Sexual selection protects against extinction

Reproduction through sex carries substantial costs, mainly because only half of sexual adults produce offspring. It has been theorised that these costs could be countered if sex allows sexual selection to clear the universal fitness constraint of mutation load. Under sexual selection, competition between (usually) males, and mate choice by (usually) females create important intraspecific filters for reproductive success, so that only a subset of males gains paternity. If reproductive success under sexual selection is dependent on individual condition, which depends on mutation load, then sexually selected filtering through ‘genic capture’ could offset the costs of sex because it provides genetic benefits to populations. Here, we test this theory experimentally by comparing whether populations with histories of strong versus weak sexual selection purge mutation load and resist extinction differently. After evolving replicate populations of the flour beetle Tribolium castaneum for ~7 years under conditions that differed solely in the strengths of sexual selection, we revealed mutation load using inbreeding. Lineages from populations that had previously experienced strong sexual selection were resilient to extinction and maintained fitness under inbreeding, with some families continuing to survive after 20 generations of sib × sib mating. By contrast, lineages derived from populations that experienced weak or non-existent sexual selection showed rapid fitness declines under inbreeding, and all were extinct after generation 10. Multiple mutations across the genome with individually small effects can be difficult to clear, yet sum to a significant fitness load; our findings reveal that sexual selection reduces this load, improving population viability in the face of genetic stress

Simpson's paradox and calculation of number needed to treat from meta-analysis

BACKGROUND: Calculation of numbers needed to treat (NNT) is more complex from meta-analysis than from single trials. Treating the data as if it all came from one trial may lead to misleading results when the trial arms are imbalanced. DISCUSSION: An example is shown from a published Cochrane review in which the benefit of nursing intervention for smoking cessation is shown by formal meta-analysis of the individual trial results. However if these patients were added together as if they all came from one trial the direction of the effect appears to be reversed (due to Simpson's paradox). Whilst NNT from meta-analysis can be calculated from pooled Risk Differences, this is unlikely to be a stable method unless the event rates in the control groups are very similar. Since in practice event rates vary considerably, the use a relative measure, such as Odds Ratio or Relative Risk is advocated. These can be applied to different levels of baseline risk to generate a risk specific NNT for the treatment. SUMMARY: The method used to calculate NNT from meta-analysis should be clearly stated, and adding the patients from separate trials as if they all came from one trial should be avoided

The 'At-risk mental state' for psychosis in adolescents : clinical presentation, transition and remission.

Despite increased efforts over the last decade to prospectively identify individuals at ultra-high risk of developing a psychotic illness, limited attention has been specifically directed towards adolescent populations (<18 years). In order to evaluate how those under 18 fulfilling the operationalised criteria for an At-Risk Mental State (ARMS) present and fare over time, we conducted an observational study. Participants (N = 30) generally reported a high degree of functional disability and frequent and distressing perceptual disturbance, mainly in the form of auditory hallucinations. Seventy percent (21/30) were found to fulfil the criteria for a co-morbid ICD-10 listed mental health disorder, with mood (affective; 13/30) disorders being most prevalent. Overall transition rates to psychosis were low at 24 months follow-up (2/28; 7.1 %) whilst many participants demonstrated a significant reduction in psychotic-like symptoms. The generalisation of these findings may be limited due to the small sample size and require replication in a larger sample

Smoking Cessation Quitlines in Europe: Matching Services to Callers' Characteristics

