the Surveillance Capacity of State-based Diabetes Prevention and Control Programs: The Diabetes Indicators and Data Sources Internet Tool (DIDIT) 
Preventing Chronic Disease  2005;2(3):A14.
The Diabetes Indicators and Data Sources Internet Tool (DIDIT) is an interactive Web-based resource with information on 38 diabetes indicators (e.g., diabetes-associated complications, care, lifestyle) and 12 associated data sources frequently used by state diabetes prevention and control programs. This tool is designed to strengthen the ability of states to conduct diabetes surveillance and to promote consistency in defining and tracking indicators across states. In this way, the DIDIT supports one of the 10 essential public health services: the timely and accurate assessment of public health.
In addition to serving as a central repository of information on diabetes surveillance, the DIDIT also allows users to share experiences of using these indicators and data sources in their diabetes surveillance activities, data analysis, and tracking of diabetes-related objectives stated by Healthy People 2010. The DIDIT is an innovative approach to enhancing public health surveillance at the state and national levels.
PMCID: PMC1364523  PMID: 15963316

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