A study on episodic memory reconsolidation that tells us more about consolidation

Awake quiescence immediately after encoding is conducive to episodic memory consolidation. Retrieval can render episodic memories labile again, but reconsolidation can modify and re-strengthen them. It remained unknown whether awake quiescence after retrieval supports episodic memory reconsolidation. We sought to examine this question via an object-location memory paradigm. We failed to probe the effect of quiescence on reconsolidation, but we did observe an unforeseen ‘delayed’ effect of quiescence on consolidation. Our findings reveal that the beneficial effect of quiescence on episodic memory consolidation is not restricted to immediately following encoding but can be achieved at a delayed stage and even following a period of task engagement

Protocol for a systematic scoping review of reasons given to justify the performance of randomised controlled trials.

IntroductionRandomised controlled trials (RCTs) are widely viewed to generate the most reliable medical knowledge. However, RCTs are not always scientifically necessary and therefore not always ethical. Unfortunately, it is not clear when an RCT is not necessary or how this should be established. This study seeks to systematically catalogue justifications offered throughout the medical and ethics literature for performing randomisation within clinical trials.Methods and analysisWe will systematically search electronic databases of the medical literature including MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Clinical Trials Register, Web of Science Proceedings, ClinicalTrials.gov; databases of philosophical literature including Philosopher's Index, Phil Papers, JSTOR, Periodicals Archive Online, Project MUSE, National Reference Centre for Bioethics; the library catalogue at the University of Ottawa; bibliographies of retrieved papers; and the grey literature. We will also pursue suggestions from experts in the fields of medical ethics, philosophy and clinical trial methodology. Article screening, selection and data extraction will be performed by two independent reviewers based on prespecified inclusion/exclusion criteria. A third reviewer will be consulted to resolve any discrepancies. We will then extract the reasons given to justify randomisation using methodology established to extract data in a defensible, systematic manner. We will track the reasons given, their frequency of use and changes over time. Finally, using grounded theory, we will combine the reasons into broader themes. These themes will form the foundation of our subsequent analysis from qualitative and quantitative perspectives. This review will map existing arguments that clinicians, ethicists and philosophers use to ethically justify randomisation in clinical trials.Ethics and disseminationNo research ethics board approval is necessary because we are not examining patient-level data. This protocol complies with the reported guidance for conducting systematic scoping reviews. The findings of this paper will be disseminated via presentations and academic publication. In a subsequent phase of this research, we hope to engage with stakeholders and translate any recommendations derived from our findings into operational guidelines

Grandmothers’ care practices in areas of high deprivation of Scotland:the potential for health promotion

In many families grandparents play an essential role by providing secondary care for grandchildren. The family is a key setting for promoting children’s health; however, studies describing health initiatives with grandparents are rare. Grandparents could play an important role in promoting health for their grandchildren within their families and communities. The aim of this study was to examine the care practices of grandparents in families living in areas of high deprivation, and to consider the extent to which grandparents could be at the centre of health-promoting initiatives for children. A family practices approach was used to examine care practices within the framework of family resource (assets/capitals) use. In-depth interviews were carried out with grandmothers (n = 15) and mothers (n = 15) living in areas of high deprivation in Scotland. The results are presented as three economies of family living—political, moral and emotional. Grandparent care was described as a form of social capital, central to the wellbeing of the families, and enabled parents to access education and employment. Grandparent care was supported through families’ ability to access cultural amenities and green space (political). Grandparents’ care practices were described as either being responsible or fun (moral). Love appeared to be at the centre of grandparents’ care (emotional). The strengths and weaknesses of this framework were examined in relation to developing initiatives with grandparents. With further development work, grandparents could be the focus of health initiatives with their grandchildren with the support of appropriate policies and resources within their communities

An Inpatient Patient Safety Curriculum for Pediatric Residents.

Introduction: Patient safety is recognized as an important part of pediatric resident education. There is a lack of published safety curricula targeting pediatric residents. A local needs assessment showed that while residents felt safety was an important part of their current and future jobs, they did not feel prepared to apply safety principles to their future careers or participate in a root cause analysis (RCA). Methods: This curriculum was delivered to senior-level pediatric and multiple-board residents during five monthly, hour-long, multidisciplinary sessions. Sessions covered systems-based thinking, terminology, the second victim phenomenon, RCA, and medication errors, while providing feedback on recent event reports filed by residents. Resident knowledge, attitudes, and reporting behavior were evaluated prior to and following the curriculum. Results: Attendees showed statistically significant improved safety attitudes and preparedness to apply safety to their future endeavors; conversely, there were no significant changes in nonattendees. There were no significant changes in knowledge scores or event reporting. Answers to qualitative questions identified learning about the reporting process, RCAs, and follow-up on filed event reports as valuable parts of the curriculum. Residents desired more time to debrief about safety events. Discussion: The curriculum succeeded in engaging residents in patient safety and making them feel prepared for future practice. Residents showed a dissonance between their intentions to report and their actual reporting behaviors, the reasons for which require further exploration. Residents desired a forum to deal with the emotions involved in errors. This curriculum is easily transferable to other institutions with minor modifications

