Parkinson disease (PD) is characterized by the progressive loss of nigral dopamine neurons and the presence of accumulations containing the disease-causing protein SNCA/α-synuclein. Here we review our recent findings describing how SNCA impairs the function of the master regulator of the autophagy-lysosomal pathway (ALP), the transcription factor EB (TFEB), and that genetic or pharmacological stim

BACKGROUND Nivolumab was associated with higher rates of objective response than chemotherapy in a phase 3 study involving patients with ipilimumab-refractory metastatic melanoma. The use of nivolumab in previously untreated patients with advanced melanoma has not been tested in a phase 3 controlled study. METHODS We randomly assigned 418 previously untreated patients who had metastatic melanoma w

To update the guidelines of the Contrast Media Safety Committee (CMSC) of the European Society of Urogenital Radiology (ESUR) on nephrogenic systemic fibrosis and gadolinium-based contrast media. Topics reviewed include the history, clinical features and prevalence of nephrogenic systemic fibrosis and the current understanding of its pathophysiology. The risk factors for NSF are discussed and prop

Understanding of the genetic basis of type 2 diabetes (T2D) has progressed rapidly, but the interactions between common genetic variants and lifestyle risk factors have not been systematically investigated in studies with adequate statistical power. Therefore, we aimed to quantify the combined effects of genetic and lifestyle factors on risk of T2D in order to inform strategies for prevention.

Measurements and simulations to investigate the contributing factors to the peak-to-valley (PTV) ratio have been both experimentally determined as well as Monte Carlo simulated for a well-characterised HPGe n-type detector together with a Cs-137 gamma source encapsulated in thin polystyrene. Measurements were carried out in a low-background gamma counting facility at Lund University. The results o

In 1978 Wolfgang Helfrich published a paper (Helfrich W. Z Naturforsch 1978; 33a:305) where he introduced the notion of an undulation force between bilayers. This is caused by thermal excitations of the bending modes being restricted by the presence of neighboring layers. Although there is now a consensus on the qualitative picture put forward by Helfrich there is still a debate concerning the qua

Downscaled climate model projections from phase 5 of the Coupled Model Intercomparison Project (CMIP5) were used to force a dynamic vegetation agricultural model (Agro-IBIS) and simulate yield responses to historical climate and two future emissions scenarios for maize in the U.S. Midwest and wheat in southeastern Australia. In addition to mean changes in yield, the frequency of high- and low-yiel

Background: As new combinations of inhaled corticosteroids (ICSs) and long-acting beta(2)-agonists (LABAs) become available for the treatment of asthma, it will be important to determine criteria against which they can be evaluated. The aim of this study was to assess which attributes of combination therapy physicians consider most important. Methods: Primary and secondary care asthma specialists

This article examines the modern concept of literary value. Since the late 18th century, the problem of literary value has been regarded, from the point of view of the so called double discourse of value, as a presupposed opposition between material and spiritual ”economies”. Many Romanticist and Modernist authors believe that literature – and in a broader sense art and aesthetics – constitute a v

In the mid 2000s the oil and gas industry was hit by what might be best described as a 'wall of cash' as oil prices successively reached new record levels and access to external financing improved greatly. In this article we investigate what this sudden abundance of liquidity implied for the investment-cash flow relationship, the interpretation of which continues to generate controversy in the lit

Abstract Aim: The aim of this study was to explore experiences of mobility device (MD) use among very old single-living Swedish men. Methods: A multiple case study of three men, involving quantitative and qualitative data, was used in an embedded mixed methods design and presented in three narrative stories. To capture differences and similarities in the use of MDs a cross-case analysis was conduc

To study the relationship between macular function assessed by multifocal electroretinogram (mfERG) and morphological changes evaluated with optical coherence tomography (OCT) and fundus photography in patients with drusen maculopathy.

In the Bas-Draa Inlier (Anti-Atlas, Morocco), the Paleoproterozoic basement which is cut by the Ediacaran Taourgha granite is also crosscut by numerous dykes of a variety of trends, mostly of uncertain age. Two doleritic dykes are dated by the ID-TIMS U-Pb method on baddeleyite and yield emplacement ages of 1381 +/- 8 Ma (MSWD = 0.84) and 1384 +/- 6 Ma (MSWD = 1.4) determined for a N135 degrees E

The X chromosome (chrX) represents one potential source for the "missing heritability" for complex phenotypes, which thus far has remained underanalyzed in genome-wide association studies (GWAS). Here we demonstrate the benefits of including chrX in GWAS by assessing the contribution of 404,862 chrX SNPs to levels of twelve commonly studied cardiometabolic and anthropometric traits in 19,697 Finni

Arctic areas of deep-water convection have a large potential for export of organic carbon from surface waters into the deep sea and, therefore, are an important part of the global carbon cycle. As the Arctic is reportedly heating up faster than any other part of the planet, temperature-driven changes in the biogeochemical cycling in these areas can be very significant. Here, we study the regulatio

The evolution of striking phenotypes on islands is a well-known phenomenon, and there has been a long-standing debate on the patterns of body size evolution on islands. The ecological causes driving divergence in insular populations are, however, poorly understood. Reduced predator fauna is expected to lower escape propensity, increase body size and relax selection for crypsis in small-bodied, ins

The prognosis for malignant gliomas remains poor, and new treatments are urgently needed. Targeted suicide gene therapy exploits the enzymatic conversion of a prodrug, such as a nucleoside analog, into a cytotoxic compound. Although this therapeutic strategy has been considered a promising regimen for central nervous system (CNS) tumors, several obstacles have been encountered such as inefficient