Using expert-elicitation to deliver biodiversity monitoring priorities on a Mediterranean island.

Biodiversity monitoring plays an essential role in tracking changes in ecosystems, species distributions and abundances across the globe. Data collected through both structured and unstructured biodiversity recording can inform conservation measures designed to reduce, prevent, and reverse declines in valued biodiversity of many types. However, given that resources for biodiversity monitoring are limited, it is important that funding bodies prioritise investments relative to the requirements in any given region. We addressed this prioritisation requirement for a biodiverse Mediterranean island (Cyprus) using a three-stage process of expert-elicitation. This resulted in a structured list of twenty biodiversity monitoring needs; specifically, a hierarchy of three groups of these needs was created using a consensus approach. The most highly prioritised biodiversity monitoring needs were those related to the development of robust survey methodologies, and those ensuring that sufficiently skilled citizens are available to contribute. We discuss ways that the results of our expert-elicitation process could be used to support current and future biodiversity monitoring in Cyprus.

Voluntary monitoring systems for pig health and welfare in the UK: Comparative analysis of prevalence and temporal patterns of selected non-respiratory post mortem conditions.

Collection of abattoir data related to public health is common worldwide. Standardised on-going programmes that collect information from abattoirs that inform producers about the presence and frequency of disease that are important to them rather than public health hazards are less common. The three voluntary pig health schemes, implemented in the United Kingdom, are integrated systems which capture information on different macroscopic disease conditions detected in slaughtered pigs. Many of these conditions have been associated with a reduction in performance traits and consequent increases in production costs. The schemes are the Wholesome Pigs Scotland in Scotland, the British Pig Health Scheme in England and Wales and the Pig Regen Ltd. health and welfare checks in Northern Ireland. In this study, four post mortem conditions (pericarditis, milk spots, papular dermatitis and tail damage) were surveyed and analysed over a ten and half year period, with the aim to compare the prevalence, monthly variations, and yearly trends between schemes. Liver milk spot was the most frequently recorded condition while tail damage was the least frequently observed condition. The prevalence of papular dermatitis was relatively low compared to liver milk spot and pericarditis in the three schemes. A general decreasing trend was observed for milk spots and papular dermatitis for all three schemes. The prevalence of pericarditis increased in Northern Ireland and England and Wales; while Scotland in recent years showed a decreasing trend. An increasing trend of tail damage was depicted in Scotland and Northern Ireland until 2013/2014 followed by a decline in recent years compared to that of England and Wales with a decreasing trend over the full study period. Monthly effects were more evident for milk spots and papular dermatitis. Similarity of the modus operandi of the schemes made the comparison of temporal variations and patterns in gross pathology between countries possible over time, especially between countries with similar pig production profile. This study of temporal patterns enables early detection of prevalence increases and alerts industry and researchers to investigate the reasons behind such changes. These schemes are, therefore, valuable assets for endemic disease surveillance, early warning for emerging disease and also for monitoring of welfare outcomes.

Comparison of Respiratory Disease Prevalence among Voluntary Monitoring Systems for Pig Health and Welfare in the UK.

Surveillance of animal diseases provides information essential for the protection of animal health and ultimately public health. The voluntary pig health schemes, implemented in the United Kingdom, are integrated systems which capture information on different macroscopic disease conditions detected in slaughtered pigs. Many of these conditions have been associated with a reduction in performance traits and consequent increases in production costs. The schemes are the Wholesome Pigs Scotland in Scotland, the BPEX Pig Health Scheme in England and Wales and the Pig Regen Ltd. health and welfare checks done in Northern Ireland. This report set out to compare the prevalence of four respiratory conditions (enzootic pneumonia-like lesions, pleurisy, pleuropneumonia lesions and abscesses in the lung) assessed by these three Pig Health Schemes. The seasonal variations and year trends associated with the conditions in each scheme are presented. The paper also highlights the differences in prevalence for each condition across these schemes and areas where further research is needed. A general increase in the prevalence of enzootic pneumonia like lesions was observed in Scotland, England and Wales since 2009, while a general decrease was observed in Northern Ireland over the years of the scheme. Pleurisy prevalence has increased since 2010 in all three schemes, whilst pleuropneumonia has been decreasing. Prevalence of abscesses in the lung has decreased in England, Wales and Northern Ireland but has increased in Scotland. This analysis highlights the value of surveillance schemes based on abattoir pathology monitoring of four respiratory lesions. The outputs at scheme level have significant value as indicators of endemic and emerging disease, and for producers and herd veterinarians in planning and evaluating herd health control programs when comparing individual farm results with national averages.

