Multiply imputing missing values arising by design in transplant survival data

In this article, we address a missing data problem that occurs in transplant survival studies. Recipients of organ transplants are followed up from transplantation and their survival times recorded, together with various explanatory variables. Due to differences in data collection procedures in different centers or over time, a particular explanatory variable (or set of variables) may only be recorded for certain recipients, which results in this variable being missing for a substantial number of records in the data. The variable may also turn out to be an important predictor of survival and so it is important to handle this missing‐by‐design problem appropriately. Consensus in the literature is to handle this problem with complete case analysis, as the missing data are assumed to arise under an appropriate missing at random mechanism that gives consistent estimates here. Specifically, the missing values can reasonably be assumed not to be related to the survival time. In this article, we investigate the potential for multiple imputation to handle this problem in a relevant study on survival after kidney transplantation, and show that it comprehensively outperforms complete case analysis on a range of measures. This is a particularly important finding in the medical context as imputing large amounts of missing data is often viewed with scepticism

Escalas de marginalidad y huellas de procesos entrelazados : lo ambiental, lo económico y lo demográfico en El Central, Departamento de San Martín, Mendoza

El distrito rural El Central, en el Departamento de San Martín, Mendoza, se presenta como un lugar con marginalidad social y desarticulación territorial. Se ubica cerca del río Mendoza,en el oasis norte y a 60 km. de la capital provincial. En su territorio y en su comunidad hay huellas de otras épocas, que motivaron a indagar sobre los orígenes de esta prolongada situación de marginalidad, con pocas perspectivas de crecimiento. Se presenta una síntesis de los procesos que se entrelazan dando origen a la situación actual, en lo demográfico, lo económico y lo ambiental. Se utiliza información surgida de diferentes fuentes: resultados de proyectos anteriores; una encuesta tipo censo realizada en forma conjunta entre el equipo de investigación, pobladores locales y estudiantes, documentos históricos e institucionales disponibles en El Central.“El Central" is a rural district located in the department of San Martin, Mendoza,which presents itself as socially marginal and territorially disjointed. It is located next to the Mendoza River, 60 km away from the capital city. There are traces of other times in its territory and community which motivated us to find out the origins of this prolonged marginal situation with few prospects of growth. A synthesis of the intertwining processes is presented, giving rise to the current situation considering demographic, economic and environmental dimensions. We use information from different sources: results of previous projects, a census survey conducted jointly by the research team, local interviews, local inhabitants and students, historical and institutional documents available in “El Central".Fil: Molina, Gladys. Universidad Nacional de Cuyo. Facultad de Filosofía y Letras. Instituto de GeografíaFil: Schilan, Rosa . Universidad Nacional de Cuyo. Facultad de Filosofía y Letras. Instituto de GeografíaFil: Ortega, Laura. CONICET. INCIHUSA (Instituto de Ciencias Sociales, Humanas y Ambientales)Fil: Schmidt, Margarita. Universidad Nacional de Cuyo. Facultad de Filosofía y Letras. Instituto de GeografíaFil: Riba, Laura. Universidad Nacional de Cuyo. Facultad de Filosofía y Letras. Instituto de GeografíaFil: Urra Collett, Claudio. Universidad Nacional de Cuyo. Facultad de Filosofía y Letras. Instituto de Geografí

Incidence of adult Huntington's disease in the UK: a UK-based primary care study and a systematic review.

