Sexual Attraction to Others: A Comparison of Two Models of Alloerotic Responding in Men

The penile response profiles of homosexual and heterosexual pedophiles, hebephiles, and teleiophiles to laboratory stimuli depicting male and female children and adults may be conceptualized as a series of overlapping stimulus generalization gradients. This study used such profile data to compare two models of alloerotic responding (sexual responding to other people) in men. The first model was based on the notion that men respond to a potential sexual object as a compound stimulus made up of an age component and a gender component. The second model was based on the notion that men respond to a potential sexual object as a gestalt, which they evaluate in terms of global similarity to other potential sexual objects. The analytic strategy was to compare the accuracy of these models in predicting a man’s penile response to each of his less arousing (nonpreferred) stimulus categories from his response to his most arousing (preferred) stimulus category. Both models based their predictions on the degree of dissimilarity between the preferred stimulus category and a given nonpreferred stimulus category, but each model used its own measure of dissimilarity. According to the first model (“summation model”), penile response should vary inversely as the sum of stimulus differences on separate dimensions of age and gender. According to the second model (“bipolar model”), penile response should vary inversely as the distance between stimulus categories on a single, bipolar dimension of morphological similarity—a dimension on which children are located near the middle, and adult men and women are located at opposite ends. The subjects were 2,278 male patients referred to a specialty clinic for phallometric assessment of their erotic preferences. Comparisons of goodness of fit to the observed data favored the unidimensional bipolar model

Exploration of a potent PI3 kinase/mTOR inhibitor as a novel anti-fibrotic agent in IPF

© 2016 BMJ Publishing Group Ltd & British Thoracic Society.Rationale Idiopathic pulmonary fibrosis (IPF) is the most rapidly progressive and fatal of all fibrotic conditions with no curative therapies. Common pathomechanisms between IPF and cancer are increasingly recognised, including dysfunctional pan-PI3 kinase (PI3K) signalling as a driver of aberrant proliferative responses. GSK2126458 is a novel, potent, PI3K/mammalian target of rapamycin (mTOR) inhibitor which has recently completed phase I trials in the oncology setting. Our aim was to establish a scientific and dosing framework for PI3K inhibition with this agent in IPF at a clinically developable dose. Methods We explored evidence for pathway signalling in IPF lung tissue and examined the potency of GSK2126458 in fibroblast functional assays and precision-cut IPF lung tissue. We further explored the potential of IPF patient-derived bronchoalveolar lavage (BAL) cells to serve as pharmacodynamic biosensors to monitor GSK2126458 target engagement within the lung. Results We provide evidence for PI3K pathway activation in fibrotic foci, the cardinal lesions in IPF. GSK2126458 inhibited PI3K signalling and functional responses in IPF-derived lung fibroblasts, inhibiting Akt phosphorylation in IPF lung tissue and BAL derived cells with comparable potency. Integration of these data with GSK2126458 pharmacokinetic data from clinical trials in cancer enabled modelling of an optimal dosing regimen for patients with IPF. Conclusions Our data define PI3K as a promising therapeutic target in IPF and provide a scientific and dosing framework for progressing GSK2126458 to clinical testing in this disease setting. A proof-ofmechanism trial of this agent is currently underway. Trial registration number NCT01725139, pre-clinical

An approach to holistically assess (dairy) farm eco-efficiency by combining Life Cycle Analysis with Data Envelopment Analysis models and methodologies

Eco-efficiency is a useful guide to dairy farm sustainability analysis aimed at increasing output (physical or value added) and minimizing environmental impacts (EIs). Widely used partial eco-efficiency ratios (EIs per some functional unit, e.g. kg milk) can be problematic because (i) substitution possibilities between EIs are ignored, (ii) multiple ratios can complicate decision making and (iii) EIs are not usually associated with just the functional unit in the ratio's denominator. The objective of this study was to demonstrate a 'global' eco-efficiency modelling framework dealing with issues (i) to (iii) by combining Life Cycle Analysis (LCA) data and the multiple-input, multiple-output production efficiency method Data Envelopment Analysis (DEA). With DEA each dairy farm's outputs and LCA-derived EIs are aggregated into a single, relative, bounded, dimensionless eco-efficiency score, thus overcoming issues (i) to (iii). A novelty of this study is that a model providing a number of additional desirable properties was employed, known as the Range Adjusted Measure (RAM) of inefficiency. These properties altogether make RAM advantageous over other DEA models and are as follows. First, RAM is able to simultaneously minimize EIs and maximize outputs. Second, it indicates which EIs and/or outputs contribute the most to a farm's eco-inefficiency. Third it can be used to rank farms in terms of eco-efficiency scores. Thus, non-parametric rank tests can be employed to test for significant differences in terms of eco-efficiency score ranks between different farm groups. An additional DEA methodology was employed to 'correct' the farms' eco-efficiency scores for inefficiencies attributed to managerial factors. By removing managerial inefficiencies it was possible to detect differences in eco-efficiency between farms solely attributed to uncontrollable factors such as region. Such analysis is lacking in previous dairy studies combining LCA with DEA. RAM and the 'corrective' methodology were demonstrated with LCA data from French specialized dairy farms grouped by region (West France, Continental France) and feeding strategy (regardless of region). Mean eco-efficiency score ranks were significantly higher for farms with 30% maize in the total forage area before correcting for managerial inefficiencies. Mean eco-efficiency score ranks were higher for West than Continental farms, but significantly higher only after correcting for managerial inefficiencies. These results helped identify the eco-efficiency potential of each region and feeding strategy and could therefore aid advisors and policy makers at farm or region/sector level. The proposed framework helped better measure and understand (dairy) farm eco-efficiency, both within and between different farm groups

