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Protocols are invaluable documents for any research study, especially for prediction model studies. However, the mere existence of a protocol is insufficient if key details are omitted. We reviewed the reporting content and details of the proposed design and methods reported in published protocols for prediction model research. We searched MEDLINE, Embase, and the Web of Science Core Collection for protocols for studies developing or validating a diagnostic or prognostic model using any modeling approach in any clinical area. We screened protocols published between Jan 1, 2022 and June 30, 2022. We used the abstract, introduction, methods, and discussion sections of The Transparent Reporting of a multivariable prediction model of Individual Prognosis Or Diagnosis (TRIPOD) statement to inform data extraction. We identified 30 protocols, of which 28 were describing plans for model development and six for model validation. All protocols were open access, including a preprint. 15 protocols reported prospectively collecting data. 21 protocols planned to use clustered data, of which one-third planned methods to account for it. A planned sample size was reported for 93% development and 67% validation analyses. 16 protocols reported details of study registration, but all protocols reported a statement on ethics approval. Plans for data sharing were reported in 13 protocols. Protocols for prediction model studies are uncommon, and few are made publicly available. Those that are available were reasonably well-reported and often described their methods following current prediction model research recommendations, likely leading to better reporting and methods in the actual study.

Introduction Despite a proliferation of statistical methodologies and developments within randomised controlled trials (RCTs) in recent decades, it is unclear which approaches are being implemented in practice. Oxford Clinical Trials Research Unit (OCTRU) is a UK Clinical Research Collaboration (UKCRC) registered Clinical Trials Unit (CTU) that has been operational since 2013 based in the Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences at the University of Oxford. We performed a review of all published RCTs conducted within OCTRU, with particular emphasis on trial methodology, statistical study design and statistical analysis. Methods Studies were considered eligible if they were: RCTs conducted by OCTRU, have been completed and disseminated their primary results. Studies were ineligible if they were: a pilot or feasibility trial, a simulation study, a secondary analysis of an existing RCT, or a phase I trial. Phase II trials were considered if they were randomised. We performed double data extraction of all fields for all eligible trials. General trial information, such as primary disease area, main funding source, sample size, trial design and analysis information (e.g. number of study outcomes and analyses performed), were extracted and summarised. An analysis was defined as any time a statistical model was fit or a corresponding statistical test (e.g. χ 2 test) and/or estimation of a parameter was performed. Results Of the 142 OCTRU studies registered & funded (as of June 2023), 70 were completed and written up and 27 were eligible at the time of this review. The rest were ongoing or found to be ineligible. Included studies were published between 2014 and 2023, the majority in the last 5 years (20/27, 74% published between 2020 and 2023). All trials were multi-centre, prospectively designed and referred to both a study protocol and sample size justification (usually a power calculation) in their published results. Most included studies had elements of what could be referred to as a ‘standard’ RCT; used a parallel group design (93%), powered with superiority question (26/27, 96%), had two randomised groups (23/27, 85%) or used an equal allocation ratio (25/27, 93%). The median sample size was 451 (interquartile range: 238–836). The median total number of analyses performed was 22 (Interquartile range: 14–30) with the most analyses performed within a single trial being 69. Eighty-one per cent (22/27) of trials had a primary outcome with either binary or continuous data. Linear mixed effects, linear regression or logistic regression was used as the primary analysis model in 74% of the 27 trials. All trials that included at least one analysis (26/27) featured at least one additional analysis on the primary outcome, the most popular additional analyses were on an alternative population (for example a per-protocol population), occurring in 20/27, 74% of all trials, or a subgroup (18/27, 67%)). Conclusions This review summarises RCTs conducted by one academic UKCRC-registered CTU with a focus on the trial design and statistical analysis. We found most RCTs adopted what could be considered a ‘standard’ design, using appropriate, but not complex, analysis methods. Consideration of variation in practice across other groups, both academic and commercial, through a larger review would allow systematic exploration of methodological differences, less common study design usage, and would enable a fuller understanding of practice, outcomes, and methods used in different clinical areas and contexts.

