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New strategies for the conduct of clinical trials in paediatric Pulmonary Arterial Hypertension (PAH): Outcome of a multi-stakeholder meeting with patients, academia, industry and regulators held at EMA on Monday 12th June 2017

Aims: Drug development for paediatric pulmonary arterial hypertension (PAH) ispressingly needed. Experts from the US Food and Drug Administration, EuropeanMedicines Agency, Health Canada, key opinion leaders, academia, patients, and industry representatives held a workshop on 12th June 2017 dedicated to addressing challenges and unmet needs. This report summarises the approaches proposed during th

Association between added sugar intake and mortality is nonlinear and dependent on sugar source in 2 Swedish population-based prospective cohorts

Background: Although sugar consumption has been associated with several risk factors for cardiometabolic diseases, evidence for harmful long-term effects is lacking. In addition, most studies have focused on sugar-sweetened beverages (SSBs), not sugar per se. Objective: The aim of this study was to examine the associations between added and free sugar intake, intake of different sugar sources, a

Nutritional impact on Immunological maturation during Childhood in relation to the Environment (NICE) : A prospective birth cohort in northern Sweden

Introduction Prenatal and neonatal environmental factors, such as nutrition, microbes and toxicants, may affect health throughout life. Many diseases, such as allergy and impaired child development, may be programmed already in utero or during early infancy. Birth cohorts are important tools to study associations between early life exposure and disease risk. Here, we describe the study protocol of

Evidence for Anisotropic Electronic Coupling of Charge Transfer States in Weakly Interacting Organic Semiconductor Mixtures

We present a comprehensive investigation of the charge-transfer (CT) effect in weakly interacting organic semiconductor mixtures. The donor-acceptor pair diindenoperylene (DIP) and N,N′-bis(2-ethylhexyl)-1,7-dicyanoperylene-3,4/9,10-bis(dicarboxyimide) (PDIR-CN2) has been chosen as a model system. A wide range of experimental methods was used in order to characterize the structural, optical, elect

Cerebellar Exposure to Cell-Free Hemoglobin Following Preterm Intraventricular Hemorrhage : Causal in Cerebellar Damage?

Decreased cerebellar volume is associated with intraventricular hemorrhage (IVH) in very preterm infants and may be a principal component in neurodevelopmental impairment. Cerebellar deposition of blood products from the subarachnoid space has been suggested as a causal mechanism in cerebellar underdevelopment following IVH. Using the preterm rabbit pup IVH model, we evaluated the effects of IVH i

Dendritic cell migration to skin-draining lymph nodes is controlled by dermatan sulfate and determines adaptive immunity magnitude

For full activation of naïve adaptive lymphocytes in skin-draining lymph nodes (LNs), presentation of peptide:MHC complexes by LN-resident and skin-derived dendritic cells (DCs) that encountered antigens (Ags) is an absolute prerequisite. To get to the nearest draining LN upon intradermal immunization, DCs need to migrate from the infection site to the afferent lymphatics, which can only be reache

Neutrophils Lose the Capacity to Suppress T Cell Proliferation Upon Migration Towards Inflamed Joints in Juvenile Idiopathic Arthritis

Neutrophils are highly abundant in synovial fluid of rheumatic inflamed joints. In oligoarticular juvenile idiopathic arthritis (JIA), synovial fluid neutrophils have impaired effector functions and altered phenotype. We hypothesized that these alterations might impact the immunoregulatory interplay between neutrophils and T cells. In this study we analyzed the suppressive effect of neutrophils, i

NUDT15 polymorphism influences the metabolism and therapeutic effects of acyclovir and ganciclovir

Nucleobase and nucleoside analogs (NNA) are widely used as anti-viral and anti-cancer agents, and NNA phosphorylation is essential for the activity of this class of drugs. Recently, diphosphatase NUDT15 was linked to thiopurine metabolism with NUDT15 polymorphism associated with drug toxicity in patients. Profiling NNA drugs, we identify acyclovir (ACV) and ganciclovir (GCV) as two new NNAs metabo

Incidence of tuberculosis and early mortality in a large cohort of HIV infected patients receiving antiretroviral therapy in a tertiary hospital in Addis Ababa, Ethiopia

Preceding studies on morbidities and mortalities associated with TB in a cohort of HIV care indicate high incidence of TB development and premature death among patients on highly active antiretroviral treatment (HAART). This study aims to measure the rate of TB, TB mortality, and associated risk factors following commencement of HAART in a cohort of patients attending HIV care in Ethiopia. Patient

Short-term exposure to ambient particle gamma radioactivity is associated with increased risk for all-cause non-accidental and cardiovascular mortality

