Reconstructing the Social Fabric amid On-going Violence: Attitudes toward Reconciliation and Structural Transformation in Colombia

Given the increase of reconciliation processes initiated amid on-going violence, this study focuses on community reconciliation and its relation to structural transformation, or social reconstruction through reforming unjust institutions and practices that facilitate protracted violent conflict. Drawing lessons from the Caribbean coast of Colombia, mixed method analyses include eight in-depth interviews and 184 surveys. Four key dimensions of reconciliation – truth, justice, mercy, peace – are examined. In the interviews, participants prioritize reconstructing the truth and bringing perpetrators to justice as essential aspects of reconciliation. Notions of mercy and forgiveness are less apparent. For the participants, sustainable peace is dependent on structural transformation to improve livelihoods. These data, however, do not indicate how this understanding of reconciliation may relate to individual participation in reconciliation processes. Complementing the qualitative data, quantitative analyses identify some broad patterns that relate to participation in reconciliation events. Compared to those who did not participate, individuals who engaged in reconciliation initiatives report higher levels of personal experience with violence, live alongside demobilized paramilitaries, are more engaged in civic life, and express greater preference for structural transformation. The paper concludes with policy implications that integrate reconciliation and structural transformation to deepen efforts to rebuild the social fabric amid violence.

SN 2010ay is a Luminous and Broad-lined Type Ic Supernova within a Low-metallicity Host Galaxy

We report on our serendipitous pre-discovery detection and follow-up observations of the broad-lined Type Ic supernova (SN Ic) 2010ay at z = 0.067 imaged by the Pan-STARRS1 3π survey just ~4 days after explosion. The supernova (SN) had a peak luminosity, MR ≈ -20.2 mag, significantly more luminous than known GRB-SNe and one of the most luminous SNe Ib/c ever discovered. The absorption velocity of SN 2010ay is v Si ≈ 19 × 103 km s-1 at ~40 days after explosion, 2-5 times higher than other broad-lined SNe and similar to the GRB-SN 2010bh at comparable epochs. Moreover, the velocity declines ~2 times slower than other SNe Ic-BL and GRB-SNe. Assuming that the optical emission is powered by radioactive decay, the peak magnitude implies the synthesis of an unusually large mass of 56Ni, M Ni = 0.9 M ⊙. Applying scaling relations to the light curve, we estimate a total ejecta mass, M ej ≈ 4.7 M ⊙, and total kinetic energy, EK ≈ 11 × 1051 erg. The ratio of M Ni to M ej is ~2 times as large for SN 2010ay as typical GRB-SNe and may suggest an additional energy reservoir. The metallicity (log (O/H)PP04 + 12 = 8.19) of the explosion site within the host galaxy places SN 2010ay in the low-metallicity regime populated by GRB-SNe, and ~0.5(0.2) dex lower than that typically measured for the host environments of normal (broad-lined) SNe Ic. We constrain any gamma-ray emission with E γ ~ 1048 erg. We therefore rule out the association of a relativistic outflow like those that accompanied SN 1998bw and traditional long-duration gamma-ray bursts (GRBs), but we place less-stringent constraints on a weak afterglow like that seen from XRF 060218. If this SN did not harbor a GRB, these observations challenge the importance of progenitor metallicity for the production of relativistic ejecta and suggest that other parameters also play a key role.

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.

Systematic review of tools to measure outcomes for young children with autism spectrum disorder

BACKGROUND: The needs of children with autism spectrum disorder (ASD) are complex and this is reflected in the number and diversity of outcomes assessed and measurement tools used to collect evidence about children's progress. Relevant outcomes include improvement in core ASD impairments, such as communication, social awareness, sensory sensitivities and repetitiveness; skills such as social functioning and play; participation outcomes such as social inclusion; and parent and family impact.

OBJECTIVES: To examine the measurement properties of tools used to measure progress and outcomes in children with ASD up to the age of 6 years. To identify outcome areas regarded as important by people with ASD and parents.

METHODS: The MeASURe (Measurement in Autism Spectrum disorder Under Review) research collaboration included ASD experts and review methodologists. We undertook systematic review of tools used in ASD early intervention and observational studies from 1992 to 2013; systematic review, using the COSMIN checklist (Consensus-based Standards for the selection of health Measurement Instruments) of papers addressing the measurement properties of identified tools in children with ASD; and synthesis of evidence and gaps. The review design and process was informed throughout by consultation with stakeholders including parents, young people with ASD, clinicians and researchers.

RESULTS: The conceptual framework developed for the review was drawn from the International Classification of Functioning, Disability and Health, including the domains 'Impairments', 'Activity Level Indicators', 'Participation', and 'Family Measures'. In review 1, 10,154 papers were sifted - 3091 by full text - and data extracted from 184; in total, 131 tools were identified, excluding observational coding, study-specific measures and those not in English. In review 2, 2665 papers were sifted and data concerning measurement properties of 57 (43%) tools were extracted from 128 papers. Evidence for the measurement properties of the reviewed tools was combined with information about their accessibility and presentation. Twelve tools were identified as having the strongest supporting evidence, the majority measuring autism characteristics and problem behaviour. The patchy evidence and limited scope of outcomes measured mean these tools do not constitute a 'recommended battery' for use. In particular, there is little evidence that the identified tools would be good at detecting change in intervention studies. The obvious gaps in available outcome measurement include well-being and participation outcomes for children, and family quality-of-life outcomes, domains particularly valued by our informants (young people with ASD and parents).

CONCLUSIONS: This is the first systematic review of the quality and appropriateness of tools designed to monitor progress and outcomes of young children with ASD. Although it was not possible to recommend fully robust tools at this stage, the review consolidates what is known about the field and will act as a benchmark for future developments. With input from parents and other stakeholders, recommendations are made about priority targets for research.

FUTURE WORK: Priorities include development of a tool to measure child quality of life in ASD, and validation of a potential primary outcome tool for trials of early social communication intervention.

STUDY REGISTRATION: This study is registered as PROSPERO CRD42012002223.

FUNDING: The National Institute for Health Research Health Technology Assessment programme.