Seasonal variation of the three-dimensional mean circulation over the Scotian Shelf

The seasonal-mean circulation over the Scotian Shelf is studied numerically by computing mean and tidal current fields for winter, spring, and summer using a three-dimensional nonlinear diagnostic model. The mean current fields are forced by seasonal-mean baroclinic pressure gradients, tidal rectification, uniform wind stresses, and associated barotropic pressure gradients. A historical hydrographic database is used to determine the climatological mean baroclinic forcing. Upstream open boundary conditions are estimated from the density fields to give no normal geostrophic bottom flow and are specified as either along-boundary elevation gradients or depth-integrated normal velocities. The numerical solutions for nominal bimonthly periods (January–February, April–May, and July–August) reveal the dominant southwestward nearshore and shelf-break flows of relatively cool and fresh shelf water from the Gulf of St. Lawrence and Newfoundland Shelf, with speeds up to about 20 cm/s. The seasonal intensification of the southwestward flows is reproduced by the model, with the transport increasing from 0.3 Sv in summer to 0.9 Sv in winter on the inner Halifax section. There are also pronounced topographic-scale influences of submarine banks, basins, and cross-shelf channels on the circulation, such as anticyclonic gyres over banks and cyclonic gyres over basins. Baroclinicity is the dominant forcing throughout the domain, but tidal rectification is comparable on the southwestern Scotian Shelf (e.g., about 0.2 Sv recirculating transport around Browns Bank for all the periods). The mean wind stress generates offshore surface drift in winter. The solutions are in approximate agreement with observed currents and transports over the Scotian Shelf, although there are local discrepancies

Tidal rectification and frontal circulation on the sides of Georges Bank

Using Wright and Loder\u27s (l985a,b) depth-dependent tidal rectification model and Garrett and Loder\u27s (1981) diagnostic frontal circulation model, predictions of the residual circulation associated with the topographic rectification of tidal currents and the summertime density field on the northwestern and open ocean sides of Georges Bank are made and compared with observations. In general, the estimates of both wintertime and summertime along-isobath currents are in qualitative agreement with observations, but the agreement between predicted and observed cross-isobath currents is poor. The circulation associated with tidal rectification is primarily along isobaths in an anticyclonic sense around the Bank at all depths. The cross-isobath circulation is much weaker and, in the Eulerian specification, is dominated by two cells with opposing current directions. However, a significant Stokes velocity is predicted such that the along-isobath Lagrangian current is generally less than its Eulerian counterpart, and the cross-isobath Lagrangian current is sometimes in the opposite direction to its Eulerian counterpart. Both the along-isobath and cross-isobath currents associated with tidal rectification are predicted to be significantly stronger in summer than in winter due to a reduction in the strength of friction as a result of reduced wind stress and increased density stratification.An additional contribution to the anticyclonic circulation around Georges Bank is associated directly with the summertime tidal front around the Bank. This flow component is predicted to form a second intense along-isobath jet on the northwestern side, slightly off-bank of that due to tidal rectification, and a broader flow on the open ocean side. The associated cross-isobath circulation is predicted to be much weaker than the along-isobath circulation, with a general on-bank bottom flow on both sides of the Bank

Interaction between the tidal and seasonal variability of the Gulf of Maine and Scotian Shelf Region

As part of a broader study of ocean downscaling, the seasonal and tidal variability of the Gulf of Maine and Scotian shelf, and their dynamical interaction, are investigated using a high-resolution (1/36°) circulation model. The model’s seasonal hydrography and circulation, and its tidal elevations and currents, are compared with an observed seasonal climatology, local observations, and results from previous studies. Numerical experiments with and without density stratification demonstrate the influence of stratification on the tides. The model is then used to interpret the physical mechanisms responsible for the largest seasonal variations in the M2 surface current that occur over, and to the north of, Georges Bank. The model generates a striation pattern of alternating highs and lows, aligned with Georges Bank, in the M2 surface summer maximum speed in the Gulf of Maine. The striations are consistent with observations by a high-frequency coastal radar system and can be explained in terms of a linear superposition of the barotropic tide and the first-mode baroclinic tide, generated on the north side of Georges Bank, as it propagates into the Gulf of Maine. The seasonal changes in tidal currents in the well-mixed area on Georges Bank are due to a combination of increased sea level gradients, and lower vertical viscosity, in summer

Increased expression of the 5-HT transporter confers a low-anxiety phenotype linked to decreased 5-HT transmission

