Statistical analysis plan for the Stroke Oxygen Study (SO₂S): a multi-center randomized controlled trial to assess whether routine oxygen supplementation in the first 72 hours after a stroke improves long-term outcome.

BACKGROUND: The Stroke Oxygen Study (SO₂S) is a multi-center randomized controlled trial of oxygen supplementation in patients with acute stroke. The main hypothesis for the trial is that fixed-dose oxygen treatment during the first 3 days after an acute stroke improves outcome. The secondary hypothesis is that restricting oxygen supplementation to night time only is more effective than continuous supplementation. This paper describes the statistical analysis plan for the study. METHODS AND DESIGN: Patients (n = 8000) are randomized to three groups: (1) continuous oxygen supplementation for 72 hours; (2) nocturnal oxygen supplementation for three nights; and (3) no routine oxygen supplementation. Outcomes are recorded at 7 days, 90 days, 6 months, and 12 months. The primary outcome measure is the modified Rankin scale at 90 days. Data will be analyzed according to the intention-to-treat principle. Methods of statistical analysis are described, including the handling of missing data, the covariates used in adjusted analyses, planned subgroups analyses, and planned sensitivity analyses. TRIAL REGISTRATION: This trial is registered with the ISRCTN register, number ISRCTN52416964 (30 September 2005)

Management of patients with persistent medically unexplained symptoms: a descriptive study

Background: In 2013 the Dutch guideline for management of medically unexplained symptoms (MUS) was published. The aim of this study is to assess medical care for patients with persistent MUS as recorded in their electronic medical records, to investigate if this is in line with the national guideline for persistent MUS and whether there are changes in care over time. Methods: We conducted an observational study of adult primary care patients with MUS. Routinely recorded health care data were extracted from electronic medical records of patients participating in an ongoing randomised controlled trial in 30 general practices in the Netherlands. Data on general practitioners’ (GPs’) management strategies during MUS consultations were collected in a 5-year period for each patient prior. Management strategies were categorised according to the options offered in the Dutch guideline. Changes in management over time were analysed. Results: Data were collected from 1035 MUS consultations (77 patients). Beside history-taking, the most frequently used diagnostic strategies were physical examination (24.5%) and additional investigations by the GP (11.1%). Frequently used therapeutic strategies were prescribing medication (24.6%) and providing explanations (11.2%). As MUS symptoms persisted, GPs adjusted medication, discussed progress and scheduled follow-up appointments more frequently. The least frequently used strategies were exploration of all complaint dimensions (i.e. somatic, cognitive, emotional, behavioural and social) (3.5%) and referral to a psychologist (0.5%) or psychiatrist (0.1%). Conclusions: Management of Dutch GPs is partly in line with the Dutch guideline. Medication was possibly prescribed more frequently than recommended, whereas exploration of all complaint dimensions, shared problem definition and referral to mental health care were used less

Inflammatory and haematological markers in the maternal, umbilical cord and infant circulation in histological chorioamnionitis

BACKGROUND: The relationship between histological chorioamnionitis and haematological and biochemical markers in mothers and infants at delivery, and in infants postnatally, is incompletely characterised. These markers are widely used in the diagnosis of maternal and neonatal infection. Our objective was to investigate the effects of histological chorioamnionitis (HCA) on haematological and biochemical inflammatory markers in mothers and infants at delivery, and in infants post-delivery. METHODS: Two hundred and forty seven mothers, delivering 325 infants, were recruited at the only tertiary perinatal centre in Western Australia. Placentae were assessed for evidence of HCA using a semi-quantitative scoring system. Maternal high sensitivity C-reactive protein (hsCRP), procalcitonin, and umbilical cord hsCRP, procalcitonin, white cell count and absolute neutrophil count were measured at delivery. In infants where sepsis was clinically suspected, postnatal CRP, white cell count and absolute neutrophil count were measured up to 48 hours of age. The effect of HCA on maternal, cord and neonatal markers was evaluated by multivariable regression analysis. RESULTS: The median gestational age was 34 weeks and HCA was present in 26 of 247 (10.5%) placentae. Mothers whose pregnancies were complicated by HCA had higher hsCRP (median 26 (range 2-107) versus 5.6 (0-108) mg/L; P<0.001). Histological chorioamnionitis was associated with higher umbilical cord hsCRP (75(th) percentile 2.91 mg/L (range 0-63.9) versus 75(th) percentile 0 mg/L (0-45.6); P<0.001) and procalcitonin (median 0.293 (range 0.05-27.37) versus median 0.064 (range 0.01-5.24) ug/L; P<0.001), with a sustained increase in neonatal absolute neutrophil count (median 4.5 (0.1-26.4)x10(9)/L versus 3.0 (0.1-17.8)x10(9)/L), and CRP up to 48 hours post-partum (median 10 versus 6.5 mg/L) (P<0.05 for each). CONCLUSION: Histological chorioamnionitis is associated with modest systemic inflammation in maternal and cord blood. These systemic changes may increase postnatally, potentially undermining their utility in the diagnosis of early-onset neonatal infection

