Early-type stars observed in the ESO UVES Paranal Observatory Project - V. Time-variable interstellar absorption

The structure and properties of the diffuse interstellar medium (ISM) on small scales, sub-au to 1 pc, are poorly understood. We compare interstellar absorption-lines, observed towards a selection of O- and B-type stars at two or more epochs, to search for variations over time caused by the transverse motion of each star combined with changes in the structure in the foreground ISM. Two sets of data were used: 83 VLT- UVES spectra with approximately 6 yr between epochs and 21 McDonald observatory 2.7m telescope echelle spectra with 6 - 20 yr between epochs, over a range of scales from 0 - 360 au. The interstellar absorption-lines observed at the two epochs were subtracted and searched for any residuals due to changes in the foreground ISM. Of the 104 sightlines investigated with typically five or more components in Na I D, possible temporal variation was identified in five UVES spectra (six components), in Ca II, Ca I and/or Na I absorption-lines. The variations detected range from 7\% to a factor of 3.6 in column density. No variation was found in any other interstellar species. Most sightlines show no variation, with 3{\sigma} upper limits to changes of the order 0.1 - 0.3 dex in Ca II and Na I. These variations observed imply that fine-scale structure is present in the ISM, but at the resolution available in this study, is not very common at visible wavelengths. A determination of the electron densities and lower limits to the total number density of a sample of the sightlines implies that there is no striking difference between these parameters in sightlines with, and sightlines without, varying components.

SN 2009ib: a Type II-P supernova with an unusually long plateau

We present optical and near-infrared photometry and spectroscopy of SN 2009ib, a Type II-P supernova in NGC 1559. This object has moderate brightness, similar to those of the intermediate-luminosity SNe 2008in and 2009N. Its plateau phase is unusually long, lasting for about 130 d after explosion. The spectra are similar to those of the subluminous SN 2002gd, with moderate expansion velocities. We estimate the Ni-56 mass produced as 0.046 +/- A 0.015 M-aS (TM). We determine the distance to SN 2009ib using both the expanding photosphere method (EPM) and the standard candle method. We also apply EPM to SN 1986L, a Type II-P SN that exploded in the same galaxy. Combining the results of different methods, we conclude the distance to NGC 1559 as D = 19.8 +/- A 3.0 Mpc. We examine archival, pre-explosion images of the field taken with the Hubble Space Telescope, and find a faint source at the position of the SN, which has a yellow colour [(V - I)(0) = 0.85 mag]. Assuming it is a single star, we estimate its initial mass as M-ZAMS = 20 M-aS (TM). We also examine the possibility, that instead of the yellow source the progenitor of SN 2009ib is a red supergiant star too faint to be detected. In this case, we estimate the upper limit for the initial zero-age main sequence (ZAMS) mass of the progenitor to be similar to 14-17 M-aS (TM). In addition, we infer the physical properties of the progenitor at the explosion via hydrodynamical modelling of the observables, and estimate the total energy as similar to 0.55 x 10(51) erg, the pre-explosion radius as similar to 400 R-aS (TM), and the ejected envelope mass as similar to 15 M-aS (TM), which implies that the mass of the progenitor before explosion was similar to 16.5-17 M-aS (TM).

Multidimensional rehabilitation programmes for adult cancer survivors

Background: Multidimensional rehabilitation programmes (MDRPs) have developed in response to the growing number of people living with and surviving cancer. MDRPs comprise a physical component and a psychosocial component. Studies of the effectiveness of these programmes have not been reviewed and synthesised.

Objectives: To conduct a systematic review of studies examining the effectiveness of MDRPs in terms of maintaining or improving the physical and psychosocial well-being of adult cancer survivors.

Search methods: We conducted electronic searches in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL and PsychINFO up to February 2012.

Selection criteria: Selection criteria focused on randomised controlled trials (RCTs) of multidimensional interventions for adult cancer survivors. Interventions had to include a physical component and a psychosocial component and to have been carried out on two or more occasions following completion of primary cancer treatment. Outcomes had to be assessed using validated measures of physical health and psychosocial well-being. Non-English language papers were included.

