Chemical vapor deposition and infiltration for the production of tungsten fiber reinforced tungsten composite material

Contribution submission to the conference Regensburg 2016Chemical vapor deposition and infiltration for the productionof tungsten fiber reinforced tungsten composite material —∙Martin Aumann1, Jan Willem Coenen1, Hanns Gietl2, TillHoeschen2, Johann Riesch2, Klaus Schmid2, Rudolf Neu2, andChristian Linsmeier1 — 1Forschungszentrum Juelich GmbH, Institutfür Energie- und Klimaforschung, 52425 Juelich — 2Max-Planck-Institut für Plasmaphysik, 85748 GarchingDue to its high melting point, high corrosion resistance and its preferableproperties in terms of hydrogen retention, tungsten is a promisingcandidate in future nuclear fusion devices. However, the mechanicalbehavior of tungsten is crucial, as it is inherently brittle at room temperature.As possibility to overcome this brittleness, a composite materialcan be formed, which shows pseudo-ductility and therefore avoidscatastrophic failure of the material. A possibility to produce such aWf/W-composite is chemical vapor deposition and chemical vapor infiltration,where tungsten is deposited on small tungsten wires throughthe reaction of WF6 and H2. With ongoing infiltration time, pores areformed between the fibers, which decrease in size through the chemicalreaction. For better process understanding, a pore model was established,which solves the mass balance inside the pore and the resultingpore diameter simultaneously. It shows a significant difference in diameterfor longer infiltration times. This behavior shall be proved inexperiments with an experimental pore, which is similar to the simulatedone. Furthermore also kinetic investigations on the chemicalsurface reaction are carried out to increase the process understanding.Part: MMType: Vortrag;TalkTopic: Transport (Diffusion, Leitfähigkeit,Wärme)/ Transport (Diffusion,conductivity, heat)Email: [email protected]

Dim light, sleep tight, and wake up bright:Sleep optimization in athletes by means of light regulation

Despite an elevated recovery need, research indicates that athletes often exhibit relatively poor sleep. Timing and consolidation of sleep is driven by the circadian system, which requires periodic light–dark exposure for stable entrainment to the 24-hour day, but is often disturbed due to underexposure to light in the morning (e.g. low-level indoor lighting) and overexposure to light in the evening (e.g. environmental and screen-light). This study examined whether combining fixed sleep schedules with light regulation leads to more consolidated sleep. Morning light exposure was increased using light-emitting goggles, whereas evening light exposure was reduced using amber-lens glasses. Using a within-subject crossover design, twenty-six athletes (14 female, 12 male) were randomly assigned to start the intervention with the light-regulation-week or the no light-regulation-week. Sleep was monitored by means of sleep diaries and actigraphy. Due to low protocol adherence regarding the fixed sleep-wake schedules, two datasets were constructed; one including athletes who kept a strict sleep-wake schedule (N = 8), and one that also included athletes with a more lenient sleep-wake schedule (N = 25). In case of a lenient sleep-wake schedule, light regulation improved self-reported sleep onset latency (Δ SOL = 8 min). This effect was stronger (Δ SOL = 17 min) and complemented by enhanced subjective sleep quality in case of a strict sleep-wake schedule. None of the actigraphy-based estimates differed significantly between conditions. To conclude, light regulation may be considered a potentially effective strategy to improve subjective sleep, but less obtrusive methods should be explored to increase protocol compliance.</p

Cognitive and neurological outcome of patients in the Dutch pyridoxine-dependent epilepsy (PDE-ALDH7A1) cohort, a cross- sectional study

Item does not contain fulltextBACKGROUND: Pyridoxine monotherapy in PDE-ALDH7A1 often results in adequate seizure control, but neurodevelopmental outcome varies. Detailed long-term neurological outcome is unknown. Here we present the cognitive and neurological features of the Dutch PDE-ALDH7A1 cohort. METHODS: Neurological outcome was assessed in 24 patients (age 1-26 years); classified as normal, complex minor neurological dysfunction (complex MND) or abnormal. Intelligence quotient (IQ) was derived from standardized IQ tests with five severity levels of intellectual disability (ID). MRI's and treatments were assessed. RESULTS: Ten patients (42%) showed unremarkable neurological examination, 11 (46%) complex MND, and 3 (12%) cerebral palsy (CP). Minor coordination problems were identified in 17 (71%), fine motor disability in 11 (46%), posture/muscle tone deviancies in 11 (46%) and abnormal reflexes in 8 (33%). Six patients (25%) had an IQ > 85, 7 (29%) borderline, 7 (29%) mild, 3 (13%) moderate, and 1 severe ID. Cerebral ventriculomegaly on MRI was progressive in 11. Three patients showed normal neurologic exam, IQ, and MRI. Eleven patients were treated with pyridoxine only and 13 by additional lysine reduction therapy (LRT). LRT started at age <3 years demonstrated beneficial effect on IQ results in 3 patients. DISCUSSION: Complex MND and CP occurred more frequently in PDE-ALDH7A1 (46% and 12%) than in general population (7% and 0.2%, Peters et al., 2011, Schaefer et al., 2008). Twenty-five percent had a normal IQ. Although LRT shows potential to improve outcomes, data are heterogeneous in small patient numbers. More research with longer follow-up via the International PDE Registry (www.pdeonline.org) is needed