<p>Abstract</p> <p>Background</p> <p>Telephone quitlines offer a wide range of services to callers, including advice and counsel, and information on pharmacotherapy for smoking cessation. But, little is known about what specific quitline services are offered to smokers and whether these services are appropriately matched to characteristics of smokers. This study examines how quitline services are matched to callers' level of addiction, educational level, stage-of-change with quitting, and whether they are referred by a doctor or other health professional.</p> <p>Methods</p> <p>Between February 2005 and April 2006, 3,585 callers to seven European quitlines responded to our survey. During the course of and immediately after the call, quitline counsellors collected descriptive data on callers' characteristics and the services they used. We then conducted four logistic regression analyses to examine the relationship between quitline services and the four caller characteristics.</p> <p>Results</p> <p>Forty three percent of all callers received information on pharmacotherapy - most often nicotine patches and nicotine gum - from the counsellor. As we predicted, these callers were the heavy smokers. There was a direct correlation between the length of the conversations between the counsellor and the educational level of the smoker: the lower the education of the smoker, the shorter the call. However, we found no significant association between any other type of service and the educational level of caller. We also found a correlation between the smoker's stage of quitting and the type of advice a counsellor gives. Smokers in the action stage of quitting were more likely to receive advice (in two quitlines) or counselling (in two quitlines) than those in the preparation stage, who were less likely to be referred (in three quitlines). Very few of the total number of calls (10.7%) were from referrals by health professionals. Referred callers were more likely to receive counselling, but this was found only in four of seven quitlines.</p> <p>Conclusion</p> <p>Most of the services quitlines offer to smokers favour heavy smokers and those at a more advanced stage of cessation, but not based on their educational level. Thus, we recommend that European quitlines extend and tailor their services to include less-educated smokers.</p

Prevention of Vitamin D deficiency in infancy: daily 400 IU vitamin D is sufficient

<p>Summary</p> <p>Aim-objective</p> <p>Vitamin D deficiency and rickets in developing countries continues to be a major health problem. Additionally, the increase of cases of rickets in children of some ethnic groups in the United States and European countries has provided this issue to be updated. Obviously, powerful strategies are necessary to prevent vitamin D deficiency nation-wide. In 2005, a nationwide prevention program for vitamin D deficiency was initiated, recommending 400 IU vitamin D per a day.</p> <p>This study was designed to evaluate the efficacy of the prevention program.</p> <p>Methods</p> <p>Eighty-five infants who were recalled as part of the national screening program for congenital hypothyroidism between February 2010 and August 2010 at Kocaeli University Children's Hospital were evaluated in terms of their vitamin D status as well. All babies had been provided with free vitamin D (Cholecalciferol) solution and recommended to receive 400 IU (3 drops) daily. Information regarding the age at start of supplementation, the dosage and compliance were obtained from the mothers with face-to-face interview. Serum 25-hydroxy vitamin D (25-OH-D), alkaline phosphatase (AP), parathormone (PTH) levels were measured.</p> <p>Results</p> <p>The mean age at which Vitamin D3 supplementation began was 16.5 ± 20.7 (3-120) days. Ninety percent of cases (n:76) were receiving 3 drops (400 IU) vitamin D3 per day as recommended; 70% of cases (n:59) were given vitamin D3 regularly, the remainder had imperfect compliance. Among those children who are older than 12 months, only 20% continued vitamin D supplementation. No subject had clinical signs of rickets. The mean 25-OH-D level was 42,5 ± 25,8 (median: 38.3) ng/ml. Ten subjects (12%) had their serum 25-OH-D levels lower than 20 ng/ml (6 between 15-20 ng/ml, 3 between 5-15 ng/ml and only one < 5 ng/ml).</p> <p>Conclusions</p> <p>400 U/day vitamin D seems adequate to prevent vitamin D deficiency. However, we believe that the program for preventing vitamin D deficiency in Turkey, needs to be reinforced to start immediately after birth, and to continue beyond 1 year of age at 400U regular daily dosage.</p

A proposal for a coordinated effort for the determination of brainwide neuroanatomical connectivity in model organisms at a mesoscopic scale

