A wide bandwidth free-electron laser with mode locking using current modulation

A new scheme for mode locking a free-electron laser (FEL) amplifier is proposed based on electron beam current modulation. It is found that certain properties of the original concept (Thompson and McNeil 2008 Phys. Rev. Lett. 100 203901), based on the energy modulation of electrons, are improved, including the spectral brightness of the source and the purity of the series of short pulses. Numerical comparisons are made between the new and old schemes and between a mode-locked FEL and a self-amplified spontaneous emission FEL. Illustrative examples using a hypothetical mode-locked FEL amplifier are provided. The ability to generate intense coherent radiation with a large bandwidth is demonstrated

LRP2 mediates folate uptake in the developing neural tube

The low-density lipoprotein (LDL) receptor-related protein 2 (LRP2) is a multifunctional cell surface receptor expressed in the embryonic neuroepithelium. Loss of LRP2 in the developing murine central nervous system (CNS) causes impaired closure of the rostral neural tube at embryonic stage (E) 9.0. Similar neural tube defects (NTDs) have previously been attributed to impaired folate metabolism in mice. We therefore asked whether LRP2 might be required for delivery of folate to neuroepithelial cells during neurulation. Uptake assays in whole embryo cultures showed that LRP2 deficient neuroepithelial cells are unable to mediate uptake of folate bound to soluble folate receptor 1 (sFOLR1). Consequently, folate concentrations are significantly reduced in Lrp2(-/-) embryos compared to control littermates. Moreover, the folic acid dependent gene Alx3 is significantly down regulated in Lrp2 mutants. In conclusion, we show that LRP2 is essential for cellular folate uptake in the developing neural tube, a crucial step for proper neural tube closure

LINAC DESIGN FOR AN ARRAY OF SOFT X-RAY FREE ELECTRON LASERS

The design of the linac delivering electron bunches into ten independent soft x-ray free electron lasers (FELs) producing light at 1 nm and longer wavelengths is presented. The bunch repetition rate in the linac is 1 MHz and 100 kHz in each of ten FEL beam lines. Various issues regarding machine layout and lattice, bunch compression, collimation, and the beam switch yard are discussed. Particular attention is given to collective effects. A demanding goal is to preserve both a low beam slice emittance and low slice energy spread during acceleration, bunch compression and distribution of the electron bunches into the array of FEL beamlines. Detailed studies of the effect of the electron beam microbunching caused by longitudinal space-charge forces and coherent synchrotron radiation (CSR) have been carried out and their results are presented

Prevalence of Trachoma in Unity State, South Sudan: Results from a Large-Scale Population-Based Survey and Potential Implications for Further Surveys

Large parts of South Sudan are thought to be trachoma endemic but baseline data, required to initiate interventions, are few. District-by-district surveys, currently recommended by the World Health Organization (WHO), are often not financially or logistically viable. We therefore adapted existing WHO guidelines and combined eight counties (equivalent to districts) of Unity State into one survey area, randomly sampling 40 villages using a population-based survey design. This decision was based on a trachoma risk map and a trachoma rapid assessment, both identifying the state as likely to be highly endemic. The survey confirmed trachoma as being hyperendemic throughout Unity State, meaning that large-scale intervention should be initiated now. Simulation studies were conducted to determine the likely outcome if fewer (n = 20) or more (n = 60) villages had been sampled, confirming that precision decreased or increased, respectively. Importantly, simulation results also showed that all three sample sizes would have led to the same conclusion, namely the need for large-scale intervention. This finding suggests that district-by-district surveys may not be required for areas where trachoma is suspected to be highly prevalent but that are lacking baseline data; instead districts may be combined into a larger survey area

Clinical characteristics of Polish patients with ANCA-associated vasculitides-retrospective analysis of POLVAS registry

