Tectonics of the central Andes

Acquisition of nearly complete coverage of Thematic Mapper data for the central Andes between about 15 to 34 degrees S has stimulated a comprehensive and unprecedented study of the interaction of tectonics and climate in a young and actively developing major continental mountain belt. The current state of the synoptic mapping of key physiographic, tectonic, and climatic indicators of the dynamics of the mountain/climate system are briefly reviewed

How important is randomisation in a stepped wedge trial?

In cluster randomised trials, randomisation increases internal study validity. If enough clusters are randomised, an unadjusted analysis should be unbiased. If a smaller number of clusters are included, stratified or matched randomisation can increase comparability between trial arms. In addition, an adjusted analysis may be required; nevertheless, randomisation removes the possibility for systematically biased allocation and increases transparency. In stepped wedge trials, clusters are randomised to receive an intervention at different start times ('steps'), and all clusters eventually receive it. In a recent study protocol for a 'modified stepped wedge trial', the investigators considered randomisation of the clusters (hospital wards), but decided against it for ethical and logistical reasons, and under the assumption that it would not add much to the rigour of the evaluation. We show that the benefits of randomisation for cluster randomised trials also apply to stepped wedge trials. The biggest additional issue for stepped wedge trials in relation to parallel cluster randomised trials is the need to control for secular trends in the outcome. Analysis of stepped wedge trials can in theory be based on 'horizontal' or 'vertical' comparisons. Horizontal comparisons are based on measurements taken before and after the intervention is introduced in each cluster, and are unbiased if there are no secular trends. Vertical comparisons are based on outcome measurements from clusters that have switched to the intervention condition and those from clusters that have yet to switch, and are unbiased under randomisation since at any time point, which clusters are in intervention and control conditions will have been determined at random. Secular outcome trends are a possibility in many settings. Many stepped wedge trials are analysed with a mixed model, including a random effect for cluster and fixed effects for time period to account for secular trends, thereby combining both vertical and horizontal comparisons of intervention and control clusters. The importance of randomisation in a stepped wedge trial is that the effects of time can be estimated from the data, and bias from secular trends that would otherwise arise can be controlled for, provided the trends are correctly specified in the model

Xpert MTB/RIF - why the lack of morbidity and mortality impact in intervention trials?

Compared with smear microscopy, the Xpert MTB/RIF assay (Xpert), with superior accuracy and capacity to diagnose rifampicin resistance, has advanced TB diagnostic capability. However, recent trials of Xpert impact have not demonstrated reductions in patient morbidity and mortality. We conducted a narrative review of Xpert impact trials to summarize which patient-relevant outcomes Xpert has improved and explore reasons for no observed morbidity or mortality reductions. We searched PubMed, Google Scholar, Cochrane Library and Embase and identified eight trials meeting inclusion criteria: three individually randomized, three cluster-randomized, and two pre-post trials. In six trials Xpert increased diagnostic yield of bacteriologically-confirmed TB from sputa and in four trials Xpert shortened time to TB treatment. However, all-cause mortality was similar between arms in all six trials reporting this outcome, and the only trial to assess Xpert impact on morbidity reported no impact. Trial characteristics that might explain lack of observed impact on morbidity and mortality include: higher rates of empiric TB treatment in microscopy compared with Xpert arms, enrollment of study populations not comprised exclusively of populations most likely to benefit from Xpert, and health system weaknesses. So far as equipoise exists, future trials that address past limitations are needed to inform Xpert use in resource-limited settings

Viral suppression following switch to second-line antiretroviral therapy: associations with nucleoside reverse transcriptase inhibitor resistance and subtherapeutic drug concentrations prior to switch.

BACKGROUND: High rates of second-line antiretroviral treatment (ART) failure are reported. The association with resistance and nonadherence on switching to second-line ART requires clarification. METHODS: Using prospectively collected data from patients in South Africa, we constructed a cohort of patients switched to second-line ART (1 January 2003 through 31 December 2008). Genotyping and drug concentrations (lamivudine, nevirapine, and efavirenz) were measured on stored samples preswitch. Their association with viral load (VL) <400 copies/mL by 15 months was assessed using modified Poisson regression. RESULTS: One hundred twenty-two of 417 patients (49% male; median age, 36 years) had genotyping (n = 115) and/or drug concentrations (n = 80) measured. Median CD4 count and VL at switch were 177 cells/µL (interquartile range [IQR], 77-263) and 4.3 log10 copies/mL (IQR, 3.8-4.7), respectively. Fifty-five percent (n = 44/80) had subtherapeutic drug concentrations preswitch. More patients with therapeutic vs subtherapeutic ART had resistance (n = 73): no major mutations (3% vs 51%), nonnucleoside reverse transcriptase inhibitor (94% vs 44%), M184V/I (94% vs 26%), and ≥ 1 thymidine analogue mutations (47% vs 18%), all P = .01; and nucleoside reverse transcriptase inhibitor (NRTI) cross-resistance mutations (26% vs 13%, P = .23). Following switch, 68% (n = 83/122) achieved VL <400 copies/mL. Absence of NRTI mutations and subtherapeutic ART preswitch were associated with failure to achieve VL <400 copies/mL. CONCLUSIONS: Nonadherence, suggested by subtherapeutic ART with/without major resistance mutations, significantly contributed to failure when switching regimen. Unresolved nonadherence, not NRTI resistance, drives early second-line failure