In this era of complete genomes, our knowledge of neuroanatomical circuitry remains surprisingly sparse. Such knowledge is however critical both for basic and clinical research into brain function. Here we advocate for a concerted effort to fill this gap, through systematic, experimental mapping of neural circuits at a mesoscopic scale of resolution suitable for comprehensive, brain-wide coverage, using injections of tracers or viral vectors. We detail the scientific and medical rationale and briefly review existing knowledge and experimental techniques. We define a set of desiderata, including brain-wide coverage; validated and extensible experimental techniques suitable for standardization and automation; centralized, open access data repository; compatibility with existing resources, and tractability with current informatics technology. We discuss a hypothetical but tractable plan for mouse, additional efforts for the macaque, and technique development for human. We estimate that the mouse connectivity project could be completed within five years with a comparatively modest budget.Comment: 41 page

Protocol for the proactive or reactive telephone smoking cessation support (PORTSSS) trial

Background: Telephone quit lines are accessible to many smokers and are used to engage motivated smokers to make quit attempts. Smoking cessation counselling provided via telephone can either be reactive (i.e. primarily involving the provision of evidence-based information), or proactive (i.e. primarily involving repeated, sequenced calls from and interaction with trained cessation counsellors). Some studies have found proactive telephone counselling more effective and this trial will investigate whether or not proactive telephone support for smoking cessation, delivered through the National Health Service (NHS) Smoking Helpline is more effective or cost-effective than reactive support. It will also investigate whether or not providing nicotine replacement therapy (NRT), in addition to telephone counselling, has an adjunctive impact on smoking cessation rates and whether or not this is cost effective. Methods: This will be a parallel group, factorial design RCT, conducted through the English national NHS Smoking Helpline which is run from headquarters in Glasgow. Participants will be smokers who call the helpline from any location in England and who wish to stop smoking. If 644 participants are recruited to four equally-sized trial groups (total sample size = 2576), the trial will have 90% power for detecting a treatment effect (Odds Ratio) of 1.5 for each of the two interventions: i) proactive versus reactive support and ii) the offer of NRT versus no offer. The primary outcome measure for the study is self-reported, prolonged abstinence from smoking for at least six months following an agreed quit date. A concurrent health economic evaluation will investigate the cost effectiveness of the two interventions when delivered via a telephone helpline. Discussion: The PORTSSS trial will provide high quality evidence to determine the most appropriate kind of counselling which should be provided via the NHS Smoking Helpline and also whether or not an additional offer of cost-free NRT is effective and cost effective for smoking cessation. Trial Registration: (clinicaltrials.gov): NCT0077594

Evaluating the effectiveness of a schools-based programme to promote exercise self-efficacy in children and young people with risk factors for obesity: Steps to active kids (STAK)

<p>Abstract</p> <p>Background</p> <p>Low levels of physical activity in children have been linked to an increased risk of obesity, but many children lack confidence in relation to exercise (exercise self-efficacy). Factors which can impact on confidence include a chronic health condition such as asthma, poor motor skills and being overweight. Increasing levels of physical activity have obvious benefits for children with asthma and children who are overweight, but few activity interventions with children specifically target children with low exercise self-efficacy (ESE). This study aims to evaluate the efficacy and feasibility of a schools-based activity programme suitable for children with risk factors for adult obesity, including asthma, overweight and low exercise self-efficacy.</p> <p>Methods/Design</p> <p>A clustered (at the level of school) RCT will be used to compare a targeted, 10 week, stepped activity programme (activity diary, dance DVD, circuit-training and motivational interviewing) designed to promote ESE. We will recruit 20 primary schools to participate in the intervention and 9-11 year old children will be screened for low levels of ESE, asthma and overweight. In order to provide sufficient power to detect a difference in primary outcomes (Body Mass Index-BMI & ESE at 12 month follow-up) between children in the intervention schools and control schools, the target sample size is 396. Assessments of BMI, ESE, waist circumference, peak flow, activity levels and emotional and behavioural difficulties will be made at baseline, 4 months and 12 month follow-up.</p> <p>Discussion</p> <p>We aim to increase ESE and levels of physical activity in children with risk factors for adult obesity. The outcomes of this study will inform policy makers about the feasibility, acceptability and effectiveness of delivering targeted health interventions within a school setting.</p> <p>Trial Registration</p> <p>ISRCTN Register no. <a href="http://www.controlled-trials.com/ISRCTN12650001">ISRCTN12650001</a></p

