G-CSF Prevents the Progression of Structural Disintegration of White Matter Tracts in Amyotrophic Lateral Sclerosis: A Pilot Trial

Background: The hematopoietic protein Granulocyte-colony stimulating factor (G-CSF) has neuroprotective and regenerative properties. The G-CSF receptor is expressed by motoneurons, and G-CSF protects cultured motoneuronal cells from apoptosis. It therefore appears as an attractive and feasible drug candidate for the treatment of amyotrophic lateral sclerosis (ALS). The current pilot study was performed to determine whether treatment with G-CSF in ALS patients is feasible.Methods: Ten patients with definite ALS were entered into a double-blind, placebo-controlled, randomized trial. Patients received either 10 mu g/kg BW G-CSF or placebo subcutaneously for the first 10 days and from day 20 to 25 of the study. Clinical outcome was assessed by changes in the ALS functional rating scale (ALSFRS), a comprehensive neuropsychological test battery, and by examining hand activities of daily living over the course of the study (100 days). The total number of adverse events (AE) and treatment-related AEs, discontinuation due to treatment-related AEs, laboratory parameters including leukocyte, erythrocyte, and platelet count, as well as vital signs were examined as safety endpoints. Furthermore, we explored potential effects of G-CSF on structural cerebral abnormalities on the basis of voxel-wise statistics of Diffusion Tensor Imaging (DTI), brain volumetry, and voxel-based morphometry.Results: Treatment was well-tolerated. No significant differences were found between groups in clinical tests and brain volumetry from baseline to day 100. However, DTI analysis revealed significant reductions of fractional anisotropy (FA) encompassing diffuse areas of the brain when patients were compared to controls. On longitudinal analysis, the placebo group showed significant greater and more widespread decline in FA than the ALS patients treated with G-CSF.Conclusions: Subcutaneous G-CSF treatment in ALS patients appears as feasible approach. Although exploratory analysis of clinical data showed no significant effect, DTI measurements suggest that the widespread and progressive microstructural neural damage in ALS can be modulated by G-CSF treatment. These findings may carry significant implications for further clinical trials on ALS using growth factors

Tenofovir-Diphosphate as a Marker of HIV Pre-exposure Prophylaxis Use Among East African Men and Women

Background: Controlled pharmacokinetic (PK) studies in United States populations have defined categories of tenofovir-diphosphate (TFV-DP) in dried blood spots (DBS) for various pre-exposure prophylaxis (PrEP) adherence targets. It is unknown how these categories perform in other populations. Therefore, we evaluated the sensitivity and specificity of these PK-derived categories compared to daily medication electronic adherence monitoring (MEMS) data among East African men and women using daily PrEP.Methods: Participants were enrolled as members of HIV serodiscordant couples as part of an open-label PrEP study in Kenya and Uganda. Blood samples were taken at quarterly visits and stored as DBS, which were analyzed for TFV-DP concentrations.Results: Among 150 samples from 103 participants, MEMs data indicated that 87 (58%) took ≥4 doses and 62 (41%) took ≥6 per week consistently over the 4 weeks prior to sample collection. Sensitivities of DBS TFV-DP levels were 62% for the ≥4 doses/week category (≥700 fmol/punch TFV-DP) and 44% for the ≥6 doses/week category (≥1050 fmol/punch TFV-DP); specificities were 86 and 94%, respectively. There were no statistically significant differences in these sensitivities and specificities by gender.Conclusion: In this sample of East African PrEP users, categories of TFV-DP concentrations developed from directly observed PrEP use among United States populations had high specificity but lower than expected sensitivity. Sensitivity was lowest when MEMS data indicated high adherence (i.e., ≥6 doses/week). PrEP studies and implementation programs should carefully consider the sensitivity and specificity of the TFV-DP levels used for adherence feedback

Comprehensive Evaluation of Corticospinal Tract Metabolites in Amyotrophic Lateral Sclerosis Using Whole-Brain 1H MR Spectroscopy

Changes in the distribution of the proton magnetic resonance spectroscopy (MRS) observed metabolites N-acetyl aspartate (NAA), total-choline (Cho), and total-creatine (Cre) in the entire intracranial corticospinal tract (CST) including the primary motor cortex were evaluated in patients with amyotrophic lateral sclerosis (ALS). The study included 38 sporadic definite-ALS subjects and 70 age-matched control subjects. All received whole-brain MR imaging and spectroscopic imaging scans at 3T and clinical neurological assessments including percentage maximum forced vital capacity (FVC) and upper motor neuron (UMN) function. Differences in each individual metabolite and its ratio distributions were evaluated in the entire intracranial CST and in five segments along the length of the CST (at the levels of precentral gyrus (PCG), centrum semiovale (CS), corona radiata (CR), posterior limb of internal capsule (PLIC) and cerebral peduncle (CP)). Major findings included significantly decreased NAA and increased Cho and Cho/NAA in the entire intracranial CST, with the largest differences for Cho/NAA in all the groups. Significant correlations between Cho/NAA in the entire intracranial CST and the right finger tap rate were noted. Of the ten bilateral CST segments, significantly decreased NAA in 4 segments, increased Cho in 5 segments and increased Cho/NAA in all the segments were found. Significant left versus right CST asymmetries were found only in ALS for Cho/NAA in the CS. Among the significant correlations found between Cho/NAA and the clinical assessments included the left-PCG versus FVC and right finger tap rate, left -CR versus FVC and right finger tap rate, and left PLIC versus FVC and right foot tap rate. These results demonstrate that a significant and bilaterally asymmetric alteration of metabolites occurs along the length of the entire intracranial CST in ALS, and the MRS metrics in the segments correlate with measures of disease severity and UMN function

