Closing the sea surface mixed layer temperature budget from in situ observations alone: Operation Advection during BoBBLE

Sea surface temperature (SST) is a fundamental driver of tropical weather systems such as monsoon rainfall and tropical cyclones. However, understanding of the factors that control SST variability is lacking, especially during the monsoons when in situ observations are sparse. Here we use a ground-breaking observational approach to determine the controls on the SST variability in the southern Bay of Bengal. We achieve this through the first full closure of the ocean mixed layer energy budget derived entirely from in situ observations during the Bay of Bengal Boundary Layer Experiment (BoBBLE). Locally measured horizontal advection and entrainment contribute more significantly than expected to SST evolution and thus oceanic variability during the observation period. These processes are poorly resolved by state-of-the-art climate models, which may contribute to poor representation of monsoon rainfall variability. The novel techniques presented here provide a blueprint for future observational experiments to quantify the mixed layer heat budget on longer time scales and to evaluate these processes in models

E-cadherin can limit the transforming properties of activating β-catenin mutations

Wnt pathway deregulation is a common characteristic of many cancers. But only Colorectal Cancer predominantly harbours mutations in APC, whereas other cancer types (hepatocellular carcinoma, solid pseudopapillary tumours of pancreas) have activating mutations in β-catenin (CTNNB1). We have compared the dynamics and the potency of β-catenin mutations in vivo. Within the murine small intestine (SI), an activating mutation of β-catenin took much longer to achieve a Wnt deregulation and acquire a crypt-progenitor-cell (CPC) phenotype than Apc or Gsk3 loss. Within the colon, a single activating mutation of β-catenin was unable to drive Wnt deregulation or induce the CPC phenotype. This ability of β-catenin mutation to differentially transform the SI versus the colon correlated with significantly higher expression of the β-catenin binding partner E-cadherin. This increased expression is associated with a higher number of E-cadherin:β-catenin complexes at the membrane. Reduction of E-cadherin synergised with an activating mutation of β-catenin so there was now a rapid CPC phenotype within the colon and SI. Thus there is a threshold of β-catenin that is required to drive transformation and E-cadherin can act as a buffer to prevent β-catenin accumulation

Weight management interventions in adults with intellectual disabilities and obesity: a systematic review of the evidence

o evaluate the clinical effectiveness of weight management interventions in adults with intellectual disabilities (ID) and obesity using recommendations from current clinical guidelines for the first line management of obesity in adults. Full papers on lifestyle modification interventions published between 1982 to 2011 were sought by searching the Medline, Embase, PsycINFO and CINAHL databases. Studies were evaluated based on 1) intervention components, 2) methodology, 3) attrition rate 4) reported weight loss and 5) duration of follow up. Twenty two studies met the inclusion criteria. The interventions were classified according to inclusion of the following components: behaviour change alone, behaviour change plus physical activity, dietary advice or physical activity alone, dietary plus physical activity advice and multi-component (all three components). The majority of the studies had the same methodological limitations: no sample size justification, small heterogeneous samples, no information on randomisation methodologies. Eight studies were classified as multi-component interventions, of which one study used a 600 kilocalorie (2510 kilojoule) daily energy deficit diet. Study durations were mostly below the duration recommended in clinical guidelines and varied widely. No study included an exercise program promoting 225–300 minutes or more of moderate intensity physical activity per week but the majority of the studies used the same behaviour change techniques. Three studies reported clinically significant weight loss (≥ 5%) at six months post intervention. Current data indicate weight management interventions in those with ID differ from recommended practice and further studies to examine the effectiveness of multi-component weight management interventions for adults with ID and obesity are justified

Wheat is an emerging exposure route for arsenic in Bihar, India

In arsenic (As) endemic areas of south-east Asia, where a subsistence rice-based diet is 19 prevalent, As exposure from food is mainly focused on rice intake. However, consumption of 20 wheat is substantial and increasing. We present a probabilistic assessment of increased cancer 21 risk from wheat-based food intake in a study population of rural Bihar, India where As exposure 22 is endemic. Total As in wheat grains (43.64±48.19 μg/kg, n=72) collected from 77 households 23 across 19 villages was found to be lower than reported As in wheat grains from other south-24 east Asian countries but higher than a previous study from Bihar. As concentration in wheat flour was used for risk estimation, bearing in mind that it was the 26 flour obtained after indigenous household processing of the grains that was used for making 27 the home-made bread (chapati) which contributed 95% of wheat intake for the studied 28 population. Interestingly, while 78% of the surveyed participants (n=154) consumed rice every 29 day, chapati was consumed every day by 99.5% of the participants. In contrast to previous 30 studies, where As concentration in wheat grain was found to be lower than the flour due to the 31 removal of the bran on grinding, we did not find any appreciable lowering of arsenic in the 32 wheat flour (49.80±74.08 μg/kg, n=58), most likely due to external contamination during 33 processing and grinding. Estimated gender adjusted excess lifetime cancer risk of 1.23x10-4 for 34 the studied rural population of Bihar indicated risk higher than the 10-4-10-6 range, typically 35 used by the USEPA as a threshold to guide regulatory values. Hence, our findings suggest As 36 exposure from wheat-based food intake to be of concern not only in As endemic areas of rural 37 Bihar but also in non-endemic areas with similar wheat-based diet due to public distribution of 38 the wheat across India

Induction Chemotherapy Followed by Chemo-intensity-modulated Radiotherapy for Locally Advanced Nasopharyngeal Cancer.