Polymorphisms in the superoxide dismutase-3 gene are associated with emphysema in COPD.

Superoxide dismutase-3 (SOD3) is a major extracellular antioxidant enzyme, and previous studies have indicated a possible role of this gene in chronic obstructive pulmonary disease (COPD). We hypothesized that polymorphisms in the SOD3 gene would be associated with COPD and COPD-related phenotypes. We genotyped three SOD3 polymorphisms (rs8192287 (E1), rs8192288 (I1), and rs1799895 (R213G)) in a case-control cohort, with severe COPD cases from the National Emphysema Treatment Trial (NETT, n = 389) and smoking controls from the Normative Aging Study (NAS, n = 472). We examined whether the single nucleotide polymorphisms (SNPs) were associated with COPD status, lung function variables, and quantitative computed tomography (CT) measurements of emphysema and airway wall thickness. Furthermore, we tried to replicate our initial findings in two family-based studies, the International COPD Genetics Network (ICGN, n = 3061) and the Boston Early-Onset COPD Study (EOCOPD, n = 949). In NETT COPD cases, the minor alleles of SNPs E1 and I1 were associated with a higher percentage of emphysema (%LAA950) on chest CT scan (p = .029 and p = .0058). The association with E1 was replicated in the ICGN family study, where the minor allele was associated with more emphysema (p = .048). Airway wall thickness was positively associated with the E1 SNP in ICGN; however, this finding was not confirmed in NETT. Quantitative CT data were not available in EOCOPD. The SNPs were not associated with lung function variables or COPD status in any of the populations. In conclusion, polymorphisms in the SOD3 gene were associated with CT emphysema but not COPD susceptibility, highlighting the importance of phenotype definition in COPD genetics studies.

Lipid and endothelium-related genes, ambient particulate matter, and heart rate variability--the VA Normative Aging Study.

BACKGROUND: Many studies have shown that exposures to air pollution are associated with cardiovascular events, although the mechanism remains to be clarified. To identify whether exposures to ambient particles act on autonomic function via the lipid/endothelial metabolism pathway, whether effects of particulate matter <2.5 mum in aerodynamic diameter (PM(2.5)) on heart rate variability (HRV) were modified by gene polymorphisms related to those pathways were evaluated. METHODS: HRV and gene data from the Normative Aging Study and PM(2.5) from a monitor located a kilometre from the examination site were used. A mixed model was fitted to investigate the associations between PM(2.5) and repeated measurements of HRV by gene polymorphisms of apolipoprotein E (APOE), lipoprotein lipase (LPL) and vascular endothelial growth factor (VEGF) adjusting for potential confounders chosen a priori. RESULTS: A 10 microg/m(3) increase in PM(2.5) in the 2 days before the examination was associated with 3.8% (95% CI 0.2% to 7.4%), 7.8% (95 CI 0.4% to 15.3%) and 10.6% (95% CI 1.8% to 19.4%) decreases of the standard deviation of normal-to-normal intervals, the low frequency and the high frequency, respectively. Overall, carriers of wild-type APOE, LPL and VEGF genes had stronger effects of particles on HRV than those with hetero- or homozygous types. Variations of LPL-N291S, LPL-D9N and APOE-G113C significantly modified effects of PM(2.5) on HRV. CONCLUSION: Associations between PM(2.5) and HRV were modified by gene polymorphisms of APOE, LPL and VEGF; the biological metabolism remains to be identified.

Ozone exposure, antioxidant genes, and lung function in an elderly cohort: VA normative aging study.