Tuberculosis control in South African gold mines: mathematical modeling of a trial of community-wide isoniazid preventive therapy.

A recent major cluster randomized trial of screening, active disease treatment, and mass isoniazid preventive therapy for 9 months during 2006-2011 among South African gold miners showed reduced individual-level tuberculosis incidence but no detectable population-level impact. We fitted a dynamic mathematical model to trial data and explored 1) factors contributing to the lack of population-level impact, 2) the best-achievable impact if all implementation characteristics were increased to the highest level achieved during the trial ("optimized intervention"), and 3) how tuberculosis might be better controlled with additional interventions (improving diagnostics, reducing treatment delay, providing isoniazid preventive therapy continuously to human immunodeficiency virus-positive people, or scaling up antiretroviral treatment coverage) individually and in combination. We found the following: 1) The model suggests that a small proportion of latent infections among human immunodeficiency virus-positive people were cured, which could have been a key factor explaining the lack of detectable population-level impact. 2) The optimized implementation increased impact by only 10%. 3) Implementing additional interventions individually and in combination led to up to 30% and 75% reductions, respectively, in tuberculosis incidence after 10 years. Tuberculosis control requires a combination prevention approach, including health systems strengthening to minimize treatment delay, improving diagnostics, increased antiretroviral treatment coverage, and effective preventive treatment regimens

Transitions in general practice training : quantifying epidemiological variation in trainees' experiences and clinical behaviours

Background: General Practice training in Australia is delivered through the apprenticeship model. General Practice supervisors support trainees transitioning from hospital-based work towards competent independent community-based practice. The timing and manner in which support should be provided is still not well understood. This study aimed to establish the variation in clinical and educational experiences and behaviours, and location, of general practice trainees’ consultations by stage of their vocational training. It was hypothesised that change is greater in earlier stages of training. Methods: A cross-sectional analysis of data (2010–2018) from the Registrar Clinical Encounters in Training (ReCEnT) study, an ongoing cohort study of Australian GP registrars’ in-consultation clinical and educational experience and behaviours. Multinomial logistic regression assessed the association of demographic, educational, and clinical factors in different stages of training. The outcome factor was the training term. Results: Two thousand four hundred sixteen registrars contributed data for 321,414 patient consultations. For several important variables (seeing patients with chronic disease; new patients; seeking in-consultation information or assistance; ordering pathology and imaging; and working in a small or regional practice), odds ratios were considerably greater for comparisons of Term 1 and 3, relative to comparisons of Term 2 and 3. Conclusion: Differences experienced in demographic, clinical and educational factors are significantly more pronounced earlier in registrars’ training. This funding has educational and training implications with respect to resource allocation, trainee supervision and curriculum design. Sociocultural learning theory enables an understanding of the impact of transitions on, and how to support, general practice trainees and supervisors

Stepped wedge randomised controlled trials: systematic review of studies published between 2010 and 2014.

BACKGROUND: In a stepped wedge, cluster randomised trial, clusters receive the intervention at different time points, and the order in which they received it is randomised. Previous systematic reviews of stepped wedge trials have documented a steady rise in their use between 1987 and 2010, which was attributed to the design's perceived logistical and analytical advantages. However, the interventions included in these systematic reviews were often poorly reported and did not adequately describe the analysis and/or methodology used. Since 2010, a number of additional stepped wedge trials have been published. This article aims to update previous systematic reviews, and consider what interventions were tested and the rationale given for using a stepped wedge design. METHODS: We searched PubMed, PsychINFO, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Web of Science, the Cochrane Library and the Current Controlled Trials Register for articles published between January 2010 and May 2014. We considered stepped wedge randomised controlled trials in all fields of research. We independently extracted data from retrieved articles and reviewed them. Interventions were then coded using the functions specified by the Behaviour Change Wheel, and for behaviour change techniques using a validated taxonomy. RESULTS: Our review identified 37 stepped wedge trials, reported in 10 articles presenting trial results, one conference abstract, 21 protocol or study design articles and five trial registrations. These were mostly conducted in developed countries (n = 30), and within healthcare organisations (n = 28). A total of 33 of the interventions were educationally based, with the most commonly used behaviour change techniques being 'instruction on how to perform a behaviour' (n = 32) and 'persuasive source' (n = 25). Authors gave a wide range of reasons for the use of the stepped wedge trial design, including ethical considerations, logistical, financial and methodological. The adequacy of reporting varied across studies: many did not provide sufficient detail regarding the methodology or calculation of the required sample size. CONCLUSIONS: The popularity of stepped wedge trials has increased since 2010, predominantly in high-income countries. However, there is a need for further guidance on their reporting and analysis

