Childhood Adversity and Affective Touch Perception: A Comparison of United Kingdom Care Leavers and Non-care Leavers.

In the United Kingdom, the most common reasons for a child to come under the care of social services are neglect and abuse. Such early childhood adversity is a risk factor for social-isolation and poor mental health in adulthood. Touch is a key channel for nurturing interactions, and previous studies have shown links between early somatosensory input, experience dependent neural plasticity, and later life emotional functioning. The aim of the present study was to test the relationship between childhood neglect/abuse and later life experiences, attitudes, and hedonic ratings of affective touch. Here, affective touch is defined as low force, dynamic touch which C-Tactile afferents (CTs) respond optimally to. We hypothesized that a childhood lacking in early nurturing tactile stimulation would be associated with reduced sensitivity to socially relevant affective touch in adulthood. To test this, 19 care leavers (average 9.32 ± 3.70 years in foster care) and 32 non-care leavers were recruited through opportunity sampling (mean age = 21.25 ± 1.74 years). Participants completed a range of psychophysical somatosensory tests. First, they rated the pleasantness of CT-optimal (3 cm/s) and non-CT-optimal (0.3 and 30 cm/s) stroking touch applied to their forearm, both robotically and by an experimenter. They also made vicarious ratings of the anticipated pleasantness of social tactile interactions depicted in a series of videos. Finally, they filled in the Childhood Trauma Questionnaire (CTQ) and the Touch Experiences and Attitudes Questionnaire (TEAQ). As expected, care leavers reported significantly higher levels of childhood trauma than the control group. They also reported significantly lower levels of positive childhood touch compared to non-care leavers, but their attitudes and experiences of current intimate and affiliative touch did not differ. Across all psychophysical tests, care leavers showed specific reduction in sensitivity to the affective value of CT targeted 3 cm/s touch. The results of this study support the hypothesis that a lack of nurturing touch in early developmental periods leads to blunted sensitivity to the specific social value of affective touch. Future research should investigate the neural and physiological mechanisms underlying the observed effect

How do informal information sources influence women’s decision-making for birth? A meta-synthesis of qualitative studies

Background: Women approach birth using various methods of preparation drawing from conventional healthcare providers alongside informal information sources (IIS) outside the professional healthcare context. An investigation of the forms in which these informal information sources are accessed and negotiated by women, and how these disconnected and often conflicting elements influence women’s decision-making process for birth have yet to be evaluated. The level of antenatal preparedness women feel can have significant and long lasting implications on their birth experience and transition into motherhood and beyond. The aim of this study was to provide a deeper understanding of how informal information sources influence women’s preparation for birth. Methods: Seven electronic databases were searched with predetermined search terms. No limitations were imposed for year of publication. English language studies using qualitative methods exploring women’s experiences of informal information sources and their impact upon women’s birth preparation were included, subject to a quality appraisal framework. Searches were initiated in February 2016 and completed by March 2016. Studies were synthesised using an interpretive meta-ethnographic approach. Results: Fourteen studies were included for the final synthesis from Great Britain, Australia, Canada and the United States. Four main themes were identified: Menu Birth; Information Heaven/Hell; Spheres of Support; and Trust. It is evident that women do not enter pregnancy as empty vessels devoid of a conceptual framework, but rather have a pre-constructed embodied knowledge base upon which other information is superimposed. Allied to this, it is clear that informal information was sought to mitigate against the widespread experience of discordant information provided by maternity professionals. Conclusion: Women’s access to the deluge of informal information sources in mainstream media during pregnancy have significant impact on decision making for birth. These informal sources redefine the power dynamic between women and maternal healthcare providers, simultaneously increasing levels of anxiety and challenging women’s pre- existing ideations and aspirations of personal birth processes. A lack of awareness by some professionals of women’s information seeking behaviours generates barriers to women-centred support, leaving an experience expectation mismatch unchecked

Effect of a serogroup A meningococcal conjugate vaccine (PsA-TT) on serogroup A meningococcal meningitis and carriage in Chad: a community study [corrected].