BACKGROUND: Ozone (O3) exposure is known to cause oxidative stress. This study investigated the acute effects of O(3) on lung function in the elderly, a suspected risk group. It then investigated whether genetic polymorphisms of antioxidant genes (heme oxygenase-1 (HMOX1) and glutathione S-transferase pi (GSTP1)) modified these associations. METHODS: 1100 elderly men from the Normative Aging Study were examined whose lung function (forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1)) was measured every 3 years from 1995 to 2005. The study genotyped the GSTP1 Ile105Val and Ala114Val polymorphisms and the (GT)n repeat polymorphism in the HMOX1 promoter, classifying repeats as short (n<25) or long (n> or =25). Ambient O(3) was measured continuously at locations in the Greater Boston area. Mixed linear models were used, adjusting for known confounders. RESULTS: A 15 ppb increase in O(3) during the previous 48 h was associated with a 1.25% decrease in FEV(1) (95% CI: -1.96% to -0.54%). This estimated effect was worsened with either the presence of a long (GT)n repeat in HMOX1 (-1.38%, 95% CI: -2.11% to -0.65%) or the presence of an allele coding for Val105 in GSTP1 (-1.69%, 95% CI: -2.63% to -0.75%). A stronger estimated effect of O(3) on FEV(1) was found in subjects carrying both the GSTP1 105Val variant and the HMOX1 long (GT)n repeat (-1.94%, 95% CI: -2.89% to -0.98%). Similar associations were also found between FVC and O(3) exposure. CONCLUSIONS: Our results suggest that O(3) has an acute effect on lung function in the elderly, and the effects may be modified by the presence of specific polymorphisms in antioxidant genes.

Angry breathing: A prospective study of hostility and lung function in the Normative Aging Study.

BACKGROUND: Hostility and anger are risk factors for, or co-occur with, many health problems of older adults such as cardiovascular diseases, all-cause mortality, and asthma. Evidence that negative emotions are associated with chronic airways obstruction suggests a possible role for hostility in the maintenance and decline of pulmonary function. This study tests the hypothesis that hostility contributes to a faster rate of decline in lung function in older adults. METHODS: A prospective examination was undertaken of the effect of hostility on change in lung function over time. Data are from the VA Normative Aging Study, an ongoing cohort of older men. Hostility was measured in 1986 in 670 men who also had an average of three pulmonary function examinations obtained over an average of 8.2 years of follow up. Hostility was ascertained using the 50-item MMPI based Cook-Medley Hostility Scale. Pulmonary function was assessed using spirometric tests to obtain measures of forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC). RESULTS: Baseline pulmonary function differed between high and medium/low hostility groups (mean (SE) percent predicted FEV(1) 88.9 (18.5) v 95.3 (16.9) and FVC 92.5 (16.5) v 98.9 (15.9), respectively; p < 0.01 for both). This overall association between higher hostility and reduced lung function remained significant after adjusting for smoking and education, although the effect size was attenuated for both FEV1 and FVC. Higher hostility was associated with a more rapid decline in lung function, and this effect was unchanged and remained significant for FEV1)in multivariate models but was attenuated for FVC. Each standard deviation increase in hostility was associated with a loss in FEV1 of approximately 9 ml/year. CONCLUSIONS: This study is one of the first to show prospectively that hostility is associated with poorer pulmonary function and more rapid rates of decline among older men.

Delta-aminolevulinic acid dehydratase polymorphism and the relation between low level lead exposure and the Mini-Mental Status Examination in older men: the Normative Aging Study.

OBJECTIVE: To determine whether a polymorphism the in delta-aminolevulinic acid dehydratase (ALAD) gene modifies the neurotoxicity of lead in older adults. METHODS: The authors studied men participating in the Department of Veterans Affairs' Normative Aging Study, assessing their recent exposure to lead by measuring blood lead (n = 915) at each triennial clinic visit, and, beginning in 1991, assessing their cumulative exposure by measuring lead levels in tibia (n = 722) and patella (n = 720), using K-shell x ray fluorescence. Starting in 1993 and again at each triennial visit, the authors administered the Mini-Mental State Examination (MMSE) to assess their cognitive functioning. The relation of the lead biomarkers to MMSE score was evaluated and this association was compared among men who carried the variant allele, ALAD-2, versus men without the allele. RESULTS: Sixteen per cent of men carried the ALAD-2 allele. Median tibia and patella lead levels (first-third quartile) were 19 (13-28) and 27 (18-39) microg/g. Blood lead levels were consistent with non-occupational exposure: only 6% of men had levels > or =10 microg/dl. In multivariable adjusted analyses, higher levels of blood lead were associated with poorer performance on the MMSE. This association was most pronounced among ALAD-2 carriers, among whom a 3 microg/dl increment in blood lead (the interquartile range) was associated with a 0.26 point lower mean MMSE score (95% CI -0.54 to 0.01), compared with a 0.04 point lower score (95% CI -0.16 to 0.07) among non-carriers. The modest 0.22 point difference in these associations did not attain statistical significance, however (p(interaction) = 0.13). The associations between bone lead levels and MMSE score did not vary by ALAD-2 status. CONCLUSIONS: Although not statistically significant, these findings suggest that ALAD genotype may modify blood lead's adverse association with cognition among older men who had community exposures to lead. However, despite a relatively large sample size and the use of sensitive methods for measuring lead burden, the evidence overall was fairly weak.