Analysis and reporting of stepped wedge randomised controlled trials: synthesis and critical appraisal of published studies, 2010 to 2014

Background Stepped wedge cluster randomised trials introduce interventions to groups of clusters in a random order and have been used to evaluate interventions for health and wellbeing. Standardised guidance for reporting stepped wedge trials is currently absent, and a range of potential analytic approaches have been described. Methods We systematically identified and reviewed recently published (2010 to 2014) analyses of stepped wedge trials. We extracted data and described the range of reporting and analysis approaches taken across all studies. We critically appraised the strategy described by three trials chosen to reflect a range of design characteristics. Results Ten reports of completed analyses were identified. Reporting varied: seven of the studies included a CONSORT diagram, and only five also included a diagram of the intervention rollout. Seven assessed the balance achieved by randomisation, and there was considerable heterogeneity among the approaches used. Only six reported the trend in the outcome over time. All used both ‘horizontal’ and ‘vertical’ information to estimate the intervention effect: eight adjusted for time with a fixed effect, one used time as a condition using a Cox proportional hazards model, and one did not account for time trends. The majority used simple random effects to account for clustering and repeat measures, assuming a common intervention effect across clusters. Outcome data from before and after the rollout period were often included in the primary analysis. Potential lags in the outcome response to the intervention were rarely investigated. We use three case studies to illustrate different approaches to analysis and reporting. Conclusions There is considerable heterogeneity in the reporting of stepped wedge cluster randomised trials. Correct specification of the time-trend underlies the validity of the analytical approaches. The possibility that intervention effects vary by cluster or over time should be considered. Further work should be done to standardise the reporting of the design, attrition, balance, and time-trends in stepped wedge trials

Model-informed classification of broadband acoustic backscatter from zooplankton in an in situ mesocosm

Funding: The fieldwork was registered in the Research in Svalbard database (RiS ID 11578). Fieldwork and research were financed by Arctic Field Grant Project AZKABAN-light (Norwegian Research Council project no. 322 332), Deep Impact (Norwegian Research Council project no. 300 333), Deeper Impact (Norwegian Research Council project no. 329 305), Marine Alliance for Science and Technology in Scotland (MASTS), the Ocean Frontier Institute (SCORE grant no. HR09011), and Glider Phase II financed by ConocoPhillips Skandinavia AS. Geir Pedersen’s participation was co-funded by CRIMAC (Norwegian Research Council project no. 309 512). Maxime Geoffroy was financially supported by the Ocean Frontier Institute of the Canada First Research Excellence Fund, the Natural Sciences and Engineering Research Council Discovery Grant Programme, the ArcticNet Network of Centres of Excellence Canada, the Research Council of Norway Grant Deep Impact, and the Fisheries and Oceans Canada through the Atlantic Fisheries Fund.Classification of zooplankton to species with broadband echosounder data could increase the taxonomic resolution of acoustic surveys and reduce the dependence on net and trawl samples for ‘ground truthing’. Supervised classification with broadband echosounder data is limited by the acquisition of validated data required to train machine learning algorithms (‘classifiers’). We tested the hypothesis that acoustic scattering models could be used to train classifiers for remote classification of zooplankton. Three classifiers were trained with data from scattering models of four Arctic zooplankton groups (copepods, euphausiids, chaetognaths, and hydrozoans). We evaluated classifier predictions against observations of a mixed zooplankton community in a submerged purpose-built mesocosm (12 m3) insonified with broadband transmissions (185–255 kHz). The mesocosm was deployed from a wharf in Ny-Ålesund, Svalbard, during the Arctic polar night in January 2022. We detected 7722 tracked single targets, which were used to evaluate the classifier predictions of measured zooplankton targets. The classifiers could differentiate copepods from the other groups reasonably well, but they could not differentiate euphausiids, chaetognaths, and hydrozoans reliably due to the similarities in their modelled target spectra. We recommend that model-informed classification of zooplankton from broadband acoustic signals be used with caution until a better understanding of in situ target spectra variability is gained.Publisher PDFPeer reviewe