Cholesterol and the risk of grade-specific prostate cancer incidence: evidence from two large prospective cohort studies with up to 37 years' follow up

<b>Background</b> High cholesterol may be a modifiable risk factor for prostate cancer but results have been inconsistent and subject to potential "reverse causality" where undetected disease modifies cholesterol prior to diagnosis.<p></p> <b>Methods</b> We conducted a prospective cohort study of 12,926 men who were enrolled in the Midspan studies between 1970 and 1976 and followed up to 31st December 2007. We used Cox-Proportional Hazards Models to evaluate the association between baseline plasma cholesterol and Gleason grade-specific prostate cancer incidence. We excluded cancers detected within at least 5 years of cholesterol assay.<p></p> <b>Results</b> 650 men developed prostate cancer in up to 37 years' follow-up. Baseline plasma cholesterol was positively associated with hazard of high grade (Gleason score[greater than or equal to]8) prostate cancer incidence (n=119). The association was greatest among men in the 4th highest quintile for cholesterol, 6.1 to <6.69 mmol/l, Hazard Ratio 2.28, 95% CI 1.27 to 4.10, compared with the baseline of <5.05 mmol/l. This association remained significant after adjustment for body mass index, smoking and socioeconomic status.<p></p> <b>Conclusions</b> Men with higher cholesterol are at greater risk of developing high-grade prostate cancer but not overall risk of prostate cancer. Interventions to minimise metabolic risk factors may have a role in reducing incidence of aggressive prostate cancer

Lady Gaga as (dis)simulacrum of monstrosity

Lady Gaga’s celebrity DNA revolves around the notion of monstrosity, an extensively researched concept in postmodern cultural studies. The analysis that is offered in this paper is largely informed by Deleuze and Guattari’s notion of monstrosity, as well as by their approach to the study of sign-systems that was deployed in A Thousand Plateaus. By drawing on biographical and archival visual data, with a focus on the relatively underexplored live show, an elucidation is afforded of what is really monstrous about Lady Gaga. The main argument put forward is that monstrosity as sign seeks to appropriate the horizon of unlimited semiosis as radical alterity and openness to signifying possibilities. In this context it is held that Gaga effectively delimits her unique semioscape; however, any claims to monstrosity are undercut by the inherent limits of a representationalist approach in sufficiently engulfing this concept. Gaga is monstrous for her community insofar as she demands of her fans to project their semiosic horizon onto her as a simulacrum of infinite semiosis. However, this simulacrum may only be evinced in a feigned manner as a (dis)simulacrum. The analysis of imagery from seminal live shows during 2011–2012 shows that Gaga’s presumed monstrosity is more akin to hyperdifferentiation as simultaneous employment of heterogeneous and potentially dissonant inter pares cultural representations. The article concludes with a problematisation of audience effects in the light of Gaga’s adoption of a schematic and post-representationalist strategy in the event of her strategy’s emulation by competitive artists

Mortality from suicide and other external cause injuries in China: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>Premature death from suicide is a leading cause of death worldwide. However, the pattern and risk factors for suicide and other external cause injuries are not well understood. This study investigates mortality from suicide and other injuries and associated risk factors in China.</p> <p>Methods</p> <p>A prospective cohort study of 169,871 Chinese adults aged 40 years and older was conducted. Mortality due to suicide or other external cause injuries was recorded.</p> <p>Results</p> <p>Mortality from all external causes was 58.7/100,000 (72.3 in men and 44.4 in women): 14.1/100,000 (14.2 in men and 14.2 in women) for suicide and 44.6/100,000 (58.1 in men and 30.2 in women) for other external cause injuries. Transport accidents (17.2/100,000 overall, 23.4 in men and 10.8 in women), accidental poisoning (7.5/100,000 overall, 10.2 in men and 4.8 in women), and accidental falls (5.7/100,000 overall, 6.5 in men and 5.0 in women) were the three leading causes of death from other external cause injuries in China. In the multivariable analysis, male sex (relative risk [RR] 1.56, 95% confidence interval [CI] 1.03-2.38), age 70 years and older (2.27, 1.29-3.98), living in north China (1.68, 1.20-2.36) and rural residence (2.82, 1.76-4.51) were associated with increased mortality from suicide. Male sex (RR 2.50, 95% CI 1.95-3.20), age 60-69 years (1.93, 1.45-2.58) and 70 years and older (3.58, 2.58-4.97), rural residence (2.29, 1.77-2.96), and having no education (1.56, 1.00-2.43) were associated with increased mortality from other external cause injuries, while overweight (0.60, 0.43-0.83) was associated with decreased risk of mortality from other external cause injuries.</p> <p>Conclusions</p> <p>External cause mortality has become a major public health problem in China. Developing an integrated national program for the prevention of mortality due to external cause injuries in China is warranted.</p

