108 research outputs found

    Institutional Transformation in the Agricultural Sector of the former Soviet Bloc

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    This article discusses popular explanations for the demise of farm enterprises in Mongolia, such as: reduced state funding, corrupt and self-interested rural elites, and the (supposed) drastic central privatisation policy. It argues that these factors are insufficient to explain the collectives' demise, as they are largely true also for Russia, where no widespread break-up of farm enterprises took place. Farm enterprises in Russia, despite financial difficulties, show remarkable resilience as large-scale units. A tendency which can be observed in general, as well as in most of the regions bordering Mongolia with a similar type of (semi) - pastoralist livestock farming, Therefore, this article takes a look at the level of the Mongolian farm enterprise, and considers the socio-economic specifics of these enterprises to discover the incentives for employees and managers to disband (or leave) these enterprises. In doing so it pays attention to formal structures and informal social structures related to property and production, within a tentative comparison with Russia

    Exploring the limits to sustainable pellet production for international markets: The impact of increasing pellet production in the US Southeast on feedstock use, production cost and carbon sequestration in forest areas

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    With rising demand for wood pellets from the US Southeast (US SE), the environmental limits to additional biomass demand are increasingly questioned. This study analyses the impact of increased pellet production in the US SE until 2030 on feedstock allocation, carbon flux in forest areas and costs of pre-treatment and transport of feedstock and pellets. This by linking locations of forest biomass supply and demand through supply-side logistics, allocating feedstock based on lowest costs of pre-treatment, transport of feedstock and pellets, for the entire wood products sector. The impact is analysed for different scenarios with varied pellet production levels, additional inclusion of logging residues and optimization either on costs or on maintaining total carbon stock in sourcing areas of new pellet mills. In a scenario of 20 Mt pellet production, the roundwood share increases from 0% in 2020 to 37% pulplogs and 11% sawlogs in 2030. Costs increase with 57% towards 2030 compared to 2020, largely because of higher costs for pulplogs and sawlogs. In a scenario without pellet production, forest carbon removal in the US SE is 3 Mt CO2/year lower than in 2020. In the Reference scenario, additional carbon removal of 6, 21 and 38 Mt CO2/year is observed for 10, 20 and 30 Mt pellet production, respectively. In all cases, the forests of the US SE remain a net sink until 2030. The impact of a selection criteria for new pellet mill locations based on keeping local growth/drain ratios above 1 in sourcing areas is small since this mostly results in displacement of impacts and does not affect the total feedstock availability. Additional mobilization of logging residues is a key strategy to reduce carbon impacts, resulting in a smaller additional flux of 2, 11 and 29 Mt CO2/year for 10–30 Mt pellet production

    Proteomics Based Identification of Proteins with Deregulated Expression in B Cell Lymphomas

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    Follicular lymphoma and diffuse large B cell lymphomas comprise the main entities of adult B cell malignancies. Although multiple disease driving gene aberrations have been identified by gene expression and genomic studies, only a few studies focused at the protein level. We applied 2 dimensional gel electrophoresis to compare seven GC B cell non Hodgkin lymphoma (NHL) cell lines with a lymphoblastoid cell line (LCL). An average of 130 spots were at least two folds different in intensity between NHL cell lines and the LCL. We selected approximately 38 protein spots per NHL cell line and linked them to 145 unique spots based on the location in the gel. 34 spots that were found altered in at least three NHL cell lines when compared to LCL, were submitted for LC-MS/MS. This resulted in 28 unique proteins, a substantial proportion of these proteins were involved in cell motility and cell metabolism. Loss of expression of B2M, and gain of expression of PRDX1 and PPIA was confirmed in the cell lines and primary lymphoma tissue. Moreover, inhibition of PPIA with cyclosporine A blocked cell growth of the cell lines, the effect size was associated with the PPIA expression levels. In conclusion, we identified multiple differentially expressed proteins by 2-D proteomics, and showed that some of these proteins might play a role in the pathogenesis of NHL

    Health-related quality of life and functional ability in patients with early arthritis during remission steered treatment: results of the IMPROVED study

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    INTRODUCTION: The aim of this study was to investigate patient reported outcomes (PROs) of functional ability and health related quality of life (HRQoL) in patients with early (rheumatoid) arthritis during one year of remission steered treatment. METHODS: In this study, 610 patients with early rheumatoid arthritis (RA) or undifferentiated arthritis (UA) were treated with methotrexate (MTX) and tapered high dose of prednisone. Patients in early remission (Disease Activity Score (DAS) <1.6 after 4 months) tapered prednisone to zero and when in persistent remission, also tapered MTX. Patients not in early remission were randomized to either MTX + hydroxychloroquine + sulphasalazine + prednisone (arm 1) or to MTX + adalimumab (arm 2). Every 4 months, patients filled out the Health Assessment Questionnaire (HAQ) and the McMaster Toronto Arthritis Patient Preference Questionnaire (MACTAR), the Short Form 36 (SF-36) and visual analogue scales (VAS). Change scores were compared between treatment groups. The association with achieving remission was analyzed using linear mixed models. RESULTS: During year 1, patients who achieved early remission had the most improvement in PROs with scores comparable to the general population. Patients in the randomization arms showed less improvement. Scores were comparable between the arms. There was a significant association between achieving remission and scores of HAQ, MACTAR and physical HRQoL. CONCLUSIONS: In early arthritis, PROs of functional ability and HRQoL after one year of remission steered treatment reach normal values in patients who achieved early remission. In patients not in early remission, who were randomized to two strategy arms, PROs improved less, with similar scores in both treatment arms. TRIAL REGISTRATIONS: ISRCTN11916566 and EudraCT2006-006186-1