OBJECTIVES: The prevalence of Huntington's disease (HD) recorded in the UK primary care records has increased twofold between 1990 and 2010. This investigation was undertaken to assess whether this might be due to an increased incidence. We have also undertaken a systematic review of published estimates of the incidence of HD. SETTING: Incident patients with a new diagnosis of HD were identified from the primary care records of the Clinical Practice Research Datalink (CPRD). The systematic review included all published estimates of the incidence of HD in defined populations. PARTICIPANTS: A total of 393 incident cases of HD were identified from the CPRD database between 1990 and 2010 from a total population of 9,282,126 persons. PRIMARY AND SECONDARY OUTCOME MEASURES: The incidence of HD per million person-years was estimated. From the systematic review, the extent of heterogeneity of published estimates of the incidence of HD was examined using the I(2) statistic. RESULTS: The data showed that the incidence of HD has remained constant between 1990 and 2010 with an overall rate of 7.2 (95% CI 6.5 to 7.9) per million person-years. The systematic review identified 14 independent estimates of incidence with substantial heterogeneity and consistently lower rates reported in studies from East Asia compared with those from Australia, North America and some--though not all--those from Europe. Differences in incidence estimates did not appear to be explained solely by differences in case ascertainment or diagnostic methods. CONCLUSIONS: The rise in the prevalence of diagnosed HD in the UK, between 1990 and 2010, cannot be attributed to an increase in incidence. Globally, estimates of the incidence of HD show evidence of substantial heterogeneity with consistently lower rates in East Asia and parts of Europe. Modifiers may play an important role in determining the vulnerability of different populations to expansions of the HD allele

A mechanistically and operationally simple route to metal-N-heterocyclic carbene (NHC) Complexes

We gratefully acknowledge VLAIO (SBO project CO2PERATE), King Saud University (Distinguished Scientist Fellowship Program) and King Abdullah University of Science and Technology for support. The Special Research Fund (BOF) of Ghent University is also acknowledged (Doctoral Scholarship to N.V.T.). COST action (CA15106-CHAOS) is thanked for mobility support to N.V.T. Umicore AG is acknowledged for generous gifts of materials.We have been puzzled by the involvement of weak organic and inorganic bases in the synthesis of metal‐N‐heterocyclic carbene (NHC) complexes. Such bases are insufficiently strong to permit the presumed required deprotonation of the azolium salt (the carbene precursor) prior to metal binding. Experimental and computational studies provide support for a base‐assisted concerted process that does not require free NHC formation. The synthetic protocol was found applicable to a number of Transition Metal‐ and Main Group‐centered NHC compounds and could become the synthetic route of choice to form M‐NHC bonds.PostprintPeer reviewe

Out of the box: how bees orient in an ambiguous environment

Dittmar L, Stürzl W, Jetzschke S, Mertes M, Boeddeker N. Out of the box: how bees orient in an ambiguous environment. Animal Behaviour. 2014;89:13-21.How do bees employ multiple visual cues for homing? They could either combine the available cues using a view-based computational mechanism or pick one cue. We tested these strategies by training honeybees, Apis mellifera carnica, and bumblebees, Bombus terrestris, to locate food in one of the four corners of a box-shaped flight arena, providing multiple and also ambiguous cues. In tests, bees confused the diagonally opposite corners, which looked the same from the inside of the box owing to its rectangular shape and because these corners carried the same local colour cues. These 'rotational errors' indicate that the bees did not use compass information inferred from the geomagnetic field under our experimental conditions. When we then swapped cues between corners, bees preferred corners that had local cues similar to the trained corner, even when the geometric relations were incorrect. Apparently, they relied on views, a finding that we corroborated by computer simulations in which we assumed that bees try to match a memorized view of the goal location with the current view when they return to the box. However, when extra visual cues outside the box were provided, bees were able to resolve the ambiguity and locate the correct corner. We show that this performance cannot be explained by view matching from inside the box. Indeed, the bees adapted their behaviour and actively acquired information by leaving the arena and flying towards the cues outside the box. From there they re-entered the arena at the correct corner, now ignoring local cues that previously dominated their choices. All individuals of both species came up with this new behavioural strategy for solving the problem provided by the local ambiguity within the box. Thus both species seemed to be solving the ambiguous task by using their route memory, which is always available during their natural foraging behaviour. (C) 2014 The Association for the Study of Animal Behaviour. Published by Elsevier Ltd. All rights reserved