Reproducibility of the airway response to an exercise protocol standardized for intensity, duration, and inspired air conditions, in subjects with symptoms suggestive of asthma

<p>Abstract</p> <p>Background</p> <p>Exercise testing to aid diagnosis of exercise-induced bronchoconstriction (EIB) is commonly performed. Reproducibility of the airway response to a standardized exercise protocol has not been reported in subjects being evaluated with mild symptoms suggestive of asthma but without a definite diagnosis. This study examined reproducibility of % fall in FEV₁and area under the FEV₁time curve for 30 minutes in response to two exercise tests performed with the same intensity and duration of exercise, and inspired air conditions.</p> <p>Methods</p> <p>Subjects with mild symptoms of asthma exercised twice within approximately 4 days by running for 8 minutes on a motorized treadmill breathing dry air at an intensity to induce a heart rate between 80-90% predicted maximum; reproducibility of the airway response was expressed as the 95% probability interval.</p> <p>Results</p> <p>Of 373 subjects challenged twice 161 were positive (≥10% fall FEV₁on at least one challenge). The EIB was mild and 77% of subjects had <15% fall on both challenges. Agreement between results was 76.1% with 56.8% (212) negative (< 10% fall FEV₁) and 19.3% (72) positive on both challenges. The remaining 23.9% of subjects had only one positive test. The 95% probability interval for reproducibility of the % fall in FEV₁and AUC_0-30min was ± 9.7% and ± 251% for all 278 adults and ± 13.4% and ± 279% for all 95 children. The 95% probability interval for reproducibility of % fall in FEV₁and AUC_{0-30 min}for the 72 subjects with two tests ≥10% fall FEV₁was ± 14.6% and ± 373% and for the 34 subjects with two tests ≥15% fall FEV₁it was ± 12.2% and ± 411%. Heart rate and estimated ventilation achieved were not significantly different either on the two test days or when one test result was positive and one was negative.</p> <p>Conclusions</p> <p>Under standardized, well controlled conditions for exercise challenge, the majority of subjects with mild symptoms of asthma demonstrated agreement in test results. Performing two tests may need to be considered when using exercise to exclude or diagnose EIB, when prescribing prophylactic treatment to prevent EIB and when designing protocols for clinical trials.</p

Body indices and basic vital signs in Helicobacter pylori positive and negative persons

It has been hypothesized that Helicobacter pylori (Hp) infection may contribute to reduced stature, risk of hypertension or obesity. The aim was to evaluate body indices in Hp positive and negative persons. A total of 2436 subjects (4–100 years old) were tested for Hp status by 13Curea breath test. Data on height and weight were collected for 84%, and blood pressure for 80% of the study subjects. The prevalence of Hp infection was 41.6%. The odds ratio for a 10-year increase in age was 1.21 (95% CI 1.17–1.25, p-value <0.001). Statistically significant negative association of Hp positivity with body height was most pronounced in the younger age groups, while a positive association of Hp positivity with body mass index was only seen in those aged 15+ years. There was a negative effect of Hp positivity on systolic and diastolic blood pressure in subjects below 25 and a relatively strong positive effect on blood pressure in subjects over 65 years. Residual confounding by social characteristics as a possible explanation for the associations of Hp positivity with height and blood pressure cannot be excluded. Unmeasured factors related to social and family environment may cause the apparent association between Hp positivity and children’s growth and blood pressure

Dynamic Emotional and Neural Responses to Music Depend on Performance Expression and Listener Experience