The effects of new life-prolonging drugs for metastatic castration-resistant prostate cancer (mCRPC) patients in a real-world population

Item does not contain fulltextBACKGROUND: In 2004 docetaxel was the first life-prolonging drug (LPD) registered for metastatic castration-resistant prostate cancer (mCRPC) patients. Between 2011 and 2014 new LPDs for mCRPC (cabazitaxel, abiraterone, enzalutamide, and radium-223) were introduced in the Netherlands. The objective of this study is to assess the impact of the introduction of new LPDs on treatment patterns and overall survival (OS) over time. PATIENTS AND METHODS: CRPC patients diagnosed in the years 2010-2016 in the observational, retrospective CAPRI registry (20 hospitals) were included and followed up to 2018. Two subgroups were analyzed: treatment-naïve patients (subgroup 1, n = 3600) and post-docetaxel patients (subgroup 2, n = 1355). RESULTS: In both subgroups, the use of any LPD increased: from 57% (2010-2011) to 69% (2014-2015) in subgroup 1 and from 65% (2011-2012) to 79% (2015-2016) in subgroup 2. Chemotherapy as first mCRPC-treatment (i.e., docetaxel) and first post-docetaxel treatment (i.e., cabazitaxel or docetaxel rechallenge) decreased (46-29% and 20-9% in subgroup 1 and 2, respectively), while the use of androgen-receptor targeting treatments (ART) increased from 11% to 39% and 46% to 64% in subgroup 1 and 2, respectively. In subgroup 1, median OS (mOS) from diagnosis CRPC increased from 28.5 months to 31.0 months (p = 0.196). In subgroup 2, mOS from progression on docetaxel increased from 7.9 months to 12.5 months (p < 0.001). After multiple imputations of missing values, in multivariable cox-regression analysis with known prognostic parameters, the treatment period was independent significant for OS in subgroup 1 (2014-2015 vs. 2010-2011 with HR 0.749, p < 0.001) and subgroup 2 (2015-2016 vs. 2011-2012 with HR 0.811, p = 0.037). CONCLUSION: Since 2010, a larger proportion of mCRPC patients was treated with LPDs, which was related to an increased mOS

Novel associations for hypothyroidism include known autoimmune risk loci

Hypothyroidism is the most common thyroid disorder, affecting about 5% of the general population. Here we present the first large genome-wide association study of hypothyroidism, in 2,564 cases and 24,448 controls from the customer base of 23andMe, Inc., a personal genetics company. We identify four genome-wide significant associations, two of which are well known to be involved with a large spectrum of autoimmune diseases: rs6679677 near _PTPN22_ and rs3184504 in _SH2B3_ (p-values 3.5e-13 and 3.0e-11, respectively). We also report associations with rs4915077 near _VAV3_ (p-value 8.3e-11), another gene involved in immune function, and rs965513 near _FOXE1_ (p-value 3.1e-14). Of these, the association with _PTPN22_ confirms a recent small candidate gene study, and _FOXE1_ was previously known to be associated with thyroid-stimulating hormone (TSH) levels. Although _SH2B3_ has been previously linked with a number of autoimmune diseases, this is the first report of its association with thyroid disease. The _VAV3_ association is novel. These results suggest heterogeneity in the genetic etiology of hypothyroidism, implicating genes involved in both autoimmune disorders and thyroid function. Using a genetic risk profile score based on the top association from each of the four genome-wide significant regions in our study, the relative risk between the highest and lowest deciles of genetic risk is 2.1

A replication study confirms the association of TNFSF4 (OX40L) polymorphisms with systemic sclerosis in a large European cohort