Anthropogenic climate change is predicted to be a major cause of species extinctions in the next 100 years. But what will actually cause these extinctions? For example, will it be limited physiological tolerance to high temperatures, changing biotic interactions or other factors? Here, we systematically review the proximate causes of climate-change related extinctions and their empirical support. We find 136 case studies of climatic impacts that are potentially relevant to this topic. However, only seven identified proximate causes of demonstrated local extinctions due to anthropogenic climate change. Among these seven studies, the proximate causes vary widely. Surprisingly, none show a straightforward relationship between local extinction and limited tolerances to high temperature. Instead, many studies implicate species interactions as an important proximate cause, especially decreases in food availability. We find very similar patterns in studies showing decreases in abundance associated with climate change, and in those studies showing impacts of climatic oscillations. Collectively, these results highlight our disturbingly limited knowledge of this crucial issue but also support the idea that changing species interactions are an important cause of documented population declines and extinctions related to climate change. Finally, we briefly outline general research strategies for identifying these proximate causes in future studies.

Aim The factors that set species range limits underlie many patterns in ecology, evolution, biogeography and conservation. These factors have been the subject of several reviews, but there has been no systematic review of the causes of warm-edge limits (low elevations and latitudes). Understanding these causes is urgent, given that the factors that set these limits might also drive extinction at warm edges as global climate changes. Many authors have suggested that warm-edge limits are set by biotic factors (particularly competition) whereas others have stressed abiotic factors (particularly temperature). We synthesize the known causes of species' warm-edge range limits, with emphasis on the underlying mechanisms (proximate causes). Location Global. Methods We systematically searched the literature for studies testing the causes of warm-edge range limits. Results We found 125 studies that address the causes of warm-edge limits, from a search including > 4000 studies. Among the species in these studies, abiotic factors are supported more often than biotic factors in setting species range limits at warm edges, in contrast to the widely held view that biotic factors are more important. Studies that test both types of factors support abiotic factors significantly more frequently. In addition, only 23 studies (61 species) identified proximate causes of these limits, and these overwhelmingly support physiological tolerances to abiotic factors (primarily temperature). Only eight species with identified proximate causes were tested for both biotic and abiotic factors, but the majority support abiotic factors. Main conclusions Although it is often assumed that warm-edge limits are set by biotic factors, our review shows that abiotic factors are supported more often among the species in these 125 studies. However, few studies both identify proximate causes and test alternative mechanisms, or examine the interaction between biotic and abiotic factors. Filling these gaps should be a high priority as warm-edge populations are increasingly driven to extinction by climate change.

The population aging on the Autism Spectrum (AS) faces disproportionate physical and mental health comorbidities. This research describes self-care practices, including physical activity (PA), nutrition, and spirituality, and the impact of these practices on the health and well-being of older adults on the AS. Researchers conducted semi-structured interviews (N = 30) with older adults (age 50+ years) on the AS on the following topics: health, employment, relationships, and services/supports. Data were analyzed using Dedoose software and a constant comparative method. Participants described self-reported health benefits of their PA. Participants who engaged with organizations reported receiving instrumental support and fulfillment. Several themes emerged regarding socialization and routines in self-care in older adults on the AS, which may inform interventions.

This study explores factors associated with participation in moderate physical activity and muscle strengthening activity in adults with autism receiving state services (age: 18–78 years). Researchers analyzed the National Core Indicators-In Person Survey (2017–2018) data using multilevel mixed effects logistic regression. Older adults on the autism spectrum engaged in both moderate physical activity and muscle strengthening activity less often than younger adults on the autism spectrum (OR 0.99; p < 0.05; OR 0.98; p < 0.001). Individuals reportedly in fair/poor health had 50% lower odds of engaging in moderate physical activity and 30% lower odds of engaging in muscle strengthening compared to those in good/ excellent health (OR 0.50; p < 0.001; OR 0.70; p < 0.001). Moderate physical activity/muscle strengthening initiatives may help foster this group’s healthy aging.

