Transition from fractal-dendritic to compact islands for the 2D-ferroelectric SnSe on graphene/Ir(111).

Epitaxial growth is a versatile method to prepare two-dimensional van der Waals ferroelectrics like group IV monochalcogenides which have potential for novel electronic devices and sensors. We systematically study SnSe monolayer islands grown by molecular beam epitaxy, especially the effect of annealing temperature on shape and morphology of the edges. Characterization of the samples by scanning tunneling microscopy reveals that the shape of the islands changes from fractal-dendritic after deposition at room temperature to a compact rhombic shape through annealing, but ripening processes are absent up to the desorption temperature. A two-step growth process leads to large, epitaxially aligned rhombic islands bounded by well-defined110-edges (armchair-like), which we claim to be the equilibrium shape of the stoichiometric SnSe monolayer islands. The relaxation of the energetically favorable edges is detected in atomically resolved STM images. The experimental findings are supported by the results of our first-principles calculations, which provide insights into the energetics of the edges, their reconstructions, and yields the equilibrium shapes of the islands which are in good agreement with the experiment.

Impact of previous hepatitis B infection on the clinical outcomes from chronic hepatitis C? A population-level analysis.

Chronic coinfection with hepatitis C virus (HCV) and hepatitis B virus (HBV) is associated with adverse liver outcomes. The clinical impact of previous HBV infection on liver disease in HCV infection is unknown. We aimed at determining any association of previous HBV infection with liver outcomes using antibodies to the hepatitis B core antigen (HBcAb) positivity as a marker of exposure. The Scottish Hepatitis C Clinical Database containing data for all patients attending HCV clinics in participating health boards was linked to the HBV diagnostic registry and mortality data from Information Services Division, Scotland. Survival analyses with competing risks were constructed for time from the first appointment to decompensated cirrhosis, hepatocellular carcinoma (HCC) and liver-related mortality. Records of 8513 chronic HCV patients were included in the analyses (87 HBcAb positive and HBV surface antigen [HBsAg] positive, 1577 HBcAb positive and HBsAg negative, and 6849 HBcAb negative). Multivariate cause-specific proportional hazards models showed previous HBV infection (HBcAb positive and HBsAg negative) significantly increased the risks of decompensated cirrhosis (hazard ratio [HR]: 1.29, 95% CI: 1.01-1.65) and HCC (HR: 1.64, 95% CI: 1.09-2.49), but not liver-related death (HR: 1.02, 95% CI: 0.80-1.30). This is the largest study to date showing an association between previous HBV infection and certain adverse liver outcomes in HCV infection. Our analyses add significantly to evidence which suggests that HBV infection adversely affects liver health despite apparent clearance. This has important implications for HBV vaccination policy and indications for prioritization of HCV therapy.

Combined use of hyperbaric oxygen and sprayed keratinocyte suspension to tackle a difficult wound.

This is the first reported case in the literature to combine the use of a well established therapy to achieve wound healing (ie hyperbaric oxygen treatment) and a novel sprayed keratinocyte suspension technique to treat a challenging wound successfully. The merits and potential issues associated with these treatments are outlined and the case is detailed.

Attendance at specialist hepatitis clinics and initiation of antiviral treatment among persons chronically infected with hepatitis C: examining the early impact of Scotland's Hepatitis C Action Plan.

Primary goals of the Hepatitis C Action Plan for Scotland Phase II (May 2008-March 2011) were to increase, among persons chronically infected with the hepatitis C (HCV) virus, attendance at specialist outpatient clinics and initiation on antiviral therapy. We evaluated progress towards these goals by comparing the odds, across time, of (a) first clinic attendance within 12 months of HCV diagnosis (n = 9747) and (b) initiation on antiviral treatment within 12 months of first attendance (n = 5736). Record linkage between the national HCV diagnosis (1996-2009) and HCV clinical (1996-2010) databases and logistic regression analyses were conducted for both outcomes. For outcome (a), 32% and 45% in the respective pre-Phase II (before 1 May 2008) and Phase II periods attended a specialist clinic within 12 months of diagnosis; the odds of attendance within 12 months increased over time (OR = 1.05 per year, 95% CI: 1.04-1.07), but was not significantly greater for persons diagnosed with HCV in the Phase II era, compared with the pre-Phase II era (OR = 1.1, 95% CI: 0.9-1.3), after adjustment for temporal trend. For outcome (b), 13% and 28% were initiated on treatment within 12 months of their first clinic attendance in the pre-Phase II and Phase II periods, respectively. Higher odds of treatment initiation were associated with first clinic attendance in the Phase II (OR = 1.9, 95% CI: 1.5-2.4), compared with the pre-Phase II era. Results were consistent with a positive impact of the Hepatitis C Action Plan on the treatment of chronically infected individuals, but further monitoring is required to confirm a sustained effect.

