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The article presents the results of a study which investigated the accuracy of submaximal treadmill running tests in measuring maximal oxygen consumption. An overview of related previous research is provided, detailing indirect alternatives to maximal exercise to lower participant risk of injury. Details of the experiment protocol are also presented, including interval oxygen consumption and expired gas measurements.

Background: Motivational conflict is central to alcohol dependence, with patients reporting motivation to limit their drinking at the same time as urges to drink alcohol. In addition, dual process models of addiction emphasise the power of automatic cognitive processes, particularly automatic approach responses elicited by alcohol-related cues, as determinants of drinking behavior. We aimed to examine the strength of automatic and self-reported alcohol approach and avoidance tendencies among alcohol-dependent inpatients relative to matched controls. Methods:enbsp; A total of 63 alcohol-dependent patients undergoing detoxification and 64 light-drinking controls completed a stimulus-response compatibility (SRC) task, which assesses the speed of categorization of alcohol-related pictures by making symbolic approach and avoidance movements. We also included modified versions of the SRC task to assess automatic motivational conflict, that is, strong approach and avoidance tendencies elicited simultaneously by alcohol-related cues. Results: There were no differences between alcohol-dependent patients and controls on the SRC task, although individual differences in the quantity of alcohol consumed before entering treatment were significantly positively correlated with the strength of approach (but not avoidance) tendencies elicited by alcohol-related cues. Automatic approach tendencies were also positively correlated with self-reported 'approach' inclinations and negatively correlated with self-reported 'avoidance' inclinations. Conclusions: Although alcohol-dependent patients and matched controls did not differ on automatic approach and avoidance tendencies elicited by alcohol-related cues, individual differences in the quantity of alcohol consumed before entering treatment were associated with the strength of automatic approach tendencies elicited by alcohol cues. [ABSTRACT FROM AUTHOR]

Background: It is not clear whether there is a large difference in acute hemodynamic response (AHR) to left ventricle (LV) pacing in different regions of the same coronary sinus (CS) vein. Using the four electrodes available on a Quartet LV lead, we evaluated the AHR to pacing within individual branches of the CS. Methods: An acute hemodynamic study was attempted in 20 patients. In each patient, we assessed AHR in a number of CS veins and along a significant proportion of each CS branch using three different bipolar configurations. We compared the AHR achieved when pacing using each different vector and also the highest AHR achieved in any position within the same patient with the lowest achieved in that patient. Results : Sixty-four different CS positions in 19 patients were successfully assessed. No significant difference in AHR was found overall between the three vectors tested. The mean percentage difference in AHR between the CS branch vectors with the lowest and highest dP/dtmax was +6.5 ± 5.4% (P < 0.001). A much larger difference of +16.9 ± 6.1% (P < 0.001) was seen when comparing the highest and lowest AHR achieved using any vector in any position within the same patient. Conclusion: A small difference in AHR is seen when pacing within the same branch of the CS compared to pacing in different branches in the same patient. This suggests that although the site of LV lead placement is important, the position within a CS branch is less important than choosing the right vein. (PACE 2012; 35:196-203) [ABSTRACT FROM AUTHOR]

This study examined the impact of caffeine ingestion on field hockey skill performance following high-intensity fatigue. Thirteen male hockey players (mean age = 21.1 ± 1.2 years) performed hockey sprint dribble and ball handling tests at rest and after a bout of total body fatigue (90% maximal capacity) following caffeine (5mg kg−1) or placebo ingestion. Sprint dribble times were slower postfatigue compared with rest but were significantly faster postfatigue with caffeine compared with postfatigue with placebo ingestion (P < 0.01). Ball handling scores were higher at rest compared with postfatigue, but scores postfatigue were higher following caffeine than placebo ingestion (P < 0.01). Rating of perceived exhaustion (RPE) was lower (P < 0.01) and readiness to invest physical (P < 0.01) and mental effort (P = 0.01) were significantly higher in the caffeine condition. Caffeine ingestion may therefore be effective in offsetting decrements in skilled performance associated with fatigue. [ABSTRACT FROM AUTHOR]

This study tested, with a sample of United Kingdom (UK) trainee clinical psychologists, part of an existing model of factors that influence clinical psychologists' levels of research activity, in which gender identity is hypothesized to influence research self-efficacy and this in turn strength of intention to do research. A sample of 121 trainee clinical psychologists (56 men and 65 women) completed a measure of gender identity, research intention, and a research self-efficacy scale. Results indicated no differences in levels of research intention or research self-efficacy between the biological sexes or according to category-based gender identities (masculine and feminine). However, masculinity as a scale quantity was statistically significantly related to stronger research intention, preference for conducting quantitative research and research self-efficacy. Multiple regression analysis provided evidence that research self-efficacy may mediate between masculinity and strength of research intention. Research self-efficacy was the strongest predictor of intention to do research in the future. Findings have relevance for clinical psychology training as research activity directly impacts upon advances in the discipline of clinical psychology, implementation of research into practice, and evaluation of psychological therapies. Copyright © 2010 John Wiley & Sons, Ltd. Key Practitioner Message: • Clinical psychologists' research activity is important for the advancement of the clinical psychology profession but relatively few clinical psychologists appear to engage in research activity. • In a national sample of male and female UK trainee clinical psychologists, trainees' research self-efficacy was strongly positively correlated with intention to do research in the future. • Scores on a measure of masculinity also predicted research intention, and research self-efficacy mediated the relationship between masculinity and intention. • Clinical psychology training courses might seek to increase trainees' research self-efficacy by exploring factors hypothesized to enhance the research training environment and that have predicted greater practitioner research activity in previous literature. • Because research activity tends to be seen as stereotypically a more male activity, it may also be worth challenging or encouraging trainees to reflect on stereotypical views of gender and research. [ABSTRACT FROM AUTHOR]

There has been concern regarding potentially higher failure rates of metal-on-metal (MoM) bearings in obese patients, and possible adverse reaction to metal debris (ARMD). Elevated chromium (Cr) and cobalt (Co) levels in the blood indicate excess wear, and may predict secondary soft-tissue damage. We investigated the effect of obesity on blood Cr and Co levels in patients with MoM bearings. We reviewed data on 75 patients with hip resurfacing and MoM total hip arthroplasty (THA) at an average of 4 years follow-up. We excluded patients with factors that can affect metal ion levels including other metal implants, bilateral MoM bearings or during the 'running-in' phase. The patients were classified into two groups; obese (n=27) and control (n=48) depending on a body mass index (BMI) ≥ 30 kg/m2. There was no significant difference between the groups with regards to age, gender, renal function, cup inclination, implant type, femoral head size, time interval between operation and metal ion levels or the number of symptomatic patients. There was a trend for lower Cr and Co levels in the obese group but this was not statistically significant (p= 0.17 & 0.07, respectively). There was no correlation between the BMI and Cr or Co levels (Spearman's correlation coefficient r = - 0.13/p = 0.26 & - 0. 2/p = 0.1, respectively). There was no evidence of higher metal ion levels, suggestive of increased wear, in obese patients with MoM bearings. [ABSTRACT FROM AUTHOR]