BACKGROUND: A serogroup A meningococcal polysaccharide-tetanus toxoid conjugate vaccine (PsA-TT, MenAfriVac) was licensed in India in 2009, and pre-qualified by WHO in 2010, on the basis of its safety and immunogenicity. This vaccine is now being deployed across the African meningitis belt. We studied the effect of PsA-TT on meningococcal meningitis and carriage in Chad during a serogroup A meningococcal meningitis epidemic. METHODS: We obtained data for the incidence of meningitis before and after vaccination from national records between January, 2009, and June, 2012. In 2012, surveillance was enhanced in regions where vaccination with PsA-TT had been undertaken in 2011, and in one district where a reactive vaccination campaign in response to an outbreak of meningitis was undertaken. Meningococcal carriage was studied in an age-stratified sample of residents aged 1-29 years of a rural area roughly 13-15 and 2-4 months before and 4-6 months after vaccination. Meningococci obtained from cerebrospinal fluid or oropharyngeal swabs were characterised by conventional microbiological and molecular methods. FINDINGS: Roughly 1·8 million individuals aged 1-29 years received one dose of PsA-TT during a vaccination campaign in three regions of Chad in and around the capital N'Djamena during 10 days in December, 2011. The incidence of meningitis during the 2012 meningitis season in these three regions was 2·48 per 100,000 (57 cases in the 2·3 million population), whereas in regions without mass vaccination, incidence was 43·8 per 100,000 (3809 cases per 8·7 million population), a 94% difference in crude incidence (p<0·0001), and an incidence rate ratio of 0·096 (95% CI 0·046-0·198). Despite enhanced surveillance, no case of serogroup A meningococcal meningitis was reported in the three vaccinated regions. 32 serogroup A carriers were identified in 4278 age-stratified individuals (0·75%) living in a rural area near the capital 2-4 months before vaccination, whereas only one serogroup A meningococcus was isolated in 5001 people living in the same community 4-6 months after vaccination (adjusted odds ratio 0·019, 95% CI 0·002-0·138; p<0·0001). INTERPRETATION: PSA-TT was highly effective at prevention of serogroup A invasive meningococcal disease and carriage in Chad. How long this protection will persist needs to be established. FUNDING: The Bill & Melinda Gates Foundation, the Wellcome Trust, and Médecins Sans Frontères

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Nano-Cr-film-based solar selective absorber with high photo-thermal conversion efficiency and good thermal stability

Optical properties and thermal stability of the solar selective absorber based on the metal/dielectric four-layer film structure were investigated in the variable temperature region. Numerical calculations were performed to simulate the spectral properties of multilayer stacks with different metal materials and film thickness. The typical four-layer film structure using the transition metal Cr as the thin solar absorbing layer [SiO2(90nm)/Cr(10nm)/SiO2(80nm)/Al (≥100nm)] was fabricated on the Si or K9 glass substrate by using the magnetron sputtering method. The results indicate that the metal/dielectric film structure has a good spectral selective property suitable for solar thermal applications with solar absorption efficiency higher than 95% in the 400-1200nm wavelength range and a very low thermal emittance in the infrared region. The solar selective absorber with the thin Cr layer has shown a good thermal stability up to the temperature of 873K under vacuum atmosphere. The experimental results are in good agreement with the calculated spectral results.This paper was published in Optics Express 20 (2012): 28953 and is made available as an electronic reprint with the permission of OSA. The paper can be found at the following URL on the OSA website: doi:10.1364/OE.20.028953. Systematic or multiple reproduction or distribution to multiple locations via electronic or other means is prohibited and is subject to penalties under law."</p

Loss-of-function mutations in the X-linked biglycan gene cause a severe syndromic form of thoracic aortic aneurysms and dissections.

Thoracic aortic aneurysm and dissection (TAAD) is typically inherited in an autosomal dominant manner, but rare X-linked families have been described. So far, the only known X-linked gene is FLNA, which is associated with the periventricular nodular heterotopia type of Ehlers-Danlos syndrome. However, mutations in this gene explain only a small number of X-linked TAAD families. We performed targeted resequencing of 368 candidate genes in a cohort of 11 molecularly unexplained Marfan probands. Subsequently, Sanger sequencing of BGN in 360 male and 155 female molecularly unexplained TAAD probands was performed. We found five individuals with loss-of-function mutations in BGN encoding the small leucine-rich proteoglycan biglycan. The clinical phenotype is characterized by early-onset aortic aneurysm and dissection. Other recurrent findings include hypertelorism, pectus deformity, joint hypermobility, contractures, and mild skeletal dysplasia. Fluorescent staining revealed an increase in TGF-β signaling, evidenced by an increase in nuclear pSMAD2 in the aortic wall. Our results are in line with those of prior reports demonstrating that Bgn-deficient male BALB/cA mice die from aortic rupture. In conclusion, BGN gene defects in humans cause an X-linked syndromic form of severe TAAD that is associated with preservation of elastic fibers and increased TGF-β signaling.Genet Med 19 4, 386-395

The opposing transcriptional functions of Sin3a and c-Myc are required to maintain tissue homeostasis.

