Effort/reward imbalance and sedentary lifestyle: an observational study in a large occupational cohort

Objectives: To investigate the association between effort/reward imbalance (ERI) at work and sedentary lifestyle.

Work stress, smoking status, and smoking intensity: an observational study of 46 190 employees

Study objective: To examine the relation between work stress, as indicated by the job strain model, and the effort-reward imbalance model, and smoking.

Observational and Dynamical Characterization of Main-belt Comet P/2010 R2 (La Sagra)

We present observations of the recently discovered comet-like main-belt object P/2010 R2 (La Sagra) obtained by Pan-STARRS1 and the Faulkes Telescope-North on Haleakala in Hawaii, the University of Hawaii 2.2 m, Gemini-North, and Keck I telescopes on Mauna Kea, the Danish 1.54 m telescope (operated by the MiNDSTEp consortium) at La Silla, and the Isaac Newton Telescope on La Palma. An antisolar dust tail is observed to be present from 2010 August through 2011 February, while a dust trail aligned with the object's orbit plane is also observed from 2010 December through 2011 August. Assuming typical phase darkening behavior, P/La Sagra is seen to increase in brightness by >1 mag between 2010 August and December, suggesting that dust production is ongoing over this period. These results strongly suggest that the observed activity is cometary in nature (i.e., driven by the sublimation of volatile material), and that P/La Sagra is therefore the most recent main-belt comet to be discovered. We find an approximate absolute magnitude for the nucleus of HR = 17.9 ± 0.2 mag, corresponding to a nucleus radius of ~0.7 km, assuming an albedo of p = 0.05. Comparing the observed scattering surface areas of the dust coma to that of the nucleus when P/La Sagra was active, we find dust-to-nucleus area ratios of Ad /AN = 30-60, comparable to those computed for fellow main-belt comets 238P/Read and P/2008 R1 (Garradd), and one to two orders of magnitude larger than for two other main-belt comets (133P/Elst-Pizarro and 176P/LINEAR). Using optical spectroscopy to search for CN emission, we do not detect any conclusive evidence of sublimation products (i.e., gas emission), finding an upper limit CN production rate of Q CN 100 Myr, suggesting that it is likely native to its current location and that its composition is likely representative of other objects in the same region of the main belt, though the relatively close proximity of the 13:6 mean-motion resonance with Jupiter and the (3,-2,-1) three-body mean-motion resonance with Jupiter and Saturn mean that dynamical instability on larger timescales cannot be ruled out.

Breast-feeding and childhood-onset type 1 diabetes:A pooled analysis of individual participant data from 43 observational studies

OBJECTIVE: To investigate if there is a reduced risk of type 1 diabetes in children breastfed or exclusively breastfed by performing a pooled analysis with adjustment for recognized confounders.
RESEARCH DESIGN AND METHODS: Relevant studies were identified from literature searches using MEDLINE, Web of Science, and EMBASE. Authors of relevant studies were asked to provide individual participant data or conduct prespecified analyses. Meta-analysis techniques were used to combine odds ratios (ORs) and investigate heterogeneity between studies.
RESULTS: Data were available from 43 studies including 9,874 patients with type 1 diabetes. Overall, there was a reduction in the risk of diabetes after exclusive breast-feeding for >2 weeks (20 studies; OR = 0.75, 95% CI 0.64-0.88), the association after exclusive breast-feeding for >3 months was weaker (30 studies; OR = 0.87, 95% CI 0.75-1.00), and no association was observed after (nonexclusive) breast-feeding for >2 weeks (28 studies; OR = 0.93, 95% CI 0.81-1.07) or >3 months (29 studies; OR = 0.88, 95% CI 0.78-1.00). These associations were all subject to marked heterogeneity (I(2) = 58, 76, 54, and 68%, respectively). In studies with lower risk of bias, the reduced risk after exclusive breast-feeding for >2 weeks remained (12 studies; OR = 0.86, 95% CI 0.75-0.99), and heterogeneity was reduced (I(2) = 0%). Adjustments for potential confounders altered these estimates very little.
CONCLUSIONS: The pooled analysis suggests weak protective associations between exclusive breast-feeding and type 1 diabetes risk. However, these findings are difficult to interpret because of the marked variation in effect and possible biases (particularly recall bias) inherent in the included studies.

