51628 research outputs found
Sort by
Antibody-Independent Functions of B cells in Multiple Sclerosis
Full text linkMultiple sclerosis (MS) is a chronic immune-mediated disease of the central nervoussystem (CNS). Various pro-inflammatory immune cells mediate local pathology. CD20 depletion therapies and genome-wide association studies (GWAS) have shown that the contribution of B cells to the pathogenesis of MS is indisputable. The strong and rapid beneficial clinical effects of anti-CD20 treatment in MS patients has revealed that B cells serve as antigen-presenting rather than antibody-producing cells in the periphery. Although pro-inflammatory Th-cell responses are significantly reduced in these patients, the exact underlying antibody-independent functions of B cells in MS are poorly understood. B cells activate TH cells through the presentation of antigens, expression of costimulatory molecules and secretion of cytokines. In this thesis, we aimed to uncover genes and pathways that are functionally altered in human B cells and potentially contribute to MS. To study this, we made use of gene silencing and functional assays related to B- and Th-cell interaction and took advantage of recent GWAS data, different MS cohorts and the effects of immunosuppressive conditions and treatment on disease activity
Complex Regional Pain Syndrome: the search for inflammatory biomarkers
Full text linkThe purpose of this manuscript was to study the role of inflammatory biomarkers in the diagnosis and management of Complex Regional Pain Syndrome
Automatic Configuration of Fast Automated Multi‐Objective Treatment Planning in Radiotherapy
Full text linkAt Erasmus MC, automated plan generation is used to treat cancer patients. The system for automated planning is called Erasmus-iCycle which is used to consistently generate a high-quality and Pareto-optimal treatment plan with optimized beam directions for each patient. In this thesis, a new planning method, the lexicographic reference point method (LRPM), was developed and implemented in Erasmus-iCycle. The LRPM aims to improve the clinically used planning method in Erasmus-iCycle in two ways. Firstly, the LRPM should decrease the computation time of automatically generating a plan without compromising in its quality. Secondly, instead of the manual time-consuming and labour-intensive configuration procedure of the clinically used planning method, the LRPM should come with an automatic configuration procedure
The Right to Claim Innocence in Poland
Full text linkWrongful convictions and miscarriages of justice, their reasons and effects, only rarely become the subject of academic debate in Poland. This article aims at filling this gap and providing a discussion on the current challenges of mechanisms available in Polish law focused on the verification of final judgments based on innocence claims. While there are two procedures designed to move such judgment: cassation and the reopening of criminal proceedings, only the latter aims at the verification of new facts and evidence, and this work remains focused exactly on that issue. The article begins with a case study of the famous Komenda case, which resulted in a successful innocence claim, serving as a good, though rare, example of reopening a case and acquitting the convict immediately and allows for discussing the reasons that commonly stand behind wrongful convictions in Poland. Furthermore, the article examines the innocence claim grounds as regulated in the Polish criminal procedure and their interpretation under the current case law. It also presents the procedure concerning the revision of the case. The work additionally provides the analysis of the use of innocence claim in practice, feeding on the statistical data and explaining tendencies in application for revision of a case. It also presents the efforts of the Polish Ombudsman and NGOs to raise public awareness in that field. The final conclusions address the main challenges that the Polish system faces concerning innocence claims and indicates the direction in which the system should go
Overturning Wrongful Convictions by Wayof the Extraordinary Review
Full text linkAccording to the traditional view, the ultimate aim of the extraordinary review (recurso de revisión) provided in the Spanish justice system was to deal with wrongful criminal convictions and correct those serious miscarriages of justice which became apparent only after the judgment had become final. However, the 2015 reform called this traditional view into question by formally including two additional grounds for review that are not necessarily related to the correcting miscarriages or blatant mistakes in the assessment of the facts made by the sentencing court. This paper aims to give an overview of the extraordinary review in Spain. To that end it will first address the legal framework and its practical implementation, as well as present pitfalls and best practices. Finally, future trends and challenges will be identified in order to improve the protection of defendants who have suffered a wrongful conviction
