Patients with rare endocrine conditions have corresponding views on unmet needs in clinical research

Purpose European Reference Network on Rare Endocrine Conditions' (Endo-ERN) mission is to reduce and ultimately abolish inequalities in care for patients with rare endocrine conditions in Europe. This study assesses which themes related to rare endocrine conditions are prioritized by patients for clinical research. Methods A survey was developed, translated into 22 different European languages, and distributed to patients with rare endocrine conditions. Patients were asked to give priority scores to listed prespecified topics: fertility, heritability, tiredness, daily medicine intake, sleep quality, physical discomfort, and ability to work, partake in social life, and sports. They were also asked to suggest further important areas for research in open fields. Results After data cleaning, 1378 survey responses were analyzed. Most responses were received from Northern (47%) and Western Europeans (39%), while Southern (11%) and Eastern Europe (2%) were underrepresented. Respondents were most interested in research concerning ability to participate in social life and work. Patients suggested key areas to work: long-term side effects of medical treatments and quality of life. Some priorities differed between disease groups, both for prespecified and open topics and reflected aspects of patients' individual conditions. Conclusions With this large survey, Endo-ERN gained insight into patients' unmet needs in scientific research. Patients prioritized research on ability to work and participation in social activities, though needs differ between the disease groups. Clinical experts should incorporate the results of this survey into the design of future studies on rare endocrine conditions. We aim to utilize these results in designing patient-reported outcome measures for the disease areas covered by Endo-ERN

Comparison of baseline drinking practices, knowledge, and attitudes of adult s residing in communities taking part in the FAS prevention study in South Africa

Foetal Alcohol Syndrome (FAS) has been identified as among the most serious consequences associated with hazardous and harmful drinking in the Western Cape province, South Africa. Community surveys were conducted in two wine growing regions in this province to assess drinking behaviour, guide interventions and serve as a baseline for assessing the impact of population-level interventions. As part of a cross-sectional comparative study interviews were conducted with 384 and 209 randomly selected adults in the prevention (PC) and comparison communities (CC) respectively. Over 80% of respondents resided in urban areas, except inthe CC, where 61% of males resided on farms. Symptoms of hazardous or harmful drinking were reported by 16.0% of females and 32.5% of males in the PC, while 19.3% of females and 56.2% of males in the CC reported such drinking. Over two-thirds of respondents indicated that it was equally harmful for a woman to drink during any of the trimesters of pregnancy, but more than 30% of the women interviewed had never had a health worker speak to them about the effects of drinking during pregnancy. Over 10% had never heard of fetal alcohol syndrome. The findings reinforce the need for interventions to address hazardous/harmful use of alcohol inboth communities and also to address gaps in knowledge regarding the effects of drinking during pregnancy.Key Words: Alcohol, epidemiology, pregnancy, South Afric

Total evidence phylogeny of platyrrhine primates and a comparison of undated and tip-dating approaches

There have been multiple published phylogenetic analyses of platyrrhine primates (New World monkeys) using both morphological and molecular data, but relatively few that have integrated both types of data into a total evidence approach. Here, we present phylogenetic analyses of Recent and fossil platyrrhines, based on a total evidence dataset of 418 morphological characters and 10.2 kilobases of DNA sequence data from 17 nuclear genes taken from previous studies, using undated and tip-dating approaches in a Bayesian framework. We compare the results of these analyses with molecular scaffold analyses using maximum parsimony and Bayesian approaches, and we use a formal information theoretic approach to identify unstable taxa. After a posteriori pruning of unstable taxa, the undated and tip-dating topologies appear congruent with recent molecular analyses and support largely similar relationships, with strong support for Stirtonia as a stem alouattine, Neosaimiri as a stem saimirine, Cebupithecia as a stem pitheciine, and Lagonimico as a stem callitrichid. Both analyses find three Greater Antillean subfossil platyrrhines (Xenothrix, Antillothrix, and Paralouatta) to form a clade that is related to Callicebus, congruent with a single dispersal event by the ancestor of this clade to the Greater Antilles. They also suggest that the fossil Proteropithecia may not be closely related to pitheciines, and that all known platyrrhines older than the Middle Miocene are stem taxa. Notably, the undated analysis found the Early Miocene Panamacebus (currently recognized as the oldest known cebid) to be unstable, and the tip-dating analysis placed it outside crown Platyrrhini. Our tip-dating analysis supports a late Oligocene or earliest Miocene (20.8–27.0 Ma) age for crown Platyrrhini, congruent with recent molecular clock analyses

Black Holes in Modified Gravity (MOG)

The field equations for Scalar-Tensor-Vector-Gravity (STVG) or modified gravity (MOG) have a static, spherically symmetric black hole solution determined by the mass $M$ with two horizons. The strength of the gravitational constant is $G=G_N(1+\alpha)$ where $\alpha$ is a parameter. A regular singularity-free MOG solution is derived using a nonlinear field dynamics for the repulsive gravitational field component and a reasonable physical energy-momentum tensor. The Kruskal-Szekeres completion of the MOG black hole solution is obtained. The Kerr-MOG black hole solution is determined by the mass $M$, the parameter $\alpha$ and the spin angular momentum $J=Ma$. The equations of motion and the stability condition of a test particle orbiting the MOG black hole are derived, and the radius of the black hole photosphere and the shadows cast by the Schwarzschild-MOG and Kerr-MOG black holes are calculated. A traversable wormhole solution is constructed with a throat stabilized by the repulsive component of the gravitational field.Comment: 14 pages, 3 figures. Upgraded version of paper to match published version in European Physics Journal

