Intestinal fungi contribute to development of alcoholic liver disease

This study was supported in part by NIH grants R01 AA020703, U01 AA021856 and by Award Number I01BX002213 from the Biomedical Laboratory Research & Development Service of the VA Office of Research and Development (to B.S.). K.H. was supported by a DFG (Deutsche Forschungsgemeinschaft) fellowship (HO/ 5690/1-1). S.B. was supported by a grant from the Swiss National Science Foundation (P2SKP3_158649). G.G. received funding from the Yale Liver Center NIH P30 DK34989 and R.B. from NIAAA grant U01 AA021908. A.K. received support from NIH grants RC2 AA019405, R01 AA020216 and R01 AA023417. G.D.B. is supported by funds from the Wellcome Trust. We acknowledge the Human Tissue and Cell Research (HTCR) Foundation for making human tissue available for research and Hepacult GmbH (Munich, Germany) for providing primary human hepatocytes for in vitro analyses. We thank Dr. Chien-Yu Lin Department of Medicine, Fu-Jen Catholic University, Taiwan for statistical analysis.Peer reviewedPublisher PD

Mesoscale productivity fronts and local fishing opportunities in the European Seas

This study evaluates the relationship between both commercial and scientific spatial fisheries data and a new satellite-based estimate of potential fish production (Ocean Productivity available to Fish, OPFish) in the European Seas. To construct OPFish, we used productivity frontal features derived from chlorophyll-a horizontal gradients, which characterize 10%–20% of the global phytoplankton production that effectively fuels higher trophic levels. OPFish is relatively consistent with the spatial distribution of both pelagic and demersal fish landings and catches per unit of effort (LPUEs and CPUEs, respectively). An index of harvest relative to ocean productivity (HP index) is calculated by dividing these LPUEs or CPUEs with OPFish. The HP index reflects the intensity of fishing by gear type with regard to local fish production. Low HP levels indicate lower LPUEs or CPUEs than expected from oceanic production, suggesting over-exploitation, while high HP levels imply more sustainable fishing. HP allows comparing the production-dependent suitability of local fishing intensities. Our results from bottom trawl data highlight that over-exploitation of demersal species from the shelves is twice as high in the Mediterranean Sea than in the North-East Atlantic. The estimate of HP index by dominant pelagic and demersal gears suggests that midwater and bottom otter trawls are associated with the lowest and highest overfishing, respectively. The contrasts of fishing intensity at local scales captured by the HP index suggest that accounting for the local potential fish production can promote fisheries sustainability in the context of ecosystem-based fisheries management as required by international marine policies

Mesoscale productivity fronts and local fishing opportunities in the European Seas. Fish and Fisheries

This study evaluates the relationship between both commercial and scientific spatial fisheries data and a new satellite-based estimate of potential fish production (Ocean Productivity available to Fish, OPFish) in the European Seas. To construct OPFish, we used productivity frontal features derived from chlorophyll-a horizontal gradients, which characterize 10%–20% of the global phytoplankton production that effectively fuels higher trophic levels. OPFish is relatively consistent with the spatial distribution of both pelagic and demersal fish landings and catches per unit of effort (LPUEs and CPUEs, respectively). An index of harvest relative to ocean productivity (HP index) is calculated by dividing these LPUEs or CPUEs with OPFish. The HP index reflects the intensity of fishing by gear type with regard to local fish production. Low HP levels indicate lower LPUEs or CPUEs than expected from oceanic production, suggesting over-exploitation, while high HP levels imply more sustainable fishing. HP allows comparing the production-dependent suitability of local fishing intensities. Our results from bottom trawl data highlight that over-exploitation of demersal species from the shelves is twice as high in the Mediterranean Sea than in the North-East Atlantic. The estimate of HP index by dominant pelagic and demersal gears suggests that midwater and bottom otter trawls are associated with the lowest and highest overfishing, respectively. The contrasts of fishing intensity at local scales captured by the HP index suggest that accounting for the local potential fish production can promote fisheries sustainability in the context of ecosystem-based fisheries management as required by international marine policies

Anticipatory anti-colonial writing in R.K. Narayan's Swami and Friends and Mulk Raj Anand's Untouchable

