Research Questions Guiding Selection of an Appropriate Research Method

Research objects and research outcomes are proposed to act as a guide to select a proper research method. We, however, recommend that the research question as the essential factor of the research process should guide selection. Based on this idea we here develop taxonomy of research approaches with six categories. Taxonomy is then compared with three other classifications of research methods by using the comprehensiveness, parsimony and usefulness criteria

Non-alcoholic fatty liver disease and risk of type 2 diabetes

Non-alcoholic fatty liver disease (NAFLD) covers a spectrum of liver disease from simple steatosis to non-alcoholic steatohepatitis (NASH) and cirrhosis. NAFLD is commonly associated with features of the metabolic/insulin resistance syndrome ('Metabolic/Obese NAFLD') and may therefore predict type 2 diabetes (T2DM). For this review, we searched for prospective studies examining whether NAFLD predicts T2DM, and if so, whether this occurs independently of factors such as age and obesity. These studies included NAFLD diagnosed by ultrasonography (n = 6) or liver enzymes (n = 14). All ultrasonography studies found NAFLD to predict the risk of T2DM independently of age, and in 4 out of 6 studies NAFLD was also a predictor independently of BMI. NAFLD was a predictor of T2DM in all 14 studies where NAFLD was diagnosed by liver enzymes. In 12 of these studies, ALT or AST or GGT were significant predictors of T2DM risk, independently of age and BMI. NAFLD, however, is heterogeneous and may also be caused by common genetic variants. The I148M variant in PNPLA3 and the E167K variant in TM6SF2 are both associated with increased liver fat content, but not features of the metabolic/insulin resistance syndrome. These genetic forms of NAFLD predict NASH and cirrhosis but not T2DM. Taken together these data imply that 'Metabolic/Obese NAFLD' predicts T2DM independently of age and obesity and support the role of hepatic insulin resistance in the pathogenesis of this disease. (C) 2016 Elsevier Ltd. All rights reserved.Peer reviewe

Stellar activity as noise in exoplanet detection I. Methods and application to solar-like stars and activity cycles

The detection of exoplanets using any method is prone to confusion due to the intrinsic variability of the host star. We investigate the effect of cool starspots on the detectability of the exoplanets around solar-like stars using the radial velocity method. For investigating this activity-caused "jitter" we calculate synthetic spectra using radiative transfer, known stellar atomic and molecular lines, different surface spot configurations, and an added planetary signal. Here, the methods are described in detail, tested and compared to previously published studies. The methods are also applied to investigate the activity jitter in old and young solar-like stars, and over a solar-like activity cycles. We find that the mean full jitter amplitude obtained from the spot surfaces mimicking the solar activity varies during the cycle approximately between 1 m/s and 9 m/s. With a realistic observing frequency a Neptune mass planet on a one year orbit can be reliably recovered. On the other hand, the recovery of an Earth mass planet on a similar orbit is not feasible with high significance. The methods developed in this study have a great potential for doing statistical studies of planet detectability, and also for investigating the effect of stellar activity on recovered planetary parameters.Comment: Accepted to MNRA

Clinical findings in relation to mortality in non-tuberculous mycobacterial infections : patients with Mycobacterium avium complex have better survival than patients with other mycobacteria