Gel mobility shift scanning of pectin-inducible promoter from Penicillium griseoroseum reveals the involvement of a CCAAT element in the expression of a polygalacturonase gene

Previous reports have described pgg2, a polygalacturonase-encoding gene of Penicillium griseoroseum, as an attractive model for transcriptional regulation studies, due to its high expression throughout several in vitro growth conditions, even in the presence of non-inducing sugars such as sucrose. A search for regulatory motifs in the 5' upstream regulatory sequence of pgg2 identified a putative CCAAT box that could justify this expression profile. This element, located 270 bp upstream of the translational start codon, was tested as binding target for regulatory proteins. Analysis of a 170 bp promoter fragment by electrophoretic mobility shift assay (EMSA) with nuclear extracts prepared from mycelia grown in pectin-containing culture medium revealed a high mobility complex that was subsequently confirmed by analyzing it with a double-stranded oligonucleotide spanning the CCAAT motif. A substitution in the core sequence for GTAGG partially abolished the formation of specific complexes, showing the involvement of the CCAAT box in the regulation of the polygalacturonase gene studied

A Review of the Theoretical Basis, Effects, and Cost Effectiveness of Online Smoking Cessation Interventions in the Netherlands: A Mixed-Methods Approach

Background: Tobacco smoking is a worldwide public health problem. In 2015, 26.3% of the Dutch population aged 18 years and older smoked, 74.4% of them daily. More and more people have access to the Internet worldwide; approximately 94% of the Dutch population have online access. Internet-based smoking cessation interventions (online cessation interventions) provide an opportunity to tackle the scourge of tobacco. Objective: The goal of this paper was to provide an overview of online cessation interventions in the Netherlands, while exploring their effectivity, cost effectiveness, and theoretical basis. Methods: A mixed-methods approach was used to identify Dutch online cessation interventions, using (1) a scientific literature search, (2) a grey literature search, and (3) expert input. For the scientific literature, the Cochrane review was used and updated by two independent researchers (n=651 identified studies), screening titles, abstracts, and then full-text studies between 2013 and 2016 (CENTRAL, MEDLINE, and EMBASE). For the grey literature, the researchers conducted a Google search (n=100 websites), screening for titles and first pages. Including expert input, this resulted in six interventions identified in the scientific literature and 39 interventions via the grey literature. Extracted data included effectiveness, cost effectiveness, theoretical factors, and behavior change techniques used. Results: Overall, many interventions (45 identified) were offered. Of the 45 that we identified, only six that were included in trials provided data on effectiveness. Four of these were shown to be effective and cost effective. In the scientific literature, 83% (5/6) of these interventions included changing attitudes, providing social support, increasing self-efficacy, motivating smokers to make concrete action plans to prepare their attempts to quit and to cope with challenges, supporting identity change and advising on changing routines, coping, and medication use. In all, 50% (3/6) of the interventions included a reward for abstinence. Interventions identified in the grey literature were less consistent, with inclusion of each theoretical factor ranging from 31% to 67% and of each behavior change technique ranging from 28% to 54%. Conclusions: Although the Internet may provide the opportunity to offer various smoking cessation programs, the user is left bewildered as far as efficacy is concerned, as most of these data are not available nor offered to the smokers. Clear regulations about the effectiveness of these interventions need to be devised to avoid disappointment and failed quitting attempts. Thus, there is a need for policy regulations to regulate the proliferation of these interventions and to foster their quality in the Netherlands.Mir

Health status in non-dystrophic myotonias: close relation with pain and fatigue

To determine self-reported health status in non-dystrophic myotonias (NDM) and its relationship to painful myotonia and fatigue. In a cross-sectional study, 32 NDM patients with chloride and 30 with sodium channelopathies, all off treatment, completed a standardised interview, the fatigue assessment scale (FAS), and the 36-item Short-Form Health Survey (SF-36). Beside formal assessment of pain, assessment of painful or painless myotonia was determined. The domain scores of the SF-36 were compared with Dutch community scores. Apart from the relationship among SF-36 scores and (1) painful myotonia and (2) fatigue, regression analyses in both NDM groups were conducted to determine the strongest determinants of the SF-36 domains general health perception, physical component (PCS) and mental component summary (MCS). All physically oriented SF-36 domains in both NDM groups (P ≤ 0.01) and social functioning in the patients with sodium channelopathies (P = 0.048) were substantially lower relative to the Dutch community scores. The patients with painful myotonia (41.9%) scored substantially (P < 0.05) lower on most SF-36 domains than the patients without painful myotonia (58.1%). Fatigued patients (53.2%) scored substantially lower (P ≤ 0.01) on all SF-36 domains than their non-fatigued counterparts (46.8%). The regression analysis showed that fatigue was the strongest predictor for the general-health perception and painful myotonia for the physical-component summary. None of the patients showed below-norm scores on the domain mental-component summary. The impact of NDM on the physical domains of patients’ health status is substantial, and particularly painful myotonia and fatigue tend to impede their physical functioning