A commonly occurring polymorphic variant of the human 5-hydroxytryptamine (5-HT) transporter (5-HTT) gene that increases 5-HTT expression has been associated with reduced anxiety levels in human volunteer and patient populations. However, it is not known whether this linkage between genotype and anxiety relates to variation in 5-HTT expression and consequent changes in 5-HT transmission. Here we test this hypothesis by measuring the neurochemical and behavioral characteristics of a mouse genetically engineered to overexpress the 5-HTT. Transgenic mice overexpressing the human 5-HTT (h5-HTT) were produced from a 500 kb yeast artificial chromosome construct. These transgenic mice showed the presence of h5-HTT mRNA in the midbrain raphe nuclei, as well as a twofold to threefold increase in 5-HTT binding sites in the raphe nuclei and a range of forebrain regions. The transgenic mice had reduced regional brain whole-tissue levels of 5-HT and, in microdialysis experiments, decreased brain extracellular 5-HT, which reversed on administration of the 5-HTT inhibitor paroxetine. Compared with wild-type mice, the transgenic mice exhibited a low-anxiety phenotype in plus maze and hyponeophagia tests. Furthermore, in the plus maze test, the low-anxiety phenotype of the transgenic mice was reversed by acute administration of paroxetine, suggesting a direct link between the behavior, 5-HTT overexpression, and low extracellular 5-HT. In toto, these findings demonstrate that associations between increased 5-HTT expression and anxiety can be modeled in mice and may be specifically mediated by decreases in 5-HT transmission.</p

CONSORT 2025 statement: Updated guideline for reporting randomised trials

BACKGROUND: Well designed and properly executed randomised trials are considered the most reliable evidence on the benefits of healthcare interventions. However, there is overwhelming evidence that the quality of reporting is not optimal. The CONSORT (Consolidated Standards of Reporting Trials) statement was designed to improve the quality of reporting and provides a minimum set of items to be included in a report of a randomised trial. CONSORT was first published in 1996, then updated in 2001 and 2010. Here, we present the updated CONSORT 2025 statement, which aims to account for recent methodological advancements and feedback from end users. METHODS: We conducted a scoping review of the literature and developed a project-specific database of empirical and theoretical evidence related to CONSORT, to generate a list of potential changes to the checklist. The list was enriched with recommendations provided by the lead authors of existing CONSORT extensions (Harms, Outcomes, Non-pharmacological Treatment), other related reporting guidelines (TIDieR) and recommendations from other sources (e.g., personal communications). The list of potential changes to the checklist was assessed in a large, international, online, three-round Delphi survey involving 317 participants and discussed at a two-day online expert consensus meeting of 30 invited international experts. RESULTS: We have made substantive changes to the CONSORT checklist. We added seven new checklist items, revised three items, deleted one item, and integrated several items from key CONSORT extensions. We also restructured the CONSORT checklist, with a new section on open science. The CONSORT 2025 statement consists of a 30-item checklist of essential items that should be included when reporting the results of a randomised trial and a diagram for documenting the flow of participants through the trial. To facilitate implementation of CONSORT 2025, we have also developed an expanded version of the CONSORT 2025 checklist, with bullet points eliciting critical elements of each item. CONCLUSIONS: Authors, editors, reviewers, and other potential users should use CONSORT 2025 when writing and evaluating manuscripts of randomised trials to ensure that trial reports are clear and transparent

SPIRIT 2025 statement: Updated guideline for protocols of randomised trials

Importance The protocol of a randomised trial is the foundation for study planning, conduct, reporting, and external review. However, trial protocols vary in their completeness and often do not address key elements of design and conduct. The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) statement was first published in 2013 as guidance to improve the completeness of trial protocols. Periodic updates incorporating the latest evidence and best practices are needed to ensure that the guidance remains relevant to users. Objective To systematically update the SPIRIT recommendations for minimum items to address in the protocol of a randomised trial. Design We completed a scoping review and developed a project specific database of empirical and theoretical evidence to generate a list of potential changes to the SPIRIT 2013 checklist. The list was enriched with recommendations provided by lead authors of existing SPIRIT/CONSORT (Consolidated Standards of Reporting Trials) extensions (Harms, Outcomes, Non-pharmacological Treatment) and other reporting guidelines (TIDieR). The potential modifications were rated in a three-round Delphi survey followed by a consensus meeting. Findings Overall, 317 individuals participated in the Delphi consensus process and 30 experts attended the consensus meeting. The process led to the addition of two new protocol items, revision to five items, deletion/merger of five items, and integration of key items from other relevant reporting guidelines. Notable changes include a new open science section, additional emphasis on the assessment of harms and description of interventions and comparators, and a new item on how patients and the public will be involved in trial design, conduct, and reporting. The updated SPIRIT 2025 statement consists of an evidence-based checklist of 34 minimum items to address in a trial protocol, along with a diagram illustrating the schedule of enrolment, interventions, and assessments for trial participants. To facilitate implementation, we also developed an expanded version of the SPIRIT 2025 checklist and an accompanying explanation and elaboration document. Conclusions and relevance Widespread endorsement and adherence to the updated SPIRIT 2025 statement have the potential to enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, funders, research ethics committees, journals, trial registries, policymakers, regulators, and other reviewers