Associations between maternal characteristics and pregnancy-related stress among low-risk mothers: An observational cross-sectional study

Background: Pregnancy is viewed as a major life event and, while the majority of healthy, low-risk women adapt well to pregnancy, there are those whose levels of stress are heightened by the experience.

Objectives: To determine the level of pregnancy-related stress experienced by a group of healthy, low-risk pregnant women and to relate the level of stress with a number of maternal characteristics.

Design: An observational cross-sectional study.

Setting: A large, urban maternity centre in Northern Ireland.

Participants: Of the 306 pregnant women who were invited to participate, 278 provided informed consent and were administered one self-complete questionnaire. Due to the withdrawal criteria, 15 questionnaires were removed from the analysis, resulting in a final sample of 263 healthy, low-risk pregnant women.

Methods: Levels of stress were measured using a self-report measure designed to assess specific worries and concerns relating to pregnancy. Maternal characteristics collected included age, marital status, social status, parity, obstetric history, perceived health status and 'wantedness' for the pregnancy. Regression analysis was undertaken using an ordinary linear regression model.

Results: The mean prenatal distress score in the sample was 15.1 (SD = 7.4; range 0-46). The regression model showed that women who had had previous pregnancies, with or without complications, had significantly lower mean prenatal distress scores than primiparous women (p < 0.01). Women reporting poorer physical health had higher mean prenatal distress scores than those who reported at least average health, while women aged 16-20 experienced a mean increase in the reported prenatal distress score (p < 0.05) in comparison to the reference group of 36 years and over.

Conclusions: This study brings to light the prevalence of pregnancy-related stress within a sample representative of healthy, low-risk women. Current antenatal care is ill-equipped to identify women suffering from high levels of stress; yet a growing body of research evidence links stress with adverse pregnancy outcomes. This study emphasises that healthy, low-risk women experience a range of pregnancy-related stress and identification of stress levels, either through the use of a simple stress measurement tool or through the associated factors identified within this research study, provides valuable data on maternal well-being. (C) 2010 Elsevier Ltd. All rights reserved.

Who makes prescribing decisions in hospital inpatients?:An observational study

Errors involving drug prescriptions are a key target for patient safety initiatives. Recent studies have focused on error rates across different grades of doctors in order to target interventions. However, many prescriptions are not instigated by the doctor who writes them. It is important to clarify how often this occurs in order to interpret these studies and create interventions. This study aimed to provisionally quantify and describe prescriptions where the identity of the decision maker and prescription writer differed.

Observational Constraints on the Catastrophic Disruption Rate of Small Main Belt Asteroids

We have calculated 90% confidence limits on the steady-state rate of catastrophic disruptions of main belt asteroids in terms of the absolute magnitude at which one catastrophic disruption occurs per year  as a function of the post-disruption increase in brightness (Δm) and subsequent brightness decay rate (τ  ). The confidence limits were calculated using the brightest unknown main belt asteroid (V=18.5) detected with the Pan-STARRS1 (Pan-STARRS1) telescope. We measured the Pan-STARRS1’s catastrophic disruption detection efficiency over a 453-day interval using the Pan-STARRS moving object processing system (MOPS) and a simple model for the catastrophic disruption event’s photometric behavior in a small aperture centered on the catastrophic disruption event. We then calculated the  contours in the ranges from  and  encompassing measured values from known cratering and disruption events and our model’s predictions. Our simplistic catastrophic disruption model suggests that  and  which would imply that H_0≳28—strongly inconsistent withH_{0,B2005=23.26±0.02} predicted by Bottke et al. (Bottke, W.F., Durda, D.D., Nesvorný, D., Jedicke, R., Morbidelli, A., Vokrouhlický, D., Levison, H.F. [2005]. Icarus, 179, 63–94.) using purely collisional models. However, if we assume that H_0=H0,B2005 our results constrain , inconsistent with our simplistic impact-generated catastrophic disruption model. We postulate that the solution to the discrepancy is that >99% of main belt catastrophic disruptions in the size range to which this study was sensitive (∼100 m) are not impact-generated, but are instead due to fainter rotational breakups, of which the recent discoveries of disrupted asteroids P/2013 P5 and P/2013 R3 are probable examples. We estimate that current and upcoming asteroid surveys may discover up to 10 catastrophic disruptions/year brighter than V=18.5.