Background: Asthma and chronic obstructive pulmonary disease (COPD) display features of overlap in airway physiology and airway inflammation. Whether inflammatory phenotypes in airway disease describe similar mediator expression is unknown. Objectives: To explore the relationship of airway inflammation and cytokine and chemokine expression in asthma and COPD. Methods: Subjects with asthma and COPD (n = 54 and n = 49) were studied. Clinical characteristics and sputum were collected at entry into the study. A 2-step sputum processing method was performed for supernatant and cytospin preparation. Meso Scale Discovery and Luminex platforms were used to measure cytokines, chemokines and matrix metalloproteinase levels. Results: Analytes sensitive to dithiothreitol (DTT) that had increased recovery in the 2-step sputum process were IL-1β, 4, 5, 10, 13, IFN-γ, TNFRI, GM-CSF, CCL2, 3, 4, 5, 13 and 17. There was a differential expression in IL-8, TNFRI and TNFRII between asthma and COPD [mean fold difference (95% CI): IL-8, 2.6 (1.3-5.4), p = 0.01; TNFRI, 2.1 (1.3-5.4), p = 0.03; TNFRII, 2.6 (1.2-5.6), p = 0.02]. In neutrophilic and eosinophilic airway inflammation, TNFα, TNFRI, TNFRII, IL-6, IL-8 and IL-5 could differentiate between these phenotypes. However, these phenotypes were unrelated to the diagnosis of asthma or COPD. Conclusion: Recovery of sputum mediators sensitive to DTT can be improved using the described sputum processing technique. Within airway inflammatory sub-phenotypes there is a differential pattern of mediator expression that is independent of disease. Whether these inflammatory phenotypes in asthma and COPD confer distinct pathogeneses, therapeutic responses and clinical phenotypes needs to be further evaluated. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Context: Many active people finish exercise hypohydrated, so effective rehydration after exercise is an important consideration. Objective: To determine the effects of a rehydration solution containing whey protein isolate on fluid balance after exercise- induced dehydration. Design: Randomized controlled clinical trial. Setting: University research laboratory. Patients or Other Participants: Twelve healthy men (age = 21 ±1 years, height = 1.82 ± 0.08 m, mass = 82.71 ±10.31 kg) participated. Intervention(s): Participants reduced body mass by 1.86% ±0.07% after intermittent exercise in the heat and re- hydrated with a volume of drink in liters equivalent to 1.5 times their body mass loss in kilograms of a solution of either 65 g/L carbohydrate (trial C) or 50 g/L carbohydrate and 15 g/L whey protein isolate (trial CP). Solutions were matched for energy density and electrolyte content. Urine samples were collected before and after exercise and for 4 hours after rehydration. Main Outcome Measure(s): We measured urine volume, drink retention, net fluid balance, urine osmolality, and subjective responses. Drink retention was calculated as the difference between the volume of drink ingested and urine produced. Net fluid balance was calculated from fluid gained through drink ingestion and fluid lost through sweat and urine production. Results: Total cumulative urine output after rehydration was not different between trial C (1173 ±481 mL) and trial CP (1180±330 mL) (F1=0.002, P=.96), and drink retention during the study also was not different between trial C (50% ±18%) and trial CP (49%±13%) (t11=-0.159, P=.88). At the end of the study, net fluid balance was negative compared with baseline for trial C (-432±436 mL) (t11 =3.433, P=.03) and trial CP (-432±302 mL) (t11=4.958, P=.003). Conclusions: When matched for energy density and electrolyte content, a solution of carbohydrate and whey protein isolate neither increased nor decreased rehydration compared with a solution of carbohydrate. [ABSTRACT FROM AUTHOR]

Aims: The current study investigated the effect of a media health message for drinking on risk perception estimates (comparative optimism). Methods: Sixty-five young adults who regularly drink alcohol watched an anti-drinking scenario (having an accident due to drinking). There were two intervention conditions: 30 participants ‘imagined’ they were part of the scenario, and 35 ‘watched’ the scenario. They then completed four comparative optimism estimates comparing themselves to those the same age and gender with similar drinking habits. The four comparisons were of their likelihood of being involved in an accident due to drinking; having unprotected sex, when under the influence of alcohol; having a car accident due to drinking (drivers only) and developing cirrhosis. There was also a control group (n = 59) who just completed the questionnaires. Results: Both intervention groups reported significantly lower comparative optimism for accident, unprotected sex and car accident than the control group. The ‘imagine’ group reported significantly lower comparative optimism than the ‘watch’ group for accidents. Conclusions. These results highlighted that media messages can successfully change people's risk perception, and also that imagination can be a powerful tool in changing risk perceptions associated with binge drinking. [ABSTRACT FROM AUTHOR]

Purpose – An earlier study of health and social services professionals in community teams for people with intellectual disabilities (CTIDs) identified a number of significant gaps in their knowledge of mental capacity issues. The present study aims to ascertain the knowledge of staff working in residential services for people with intellectual disabilities. Design/methodology/approach – Participants were staff working in three specialist residential settings catering to people with intellectual disabilities: qualified nurses working in the UK National Health Service (NHS) and in independent-sector continuing health care settings; and senior staff in residential houses. They were administered the same structured interview as in the earlier study, which was constructed around three scenarios concerning a financial/legal issue, a health issue, and a relationships issue, as well as a set of ten "true/false" statements. Their performance was compared with that of two reference groups, the earlier CTID participants, and a group of staff working in generic (i.e. other than specialist intellectual disability) NHS services. Findings – No differences in interview performance were found between the three groups of residential carers, who performed better than generic NHS staff but worse than CTID professionals. However, the three residential groups did differ in their self-ratings of how well-informed and confident they felt in relation to mental capacity issues. Originality/value – The study shows that staff working in residential services for people with intellectual disabilities have only a limited understanding of mental capacity issues and their confidence in their own knowledge may not be a good guide to their ability to deal with such issues when they arise in practice. [ABSTRACT FROM AUTHOR]

Background: Recent evidence suggests that the duodenum can regulate iron absorption independently of hepcidin via the transcription factor Hif-2α acting directly on the transcription of the proteins involved in the iron transport. The current study investigates the temporal relationship between Dcytb and Hif-2α during early hypoxic stimulus in the enterocyte in vivo. Methods: Duodenal Dcytb and Hif-2α protein expression was analysed by Western blot technique while gene regulation was determined by quantitative PCR. Results: Both Dcytb and Hif-2α protein expression were increased during the first hours of hypoxic duration. A change in hepcidin expression however, was significant only at 72 h hypoxia. Increased iron absorption reported in early hypoxia could be accounted for in part by the enhancement of Dcytb expression by Hif-2α in the duodenum. Conclusion: Modulation of Hif-2α predominates over hepcidin in the regulation of intestinal iron absorption during short hypoxic duration. The intestine exerts regulatory mechanisms in the dietary absorption of iron into systemic circulation. [ABSTRACT FROM AUTHOR]

Background: Posterolateral corner (PLC) injuries are difficult to diagnose and cause significant morbidity. The ideal method for the dial test and its accuracy remain unclear.Purpose: This study compares the accuracy of measuring tibial external rotation at the skeletal level to measuring the patella-tubercle angle (PTA) and the thigh-foot angle (TFA) in the supine position to assess the most accurate method to measure rotation during the dial test.Study Design: Controlled laboratory study.Methods: Measurements were compared simultaneously using rotational goniometers at a cutaneous splint over the tibia, at a foot splint, and directly from the tibial skeleton. Six lower limbs were used. The femur was held rigidly and the knee tested at 90° and 30° of flexion. External rotation torque up to 8 N·m was applied through the foot splint, and the rotations were measured by 2 testers.Results: Measurements at the tibial splint and directly on the tibia showed significant correlation at both knee flexion angles. The mean tibial external rotation was 24° at 90° of flexion and 26° at 30° of flexion (P < .05). The soft tissue effect caused the tibial splint to overestimate rotations by a mean of 6° and 9° at 90° and 30° of flexion, respectively. Foot splint measurements did not correlate significantly with tibial rotation, overestimating rotations by a mean of 103%. Intratester and intertester intraclass correlations were significant for the skin-mounted tibial splint measurements at both flexion angles but not for foot splint measurements at either flexion angles.Conclusion: Rotation of the foot did not accurately represent the tibial external rotation at the knee, which could be measured more accurately by an instrument resting on the skin via a molded tibial splint. These results suggest that the PTA, and not the TFA, should be used in the dial test. This would support the use of the supine position during the dial test.Clinical Relevance: The dial test is a commonly used method for diagnosing PLC injuries. This study helps to identify the ideal position and measuring points to use for this test; measurements based on the tibia were more accurate than those that used rotation of the foot. [ABSTRACT FROM AUTHOR]

BACKGROUND: Soy-based infant formula contains high levels of isoflavones. These estrogen-like compounds have been shown to induce changes in sexually dimorphic behaviors in animals exposed in early development. OBJECTIVE: We examined gender-role play behavior in relation to soy-based and non-soy-based infant feeding methods among children in the Avon Longitudinal Study of Parents and Children. METHODS: We studied 3,664 boys and 3,412 girls. Four exposure categories were created using data from questionnaires administered at 6 and 15 months postpartum: primarily breast, early formula (referent), early soy, and late soy. Gender-role play behavior was assessed using the Pre-School Activities Inventory (PSAI). Associations between infant feeding and PSAI scores at 42 months of age were assessed using linear regression. Post hoc analyses of PSAI scores at 30 and 57 months were also conducted. RESULTS: Early-infancy soy use was reported for approximately 2% of participants. Mean [95% confidence interval (CI)] PSAI scores at 42 months were 62.3 (62.0, 62.6) and 36.9 (36.6, 37.2) for boys and girls, respectively. After adjustment, early soy (vs. early formula) feeding was associated with higher (less feminine) PSAI scores in girls (β = 2.66; 95% CI: 0.19, 5.12) but was not significantly associated with PSAI scores in boys. The association between soy exposure and PSAI scores in girls was substantially attenuated at 30 and 57 months. CONCLUSIONS: Although not consistent throughout childhood, early-life soy exposure was associated with less female-typical play behavior in girls at 42 months of age. Soy exposure was not significantly associated with play behavior in boys. [ABSTRACT FROM AUTHOR]