Aims To determine the toxicity and tumour control rates after chemo-intensity-modulated radiotherapy (chemo-IMRT) for locally advanced nasopharyngeal cancers (LA-NPC).Materials and methods Patients with LA-NPC were enrolled in a trial to receive induction chemotherapy followed by parotid-sparing chemo-IMRT. The primary site and involved nodal levels received 65 Gy in 30 fractions and at risk nodal levels received 54 Gy in 30 fractions. Incidence of ≥grade 2 subjective xerostomia was the primary end point. Secondary end points included incidences of acute and late toxicities and survival outcomes.Results Forty-two patients with American Joint Committee on Cancer stages II (12%), III (26%) and IV (62%) (World Health Organization subtype: I [5%]; II [40%]; III [55%]) completed treatment between January 2006 and April 2010 with a median follow-up of 32 months. Incidences of ≥grade 2 acute toxicities were: dysphagia 83%; xerostomia 76%; mucositis 97%; pain 76%; fatigue 99% and ototoxicity 12%. At 12 months, ≥grade 2 subjective xerostomia was observed in 31%, ototoxicitiy in 13% and dysphagia in 4%. Two year locoregional control was 86.2% (95% confidence interval: 70.0-94.0) with 2 year progression-free survival at 78.4% (61.4-88.6) and 2 year overall survival at 85.9% (69.3-93.9).Conclusions Chemo-IMRT for LA-NPC is feasible with good survival outcomes. At 1 year, 31% experience ≥grade 2 subjective xerostomia

Retrivability in The Danish National Hospital Registry of HIV and hepatitis B and C coinfection diagnoses of patients managed in HIV centers 1995–2004

<p>Abstract</p> <p>Background</p> <p>Hospital-based discharge registries are used increasingly for longitudinal epidemiological studies of HIV. We examined completeness of registration of HIV infections and of chronic hepatitis B (HBV) and hepatitis C (HCV) coinfections in the Danish National Hospital Registry (DNHR) covering all Danish hospitals.</p> <p>Methods</p> <p>The Danish HIV Cohort Study (DHCS) encompasses all HIV-infected patients treated in Danish HIV clinics since 1 January 1995. All 2,033 Danish patients in DHCS diagnosed with HIV-1 during the 10-year period from 1 January 1995 to 31 December 2004 were included in the current analysis. We used the DHCS as a reference to examine the completeness of HIV and of HBV and HCV coinfections recorded in DNHR. Cox regression analysis was used to estimate hazard ratios of time to diagnosis of HIV in DNHR compared to DHCS.</p> <p>Results</p> <p>Of the 2,033 HIV patients in DHCS, a total of 2,006 (99%) were registered with HIV in DNHR. Of these, 1,888 (93%) were registered in DNHR within one year of their first positive HIV test. A CD4 < 200 cells/μl, a viral load >= 100,000 copies/ml and being diagnosed after 1 January 2000, were associated with earlier registration in DNHR, both in crude and adjusted analyses. Thirty (23%) HIV patients registered with chronic HBV (n = 129) in DHCS and 126 (48%) of HIV patients with HCV (n = 264) in DHCS were registered with these diagnoses in the DNHR. Further 17 and 8 patients were registered with HBV and HCV respectively in DNHR, but not in DHCS. The positive predictive values of being registered with HBV and HCV in DHCS were thereby estimated to 0.88 and 0.97 and in DNHR to 0.32 and 0.54.</p> <p>Conclusion</p> <p>The study demonstrates that secondary data from national hospital databases may be reliable for identification of patients diagnosed with HIV infection. However, the predictive value of co-morbidity data may be low.</p

Negative emotions in children with newly diagnosed epilepsy.

Purpose: To understand the emotional predicament in children with recently diagnosed idiopathic or cryptogenic epilepsy. Methods: We used the well-tried method of structured projection for the first time in children with epilepsy. Thirty-six children with epilepsy, aged 7-15 years (mean age, 9.5 years) and in 35 control children aged 7-15 years (mean age, 9.4 years), attributed shame and guilt in relation to three types of situation (non- illness related, illness related, and epilepsy related). Children were evaluated twice: shortly after diagnosis, before antiepileptic drug (AED) use and after an interval of 3 months. Results: Children with epilepsy and healthy controls were similar in their way of attributing shame and guilt. However, the type of situation was of influence: Both children with epilepsy and healthy children attributed more shame to incompetence due to epilepsy than to incompetence due to other illnesses. Conclusions: Increased affective problems in childhood epilepsy cannot be explained by excessive attribution of shame and guilt, affects known to be important precursors of psychopathology, yet both healthy children and children with epilepsy attribute more shame to epilepsy than to other illnesses. Epilepsy is not like any other disease

Gene set analysis exploiting the topology of a pathway

<p>Abstract</p> <p>Background</p> <p>Recently, a great effort in microarray data analysis is directed towards the study of the so-called gene sets. A gene set is defined by genes that are, somehow, functionally related. For example, genes appearing in a known biological pathway naturally define a gene set. The gene sets are usually identified from a priori biological knowledge. Nowadays, many bioinformatics resources store such kind of knowledge (see, for example, the Kyoto Encyclopedia of Genes and Genomes, among others). Although pathways maps carry important information about the structure of correlation among genes that should not be neglected, the currently available multivariate methods for gene set analysis do not fully exploit it.</p> <p>Results</p> <p>We propose a novel gene set analysis specifically designed for gene sets defined by pathways. Such analysis, based on graphical models, explicitly incorporates the dependence structure among genes highlighted by the topology of pathways. The analysis is designed to be used for overall surveillance of changes in a pathway in different experimental conditions. In fact, under different circumstances, not only the expression of the genes in a pathway, but also the strength of their relations may change. The methods resulting from the proposal allow both to test for variations in the strength of the links, and to properly account for heteroschedasticity in the usual tests for differential expression.</p> <p>Conclusions</p> <p>The use of graphical models allows a deeper look at the components of the pathway that can be tested separately and compared marginally. In this way it is possible to test single components of the pathway and highlight only those involved in its deregulation.</p