Family-based interventions for reducing sedentary time in youth: a systematic review of randomized controlled trials.

Family involvement in interventions to reduce sedentary time may help foster appropriate long-term screen-based habits in children. This review systematically synthesized evidence from randomized controlled trials of interventions with a family component that targeted reduction of sedentary time, including TV viewing, video games and computer use, in children. MEDLINE, PubMed, PsycInfo, CINAHL and Embase were searched from inception through March 2012. Seventeen articles were considered eligible and included in the review. Studies were judged to be at low-to-moderate risk of bias. Despite inconsistent study results, level of parental involvement, rather than the setting itself, appeared an important determinant of intervention success. Studies including a parental component of medium-to-high intensity were consistently associated with statistically significant changes in sedentary behaviours. Participant age was also identified as a determinant of intervention outcomes; all three studies conducted in pre-school children demonstrated significant decreases in sedentary time. Finally, TV exposure appeared to be related to changes in energy intake rather than physical activity. Future studies should assess the effects of greater parental involvement and child age on success of sedentary behaviour interventions. More research is required to better understand the relationship between screen time and health behaviours, particularly energy intake.

Fanconi's anaemia and unilateral thumb polydactyly--don't miss it.

Fanconi's anaemia (FA) is a rare, life threatening inherited syndrome. Patients usually present late in the first decade of life with aplastic anaemia or acute myeloid leukaemia. FA children are also at high risk of solid organ tumours, anogenital squamous cancers, and endocrinopathies. These patients can present with unilateral radial abnormalities including thumb duplication. Hand surgeons can help achieve early diagnosis and improved survival in this group by early referral for screening. In a retrospective study of 202 children with radial ray anomalies seen over a 20 year period seven children had FA. Of these seven with FA, four had bilateral thumb hypoplasia and three had unilateral thumb anomalies--two unilateral thumb hypoplasias and one thumb duplication. The three children with unilateral anomalies were diagnosed late, presenting with bone marrow failure. All three have subsequently died following late bone marrow transplants. This study highlights the link between unilateral radial anomalies, including thumb duplication and FA and the importance of early genetic referral for diagnosis and surveillance.

Time-dependent effects of Prkce deletion on glucose homeostasis and hepatic lipid metabolism on dietary lipid oversupply in mice.

AIMS/HYPOTHESIS: We examined the time-dependent effects of deletion of the gene encoding protein kinase C epsilon (Prkce) on glucose homeostasis, insulin secretion and hepatic lipid metabolism in fat-fed mice. METHODS: Prkce(-/-) and wild-type (WT) mice were fed a high-fat diet for 1 to 16 weeks and subjected to i.p. glucose tolerance tests (ipGTT) and indirect calorimetry. We also investigated gene expression and protein levels by RT-PCR, quantitative protein profiling (isobaric tag for relative and absolute quantification; iTRAQ) and immunoblotting. Lipid levels, mitochondrial oxidative capacity and lipid metabolism were assessed in liver and primary hepatocytes. RESULTS: While fat-fed WT mice became glucose intolerant after 1 week, Prkce(-/-) mice exhibited normal glucose and insulin levels. iTRAQ suggested differences in lipid metabolism and oxidative phosphorylation between fat-fed WT and Prkce(-/-) animals. Liver triacylglycerols were increased in fat-fed Prkce(-/-) mice, resulting from altered lipid partitioning which promoted esterification of fatty acids in hepatocytes. In WT mice, fat feeding elevated oxygen consumption in vivo and in isolated liver mitochondria, but these increases were not seen in Prkce(-/-) mice. Prkce(-/-) hepatocytes also exhibited reduced production of reactive oxygen species (ROS) in the presence of palmitate. After 16 weeks of fat feeding, however, the improved glucose tolerance in fat-fed Prkce(-/-) mice was instead associated with increased insulin secretion during ipGTT, as we have previously reported. CONCLUSIONS/INTERPRETATION: Prkce deletion ameliorates diet-induced glucose intolerance via two temporally distinct phenotypes. Protection against insulin resistance is associated with changes in hepatic lipid partitioning, which may reduce the acute inhibitory effects of fatty acid catabolism, such as ROS generation. In the longer term, enhancement of glucose-stimulated insulin secretion prevails.

Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial.