&lt;p&gt;&lt;b&gt;Objectives&lt;/b&gt; The aim of this study was to confirm the influence of TNFSF4 polymorphisms on systemic sclerosis (SSc) susceptibility and phenotypic features.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods&lt;/b&gt; A total of 8 European populations of Caucasian ancestry were included, comprising 3014 patients with SSc and 3125 healthy controls. Four genetic variants of TNFSF4 gene promoter (rs1234314, rs844644, rs844648 and rs12039904) were selected as genetic markers.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results&lt;/b&gt; A pooled analysis revealed the association of rs1234314 and rs12039904 polymorphisms with SSc (OR 1.15, 95% CI 1.02 to 1.31; OR 1.18, 95% CI 1.08 to 1.29, respectively). Significant association of the four tested variants with patients with limited cutaneous SSc (lcSSc) was revealed (rs1234314 OR 1.22, 95% CI 1.07 to 1.38; rs844644 OR 0.91, 95% CI 0.83 to 0.99; rs844648 OR 1.10, 95% CI 1.01 to 1.20 and rs12039904 OR 1.20, 95% CI 1.09 to 1.33). Association of rs1234314, rs844648 and rs12039904 minor alleles with patients positive for anti-centromere antibodies (ACA) remained significant (OR 1.23, 95% CI 1.10 to 1.37; OR 1.12, 95% CI 1.01 to 1.25; OR 1.22, 95% CI 1.07 to 1.38, respectively). Haplotype analysis confirmed a protective haplotype associated with SSc, lcSSc and ACA positive subgroups (OR 0.88, 95% CI 0.82 to 0.96; OR 0.88, 95% CI 0.80 to 0.96; OR 0.86, 95% CI 0.77 to 0.97, respectively) and revealed a new risk haplotype associated with the same groups of patients (OR 1.14, 95% CI 1.03 to 1.26; OR 1.20, 95% CI 1.08 to 1.35; OR 1.23, 95% CI 1.07 to 1.42, respectively).&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions&lt;/b&gt; The data confirm the influence of TNFSF4 polymorphisms in SSc genetic susceptibility, especially in subsets of patients positive for lcSSc and ACA.&lt;/p&gt

Influence of patient symptoms and physical findings on general practitioners' treatment of respiratory tract infections: a direct observation study

BACKGROUND: The high rate of antibiotic prescriptions general practitioners (GPs) make for respiratory tract infections (RTI) are often explained by non-medical reasons e.g. an effort to meet patient expectations. Additionally, it is known that GPs to some extent believe in the necessity of antibiotic treatment in patients with assumed bacterial infections and therefore attempt to distinguish between viral and bacterial infections by history taking and physical examination. The influence of patient complaints and physical examination findings on GPs' prescribing behaviour was mostly investigated by indirect methods such as questionnaires. METHODS: Direct, structured observation during a winter "cough an cold period" in 30 (single handed) general practices. All 273 patients with symptoms of RTI (age above 14, median 37 years, 51% female) were included. RESULTS: The most frequent diagnoses were 'uncomplicated upper RTI/common cold' (43%) followed by 'bronchitis' (26%). On average, 1.8 (95%-confidence interval (CI): 1.7–2.0) medicines per patient were prescribed (cough-and-cold preparations in 88% of the patients, antibiotics in 49%). Medical predictors of antibiotic prescribing were pathological findings in physical examination such as coated tonsils (odds ratio (OR) 15.4, 95%-CI: 3.6–66.2) and unspecific symptoms like fatigue (OR 3.1, 95%-CI 1.4–6.7), fever (OR 2.2, 95%-CI: 1.1–4.5) and yellow sputum (OR 2.1, 95%-CI: 1.1–4.1). Analysed predictors explained 70% of the variance of antibiotic prescribing (R(2 )= 0,696). Efforts to reduce antibiotic prescribing, e.g. recommendations for self-medication, counselling on home remedies or delayed antibiotic prescribing were rare. CONCLUSIONS: Patient complaints and pathological results in physical examination were strong predictors of antibiotic prescribing. Efforts to reduce antibiotic prescribing should account for GPs' beliefs in those (non evidence based) predictors. The method of direct observation was shown to be accepted both by patients and GPs and offered detailed insights into the GP-patient-interaction

Third-line Life-prolonging Drug Treatment in a Real-world Metastatic Castration-resistant Prostate Cancer Population:Results from the Dutch Castration-resistant Prostate Cancer Registry

Third-line life-prolonging drugs (LPDs) might not be appropriate for all metastatic castration-resistant prostate cancer patients. We developed a prognostic model and identified a high-risk subgroup in which no meaningful benefit from third-line LPDs is derived in clinical practice