Guidelines for time-to-event end-point definitions in adjuvant randomised trials for patients with localised colon cancer: Results of the DATECAN initiative.

BACKGROUND: The variability of definitions for time-to-event (TTE) end-points impacts the conclusions of randomised clinical trials (RCTs). The Definition for the Assessment of Time-to-event Endpoints in CANcer (DATECAN) initiative aims to provide consensus definitions for TTE end-points used in RCTs. Here, we formulate guidelines for adjuvant colon cancer RCTs. METHODS: We performed a literature review to identify TTE end-points and events included in their definition in RCT publications. Then, a consensus was reached among a panel of international experts, using a formal modified Delphi method, with 2 rounds of questionnaires and an in-person meeting. RESULTS: Twenty-four experts scored 72 events involved in 6 TTE end-points. Consensus was reached for 24%, 57% and 100% events after the first round, second round and in-person meeting. For RCTs not using overall survival as their primary end-point, the experts recommend using disease-free survival (DFS) rather than recurrence-free survival (RFS) or time to recurrence (TTR) as the primary end-point. The consensus definition of DFS includes all causes of death, second primary colorectal cancers (CRCs), anastomotic relapse and metastatic relapse as an event, but not second primary non-CRCs. Events included in the RFS definition are the same as for DFS with the exception of second primary CRCs. The consensus definition of TTR includes anastomotic or metastatic relapse, death with evidence of recurrence and death from CC cause. CONCLUSION: Standardised definitions of TTE end-points ensure the reproducibility of the end-points between RCTs and facilitate cross-trial comparisons. These definitions should be integrated in standard practice for the design, reporting and interpretation of adjuvant CC RCTs.

Myoscape controls cardiac calcium cycling and contractility via regulation of L-type calcium channel surface expression.

Calcium signalling plays a critical role in the pathogenesis of heart failure. Here we describe a cardiac protein named Myoscape/FAM40B/STRIP2, which directly interacts with the L-type calcium channel. Knockdown of Myoscape in cardiomyocytes decreases calcium transients associated with smaller Ca(2+) amplitudes and a lower diastolic Ca(2+) content. Likewise, L-type calcium channel currents are significantly diminished on Myoscape ablation, and downregulation of Myoscape significantly reduces contractility of cardiomyocytes. Conversely, overexpression of Myoscape increases global Ca(2+) transients and enhances L-type Ca(2+) channel currents, and is sufficient to restore decreased currents in failing cardiomyocytes. In vivo, both Myoscape-depleted morphant zebrafish and Myoscape knockout (KO) mice display impairment of cardiac function progressing to advanced heart failure. Mechanistically, Myoscape-deficient mice show reduced L-type Ca(2+)currents, cell capacity and calcium current densities as a result of diminished LTCC surface expression. Finally, Myoscape expression is reduced in hearts from patients suffering of terminal heart failure, implying a role in human disease.

Patient safety: nursing students' perspectives and the role of nursing education to provide safe care.

BACKGROUND AND AIM: Nurses as the largest group of healthcare providers are in the best position to improve patient safety. In preparing future nurses, nurse educators have an important role in developing the knowledge, skills and attitudes among nursing students related to patient safety. The aim of this study was to explore Iranian nursing students' perspectives regarding patient safety and the role of nursing education in developing their capabilities to provide safe care. METHODS: A purposeful sampling strategy was used to recruit 17 junior and senior nursing students for qualitative, semi-structured interviews. Content analysis of the interview transcripts was conducted to identify several relevant themes. FINDINGS: Three main themes emerged from the data analysis: 'safety as patient comfort', 'not being knowledgeable or experienced enough' and 'being helped to internalise the principles and values of patient safety'. The third theme consisted of two categories: 'adopting a humanistic approach towards patients' and 'practising conscientiously in the workplace'. CONCLUSION: The present study adds insights on how nursing students understand and may be helped to internalise concepts of patient safety within their practice. Nursing education curriculum designers need to go beyond theoretical concepts of patient safety education and devise strategies to increase the application of safety knowledge and competencies in nursing practice.

Use of AFLP and RAPD molecular genetic markers and cytogenetic analysis to explore relationships among taxa of the Patagonian Bromus setifolius complex.