BACKGROUND: Trial findings show cognitive behaviour therapy (CBT) and graded exercise therapy (GET) can be effective treatments for chronic fatigue syndrome, but patients' organisations have reported that these treatments can be harmful and favour pacing and specialist health care. We aimed to assess effectiveness and safety of all four treatments. METHODS: In our parallel-group randomised trial, patients meeting Oxford criteria for chronic fatigue syndrome were recruited from six secondary-care clinics in the UK and randomly allocated by computer-generated sequence to receive specialist medical care (SMC) alone or with adaptive pacing therapy (APT), CBT, or GET. Primary outcomes were fatigue (measured by Chalder fatigue questionnaire score) and physical function (measured by short form-36 subscale score) up to 52 weeks after randomisation, and safety was assessed primarily by recording all serious adverse events, including serious adverse reactions to trial treatments. Primary outcomes were rated by participants, who were necessarily unmasked to treatment assignment; the statistician was masked to treatment assignment for the analysis of primary outcomes. We used longitudinal regression models to compare SMC alone with other treatments, APT with CBT, and APT with GET. The final analysis included all participants for whom we had data for primary outcomes. This trial is registered at http://isrctn.org, number ISRCTN54285094. FINDINGS: We recruited 641 eligible patients, of whom 160 were assigned to the APT group, 161 to the CBT group, 160 to the GET group, and 160 to the SMC-alone group. Compared with SMC alone, mean fatigue scores at 52 weeks were 3·4 (95% CI 1·8 to 5·0) points lower for CBT (p = 0·0001) and 3·2 (1·7 to 4·8) points lower for GET (p = 0·0003), but did not differ for APT (0·7 [-0·9 to 2·3] points lower; p = 0·38). Compared with SMC alone, mean physical function scores were 7·1 (2·0 to 12·1) points higher for CBT (p = 0·0068) and 9·4 (4·4 to 14·4) points higher for GET (p = 0·0005), but did not differ for APT (3·4 [-1·6 to 8·4] points lower; p=0·18). Compared with APT, CBT and GET were associated with less fatigue (CBT p = 0·0027; GET p = 0·0059) and better physical function (CBT p=0·0002; GET p<0·0001). Subgroup analysis of 427 participants meeting international criteria for chronic fatigue syndrome and 329 participants meeting London criteria for myalgic encephalomyelitis yielded equivalent results. Serious adverse reactions were recorded in two (1%) of 159 participants in the APT group, three (2%) of 161 in the CBT group, two (1%) of 160 in the GET group, and two (1%) of 160 in the SMC-alone group. INTERPRETATION: CBT and GET can safely be added to SMC to moderately improve outcomes for chronic fatigue syndrome, but APT is not an effective addition. FUNDING: UK Medical Research Council, Department of Health for England, Scottish Chief Scientist Office, Department for Work and Pensions.

Objectively measured physical activity and obesity prevention in children, adolescents and adults: a systematic review of prospective studies.

This study aimed at synthesizing the prospective associations between measured physical activity (PA) and change in adiposity in children, adolescents and adults following from two previous reviews. Search terms were adapted and a systematic literature search was conducted (January 2000-September 2008) and later updated (up to October 2009), considering observational and intervention studies of weight gain that measured both PA and body composition. Sixteen observational studies (six comprising adults) and five trials (one comprising adults) were eligible. For consistency, whenever possible either baseline PA energy expenditure or accelerometer output (counts min(-1) ) and change in per cent body fat were the extracted exposure and outcome measures. Results of observational studies suggest that PA is not strongly prospectively related with adiposity: five studies on children and three on adults reported no association between baseline PA and change in adiposity, one study found a weak positive association and the other studies observed a weak negative association. Negative associations were more frequently observed in studies that analysed the association between change in the exposure and outcome. Intervention studies show generally no effect on either PA or adiposity. In conclusion, despite the well-established health benefits of PA, it may not be a key determinant of excessive gain in adiposity.

Overexpression of the orphan receptor Nur77 alters glucose metabolism in rat muscle cells and rat muscle in vivo.

AIMS/HYPOTHESIS: A hallmark feature of the metabolic syndrome is abnormal glucose metabolism which can be improved by exercise. Recently the orphan nuclear receptor subfamily 4, group A, member 1 (NUR77) was found to be induced by exercise in muscle and was linked to transcriptional control of genes involved in lipid and glucose metabolism. Here we investigated if overexpression of Nur77 (also known as Nr4a1) in skeletal muscle has functional consequences for lipid and/or glucose metabolism. METHODS: L6 rat skeletal muscle myotubes were infected with a Nur77-coding adenovirus and lipid and glucose oxidation was measured. Nur77 was also overexpressed in skeletal muscle of chow- and fat-fed rats and the effects on glucose and lipid metabolism evaluated. RESULTS: Nur77 overexpression had no effect on lipid oxidation in L6 cells or rat muscle, but did increase glucose oxidation and glycogen synthesis in L6 cells. In chow- and high-fat-fed rats, Nur77 overexpression by electrotransfer significantly increased basal glucose uptake and glycogen synthesis, but no increase in insulin-stimulated glucose metabolism was observed. Nur77 electrotransfer was associated with increased production of GLUT4 and glycogenin and increased hexokinase and phosphofructokinase activity. Interestingly, Nur77 expression in muscle biopsies from obese men was significantly lower than in those from lean men and was closely correlated with body-fat content and insulin sensitivity. CONCLUSIONS/INTERPRETATION: Our data provide compelling evidence that NUR77 is a functional regulator of glucose metabolism in skeletal muscle in vivo. Importantly, the diminished content in muscle of obese insulin-resistant men suggests that it might be a potential therapeutic target for the treatment of dysregulated glucose metabolism.