The Hope and Adaptation Scale (HAS): establishing face and content validity

Purpose: To develop and test the face and content validity of a scale that assesses an individual’s adaptation and expression of hope to a life changing events, disease or trauma. Method: The Hope and Adaptation Scale was developed and tested across three stages. Stage 1 involved the use of a review of literature to conceptually map the tool. Stage 2 required exploratory investigations of the questionnaire by members of an expert panel. Stage 3 assessed the construct validity of the resulting scale. Results: Through the processes of Stage 1 and 2, the tool was developed and reduced to a 3-item scale that assessed a spectrum of hope-related responses and a spectrum of adaptation-related responses. Stage 3 identified fifteen independent health care professionals who assessed the scale. The content validity index of the resultant scale was 0.6 that was above the required level to be acceptable. The hope spectrum responses scored the highest content validity ratio (0.73). Discussion: The proposed scale appears to have face and content validity for application to a various number of events, disease or trauma experiences. Further testing of the scale is required for application in specific population groups

Assessment of ibrutinib plus rituximab in front-line CLL (FLAIR trial): study protocol for a phase III randomised controlled trial

Background Treatment of chronic lymphocytic leukaemia (CLL) has seen a substantial improvement over the last few years. Combination immunochemotherapy, such as fludarabine, cyclophosphamide and rituximab (FCR), is now standard first-line therapy. However, the majority of patients relapse and require further therapy, and so new, effective, targeted therapies that improve remission rates, reduce relapses, and have fewer side effects, are required. The FLAIR trial will assess whether ibrutinib plus rituximab (IR) is superior to FCR in terms of progression-free survival (PFS). Methods/design FLAIR is a phase III, multicentre, randomised, controlled, open, parallel-group trial in patients with previously untreated CLL. A total of 754 participants will be randomised on a 1:1 basis to receive standard therapy with FCR or IR. Participants randomised to FCR will receive a maximum of six 28-day treatment cycles. Participants randomised to IR will receive six 28-day cycles of rituximab, and ibrutinib taken daily for 6 years until minimal residual disease (MRD) negativity has been recorded for the same amount of time as it took to become MRD negative, or until disease progression. The primary endpoint is PFS according to the International Workshop on CLL (IWCLL) criteria. Secondary endpoints include: overall survival; proportion of participants with undetectable MRD; response to therapy by IWCLL criteria; safety and toxicity; health-related quality of life (QoL); and cost-effectiveness. Discussion The trial aims to provide evidence for the future first-line treatment of CLL patients by assessing whether IR is superior to FCR in terms of PFS, and whether toxicity rates are favourable. Trial registration ISRCTN01844152. Registered on 8 August 2014, EudraCT number 2013-001944-76. Registered on 26 April 2013

GA101 (obinutuzumab) monocLonal Antibody as Consolidation Therapy In CLL (GALACTIC) trial: study protocol for a phase II/III randomised controlled trial

Background: Chronic lymphocytic leukaemia (CLL) is the most common adult leukaemia. Achieving minimal residual disease (MRD) negativity in CLL is an independent predictor of survival even with a variety of different treatment approaches and regardless of the line of therapy. Methods/design: GA101 (obinutuzumab) monocLonal Antibody as Consolidation Therapy In CLL (GALACTIC) is a seamless phase II/III, multi-centre, randomised, controlled, open, parallel-group trial for patients with CLL who have recently responded to chemotherapy. Participants will be randomised to receive either obinutuzumab (GA-101) consolidation or no treatment (as is standard). The phase II trial will assess safety and short-term efficacy in order to advise on continuation to a phase III trial. The primary objective for phase III is to assess the effect of consolidation therapy on progression-free survival (PFS). One hundred eighty-eight participants are planned to be recruited from forty research centres in the United Kingdom. Discussion: There is evidence that achieving MRD eradication with alemtuzumab consolidation is associated with improvements in survival and time to progression. This trial will assess whether obinutuzumab is safe in a consolidation setting and effective at eradicating MRD and improving PFS. Trial registration: ISRCTN, 64035629. Registered on 12 January 2015. EudraCT, 2014-000880-42. Registered on 12 November 2014