Bromus setifolius var. pictus (Hook) Skottsb., B. setifolius var. setifolius Presl. and B.setifolius var. brevifolius Ness are three native Patagonian taxa in the section Pnigma Dumort of the genus Bromus L. AFLP and RAPD analysis, in conjunction with genetic distance measurements and statistical techniques, revealed variation within this group and indicated that B. setifolius var. brevifolius was closely related to B. setifolius var. pictus, with both taxa being more distantly related to B. setifolius var. setifolius. Cytogenetic analysis confirmed the chromosomal number of B. setifolius var. pictus (2n = 70) and B. setifolius var. setifolius (2n = 28) and showed for the first time that B. setifolius var. brevifolius had 2n = 70. The combination of molecular genetic and cytogenetic evidence supported a species status for two of the three taxa and suggested hypotheses for the evolutionary origin of these complex taxa. Species status was also indicated for B. setifolius var. setifolius. Based on these findings, we suggest that B. setifolius var. pictus be referred to as B. pictus Hook var. pictus, and B. setifolius var brevifolius as B. pictus Hook var brevifolius. The correlation between AFLP diversity and variation in ecological parameters suggested that this marker system could be used to assess breeding progress and to monitor the domestication of Patagonian Bromus species for agronomic use.

Use of AFLP and RAPD molecular genetic markers and cytogenetic analysis to explore relationships among taxa of the Patagonian Bromus setifolius complex

Bromus setifolius var. pictus (Hook) Skottsb., B. setifolius var. setifolius Presl. and B. setifolius var. brevifolius Ness are three native Patagonian taxa in the section Pnigma Dumort of the genus Bromus L. AFLP and RAPD analysis, in conjunction with genetic distance measurements and statistical techniques, revealed variation within this group and indicated that B. setifolius var. brevifolius was closely related to B. setifolius var. pictus, with both taxa being more distantly related to B. setifolius var. setifolius. Cytogenetic analysis confirmed the chromosomal number of B. setifolius var. pictus (2n = 70) and B. setifolius var. setifolius (2n = 28) and showed for the first time that B. setifolius var. brevifolius had 2n = 70. The combination of molecular genetic and cytogenetic evidence supported a species status for two of the three taxa and suggested hypotheses for the evolutionary origin of these complex taxa. Species status was also indicated for B. setifolius var. setifolius. Based on these findings, we suggest that B. setifolius var. pictus be referred to as B. pictus Hook var. pictus, and B. setifolius var brevifolius as B. pictus Hook var brevifolius. The correlation between AFLP diversity and variation in ecological parameters suggested that this marker system could be used to assess breeding progress and to monitor the domestication of Patagonian Bromus species for agronomic use.

Building safer systems by ecological design: using restoration science to develop a medication safety intervention.

BACKGROUND: Experts call for stronger safety cultures and transparent reporting practices to increase medication safety in today's strained healthcare environments. The field of ecological restoration is concerned with the effective, efficient, and sustainable repair and recovery of ecosystems that have been degraded, damaged, or destroyed. A study was undertaken to determine whether the lessons of restoration science can be adapted to the study of medication safety issues. METHODS: Working with 26 practitioners, the principles of good restoration were used to design and pilot an innovative multifaceted medication safety intervention. The intervention included focus groups with practitioners, the construction and administration of a research based medication safety inventory, repeat digital photography of environmental safety issues, and targeted environmental modifications. RESULTS: Participants were most concerned about staff education and the physical environment for medication administration. Ward staff used the research to build a healthy reporting culture, introduce regular discussions of near misses, develop education strategies, redesign delivery and storage processes, and renovate the environment. CONCLUSIONS: Members of a busy hospital ward successfully adapted methods of restoration science to study, redesign, and strengthen medication safety practices and ward safety culture within existing resources. Further research will be conducted to test the merits of restoration science for health care.

Nursing in a technological world: searching for healing communities.

A research dialectic between philosophy of technology and nurses' work in acute care surfaces parallel technological practices that threaten the healing nature of two modern projects: health care and ecological restoration. A metaphor of ecological restoration is used to explore the consequences of denatured health care work for the welfare of patients, families, practitioners, and healing communities. It is argued that in health care systems where the mismatch between treatment options and resources for care steadily grows, the nursing discipline must develop ecological literacy for a technological world.