In recent years rates of smoking in pregnancy in England have declined, from 11.7% of pregnant women in 2014/15, to 5.9% in quarter 3 2024/25, according to the latest smoking at the time of delivery (SATOD) figures.1 This is remarkable progress and suggests that a target set in the 2017 Tobacco Control Plan for England2—to reduce rates of smoking to less than 6% of pregnant women and other pregnant people by 2022—has finally been met. Introduced in 2016, the care bundle has driven a shift from largely voluntary, inconsistent uptake of best practice to a more systematic approach. Since 2019, it has been enhanced by dedicated funding for NHS tobacco dependence treatment services, enabling trusts to embed cessation support within maternity services. Available from: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD004307.pub7/full 6 Boyd KA Briggs AH Bauld L Sinclair L Tappin D. Are financial incentives cost-effective to support smoking cessation during pregnancy?

Neoadjuvant chemotherapy (NACT) is used in locally advanced breast cancer to reduce tumour burden prior to surgical resection. However, only a subset of NACT treated patients will respond to treatment or achieve a pathologic complete response (pCR). This multicenter, prospective study (CTRIAL-IE (ICORG) 10-11 study) evaluated circulating microRNA as novel non-invasive prognostic biomarkers of NACT response in breast cancer. Selected circulating microRNAs (Let-7a, miR-21, miR-145, miR-155, miR-195) were quantified from patients undergoing standard of care NACT treatment (n = 114) from whole blood at collected at diagnosis, and the association with NACT response and clinicopathological features evaluated. NACT responders had significantly lower levels of miR-21 (p = 0.036) and miR-195 (p = 0.017), compared to non-responders. Evaluating all breast cancer cases miR-21 was found to be an independent predictor of response (OR 0.538, 95% CI 0.308–0.943, p < 0.05). Luminal cancer NACT responders were found to have significantly decreased levels of miR-145 (p = 0.033) and miR-21 (p = 0.048), compared to non-responders. This study demonstrates the prognostic ability of miR-21, miR-195 and miR-145 as circulating biomarkers stratifying breast cancer patients by NACT response, identifying patients that will derive the maximum benefit from chemotherapy.

PurposePrescribing NAC for breast cancer is a pragmatic treatment strategy for several reasons; however, certain patients suffer chemotherapy-induced toxicities. Unfortunately, identifying patients at risk of toxicity often proves challenging. MiRNAs are small non-coding RNA molecules which modulate genetic expression. The aim of this study was to determine whether circulating miRNAs are sensitive biomarkers that can identify the patients likely to suffer treatment-related toxicities to neoadjuvant chemotherapy (NAC) for primary breast cancer.MethodsThis secondary exploratory from the prospective, multicentre translational research trial (CTRIAL ICORG10/11–NCT01722851) recruited 101 patients treated with NAC for breast cancer, from eight treatment sites across Ireland. A predetermined five miRNAs panel was quantified using RQ-PCR from patient bloods at diagnosis. MiRNA expression was correlated with chemotherapy-induced toxicities. Regression analyses was performed using SPSS v26.0.ResultsOne hundred and one patients with median age of 55 years were recruited (range: 25–76). The mean tumour size was 36 mm and 60.4% had nodal involvement (n = 61) Overall, 33.7% of patients developed peripheral neuropathies (n = 34), 28.7% developed neutropenia (n = 29), and 5.9% developed anaemia (n = 6). Reduced miR-195 predicted patients likely to develop neutropenia (P = 0.048), while increased miR-10b predicted those likely to develop anaemia (P = 0.049). Increased miR-145 predicted those experiencing nausea and vomiting (P = 0.019), while decreased miR-21 predicted the development of mucositis (P = 0.008).ConclusionThis is the first study which illustrates the value of measuring circulatory miRNA to predict patient-specific toxicities to NAC. These results support the ideology that circulatory miRNAs are biomarkers with utility in predicting chemotherapy toxicity as well as treatment response.

Public safety officials told legislators in Annapolis yesterday that they support Mayor Martin O'Malley's plan to reform the Baltimore court system but said it could cost the state millions of dollars. The officials, who run the Baltimore jail, said they would need at least $1.3 million annually to pay for 34 new employees and additional money to remodel the courtroom area to comply with the mayor's request. Despite such concerns, O'Malley said yesterday that he will push to have the courtroom at the city jail turned into a clearinghouse for minor cases by April 10.