How the proto-oncogene c-Myc balances the processes of stem-cell self-renewal, proliferation and differentiation in adult tissues is largely unknown. We explored c-Myc's transcriptional roles at the epidermal differentiation complex, a locus essential for skin maturation. Binding of c-Myc can simultaneously recruit (Klf4, Ovol-1) and displace (Cebpa, Mxi1 and Sin3a) specific sets of differentiation-specific transcriptional regulators to epidermal differentiation complex genes. We found that Sin3a causes deacetylation of c-Myc protein to directly repress c-Myc activity. In the absence of Sin3a, genomic recruitment of c-Myc to the epidermal differentiation complex is enhanced, and re-activation of c-Myc-target genes drives aberrant epidermal proliferation and differentiation. Simultaneous deletion of c-Myc and Sin3a reverts the skin phenotype to normal. Our results identify how the balance of two transcriptional key regulators can maintain tissue homeostasis through a negative feedback loop

Valorizing the 'Irulas' traditional knowledge of medicinal plants in the Kodiakkarai Reserve Forest, India

A mounting body of critical research is raising the credibility of Traditional Knowledge (TK) in scientific studies. These studies have gained credibility because their claims are supported by methods that are repeatable and provide data for quantitative analyses that can be used to assess confidence in the results. The theoretical importance of our study is to test consensus (reliability/replicable) of TK within one ancient culture; the Irulas of the Kodiakkarai Reserve Forest (KRF), India. We calculated relative frequency (RF) and consensus factor (Fic) of TK from 120 Irulas informants knowledgeable of medicinal plants. Our research indicates a high consensus of the Irulas TK concerning medicinal plants. The Irulas revealed a diversity of plants that have medicinal and nutritional utility in their culture and specific ethnotaxa used to treat a variety of illnesses and promote general good health in their communities. Throughout history aboriginal people have been the custodians of bio-diversity and have sustained healthy life-styles in an environmentally sustainable manner. However this knowledge has not been transferred to modern society. We suggest this may be due to the asymmetry between scientific and TK, which demands a new approach that considers the assemblage of TK and scientific knowledge. A greater understanding of TK is beginning to emerge based on our research with both the Irulas and Malasars; they believe that a healthy lifestyle is founded on a healthy environment. These aboriginal groups chose to share this knowledge with society-at-large in order to promote a global lifestyle of health and environmental sustainability

Evaluation of Nephroprotective and Immunomodulatory Activities of Antioxidants in Combination with Cisplatin against Murine Visceral Leishmaniasis

Leishmaniasis, a neglected tropical disease (NTD) caused by Leishmania, has been put on the World Health Organization agenda for eradication as a part of their Special Programme for Tropical Diseases Research. Visceral leishmaniasis (VL) is a life-threatening disease when no treatment is given. Most of the drugs still used to treat VL are often expensive, difficult to administer, have serious side effects, and several are becoming ineffective because of increasing parasite resistance. Cisplatin is a first-generation platinum-containing drug, used in the treatment of various solid tumors. We have for the first time characterized the in vivo effect of cisplatin in murine experimental visceral leishmaniasis, but at higher doses it is nephrotoxic. Considering the above findings, the present study was designed to evaluate the protective efficacy of the drug in combination with various antioxidants to reduce or prevent cisplatin-induced nephrotoxicity. Drug treatment induces a higher secretion of Th1 cytokines, diminution in parasite burden, and the supplementation of antioxidants which are antagonists of the toxicity helps in reducing the nephrotoxicity

Population‐based cohort study of outcomes following cholecystectomy for benign gallbladder diseases

Background The aim was to describe the management of benign gallbladder disease and identify characteristics associated with all‐cause 30‐day readmissions and complications in a prospective population‐based cohort. Methods Data were collected on consecutive patients undergoing cholecystectomy in acute UK and Irish hospitals between 1 March and 1 May 2014. Potential explanatory variables influencing all‐cause 30‐day readmissions and complications were analysed by means of multilevel, multivariable logistic regression modelling using a two‐level hierarchical structure with patients (level 1) nested within hospitals (level 2). Results Data were collected on 8909 patients undergoing cholecystectomy from 167 hospitals. Some 1451 cholecystectomies (16·3 per cent) were performed as an emergency, 4165 (46·8 per cent) as elective operations, and 3293 patients (37·0 per cent) had had at least one previous emergency admission, but had surgery on a delayed basis. The readmission and complication rates at 30 days were 7·1 per cent (633 of 8909) and 10·8 per cent (962 of 8909) respectively. Both readmissions and complications were independently associated with increasing ASA fitness grade, duration of surgery, and increasing numbers of emergency admissions with gallbladder disease before cholecystectomy. No identifiable hospital characteristics were linked to readmissions and complications. Conclusion Readmissions and complications following cholecystectomy are common and associated with patient and disease characteristics