Glucuronidation by UGT1A1 Is the Dominant Pathway of the Metabolic Disposition of Belinostat in Liver Cancer Patients

10.1371/journal.pone.0054522PLoS ONE81

Quantitative Microscopy Reveals Centromeric Chromatin Stability, Size, and Cell Cycle Mechanisms to Maintain Centromere Homeostasis

The deposited item is a book chapter and is part of the series "Centromeres and Kinetochores" published by the publisher Springer Verlag. The deposited book chapter is a post-print version and has been submitted to peer reviewing. There is no public supplementary material available for this publication. This publication hasn't any creative commons license associated.Centromeres are chromatin domains specified by nucleosomes containing the histone H3 variant, CENP-A. This unique centromeric structure is at the heart of a strong self-templating epigenetic mechanism that renders centromeres heritable. We review how specific quantitative microscopy approaches have contributed to the determination of the copy number, architecture, size, and dynamics of centromeric chromatin and its associated centromere complex and kinetochore. These efforts revealed that the key to long-term centromere maintenance is the slow turnover of CENP-A nucleosomes, a critical size of the chromatin domain and its cell cycle-coupled replication. These features come together to maintain homeostasis of a chromatin locus that directs its own epigenetic inheritance and facilitates the assembly of the mitotic kinetochore.There are no funders and sponsors indicated explicitly in the document.info:eu-repo/semantics/publishedVersio

Bulk ion heating with ICRH in JET DT plasmas

Reactor relevant ICRH scenarios have been assessed during DT experiments on the JET tokamak using H mode divertor discharges with ITER-like shapes and safety factors. Deuterium minority heating in tritium plasmas was demonstrated for the first time. For 9% deuterium, an ICRH power of 6 MW gave 1.66 MW of fusion power from reactions between suprathermal deuterons and thermal tritons. The Q value of the steady state discharge reached 0.22 for the length of the RF flat-top (2.7 s), corresponding to three plasma energy replacement times. The Doppler broadened neutron spectrum showed a deuteron energy of 125 keV, which was optimum for fusion and close to the critical energy. Thus, strong bulk ion heating was obtained at the same time as high fusion efficiency. Deuterium fractions around 20% produced the strongest ion heating together with a strong reduction of the suprathermal deuteron tail. The ELMs had low amplitude and high frequency and each ELM transported less plasma energy content than the 1% required by ITER. The energy confinement time, on the ITERH97-P scale, was 0.90, which is sufficient for ignition in ITER. 3He minority heating, in approximately 50:50 D:T plasmas with up to 10% 3He, also demonstrated strong bulk ion heating. Central ion temperatures up to 13 keV were achieved, together with central electron temperatures up to 12 keV. The normalized H mode confinement time was 0.95. Second harmonic tritium heating produced energetic tritons above the critical energy. This scheme heats the electrons in JET, unlike in ITER where the lower power density will allow mainly ion heating. The inverted scenario of tritium minority ICRH in a deuterium plasma was demonstrated as a successful heating method producing both suprathermal neutrons and bulk ion heating. Theoretical calculations of the DT reactivity mostly give excellent agreement with the measured reaction rates