The aim of this work was to investigate the effect of a daily mixed nutritional supplement upon body composition, physical performance, and circulating anabolic hormones in soldiers undergoing arduous training. Thirty males received either a habitual diet alone (CON, n = 15) or with the addition of a daily mixed supplement (SUP, n = 15) of ∼5.1 MJ·d-1 during 8 weeks of training. Body composition (DEXA), maximal dynamic lift strength (MDLS), and vertical jump (VJ) were assessed, and resting blood samples were collected before and after training. Blood analysis included insulin-like growth factors (IGF-1, IGF BP-1, and IGF BP-3), testosterone, and cortisol. There were no group differences at baseline. Body mass loss (mean ± SD) (CON 5.0 ± 2.3, SUP 1.6 ± 1.5 kg), lean mass loss (CON 2.0 ± 1.5, SUP 0.7 ± 1.5 kg), and fat mass loss (CON 3.0 ± 1.6, SUP 0.9 ± 1.8 kg) were significantly blunted by SUP. CON experienced significant decrements in MDLS (14%), VJ (10%), and explosive leg power (11%) that were prevented by SUP. Military training significantly reduced circulating IGF-1 (28%), testosterone (19%), and the testosterone:cortisol ratio (24%) with no effect of SUP. Circulating IGF BP-1 concentration and cortisol remained unchanged throughout, although SUP abolished the significant decrease in circulating IGF BP-3 (20%) on CON. In conclusion, a daily mixed nutritional supplement attenuated decreases in body mass and lean mass and prevented the decrease in physical performance during an arduous military training program. [ABSTRACT FROM AUTHOR]

Muscle metabolism is increased following exercise in healthy individuals, affecting exercise metabolism during subsequent physical work. We hypothesized that following heavy-intensity exercise (HIE), disease factors in children with cystic fibrosis (CF) would further exacerbate exercise metabolism and perceived exertion during subsequent exercise. Nineteen children with CF (age, 13.4 ± 3.1 years; 10 female) and 19 healthy controls (age, 13.8 ± 3.5 years; 10 female) performed 10 bouts of HIE interspersed with 1 min of recovery between each bout. Three minutes later participants completed a 10-min moderate-intensity exercise (MIE) test (test 1). The MIE test was subsequently repeated 1 h (test 2) and 24 h (test 3) later. Each MIE test was identical and participants exercised at individualized work rates, calibrated by an initial graded maximal cardiopulmonary exercise test, while metabolic and perceived exertion measurements were taken. Following HIE, mixed-model ANOVAs showed a significant difference in oxygen uptake (VO2) and rating of perceived exertion (RPE) between the 2 groups across the MIE tests (p < 0.01). In controls, VO2 (L·min-1) and RPE decreased significantly from test 1 to test 2 (p < 0.01) and test 2 to test 3 (p < 0.05). However, in children with CF, VO2 (L·min-1) increased significantly from test 1 to test 2 (p < 0.01), while RPE did not differ, both VO2 and RPE decreased significantly from test 2 to test 3 (p < 0.01). In conclusion, following HIE the metabolic and perceptual responses to MIE in both groups decreased 24 h later during test 3. These data show that children with mild-to-moderate CF have the capability to perform HIE and 24 h allows sufficient time for recovery. [ABSTRACT FROM AUTHOR]

BackgroundThe DSM-V Working Group is currently re-evaluating distress as a primary diagnostic criterion for female sexual dysfunction (FSD). Here, for the first time, we explored the epidemiology of sexual distress and its putative aetiological relationship to FSD by estimating the influence of genetic and environmental risk factors.MethodQuestionnaire data on a representative sample of 930 British female twins using validated scales of FSD and sexual distress were subject to variance components analyses to quantify latent genetic and environmental factors influencing phenotypic variation and covariation. Multiple regression analyses were used to identify other potential risk factors of sexual distress.ResultsOf 319 women with any sexual problems, only 36.5% reported distress. Of women classified as functional, 16.5% felt sexual distress. Sexual distress had a heritability of 44% [95% confidence interval (CI) 0.33–0.54]. Bivariate analysis suggested that the majority (91% CI 86–99%) of the covariance between sexual distress and FSD was due to unique environmental effects common to both traits. Associations were found between sexual distress and other risk variables, including relationship dissatisfaction [odds ratio (OR) 1.6, p<0.001], anxiety sensitivity and obsessive–compulsive symptomatology (OR 1.2, p<0.01, for both).ConclusionsThere seems to be a weak phenotypic and genetic basis for including sexual distress as a diagnostic indicator of FSD. Instead, the data indicate that unrelated psychological factors play an important role in sexual distress and tentatively suggest that sexual distress is less a consequence of FSD and more related to general anxiety among women. [ABSTRACT FROM PUBLISHER]

The article presents a study which is aimed to identify the prognostic indicators for short-term improvement in primary care patients with acute and persistent musculoskeletal conditions. The researchers have measured the episodes of musculoskeletal pain and self-report improvement outcomes using multivariate regression analysis. The study reinforces the elusive nature of baseline characteristics that can predict early outcomes for patients with persistent painful musculoskeletal conditions.

Background: A gluten-free diet is the only treatment for patients with coeliac disease, although it can be burdensome to follow and result in inadequate nutrient intake. The cost and availability of a gluten-free diet has been cited as a cause of incomplete dietary compliance; however, this has not been extensively investigated. The aim was to investigate the availability and cost of gluten-free foods across a wide range of stores. Methods: The availability and cost of 20 foods (both wheat-based and everyday foods) was surveyed at 30 different stores across five different store categories. For each of the 20 foods, four products were selected (branded gluten-free, cheapest gluten-free, branded standard, cheapest standard) resulting in sampling of up to 80 products in each of the 30 stores. Results: In general, there was limited availability of gluten-free foods, with an average of 8.2 of the 20 (41%) foods being available in a gluten-free version per store. Regular supermarkets had a greater availability (18.0/20, 90%), whereas budget supermarkets (1.8/20, 9%) and corner shops (1.8/20, 9%) had almost no gluten-free versions ( P < 0.001). All 10 gluten-free versions of wheat-based foods were more costly than their standard counterparts (76-518% more expensive; P < 0.001). Some gluten-free versions of everyday foods were also more costly than standard counterparts (2-124%). Conclusions: There is limited availability of gluten-free foods and they are generally more expensive than their standard counterparts. This may impact on compliance to a gluten-free diet, with potential nutritional and clinical consequences, together with an increased risk of complications. [ABSTRACT FROM AUTHOR]

Background: Weight loss in patients with cancer is common and associated with a poorer survival and quality of life. Benefits from nutritional interventions are unclear. The present study assessed the effect of dietary advice and/or oral nutritional supplements on survival, nutritional endpoints and quality of life in patients with weight loss receiving palliative chemotherapy for gastrointestinal and non-small cell lung cancers or mesothelioma. Methods: Participants were randomly assigned to receive no intervention, dietary advice, a nutritional supplement or dietary advice plus supplement before the start of chemotherapy. Patients were followed for 1 year. Survival, nutritional status and quality of life were assessed. Results: In total, 256 men and 102 women (median age, 66 years; range 24-88 years) with gastrointestinal ( n = 277) and lung ( n = 81) cancers were recruited. Median (range) follow-up was 6 (0-49) months. One-year survival was 38.6% (95% confidence interval 33.3-43.9). No differences in survival, weight or quality of life between groups were seen. Patients surviving beyond 26 weeks experienced significant weight gain from baseline to 12 weeks, although this was independent of nutritional intervention. Conclusions: Simple nutritional interventions did not improve clinical or nutritional outcomes or quality of life. Weight gain predicted a longer survival but occurred independently of nutritional intervention. [ABSTRACT FROM AUTHOR]

