Gender- and age-related differences in clinical presentation and management of outpatients with stable coronary artery disease

<br>Introduction: Contemporary generalizable data on the demographics and management of outpatients with stable coronary artery disease (CAD) in routine clinical practice are sparse. Using the data from the CLARIFY registry we describe gender- and age-related differences in baseline characteristics and management of these patients across broad geographic regions.</br> <br>Methods: This international, prospective, observational, longitudinal registry enrolled stable CAD outpatients from 45 countries in Africa, Asia, Australia, Europe, the Middle East, and North, Central, and South America.</br> <br>Results: Baseline data were available for 33 280 patients. Mean (SD) age was 64 (10.5) years and 22.5% of patients were female. The prevalence of CAD risk factors was generally higher in women than in men. Women were older (66.6 vs 63.4 years), more frequently diagnosed with diabetes (33% vs 28%), hypertension (79% vs 69%), and higher resting heart rate (69 vs 67 bpm), and were less physically active. Smoking and a history of myocardial infarction were more common in men. Women were more likely to have angina (28% vs 20%), but less likely to have undergone revascularization procedures. CAD was more likely to be asymptomatic in older patients perhaps because of reduced levels of physical activity. Prescription of evidence-based medication for secondary prevention varied with age, with patients ≥ 75 years treated less often with beta blockers, aspirin and angiotensin-converting enzyme inhibitors than patients < 65 years.</br> <br>Conclusions: Important gender-related differences in clinical characteristics and management continue to exist in all age groups of outpatients with stable CAD.</br&gt

Unknotting night-time muscle cramp: a survey of patient experience, help-seeking behaviour and perceived treatment effectiveness

Background: Night-time calf cramping affects approximately 1 in 3 adults. The aim of this study was to explore the experience of night-time calf cramp; if and where people seek treatment advice; and perceived treatment effectiveness. Methods: 80 adults who experienced night-time calf cramp at least once per week were recruited from the Hunter region, NSW, Australia through newspaper, radio and television advertisements. All participants completed a pilot-tested survey about muscle cramp. Quantitative data were analysed with independent-sample t-tests, Chi square tests and Fisher’s tests. Qualitative data were transcribed and sorted into categories to identify themes. Results: Median recalled age of first night-time calf cramp was 50 years. Most participants recalled being awoken from sleep by cramping, and experiencing cramping of either calf muscle, calf-muscle soreness in the days following cramp and cramping during day-time. Despite current therapies, mean usual pain intensity was 66 mm on a 100 mm visual analogue scale. Participants described their cramps as being ‘unbearable’, ‘unmanageable’ and ‘cruel’. One participant stated that ‘sometimes I just wish I could cut my legs open’ and another reported ‘getting about 2h sleep a night due to cramps’. Most participants had sought advice about their night-time calf cramps from a health professional. Participants identified 49 different interventions used to prevent night-time calf cramp. Of all treatment ratings, 68% described the intervention used to prevent cramp as being ‘useless’ or of ‘a little help’. Of 14 participants who provided additional information regarding their use of quinine, eight had a current prescription of quinine for muscle cramp at the time of the survey. None had been asked by their prescribing doctor to stop using quinine. Conclusion: Night time calf cramps typically woke sufferers from sleep, affected either leg and caused ongoing pain. Most participants experienced little or no relief with current therapies used to prevent muscle cramp. Most people who were taking quinine for muscle cramp were unaware that the Australian Therapeutic Goods Administration withdrew support of quinine for muscle cramp in 2004 due to the risk of thrombocytopaenia. Case-control studies are required to identify therapeutic targets so that clinical trials can evaluate safe interventions to prevent recurrent cramp

A Novel Animal Model of Borrelia recurrentis Louse-Borne Relapsing Fever Borreliosis Using Immunodeficient Mice

Louse-borne relapsing fever (LBRF) borreliosis is caused by Borrelia recurrentis, and it is a deadly although treatable disease that is endemic in the Horn of Africa but has epidemic potential. Research on LBRF has been severely hampered because successful infection with B. recurrentis has been achieved only in primates (i.e., not in other laboratory or domestic animals). Here, we present the first non-primate animal model of LBRF, using SCID (-B, -T cells) and SCID BEIGE (-B, -T, -NK cells) immunocompromised mice. These animals were infected with B. recurrentis A11 or A17, or with B. duttonii 1120K3 as controls. B. recurrentis caused a relatively mild but persistent infection in SCID and SCID BEIGE mice, but did not proliferate in NUDE (-T) and BALB/c (wild-type) mice. B. duttonii was infectious but not lethal in all animals. These findings demonstrate that the immune response can limit relapsing fever even in the absence of humoral defense mechanisms. To study the significance of phagocytic cells in this context, we induced systemic depletion of such cells in the experimental mice by injecting them with clodronate liposomes, which resulted in uncontrolled B. duttonii growth and a one-hundred-fold increase in B. recurrentis titers in blood. This observation highlights the role of macrophages and other phagocytes in controlling relapsing fever infection. B. recurrentis evolved from B. duttonii to become a primate-specific pathogen that has lost the ability to infect immunocompetent rodents, probably through genetic degeneration. Here, we describe a novel animal model of B. recurrentis based on B- and T-cell-deficient mice, which we believe will be very valuable in future research on LBRF. Our study also reveals the importance of B-cells and phagocytes in controlling relapsing fever infection

