Methodological criteria for the assessment of moderators in systematic reviews of randomised controlled trials : a consensus study

Background: Current methodological guidelines provide advice about the assessment of sub-group analysis within RCTs, but do not specify explicit criteria for assessment. Our objective was to provide researchers with a set of criteria that will facilitate the grading of evidence for moderators, in systematic reviews. Method: We developed a set of criteria from methodological manuscripts (n = 18) using snowballing technique, and electronic database searches. Criteria were reviewed by an international Delphi panel (n = 21), comprising authors who have published methodological papers in this area, and researchers who have been active in the study of sub-group analysis in RCTs. We used the Research ANd Development/University of California Los Angeles appropriateness method to assess consensus on the quantitative data. Free responses were coded for consensus and disagreement. In a subsequent round additional criteria were extracted from the Cochrane Reviewers’ Handbook, and the process was repeated. Results: The recommendations are that meta-analysts report both confirmatory and exploratory findings for subgroups analysis. Confirmatory findings must only come from studies in which a specific theory/evidence based apriori statement is made. Exploratory findings may be used to inform future/subsequent trials. However, for inclusion in the meta-analysis of moderators, the following additional criteria should be applied to each study: Baseline factors should be measured prior to randomisation, measurement of baseline factors should be of adequate reliability and validity, and a specific test of the interaction between baseline factors and interventions must be presented. Conclusions: There is consensus from a group of 21 international experts that methodological criteria to assess moderators within systematic reviews of RCTs is both timely and necessary. The consensus from the experts resulted in five criteria divided into two groups when synthesising evidence: confirmatory findings to support hypotheses about moderators and exploratory findings to inform future research. These recommendations are discussed in reference to previous recommendations for evaluating and reporting moderator studies

Seasonal and annual fluxes of nutrients and organic matter from large rivers to the Arctic Ocean and surrounding seas

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Estuaries and Coasts 35 (2012): 369-382, doi:10.1007/s12237-011-9386-6.River inputs of nutrients and organic matter impact the biogeochemistry of arctic estuaries and the Arctic Ocean as a whole, yet there is considerable uncertainty about the magnitude of fluvial fluxes at the pan-arctic scale. Samples from the six largest arctic rivers, with a combined watershed area of 11.3 x 106 km2, have revealed strong seasonal variations in constituent concentrations and fluxes within rivers as well as large differences among the rivers. Specifically, we investigate fluxes of dissolved organic carbon, dissolved organic nitrogen, total dissolved phosphorus, dissolved inorganic nitrogen, nitrate, and silica. This is the first time that seasonal and annual constituent fluxes have been determined using consistent sampling and analytical methods at the pan arctic scale, and consequently provide the best available estimates for constituent flux from land to the Arctic Ocean and surrounding seas. Given the large inputs of river water to the relatively small Arctic Ocean, and the dramatic impacts that climate change is having in the Arctic, it is particularly urgent that we establish the contemporary river fluxes so that we will be able to detect future changes and evaluate the impact of the changes on the biogeochemistry of the receiving coastal and ocean systems.This work was supported by the National Science Foundation through grants OPP-0229302, OPP-0519840, OPP-0732522, and OPP-0732944. Additional support was provided by the U. S. Geological Survey (Yukon River) and the Department of Indian and Northern Affairs (Mackenzie River)

The processing and impact of dissolved riverine nitrogen in the Arctic Ocean

© The Author(s), 2011. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Estuaries and Coasts 35 (2012): 401-415, doi:10.1007/s12237-011-9417-3.Although the Arctic Ocean is the most riverine-influenced of all of the world’s oceans, the importance of terrigenous nutrients in this environment is poorly understood. This study couples estimates of circumpolar riverine nutrient fluxes from the PARTNERS (Pan-Arctic River Transport of Nutrients, Organic Matter, and Suspended Sediments) Project with a regionally configured version of the MIT general circulation model to develop estimates of the distribution and availability of dissolved riverine N in the Arctic Ocean, assess its importance for primary production, and compare these estimates to potential bacterial production fueled by riverine C. Because riverine dissolved organic nitrogen is remineralized slowly, riverine N is available for uptake well into the open ocean. Despite this, we estimate that even when recycling is considered, riverine N may support 0.5–1.5 Tmol C year−1 of primary production, a small proportion of total Arctic Ocean photosynthesis. Rapid uptake of dissolved inorganic nitrogen coupled with relatively high rates of dissolved organic nitrogen regeneration in N-limited nearshore regions, however, leads to potential localized rates of riverine-supported photosynthesis that represent a substantial proportion of nearshore production.Funding for this work was provided through NSFOPP- 0229302 and NSF-OPP-0732985.Support to SET was additionally provided by an NSERC Postdoctoral Fellowship