Objective Rituximab appears to be effective in many studies of systemic lupus erythematosus (SLE), with variable initial clinical response and time to relapse. However, results of a randomized controlled trial of rituximab were negative. This study was undertaken to evaluate the effectiveness of rituximab in SLE, using highly sensitive flow cytometry (HSFC), which can define B cell numbers 50-100 times lower than conventional techniques and predicts responses in rheumatoid arthritis. Methods Thirty-nine patients with active SLE were started on a standard regimen of rituximab with intravenous and oral steroids. Clinical response and relapse were defined using the British Isles Lupus Assessment Group (BILAG) index with criteria for major clinical response, partial clinical response, and nonresponse. HSFC, including analysis of B cell subsets, was performed. Results There was a significant reduction from baseline in global BILAG score at all time points analyzed ( P < 0.0001), and major clinical response and partial clinical response rates were 51% and 31%, respectively. Time to relapse was highly variable. Fifty percent of the patients relapsed after 6-18 months (earlier relapse); the remainder relapsed at a slower rate (later relapse). B cell depletion and repopulation were variable and were predictive of these clinical outcomes. There was a persistent B cell presence in 21 patients after 2 infusions of rituximab, which included all 7 patients with no response ( P = 0.012 versus patients with complete depletion of B cells). Memory B cell ( P = 0.02) and plasmablast ( P < 0.001) repopulation after 26 weeks was markedly faster in patients with earlier relapse versus patients with later relapse. Conclusion Our findings indicate that rituximab is effective in SLE, and clinical responses are supported by close correlation with B cell numbers. HSFC is a valuable tool in the assessment and prediction of response in SLE. [ABSTRACT FROM AUTHOR]

Summary: Premenopausal women with low calcium intakes consumed calcium-fortified ice cream daily for 28 days. Bone markers, NTX, CTX and PTH decreased significantly by 7 days, with some evidence of a calcium dose-dependent effect. Bone marker responses were observed within 1 h of consuming ice cream. Body weight remained constant over 28 days. Introduction: Dietary calcium is important for lifelong bone health. Milk is a good source of bioavailable calcium, but consumption has declined among young adults. The aims were to determine whether calcium-fortified ice cream, a palatable source of calcium, produces significant, sustainable changes in bone turnover markers and parathyroid hormone (PTH) in premenopausal women with calcium intake below recommended UK levels. Methods: Eighty women, ages 20-39 years (calcium intake <750 mg/day) were randomised to consume lower saturated fat/sugar ice cream containing 96, 244, 459 or 676 mg calcium daily for 28 days. Urinary NTX/Cr, serum CTX, PINP, 1,25D and PTH were measured (baseline, days 1, 7 and 28). Acute changes in CTX and PTH were measured over 5 h ( n = 29 women). Results: There were significant mean decreases by 7 days in NTX/Cr, CTX, PTH and 1,25D and increases in PINP (one sample t tests), with a significant dose-dependent effect on CTX analysis of covariance. Only CTX remained suppressed at 28 days. Serum CTX and PTH decreased within 1 h. Body weight did not change significantly between baseline and 28 days. Conclusions: Daily consumption of calcium-fortified ice cream by premenopausal women may significantly reduce levels of the bone resorption marker serum CTX, without stimulating weight gain. The ice cream could be incorporated into the diet to replace low-calcium snacks and thus help individuals with habitually low calcium intakes to meet recommended intakes. The 244 mg calcium preparation would provide more than a quarter of the UK daily recommended nutrient intake for premenopausal women. [ABSTRACT FROM AUTHOR]

Objectives. Behçet’s disease (BD) is more severe among young males and disease severity decreases with age. Therefore, the effect of disease activity, gender and age on platelet and neutrophil activation in whole blood taken from patients with BD was investigated.Methods. Using an anti-coagulant Tripotassium ethylenediaminetetra acetic acid (K3EDTA) plus citrate-theophylline-adenosine-dipyridamole (CTAD) (K3EDTA/CTAD) that preserves the degree of platelet activation that exists in vivo, we assessed neutrophil and platelet activation, microparticles, and monocyte and neutrophil–platelet aggregate formation in 43 BD patients using flow cytometry. This is the first description of platelet activation and microparticles in BD patients using this methodology.Results. Inactive [2.78 (0.56)%, P = 0.0009; 3.11 (0.78)%, P < 0.0001] and active [2.28 (0.84)%, P < 0.0001; 3.071 (0.67)%, P = 0.0031] BD patients had significantly higher percentages of CD62P-expressing platelets and CD62P+ platelet microparticles as compared with healthy controls (HCs) [0.84 (0.1)% and 1.23 (0.14)%], respectively. The percentages of CD62P+ platelets and CD62P+ platelet microparticles in female and male BD patients were also significantly higher than those expressed by female and male HCs. The percentages of CD62P+ microparticles were significantly increased in the 20–30-(P = 0.0301) and 31–50-(P < 0.0162) year age ranges, but not in the >50-year age group of BD patients.Conclusion. BD is a rare, chronic multi-systemic vasculitis and interaction of activated platelets with leucocytes has been linked to pathological disorders associated with vascular inflammation. Importantly, this study demonstrates that platelet microparticle activation is increased in BD. Also, this is the first report in which changes in platelet activation in BD are concordant with the observations that BD disease activity diminishes with age. [ABSTRACT FROM PUBLISHER]

Allen EM, Matthews JB, O' Halloran DJ, Griffiths HR, Chapple IL: Oxidative and inflammatory status in Type 2 diabetes patients with periodontitis. J Clin Periodontol 2011; 38: 894-901. 38: 894-901. doi: 10.1111/j.1600-051X.2011.01764.x. Abstract Aim: To determine the impact of periodontitis on oxidative/inflammatory status and diabetes control in Type 2 diabetes. Materials and Methods: A comparative study of 20 Type 2 diabetes patients with periodontitis [body mass index (BMI) 31+5], 20-age/gender-matched, non-periodontitis Type 2 diabetes controls (BMI 29+6) and 20 non-diabetes periodontitis controls (BMI 25+4) had periodontal examinations and fasting blood samples collected. Oxidative stress was determined by plasma small molecule antioxidant capacity (pSMAC) and protein carbonyl levels; inflammatory status by total/differential leucocytes, fibrinogen and high sensitivity C-reactive protein (hsCRP); diabetes status by fasting glucose, HbA1c, lipid profile, insulin resistance and secretion. Statistical analysis was performed using SPSS. Results: pSMAC was lower ( p=0.03) and protein carbonyls higher ( p=0.007) in Type 2 diabetes patients with periodontitis compared with those without periodontitis. Periodontitis was associated with significantly higher HbA1c ( p=0.002) and fasting glucose levels ( p=0.04) and with lower β-cell function (HOMA- β; p=0.01) in diabetes patients. Periodontitis had little effect on inflammatory markers or lipid profiles, but Type 2 diabetes patients with periodontitis had higher levels of hsCRP than those without diabetes ( p=0.004) and the lowest levels of HDL-cholesterol of all groups. Conclusion: Periodontitis is associated with increased oxidative stress and compromised glycaemic control in Type 2 diabetes patients. [ABSTRACT FROM AUTHOR]

Background: Soft tissue fibrosis is a common consequence of breast cancer treatment and chronic lymphoedema. It can compromise function and quality of life, but research regarding interventions is limited. Aims: To assess the efficacy of using JoViPitPak® (JoviPak Corporation) to influence soft tissue fibrosis change by looking at tissue density, perceived cosmesis and perceived breast pain. Methods: This case series examined four breast cancer patients with stage 2 lymphoedema, post lumpectomy surgery and radiation therapy. All patients were instructed in manual lymphatic drainage (MLD) and utilised elastic compression for breast oedema before receiving treatment for soft tissue fibrosis. Treatment consisted of using JoViPitPak®, a compression garment developed specifically for treatment of soft tissue fibrosis, which was worn upon the breast under elastic compression for two hours each day for three weeks. Pre- and post-treatment fibrosis was assessed with tissue tonometry, perception of cosmesis was assessed with a questionnaire, and breast pain was measured using an analogue pain scale. Results: Patients demonstrated decreased tissue density, increased perceived cosmesis and a decrease in perceived breast pain. Conclusion: The JoViPitPak® was efficacious in reducing the effects of soft tissue fibrosis. Additional randomised studies are warranted to further assess the efficacy of this treatment approach. Declaration of interest: None. [ABSTRACT FROM AUTHOR]