Following, Othering, Taking Over: Research Participants Redefining the Field through Mobile Communication Technology
Full text linkBased on fieldwork with migrants and border populations in
Central America and the story of a young Congolese woman in particular,
this article discusses how research participants’ use of mobile communication
technology provokes a redefinition of the ethnographic field. Increasingly
popular trajectory research often sets out to follow migrants, yet a
focus on migrants keeping in touch with researchers at their own initiative
and discretion, following them, reveals entanglements of selective on- and
offline engagement and self-representation. Critical exploration of research
participants’ differentiated use of digital technology for navigating a social
environment that includes the researcher herself not only transforms our
understanding of the field in empirical, ethical, and methodological terms,
but also counteracts potentially voyeuristic and life-threatening practices
of following people on the mov
Progression of Behavioral Disturbances and Neuropsychiatric Symptoms in Patients With Genetic Frontotemporal Dementia
Full text linkImportance: Behavioral disturbances are core features of frontotemporal dementia (FTD); however, symptom progression across the course of disease is not well characterized in genetic FTD. Objective: To investigate behavioral symptom frequency and severity and their evolution and progression in different forms of genetic FTD. Design, Setting, and Participants: This longitudinal cohort study, the international Genetic FTD Initiative (GENFI), was conducted from January 30, 2012, to May 31, 2019, at 23 multicenter specialist tertiary FTD research clinics in the United Kingdom, the Netherlands, Belgium, France, Spain, Portugal, Italy, Germany, Sweden, Finland, and Canada. Participants included a consecutive sample of 232 symptomatic FTD gene variation carriers comprising 115 with variations in C9orf72, 78 in GRN, and 39 in MAPT. A total of 101 carriers had at least 1 follow-up evaluation (for a total of 400 assessments). Gene variations were included only if considered pathogenetic. Main Outcomes and Measures: Behavioral and neuropsychiatric symptoms were assessed across disease duration and evaluated from symptom onset. Hierarchical generalized linear mixed models were used to model behavioral and neuropsychiatric measures as a function of disease duration and variation. Results: Of 232 patients with FTD, 115 (49.6%) had a C9orf72 expansion (median [interquartile range (IQR)] age at evaluation, 64.3 [57.5-69.7] years; 72 men [62.6%]; 115 White patients [100%]), 78 (33.6%) had a GRN variant (median [IQR] age, 63.4 [58.3-68.8] years; 40 women [51.3%]; 77 White patients [98.7%]), and 39 (16.8%) had a MAPT variant (median [IQR] age, 56.3 [49.9-62.4] years; 25 men [64.1%]; 37 White patients [94.9%]). All core behavioral symptoms, including disinhibition, apathy, loss of empathy, perseverative behavior, and hyperorality, were highly expressed in all gene variant carriers (>50% patients), with apathy being one of the most common and severe symptoms throughout the disease course (51.7%-100% of patients). Patients with MAPT variants showed the highest frequency and severity of most behavioral symptoms, particularly disinhibition (79.3%-100% of patients) and compulsive behavior (64.3%-100% of patients), compared with C9orf72 carriers (51.7%-95.8% of patients with disinhibition and 34.5%-75.0% with compulsive behavior) and GRN carriers (38.2%-100% with disinhibition and 20.6%-100% with compulsive behavior). Alongside behavioral symptoms, neuropsychiatric symptoms were very frequently reported in patients with genetic FTD: anxiety and depression were most common in GRN carriers (23.8%-100% of patients) and MAPT carriers (26.1%-77.8% of patients); hallucinations, particularly auditory and visual, were most common in C9orf72 carriers (10.3%-54.5% of patients). Most behavioral and neuropsychiatric symptoms increased in the early-intermediate phases and plateaued in the late stages of disease, except for depression, which steadily declined in C9orf72 carriers, and depression and anxiety, which surged only in the late stages in GRN carriers. Conclusions and Relevance: This cohort study suggests that behavioral and neuropsychiatric disturbances differ between the common FTD gene variants and have different trajectories throughout the course of disease. These findings have crucial implications for counseling patients and caregivers and for the design of disease-modifying treatment trials in genetic FTD