Loss of Cited2 affects trophoblast formation and vascularization of the mouse placenta.

Cited2 is widely expressed in the developing embryo and in extraembryonic tissues including the placenta. Gene expression can be induced by a number of factors; most notably by the hypoxia inducible transcription factor, HIF1, under low oxygen conditions. Cited2 encodes for a transcriptional co-factor that in vitro can act as both a positive and negative regulator of transcription. This function is due to its interaction with CBP/p300 and appears to depend on whether Cited2 enables CBP/p300 to interact with the basic transcriptional machinery, or if its binding prevents such an interaction from occurring. Here, we report a novel function for Cited2 in placenta formation, following gene deletion in mouse. In the absence of Cited2 the placenta and embryo are significantly small from 12.5 and 14.5 dpc respectively, and death occurs in utero. Cited2 null placentas have fewer differentiated trophoblast cell types; specifically there is a reduction in trophoblast giant cells, spongiotrophoblasts and glycogen cells. In addition, the fetal vasculature of the placenta is disorganised and there are fewer anastomosing capillaries. Given that Cited2 is expressed in both trophoblasts and the fetal vasculature, the observed defects fit well with the sites of gene expression. We conclude that Cited2 is required for normal placental development and vascularisation, and hence for embryo viability.

Mutation of the LUNATIC FRINGE gene in humans causes spondylocostal dysostosis with a severe vertebral phenotype.

The spondylocostal dysostoses (SCDs) are a heterogeneous group of vertebral malsegmentation disorders that arise during embryonic development by a disruption of somitogenesis. Previously, we had identified two genes that cause a subset of autosomal recessive forms of this disease: DLL3 (SCD1) and MESP2 (SCD2). These genes are important components of the Notch signaling pathway, which has multiple roles in development and disease. Here, we have used a candidate-gene approach to identify a mutation in a third Notch pathway gene, LUNATIC FRINGE (LFNG), in a family with autosomal recessive SCD. LFNG encodes a glycosyltransferase that modifies the Notch family of cell-surface receptors, a key step in the regulation of this signaling pathway. A missense mutation was identified in a highly conserved phenylalanine close to the active site of the enzyme. Functional analysis revealed that the mutant LFNG was not localized to the correct compartment of the cell, was unable to modulate Notch signaling in a cell-based assay, and was enzymatically inactive. This represents the first known mutation in the human LFNG gene and reinforces the hypothesis that proper regulation of the Notch signaling pathway is an absolute requirement for the correct patterning of the axial skeleton.

Kousseff syndrome: a causally heterogeneous disorder.

The existence of Kousseff syndrome as a distinct entity has been thrown into doubt by a recent study conducted on the family originally reported by Kousseff. In all cases where chromosome 22q11.2 FISH testing has been undertaken, including the original sibship, a chromosome 22q11.2-microdeletion has been identified. We report two cases of sacral myelomeningocele associated with a conotruncal cardiac anomaly or "Kousseff syndrome." The first case, a 4-year-old girl, had a sacral myelomeningocele, tetralogy of Fallot, microcephaly, hydrocephalus, hypoplasia of the corpus callosum and mild-moderate developmental delay. Chromosome 22q11.2 FISH was normal and the facial phenotype was not that of velocardiofacial syndrome. Sequencing of the entire coding region of CITED2 did not reveal a mutation. The second case, a male infant, was found to have a 22q11.2-microdeletion. These cases confirm Kousseff syndrome to be a causally heterogeneous disorder.

Association of body mass index with the development of methacholine airway hyperresponsiveness in men: the Normative Aging Study.