Apart from its natural relevance to cognition, music provides a window into the intimate relationships between production, perception, experience, and emotion. Here, emotional responses and neural activity were observed as they evolved together with stimulus parameters over several minutes. Participants listened to a skilled music performance that included the natural fluctuations in timing and sound intensity that musicians use to evoke emotional responses. A mechanical performance of the same piece served as a control. Before and after fMRI scanning, participants reported real-time emotional responses on a 2-dimensional rating scale (arousal and valence) as they listened to each performance. During fMRI scanning, participants listened without reporting emotional responses. Limbic and paralimbic brain areas responded to the expressive dynamics of human music performance, and both emotion and reward related activations during music listening were dependent upon musical training. Moreover, dynamic changes in timing predicted ratings of emotional arousal, as well as real-time changes in neural activity. BOLD signal changes correlated with expressive timing fluctuations in cortical and subcortical motor areas consistent with pulse perception, and in a network consistent with the human mirror neuron system. These findings show that expressive music performance evokes emotion and reward related neural activations, and that music's affective impact on the brains of listeners is altered by musical training. Our observations are consistent with the idea that music performance evokes an emotional response through a form of empathy that is based, at least in part, on the perception of movement and on violations of pulse-based temporal expectancies

Microstructural Abnormalities in Subcortical Reward Circuitry of Subjects with Major Depressive Disorder

Previous studies of major depressive disorder (MDD) have focused on abnormalities in the prefrontal cortex and medial temporal regions. There has been little investigation in MDD of midbrain and subcortical regions central to reward/aversion function, such as the ventral tegmental area/substantia nigra (VTA/SN), and medial forebrain bundle (MFB).We investigated the microstructural integrity of this circuitry using diffusion tensor imaging (DTI) in 22 MDD subjects and compared them with 22 matched healthy control subjects. Fractional anisotropy (FA) values were increased in the right VT and reduced in dorsolateral prefrontal white matter in MDD subjects. Follow-up analysis suggested two distinct subgroups of MDD patients, which exhibited non-overlapping abnormalities in reward/aversion circuitry. The MDD subgroup with abnormal FA values in VT exhibited significantly greater trait anxiety than the subgroup with normal FA values in VT, but the subgroups did not differ in levels of anhedonia, sadness, or overall depression severity.These findings suggest that MDD may be associated with abnormal microstructure in brain reward/aversion regions, and that there may be at least two subtypes of microstructural abnormalities which each impact core symptoms of depression

Safety profile and clinical activity of multiple subcutaneous doses of MEDI-528, a humanized anti-interleukin-9 monoclonal antibody, in two randomized phase 2a studies in subjects with asthma

<p>Abstract</p> <p>Background</p> <p>Interleukin-9 (IL-9)-targeted therapies may offer a novel approach for treating asthmatics. Two randomized placebo-controlled studies were conducted to assess the safety profile and potential efficacy of multiple subcutaneous doses of MEDI-528, a humanized anti-IL-9 monoclonal antibody, in asthmatics.</p> <p>Methods</p> <p>Study 1: adults (18-65 years) with mild asthma received MEDI-528 (0.3, 1, 3 mg/kg) or placebo subcutaneously twice weekly for 4 weeks. Study 2: adults (18-50 years) with stable, mild to moderate asthma and exercise-induced bronchoconstriction received 50 mg MEDI-528 or placebo subcutaneously twice weekly for 4 weeks. Adverse events (AEs), pharmacokinetics (PK), immunogenicity, asthma control (including asthma exacerbations), and exercise challenge test were evaluated in study 1, study 2, or both.</p> <p>Results</p> <p>In study 1 (N = 36), MEDI-528 showed linear serum PK; no anti-MEDI-528 antibodies were detected. Asthma control: 1/27 MEDI-528-treated subjects had 1 asthma exacerbation, and 2/9 placebo-treated subjects had a total of 4 asthma exacerbations (one considered a serious AE). In study 2, MEDI-528 (n = 7) elicited a trend in the reduction in mean maximum decrease in FEV₁post-exercise compared to placebo (n = 2) (-6.49% MEDI-528 vs -12.60% placebo; -1.40% vs -20.10%; -5.04% vs -15.20% at study days 28, 56, and 150, respectively). Study 2 was halted prematurely due to a serious AE in an asymptomatic MEDI-528-treated subject who had an abnormal brain magnetic resonance imaging that was found to be an artifact on further evaluation.</p> <p>Conclusions</p> <p>In these studies, MEDI-528 showed an acceptable safety profile and findings suggestive of clinical activity that support continued study in subjects with mild to moderate asthma.</p> <p>Trial registration</p> <p>ClinicalTrials (NCT): <a href="http://www.clinicaltrials.gov/ct2/show/NCT00507130">NCT00507130</a> and ClinicalTrials (NCT): <a href="http://www.clinicaltrials.gov/ct2/show/NCT00590720">NCT00590720</a></p