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The 2010 Nagoya Protocol is an international framework for access and benefit sharing (ABS) of the use of genetic and biological resources, with particular focus on indigenous communities. This is especially important in Africa, where local communities have a close reliance on environmental resources and ecosystems. However, national legislation and policies commonly lag behind international agreements, and this poses challenges for legal compliance as well as practical applications. This study reviews the academic literature on the Nagoya Protocol and ABS applications, and then considers the implications of this analysis for research in Africa. Results show that there is uneven engagement with the principles of the Nagoya Protocol across different academic disciplines; local communities are sometimes sidelined in these studies; and only 8% of researchers in the literature analysed are located in Africa. Future developments should focus on ensuring national compliance with the Nagoya Protocol, and that researchers and industry work in partnership with local African communities on ABS issues.

We consider two local reparations cases--the Evanston Restorative Housing Program and Chicago reparations for police torture survivors. We argue that the programs are shaped by the differing political opportunities, the local context, and the social location of their advocates given that one was constructed within government systems in Evanston and the other largely by grassroots organizers in Chicago. Furthermore, both programs are criticized to varying degrees as being exclusive in their design and implementation. We term this exclusion a process of deliberative marginalization, whereby some of the most vulnerable and most directly affected beneficiaries of a redress initiative are left out of deliberations and implementation decisions about the initiative's design. Subsequently, this study shows both the promise and constraints of reparations policy at the level of local government.

Introduction Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling condition that can affect adolescents during a vulnerable period of development. The underlying biological mechanisms for ME/CFS remain unclear and have rarely been investigated in the adolescent population, despite this period representing an age peak in the overall incidence. The primary objective of this is to provide a foundational set of biological data on adolescent ME/CFS patients. Data generated will be compared with controls and over several time points within each patient to potentially develop a biomarker signature of the disease, identify subsets or clusters of patients, and to unveil the pathomechanisms of the disease.Methods and analysis This protocol paper outlines a comprehensive, multilevel, longitudinal, observational study in paediatric ME/CFS. ME/CFS patients aged 12–19 years and controls will donate biosamples of urine, blood, and peripheral blood mononuclear cells for an in-depth omics profiling analysis (whole-genome sequencing, metabolomics and quantitative proteomics) while being assessed by gold-standard clinical and neuropsychological measures. ME/CFS patients will then be provided with a take-home kit that enables them to collect urine and blood microsamples during an average day and during days when they are experiencing postexertional malaise. The longitudinal repeated-measures study design is optimal for studying heterogeneous chronic diseases like ME/CFS as it can detect subtle changes, control for individual differences, enhance precision and boost statistical power. The outcomes of this research have the potential to identify biomarker signatures, aid in understanding the underlying mechanisms, and ultimately, improve the lives of children with ME/CFS.Ethics and dissemination This project was approved by the Royal Children’s Hospital’s Human Research Ethics Committee (HREC 74175). Findings from this study will be disseminated through peer-reviewed journal publications and presentations at relevant conferences. All participants will be provided with a summary of the study’s findings once the project is completed.

Background Cognitive impairment after stroke is common and is present in up to 60% of survivors. Stroke severity, indicated by both volume and location, is the most consequential predictor of cognitive impairment, with severe strokes predicting higher chances of cognitive impairment. The current investigation examines the associations of 2 stroke severity ratings and a caregiver‐report of poststroke functioning with longitudinal cognitive outcomes. Methods and Results One hundred fifty‐seven caregivers and stroke survivor dyads participated in the CARES (Caring for Adults Recovering From the Effects of Stroke) project, an ancillary study of the REGARDS (Reasons for Geographic and Racial Differences in Stroke) national cohort study. The Glasgow Outcome Scale and modified Rankin Scale scores collected at hospitalization discharge were included as 2 primary predictors of cognitive impairment. The number of caregiver‐reported problems and impairments at 9 months following stroke were included as a third predictor. Cognition was measured using a biennial telephone battery and included the domains of learning, memory, and executive functioning. Multiple cognitive assessments were analyzed up to 5 years poststroke, controlling for prestroke cognition and demographic variables of the stroke survivor. Separate mixed models showed significant main effects of the Glasgow Outcome Scale (b=0.3380 [95% CI, 0.14–0.5]; P=0.0009), modified Rankin Scale (b=−0.2119 [95% CI, −0.32 to −0.10]; P=0.0002), and caregiver‐reported problems (b=−0.0671 [95% CI, −0.09 to −0.04]; P