Objective To determine the contributions of angiogenesis to inflammation, joint damage, and pain behavior in a rat meniscal transection model of osteoarthritis (OA). Methods OA was induced in male Lewis rats (n = 8 per group) by meniscal transection. Animals were orally dosed with dexamethasone (0.1 mg/kg/day), indomethacin (2 mg/kg/day), or the specific angiogenesis inhibitor PPI-2458 (5 mg/kg every other day). Controls consisted of naive and vehicle-treated rats. Synovial inflammation was measured as the macrophage fractional area (expressed as the percentage), thickness of the synovial lining, and joint swelling. Synovial angiogenesis was measured using the endothelial cell proliferation index and vascular density. Channels positive for vessels at the osteochondral junction were assessed (osteochondral angiogenesis). Medial tibial plateaus were assessed for chondropathy, osteophytosis, and channels crossing the osteochondral junction. Pain behavior was measured as weight-bearing asymmetry. Results Dexamethasone and indomethacin each reduced pain behavior, synovial inflammation, and synovial angiogenesis 35 days after meniscal transection. Dexamethasone reduced, but indomethacin had no significant effect on, the total joint damage score. PPI-2458 treatment reduced synovial and osteochondral angiogenesis, synovial inflammation, joint damage, and pain behavior. Conclusion Our findings indicate that synovial inflammation and joint damage are closely associated with pain behavior in the meniscal transection model of OA. Inhibition of angiogenesis may reduce pain behavior both by reducing synovitis and by preventing structural change. Targeting angiogenesis could therefore prove useful in reducing pain and structural damage in OA. [ABSTRACT FROM AUTHOR]

Objective To assess the role of the activating receptor NKG2D in arthritis. Methods Levels of NKG2D and its ligands were determined by fluorescence-activated cell sorting, real-time polymerase chain reaction, and immunohistochemistry in rheumatoid arthritis (RA) synovial membrane tissue and in paw tissue from arthritic mice. Arthritis was induced in DBA/1 mice by immunization with type II collagen, and mice were treated intraperitoneally with a blocking anti-NKG2D antibody (CX5) on days 1, 5, and 8 after clinical onset and were monitored for 10 days. Results We demonstrated expression of NKG2D and its ligands on human RA synovial cells and extended this finding to the paws of arthritic mice. Expression of messenger RNA for the NKG2D ligand Rae-1 was up-regulated, and NKG2D was present predominantly on natural killer (NK) and CD4+ T cells, in arthritic paw cell isolates. NKG2D was down-modulated during the progression of collagen-induced arthritis (CIA). NKG2D expression in arthritic paws was demonstrated by immunohistochemistry. Blockade of NKG2D ameliorated established CIA, with significant reductions in clinical scores and paw swelling. Histologic analysis of arthritic joints from anti-NKG2D-treated mice demonstrated significant joint protection, compared with control mice. Moreover, anti-NKG2D treatment significantly reduced both interleukin-17 production from CD4+ T cells in arthritic paws and splenic NK cell cytotoxic effector functions in vivo and in vitro. Conclusion Our findings indicate that blockade of NKG2D in a murine model and in human explants has beneficial therapeutic potential that merits further investigation in RA. [ABSTRACT FROM AUTHOR]

Medical Education 2011: 45: 886-893 CONTEXT Multi-source feedback (MSF) and patient feedback (PF) are used increasingly around the world to assess and quality-assure clinical practice. However, concerns about the evidence for their utility pertain to their ability to identify poor performance, the impact of allowing assessees to select their own assessors and the many confounders that may undermine validity. METHODS This study was conducted in conjunction with the National Clinical Assessment Service (NCAS) in the UK and used established MSF and PF instruments to assess doctors in potential difficulty. Multi-source feedback assessors were nominated by both the practitioner (Pnom) and the referring body (RBnom). Demographics were collected to elucidate any differences found. Ratings generated by MSF and PF were compared with one another and with findings of a previous study that provided a normative cohort. RESULTS Using MSF, NCAS-assessed doctors scored significantly lower than the reference cohort. Nineteen (28%) NCAS-assessed doctors achieved scores that were less than satisfactory. This rose to 50% when only RBnom assessors were used. Overall, ratings awarded by RBnom assessors were significantly lower than those awarded by Pnom assessors. Collected demographics did not help to explain the difference. Only one NCAS-assessed doctor scored below average according to PF. Doctors in the NCAS-assessed group did not score significantly lower than the reference cohort in PF. Doctor assessment scores awarded by patients were significantly higher than those awarded by colleagues. CONCLUSIONS Although colleagues appear to report poor performance using MSF, patients fail to report concurrent findings. This challenges the validity of PF as it is currently constructed. Scores in MSF differ significantly depending on whether they are practitioner- or third party-nominated. Previously recognised confounding factors do not help to explain this difference. [ABSTRACT FROM AUTHOR]

Purpose To investigate the effect of varying source-to-image distance (SID) on image quality and radiation dose using direct digital radiography (DR). Methods An anthropomorphic pelvic phantom was positioned for a standard anteroposterior DR examination. The SID was initially set at 100 cm, and the tube potential remained constant at 80 kVp. Two exposures were taken at this SID, and the entrance surface dose (ESD) and effective dose (ED) were calculated. Images were sent to a reporting-grade picture archiving and communication system workstation for image quality analysis. The SID was then varied by 10-cm intervals, up to its maximum (80 cm to 147 cm), with 2 exposures taken for each interval. Grid usage also was varied to determine its effect on radiation dose and image quality. Image quality was assessed by 4 observers (2 images per SID interval) who were blinded to the measurements, using a rating system adapted from the European Guidelines on Quality Criteria for Diagnostic Radiographic Images. Results Increasing SID results in lower ESD and ED compared with the standard 100-cm SID (147 cm: 2.56 mGy and 0.44 mSv, respectively, vs 100 cm: 3.00 mGy and 0.51 mSv, respectively; P < .05). Reduction of the SID resulted in an increased ESD and ED (80 cm: 3.79 mGy and 0.65 mSv, respectively; P < .05). Analysis of the resultant images demonstrated a statistically nonsignificant minor increase in image quality when increasing SID (P = .276). Image quality for 60 cm, 80 cm, 100 cm, 120 cm, 140 cm, and 147 cm was given a mean score of 17.5, 30, 31, 33, 33, and 32, respectively. Removal of the grid resulted in lower image quality but a significantly lower overall ESD and ED. Conclusion Significant reductions in ESD and ED can be achieved, without loss of image quality, with a larger-than-normal SID for AP pelvic DR examinations. [ABSTRACT FROM AUTHOR]

Purpose: Psychological problems are common complications following stroke and have an impact on all aspects of recovery. This article investigates levels of psychological distress in patients during hospital admission and after discharge into the community. Early detection and review of poststroke psychological problems may optimize recovery from stroke as recommended in the national stroke guideline. Currently, there are very few follow-up investigations on poststroke mood disorders available that could inform clinical practice. Method: Psychological symptoms were defined as poststroke anxiety and depression and were measured using the Hospital Anxiety and Depression Scale (HADS). Revised cutoff scores for this clinical group were applied. Seventy-seven stroke patients were assessed in the hospital. Forty-two patients from this sample were reassessed after their discharge into the community. Results: Patients in the hospital sample presented with mean anxiety and depression scores above the recommended cutoff for stroke. Far more than 50% of male and female patients presented with heightened psychological distress. Psychological symptoms were slightly less intense and less frequent in the follow-up after discharge sample. The differences between the HADS outcomes of hospitalized and community patients were nonsignificant but remained beyond cutoff for more than 50% of follow-up patients. Conclusion: The study highlights the importance of mood assessments for all stroke patients. The percentage of patients with residual psychological problems was lower than that reported in the literature. However, it is highly recommended for those patients with chronic poststroke psychological distress to have access to specialist psychological interventions. [ABSTRACT FROM AUTHOR]

