Cosmological Implications of Neutrinos

The lectures describe several cosmological effects produced by neutrinos. Upper and lower cosmological limits on neutrino mass are derived. The role that neutrinos may play in formation of large scale structure of the universe is described and neutrino mass limits are presented. Effects of neutrinos on cosmological background radiation and on big bang nucleosynthesis are discussed. Limits on the number of neutrino flavors and mass/mixing are given.Comment: 41 page, 7 figures; lectures presented at ITEP Winter School, February, 2002; to be published in the Proceeding

Prevention and management of foot problems in diabetes: a summary guidance for daily practice 2015, based on the IWGDF guidance documents

In this Summary Guidance for Daily Practice', we describe the basic principles of prevention and management of foot problems in persons with diabetes. This summary is based on the International Working Group on the Diabetic Foot (IWGDF) Guidance 2015. There are five key elements that underpin prevention of foot problems: (1) identification of the at-risk foot; (2) regular inspection and examination of the at-risk foot; (3) education of patient, family and healthcare providers; (4) routine wearing of appropriate footwear; and (5) treatment of pre-ulcerative signs. Healthcare providers should follow a standardized and consistent strategy for evaluating a foot wound, as this will guide further evaluation and therapy. The following items must be addressed: type, cause, site and depth, and signs of infection. There are seven key elements that underpin ulcer treatment: (1) relief of pressure and protection of the ulcer; (2) restoration of skin perfusion; (3) treatment of infection; (4) metabolic control and treatment of co-morbidity; (5) local wound care; (6) education for patient and relatives; and (7) prevention of recurrence. Finally, successful efforts to prevent and manage foot problems in diabetes depend upon a well-organized team, using a holistic approach in which the ulcer is seen as a sign of multi-organ disease, and integrating the various disciplines involved

IWGDF guidance on the diagnosis, prognosis and management of peripheral artery disease in patients with foot ulcers in diabetes

Recommendations Examine a patient with diabetes annually for the presence of peripheral artery disease (PAD); this should include, at a minimum, taking a history and palpating foot pulses. (GRADE strength of recommendation: strong; quality of evidence: low) Evaluate a patient with diabetes and a foot ulcer for the presence of PAD. Determine, as part of this examination, ankle or pedal Doppler arterial waveforms; measure both ankle systolic pressure and systolic ankle brachial index (ABI). (strong; low) We recommend the use of bedside non-invasive tests to exclude PAD. No single modality has been shown to be optimal. Measuring ABI (with In patients with a foot ulcer in diabetes and PAD, no specific symptoms or signs of PAD reliably predict healing of the ulcer. However, one of the following simple bedside tests should be used to inform the patient and healthcare professional about the healing potential of the ulcer. Any of the following findings increases the pre-test probability of healing by at least 25%: a skin perfusion pressure 40mmHg, a toe pressure 30mmHg or a transcutaneous oxygen pressure (TcPO2) 25mmHg. (strong; moderate) Consider urgent vascular imaging and revascularisation in patients with a foot ulcer in diabetes where the toe pressure is Consider vascular imaging and revascularisation in all patients with a foot ulcer in diabetes and PAD, irrespective of the results of bedside tests, when the ulcer does not improve within 6weeks despite optimal management. (strong; low) Diabetic microangiopathy should not be considered to be the cause of poor wound healing in patients with a foot ulcer. (strong; low) In patients with a non-healing ulcer with either an ankle pressure Colour Doppler ultrasound, computed tomography angiography, magnetic resonance angiography or intra-arterial digital subtraction angiography can each be used to obtain anatomical information when revascularisation is being considered. The entire lower extremity arterial circulation should be evaluated, with detailed visualisation of below-the-knee and pedal arteries. (strong; low) The aim of revascularisation is to restore direct flow to at least one of the foot arteries, preferably the artery that supplies the anatomical region of the wound, with the aim of achieving a minimum skin perfusion pressure 40mmHg, a toe pressure 30mmHg or a TcPO2 25mmHg. (strong; low) A centre treating patients with a foot ulcer in diabetes should have the expertise in and rapid access to facilities necessary to diagnose and treat PAD; both endovascular techniques and bypass surgery should be available. (strong; low) There is inadequate evidence to establish which revascularisation technique is superior, and decisions should be made in a multidisciplinary team on a number of individual factors, such as morphological distribution of PAD, availability of autogenous vein, patient co-morbidities and local expertise. (strong; low) After a revascularisation procedure for a foot ulcer in diabetes, the patient should be treated by a multidisciplinary team as part of a comprehensive care plan. (strong; low) Patients with signs of PAD and a foot infection are at particularly high risk for major limb amputation and require emergency treatment. (strong; moderate) Avoid revascularisation in patients in whom, from the patient perspective, the risk-benefit ratio for the probability of success is unfavourable. (strong; low) All patients with diabetes and an ischaemic foot ulcer should receive aggressive cardiovascular risk management including support for cessation of smoking, treatment of hypertension and prescription of a statin as well as low-dose aspirin or clopidogrel. (strong; low