ObjectiveThe Dietary Guidelines for Americans has recommended consumption of a Mediterranean diet (MD) for overall health and wellbeing, and the US News & World Report has ranked the MD as the top diet overall for the past six consecutive years. However, it is uncertain if university students in the United States (US) have increased their adoption of this dietary approach over these past six years.DesignLongitudinal cross-sectional survey conducted in three cohorts (2018, 2020, 2022) utilizing regression models to assess MD Adherence and other relevant outcomes variables.SettingUniversity in the southern US.ParticipantsStudents (n = 761) enrolled in undergraduate introductory nutrition course.ResultsSurvey respondents were 83% female, 91% white, and 97% ages 18–24. Predictors of MD adherence were older age, female gender, and health-related qualifications. MD adherence was lowest in 2022. The 2022 group perceived less MD health benefits, weight loss, ethical concerns, natural content, and sensory appeal compared to the 2018 group. During the COVID-19 pandemic, changes in eating behavior were examined in the 2020 and 2022 groups. We observed that participants in the 2022 group had a greater frequency of snacking and a lower frequency of eating out compared to 2020 group.ConclusionMD adherence did not increase over time in US university students. These findings underscore the need for targeted interventions and education to promote healthier eating habits in university students.

Salt marshes are highly dynamic and biologically diverse ecosystems that serve as natural habitats for numerous salt-tolerant plants (halophytes). We investigated the bacterial communities associated with the roots and leaves of plants growing in the coastal salt marshes of the Bayfront Beach, located in Mobile, Alabama, United States. We compared external (epiphytic) and internal (endophytic) communities of both leaf and root plant organs. Using 16S rDNA amplicon sequencing methods, we identified 10 bacterial phyla and 59 different amplicon sequence variants (ASVs) at the genus level. Bacterial strains belonging to the phyla Proteobacteria, Bacteroidetes, and Firmicutes were highly abundant in both leaf and root samples. At the genus level, sequences of the genus Pseudomonas were common across all four sample types, with the highest abundance found in the leaf endophytic community. Additionally, Pantoea was found to be dominant in leaf tissue compared to roots. Our study revealed that plant habitat (internal vs. external for leaves and roots) was a determinant of the bacterial community structure. Co-occurrence network analyses enabled us to discern the intricate characteristics of bacterial taxa. Our network analysis revealed varied levels of ASV complexity in the epiphytic networks of roots and leaves compared to the endophytic networks. Overall, this study advances our understanding of the intricate composition of the bacterial microbiota in habitats (epiphytic and endophytic) and organs (leaf and root) of coastal salt marsh plants and suggests that plants might recruit habitat- and organ-specific bacteria to enhance their tolerance to salt stress.

Abstract Explanted polypropylene (PP) surgical mesh has frequently been reported to show surface alterations, such as cracks and flaking. However, to date the consequence of PP mesh degradation is not clearly understood, particularly its potential to influence the biological host response of surrounding tissues. Of particular concern is a possible host reaction to polypropylene particles released through degradation of surgical mesh in vivo. This concern is driven by previous studies which have postulated that an oxidative stress environment has the potential to etch away particles from the surface of a PP fibers. The release of such particles is of considerable significance as particles in the nano‐ to micro range have been shown to have the capacity to irritate cells and stimulate the immune system. The authors are not aware of any previous studies that have attempted to characterize, quantify or identify any particles released from PP mesh after exposure to an oxidative stress environment. Characterization of the PP mesh, post oxidative stress exposure, including identification of particles was achieved through application of a range of techniques: low voltage‐scanning electron microscopy (LV‐SEM), pyrolysis gas chromatography mass spectrometry (Pyr‐GCMS), nano‐Fourier transform infrared spectroscopy (nano‐FTIR), scattering‐type, scanning near‐field optical microscopy (s‐SNOM), atomic force microscopy (AFM), attenuated total reflectance‐Fourier transform infrared spectroscopy (ATR‐FTIR) and uniaxial tensile testing. The findings of this study indicate that oxidative stress alone is a major factor in the production of PP particle debris. PP debris identified within solution, using Pyr‐GCMS, was shown to be in order of the micron scale.