This article uses the term “anticipatory anti-colonial writing” to discuss the workings of time in R.K. Narayan’s Swami and Friends and Mulk Raj Anand’s Untouchable. Both these first novels were published in 1935 with the support of British literary personalities (Graham Greene and E.M. Forster respectively) and both feature young protagonists who, in contrasting ways, are engaged in Indian resistance to colonial rule. This study examines the difference between Narayan’s local, though ironical, resistance to the homogenizing temporal demands of empire and Anand’s awkwardly modernist, socially committed vision. I argue that a form of anticipation that explicitly looks forward to decolonization via new and transnational literary forms is a crucial feature of Untouchable that is not found in Swami and Friends, despite the latter’s anti-colonial elements. Untouchable was intended to be a “bridge between the Ganges and the Thames” and anticipates postcolonial negotiations of time that critique global inequalities and rely upon the multidirectional global connections forged by modernism

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Getting to the heart of the matter: Does aberrant interoceptive processing contribute towards emotional eating?

According to estimates from Public Health England, by 2034 70% of adults are expected to be overweight or obese, therefore understanding the underpinning aetiology is a priority. Eating in response to negative affect contributes towards obesity, however, little is known about the underlying mechanisms. Evidence that visceral afferent signals contribute towards the experience of emotion is accumulating rapidly, with the emergence of new influential models of ‘active inference’. No longer viewed as a ‘bottom up’ process, new interoceptive facets based on ‘top down’ predictions have been proposed, although at present it is unclear which aspects of interoception contribute to aberrant eating behaviour and obesity. Study one examined the link between eating behaviour, body mass index and the novel interoceptive indices; interoceptive metacognitive awareness (IAw) and interoceptive prediction error (IPE), as well as the traditional measures; interoceptive accuracy (IAc) and interoceptive sensibility (IS). The dissociation between these interoceptive indices was confirmed. Emotional eaters were characterised by a heightened interoceptive signal but reduced meta-cognitive awareness of their interoceptive abilities. In addition, emotional eating correlated with IPE; effects that could not be accounted for by differences in anxiety and depression. Study two confirmed the positive association between interoceptive accuracy and emotional eating using a novel unbiased heartbeat discrimination task based on the method of constant stimuli. Results reveal new and important mechanistic insights into the processes that may underlie problematic affect regulation in overweight populations

Gastrointestinal Dysfunction in Patients with Duchenne Muscular Dystrophy

BACKGROUND In adult patients with Duchenne muscular dystrophy (DMD) life-threatening constipation has been reported. Since gastrointestinal function in DMD has not been rigorously studied we investigated objective and subjective manifestations of gastrointestinal disturbances in DMD patients. METHODS In 33 patients with DMD, age 12-41 years, eating behavior and gastrointestinal symptoms were evaluated by questionnaires. Gastric emptying half time (T1/2) and oro-cecal transit time (OCTT) were evaluated by analyzing 13CO2 exhalation curves after ingestion of 13C labeled test meals. Colonic transit time (CTT) was measured by abdominal radiography following ingestion of radiopaque markers. RESULTS The median (quartiles) T1/2 was 187 (168, 220) minutes, the OCTT was 6.3 (5.0, 7.9) hours, both substantially longer than normal data (Goetze 2005, T1/2: 107±10; Geypens 1999, OCTT 4.3±0.1 hours). The median CTT was 60 (48, 82) hours despite extensive use of laxative measures (Meier 1995, upper limit of normal: 60 hours). T1/2 and OCTT did not correlate with symptoms evaluated by the Gastroparesis Cardinal Symptom Index (GCSI) (Spearman r = -0.3, p = 0.1; and r = -0.15, p = 0.4, respectively). CTT was not correlated with symptoms of constipation assessed by ROME III criteria (r = 0.12, p = 0.5). CONCLUSIONS DMD patients have a markedly disturbed gastrointestinal motor function. Since objective measures of impaired gastrointestinal transport are not correlated with symptoms of gastroparesis or constipation our findings suggest that measures assuring adequate intestinal transport should be taken independent of the patient's perception in order to prevent potentially life threatening constipation, particularly in older DMD patients