Performance of prognostic markers in the prediction of wound healing or amputation among patients with foot ulcers in diabetes: a systematic review

Prediction of wound healing and major amputation in patients with diabetic foot ulceration is clinically important to stratify risk and target interventions for limb salvage. No consensus exists as to which measure of peripheral artery disease (PAD) can best predict outcomes. To evaluate the prognostic utility of index PAD measures for the prediction of healing and/or major amputation among patients with active diabetic foot ulceration, two reviewers independently screened potential studies for inclusion. Two further reviewers independently extracted study data and performed an assessment of methodological quality using the Quality in Prognostic Studies instrument. Of 9476 citations reviewed, 11 studies reporting on 9 markers of PAD met the inclusion criteria. Annualized healing rates varied from 18% to 61%; corresponding major amputation rates varied from 3% to 19%. Among 10 studies, skin perfusion pressure 40mmHg, toe pressure 30mmHg (and 45mmHg) and transcutaneous pressure of oxygen (TcPO2) 25mmHg were associated with at least a 25% higher chance of healing. Four studies evaluated PAD measures for predicting major amputation. Ankle pressur

Effectiveness of bedside investigations to diagnose peripheral artery disease among people with diabetes mellitus: a systematic review

Non-invasive tests for the detection of peripheral artery disease (PAD) among individuals with diabetes mellitus are important to estimate the risk of amputation, ulceration, wound healing and the presence of cardiovascular disease, yet there are no consensus recommendations to support a particular diagnostic modality over another and to evaluate the performance of index non-invasive diagnostic tests against reference standard imaging techniques (magnetic resonance angiography, computed tomography angiography, digital subtraction angiography and colour duplex ultrasound) for the detection of PAD among patients with diabetes. Two reviewers independently screened potential studies for inclusion and extracted study data. Eligible studies evaluated an index test for PAD against a reference test. An assessment of methodological quality was performed using the quality assessment for diagnostic accuracy studies instrument. Of the 6629 studies identified, ten met the criteria for inclusion. In these studies, the patients had a median age of 60-74 years and a median duration of diabetes of 9-24years. Two studies reported exclusively on patients with symptomatic (ulcerated/infected) feet, two on patients with asymptomatic (intact) feet only, and the remaining six on patients both with and without foot ulceration. Ankle brachial index (ABI) was the most widely assessed index test. Overall, the positive likelihood ratio and negative likelihood ratio (NLR) of an ABI threshol

Effectiveness of revascularization of the ulcerated foot in patients with diabetes and peripheral artery disease:a systematic review

Symptoms or signs of peripheral artery disease (PAD) can be observed in up to 50% of the patients with a diabetic foot ulcer and is a risk factor for poor healing and amputation. In 2012, a multidisciplinary working group of the International Working Group on the Diabetic Foot published a systematic review on the effectiveness of revascularization of the ulcerated foot in patients with diabetes and PAD. This publication is an update of this review and now includes the results of a systematic search for therapies to revascularize the ulcerated foot in patients with diabetes and PAD from 1980 to June 2014. Only clinically relevant outcomes were assessed. The research conformed to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, and Scottish Intercollegiate Guidelines Network methodological scores were assigned. A total of 56 articles were eligible for full-text review. There were no randomized controlled trials, but there were four nonrandomized studies with a control group. The major outcomes following endovascular or open bypass surgery were broadly similar among the studies. Following open surgery, the 1-year limb salvage rates were a median of 85% (interquartile range of 80-90%), and following endovascular revascularization, these rates were 78% (70-89%). At 1-year follow-up, 60% or more of ulcers had healed following revascularization with either open bypass surgery or endovascular techniques. Studies appeared to demonstrate improved rates of limb salvage associated with revascularization compared with the results of conservatively treated patients in the literature. There were insufficient data to recommend one method of revascularization over another. There is a real need for standardized reporting of baseline demographic data, severity of disease and outcome reporting in this group of patients.</p