AbstractBackground: The Environmental Determinants of Islet Autoimmunity (ENDIA) pregnancy-birth cohort investigates the developmental origins of type 1 diabetes (T1D), with recruitment between 2013 and 2019. ENDIA is the first study in the world with comprehensive data and biospecimen collection during pregnancy, at birth and through childhood from at-risk children who have a first-degree relative with T1D. Environmental exposures are thought to drive the progression to clinical T1D, with pancreatic islet autoimmunity (IA) developing in genetically susceptible individuals. The exposures and key molecular mechanisms driving this progression are unknown. Persistent IA is the primary outcome of ENDIA; defined as a positive antibody for at least one of IAA, GAD, ZnT8 or IA2 on two consecutive occasions and signifies high risk of clinical T1D.Method: A nested case-control (NCC) study design with 54 cases and 161 matched controls aims to investigate associations between persistent IA and longitudinal omics exposures in ENDIA. The NCC study will analyse samples obtained from ENDIA children who have either developed persistent IA or progressed to clinical T1D (cases) and matched control children at risk of developing persistent IA. Control children were matched on sex and age, with all four autoantibodies absent within a defined window of the case’s onset date. Cases seroconverted at a median of 1.37 years (IQR 0.95, 2.56). Longitudinal omics data generated from approximately 16,000 samples of different biospecimen types, will enable evaluation of changes from pregnancy through childhood.Conclusions: This paper describes the ENDIA NCC study, omics platform design considerations and planned univariate and multivariate analyses for its longitudinal data. Methodologies for multivariate omics analysis with longitudinal data are discovery-focused and data driven. There is currently no single multivariate method tailored specifically for the longitudinal omics data that the ENDIA NCC study will generate and therefore omics analysis results will require either cross validation or independent validation.KEY MESSAGESThe ENDIA nested case-control study will utilize longitudinal omics data on approximately 16,000 samples from 190 unique children at risk of type 1 diabetes (T1D), including 54 who have developed islet autoimmunity (IA), followed during pregnancy, at birth and during early childhood, enabling the developmental origins of T1D to be explored.

IntroductionThe etiology of major depressive disorder (MDD) involves the interaction between genes and environment, including treatment. Early molecular signatures for treatment response and remission are relevant in a context of personalized medicine and stratification and reduce the time-to-decision. Therefore, we focused the analyses on patients that responded or remitted following a cognitive intervention of 8 weeks.MethodsWe used data from a randomized controlled trial (RCT) with MDD patients (N = 112) receiving a cognitive intervention. At baseline and 8 weeks, blood for DNA methylation (Illumina Infinium MethylationEPIC 850k BeadChip) was collected, as well as MADRS. First, responders (N = 24; MADRS-reduction of at least 50%) were compared with non-responders (N = 60). Then, we performed longitudinal within-individual analyses, for response (N = 21) and for remission (N = 18; MADRS smaller or equal to 9 and higher than 9 at baseline), respectively, as well as patients with no change in MADRS over time. At 8 weeks the sample comprised 84 individuals; 73 patients had DNA methylation for both time-points. The RnBeads package (R) was used for data cleaning, quality control, and differential DNA-methylation (limma). The within-individual paired longitudinal analysis was performed using Welch’s t-test. Subsequently gene-ontology (GO) pathway analyses were performed.ResultsNo CpG was genome-wide significant CpG (p < 5 × 10–8). The most significant CpG in the differential methylation analysis comparing response versus non-response was in the IQSEC1 gene (cg01601845; p = 1.53 × 10–6), linked to neurotransmission. The most significant GO-terms were linked to telomeres. The longitudinal response analysis returned 67 GO pathways with a p < 0.05. Two of the three most significant pathways were linked to sodium transport. The analysis for remission returned 46 GO terms with a p-value smaller than 0.05 with pathways linked to phosphatase regulation and synaptic functioning. The analysis with stable patients returned mainly GO-terms linked to basic cellular processes.DiscussionOur result suggest that DNA methylation can be suitable to capture early signs of treatment response and remission following a cognitive intervention in depression. Despite not being genome-wide significant, the CpG locations and GO-terms returned by our analysis comparing patients with and without cognitive impairment, are in line with prior knowledge on pathways and genes relevant for depression treatment and cognition. Our analysis provides new hypotheses for the understanding of how treatment for depression can act through DNA methylation and induce response and remission.

