Genome-wide association meta-analysis of human longevity identifies a novel locus conferring survival beyond 90 years of age

The genetic contribution to the variation in human lifespan is approximately 25%.  Despite the large number of identified disease-susceptibility loci, it is not known which loci influence population mortality.  We performed a genome-wide association meta-analysis of 7729 long-lived individuals of European descent (≥ 85 years) and 16121 younger controls (< 65 years) followed by replication in an additional set of 13060 long-lived individuals and 61156 controls. In addition, we performed a subset analysis in cases ≥ 90 years. We observed genome-wide significant association with longevity, as reflected by survival to ages beyond 90 years, at a novel locus, rs2149954, on chromosome 5q33.3 (OR = 1.10, P =1.74 x 10-8). We also confirmed association of rs4420638 on chromosome 19q13.32 (OR = 0.72, P = 3.40 x 10-36), representing the TOMM40/APOE/APOC1 locus. In a prospective meta-analysis (n = 34103) the minor allele of rs2149954 (T) on chromosome 5q33.3 associates with increased survival (HR = 0.95, P = 0.003). This allele has previously been reported to associate with low blood pressure in middle age. Interestingly, the minor allele (T) associates with decreased cardiovascular mortality risk, independent of blood pressure. We report on the first GWAS-identified longevity locus on chromosome 5q33.3 influencing survival in the general European population. The minor allele of this locus associates with low blood pressure in middle age, although the contribution of this allele to survival may be less dependent on blood pressure. Hence, the pleiotropic mechanisms by which this intragenic variation contributes to lifespan regulation have to be elucidated.

Foreskin surgery under local anaesthetic – OK? Or oh no!

Aim: Foreskin surgical procedures such as circumcision, prepuceplasty, frenuloplasty, dorsal slit, reduction of paraphimosis etc. in the adult male is usually performed by both general surgeons and urologists. Our aim was to evaluate the acceptance of performing these procedures in the day procedure unit or in the emergency unit under penile block. 
Method: Fifty patients who underwent foreskin surgeries under local anaesthetic (LA) were evaluated with their experience. Twenty patients who underwent circumcision, 20 patients who underwent foreskin preserving operations such as frenuloplasty or prepuceplasty and 10 patients who underwent other procedures such as reduction of paraphimosis (five) and dorsal slit (five) were included inthe study. The patients were asked about their symptoms such as pain or discomfort during local infiltration of lignocaine, any discomfort during the actual procedure, post-operative discomfort and general acceptance. All the patients were given penile block using smaller size needle (25 gauge, 5/8th inch orange sterile luer slip hypodermic needle) and 1% plain lignocaine. Thirty doctors from general surgery (10), urology (10) and emergency medicine (10) participated in the survey. They were asked about their opinion, confidence and preference about performing foreskin surgical procedures under LA. This included both junior trainees, middle grade doctors and consultants. The majority of middle grade doctors and consultants were fairly confident in performing procedures under LA, whereas the junior trainees in surgery, urology and emergency were lacking confidence. 
Conclusion: Penile block is a safe and effective way ofproviding sufficient anaesthesia for foreskin surgeries. Thetechnique is easy to learn. It reduces post-operative pain aswell. It can reduce the risk and cost of administering generalanaesthesia. doctors who are in training surgical specialityand emergency medicine should be encouraged to learnthe principles and technique in administering penile block.

An examination of regional policy implications pertaining to SME E-Business adoption in South-East Wales

Regional policy frameworks need to focus on strengthening the ICT infrastructure, clarifying market rules to build user confidence, developing networks, facilitating ICT-enabled clustering and infrastructure sharing.

ThermoSpots to detect hypothermia in children with severe acute malnutrition

INTRODUCTION: Hypothermia is a risk factor for increased mortality in children with severe acute malnutrition (SAM). Yet frequent temperature measurement remains unfeasible in under-resourced units in developing countries. ThermoSpot is a continuous temperature monitoring sticker designed originally for neonates. When applied to skin, its liquid crystals are designed to turn black with hypothermia and remain green with normothermia.

AIMS: To (i) estimate the diagnostic accuracy of ThermoSpots for detecting WHO-defined hypothermia (core temperature <35.5°C or peripheral temperature <35.0°C) in children with SAM and (ii) determine their acceptability amongst mothers.

METHODS: Children with SAM in a malnutrition unit in Malawi were enrolled during March-July 2010. The sensitivity and specificity of ThermoSpots were calculated by comparing the device colour against 'gold standard' rectal temperatures taken on admission and follow up peripheral temperatures taken until discharge. Guardians completed a questionnaire to assess acceptability.

RESULTS: Hypothermia was uncommon amongst the 162 children enrolled. ThermoSpot successfully detected the one rectal temperature and two peripheral temperatures recorded that met the WHO definition of hypothermia. Overall, 3/846 (0.35%) temperature measurements were in the WHO-defined hypothermia range. Interpreting the brown transition colour (between black and green) as hypothermia improved sensitivities. For milder hypothermia definitions, sensitivities declined (<35.4°C, 50.0%; <35.9°C, 39.2%). Specificity was consistently above 94%. From questionnaires, 40/43 (93%) mothers reported they were 90-100% happy with the device overall. Free-text answers revealed themes of "Skin Rashes", "User-satisfaction" and "Empowerment".

CONCLUSION: Although hypothermia was uncommon in this study, ThermoSpots successfully detected these episodes in malnourished children and were acceptable to mothers. Research in settings where hypothermia is common is needed to determine performance with certainty. Instructing users to act when the device's transition colour appears could improve accuracy. If reliable, ThermoSpots may offer simple, acceptable and continuous temperature measurement for high-burden areas and reduce the workload of over-stretched staff.

Histoire du petit Jack , par l'auteur de Sandford et Merton. Traduit de l'anglais

Titre original : The history of little Jack

Taylor & Bates Brewery & Vinegar Manufactory - Vignette

A vignette of Taylor and Bate's Brewery and Manufactory, St. Catharines.. "Manufacturers of Taylor's Celebrated Amber Ale, Porter, also, White Wine Vinegar, Dealers in Malt, Hops, Barley, &c. &c." The names listed are James Taylor and Thomas B. Bate.