Predictors of antiretroviral therapy initiation in eThekwini (Durban), South Africa: Findings from a prospective cohort study

Despite expanded antiretroviral therapy (ART) eligibility in South Africa, many people diagnosed with HIV do not initiate ART promptly, yet understanding of the reasons is limited. Using data from an 8-month prospective cohort interview study of women and men newly-diagnosed with HIV in three public-sector primary care clinics in the eThekwini (Durban) region, South Africa, 2010–2014, we examined if theoretically-relevant social-structural, social-cognitive, psychosocial, and health status indicators were associated with time to ART initiation. Of 459 diagnosed, 350 returned to the clinic for their CD4+ test results (linkage); 153 (33.3%) were ART-eligible according to treatment criteria at the time; 115 (75.2% of those eligible) initiated ART (median = 12.86 weeks [95% CI: 9.75, 15.97] after linkage). In adjusted Cox proportional hazard models, internalized stigma was associated with a 65% decrease in the rate of ART initiation (Adjusted hazard ratio [AHR] 0.35, 95% CI: 0.19–0.80) during the period less than four weeks after linkage to care, but not four or more weeks after linkage to care, suggesting that stigma-reduction interventions implemented shortly after diagnosis may accelerate ART uptake. As reported by others, older age was associated with more rapid ART initiation (AHR for 1-year age increase: 1.04, 95% CI: 1.01–1.07) and higher CD4+ cell count (≥300μL vs. <150μL) was associated with a lower rate of initiation (AHR 0.38, 95% CI: 0.19–0.80). Several other factors that were assessed prior to diagnosis, including stronger belief in traditional medicine, higher endorsement of stigma toward people living with HIV, food insecurity, and higher psychological distress, were found to be in the expected direction of association with ART initiation, but confidence intervals were wide and could not exclude a null finding

The relationship of dairy farm eco-efficiency with intensification and self-sufficiency. Evidence from the French dairy sector using Life Cycle Analysis, Data Envelopment Analysis and Partial Least Squares Structural Equation Modelling

We aimed at quantifying the extent to which agricultural management practices linked to animal production and land use affect environmental outcomes at a larger scale. Two practices closely linked to farm environmental performance at a larger scale are farming intensity, often resulting in greater off-farm environmental impacts (land, non-renewable energy use etc.) associated with the production of imported inputs (e.g. concentrates, fertilizer); and the degree of self-sufficiency, i.e. the farm’s capacity to produce goods from its own resources, with higher control over nutrient recycling and thus minimization of losses to the environment, often resulting in greater on-farm impacts (eutrophication, acidification etc.). We explored the relationship of these practices with farm environmental performance for 185 French specialized dairy farms. We used Partial Least Squares Structural Equation Modelling to build, and relate, latent variables of environmental performance, intensification and self-sufficiency. Proxy indicators reflected the latent variables for intensification (milk yield/cow, use of maize silage etc.) and self-sufficiency (home-grown feed/total feed use, on-farm energy/total energy use etc.). Environmental performance was represented by an aggregate ‘eco-efficiency’ score per farm derived from a Data Envelopment Analysis model fed with LCA and farm output data. The dataset was split into two spatially heterogeneous (bio-physical conditions, production patterns) regions. For both regions, eco-efficiency was significantly negatively related with milk yield/cow and the use of maize silage and imported concentrates. However, these results might not necessarily hold for intensive yet more self-sufficient farms. This requires further investigation with latent variables for intensification and self-sufficiency that do not largely overlap- a modelling challenge that occurred here. We conclude that the environmental ‘sustainability’ of intensive dairy farming depends on particular farming systems and circumstances, although we note that more self-sufficient farms may be preferable when they may benefit from relatively low land prices and agri-environment schemes aimed at maintaining grasslands

The Eyes Have It: Sex and Sexual Orientation Differences in Pupil Dilation Patterns

Recent research suggests profound sex and sexual orientation differences in sexual response. These results, however, are based on measures of genital arousal, which have potential limitations such as volunteer bias and differential measures for the sexes. The present study introduces a measure less affected by these limitations. We assessed the pupil dilation of 325 men and women of various sexual orientations to male and female erotic stimuli. Results supported hypotheses. In general, self-reported sexual orientation corresponded with pupil dilation to men and women. Among men, substantial dilation to both sexes was most common in bisexual-identified men. In contrast, among women, substantial dilation to both sexes was most common in heterosexual-identified women. Possible reasons for these differences are discussed. Because the measure of pupil dilation is less invasive than previous measures of sexual response, it allows for studying diverse age and cultural populations, usually not included in sexuality research

