Towards laser driven table-top coherent diffractive X-ray microscopy of cultured hippocampal neurons

Neurodegenerative diseases such as Alzheimer’s disease have a huge impact on the world population; over 44 million people worldwide and 850,000 in the UK were recorded as living with dementia in 2013. There are numerous theories attempting to explain the cause of Alzheimer’s disease. Histology from the brains of people who had Alzheimer’s disease shows neurofibilliary tangles and amyloid plaques. Their role in the mechanism of disease is not yet completely understood but we envisage that novel imaging techniques may aid understanding. We present initial data collected using confocal fluorescence microscopy and hard X-ray scanning diffractive microscopy (ptychography) on cultured neuron samples plus high resolution large field of view imaging of test samples from a soft X-ray lab based high harmonic generation (HHG) source

Ptychographic coherent diffractive imaging with orthogonal probe relaxation

Ptychography is a scanning coherent diffractive imaging (CDI) technique that relies upon a high level of stability of the illumination during the course of an experiment. This is particularly an issue for coherent short wavelength sources, where the beam intensity is usually tightly focused on the sample in order to maximize the photon flux density on the illuminated region of the sample and thus a small change in the beam position results in a significant change in illumination of the sample. We present an improved ptychographic method that allows for limited stability of the illumination wavefront and thus significantly improve the reconstruction quality without additional prior knowledge. We have tested our reconstruction method in a proof of concept experiment, where the beam instability of a visible light source was emulated using a piezo driven mirror, and also in a short wavelength microscopy CDI setup using a high harmonic generation source in the extreme ultraviolet range. Our work shows a natural extension of the ptychography method that paves the way to use ptychographic imaging with any limited pointing stability coherent source such as free electron or soft X-ray lasers and improve reconstruction quality of long duration synchrotron experiments

Economic evaluation of a community-based diagnostic pathway to stratify adults for non-alcoholic fatty liver disease: a Markov model informed by a feasibility study

Objectives: To assess the long-term cost-effectiveness of a risk stratification pathway, compared with standard care, for detecting non-alcoholic fatty liver disease (NAFLD) in primary care. Setting: Primary care general practices in England. Participants: Adults who have been identified in primary care to have a risk factor for developing NAFLD, that is, type 2 diabetes without a history of excessive alcohol use. Intervention: A community-based pathway, which utilises transient elastography and hepatologists to stratify patients at risk of NAFLD, has been implemented and demonstrated to be feasible (NCT02037867). Earlier identification could mean earlier treatments, referral to specialist, and enrolment into surveillance programmes. Design: The impact of earlier detection and treatment with the risk stratification pathway on progression to later stages of liver disease was examined using decision modelling with Markov chains to estimate lifetime health and economic effects of the two comparators. Data sources: Data from a prospective cross-sectional feasibility study indicating risk stratification pathway and standard care diagnostic accuracies, were combined with a Markov model that comprised the following states: no/mild liver disease, significant liver disease, compensated cirrhosis; decompensated cirrhosis, hepatocellular carcinoma, liver transplant and death. The model data were chosen from up-to-date UK sources, published literature and an expert panel. Outcome measure: An incremental cost-effectiveness ratio (ICER) indicating cost per quality adjusted life year (QALY) of the risk stratification pathway compared with standard care was estimated. Results: The risk stratification pathway was more effective than standard care, and cost ￡2,138 per QALY gained. The ICER was most sensitive to estimates of the rate of fibrosis progression and the effect of treatment on reducing this, and ranged from -￡1,895 to ￡7,032/QALY. The risk stratification pathway demonstrated an 85% probability of cost-effectiveness at the UK willingness-to-pay threshold of ￡20,000/QALY. Conclusions: Implementation of a community-based risk stratification pathway is likely to be cost effective

The Impact of Immigration on the Wage Distribution in Switzerland

Recent immigrants in Switzerland are overrepresented at the top of the wage distribution in high and at the bottom in low skill occupations. Basic economic theory thus suggests that immigration has led to a compression of the wage distribution in the former group and to an expansion in the latter. The data confirm this proposition for high skill occupations, but reveal effects close to zero for low skill occupations. While the estimated wage effects are of considerable magnitude at the tails of the wage distribution in high skill occupations, the effects on overall inequality are shown to be negligible

Serotonergic Contribution to Boys' Behavioral Regulation

Animal and human adult studies reveal a contribution of serotonin to behavior regulation. Whether these findings apply to children is unclear. The present study investigated serotonergic functioning in boys with a history of behavior regulation difficulties through a double-blind, acute tryptophan supplementation procedure.Participants were 23 boys (age 10 years) with a history of elevated physical aggression, recruited from a community sample. Eleven were given a chocolate milkshake supplemented with 500 mg tryptophan, and 12 received a chocolate milkshake without tryptophan. Boys engaged in a competitive reaction time game against a fictitious opponent, which assessed response to provocation, impulsivity, perspective taking, and sharing. Impulsivity was further assessed through a Go/No-Go paradigm. A computerized emotion recognition task and a staged instrumental help incident were also administered.Boys, regardless of group, responded similarly to high provocation by the fictitious opponent. However, boys in the tryptophan group adjusted their level of responding optimally as a function of the level of provocation, whereas boys in the control group significantly decreased their level of responding towards the end of the competition. Boys in the tryptophan group tended to show greater perspective taking, tended to better distinguish facial expressions of fear and happiness, and tended to provide greater instrumental help to the experimenter.The present study provides initial evidence for the feasibility of acute tryptophan supplementation in children and some effect of tryptophan supplementation on children's behaviors. Further studies are warranted to explore the potential impact of increased serotonergic functioning on boys' dominant and affiliative behaviors