We compared the clinical findings and survival in patients with Mycobacterium avium complex (MAC) and other non-tuberculous mycobacteria (NTM). A total of 167 adult non-human immunodeficiency virus (HIV) patients with at least one positive culture for NTM were included. Medical records were reviewed. The patients were categorised according to the 2007 American Thoracic Society (ATS) criteria. MAC comprised 59 % of all NTM findings. MAC patients were more often female (70 % vs. 34 %, p <0.001) and had less fatal underlying diseases (23 % vs. 47 %, p = 0.001) as compared to other NTM patients. Symptoms compatible with NTM infection had lasted for less than a year in 34 % of MAC patients but in 54 % of other NTM patients (p = 0.037). Pulmonary MAC patients had a significantly lower risk of death compared to pulmonary other NTM (hazard ratio [HR] 0.50, 95 % confidence interval [CI] 0.33-0.77, p = 0.002) or subgroup of other slowly growing NTM (HR 0.55, 95 % CI 0.31-0.99, p = 0.048) or as rapidly growing NTM (HR 0.47, 95 % CI 0.25-0.87, p = 0.02). The median survival time was 13.0 years (95 % CI 5.9-20.1) for pulmonary MAC but 4.6 years (95 % CI 3.4-5.9) for pulmonary other NTM. Serious underlying diseases (HR 3.21, 95 % CI 2.05-5.01, p <0.001) and age (HR 1.07, 95 % CI 1.04-1.09, p <0.001) were the significant predictors of mortality and female sex was a predictor of survival (HR 0.38, 95 % CI 0.24-0.59, p <0.001) in the multivariate analysis. Pulmonary MAC patients had better prognosis than pulmonary other NTM patients. The symptom onset suggests a fairly rapid disease course.Peer reviewe

Magnetic field geometry and chemical abundance distribution of the He-strong star CPD -57 3509

The magnetic field of CPD -57 3509 was recently detected in the framework of the BOB (B fields in OB stars) collaboration. We acquired low-resolution spectropolarimetric observations of CPD -57 3509 with FORS2 and high-resolution UVES observations randomly distributed over a few months to search for periodicity, to study the magnetic field geometry, and to determine the surface distribution of silicon and helium. We also obtained supplementary photometric observations at a timeline similar to the spectroscopic and spectropolarimetric observations. A period of 6.36d was detected in the measurements of the mean longitudinal magnetic field. A sinusoidal fit to our measurements allowed us to constrain the magnetic field geometry and estimate the dipole strength in the range of 3.9-4.5kG. Our application of the Doppler imaging technique revealed the presence of He I spots located around the magnetic poles, with a strong concentration at the positive pole and a weaker one around the negative pole. In contrast, high concentration Si III spots are located close to the magnetic equator. Further, our analysis of the spectral variability of CPD -57 3509 on short time scales indicates distinct changes in shape and position of line profiles possibly caused by the presence of beta Cep-like pulsations. A small periodic variability in line with the changes of the magnetic field strength is clearly seen in the photometric data.Comment: 11 pages, 5 tables, 7 figures, accepted for publication in MNRA

Pathological Angiogenesis Requires Syndecan-4 for Efficient VEGFA-Induced VE-Cadherin Internalization

Objective: VEGFA (Vascular endothelial growth factor A) and its receptor VEGFR2 (vascular endothelial growth factor receptor 2) drive angiogenesis in several pathologies, including diabetic retinopathy, wet age-related macular degeneration, and cancer. Studies suggest roles for HSPGs (heparan sulfate proteoglycans) in this process, although the nature of this involvement remains elusive. Here, we set to establish the role of the HSPG SDC4 (syndecan-4) in pathological angiogenesis. Approach and Results: We report that angiogenesis is impaired in mice null for SDC4 in models of neovascular eye disease and tumor development. Our work demonstrates that SDC4 is the only SDC whose gene expression is upregulated during pathological angiogenesis and is selectively enriched on immature vessels in retinas from diabetic retinopathy patients. Combining in vivo and tissue culture models, we identified SDC4 as a downstream mediator of functional angiogenic responses to VEGFA. We found that SDC4 resides at endothelial cell junctions, interacts with vascular endothelial cadherin, and is required for its internalization in response to VEGFA. Finally, we show that pathological angiogenic responses are inhibited in a model of wet age-related macular degeneration by targeting SDC4. Conclusions: We show that SDC4 is a downstream mediator of VEGFA-induced vascular endothelial cadherin internalization during pathological angiogenesis and a potential target for antiangiogenic therapies