Predicting morbidity in older travellers during a short-term stay in the tropics: the ELDEST study
Full text linkBACKGROUND: Older persons may suffer more from travel-related health problems because of ageing and underlying chronic disorders. Knowledge on who is more likely to have these health problems helps to tailor travel health advice more specifically. This study aimed to determine predictors of travel-related morbidity in older travellers by assessing their pre-travel characteristics and performance using physical and cognitive functioning tests. METHODS: Multicentre prospective cohort study among older travellers (≥60 years) who consulted one of the participating Dutch travel clinics. Handgrip strength and cognitive performance were measured pre-travel. Participants completed questionnaires before departure and 1 and 4 weeks after return. A diary recorded health complaints during travel until 2-week post-travel. RESULTS: In total, 477 travellers completed the study (follow-up rate of 97%). Participants' median age was 66 years. The most visited regions were South-East Asia (34%) and South Asia (14%). Median travel duration was 19 days. Polypharmacy (≥5 medications per day) was not uncommon (16%). The median Charlson Comorbidity Index (CCI) score was 0. Self-reported travel-related infectious diseases concerned primarily respiratory tract infections (21%) and gastroenteritis (10%) whereas non-infectious complaints were injuries (13%), peripheral edema (12%) and dehydration (3%). Medical assistance was sought by 18%, mostly post-travel from their general practitioner (87%). Self-reported physical and mental health-related quality of life significantly improved during and after travel. Predictors for an increased risk of travel-related morbidity were higher CCI score, more travel experience, longer travel duration, higher number of daily medications, visiting northern Africa or South-East and East Asia, and phone and social media use. CONCLUSION: Older Dutch travellers are generally fit, well-prepared and suffer not only from common infectious health problems, but also from injuries. Travel improved their self-perceived health. The predictors could be used to identify the more at-risk older traveller and to decrease travel-related morbidity by optimizing pre-travel advice
Epidemiology and (Patho)physiology of folic acid supplement use in obese women before and during pregnancy
Full text linkPreconception folic acid supplement use is a well-known method of primary prevention of neural tube defects (NTDs). Obese women are at a higher risk for having a child with a NTD. As different international recommendations on folic acid supplement use for obese women before and during pregnancy exist, this narrative review provides an overview of epidemiology of folate deficiency in obese (pre)pregnant women, elaborates on potential mechanisms underlying folate deficiency, and discusses considerations for the usage of higher doses of folic acid supplements. Women with obesity more often suffer from an absolute folate deficiency, as they are less compliant to periconceptional folic acid supplement use recommendations. In addition, their dietary folate intake is limited due to an unbalanced diet (relative malnutrition). The association of obesity and NTDs also seems to be independent of folate intake, with studies suggesting an increased need of folate (relative deficiency) due to derangements involved in other pathways. The relative folate deficiency, as a result of an increased metabolic need for folate in obese women, can be due to: (1) low-grade chronic inflammation (2) insulin resistance, (3) inositol, and (4) dysbiotic gut microbiome, which plays a role in folate production and uptake. In all these pathways, the folate-dependent one-carbon metabolism is involved. In conclusion, scientific evidence of the involvement of several folate-related pathways implies to increase the recommended folic acid supplementation in obese women. However, the physiological uptake of synthetic folic acid is limited and side-effects of unmetabolized folic acid in mothers and offspring, in particular variations in epigenetic (re)programming with long-term health effects, cannot be excluded. Therefore, we emphasize on the urgent need for further research and preconception personalized counseling on folate status, lifestyle, and medical conditions