BACKGROUND: The rising prevalence of asthma in developed nations may be associated with the rising prevalence of obesity in these same nations. The relationship between body mass index (BMI) and the development of an objective marker for asthma, methacholine airway hyperresponsiveness (AHR), was investigated in adult men. METHODS: Sixty one men who had no AHR at initial methacholine challenge testing but who developed AHR about 4 years later and 244 matched controls participated in the study. The effects of initial BMI and change in BMI on development of AHR were examined in conditional logistic regression models. RESULTS: Initial BMI was found to have a non-linear relationship with development of AHR. Compared with men with initial BMI in the middle quintile, men with BMI in the lowest quintile (BMI=19.8-24.3 kg/m(2)) and those with BMI in the highest quintile (BMI >29.4 kg/m(2)) were more likely to develop AHR: OR=7.0 (95% CI 1.8 to 27.7) and OR=10.0 (95% CI 2.6 to 37.9), respectively. These results remained significant after controlling for age, smoking, IgE level, and initial FEV(1). In addition, there was a positive linear relationship between change in BMI over the period of observation and the subsequent development of AHR. CONCLUSIONS: In this cohort of adult men, both a low BMI and a high BMI were associated with the development of AHR. For men with a low initial BMI the increased risk for development of AHR appears to be partly mediated by a gain in weight. The effect of BMI on AHR may suggest mechanisms in the observed associations between obesity and asthma.

Is the glass half empty or half full? A prospective study of optimism and coronary heart disease in the normative aging study.

OBJECTIVE: A sense of optimism, which derives from the ways individuals explain causes of daily events, has been shown to protect health, whereas pessimism has been linked to poor physical health. We examined prospectively the relationship of an optimistic or pessimistic explanatory style with coronary heart disease incidence in the Veterans Affairs Normative Aging Study, an ongoing cohort of older men. METHODS AND RESULTS: In 1986, 1306 men completed the revised Minnesota Multiphasic Personality Inventory, from which we derived the bipolar revised Optimism-Pessimism Scale. During an average of 10 years of follow-up, 162 cases of incident coronary heart disease occurred: 71 cases of incident nonfatal myocardial infarction, 31 cases of fatal coronary heart disease, and 60 cases of angina pectoris. Compared with men with high levels of pessimism, those reporting high levels of optimism had multivariate-adjusted relative risks of 0.44 (95% confidence interval = 0.26-0.74) for combined nonfatal myocardial infarction and coronary heart disease death and 0.45 (95% confidence interval = 0.29-0.68) for combined angina pectoris, nonfatal myocardial infarction, and coronary heart disease death. A dose-response relation was found between levels of optimism and each outcome (p value for trend,.002 and.0004, respectively). CONCLUSIONS: These results suggest that an optimistic explanatory style may protect against risk of coronary heart disease in older men.

Influence of bone resorption on the mobilization of lead from bone among middle-aged and elderly men: the Normative Aging Study.

Bone stores of lead accrued from environmental exposures and found in most of the general population have recently been linked to the development of hypertension, cognitive decrements, and adverse reproductive outcomes. The skeleton is the major endogenous source of lead in circulating blood, particularly under conditions of accelerated bone turnover and mineral loss, such as during pregnancy and in postmenopausal osteoporosis. We studied the influence of bone resorption rate on the release of lead from bone in 333 men, predominantly white, middle-aged and elderly (mostly retired) from the Boston area. We evaluated bone resorption by measuring cross-linked N-telopeptides of type I collagen (NTx) in 24-hr urine samples with an enzyme-linked immunosorbent assay. We used K-X-ray fluorescence to measure lead content in cortical (tibia) and trabecular (patella) bone; we used graphite furnace atomic absorption spectroscopy and inductively coupled plasma mass spectroscopy to measure lead in blood and urine, respectively. After adjustment for age and creatinine clearance, the positive relation of patella lead to urinary lead was stronger among subjects in the upper two NTx tertiles (beta for patella lead > or =0.015) than in the lowest NTx tertile (beta for patella lead = 0.008; overall p-value for interactions = 0.06). In contrast, we found no statistically significant influence of NTx tertile on the relationship of blood lead to urinary lead. As expected, the magnitude of the relationship of bone lead to urinary lead diminished after adjustment for blood lead. Nevertheless, the pattern of the relationships of bone lead to urinary lead across NTx tertiles remained unchanged. Furthermore, after adjustment for age, the relation of patella lead to blood lead was significantly stronger in the upper two NTx tertiles (beta for patella lead > or =0.125) than in the lowest NTx tertile (beta for patella lead = 0.072). The results provide evidence that bone resorption influences the release of bone lead stores (particularly patella lead) into the circulation.

The delta-aminolevulinic acid dehydratase (ALAD) polymorphism and bone and blood lead levels in community-exposed men: the Normative Aging Study.