Objective. Echocardiography is widely used in the investigation of patients with suspected SSc-associated pulmonary arterial hypertension (SSc-PAH). We investigated whether CT pulmonary angiography (CTPA) provides additive diagnostic value.Methods. Data for 89 consecutive patients with suspected SSc-PAH undergoing echocardiography, CTPA and right heart catheterization were reviewed. Pulmonary artery diameter (dPA) and ascending aorta diameter (dAA), right and left ventricular diameter (dRV and dLV) and grade of tricuspid regurgitation (TRCT) measured at CTPA and tricuspid gradient (TGECHO) at echocardiography were retrieved. A predictive equation for mean pulmonary arterial pressure (mPAP) was derived using multivariate linear regression. Multivariate Cox regression analysis was then used to assess the prognostic strength of CTPA parameters and TGECHO.Results. Absolute measures of dPA and dRV correlated weakly with mPAP. However, dPA : dAA and dRV : dLV showed stronger correlations with mPAP (dPA : dAA r = 0.42, P < 0.001; dRV : dLV r = 0.51, P < 0.001). dRV : dLV correlated more strongly with pulmonary vascular resistance than did dPA : dAA (r = 0.63 vs 0.39, P both <0.001). dPA : dAA and TGECHO were independent predictors of mPAP. A derived CT/echo composite index had a higher predictive accuracy (area under the curve = 0.95) than dPA : dAA or TGECHO although negative predictive value (NPV) was only 77%. Combining the CT/echo composite index with presence or absence of TRCT increased NPV to 100% although this observation requires further validation. dRV : dLV was the strongest prognostic factor.Conclusion. In suspected SSc-PAH, cardiac chamber and great vessel measurements at CTPA correlate with pulmonary haemodynamics and predict survival. In combination with echocardiography CTPA increases diagnostic accuracy and may identify other potential causes of breathlessness. [ABSTRACT FROM PUBLISHER]

Objective. Since 2000, we have given B-cell depletion therapy (BCDT) with rituximab to 76 patients with active SLE refractory to standard immunosuppression. Twenty-four of these patients have now received repeated cycles of BCDT. The aims of the study were to: (i) assess the efficacy and safety of repeated cycles of BCDT in treating refractory SLE; and (ii) assess whether retreatment produced a more sustained clinical response.Methods. BCDT was administered using CYC 750 mg, methylprednisolone 125–250 mg and rituximab 1 g given intravenously on two occasions, 2 weeks apart. Patients were reviewed at 1–2 monthly intervals and disease activity assessed using the BILAG activity index and serological markers. Clinical response was categorized as complete or partial remission, or no response, based on the change in BILAG scores.Results. Eighteen patients had sufficient data for detailed analysis. All were female; mean age 29.9 years; mean duration of follow-up 58.7 months. Two patients died during follow-up and there were two infusion reactions. Disease activity was significantly reduced after both cycles of BCDT at 6 months. More patients achieved disease remission after the second cycle (82 vs 61% first cycle), which was maintained in 65% at 12 months (vs 39% first cycle). The time to disease flare was significantly longer after the second cycle (P < 0.001) and 33% of our patients have still not flared to date following retreatment (mean follow-up 24.5 months).Conclusion. Repeated cycles of BCDT with rituximab are effective in treating refractory SLE and has a favourable safety profile. Retreatment may produce a more sustained clinical response. [ABSTRACT FROM PUBLISHER]

BSTRACT [ABSTRACT FROM AUTHOR]

Previous research highlighting the role sexual selection may play in the evolution of human cooperation has yet to distinguish what qualities such behaviours actually signal. The aim here was to examine whether female preferences for male cooperative behaviours are because they signal genetic or indirect phenotypic quality. This was possible by taking into account female participants' stage of menstrual cycle, as much research has shown that females at the most fertile stage show greater preferences specifically for signals of genetic quality than any other stage, particularly for short-term relationships. Therefore, different examples of cooperation (personality, costly signals, heroism) and the mate preferences for altruistic traits self-report scale were used across a series of four experiments to examine females' attitudes towards cooperation in potential mates for different relationship lengths at different stages of the menstrual cycle. The results here consistently show that female fertility had no effect on perceptions of cooperative behaviour, and that such traits were considered more important for long-term relationships. Therefore, this provides strong evidence that cooperative behaviour is important in mate choice as predominantly a signal of phenotypic rather than genetic quality. [ABSTRACT FROM AUTHOR]

Despite evidence of widespread belief in conspiracy theories, there remains a dearth of research on the individual difference correlates of conspiracist ideation. In two studies, we sought to overcome this limitation by examining correlations between conspiracist ideation and a range of individual psychological factors. In Study 1, 817 Britons indicated their agreement with conspiracist ideation concerning the July 7, 2005 (7/7), London bombings, and completed a battery of individual difference scales. Results showed that stronger belief in 7/7 conspiracy theories was predicted by stronger belief in other real-world conspiracy theories, greater exposure to conspiracist ideation, higher political cynicism, greater support for democratic principles, more negative attitudes to authority, lower self-esteem, and lower Agreeableness. In Study 2, 281 Austrians indicated their agreement with an entirely fictitious conspiracy theory and completed a battery of individual difference measures not examined in Study 1. Results showed that belief in the entirely fictitious conspiracy theory was significantly associated with stronger belief in other real-world conspiracy theories, stronger paranormal beliefs, and lower crystallized intelligence. These results are discussed in terms of the potential of identifying individual difference constellations among conspiracy theorists. [ABSTRACT FROM AUTHOR]

Abstract: Despite the known health benefits, the majority of children do not meet physical activity guidelines, with past interventions to increase physical activity yielding little success. Social and friendship networks have been shown to influence obesity, smoking and academic achievement, and peer-led interventions have successfully reduced the uptake of adolescent smoking. However, the role of social networks on physical activity is not clear. This paper investigates the extent to which friendship networks influence children’s physical activity, and attempts to quantify the association using spatial analytical techniques to account for the social influence. Physical activity data were collected for 986 children, aged 10–11 years old, from 40 schools in Bristol, UK. Data from 559 children were used for analysis. Mean accelerometer counts per minute (CPM) and mean minutes of moderate to vigorous physical activity per day (MVPA) were calculated as objective measures of physical activity. Children nominated up to 4 school-friends, and school-based friendship networks were constructed from these nominations. Networks were tested to assess whether physical activity showed spatial dependence (in terms of social proximity in social space) using Moran’s I statistic. Spatial autoregressive modelling was then used to assess the extent of spatial dependence, whilst controlling for other known predictors of physical activity. This model was compared with linear regression models for improvement in goodness-of-fit. Results indicated spatial autocorrelation of both mean MVPA (I = .346) and mean CPM (I = .284) in the data, indicating that children clustered in friendship groups with similar activity levels. Spatial autoregressive modelling of mean MVPA concurred that spatial dependence was present (ρ = .26, p < .001), and improved model fit by 31% on the linear regression model. These results demonstrate an association between physical activity levels of children and their school-friends, and indicate that spatial modelling is an informative method for incorporating the influence of school social structure into physical activity analysis. [Copyright &y& Elsevier]

Background: The posterolateral corner (PLC) resists tibial varus angulation, external rotation, and, to a lesser extent, posterior translation. It is important that reconstructions of posterolateral knee injuries restore joint laxity and patient function, but residual laxities are often observed.Hypothesis: The knee laxity after a new 4-strand PLC reconstruction would be closer to normal than after a 2-strand “modified Larson” reconstruction.Study Design: Controlled laboratory study.Methods: Fourteen intact cadaveric knees were mounted in a 6 degrees of freedom rig and subjected to the following external loading conditions: a 90-N posterior tibial force, a 5-N·m external rotation torque, and 5-N·m varus moment. Knee kinematics were recorded with an active optical tracking system for the intact, PLC-deficient, modified Larson PLC reconstruction and 4-strand PLC reconstruction.Results: With external tibial torque, the rotational laxity in 4-strand reconstruction was significantly less than in the PLC-deficient (P < .0001) and modified Larson reconstruction (P = .0112) and did not differ significantly from intact laxity at any angle of flexion. In response to posterior load, posterior translation did not change in any of the tested conditions, while the coupled external rotation laxity in 4-strand PLC reconstruction was significantly less than in the PLC-deficient (P < .0001) and modified Larson reconstruction (P < .0486) and was not significantly different from the intact movements for both reconstructions. The varus angulation-versus-flexion curves were significantly different between the PLC-deficient and both PLC reconstructions (P < .0001). The varus laxity was not significantly different between the modified Larson reconstruction, the 4-strand reconstruction, and the intact knee.Conclusion: This study showed that the rotational knee laxity in response to both external rotation and posterior translation load were significantly better after the 4-strand PLC reconstruction than after the modified Larson reconstruction, although significant differences were not found between the 2 procedures for varus laxity.Clinical Relevance: The 4-strand PLC reconstruction may produce a better biomechanical outcome, especially during external rotation and posterior translation tibial load. The authors suggest that this relates to load sharing among 4 graft strands crossing the joint. [ABSTRACT FROM AUTHOR]

