The case for allele‐specific recognition by the TCR

There is a sharp difference in how one views TCR structure–function–behaviour dependent on whether its recognition of major histocompatibility complex‐encoded restriction elements (R) is germline selected or somatically generated. The generally accepted or Standard model is built on the assumption that recognition of R is by the V regions of the αβ TCR, which is not driven by allele specificity, whereas the competing model posits that recognition of R is allele‐specific. The establishing of allele‐specific recognition of R by the TCR would rule out the Standard model and clear the road to a consideration of a competing construct, the Tritope model. Here, the case for allele‐specific recognition (germline selected) is detailed making it obvious that the Standard model is untenable.     

Prevalence of metabolic syndrome in patients with psoriasis: a cross-sectional study in Singapore

INTRODUCTIONPsoriasis is a chronic inflammatory condition that affects the skin and joints, and is associated with cardiovascular risk factors, including metabolic syndrome (MetS). We aimed to assess the prevalence of MetS in patients with psoriasis and determine whether there was a correlation between psoriasis severity and MetS in a Singapore population.METHODSThis was a cross-sectional study of patients with psoriasis, aged 18–69 years, who attended a tertiary dermatology referral centre in Singapore from October 2007 to February 2009. Fasting glucose, lipids, blood pressure, Psoriasis Area and Severity Index, and body mass index were measured. MetS was diagnosed in the presence of three or more criteria of the modified National Cholesterol Education Program Adult Treatment Panel III.RESULTSAmong 338 patients with psoriasis, there were 238 (70.4%) men and 100 (29.6%) women, who were Chinese (n = 228; 67.5%), Malay (n = 52; 15.4%) and Indian (n = 58; 17.2%). The prevalence of MetS was 45.1%. MetS was 44% more prevalent in patients older than 50 years (p = 0.02). Malay patients with psoriasis were significantly more likely to have hypertriglyceridaemia, elevated fasting plasma glucose and abdominal obesity. There was no significant correlation between psoriasis severity and risk of MetS.CONCLUSIONThe prevalence of MetS in patients with psoriasis in Singapore was 45.1%, or nearly threefold higher than the Singapore general population. Patients with psoriasis should be screened yearly for MetS and any modifiable cardiovascular risk factors should be actively controlled.     

Optimal control of a revenue management system with dynamic pricing facing linear demand

This paper considers a dynamic pricing problem over a finite horizon where demand for a product is a time‐varying linear function of price. It is assumed that at the start of the horizon there is a fixed amount of the product available. The decision problem is to determine the optimal price at each time period in order to maximize the total revenue generated from the sale of the product. In order to obtain structural results we formulate the decision problem as an optimal control problem and solve it using Pontryagin's principle. For those problems which are not easily solvable when formulated as an optimal control problem, we present a simple convergent algorithm based on Pontryagin's principle that involves solving a sequence of very small quadratic programming (QP) problems. We also consider the case where the initial inventory of the product is a decision variable. We then analyse the two‐product version of the problem where the linear demand functions are defined in the sense of Bertrand and we again solve the problem using Pontryagin's principle. A special case of the optimal control problem is solved by transforming it into a linear complementarity problem. For the two‐product problem we again present a simple algorithm that involves solving a sequence of small QP problems and also consider the case where the initial inventory levels are decision variables. Copyright © 2006 John Wiley & Sons, Ltd.     

Treatment of Tobacco Use in Preconception Care

Maternal and Child Health Journal -     

Robotic telesurgery for achalasia

The craft of surgery has always relied on the use of instruments. Innovations in surgery have paralleled innovations in instrumentation. Advances in surgical instrumentation continue today and have enabled huge strides in surgical procedures and outcomes during this generation. Computers and related technology are now changing the interface between the surgeon and the patient, and are poised to improve patient outcomes by enhancing the surgeon’s skills and training. The application of computer enhanced telemanipulators, or “robots”, may specifically enhance operations, for example Heller myotomy, that require good visualization and precise careful dissection of delicate structures. This review covers the pathophysiology of achalasia and its history of medical and surgical treatment, leading to modern robotic telesurgical approaches. Improvements in outcome from medical to standard surgical to robotic telesurgical approaches are discussed. Current operative technique for robotic telesurgical treatment of achalasia is described and the authors conclude with a glimpse of where, in the future, current research endeavors will lead us in the treatment of achalasia.     

Antimurine antibody formation following OKT3 therapy

OKT3 is an IgG2a murine monoclonal antibody directed against the CD3 antigen receptor of human T lymphocytes. A major concern with OKT3 treatment in solid organ transplant recipients is the development of antimouse antibody, which may preclude retreatment with this agent. We have administered OKT3 on 215 occasions (150 renal, 34 hepatic, 26 cardiac, 5 pancreatic) in 179 patients between April 1982 and December 1988. The mean duration of treatment was 10.5 days (range, 2-22 days). Antimouse antibody data were analyzed on the most recent 133 treatment courses where the antibody status was available pretreatment. Determination of antimouse antibody production was elicited by ELISA technology at days 0, 7, 14, and 28 of OKT3 treatment. Patients were categorized according to the antibody response as follows: (a) absence of antibody; (b) low titer (1:100); or (c) high titer (greater than or equal to 1:1000). Our earlier experience has demonstrated that retreatment with OKT3 is successful in groups a and b. The development of antimurine antibodies was analyzed with regard to the following parameters: (1) The duration of OKT3 treatment; (2) treatment type (prophylactic, primary, or secondary); (3) primary treatment or retreatment; (4) concomitant immunosuppressive regimen (double or triple therapy); (5) dosage of concomitant immunosuppressive drugs; and (6) transplant organ type. The following results were obtained. (1) Duration of treatment had no effect on antibody production (11.0 days in antibody negative and 10.0 days in antibody positive). (2) There was no difference in antibody formation rates for the first treatment of OKT3 when it was used as prophylaxis (26%), primary (19%), or secondary (27%) therapy. (3) Antibody formation rate with first treatment was 29%; with retreatment, patients who were antibody negative following first treatment became positive in 28% of cases, and retreated patients who were low titer positive following first treatment converted to high titer in 57% of cases. (4) Antibody formation was higher in patients receiving double immunosuppressive therapy (36%) than in those receiving triple immunosuppressive therapy (21%) during OKT3 treatment. (5) Concomitant immunosuppression was lower in the antibody-positive group during OKT3 therapy: steroids, 61 mg/day vs. 52 mg/day; azathioprine, 89 mg/day vs. 66 mg/day; CsA, 317 mg/day vs. 186 mg/day. (6) Antibody formation rates were lower in non-renal transplants following first treatment with OKT3 (liver 17%, heart 17%, kidney 28%); this reflects the higher doses of concomitant immunosuppressive therapy used in nonrenal transplants.(ABSTRACT TRUNCATED AT 400 WORDS)