Data collection and analysis: Pairs of review authors independently selected trials, rated their methodological quality and extracted relevant data. Although meta-analyses of primary and secondary endpoints were planned there was a high level of study heterogeneity and only one common outcome measure (SF-36) could be statistically synthesised. In addition, we conducted a narrative analysis of interventions, particularly in terms of inspecting and identifying intervention components, grouping or categorising interventions and examining potential common links and outcomes.

Main results: Twelve RCTs (comprising 1669 participants) met the eligibility criteria. We judged five studies to have a moderate risk of bias and assessed the remaining seven as having a high risk of bias. It was possible to include SF-36 physical health component scores from five studies in a meta-analysis. Participating in a MDRP was associated with an increase in SF-36 physical health component scores (mean difference (MD) 2.22, 95% confidence interval (CI) 0.12 to 4.31, P = 0.04). The findings from the narrative analysis suggested that MDRPs with a single domain or outcome focus appeared to be more successful than programmes with multiple aims. In addition, programmes that comprised participants with different types of cancer compared to cancer site-specific programmes were more likely to show positive improvements in physical outcomes. The most effective mode of service delivery appeared to be face-to-face contact supplemented with at least one follow-up telephone call. There was no evidence to indicate that MDRPs which lasted longer than six months improved outcomes beyond the level attained at six months. In addition, there was no evidence to suggest that services were more effective if they were delivered by a particular type of health professional.

Authors' conclusions: There is some evidence to support the effectiveness of brief, focused MDRPs for cancer survivors. Rigorous and methodologically sound clinical trials that include an economic analysis are required.

A study protocol for a pilot randomised trial of a structured education programme for the self-management of type 2 diabetes for adults with intellectual disabilities

BACKGROUND: The need for structured education programmes for type 2 diabetes is a high priority for many governments around the world. One such national education programme in the United Kingdom is the DESMOND Programme, which has been shown to be robust and effective for patients in general. However, these programmes are not generally targeted to people with intellectual disabilities (ID), and robust evidence on their effects for this population is lacking. We have adapted the DESMOND Programme for people with ID and type 2 diabetes to produce an amended programme known as DESMOND-ID. This protocol is for a pilot trial to determine whether a large-scale randomised trial is feasible, to test if DESMOND-ID is more effective than usual care in adults with ID for self-management of their type 2 diabetes, in particular as a means to reduce glycated haemoglobin (Hb1Ac), improve psychological wellbeing and quality of life and promote a healthier lifestyle. This protocol describes the rationale, methods, proposed analysis plan and organisational and administrative details.

METHODS/DESIGN: This trial is a two arm, individually randomised, pilot trial for adults with ID and type 2 diabetes, and their family and/or paid carers. It compares the DESMOND-ID programme with usual care. Approximately 36 adults with mild to moderate ID will be recruited from three countries in the United Kingdom. Family and/or paid carers may also participate in the study. Participants will be randomly assigned to one of two conditions using a secure computerised system with robust allocation concealment. A range of data will be collected from the adults with ID (biomedical, psychosocial and self-management strategies) and from their carers. Focus groups with all the participants will assess the acceptability of the intervention and the trial.

DISCUSSION: The lack of appropriate structured education programmes and educational materials for this population leads to secondary health conditions and may lead to premature deaths. There are significant benefits to be gained globally, if structured education programmes are adapted and shown to be successful for people with ID and other cognitive impairments.

TRIAL REGISTRATION: Registered with International Standard Randomised Controlled Trial (identifier: ISRCTN93185560 ) on 10 November 2014.

Adaptor protein-2 sigma subunit mutations causing familial hypocalciuric hypercalcaemia type 3 (FHH3) demonstrate genotype-phenotype correlations, codon bias and dominant-negative effects