Comparison of primary care models in the prevention of cardiovascular disease - a cross sectional study

<p>Abstract</p> <p>Background</p> <p>Primary care providers play an important role in preventing and managing cardiovascular disease. This study compared the quality of preventive cardiovascular care delivery amongst different primary care models.</p> <p>Methods</p> <p>This is a secondary analysis of a larger randomized control trial, known as the Improved Delivery of Cardiovascular Care (IDOCC) through Outreach Facilitation. Using baseline data collected through IDOCC, we conducted a cross-sectional study of 82 primary care practices from three delivery models in Eastern Ontario, Canada: 43 fee-for-service, 27 blended-capitation and 12 community health centres with salary-based physicians. Medical chart audits from 4,808 patients with or at high risk of developing cardiovascular disease were used to examine each practice's adherence to ten evidence-based processes of care for diabetes, chronic kidney disease, dyslipidemia, hypertension, weight management, and smoking cessation care. Generalized estimating equation models adjusting for age, sex, rurality, number of cardiovascular-related comorbidities, and year of data collection were used to compare guideline adherence amongst the three models.</p> <p>Results</p> <p>The percentage of patients with diabetes that received two hemoglobin A1c tests during the study year was significantly higher in community health centres (69%) than in fee-for-service (45%) practices (Adjusted Odds Ratio (AOR) = 2.4 [95% CI 1.4-4.2], p = 0.001). Blended capitation practices had a significantly higher percentage of patients who had their waistlines monitored than in fee-for-service practices (19% vs. 5%, AOR = 3.7 [1.8-7.8], p = 0.0006), and who were recommended a smoking cessation drug when compared to community health centres (33% vs. 16%, AOR = 2.4 [1.3-4.6], p = 0.007). Overall, quality of diabetes care was higher in community health centres, while smoking cessation care and weight management was higher in the blended-capitation models. Fee-for-service practices had the greatest gaps in care, most noticeably in diabetes care and weight management.</p> <p>Conclusions</p> <p>This study adds to the evidence suggesting that primary care delivery model impacts quality of care. These findings support current Ontario reforms to move away from the traditional fee-for-service practice.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00574808">NCT00574808</a></p

Diazepam actions in the VTA enhance social dominance and mitochondrial function in the nucleus accumbens by activation of dopamine D1 receptors.

Benzodiazepines can ameliorate social disturbances and increase social competition, particularly in high-anxious individuals. However, the neural circuits and mechanisms underlying benzodiazepines' effects in social competition are not understood. Converging evidence points to the mesolimbic system as a potential site of action for at least some benzodiazepine-mediated effects. Furthermore, mitochondrial function in the nucleus accumbens (NAc) has been causally implicated in the link between anxiety and social competitiveness. Here, we show that diazepam facilitates social dominance, ameliorating both the competitive disadvantage and low NAc mitochondrial function displayed by high-anxious rats, and identify the ventral tegmental area (VTA) as a key site of action for direct diazepam effects. We also show that intra-VTA diazepam infusion increases accumbal dopamine and DOPAC, as well as activity of dopamine D1- but not D2-containing cells. In addition, intra-NAc infusion of a D1-, but not D2, receptor agonist facilitates social dominance and mitochondrial respiration. Conversely, intra-VTA diazepam actions on social dominance and NAc mitochondrial respiration are blocked by pharmacological NAc micro-infusion of a mitochondrial complex I inhibitor or an antagonist of D1 receptors. Our data support the view that diazepam disinhibits VTA dopaminergic neurons, leading to the release of dopamine into the NAc where activation of D1-signaling transiently facilitates mitochondrial function, that is, increased respiration and enhanced ATP levels, which ultimately enhances social competitive behavior. Therefore, our findings critically involve the mesolimbic system in the facilitating effects of diazepam on social competition and highlight mitochondrial function as a potential therapeutic target for anxiety-related social dysfunctions