Objective Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rare small to medium-size vessel systemic diseases. As their clinical picture, organ involvement, and factors influencing outcome may differ between countries and geographical areas, we decided to describe a large cohort of Polish AAV patients coming from several referral centers-members of the Scientific Consortium of the Polish Vasculitis Registry (POLVAS). Methods We conducted a systematic multicenter retrospective study of adult patients diagnosed with AAV between Jan 1990 and Dec 2016 to analyze their clinical picture, organ involvement, and factors influencing outcome. Patients were enrolled to the study by nine centers (14 clinical wards) from seven Voivodeships populated by 22.3 mln inhabitants (58.2% of the Polish population). Results Participating centers included 625 AAV patients into the registry. Their distribution was as follows: 417 patients (66.7%) with GPA, 106 (17.0%) with MPA, and 102 (16.3%) with EGPA. Male-to-female ratios were almost 1:1 for GPA (210/207) and MPA (54/52), but EGPA was twice more frequent among women (34/68). Clinical manifestations and organ involvement were analyzed by clinical phenotype. Their clinical manifestations seem very similar to other European countries, but interestingly, men with GPA appeared to follow a more severe course than the women. Fifty five patients died. In GPA, two variables were significantly associated with death: permanent renal replacement therapy (PRRT) and respiratory involvement (univariate analysis). In multivariate analysis, PRRT (OR = 5.3; 95% confidence interval (CI) = 2.3–12.2), respiratory involvement (OR = 3.2; 95% CI = 1.06–9.7), and, in addition, age > 65 (OR = 2.6; 95% CI = 1.05–6.6) were independently associated with death. In MPA, also three variables were observed to be independent predictors of death: PRRT (OR = 5.7; 95% CI = 1.3–25.5), skin involvement (OR = 4.4; 95% CI = 1.02– 19.6), and age > 65 (OR = 6.3; 95% CI = 1.18–33.7). Conclusions In this first multicenter retrospective study of the Polish AAV patients, we have shown that their demographic characteristics, disease manifestations, and predictors of fatal outcome follow the same pattern as those from other European countries, with men possibly suffering from more severe course of the disease

Integrated Mapping of Neglected Tropical Diseases: Epidemiological Findings and Control Implications for Northern Bahr-el-Ghazal State, Southern Sudan

Integrated control of neglected tropical diseases (NTDs) is being scaled up in a number of developing countries, because it is thought to be more cost-effective than stand-alone control programmes. Under this approach, treatments for onchocerciasis, lymphatic filariasis (LF), schistosomiasis, soil-transmitted helminth (STH) infection, and trachoma are administered through the same delivery structure and at about the same time. A pre-requisite for implementation of integrated NTD control is information on where the targeted diseases are endemic and to what extent they overlap. This information is generated through surveys that can be labour-intensive and expensive. In Southern Sudan, all of the above diseases except onchocerciasis require further mapping before a comprehensive integrated NTD control programme can be implemented. To determine where treatment for which disease is required, integrated surveys were conducted for schistosomiasis, STH infection, LF, and loiasis, throughout one of ten states of the country. Our results show that treatment is only required for urinary schistosomiasis and STH in a few, yet separate, geographical area. This illustrates the importance of investing in disease mapping to minimize overall programme costs by being able to target interventions. Integration of survey methodologies for the above disease was practical and efficient, and minimized the effort required to collect these data

Toxic effect in the lungs of rats after inhalation exposure to benzalkonium chloride

Background: Benzalkonium chloride (BAC) is a quaternary ammonium compound (QAC) toxic to microorganisms. Inhalation is one of the major possible routes of human exposure to BAC. Materials and Methods: Experiments were performed on female Wistar rats. The rats were exposed to aerosol of BAC water solution at the target concentration of 0 (control group) and 35 mg/m3 for 5 days (6 h/day) and, after a 2-week interval, the animals were challenged (day 21) with BAC aerosol at the target concentration of 0 (control group) and 35 mg/m3 for 6 h. Results: Compared to the controls, the animals exposed to BAC aerosol were characterized by lower food intake and their body weight was significantly smaller. As regards BAC-exposed group, a significant increase was noted in relative lung mass, total protein concentration, and MIP-2 in BALF both directly after the termination of the exposure and 18 h afterwards. Significantly higher IL-6 and IgE concentrations in BALF and a decrease in the CC16 concentration in BALF were found in the exposed group immediately after the exposure. The leukocyte count in BALF was significantly higher in the animals exposed to BAC aerosol compared to the controls. In the lungs of rats exposed to BAC the following effects were observed: minimal perivascular, interstitial edema, focal aggregates of alveolar macrophages, interstitial mononuclear cell infiltrations, thickened alveolar septa and marginal lipoproteinosis. Conclusion: Inhalation of BAC induced a strong inflammatory response and a damage to the blood-air barrier. Reduced concentrations of CC16, which is an immunosuppressive and anti-inflammatory protein, in combination with increased IgE concentrations in BALF may be indicative of the immuno-inflammatory response in the animals exposed to BAC aerosol by inhalation. Histopathological examinations of tissue samples from the BAC-exposed rats revealed a number of pathological changes found only in the lungs