The adaptor protein-2 sigma subunit (AP2sigma;2) is pivotal for clathrin-mediated endocytosis of plasma membrane constituents such as the calcium-sensing receptor (CaSR). Mutations of the AP2sigma;2 Arg15 residue result in familial hypocalciuric hypercalcaemia type 3 (FHH3), a disorder of extracellular calcium (Ca<inf>o</inf>²⁺) homeostasis. To elucidate the role of AP2sigma;2 in Ca<inf>o</inf>²⁺ regulation, we investigated 65 FHH probands, without other FHH-associated mutations, for AP2sigma;2 mutations, characterized their functional consequences and investigated the genetic mechanisms leading to FHH3. AP2sigma;2 mutations were identified in 17 probands, comprising 5 Arg15Cys, 4 Arg15His and 8 Arg15Leu mutations. A genotype-phenotype correlation was observed with the Arg15Leu mutation leading to marked hypercalcaemia. FHH3 probands harboured additional phenotypes such as cognitive dysfunction. All three FHH3-causing AP2sigma;2 mutations impaired CaSR signal transduction in a dominant-negative manner. Mutational bias was observed at the AP2sigma;2 Arg15 residue as other predicted missense substitutions (Arg15Gly, Arg15Pro and Arg15Ser), which also caused CaSR loss-of-function, were not detected in FHH probands, and these mutations were found to reduce the numbers of CaSR-expressing cells. FHH3 probands had significantly greater serum calcium (sCa) and magnesium (sMg) concentrations with reduced urinary calcium to creatinine clearance ratios (CCCR) in comparison with FHH1 probands with CaSR mutations, and a calculated index of sCa × sMg/100 × CCCR, which was ≥ 5.0, had a diagnostic sensitivity and specificity of 83 and 86%, respectively, for FHH3. Thus, our studies demonstrate AP2sigma;2 mutations to result in a more severe FHH phenotype with genotype-phenotype correlations, and a dominant-negative mechanism of action with mutational bias at the Arg15 residue.

The white dwarf's carbon fraction as a secondary parameter of Type Ia supernovae

Context. Binary stellar evolution calculations predict thatChandrasekhar-mass carbon/oxygen white dwarfs (WDs) show a radiallyvarying profile for the composition with a carbon depleted core. Manyrecent multi-dimensional simulations of Type Ia supernovae (SNe Ia),however, assume the progenitor WD has a homogeneous chemicalcomposition.
Aims: In this work, we explore the impact ofdifferent initial carbon profiles of the progenitor WD on the explosionphase and on synthetic observables in the Chandrasekhar-mass delayeddetonation model. Spectra and light curves are compared to observationsto judge the validity of the model.
Methods: The explosion phaseis simulated using the finite volume supernova code Leafs, which isextended to treat different compositions of the progenitor WD. Thesynthetic observables are computed with the Monte Carlo radiativetransfer code Artis. Results: Differences in binding energies ofcarbon and oxygen lead to a lower nuclear energy release for carbondepleted material; thus, the burning fronts that develop are weaker andthe total nuclear energy release is smaller. For otherwise identicalconditions, carbon depleted models produce less 56Ni.Comparing different models with similar 56Ni yields showslower kinetic energies in the ejecta for carbon depleted models, butonly small differences in velocity distributions and line velocities inspectra. The light curve width-luminosity relation (WLR) obtained formodels with differing carbon depletion is roughly perpendicular to theobserved WLR, hence the carbon mass fraction is probably only asecondary parameter in the family of SNe Ia.
Tables 3 and 4 are available in electronic form at http://www.aanda.org

SN 2011fu: a type IIb supernova with a luminous double-peaked light curve

We present optical and near-infrared observations of the type IIb supernova (SN) 2011fu from a few days to similar to 300 d after explosion. The SN presents a double-peaked light curve (LC) similar to that of SN 1993J, although more luminous and with a longer cooling phase after the primary peak. The spectral evolution is also similar to SN 1993J's, with hydrogen dominating the spectra to similar to 40 d, then helium gaining strength, and nebular emission lines appearing from similar to 60 d post-explosion. The velocities derived from the P-Cygni absorptions are overall similar to those of other type IIb SNe. We have found a strong similarity between the oxygen and magnesium line profiles at late times, which suggests that these lines are forming at the same location within the ejecta. The hydrodynamical modelling of the pseudo-bolometric LC and the observed photospheric velocities suggest that SN 2011fu was the explosion of an extended star (R similar to 450 R-circle dot), in which 1.3 x 10(51) erg of kinetic energy were released and 0.15 M-circle dot of Ni-56 were synthesized. In addition, a better reproduction of the observed early pseudo-bolometric LC is achieved if a more massive H-rich envelope than for other type IIb SNe is considered (0.3 M-circle dot). The hydrodynamical modelling of the LC and the comparison of our late-time spectra with nebular spectral models for type IIb SNe, point to a progenitor for SN 2011fu with a Zero Age Main Sequence (ZAMS) mass of 13-18 M-circle dot.