Haemopoietic stem cell transplantation (HSCT) is a life-saving but intensive procedure associated with potentially severe adverse late effects. We aimed to determine morbidity and health-related quality of life (HRQOL) in a sample of survivors aged 8-18 years at least 1 year post HSCT for paediatric acute leukaemia, compared with a non-transplanted group of survivors matched for age, gender, initial disease and time since treatment. Families (N = 54; HSCT n= 29) recruited from four UK centres completed measures of child behaviour and school attendance, HRQOL and finances. Mothers completed measures of their own well-being. Clinical outcome data were extracted from medical records. Children in the HSCT group had significantly more late effects and had received more tests for vision, bone, dental and skin health, and thyroid, lung, and gonadal function than the non-transplanted group. HRQOL scores for the HSCT group were significantly lower in all domains compared with the non-transplanted group and population norms, but were not significantly related to clinical indices. Mothers in the HSCT group had significantly poorer mental well-being than population norms. Significant morbidity and compromised HRQOL was found in survivors of HSCT. The burden of caring for a child after HSCT has a continuing toll on mothers' well-being.The importance of counselling families about possible long-term consequences is emphasized. [ABSTRACT FROM AUTHOR]

Objective To assess the ability of pre-B cell colony-enhancing factor (PBEF) to regulate inflammation and degradative processes in inflammatory arthritis, using the small molecule inhibitor APO866 in human fibroblasts in vitro and in murine collagen-induced arthritis (CIA). Methods Enzyme-linked immunosorbent assays were used to examine regulation of expression of metalloproteinases and chemokines in human fibroblasts. The role of PBEF was further examined using APO866 in mice with CIA, with effects on disease activity assessed using radiography, histology, in vivo imaging, and quantitative polymerase chain reaction (qPCR). Results In vitro activation of human fibroblasts with PBEF promoted expression of matrix metalloproteinase 3 (MMP-3), CCL2, and CXCL8, an effect inhibited by APO866. In mice with CIA, early intervention with APO866 inhibited synovial inflammation, including chemokine-directed leukocyte infiltration, and reduced a systemic marker of inflammation, serum hyaluronic acid. APO866 blockade led to reduced expression of MMP-3 and MMP-13 in joint extracts and to a reduction in a systemic marker of cartilage erosion, serum cartilage oligomeric matrix protein. Radiologic images revealed that APO866 protected against bone erosion, while qPCR demonstrated inhibition of RANKL expression. In mice with established disease, APO866 reduced synovial inflammation and cartilage destruction, and halted bone erosion. In addition, APO866 reduced the activity of MMP-3, CCL2, and RANKL in vivo, and inhibited production of CCL2 and RANKL in synovial explants from arthritic mice, a result that was reversed with nicotinamide mononucleotide. Conclusion These findings confirm PBEF to be an important regulator of inflammation, cartilage catabolism, and bone erosion, and highlight APO866 as a promising therapeutic agent for targeting PBEF activity in inflammatory arthritis. [ABSTRACT FROM AUTHOR]

Objective Expanded populations of CD4+CD28− T cells with a cytotoxic phenotype have been repeatedly reported in patients with granulomatosis with polyangiitis (Wegener's) (GPA). In healthy individuals expansion of this T cell population follows cytomegalovirus (CMV) infection. We undertook this study to investigate whether CMV infection may be responsible for driving the expansion of CD4+CD28− T cells in GPA patients and how this might relate to clinical features. Methods Forty-eight GPA patients and 38 age-matched healthy donors were included in the study. CMV-specific IgG in serum was detected by enzyme-linked immunosorbent assay. Flow cytometric analysis was used to study T cell populations and phenotype. The presence of CMV in renal biopsy tissue from GPA patients was investigated by immunohistochemistry and polymerase chain reaction (PCR). Clinical information was obtained from patient records. Results Populations of CD4+CD28− T cells were only expanded in CMV-seropositive GPA patients and controls. In CMV-seropositive GPA patients we observed negative correlations between the percentages of CD4+CD28− T cells and both the percentage of naive T cells and the glomerular filtration rate at presentation. There was a significant association between the percentage of CD4+CD28− T cells and risk of infection and mortality. CMV could not be detected in renal tissue by PCR or immunohistochemistry. CMV seropositivity itself was not a risk factor for infection in a cohort of 182 patients with antineutrophil cytoplasmic antibody-associated vasculitis who had been recruited into clinical trials performed by the European Vasculitis Study Group. Conclusion The expansion of CD4+CD28− T cells in GPA patients is associated with CMV infection and leads to a reduction in the number of naive T cells in peripheral blood. Patients with expanded CD4+CD28− T cells have significantly increased mortality and risk of infection. [ABSTRACT FROM AUTHOR]

To describe the incidence and intensity of pain, hypotension and other epidural-related side-effects after major abdominal surgery and to identify factors associated with effective epidural analgesia. Evidence exists that up to 30% of patients with epidural analgesia still experience severe pain in clinical practice. When epidurals produce good pain relief, potentially harmful side effects can result. Data were collected prospectively from 480 consecutive general surgical patients in a large District General Hospital in the UK. Fifty-six per cent of patients were hypotensive on day one. Low pain scores were found to be a predicator for postoperative hypotension. Severe pain was associated with emergency patients, male gender, the absence of hypotension and an epidural that did not continue until planned removal. Significantly lower mean pain scores were found in patients who were 70 years of age and over. No correlation exists between chronic pain before surgery and the level of postoperative pain. This study contributes to the epidural versus standard analgesia debate by describing the population in whom epidurals are used and identifies factors associated with both the success and failure of the technique in everyday practice. The Audit Commission has proposed a standard whereby less than 5% of patients should suffer severe pain following surgery. This may prove to be an unrealistic goal with currently available techniques. As it is ward nursing staff who are primarily responsible for monitoring the effectiveness of the technique, it is important for nursing professionals to know the potential risks of postoperative epidural analgesia to be able to respond appropriately. The important measurements of an optimum acute pain assessment have been identified, based on the study results, allowing the development of a national acute pain registry to inform future practice. [ABSTRACT FROM AUTHOR]

Background: Cold water immersion reduces exercise-induced muscle damage. Benefits may partly arise from a decline in limb blood flow; however, no study has comprehensively investigated the influence of different degrees of cooling undertaken via cold water immersion on limb blood flow responses.Purpose: To determine the influence of cold (8°C) and cool (22°C) water immersion on lower limb and cutaneous blood flow.Study Design: Controlled laboratory study.Methods: Nine men were placed in a semireclined position and lowered into 8°C or 22°C water to the iliac crest for two 5-minute periods interspersed with 2 minutes of nonimmersion. Rectal and thigh skin temperature, deep and superficial muscle temperature, heart rate, mean arterial pressure, thigh cutaneous blood velocity (laser Doppler), and superficial femoral artery blood flow (duplex ultrasound) were measured during immersion and for 30 minutes after immersion. Indices of vascular conductance were calculated (flux and blood flow/mean arterial pressure).Results: Reductions in rectal temperature (8°C, 0.2° ± 0.1°C; 22°C, 0.1° ± 0.1°C) and thigh skin temperature (8°C, 6.2° ± 0.5°C; 22°C, 3.2° ± 0.2°C) were greater in 8°C water than in 22°C (P < .01). Femoral artery conductance was reduced to a similar extent immediately after immersion (~30%) and 30 minutes after immersion (~40%) under both conditions (P < .01). In contrast, there was less thigh cutaneous vasoconstriction during and after immersion in 8°C water compared with 22°C (P = .01).Conclusion: These data suggest that immersion at both temperatures resulted in similar whole limb blood flow but, paradoxically, more blood was distributed to the skin in the colder water. This suggests that colder temperatures may be associated with reduced muscle blood flow, which could provide an explanation for the benefits of cold water immersion in alleviating exercise-induced muscle damage in sports and athletic contexts.Clinical Relevance: Colder water temperatures may be more effective in the treatment of exercise-induced muscle damage and injury rehabilitation because of greater reductions in muscle blood flow. [ABSTRACT FROM PUBLISHER]