An Observational Study of Blood Concentrations and Kinetics of Methyl- and Propyl-Parabens in Neonates

Purpose: Systemic exposure to parabens in the neonatal population, in particular propyl-parabens (PPB), remains a concern. Blood concentrations and kinetics of methyl-parabens (MPB) and PPB were therefore determined in neonates receiving medicines containing these excipients.

Methods: A multi-centre, non-interventional, observational study of excipient-kinetics in neonates. ‘Dried Blood Spot’ samples were collected opportunistically at the same time as routine samples and the observations modelled using a non-linear mixed effects approach.

Results: A total of 841 blood MPB and PPB concentration data were available for evaluation from 181 pre- and term-neonates. Quantifiable blood concentrations of MPB and PPB were observed in 99% and 49% of patients, and 55% and 25% of all concentrations were above limit of detection (10 ng/ml), respectively. Only MPB data was amenable to modelling. Oral bioavailability was influenced by type of formulation and disposition was best described by a two compartment model with clearance (CL) influenced by post natal age (PNA); CL_{PNA<21 days} 0.57 versus CL_PNA>21days 0.88 L/h.

Conclusions: Daily repeated administration of parabens containing medicines can result in prolonged systemic exposure to the parent compound in neonates. Animal toxicology studies of PPB that specifically address the neonatal period are required before a permitted daily exposure for this age group can be established.

Diagnostic accuracy of loop-mediated isothermal amplification as a near-patient test for meningococcal disease in children: An observational cohort study

Background: Diagnosis of meningococcal disease relies on recognition of clinical signs and symptoms that are notoriously non-specific, variable, and often absent in the early stages of the disease. Loop-mediated isothermal amplification (LAMP) has previously been shown to be fast and effective for the molecular detection of meningococcal DNA in clinical specimens. We aimed to assess the diagnostic accuracy of meningococcal LAMP as a near-patient test in the emergency department.

Methods: For this observational cohort study of diagnostic accuracy, children aged 0-13 years presenting to the emergency department of the Royal Belfast Hospital for Sick Children (Belfast, UK) with suspected meningococcal disease were eligible for inclusion. Patients underwent a standard meningococcal pack of investigations testing for meningococcal disease. Respiratory (nasopharyngeal swab) and blood specimens were collected from patients and tested with near-patient meningococcal LAMP and the results were compared with those obtained by reference laboratory tests (culture and PCR of blood and cerebrospinal fluid).

Findings: Between Nov 1, 2009, and Jan 31, 2012, 161 eligible children presenting at the hospital underwent the meningococcal pack of investigations and were tested for meningococcal disease, of whom 148 consented and were enrolled in the study. Combined testing of respiratory and blood specimens with use of LAMP was accurate (sensitivity 89% [95% CI 72-96], specificity 100% [97-100], positive predictive value 100% [85-100]; negative predictive value 98% [93-99]) and diagnostically useful (positive likelihood ratio 213 [95% CI 13-infinity] and negative likelihood ratio 0·11 [0·04-0·32]). The median time required for near-patient testing from sample to result was 1 h 26 min (IQR 1 h 20 min-1 h 32 min).

Interpretation: Meningococcal LAMP is straightforward enough for use in any hospital with basic laboratory facilities, and near-patient testing with this method is both feasible and effective. By contrast with existing UK National Institute of Health and Care Excellence guidelines, we showed that molecular testing of non-invasive respiratory specimens from children is diagnostically accurate and clinically useful.