BACKGROUND: Recent studies have found that particulate matter (PM) attached radioactivity was associated with certain adverse health effects including increased blood pressure and lung dysfunction. However, there has been no investigation on the direct effect of PM radioactivity on mortality.METHODS: Exposures to ambient PM gamma activities were determined using U.S. EPA RadNet data. Data on daily

EMA Review of Daratumumab (Darzalex) for the Treatment of Adult Patients Newly Diagnosed with Multiple Myeloma

The use of daratumumab in combination with established regimens for the treatment of newly diagnosed multiple myeloma has recently been authorized by the European Medicines Agency based on results from three separate phase III randomized, active controlled, open-label studies that have confirmed enhanced efficacy and tolerability in both transplant-ineligible (MMY3008 and MMY3007) and transplant-e

Patients with regular physical activity before onset of rheumatoid arthritis present with milder disease

OBJECTIVES: Physical activity has been shown to decrease inflammatory markers; here we investigate the effect on the clinical presentation of rheumatoid arthritis (RA).METHODS: We used the cases from the population-based EIRA study (N=617), followed in the Swedish Rheumatology Quality Register, calculating the odds of having above median level of 28-joint disease activity score (DAS28), physician

Integrating engineering design and design analysis activities at an operational level

Computer-based design analysis is nowadays of utmost importance for most engineering design projects. However, this brings some challenges, among them that of the collaboration between engineering designers and design analysts. Since they work with, and are responsible for, different areas, they do not necessarily have full insight into each other’s way of working. The issue of integration between

Panel 6 : Vaccines

Objective: To review the literature on progress regarding (1) effectiveness of vaccines for prevention of otitis media (OM) and (2) development of vaccine antigens for OM bacterial and viral pathogens. Data Sources: PubMed database of the National Library of Science. Review Methods: We performed literature searches in PubMed for OM pathogens and candidate vaccine antigens, and we restricted the se

Microarray-based classification of a consecutive series of 121 childhood acute leukemias: prediction of leukemic and genetic subtype as well as of minimal residual disease status.

Gene expression analyses were performed on 121 consecutive childhood leukemias (87 B-lineage acute lymphoblastic leukemias (ALLs), 11 T-cell ALLs and 23 acute myeloid leukemias (AMLs)), investigated during an 8-year period at a single center. The supervised learning algorithm k-nearest neighbor was utilized to build gene expression predictors that could classify the ALLs/AMLs according to clinical

Expression of somatostatin receptor subtypes 2 and 4 in human benign prostatic hyperplasia and prostatic cancer.

BACKGROUND: The presence of receptor subtypes for the inhibitory peptide somatostatin in prostatic tissue has been a controversial issue with conflicting reports. To elucidate whether prostatic epithelial cells express mRNA for somatostatin receptor (SSTR) subtype 2 and 4, we have investigated the localization of SSTR2 and SSTR4 transcripts in prostatic tissues by in situ hybridization. METHODS: N

A population-based investigation of the autoantibody profile in mothers of children with atrioventricular block.

The objective of the study was to investigate the antigen specificity and occurrence of individual autoantibodies in mothers of children diagnosed with atrioventricular (AV) block in a nation-wide setting. Patients with AV block detected before 15 years of age were identified using national quality registries as well as a network of pediatric and adult cardiologists and rheumatologists at the six

Bruton's tyrosine kinase (Btk): function, regulation, and transformation with special emphasis on the PH domain.

Bruton's agammaglobulinemia tyrosine kinase (Btk) is a cytoplasmic tyrosine kinase important in B-lymphocyte development, differentiation, and signaling. Btk is a member of the Tec family of kinases. Mutations in the Btk gene lead to X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (Xid) in mice. Activation of Btk triggers a cascade of signaling events that culminates in t

Age Assessment of Unaccompanied Minors in Sweden and the Rights of Children

Flyktingströmmen 2015 medförde en stor ökning av antalet asylsökande till Sverige, varav många anförde att de var ensamkommande minderåriga. Inte sällan ifrågasatte myndigheterna sökandenas åldrar, vilket medförde ett behov av åldersbedömningar. Regeringen gav då i uppdrag att skyndsamt utveckla och påbörja medicinska åldersbedömningar, och en metod för detta utvecklades hastigt. Enbart under 2017In 2015, Sweden saw a large influx of asylum-seekers into the country, many of whom claimed to be unaccompanied minor. Without personal documents to attest their age, the authorities often doubted these claims of minority, prompting a need for age assessment. The government called for medical age assessments to be developed and introduced and a method for medical age assessment was hastily develop