Author Correction: The mTORC1/4E-BP1 axis represents a critical signaling node during fibrogenesis

Correction to: Nature Communications https://doi.org/10.1038/s41467-018-07858-8, published online 2 January 2019

The Metabolic Syndrome and the immediate antihypertensive effects of aerobic exercise: a randomized control design

<p>Abstract</p> <p>Background</p> <p>The metabolic syndrome (Msyn) affects about 40% of those with hypertension. The Msyn and hypertension have a common pathophysiology. Exercise is recommended for their treatment, prevention and control. The influence of the Msyn on the antihypertensive effects of aerobic exercise is not known. We examined the influence of the Msyn on the blood pressure (BP) response following low (LIGHT, 40% peak oxygen consumption, VO₂peak) and moderate (MODERATE, 60% VO₂peak) intensity, aerobic exercise.</p> <p>Methods</p> <p>Subjects were 46 men (44.3 ± 1.3 yr) with pre- to Stage 1 hypertension (145.5 ± 1.6/86.3 ± 1.2 mmHg) and borderline dyslipidemia. Men with Msyn (n = 18) had higher fasting insulin, triglycerides and homeostasis model assessment (HOMA) and lower high density lipoprotein than men without Msyn (n = 28) (p < 0.01). Subjects consumed a standard meal and 2 hr later completed one of three randomized experiments separated by 48 hr. The experiments were a non-exercise control session of seated rest and two cycle bouts (LIGHT and MODERATE). BP, insulin and glucose were measured before, during and after the 40 min experiments. Subjects left the laboratory wearing an ambulatory BP monitor for the remainder of the day. Repeated measure ANCOVA tested if BP, insulin and glucose differed over time among experiments in men without and with the Msyn with HOMA as a covariate. Multivariable regression analyses examined associations among BP, insulin, glucose and the Msyn.</p> <p>Results</p> <p>Systolic BP (SBP) was reduced 8 mmHg (p < 0.05) and diastolic BP (DBP) 5 mmHg (p = 0.052) after LIGHT compared to non-exercise control over 9 hr among men without versus with Msyn. BP was not different after MODERATE versus non-exercise control between Msyn groups (p ≥ 0.05). The factors accounting for 17% of the SBP response after LIGHT were baseline SBP (β = -0.351, r²= 0.123, p = 0.020), Msyn (β = 0.277, r²= 0.077, p = 0.069), and HOMA (β = -0.124, r²= 0.015, p = 0.424). Msyn (r²= 0.096, p = 0.036) was the only significant correlate of the DBP response after LIGHT.</p> <p>Conclusion</p> <p>Men without the Msyn respond more favorably to the antihypertensive effects of lower intensity, aerobic exercise than men with the Msyn. If future work confirms our findings, important new knowledge will be gained for the personalization of exercise prescriptions among those with hypertension and the Msyn.</p

How effective is tetracaine 4% gel, before a venipuncture, in reducing procedural pain in infants: a randomized double-blind placebo controlled trial

BACKGROUND: Procedural pain relief is sub-optimal in neonates. Topical tetracaine provides pain relief in children. Evidence of its efficacy and safety in neonates is limited. The objective of this study was to assess the efficacy and safety of topical tetracaine on the pain response of neonates during a venipuncture. METHODS: Medically stable infants greater than or equal to 24 weeks gestation, requiring a venipuncture, were included. Following randomization and double blinding, 1.1 g of tetracaine or placebo was applied to the skin for 30 minutes. Participants received oral sucrose if they met local eligibility criteria. The venipuncture was performed according to a standard protocol. A medium effect size in the pain score (corresponding to about 2 point difference in the PIPP score) was considered clinically significant, leading to a sample size of 142 infants, with 80% statistical power. Local skin reactions and immediate adverse cardiorespiratory events were noted. The primary outcome, PIPP score at 1 minute, was analysed using an independent Student's t-test. RESULTS: One hundred and forty two infants were included, 33 +/- 4 weeks gestation, 2100 +/- 900 grams and 6 +/- 3 days of age. There was almost no difference in PIPP scores at 1 minute between groups (mean difference -0.09; 95% confidence interval [CI]: -1.68 to 1.50; P = . 91). Similarly, there were no differences in PIPP scores during the 2(nd), 3(rd )and 4th minute. Duration of cry did not differ between the groups (median difference, 0; 95% CI, -3 to 0; P = . 84). The majority of infants in both groups received sucrose 24%. Sucrose had a significant effect on the PIPP score, as assessed by an ANOVA model (p = 0.0026). Local skin erythema was observed transiently in 11 infants (7 in the tetracaine and 4 in the placebo group). No serious side effect was observed. CONCLUSION: Tetracaine did not significantly decrease procedural pain in infants undergoing a venipuncture, when used in combination with routine sucrose administration