Abstract The conservation of migratory birds poses a fundamental challenge, their conservation requires coordinated action across the hemisphere, but those actions must be designed and implemented locally. To address this challenge, we describe a multilevel framework for linking broad‐scale, full annual cycle prioritizations to local conservation actions for migratory birds. We developed hemisphere‐scale spatial prioritizations for the full annual cycle of migratory birds that breed in six different ecosystems in North America. The full annual cycle prioritizations provide a hemispheric context within which regional priorities can be identified. Finer resolution, regional prioritizations can then inform local conservation actions more effectively. We describe the importance of local conservation practitioner contributions at each level of the process and provide two examples of regional spatial prioritizations that were developed to guide local action. The first example focused on coastal North and South Carolina, USA, and used information on marsh birds, shorebirds, ecological integrity, and co‐benefits for people to identify Cape Romain, South Carolina as a high‐priority site for conservation action. The second example in Colombia used information on migrant and resident birds to identify the Cauca Valley as a high‐priority site. The multilevel conceptual framework we describe is one pathway for identifying sites for implementation of local conservation actions that are guided by conservation priorities for migratory birds across their full annual cycle.

The purpose of the present study was to explore perceptions of shared reality in teacher-student partnerships in ballet, and how these perceptions were related to experiences of quality in the relationship and well-being. A longitudinal qualitative study design was adopted, with three female ballet students and their teacher participating in three semi-structured interviews each over an eight-month period. Data were analyzed using a combination of thematic and narrative analysis. Findings indicated that across the teacher-student relationships there were perceptions of a shared reality only on the professional and distanced level and not on a relational and personal level. This was achieved by a common experience of what matters in the world of ballet education as well as students finding their teacher as trustworthy. Furthermore, it appeared that the authoritarian apprenticeship culture in ballet, where the teachers give clear instructions and feedback, and where the student role is to listen and adapt to the teacher’s instructions, was a barrier to fully achieving a shared reality on a personal and deeper level. In turn, this influenced the quality of the relationship and the wellbeing of both teacher and students. The present study offers critical reflections on the cultural backdrop of teaching and learning in ballet and highlights the importance of teachers to facilitate a supportive, unconditional, and trustworthy relationship so that they can work together in a more productive manner.

Abstract Background Enhanced Recovery Pathways (ERP) have been shown to reduce racial disparities following surgery. The objective of this study is to determine whether ERP implementation mitigates racial disparities at a Veterans Affairs Hospital. Methods A retrospective cohort study was conducted using data obtained from the Veterans Affairs Surgical Quality Improvement Program. All patients undergoing elective colorectal surgery following ERP implementation were included. Current procedural terminology (CPT) codes were used to identify patients who underwent similar procedures prior to ERP implementation. Results Our study included 417 patients (314 pre-ERP vs. 103 ERP), 97.1% of which were male, with an average age of 62.32 (interquartile range (IQR): 25–90). ERP patients overall had a significantly shorter post-operative length of stay (pLOS) vs. pre-ERP patients (median 4 days (IQR: 3–6.5) vs. 6 days (IQR: 4–9) days (p

Canine Mast cell tumors (MCTs) constitute approximately 21% of all canine skin tumors. Despite the use of comprehensive grading systems, biological aggressiveness is sometimes difficult to predict, therefore there is a need for better prognostic markers. Progression in various cancers involves DNA hypermethylation, hypomethylation and epigenetic enzyme dysregulation. Therefore, global levels of 5-methylcytosine, 5-hydroxymethylcytosine and associated enzymes DNMT1, and IDH1 expression may predict MCT aggressiveness. A tissue microarray (TMA) with cores from 244 different tumor samples from 189 dogs was immunolabelled and used to quantify the global DNA methylation and hydroxymethylation levels as well as the levels of the enzymes involved in DNA methylation and their relationship with canine MCT outcome. From the immunolabelled TMA, H-scores were generated using QuPath (v0.1.2) and analyzed with associated patient data. High 5MC and DNMT1, and low IDH1 levels were associated with poorer outcome when looking at all canine MCT cases. High 5MC levels showed significance for shorter disease-free interval (DFI) in subcutaneous cases and high 5MC levels showed poorer DFI and overall survival (OS) in cases with Kiupel's grading system high grade. Cases with grade II in Patnaik's grading system showed better DFI with low levels of DNMT1 and better OS with low levels of 5MC and 5HMC. High levels of DNMT1 staining were also associated with shorter DFI for dermal MCTs. For cases that received adjuvant therapy in addition to surgery, all parameters except IDH1 were significantly associated with OS. Therefore, there is potential for DNA methylation status and levels of enzymes associated with DNA methylation pathways to better predict outcome in canine MCT, and to possibly influence treatment decisions.