Crises and collective socio-economic phenomena: simple models and challenges

Financial and economic history is strewn with bubbles and crashes, booms and busts, crises and upheavals of all sorts. Understanding the origin of these events is arguably one of the most important problems in economic theory. In this paper, we review recent efforts to include heterogeneities and interactions in models of decision. We argue that the Random Field Ising model (RFIM) indeed provides a unifying framework to account for many collective socio-economic phenomena that lead to sudden ruptures and crises. We discuss different models that can capture potentially destabilising self-referential feedback loops, induced either by herding, i.e. reference to peers, or trending, i.e. reference to the past, and account for some of the phenomenology missing in the standard models. We discuss some empirically testable predictions of these models, for example robust signatures of RFIM-like herding effects, or the logarithmic decay of spatial correlations of voting patterns. One of the most striking result, inspired by statistical physics methods, is that Adam Smith's invisible hand can badly fail at solving simple coordination problems. We also insist on the issue of time-scales, that can be extremely long in some cases, and prevent socially optimal equilibria to be reached. As a theoretical challenge, the study of so-called "detailed-balance" violating decision rules is needed to decide whether conclusions based on current models (that all assume detailed-balance) are indeed robust and generic.Comment: Review paper accepted for a special issue of J Stat Phys; several minor improvements along reviewers' comment

A First Search for coincident Gravitational Waves and High Energy Neutrinos using LIGO, Virgo and ANTARES data from 2007

We present the results of the first search for gravitational wave bursts associated with high energy neutrinos. Together, these messengers could reveal new, hidden sources that are not observed by conventional photon astronomy, particularly at high energy. Our search uses neutrinos detected by the underwater neutrino telescope ANTARES in its 5 line configuration during the period January - September 2007, which coincided with the fifth and first science runs of LIGO and Virgo, respectively. The LIGO-Virgo data were analysed for candidate gravitational-wave signals coincident in time and direction with the neutrino events. No significant coincident events were observed. We place limits on the density of joint high energy neutrino - gravitational wave emission events in the local universe, and compare them with densities of merger and core-collapse events.Comment: 19 pages, 8 figures, science summary page at http://www.ligo.org/science/Publication-S5LV_ANTARES/index.php. Public access area to figures, tables at https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=p120000

A Combination of Genomic Approaches Reveals the Role of FOXO1a in Regulating an Oxidative Stress Response Pathway

Background: While many of the phenotypic differences between human and chimpanzee may result from changes in gene regulation, only a handful of functionally important regulatory differences are currently known. As a first step towards identifying transcriptional pathways that have been remodeled in the human lineage, we focused on a transcription factor, FOXO1a, which we had previously found to be up-regulated in the human liver compared to that of three other primate species. We concentrated on this gene because of its known role in the regulation of metabolism and in longevity. Methodology: Using a combination of expression profiling following siRNA knockdown and chromatin immunoprecipitation in a human liver cell line, we identified eight novel direct transcriptional targets of FOXO1a. This set includes the gene for thioredoxin-interacting protein (TXNIP), the expression of which is directly repressed by FOXO1a. The thioredoxininteracting protein is known to inhibit the reducing activity of thioredoxin (TRX), thereby hindering the cellular response to oxidative stress and affecting life span. Conclusions: Our results provide an explanation for the repeated observations that differences in the regulation of FOXO transcription factors affect longevity. Moreover, we found that TXNIP is down-regulated in human compared to chimpanzee, consistent with the up-regulation of its direct repressor FOXO1a in humans, and with differences in longevity between th

Copy Number Variation across European Populations

Genome analysis provides a powerful approach to test for evidence of genetic variation within and between geographical regions and local populations. Copy number variants which comprise insertions, deletions and duplications of genomic sequence provide one such convenient and informative source. Here, we investigate copy number variants from genome wide scans of single nucleotide polymorphisms in three European population isolates, the island of Vis in Croatia, the islands of Orkney in Scotland and the South Tyrol in Italy. We show that whereas the overall copy number variant frequencies are similar between populations, their distribution is highly specific to the population of origin, a finding which is supported by evidence for increased kinship correlation for specific copy number variants within populations

Enhanced Syllable Discrimination Thresholds in Musicians

Speech processing inherently relies on the perception of specific, rapidly changing spectral and temporal acoustic features. Advanced acoustic perception is also integral to musical expertise, and accordingly several studies have demonstrated a significant relationship between musical training and superior processing of various aspects of speech. Speech and music appear to overlap in spectral and temporal features; however, it remains unclear which of these acoustic features, crucial for speech processing, are most closely associated with musical training. The present study examined the perceptual acuity of musicians to the acoustic components of speech necessary for intra-phonemic discrimination of synthetic syllables. We compared musicians and non-musicians on discrimination thresholds of three synthetic speech syllable continua that varied in their spectral and temporal discrimination demands, specifically voice onset time (VOT) and amplitude envelope cues in the temporal domain. Musicians demonstrated superior discrimination only for syllables that required resolution of temporal cues. Furthermore, performance on the temporal syllable continua positively correlated with the length and intensity of musical training. These findings support one potential mechanism by which musical training may selectively enhance speech perception, namely by reinforcing temporal acuity and/or perception of amplitude rise time, and implications for the translation of musical training to long-term linguistic abilities.Grammy FoundationWilliam F. Milton Fun