Oxygen Ion Escape From Venus Is Modulated by Ultra‐Low Frequency Waves

We study the solar wind‐driven, nonthermal escape of O+ ions from Venus in a global hybrid simulation. In the model, a well‐developed ion foreshock forms ahead of the Venusian quasi‐parallel bow shock under nominal upstream conditions. Large‐scale magnetosonic ultra‐low frequency (ULF) waves at 20‐ to 30‐s period are excited and convect downstream along the foreshock with the solar wind. We show that the foreshock ULF waves transmit through the bow shock in the downstream region and interact with the planetary ion acceleration, causing 25% peak‐to‐peak fluctuations in the O+ escape rate. These results demonstrate the importance of upstream plasma waves on the energization and escape of heavy ions from the planetary atmospheres.Key PointsA global hybrid simulation predicts fluctuations in the O+ escape from VenusThe fluctuations are associated with the foreshock ULF waves, which modulate the acceleration of heavy pickup ionsUpstream waves need to be taken into account in the interpretation of heavy ion erosion from unmagnetized planetsPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155962/1/grl60648_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155962/2/grl60648-sup-0001-Figure_SI-S01.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155962/3/grl60648.pd

Hypoglycaemia in Type 2 diabetes

The primary cause of hypoglycaemia in Type 2 diabetes is diabetes medication—in particular, those which raise insulin levels independently of blood glucose, such as sulphonylureas (SUs) and exogenous insulin. The risk of hypoglycaemia is increased in older patients, those with longer diabetes duration, lesser insulin reserve and perhaps in the drive for strict glycaemic control. Differing definitions, data collection methods, drug type/regimen and patient populations make comparing rates of hypoglycaemia difficult. It is clear that patients taking insulin have the highest rates of self-reported severe hypoglycaemia (25% in patients who have been taking insulin for > 5 years). SUs are associated with significantly lower rates of severe hypoglycaemia. However, large numbers of patients take SUs in the UK, and it is estimated that each year > 5000 patients will experience a severe event caused by their SU therapy which will require emergency intervention. Hypoglycaemia has substantial clinical impact, in terms of mortality, morbidity and quality of life. The cost implications of severe episodes—both direct hospital costs and indirect costs—are considerable: it is estimated that each hospital admission for severe hypoglycaemia costs around £1000. Hypoglycaemia and fear of hypoglycaemia limit the ability of current diabetes medications to achieve and maintain optimal levels of glycaemic control. Newer therapies, which focus on the incretin axis, may carry a lower risk of hypoglycaemia. Their use, and more prudent use of older therapies with low risk of hypoglycaemia, may help patients achieve improved glucose control for longer, and reduce the risk of diabetic complications

Treatment of keloid scars with intralesional triamcinolone and 5-fluorouracil injections - a randomized controlled trial

Keloids have high recurrence rates. Current first-line therapy is triamcinolone (TAC) injection, but it has been suggested that approximately 50% of keloids are steroid resistant. We compared the efficacy of intralesional 5-fluorouracil (5-FU) and triamcinalone injections in a double-blind randomized controlled trial. Forty-three patients with 50 keloid scars were treated with either intralesional TAC or 5-FU-injections over 6 months. There was no statistically significant difference in the remission rate at 6 months between the 5-FU and TAC groups (46% vs 60%, respectively). Local adverse effects were higher in the TAC group compared to the 5-FU group. Occurrence of skin atrophy in TAC group was 44% and in the 5-FU group 8% (p <0.05). Also the occurrence of telangiectasia in the TAC group was 50% and in the 5-FU 21% (p <0.05). Vascularity of the keloids, assessed by spectral imaging and immunohistochemical staining for blood vessels, after treatment decreased in the TAC group, but not in the 5-FU group (p <0.05). Fibroblast proliferation evaluated by Ki-67 staining significantly decreased in the TAC group (p <0.05) but increased in the 5-FU group (p <0.05). TAC and 5-FU injections did not differ in their clinical effectivity in this randomized study, but 5-FU injections lead to increased proliferation rate and did not affect vascular density in histological assessment. Due to the greater number of adverse effects observed after TAC treatment, 5-FU injections may be preferable for cosmetically sensitive skin areas. (C) 2018 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.Peer reviewe

Explicit representation of subgrid variability in cloud microphysics yields weaker aerosol indirect effect in the ECHAM5-HAM2 climate model

Peer reviewe