Hypertrabeculated Left Ventricular Myocardium in Relationship to Myocardial Function and Fibrosis: The Multi-Ethnic Study of Atherosclerosis

This research was supported by contracts N01-HC-95159, N01-HC-95160, N01-HC-95161, N01- HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC- 95168 and N01-HC-95169 from the National Heart, Lung, and Blood Institute, by grants UL1-TR-000040 and UL1-TR-001079 from NCRR, and by a grant from Bayer Healthcare for the use of gadolinium contrast agent. G.C. is supported by the National Institute for Health Research Rare Diseases Translational Research Collaboration (NIHR RD-TRC). J.C.M. is directly and indirectly supported by the University College London Hospitals NIHR Biomedical Research Centre and Biomedical Research Unit at Barts Hospital, respectively

Moderation in management research: What, why, when and how.

Many theories in management, psychology, and other disciplines rely on moderating variables: those which affect the strength or nature of the relationship between two other variables. Despite the near-ubiquitous nature of such effects, the methods for testing and interpreting them are not always well understood. This article introduces the concept of moderation and describes how moderator effects are tested and interpreted for a series of model types, beginning with straightforward two-way interactions with Normal outcomes, moving to three-way and curvilinear interactions, and then to models with non-Normal outcomes including binary logistic regression and Poisson regression. In particular, methods of interpreting and probing these latter model types, such as simple slope analysis and slope difference tests, are described. It then gives answers to twelve frequently asked questions about testing and interpreting moderator effects

Cognitive and environmental predictors of early literacy skills

Not all young children benefit from book exposure in preschool age. It is claimed that the ability to hold information in mind (short-term memory), to ignore distraction (inhibition), and to focus attention and stay focused (sustained attention) may have a moderating effect on children’s reactions to the home literacy environment. In a group of 228 junior kindergarten children with a native Dutch background, with a mean age of 54.29 months (SD = 2.12 months), we explored therefore the relationship between book exposure, cognitive control and early literacy skills. Parents filled in a HLE questionnaire (book sharing frequency and an author recognition checklist as indicator of parental leisure reading habits), and children completed several tests in individual sessions with the researcher (a book-cover recognition test, PPVT, letter knowledge test, the subtests categories and patterns of the SON, and cognitive control measures namely digit span of the KABC, a peg tapping task and sustained attention of the ANT). Main findings were: (1) Children’s storybook knowledge mediated the relationship between home literacy environment and literacy skills. (2) Both vocabulary and letter knowledge were predicted by book exposure. (3) Short-term memory predicted vocabulary over and above book exposure. (4) None of the cognitive control mechanisms moderated the beneficial effects of book exposure

Implementing a quality improvement programme in palliative care in care homes: a qualitative study

<p>Abstract</p> <p>Background</p> <p>An increasing number of older people reach the end of life in care homes. The aim of this study is to explore the perceived benefits of, and barriers to, implementation of the Gold Standards Framework for Care Homes (GSFCH), a quality improvement programme in palliative care.</p> <p>Methods</p> <p>Nine care homes involved in the GSFCH took part. We conducted semi-structured interviews with nine care home managers, eight nurses, nine care assistants, eleven residents and seven of their family members. We used the Framework approach to qualitative analysis. The analysis was deductive based on the key tasks of the GSFCH, the 7Cs: communication, coordination, control of symptoms, continuity, continued learning, carer support, and care of the dying. This enabled us to consider benefits of, and barriers to, individual components of the programme, as well as of the programme as a whole.</p> <p>Results</p> <p>Perceived benefits of the GSFCH included: improved symptom control and team communication; finding helpful external support and expertise; increasing staff confidence; fostering residents' choice; and boosting the reputation of the home. Perceived barriers included: increased paperwork; lack of knowledge and understanding of end of life care; costs; and gaining the cooperation of GPs. Many of the tools and tasks in the GSFCH focus on improving communication. Participants described effective communication within the homes, and with external providers such as general practitioners and specialists in palliative care. However, many had experienced problems with general practitioners. Although staff described the benefits of supportive care registers, coding predicted stage of illness and advance care planning, which included improved communication, some felt the need for more experience of using these, and there were concerns about discussing death.</p> <p>Conclusions</p> <p>Most of the barriers described by participants are relevant to other interventions to improve end of life care in care homes. There is a need to investigate the impact of quality improvement programmes in care homes, such as the GSFCH, on a wider range of outcomes for residents and their families, and to monitor the sustainability of any resulting improvements. It is also important to explore the impact of the different components of these complex interventions.</p

Is there an orthographic boost for ambiguous words during their processing?