Observational Constraints on the Progenitors of Core-Collapse Supernovae: The Case for Missing High-Mass Stars

Over the last 15 years, the supernova community has endeavoured to directly identify progenitor stars for core-collapse supernovae discovered in nearby galaxies. These precursors are often visible as resolved stars in high-resolution images from space-and ground-based telescopes. The discovery rate of progenitor stars is limited by the local supernova rate and the availability and depth of archive images of galaxies, with 18 detections of precursor objects and 27 upper limits. This review compiles these results (from 1999 to 2013) in a distance-limited sample and discusses the implications of the findings. The vast majority of the detections of progenitor stars are of type II-P, II-L, or IIb with one type Ib progenitor system detected and many more upper limits for progenitors of Ibc supernovae (14 in all). The data for these 45 supernovae progenitors illustrate a remarkable deficit of high-luminosity stars above an apparent limit of log L/L-circle dot similar or equal to 5.1 dex. For a typical Salpeter initial mass function, one would expect to have found 13 high-luminosity and high-mass progenitors by now. There is, possibly, only one object in this time-and volume-limited sample that is unambiguously high-mass (the progenitor of SN2009ip) although the nature of that supernovae is still debated. The possible biases due to the influence of circumstellar dust, the luminosity analysis, and sample selection methods are reviewed. It does not appear likely that these can explain the missing high-mass progenitor stars. This review concludes that the community's work to date shows that the observed populations of supernovae in the local Universe are not, on the whole, produced by high-mass (M greater than or similar to 18 M-circle dot) stars. Theoretical explosions of model stars also predict that black hole formation and failed supernovae tend to occur above an initial mass of M similar or equal to 18 M-circle dot. The models also suggest there is no simple single mass division for neutron star or black-hole formation and that there are islands of explodability for stars in the 8-120 M-circle dot range. The observational constraints are quite consistent with the bulk of stars above M similar or equal to 18 M-circle dot collapsing to form black holes with no visible supernovae.

Core Outcomes in Ventilation Trials (COVenT): protocol for a core outcome set using a Delphi survey with a nested randomised trial and observational cohort study

Background
Among clinical trials of interventions that aim to modify time spent on mechanical ventilation for critically ill patients there is considerable inconsistency in chosen outcomes and how they are measured. The Core Outcomes in Ventilation Trials (COVenT) study aims to develop a set of core outcomes for use in future ventilation trials in mechanically ventilated adults and children.

Methods/design
We will use a mixed methods approach that incorporates a randomised trial nested within a Delphi study and a consensus meeting. Additionally, we will conduct an observational cohort study to evaluate uptake of the core outcome set in published studies at 5 and 10 years following core outcome set publication. The three-round online Delphi study will use a list of outcomes that have been reported previously in a review of ventilation trials. The Delphi panel will include a range of stakeholder groups including patient support groups. The panel will be randomised to one of three feedback methods to assess the impact of the feedback mechanism on subsequent ranking of outcomes. A final consensus meeting will be held with stakeholder representatives to review outcomes.

Discussion
The COVenT study aims to develop a core outcome set for ventilation trials in critical care, explore the best Delphi feedback mechanism for achieving consensus and determine if participation increases use of the core outcome set in the long term.

Potentially harmful excipients in neonatal medicines: A pan-European observational study

Objectives We aimed to describe administration of eight potentially harmful excipients of interest (EOI)-parabens, polysorbate 80, propylene glycol, benzoates, saccharin sodium, sorbitol, ethanol and benzalkonium chloride-to hospitalised neonates in Europe and to identify risk factors for exposure. Methods All medicines administered to neonates during 1 day with individual prescription and demographic data were registered in a web-based point prevalence study. Excipients were identified from the Summaries of Product Characteristics. Determinants of EOI administration (geographical region, gestational age (GA), active pharmaceutical ingredient, unit level and hospital teaching status) were identified using multivariable logistical regression analysis. Results Overall 89 neonatal units from 21 countries participated. Altogether 2095 prescriptions for 530 products administered to 726 neonates were recorded. EOI were found in 638 (31%) prescriptions and were administered to 456 (63%) neonates through a relatively small number of products (n=142; 27%). Parabens, found in 71 (13%) products administered to 313 (43%) neonates, were used most frequently. EOI administration varied by geographical region, GA and route of administration. Geographical region remained a significant determinant of the use of parabens, polysorbate 80, propylene glycol and saccharin sodium after adjustment for the potential covariates including anatomical therapeutic chemical class of the active ingredient. Conclusions European neonates receive a number of potentially harmful pharmaceutical excipients. Regional differences in EOI administration suggest that EOI-free products are available and provide the potential for substitution to avoid side effects of some excipients.