Recent research has indicated that a polymorphic variant of delta-aminolevulinic acid dehydratase (ALAD) may influence an individual's level of lead in bone and blood and, as a result, may also influence an individual's susceptibility to lead toxicity. In this study, we investigated whether this ALAD polymorphism is associated with altered levels of lead in bone and blood among 726 middle-aged and elderly men who had community (nonoccupational) exposures to lead. We measured levels of blood and bone lead by graphite furnace atomic absorption spectroscopy and a K X-ray fluorescence (KXRF) instrument, respectively. We determined the ALAD MspI polymorphism in exon 4 by a polymerase chain reaction restriction fragment length polymorphism (RFLP). Of the 726 subjects, 7 (1%) and 111 (15%) were, respectively, homozygous and heterozygous for the variant allele. The mean (SD) of blood lead (micrograms per deciliter), cortical bone (tibia) lead (micrograms per gram), and trabecular bone (patella) lead (micrograms per gram) were 6.2 (4.1), 22.1 (13.5), and 31.9 (19.5) in subjects who did not have the variant allele (ALAD 1-1), and 5.7 (4.2), 21.2 (10.9), and 30.4 (17.2) in the combined subjects who were either heterozygous or homozygous for the variant allele (ALAD 1-2 and ALAD 2-2). In multivariate linear regression models that controlled for age, education, smoking, alcohol ingestion, and vitamin D intake, the ALAD 1-1 genotype was associated with cortical bone lead levels that were 2.55 microg/g [95% confidence interval (CI) 0.05-5.05] higher than those of the variant allele carriers. We found no significant differences by genotype with respect to lead levels in trabecular bone or blood. In stratified analyses and a multivariate regression model that tested for interaction, the relationship of trabecular bone lead to blood lead appeared to be significantly modified by ALAD genotype, with variant allele carriers having higher blood lead levels, but only when trabecular bone lead levels exceeded 60 microg/g. These results suggest that the variant ALAD-2 allele modifies lead kinetics possibly by decreasing lead uptake into cortical bone and increasing the mobilization of lead from trabecular bone.

Gender differences in psychophysiological responses to speech stress among older social phobics:: congruence and incongruence between self-evaluative and cardiovascular reactions.

OBJECTIVE: Evidence suggests increased cardiovascular risk and autonomic impairment among individuals with chronic anxiety. Little attention, however, has been paid to the anxiety disorder of social phobia despite its high prevalence. Additionally, gender- and age-related cardiovascular profiles have not been examined in relation to social phobia. This study investigated cardiovascular responses to a socially threatening situation among older men and women with social phobia and control subjects. METHODS: Thirty subjects with social phobia and 30 control subjects (mean age = 65 years) were assessed during baseline, paced breathing, speech preparation, and speech presentation. Electrocardiographic variables, blood pressure, respiration, and emotional state (self-reported) were monitored. Hemodynamic variables included heart rate, blood pressure, cardiac output, and systemic vascular resistance; autonomic measures were respiratory sinus arrhythmia and baroreflex sensitivity, both markers of cardiac vagal control, and 0.10-Hz systolic blood pressure variability, an index of sympathetic vasomotor tone. RESULTS: Subjects with social phobia, in contrast to nonanxious control subjects, manifested more anxiety, embarrassment, and somatic complaints in response to stress; however, physiological measures generally did not distinguish groups. Interaction effects indicated that socially phobic women were hyperresponsive to the stressor with respect to self-reported, hemodynamic, and autonomic parameters. Socially phobic men manifested no physiological differences in comparison with control subjects, but they reported more psychological and somatic complaints. CONCLUSIONS: Gender differences in subjective and physiological responses to a socially threatening situation indicate congruence between perceived social anxiety and physiological responses in older women but not men. We found no evidence of impaired cardiovascular autonomic regulation among socially phobic men despite other reports that phobically anxious men are at greater cardiovascular risk.

A telephone-linked computer system for COPD care.

The current revolution in communications technology provides an opportunity for novel approaches to management of medical illness. As economic imperatives lead to a progressive reduction in the time that health-care providers spend with their patients, computerized, telephone-linked communication systems offer an inexpensive, widely available alternative with which patients and providers can maintain contact. Such systems may be particularly useful for providing ongoing monitoring and education of patients with chronic illnesses such as COPD. In this article, we describe the general application of telephone-linked communication systems in the health-care setting. We then present in detail one such system, which provides telephone-linked care for COPD (TLC-COPD). The operation of the system is described, as are its theoretical underpinnings in social learning theory. A randomized clinical trial currently is being performed to study the effects of the TLC-COPD system. The rationale for expected improvements in disease control and quality of life, and for a reduction in acute health-care utilization, is discussed.