The present study explores the issue of why ambiguous words are recognized faster than unambiguous ones during word recognition. To this end we contrasted two different hypotheses: the semantic feedback hypothesis (Hino and Lupker in J Exp Psychol Hum Percept Perform 22:1331-1356, 1996. https://doi.org/10.1037/0096-1523.22.6.1331 ), and the hypothesis proposed by Borowsky and Masson (J Exp Psychol Learn Mem Cognit 22:63-85, 1996. https://doi.org/10.1037/0278-7393.22.1.63 ). Although both hypotheses agree that ambiguous words benefit during recognition in that they engage more semantic activation, they disagree as to whether or not this greater semantic activation feeds back to the orthographic level, hence speeding up the orthographic coding of ambiguous words. Participants were presented with ambiguous and unambiguous words in two tasks, a lexical decision task (LDT) and a two-alternative forced-choice task (2AFC). We found differences between ambiguous and unambiguous words in both the LDT and the 2AFC tasks. These results suggest that the orthographic coding of ambiguous words is boosted during word processing. This finding lends support to the semantic feedback hypothesis.This research was funded by the Spanish Ministry of Economy and Competitiveness (PSI2015-63525-P) and by the Research Promotion Program of the Universitat Rovira i Virgili (2016PFR-URV-B2-37). This has also been partially supported by the FCT (Foundation for Science and Technology) through the state budget with Reference IF/00784/2013/CP1158/CT0013. The first author also holds a grant from the Universitat Rovira i Virgili (2015PMF-PIPF-16)

Analysis of Pools of Targeted Salmonella Deletion Mutants Identifies Novel Genes Affecting Fitness during Competitive Infection in Mice

Pools of mutants of minimal complexity but maximal coverage of genes of interest facilitate screening for genes under selection in a particular environment. We constructed individual deletion mutants in 1,023 Salmonella enterica serovar Typhimurium genes, including almost all genes found in Salmonella but not in related genera. All mutations were confirmed simultaneously using a novel amplification strategy to produce labeled RNA from a T7 RNA polymerase promoter, introduced during the construction of each mutant, followed by hybridization of this labeled RNA to a Typhimurium genome tiling array. To demonstrate the ability to identify fitness phenotypes using our pool of mutants, the pool was subjected to selection by intraperitoneal injection into BALB/c mice and subsequent recovery from spleens. Changes in the representation of each mutant were monitored using T7 transcripts hybridized to a novel inexpensive minimal microarray. Among the top 120 statistically significant spleen colonization phenotypes, more than 40 were mutations in genes with no previously known role in this model. Fifteen phenotypes were tested using individual mutants in competitive assays of intraperitoneal infection in mice and eleven were confirmed, including the first two examples of attenuation for sRNA mutants in Salmonella. We refer to the method as Array-based analysis of cistrons under selection (ABACUS)

Animal welfare in studies on murine tuberculosis : assessing progress over a 12-year period and the need for further improvement

There is growing concern over the welfare of animals used in research, in particular when these animals develop pathology. The present study aims to identify the main sources of animal distress and to assess the possible implementation of refinement measures in experimental infection research, using mouse models of tuberculosis (TB) as a case study. This choice is based on the historical relevance of mouse studies in understanding the disease and the present and long-standing impact of TB on a global scale. Literature published between 1997 and 2009 was analysed, focusing on the welfare impact on the animals used and the implementation of refinement measures to reduce this impact. In this 12-year period, we observed a rise in reports of ethical approval of experiments. The proportion of studies classified into the most severe category did however not change significantly over the studied period. Information on important research parameters, such as method for euthanasia or sex of the animals, were absent in a substantial number of papers. Overall, this study shows that progress has been made in the application of humane endpoints in TB research, but that a considerable potential for improvement remains.Nuno H. Franco is funded by Fundação para a Ciência e Tecnologia (SFRH/BD/38337/2007). This work is funded by FEDER funds through the Operational Competitiveness Programme - COMPETE and by national funds through FCT - Fundação para a Ciência e Tecnologia under the project FCOMP-01-0124-FEDER-022718 (PEst-C/SAU/LA0002/2011