EARLY RADIO AND X-RAY OBSERVATIONS OF THE YOUNGEST NEARBY TYPE Ia SUPERNOVA PTF 11kly (SN 2011fe)

On 2011 August 24 (UT) the Palomar Transient Factory (PTF) discovered PTF11kly (SN 2011fe), the youngest and most nearby Type Ia supernova (SN Ia) in decades. We followed this event up in the radio (centimeter and millimeter bands) and X-ray bands, starting about a day after the estimated explosion time. We present our analysis of the radio and X-ray observations, yielding the tightest constraints yet placed on the pre-explosion mass-loss rate from the progenitor system of this supernova. We find a robust limit of from sensitive X-ray non-detections, as well as a similar limit from radio data, which depends, however, on assumptions about microphysical parameters. We discuss our results in the context of single-degenerate models for SNe Ia and find that our observations modestly disfavor symbiotic progenitor models involving a red giant donor, but cannot constrain systems accreting from main-sequence or sub-giant stars, including the popular supersoft channel. In view of the proximity of PTF11kly and the sensitivity of our prompt observations, we would have to wait for a long time (a decade or longer) in order to more meaningfully probe the circumstellar matter of SNe Ia.

SN 2011dh: DISCOVERY OF A TYPE IIb SUPERNOVA FROM A COMPACT PROGENITOR IN THE NEARBY GALAXY M51

On 2011 May 31 UT a supernova (SN) exploded in the nearby galaxy M51 (the Whirlpool Galaxy). We discovered this event using small telescopes equipped with CCD cameras and also detected it with the Palomar Transient Factory survey, rapidly confirming it to be a Type II SN. Here, we present multi-color ultraviolet through infrared photometry which is used to calculate the bolometric luminosity and a series of spectra. Our early-time observations indicate that SN 2011dh resulted from the explosion of a relatively compact progenitor star. Rapid shock-breakout cooling leads to relatively low temperatures in early-time spectra, compared to explosions of red supergiant stars, as well as a rapid early light curve decline. Optical spectra of SN 2011dh are dominated by H lines out to day 10 after explosion, after which He I lines develop. This SN is likely a member of the cIIb (compact IIb) class, with progenitor radius larger than that of SN 2008ax and smaller than the eIIb (extended IIb) SN 1993J progenitor. Our data imply that the object identified in pre-explosion Hubble Space Telescope images at the SN location is possibly a companion to the progenitor or a blended source, and not the progenitor star itself, as its radius (~1013 cm) would be highly inconsistent with constraints from our post-explosion spectra.

HPV prevalence and type-distribution in cervical cancer and premalignant lesions of the cervix: A population-based study from Northern Ireland

Assessment of Human papillomavirus (HPV) prevalence and genotype distribution is important for monitoring the impact of prophylactic HPV vaccination. This study aimed to demonstrate the HPV genotypes predominating in pre-malignant and cervical cancers in Northern Ireland (NI) before the vaccination campaign has effect. Formalin fixed paraffin embedded tissue blocks from 2,303 women aged 16-93 years throughout NI were collated between April 2011 and February 2013. HPV DNA was amplified by PCR and HPV genotyping undertaken using the Roche^® linear array detection kit. In total, 1,241 out of 1,830 eligible samples (68.0%) tested positive for HPV, with the majority of these [1,181/1,830 (64.5%)] having high-risk (HR) HPV infection; 37.4% were positive for HPV-16 (n=684) and 5.1% for HPV-18 (n=93). HPV type-specific prevalence was 48.1%, 65.9%, 81.3%, 92.2%, and 64.3% among cervical intraepithelial neoplasias (CIN) Grades I-III, squamous cell carcinomas (SCC) and adenocarcinoma (AC) cases, respectively. Most SCC cases (81.3%) had only one HPV genotype detected and almost a third (32.0%) of all cervical pathologies were HPV negative including 51.9% of CIN I (n=283), 34.1% CIN II (n=145), 18.7% of CIN III (n=146), 7.8% of SCC (n=5), and 35.7% of AC (n=5) cases. This study provides important baseline data for monitoring the effect of HPV vaccination in NI and for comparison with other UK regions. The coverage of other HR-HPV genotypes apart from 16 and 18, including HPV-45, 31, 39, and 52, and the potential for cross protection, should be considered when considering future polyvalent vaccines.

Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial

BACKGROUND: Long-term hormone therapy has been the standard of care for advanced prostate cancer since the 1940s. STAMPEDE is a randomised controlled trial using a multiarm, multistage platform design. It recruits men with high-risk, locally advanced, metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy. We report primary survival results for three research comparisons testing the addition of zoledronic acid, docetaxel, or their combination to standard of care versus standard of care alone.

METHODS: Standard of care was hormone therapy for at least 2 years; radiotherapy was encouraged for men with N0M0 disease to November, 2011, then mandated; radiotherapy was optional for men with node-positive non-metastatic (N+M0) disease. Stratified randomisation (via minimisation) allocated men 2:1:1:1 to standard of care only (SOC-only; control), standard of care plus zoledronic acid (SOC + ZA), standard of care plus docetaxel (SOC + Doc), or standard of care with both zoledronic acid and docetaxel (SOC + ZA + Doc). Zoledronic acid (4 mg) was given for six 3-weekly cycles, then 4-weekly until 2 years, and docetaxel (75 mg/m(2)) for six 3-weekly cycles with prednisolone 10 mg daily. There was no blinding to treatment allocation. The primary outcome measure was overall survival. Pairwise comparisons of research versus control had 90% power at 2·5% one-sided α for hazard ratio (HR) 0·75, requiring roughly 400 control arm deaths. Statistical analyses were undertaken with standard log-rank-type methods for time-to-event data, with hazard ratios (HRs) and 95% CIs derived from adjusted Cox models. This trial is registered at ClinicalTrials.gov (NCT00268476) and ControlledTrials.com (ISRCTN78818544).

FINDINGS: 2962 men were randomly assigned to four groups between Oct 5, 2005, and March 31, 2013. Median age was 65 years (IQR 60-71). 1817 (61%) men had M+ disease, 448 (15%) had N+/X M0, and 697 (24%) had N0M0. 165 (6%) men were previously treated with local therapy, and median prostate-specific antigen was 65 ng/mL (IQR 23-184). Median follow-up was 43 months (IQR 30-60). There were 415 deaths in the control group (347 [84%] prostate cancer). Median overall survival was 71 months (IQR 32 to not reached) for SOC-only, not reached (32 to not reached) for SOC + ZA (HR 0·94, 95% CI 0·79-1·11; p=0·450), 81 months (41 to not reached) for SOC + Doc (0·78, 0·66-0·93; p=0·006), and 76 months (39 to not reached) for SOC + ZA + Doc (0·82, 0·69-0·97; p=0·022). There was no evidence of heterogeneity in treatment effect (for any of the treatments) across prespecified subsets. Grade 3-5 adverse events were reported for 399 (32%) patients receiving SOC, 197 (32%) receiving SOC + ZA, 288 (52%) receiving SOC + Doc, and 269 (52%) receiving SOC + ZA + Doc.

INTERPRETATION: Zoledronic acid showed no evidence of survival improvement and should not be part of standard of care for this population. Docetaxel chemotherapy, given at the time of long-term hormone therapy initiation, showed evidence of improved survival accompanied by an increase in adverse events. Docetaxel treatment should become part of standard of care for adequately fit men commencing long-term hormone therapy.

FUNDING: Cancer Research UK, Medical Research Council, Novartis, Sanofi-Aventis, Pfizer, Janssen, Astellas, NIHR Clinical Research Network, Swiss Group for Clinical Cancer Research.

Nuclear magnetic resonance-determined lipoprotein subclasses and carotid intima-media thickness in type 1 diabetes

BACKGROUND: Dyslipidemia has been linked to vascular complications of Type 1 diabetes (T1DM). We investigated the prospective associations of nuclear magnetic resonance-determined lipoprotein subclass profiles (NMR-LSP) and conventional lipid profiles with carotid intima-media thickness (IMT) in T1DM.