Age-dependency in bone mass and geometry: a pQCT study on male and female master sprinters, middle and long distance runners, race-walkers and sedentary people.

OBJECTIVE: To investigate whether athletic participation allows master athletes to preserve their good bone health into old age. METHODS: Bone strength indicators of the tibia and the radius were obtained of master runners and race-walkers (n=300) competing at World and European Master Championships and of 75 sedentary controls, all aged 33-94 yrs. RESULTS: In the tibia, diaphyseal cortical area (Ar.Ct), polar moment of resistance (RPol) and trabecular bone mineral density (vBMD) were generally greater in athletes than controls at all ages. In the athletes, but not the controls, Ar.Ct, RPol (females) and trabecular vBMD were negatively correlated with age (p<0.01). Radius measures were comparable between athlete and control groups at all ages. The amalgamated data revealed negative correlations of age with Ar.Ct, RPol (females), cortical vBMD and trabecular vBMD (males; p<0.005) and positive correlations with endocortical circumference (p<0.001). CONCLUSION: This cross-sectional study found age-related differences in tibial bone strength indicators of master athletes, but not sedentary controls, thus, groups becoming more similar with advancing age. Age-related differences were noticeable in the radius too, without any obvious group difference. Results are compatible with the notion that bones adapt to exercise-specific forces throughout the human lifespan.

Reflections from a systematic review of dietary energy density and weight gain: is the inclusion of drinks valid?

The association between dietary energy density, increased energy intake and weight gain is supported by experimental evidence, but confirmation of an effect in free-living humans is limited. Experimental evidence supports a role of energy density in obesity through changes in food composition, not drinks consumption. The inclusion of drinks in the calculation creates a variable of questionable validity and has a substantive impact on the estimated energy density of the diet. We posit, based on the experimental evidence, that calculating the energy density of diets by excluding drinks and including calories from drinks as a covariate in the analysis is the most valid and reliable method of testing the relationship between energy density and weight gain in free-living humans. We demonstrate, by systematically reviewing existing observational studies of dietary energy density and weight gain in free-living humans, how current variation in the method for calculating energy density hampers the interpretation of these data. Reaching an a priori decision on the appropriate methodology will reduce the error caused by multiple comparisons and facilitate meaningful interpretation of epidemiological evidence to inform the development of effective obesity prevention strategies.

Bone mass and geometry of the tibia and the radius of master sprinters, middle and long distance runners, race-walkers and sedentary control participants: a pQCT study.

Mechanical loading is thought to be a determinant of bone mass and geometry. Both ground reaction forces and tibial strains increase with running speed. This study investigates the hypothesis that surrogates of bone strength in male and female master sprinters, middle and long distance runners and race-walkers vary according to discipline-specific mechanical loading from sedentary controls. Bone scans were obtained by peripheral Quantitative Computed Tomography (pQCT) from the tibia and from the radius in 106 sprinters, 52 middle distance runners, 93 long distance runners and 49 race-walkers who were competing at master championships, and who were aged between 35 and 94 years. Seventy-five age-matched, sedentary people served as control group. Most athletes of this study had started to practice their athletic discipline after the age of 20, but the current training regime had typically been maintained for more than a decade. As hypothesised, tibia diaphyseal bone mineral content (vBMC), cortical area and polar moment of resistance were largest in sprinters, followed in descending order by middle and long distance runners, race-walkers and controls. When compared to control people, the differences in these measures were always >13% in male and >23% in female sprinters (p<0.001). Similarly, the periosteal circumference in the tibia shaft was larger in male and female sprinters by 4% and 8%, respectively, compared to controls (p<0.001). Epiphyseal group differences were predominantly found for trabecular vBMC in both male and female sprinters, who had 15% and 18% larger values, respectively, than controls (p<0.001). In contrast, a reverse pattern was found for cortical vBMD in the tibia, and only few group differences of lower magnitude were found between athletes and control people for the radius. In conclusion, tibial bone strength indicators seemed to be related to exercise-specific peak forces, whilst cortical density was inversely related to running distance. These results may be explained in two, non-exclusive ways. Firstly, greater skeletal size may allow larger muscle forces and power to be exerted, and thus bias towards engagement in athletics. Secondly, musculoskeletal forces related to running can induce skeletal adaptation and thus enhance bone strength.