A multi-centre, UK-based, non-inferiority randomised controlled trial of 4 follow-up assessment methods in stroke survivors

Background: Recovery following a stroke is a long and ongoing process. Post-stroke follow-up after leaving the hospital is recommended. Methods for follow-up patients include face-to-face, via the telephone, post or online (internet). However, there is a debate which method is preferred by patients. This study aimed to determine whether telephone interview, online questionnaire and postal questionnaire were as acceptable as face-to-face follow-up. Methods: In a blinded, UK-wide, multi-centre, Zelen’s designed, 4-arm (postal, online, telephone, compared to face-to-face), pragmatic non-inferiority randomised controlled trial of the mode of administration, stroke survivors were randomised to postal, online, telephone and face-to-face assessment, in an equal ratio (1:1:1:1). The primary outcome was the proportion of participants that responded to the three allocation groups, compared to the face-to-face group. Subgroup analyses for age, aphasia and type and severity of stroke were carried out. A non-inferiority margin of 0.025 was used, and Holm-Bonferroni multiplicity adjustment was made. Results: Of the 2074 eligible patients randomised, 55% were male (1142/2074), with an average age of 73.0 years old (SD = 13.2). Of those randomised, 22% (116/525), 9% (47/515) and 20% (101/513) responded in postal, online and telephone, respectively, compared to 17% (89/521) in the face-to-face group. The reduction in the online response rate compared to face-to-face was found to be both inferior and not non-inferior and estimated as an 8% reduction (95% CI 3.9 to 12.0%; p < 0.001). The association with lower online completion was present regardless of age, stroke type (haemorrhage or infarct) and stroke severity. In haemorrhagic stroke, the reduction in response online, compared to face-to-face, was 21% (95% CI 10 to 32%; p value = 0.002). A secondary analysis found non-aphasic stroke survivors preferred postal completion adjusted odds ratio of 1.43 (95% CI 1.04 to 1.95; p = 0.026). Conclusions: The study found that fewer stroke survivors completed follow-up assessment using an online method, compared to face-to-face. This finding was present in all age groups. Caution should be employed when considering online follow-up methods in stroke survivors, particularly in those who have experienced a cerebrovascular haemorrhage

Integrating Dynamic Subsurface Habitat Metrics Into Species Distribution Models

Species distribution models (SDMs) have become key tools for describing and predicting species habitats. In the marine domain, environmental data used in modeling species distributions are often remotely sensed, and as such have limited capacity for interpreting the vertical structure of the water column, or are sampled in situ, offering minimal spatial and temporal coverage. Advances in ocean models have improved our capacity to explore subsurface ocean features, yet there has been limited integration of such features in SDMs. Using output from a data-assimilative configuration of the Regional Ocean Modeling System, we examine the effect of including dynamic subsurface variables in SDMs to describe the habitats of four pelagic predators in the California Current System (swordfish Xiphias gladius, blue sharks Prionace glauca, common thresher sharks Alopias vulpinus, and shortfin mako sharks lsurus oxyrinchus). Species data were obtained from the California Drift Gillnet observer program (1997-2017). We used boosted regression trees to explore the incremental improvement enabled by dynamic subsurface variables that quantify the structure and stability of the water column: isothermal layer depth and bulk buoyancy frequency. The inclusion of these dynamic subsurface variables significantly improved model explanatory power for most species. Model predictive performance also significantly improved, but only for species that had strong affiliations with dynamic variables (swordfish and shortfin mako sharks) rather than static variables (blue sharks and common thresher sharks). Geospatial predictions for all species showed the integration of isothermal layer depth and bulk buoyancy frequency contributed value at the mesoscale level (\u3c 100 km) and varied spatially throughout the study domain. These results highlight the utility of including dynamic subsurface variables in SDM development and support the continuing ecological use of biophysical output from ocean circulation models

Adapting the Marine Stewardship Council risk-based framework to estimate impacts on seabirds, marine mammals, marine turtles and sea snakes