    Clinical phenotypes of adults with monogenic and syndromic genetic obesity

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    Objective: Considering limited evidence on diagnostics of genetic obesity in adults, we evaluated phenotypes of adults with genetic obesity. Additionally, we assessed the applicability of Endocrine Society (ES) recommendations for genetic testing in pediatric obesity. Methods: We compared clinical features, including age of onset of obesity and appetite, between adults with non-syndromic monogenic obesity (MO), adults with syndromic obesity (SO), and adults with common obesity (CO) as control patients. Results: A total of 79 adults with genetic obesity (32 with MO, 47 with SO) were compared with 186 control patients with CO. Median BMI was similar among the groups: 41.2, 39.5, and 38.7 kg/m2 for patients with MO, SO, and CO, respectively. Median age of onset of obesity was 3 (IQR: 1–6) years in patients with MO, 9 (IQR: 4–13) years in patients with SO, and 21 (IQR: 13–33) years in patients with CO (p &lt; 0.001). Patients with genetic obesity more often reported increased appetite: 65.6%, 68.1%, and 33.9% in patients with MO, SO, and CO, respectively (p &lt; 0.001). Intellectual deficit and autism spectrum disorder were more prevalent in patients with SO (53.2% and 21.3%) compared with those with MO (3.1% and 6.3%) and CO (both 0.0%). The ES recommendations were fulfilled in 56.3%, 29.8%, and 2.7% of patients with MO, SO, and CO, respectively (p &lt; 0.001). Conclusions: We found distinct phenotypes in adult genetic obesity. Additionally, we demonstrated low sensitivity for detecting genetic obesity in adults using pediatric ES recommendations, necessitating specific genetic testing recommendations in adult obesity care.</p

    Performance of a [18F]Flortaucipir PET Visual Read Method Across the Alzheimer Disease Continuum and in Dementia With Lewy Bodies

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    Background and Objectives: Recently, the US Food and Drug Administration approved the tau-binding radiotracer [18F]flortaucipir and an accompanying visual read method to support the diagnostic process in cognitively impaired patients assessed for Alzheimer disease (AD). Studies evaluating this visual read method are limited. In this study, we evaluated the performance of the visual read method in participants along the AD continuum and dementia with Lewy bodies (DLB) by determining its reliability, accordance with semiquantitative analyses, and associations with clinically relevant variables. // Methods: We included participants who underwent tau-PET at Amsterdam University Medical Center. A subset underwent follow-up tau-PET. Two trained nuclear medicine physicians visually assessed all scans. Inter-reader agreement was calculated using Cohen κ. To examine the concordance of visual read tau positivity with semiquantification, we defined standardized uptake value ratio (SUVr) positivity using different threshold approaches. To evaluate the prognostic value of tau-PET visual read, we performed linear mixed models with longitudinal Mini-Mental State Examination (MMSE). // Results: We included 263 participants (mean age 68.5 years, 45.6% female), including 147 cognitively unimpaired (CU) participants, 97 amyloid-positive participants with mild cognitive impairment or AD dementia (AD), and 19 participants with DLB. The visual read inter-reader agreement was excellent (κ = 0.95, CI 0.91–0.99). None of the amyloid-negative CU participants (0/92 [0%]) and 1 amyloid-negative participant with DLB (1/12 [8.3%]) were tau-positive. Among amyloid-positive participants, 13 CU participants (13/52 [25.0%]), 85 with AD (85/97 [87.6%]), and 3 with DLB (3/7 [42.9%]) were tau-positive. Two-year follow-up visual read status was identical to baseline. Tau-PET visual read corresponded strongly to SUVr status, with up to 90.4% concordance. Visual read tau positivity was associated with a decline on the MMSE in CU participants (β = −0.52, CI −0.74 to −0.30, p < 0.001) and participants with AD (β = −0.30, CI −0.58 to −0.02, p = 0.04). // Discussion: The excellent inter-reader agreement, strong correspondence with SUVr, and longitudinal stability indicate that the visual read method is reliable and robust, supporting clinical application. Furthermore, visual read tau positivity was associated with prospective cognitive decline, highlighting its additional prognostic potential. Future studies in unselected cohorts are needed for a better generalizability to the clinical population. // Classification of Evidence: This study provides Class II evidence that [18F]flortaucipir visual read accurately distinguishes patients with low tau-tracer binding from those with high tau-tracer binding and is associated with amyloid positivity and cognitive decline. // Glossary: Aβ=β-amyloid; AD=Alzheimer disease; CU=cognitively unimpaired; DLB=dementia with Lewy bodies; US FDA=US Food and Drug Administration; GMM=Gaussian mixture model; LMM=linear mixed model; MCI=mild cognitive impairment; MMSE=Mini-Mental State Examination; OR=odds ratio; ROI=region of interest; SCD=subjective cognitive decline; SUVr=standardized uptake value ratio