The use of religious/spiritual resources may increase when dealing with the stress of a cancer diagnosis. However, there has been very little research conducted into changes in religious/spiritual beliefs and practices as a result of a cancer diagnosis outside the USA. The aim of this study was to examine the impact of a breast cancer diagnosis on patients' religious/spiritual beliefs and practices in the UK where religious practice is different. The study used two methods. One compared the religious/spiritual beliefs and practices of 202 patients newly diagnosed with breast cancer with those of a control group of healthy women ( n = 110). The other examined patients' perceived change in religious/spiritual beliefs and practices at the time of surgery with those in the year prior to surgery. The aspects of religiousness/spirituality assessed were: levels of religiosity/spirituality, strength of faith, belief in God as well as private and public practices. Patient's perceived their belief in God, strength of faith and private religious/spiritual practices to have significantly increased shortly after surgery compared with the year prior to surgery. However, there were no significant differences in religious/spiritual beliefs and practices between patients and healthy participants. Change scores demonstrated both a reduction and an increase in religious/spiritual beliefs and practices. Although belief in God, strength of faith and private religious/spiritual practices were perceived by patients to be significantly higher after their cancer diagnosis, no significant differences in religious/spiritual beliefs and practices were found between the cancer group at the time of surgery and the control group. Different methodologies appear to produce different results and may explain contradictions in past US studies. Limitations of this study are discussed and suggestions for future research are made. [ABSTRACT FROM AUTHOR]

The aim of this study was to analyse the important kinematic variables in elite men's and women's 20 km race walking. Thirty men and 30 women were analysed from video data recorded during the World Race Walking Cup. Video data were also recorded at four points during the European Cup Race Walking and 12 men and 12 women analysed from these data. Two camcorders operating at 50 Hz recorded at each race for 3D analysis. The two main performance determinants of speed were step length and cadence. Men were faster than women because of their greater step lengths but there was no difference in cadence. A reduction in step length was the initial cause of slowing down with later decreases in speed caused by reductions in cadence. Shorter contact times were important in optimising both step length and cadence, and faster athletes tended to have longer flight times than slower athletes. It was less clear which other kinematic variables were critical for successful walking, particularly with regard to joint angles. Different associations were found for some key variables in men and women, suggesting that their techniques may differ due to differences in height and mass. [ABSTRACT FROM AUTHOR]

Objective: Compulsive exercise describes a rigid, driven urge to exercise that has been reported in different populations, including eating disorder patients. This compulsion can develop at an early age and yet the measurement of compulsive exercise in adolescents is limited by inappropriate assessment techniques. This study aimed to psychometrically evaluate the Compulsive Exercise Test (CET) in a sample of adolescents. Methods: The sample consisted of 1012 adolescents aged 12–14 years old, who completed the CET, the Commitment to Exercise Scale (CES), and selected subscales from the Eating Disorder Inventory-2 (EDI-2). Results: Results confirmed the original five-factor solution of the CET. The CET’s concurrent validity with the CES, as well as the convergent validity with the EDI-2, was established. The CET was not strongly related to exercise frequency. Conclusion: The CET appears to be valid and reliable for use with adolescents. Replication with an adolescent clinical eating disorder sample is now required. [ABSTRACT FROM AUTHOR]

Diagnoses of paediatric bipolar disorder have increased over the last two decades in the United States, where high levels of comorbidity with ADHD have also been reported. To explore how British clinicians apply these diagnoses. We compared 378 young people under the age of 18 who received a diagnosis of bipolar disorder and/or ADHD from a large NHS mental health trust between 1992 and 2007. Children with bipolar disorder were rare in this sample ( n = 35, 1.0%), particularly under the age of 13 ( n = 9, 0.3%). Children with bipolar disorder presented more often with affective and psychotic symptoms than children with ADHD. Irritability was common in both disorders. Core ADHD symptoms were prevalent in both conditions but occurred in a greater proportion of children with ADHD. Our findings suggest that psychiatrists in England use the traditional adult criteria of bipolar disorder rather than the broader criteria being adopted by some practitioners in the US. [ABSTRACT FROM AUTHOR]

Introduction: The multiple mini-interview (MMI) has been shown to be a valuable tool to aid the selection of medical students. The increasing body of research data so far has not evaluated this approach in the UK, where selection for medical training has traditionally included a single unstructured or structured interview. Methods: MMI stations were developed and tested on volunteer candidates for admission to the MBBS 4 and MBBS 5 courses. Volunteers undertook their admissions interview before taking part in the MMI trial. Scores were compared between the two interview formats and any relationship with demographic details and the aptitude tests (UK Clinical Aptitude Test and Graduate Medical School Admissions Test) established. Results: MBBS 4 applicants performed just as well on the MMI as they did on the traditional interview, with the MBBS 5 applicants performing better on the MMI. MBBS 4 and MBBS 5 candidates did equally well on the MMI. There was no difference in performance related to sex or age. Discussion: MMIs are reliable, feasible and acceptable to both applicants and interviewers. Longitudinal research will shed more light on the validity of MMI as a way of measuring applicants'' potential to become professional, successful doctors. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the mental and physical health of diplomats working in a war zone. The method conducted in the study was a comparative retrospective cohort design for two groups of Great Britain diplomats who had postings in Iraq or Afghanistan. Results show that diplomats posted in Iraq and Afghanistan and individuals who experienced trauma had significantly more symptoms of posttraumatic stress disorder.

Objective: To investigate the presence of any regional myocardial deformation abnormalities in Marfan syndrome (MFS) and determine the benefits of using advanced echocardiography compared to conventional techniques. Background: Myocardial dysfunction in MFS may be caused by extracellular matrix remodeling thus, resulting in uniform reduced functionality. However, increased aortic stiffness may cause segmental ventricular abnormalities. Strain rate imaging (SRI) constitutes a validated technique to assess regional deformation in various clinical conditions. With this in mind, we aimed to investigate biventricular function in MFS using SRI. Methods: Forty-four MFS patients (mean age 30 ± 12 years, 26 men) and 49 controls without valvular disease were examined using SRI. Ejection fraction (EF) was calculated by the Simpson's biplane method. Biventricular deformation was assessed by measuring strain/strain rate. Strain values were divided by left ventricular (LV) end-diastolic volume to adjust LV deformation for geometry changes providing a strain index (SI). Aortic stiffness was evaluated using the β-stiffness index. Results: EF (%) was reduced in MFS patients (59 ± 5 vs 72 ± 4, P < 0.001), whereas β-stiffness was increased (P < 0.001). LV radial and LV and right ventricular (RV) long-axis strain values (%) were reduced in the patient group (70 ± 17 vs 93 ± 10; 19 ± 2 vs 25 ± 2; 30 ± 9 vs 36 ± 8, respectively, P < 0.001). Strain rate measurements were also reduced (P < 0.001). In a multiple regression analysis, MFS diagnosis was negatively associated with LV SI (−0.262 [−0.306, −0.219], P < 0.001). β-Stiffness was negatively associated with SI obtained from the septum, inferior and anterior walls. ROC analyses demonstrated that SRI, when compared with conventional echocardiography, had higher sensitivity and specificity in predicting biventricular dysfunction in MFS. Conclusions: Our study showed a uniform reduction in biventricular deformation in MFS. These findings suggest that assessment of myocardial function using advanced echocardiographic techniques could be more accurate in MFS patient evaluation than conventional echocardiography alone. (Echocardiography 2011;28:416-430) [ABSTRACT FROM AUTHOR]

The specifics of inflammation created by infection with Chlamydia trachomatis could be favourable to the genesis of endometriosis. To investigate this hypothesis, we studied the association between Chlamydia trachomatis specific IgG and IgA antibodies in serum and the peritoneal fluid of 51 women undergoing laparoscopic surgery. There was no significant difference between women with and without endometriosis with respect to the incidence of IgG and IgA in serum or the peritoneal fluid. The results of our preliminary study did not show any significant link between past infection with Chlamydia trachomatis and the presence of endometriosis. [ABSTRACT FROM AUTHOR]