Information available on impacts of fisheries on target or bycatch species varies greatly, requiring development of risk assessment tools to determine potentially unacceptable levels. Seabirds, marine mammals, marine turtles and sea snakes are particularly vulnerable given their extreme life histories, and data are often lacking on their populations or bycatch rates with which to quantify fisheries impacts. The Marine Stewardship Council (MSC) use a semi-quantitative Productivity Susceptibility Analysis (PSA) that is applicable to all species, target and non-target, to calculate risk of impact and to provide a score for relevant Performance Indicators for fisheries undertaking certification. The most recent MSC Fisheries Standard Review provided an opportunity to test the appropriateness of using this tool and whether it was sufficiently precautionary for seabirds, marine mammals and reptiles . The existing PSA was tested on a range of species and fisheries and reviewed in relation to literature on these species groups. New taxa-specific PSAs were produced and then reviewed by taxa-specific experts and other relevant stakeholders (e.g., assessors, fisheries managers, non-governmental conservation organizations). The conclusions of the Fishery Standard Review process were that the new taxa-specific PSAs were more appropriate than the existing PSA for assessing fisheries risk for seabirds, marine mammals and reptiles, and that, as intended, they resulted in precautionary outcomes. The taxa-specific PSAs provide useful tools for true data-deficient fisheries to assess relative risk of impact. Where some data are available, the MSC could consider developing or adapting other approaches to support robust and relevant risk assessments

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Effect of Neutralizing Monoclonal Antibody Treatment on Early Trajectories of Virologic and Immunologic Biomarkers in Patients Hospitalized With COVID-19

BACKGROUND: Neutralizing monoclonal antibodies (nmAbs) failed to show clear benefit for hospitalized patients with coronavirus disease 2019 (COVID-19). Dynamics of virologic and immunologic biomarkers remain poorly understood. METHODS: Participants enrolled in the Therapeutics for Inpatients with COVID-19 trials were randomized to nmAb versus placebo. Longitudinal differences between treatment and placebo groups in levels of plasma nucleocapsid antigen (N-Ag), anti-nucleocapsid antibody, C-reactive protein, interleukin-6, and D-dimer at enrollment, day 1, 3, and 5 were estimated using linear mixed models. A 7-point pulmonary ordinal scale assessed at day 5 was compared using proportional odds models. RESULTS: Analysis included 2149 participants enrolled between August 2020 and September 2021. Treatment resulted in 20% lower levels of plasma N-Ag compared with placebo (95% confidence interval, 12%-27%; P \u3c .001), and a steeper rate of decline through the first 5 days (P \u3c .001). The treatment difference did not vary between subgroups, and no difference was observed in trajectories of other biomarkers or the day 5 pulmonary ordinal scale. CONCLUSIONS: Our study suggests that nmAb has an antiviral effect assessed by plasma N-Ag among hospitalized patients with COVID-19, with no blunting of the endogenous anti-nucleocapsid antibody response. No effect on systemic inflammation or day 5 clinical status was observed. CLINICAL TRIALS REGISTRATION: NCT04501978

Effect of Neutralizing Monoclonal Antibody Treatment on Early Trajectories of Virologic and Immunologic Biomarkers in Patients Hospitalized With COVID-19

BACKGROUND: Neutralizing monoclonal antibodies (nmAbs) failed to show clear benefit for hospitalized patients with coronavirus disease 2019 (COVID-19). Dynamics of virologic and immunologic biomarkers remain poorly understood. METHODS: Participants enrolled in the Therapeutics for Inpatients with COVID-19 trials were randomized to nmAb versus placebo. Longitudinal differences between treatment and placebo groups in levels of plasma nucleocapsid antigen (N-Ag), anti-nucleocapsid antibody, C-reactive protein, interleukin-6, and D-dimer at enrollment, day 1, 3, and 5 were estimated using linear mixed models. A 7-point pulmonary ordinal scale assessed at day 5 was compared using proportional odds models. RESULTS: Analysis included 2149 participants enrolled between August 2020 and September 2021. Treatment resulted in 20% lower levels of plasma N-Ag compared with placebo (95% confidence interval, 12%-27%; P \u3c .001), and a steeper rate of decline through the first 5 days (P \u3c .001). The treatment difference did not vary between subgroups, and no difference was observed in trajectories of other biomarkers or the day 5 pulmonary ordinal scale. CONCLUSIONS: Our study suggests that nmAb has an antiviral effect assessed by plasma N-Ag among hospitalized patients with COVID-19, with no blunting of the endogenous anti-nucleocapsid antibody response. No effect on systemic inflammation or day 5 clinical status was observed. CLINICAL TRIALS REGISTRATION: NCT04501978