IntroductionSituational judgment tests have been adopted by medical schools to assess decision-making and ethical characteristics of applicants. These tests are hypothesized to positively affect diversity in admissions by serving as a noncognitive metric of evaluation. The purpose of this study was to evaluate the performance of the Computer-based Assessment for Sampling Personal Characteristics (CASPer) scores in relation to admissions interview evaluations.MethodsThis was a cohort study of applicants interviewing at a public school of medicine in the southeastern United States in 2018 and 2019. Applicants took the CASPer test prior to their interview day. In-person interviews consisted of a traditional interview and multiple-mini-interview (MMI) stations. Between subjects, analyses were used to compare scores from traditional interviews, MMIs, and CASPer across race, ethnicity, and gender.Results1,237 applicants were interviewed (2018: n = 608; 2019: n = 629). Fifty-seven percent identified as female. Self-identified race/ethnicity included 758 White, 118 Black or African-American, 296 Asian, 20 Native American or Alaskan Native, 1 Native Hawaiian or Other Pacific Islander, and 44 No response; 87 applicants identified as Hispanic. Black or African-American, Native American or Alaskan Native, and Hispanic applicants had significantly lower CASPer scores than other applicants. Statistically significant differences in CASPer percentiles were identified for gender and race; however, between subjects, comparisons were not significant.ConclusionsThe CASPer test showed disparate scores across racial and ethnic groups in this cohort study and may not contribute to minimizing bias in medical school admissions.

Monoclonal antibody (mAb) aggregation can present major challenges for the development of biotherapeutics. An understanding of the molecular mechanisms of mAb aggregation is highly desirable both because it allows the performance of informed risk assessments regarding the criticality of mAb aggregates and because it may facilitate rational stabilization of aggregation prone regions. Here, we report the generation and isolation of dimer species of an IgG4 mAb (mAb1) that were present in stressed material under differing levels of temperature stress. We demonstrate the power of combining established higher order techniques with non-routine analysis, such as small-angle X-ray scattering, hydrogen/deuterium exchange mass spectrometry (HDX-MS), and protein conformational array enzyme-linked immunosorbent assay (PCA ELISA), and show that dimer species formed under temperature stress are structurally distinct from those present in unstressed mAb1. Specifically, stress-induced dimers are shown to adopt a more elongated conformation with a greater degree of unfolding when compared to native dimers. Analysis by HDX-MS and PCA ELISA, supported by in silico shape and charge molecular docking, enabled the identification of residues in both the variable and constant domains that appear to play a significant role in the dimerization of mAb1. Furthermore, we show that dimers formed under temperature stress are significantly more long-lived than those present in unstressed mAb1. We also present evidence that mAb1 dimers can behave as aggregation nuclei, and that dimers produced under high-temperature stress do so to a greater extent. This work presents an advancement in our understanding of the molecular mechanisms of mAb aggregation and highlights the importance of structural characterization of dimer species during the development of mAb biotherapeutics.Abbreviations: 2DSA: 2-Dimensional Spectrum Analysis; CD: Circular Dichroism; CDR: Complementarity-Determining Region; CQA: Critical Quality Attribute; DSC: Differential Scanning Calorimetry; FTIR: Fourier Transform Infrared spectroscopy; HDX-MS: Hydrogen/Deuterium Exchange Mass Spectrometry; HIC: Hydrophobic interaction chromatography; HMWS: High Molecular Weight Species; HOS: Higher Order Structure; mAb: Monoclonal Antibody; MD: Molecular Dynamics PCA; ELISA: Protein Conformational Array Enzyme-Linked Immunosorbent Assay; Rg: Radius of Gyration; SAXS: Small Angle X-ray Scattering; SE-HPLC: Size Exclusion High Performance Liquid Chromatography; SV-AUC: Sedimentation Velocity-Analytical Ultracentrifugation