    Extensive Phenotyping for Potential Weight-Inducing Factors in an Outpatient Population with Obesity

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    Background: Obesity has been associated with miscellaneous weight-inducing determinants. A comprehensive assessment of known obesity-related factors other than diet and physical activity within one cohort is currently lacking. Objectives: To assess the prevalence of potential contributors to obesity and self-reported triggers for marked weight gain in an adult population with obesity and between obesity classes. Methods: In this observational cohort study, we assessed 408 persons with obesity (aged 41.3 ± 14.2 years, BMI 40.5 ± 6.2) visiting our obesity clinic. They were evaluated for use of weight-inducing drugs, hormonal abnormalities, menarcheal age, (high) birth weight, sleep deprivation, and obstructive sleep apnea syndrome (OSAS). We additionally assessed self-reported triggers for marked weight gain and performed genetic testing in patients suspected of genetic obesity. Results: Nearly half of the patients were using a potentially weight-inducing drug, which was also the most reported trigger for marked weight gain. For the assessed hormonal conditions, a relatively high prevalence was found for hypothyroidism (14.1%), polycystic ovary syndrome (12.0%), and male hypogonadism (41.7%). A relatively low average menarcheal age (12.6 ± 1.8 years) was reported, whereas there was a high prevalence of a high birth weight (19.5%). Sleep deprivation and OSAS were reported in, respectively, 14.5 and 13.7% of the examined patients. Obesity class appeared to have no influence on the majority of the assessed factors. Of the genetically analyzed patients, a definitive genetic diagnosis was made in 3 patients (1.9%). Conclusions: A thorough evaluation of patients with obesity yields a relatively high prevalence of various potentially weight-inducing factors. Diagnostic screening of patients with obesi

    Collagen mRNA levels changes during colorectal cancer carcinogenesis

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    <p>Abstract</p> <p>Background</p> <p>Invasive growth of epithelial cancers is a complex multi-step process which involves dissolution of the basement membrane. Type IV collagen is a major component in most basement membranes. Type VII collagen is related to anchoring fibrils and is found primarily in the basement membrane zone of stratified epithelia. Immunohistochemical studies have previously reported changes in steady-state levels of different α(IV) chains in several epithelial cancer types. In the present study we aimed to quantitatively determine the mRNA levels of <it>type IV collagen (α1/α4/α6) </it>and <it>type VII collagen (α1) </it>during colorectal cancer carcinogenesis.</p> <p>Methods</p> <p>Using quantitative RT-PCR, we have determined the mRNA levels for <it>α1(IV), α4(IV), α6(IV), and α1(VII) </it>in colorectal cancer tissue (n = 33), adenomas (n = 29) and in normal tissue from the same individuals. In addition, corresponding tissue was examined from healthy volunteers (n = 20). mRNA levels were normalized to <it>β-actin</it>. Immunohistochemical analysis of the distributions of type IV and type VII collagens were performed on normal and affected tissues from colorectal cancer patients.</p> <p>Results</p> <p>The <it>α1(IV) </it>and <it>α1(VII) </it>mRNA levels were statistically significantly higher in colorectal cancer tissue (p < 0.001) as compared to corresponding tissue from healthy controls. This is an early event as tissue from adenomas also displayed a higher level. There were small changes in the levels of <it>α4(IV)</it>. The level of <it>α6(IV) </it>was 5-fold lower in colorectal cancer tissue as compared to healthy individuals (p < 0.01). The localisation of type IV and type VII collagen was visualized by immunohistochemical staining.</p> <p>Conclusion</p> <p>Our results suggest that the down-regulation of <it>α6(IV</it>) mRNA coincides with the acquisition of invasive growth properties, whereas <it>α1(IV) </it>and <it>α1(VII) </it>mRNAs were up-regulated already in dysplastic tissue. There are no differences in collagen expression between tissues from healthy individuals and normal tissues from affected individuals.</p

    A YAP-centered mechanotransduction loop drives collective breast cancer cell invasion

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    Dense and aligned Collagen I fibers are associated with collective cancer invasion led by protrusive tumor cells, leader cells. In some breast tumors, a population of cancer cells (basal-like cells) maintain several epithelial characteristics and express the myoepithelial/basal cell marker Keratin 14 (K14). Emergence of leader cells and K14 expression are regarded as interconnected events triggered by Collagen I, however the underlying mechanisms remain unknown. Using breast carcinoma organoids, we show that Collagen I drives a force-dependent loop, specifically in basal-like cancer cells. The feed-forward loop is centered around the mechanotransducer Yap and independent of K14 expression. Yap promotes a transcriptional program that enhances Collagen I alignment and tension, which further activates Yap. Active Yap is detected in invading breast cancer cells in patients and required for collective invasion in 3D Collagen I and in the mammary fat pad of mice. Our work uncovers an essential function for Yap in leader cell selection during collective cancer invasion.</p
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