Protocol for the development of a tool (INSPECT-SR) to identify problematic randomised controlled trials in systematic reviews of health interventions

This research is funded by the NIHR Research for Patient Benefit programme (NIHR203568). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.Peer reviewe

CONSORT 2025 statement: updated guideline for reporting randomised trials

BACKGROUND: Well designed and properly executed randomised trials are considered the most reliable evidence on the benefits of healthcare interventions. However, there is overwhelming evidence that the quality of reporting is not optimal. The CONSORT (Consolidated Standards of Reporting Trials) statement was designed to improve the quality of reporting and provides a minimum set of items to be included in a report of a randomised trial. CONSORT was first published in 1996, then updated in 2001 and 2010. Here, we present the updated CONSORT 2025 statement, which aims to account for recent methodological advancements and feedback from end users. METHODS: We conducted a scoping review of the literature and developed a project-specific database of empirical and theoretical evidence related to CONSORT, to generate a list of potential changes to the checklist. The list was enriched with recommendations provided by the lead authors of existing CONSORT extensions (Harms, Outcomes, Non-pharmacological Treatment), other related reporting guidelines (TIDieR) and recommendations from other sources (eg, personal communications). The list of potential changes to the checklist was assessed in a large, international, online, three-round Delphi survey involving 317 participants and discussed at a two-day online expert consensus meeting of 30 invited international experts. RESULTS: We have made substantive changes to the CONSORT checklist. We added seven new checklist items, revised three items, deleted one item, and integrated several items from key CONSORT extensions. We also restructured the CONSORT checklist, with a new section on open science. The CONSORT 2025 statement consists of a 30-item checklist of essential items that should be included when reporting the results of a randomised trial and a diagram for documenting the flow of participants through the trial. To facilitate implementation of CONSORT 2025, we have also developed an expanded version of the CONSORT 2025 checklist, with bullet points eliciting critical elements of each item. CONCLUSION: Authors, editors, reviewers, and other potential users should use CONSORT 2025 when writing and evaluating manuscripts of randomised trials to ensure that trial reports are clear and transparent

CONSORT 2025 explanation and elaboration: updated guideline for reporting randomised trials

Summary points: The CONSORT (Consolidated Standards of Reporting Trials) 2025 statement consists of a 30-item checklist of essential items for reporting the results of randomised trials This updated explanation and elaboration article describes the rationale and scientific background for each checklist item and provide published examples of good reporting This explanation and elaboration article provides detailed guidance to enhance the use, understanding, and dissemination of CONSORT 2025, helping to ensure that trial reports are complete and transparen

SPIRIT 2025 statement: updated guideline for protocols of randomised trials

The protocol of a randomised trial is the foundation for study planning, conduct, reporting, and external review. However, trial protocols vary in their completeness and often do not address key elements of design and conduct. The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) statement was first published in 2013 as guidance to improve the completeness of trial protocols. Periodic updates incorporating the latest evidence and best practices are needed to ensure that the guidance remains relevant to users. We aimed to systematically update the SPIRIT recommendations for minimum items to address in the protocol of a randomised trial. We completed a scoping review and developed a project specific database of empirical and theoretical evidence to generate a list of potential changes to the SPIRIT 2013 checklist. The list was enriched with recommendations provided by lead authors of existing SPIRIT/CONSORT (Consolidated Standards of Reporting Trials) extensions (Harms, Outcomes, Non-pharmacological Treatment) and other reporting guidelines (TIDieR). The potential modifications were rated in a three-round Delphi survey followed by a consensus meeting. Overall, 317 individuals participated in the Delphi consensus process and 30 experts attended the consensus meeting. The process led to the addition of two new protocol items, revision to five items, deletion/merger of five items, and integration of key items from other relevant reporting guidelines. Notable changes include a new open science section, additional emphasis on the assessment of harms and description of interventions and comparators, and a new item on how patients and the public will be involved in trial design, conduct, and reporting. The updated SPIRIT 2025 statement consists of an evidence based checklist of 34 minimum items to address in a trial protocol, along with a diagram illustrating the schedule of enrolment, interventions, and assessments for trial participants. To facilitate implementation, we also developed an expanded version of the SPIRIT 2025 checklist and an accompanying explanation and elaboration document. Widespread endorsement and adherence to the updated SPIRIT 2025 statement have the potential to enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, funders, research ethics committees, journals, trial registries, policymakers, regulators, and other reviewers