Implementation of a Practice Development Model to Reduce the Wait for Autism Spectrum Diagnosis in Adults

This study examined waiting times for diagnostic assessment of Autism Spectrum Disorder in 11 adult services, prior to and following the implementation of a 12 month change program. Methods to support change are reported and a multi-level modelling approach determined the effect of the change program on overall wait times. Results were statistically significant (b = − 0.25, t(136) = − 2.88, p = 0.005). The average time individuals waited for diagnosis across all services reduced from 149.4 days prior to the change program and 119.5 days after it, with an average reduction of 29.9 days overall. This innovative intervention provides a promising framework for service improvement to reduce the wait for diagnostic assessment of ASD in adults across the range of spectrum presentations

The debt level of agricultural farms in Poland in the years 2010-2013

Przedstawiono poziom zadłużenia gospodarstw rolniczych w Polsce w zależności od wielkości ekonomicznej i typu rolniczego. Analizą objęto gospodarstwa rolnicze uczestniczące w polskim systemie FADN. Okres badań obejmował lata 2010-2013. Stwierdzono, że gospodarstwa rolnicze swoją działalność finansują głównie kapitałem własnym. Najwyższy poziom zadłużenia odnotowano w gospodarstwach bardzo dużych i wyspecjalizowanych w uprawach polowych, co wynika m.in. z większej skali działalności i kapitałochłonności produkcji w porównaniu do pozostałych analizowanych grup.The paper presents the level of debt of farms in Poland, according to the economic size and type of farming. The analysis included agricultural farms participating in the Polish FADN. The study period covered the years 2010-2013. It was found that farm agricultural finance its operations primarily in equity. The highest level debt was recorded in farms with very large and specialized in field crops, which could be due to a greater scale of operations and the capital intensity of production to the other analyzed groups

Vibrations induced by blasting works in opencast mine and shocks in underground mine

W okresie od września do listopada 2015 roku w kopalni Janina wystąpiły silne wstrząsy, które zostały zarejestrowane przez stacje KSMD monitorujące oddziaływanie robót strzałowych wykonywanych w kopalni odkrywkowej w rejonie Chrzanowa. Dokonane rejestracje oraz przeprowadzone analizy intensywności i struktury częstotliwościowej drgań, pozwoliły na porównanie oddziaływania drgań wzbudzonych w dwóch różnych źródłach - roboty strzałowe w kopalni odkrywkowej i wstrząs w kopalni podziemnej. Obliczenia i analizy przeprowadzono zgodnie z procedurami przewidzianymi dla skal SWD i GSI

The study of seismic effects and modern systems of blasting explosives

Roboty strzałowe w górnictwie odkrywkowym charakteryzują się stosowaniem dużych mas MW do jednorazowego odpalania. Serie liczą od kilku do kilkudziesięciu, a nawet kilkuset ładunków umieszczonych w długich otworach. Prace te często prowadzone są w bezpośrednim sąsiedztwie zabudowań mieszkalnych i innych obiektów budowlanych, stąd konieczność ograniczenia oddziaływania drgań ma zasadnicze znaczenie dla kopalń odkrywkowych. W artykule przedstawiono możliwości sterowania efektem sejsmicznym, poprzez stosowanie elektronicznych systemów do odpalania ładunków MW, które dają szerokie możliwości doboru opóźnień milisekundowych. Pozwala to na modyfikowanie struktury wzbudzanych drgań i może przyczynić się do minimalizacji oddziaływania robót strzałowych na otoczenie. Zwrócono również uwagę na konieczność prowadzenia badań efektu sejsmicznego, co pozwala na uniknięcie efektów niepożądanych.Blasting in opencast mining is characterized by the use of large Massem of explosives for single firing. Series count from several to tens or even hundreds of charge placed in long boreholes.These Works are often held in the immediate vicinity of residential buildings and other buildings, hence the need to reduce the impact of vibration is essential for open pit mines. This paper presents the results of seismic control capabilities through the use of electronic systems for blasting explosives which give wide selection of millisecond delays. This allows you to modify the structure induced vibration and can help to minimize the impact of blasting on the environment. Attention was also drawn to the need to research the seismic effect, thus avoiding side effects