METHODS: NMR-LSP and conventional lipids were measured in a subset of Diabetes Control and Complications Trial (DCCT) participants (n = 455) at study entry ('baseline', 1983-89), and were related to carotid IMT determined by ultrasonography during the observational follow-up of the DCCT, the Epidemiology of Diabetes Interventions and Complications (EDIC) study, at EDIC Year 12 (2004-2006). Associations were defined using multiple linear regression stratified by gender, and following adjustment for HbA1c, diabetes duration, body mass index, albuminuria, DCCT randomization group, smoking status, statin use, and ultrasound devices.

RESULTS: In men, significant positive associations were observed between some baseline NMR-subclasses of LDL (total IDL/LDL and large LDL) and common and/or internal carotid IMT, and between conventional total- and LDL-cholesterol and non-HDL-cholesterol and common carotid IMT, at EDIC Year 12; these persisted in adjusted analyses (p < 0.05). Large LDL particles and conventional triglycerides were positively associated with common carotid IMT changes over 12 years (p < 0.05). Inverse associations of mean HDL diameter and large HDL concentrations, and positive associations of small LDL with common and/or internal carotid IMT (all p < 0.05) were found, but did not persist in adjusted analyses. No significant associations were observed in women.

CONCLUSION: NMR-LSP-derived LDL particles, in addition to conventional lipid profiles, may help in identifying men with T1DM at highest risk for vascular disease.

Improving E-Assessment Systems With A focus On Adaptive Feedback And Marking

Institutions involved in the provision of tertiary education across Europe are feeling the pinch. European universities, and other higher education (HE) institutions, must operate in a climate where the pressure of government spending cuts (Garben, 2012) is in stark juxtaposition to the EU’s strategy to drive forward and maintain a growth of student numbers in the sector (eurostat, 2015).

In order to remain competitive, universities and HE institutions are making ever-greater use of electronic assessment (E-Assessment) systems (Chatzigavriil et all, 2015; Ferrell, 2012). These systems are attractive primarily because they offer a cost-effect and scalable approach for assessment. In addition to scalability, they also offer reliability, consistency and impartiality; furthermore, from the perspective of a student they are most popular because they can offer instant feedback (Walet, 2012).

There are disadvantages, though.

First, feedback is often returned to a student immediately on competition of their assessment. While it is possible to disable the instant feedback option (this is often the case during an end of semester exam period when assessment scores must be can be ratified before release), however, this option tends to be a global ‘all on’ or ‘all off’ configuration option which is controlled centrally rather than configurable on a per-assessment basis.

If a formative in-term assessment is to be taken by multiple groups of
students, each at different times, this restriction means that answers to each question will be disclosed to the first group of students undertaking the assessment. As soon as the answers are released “into the wild” the academic integrity of the assessment is lost for subsequent student groups.

Second, the style of feedback provided to a student for each question is often limited to a simple ‘correct’ or ‘incorrect’ indicator. While this type of feedback has its place, it often does not provide a student with enough insight to improve their understanding of a topic that they did not answer correctly.

Most E-Assessment systems boast a wide range of question types including Multiple Choice, Multiple Response, Free Text Entry/Text Matching and Numerical questions. The design of these types of questions is often quite restrictive and formulaic, which has a knock-on effect on the quality of feedback that can be provided in each case.

Multiple Choice Questions (MCQs) are most prevalent as they are the most prescriptive and therefore most the straightforward to mark consistently. They are also the most amenable question types, which allow easy provision of meaningful, relevant feedback to each possible outcome chosen.
Text matching questions tend to be more problematic due to their free text entry nature. Common misspellings or case-sensitivity errors can often be accounted for by the software but they are by no means fool proof, as it is very difficult to predict in advance the range of possible variations on an answer that would be considered worthy of marks by a manual marker of a paper based equivalent of the same question.

Numerical questions are similarly restricted. An answer can be checked for accuracy or whether it is within a certain range of the correct answer, but unless it is a special purpose-built mathematical E-Assessment system the system is unlikely to have computational capability and so cannot, for example, account for “method marks” which are commonly awarded in paper-based marking.

From a pedagogical perspective, the importance of providing useful formative feedback to students at a point in their learning when they can benefit from the feedback and put it to use must not be understated (Grieve et all, 2015; Ferrell, 2012).

In this work, we propose a number of software-based solutions, which will overcome the limitations and inflexibilities of existing E-Assessment systems.