The small muscle-specific protein Csl modifies cell shape and promotes myocyte fusion in an insulin-like growth factor 1-dependent manner.

We have isolated a murine cDNA encoding a 9-kD protein, Chisel (Csl), in a screen for transcriptional targets of the cardiac homeodomain factor Nkx2-5. Csl transcripts were detected in atria and ventricles of the heart and in all skeletal muscles and smooth muscles of the stomach and pulmonary veins. Csl protein was distributed throughout the cytoplasm in fetal muscles, although costameric and M-line localization to the muscle cytoskeleton became obvious after further maturation. Targeted disruption of Csl showed no overt muscle phenotype. However, ectopic expression in C2C12 myoblasts induced formation of lamellipodia in which Csl protein became tethered to membrane ruffles. Migration of these cells was retarded in a monolayer wound repair assay. Csl-expressing myoblasts differentiated and fused normally, although in the presence of insulin-like growth factor (IGF)-1 they showed dramatically enhanced fusion, leading to formation of large dysmorphogenic "myosacs." The activities of transcription factors nuclear factor of activated T cells (NFAT) and myocyte enhancer-binding factor (MEF)2, were also enhanced in an IGF-1 signaling-dependent manner. The dynamic cytoskeletal localization of Csl and its dominant effects on cell shape and behavior and transcription factor activity suggest that Csl plays a role in the regulatory network through which muscle cells coordinate their structural and functional states during growth, adaptation, and repair.

Receiver operating characteristics curve analysis of cutaneous skin test reactions to predict hay fever and asthma symptoms in the Normative Aging Study.

BACKGROUND: We used receiver operating characteristic (ROC) curves to determine optimal cutoff values and to evaluate the ability of ragweed, mixed grasses, mixed trees, and house-dust antigens to predict symptoms of hay fever and asthma. METHODS: Between 1984 and 1993, 1386 members of the Normative Aging Study cohort had at least one examination that included evaluation of cutaneous hypersensitivity to common aeroallergens by skin prick testing. Standard questionnaires based on the American Thoracic Society DLD-78 questionnaire obtained information on respiratory symptoms, illness, and smoking habits. RESULTS: Ragweed was the best univariate predictor for both hay fever and asthma symptoms: the area under the ROC curve for hay fever was 0.71 (95%) CI 0.67-0.74); for asthma, it was 0.65 (95% CI 0.55-0.75). For hay fever, dichotomizing the average reaction to four antigens at 2 mm gave a sensitivity of 56% and a specificity of 83%; at 3 mm, the sensitivity was 38% and specificity 92%. For asthma, dichotomizing the skin test reaction at 2 mm gave a sensitivity ranging from 30% for reaction to mixed grasses to 56% for the ragweed antigen reaction. CONCLUSIONS: Although in this older population skin test reactivities did not predict current asthma symptoms with high sensitivity, our results support the use of cutoff values of 2 or 3 mm as commonly used in studies of hay fever symptoms.

Bone lead and blood lead levels in relation to baseline blood pressure and the prospective development of hypertension: the Normative Aging Study.

Between 1991 and 1997, the authors studied 833 participants of the Normative Aging Study in a substudy of bone lead levels (measured by K-shell x-ray fluorescence), blood lead levels, and hypertension. Among these subjects, 337 were classified as normotensive, and 182 and 314 were classified as having borderline and definite hypertension, respectively, at baseline. These bone and blood lead levels were typical of those of community-exposed men. Among the 519 subjects with no history of definite hypertension at baseline, cross-sectional analyses revealed positive associations between systolic blood pressure and bone lead levels. Of the 474 subjects who were free from definite hypertension at baseline and had follow-up data, 74 new cases of definite hypertension were reported. Baseline bone lead levels were positively associated with incidence of hypertension. In proportional hazards models that controlled for age, age squared, body mass index, and family history of hypertension, an increase in patella (trabecular) lead from the midpoint of the lowest quintile to that of the highest quintile was associated with a rate ratio of definite hypertension of 1.71 (95% confidence interval: 1.08, 2.70). No association was found with blood lead level. These results support the hypothesis that cumulative exposure to lead, even at low levels sustained by the general population, may increase the risk of hypertension.