Re-entrant feedback processing is a key mechanism of visual object-recognition, especially under compromised viewing conditions where only sparse information is available and object features must be interpolated. Illusory Contour stimuli are commonly used in conjunction with Visual Evoked Potentials (VEP) to study these filling-in processes, with characteristic modulation of the VEP in the ∼100-150 ms timeframe associated with this re-entrant processing. Substantial inter-individual variability in timing and amplitude of feedback-related VEP modulation is observed, raising the question whether this variability might underlie inter-individual differences in the ability to form strong perceptual gestalts. Backward masking paradig ms have been used to study inter-individual variance in the ability to form robust object perceptions before processing of the mask interferes with object-recognition. Some individuals recognize objects when the time between target object and mask is extremely short, whereas others struggle to do so even at longer target-to-mask intervals. We asked whether timing and amplitude of feedback-related VEP modulations were associated with individual differences in resistance to backward masking. Participants (N=40) showed substantial performance variability in detecting Illusory Contours at intermediate target-to-mask intervals (67 ms and 117 ms), allowing us to use kmeans clustering to divide the population into four performance groups (poor, low-average, high-average, superior). There was a clear relationship between the amplitude (but not the timing) of feedback-related VEP modulation and Illusory Contour detection during backward masking. We conclude that individual differences in the strength of feedback processing in neurotypical humans lead to differences in the ability to quickly establish perceptual awareness of incomplete visual objects.

Abstract Introduction: Implementation of genome-scale sequencing in clinical care has significant challenges: the technology is highly dimensional with many kinds of potential results, results interpretation and delivery require expertise and coordination across multiple medical specialties, clinical utility may be uncertain, and there may be broader familial or societal implications beyond the individual participant. Transdisciplinary consortia and collaborative team science are well poised to address these challenges. However, understanding the complex web of organizational, institutional, physical, environmental, technologic, and other political and societal factors that influence the effectiveness of consortia is understudied. We describe our experience working in the Clinical Sequencing Evidence-Generating Research (CSER) consortium, a multi-institutional translational genomics consortium. Methods: A key aspect of the CSER consortium was the juxtaposition of site-specific measures with the need to identify consensus measures related to clinical utility and to create a core set of harmonized measures. During this harmonization process, we sought to minimize participant burden, accommodate project-specific choices, and use validated measures that allow data sharing. Results: Identifying platforms to ensure swift communication between teams and management of materials and data were essential to our harmonization efforts. Funding agencies can help consortia by clarifying key study design elements across projects during the proposal preparation phase and by providing a framework for data sharing data across participating projects. Conclusions: In summary, time and resources must be devoted to developing and implementing collaborative practices as preparatory work at the beginning of project timelines to improve the effectiveness of research consortia.

Abstract Background Here, we address a pivotal factor in Alzheimer’s prevention—identifying those at risk early, when dementia can still be avoided. Recent research highlights an accelerated forgetting phenotype as a risk factor for Alzheimer’s disease. We hypothesized that delayed recall over 4 weeks would predict cognitive decline over 1 year better than 30-min delayed recall, the current gold standard for detecting episodic memory problems which could be an early clinical manifestation of incipient Alzheimer’s disease. We also expected hippocampal subfield volumes to improve predictive accuracy. Methods Forty-six cognitively healthy older people (mean age 70.7 ± 7.97, 21/46 female), recruited from databases such as Join Dementia Research, or a local database of volunteers, performed 3 memory tasks on which delayed recall was tested after 30 min and 4 weeks, as well as Addenbrooke’s Cognitive Examination III (ACE-III) and CANTAB Paired Associates Learning. Medial temporal lobe subregion volumes were automatically measured using high-resolution 3T MRI. The ACE-III was repeated after 12 months to assess the change in cognitive ability. We used univariate linear regressions and ROC curves to assess the ability of tests of delayed recall to predict cognitive decline on ACE-III over the 12 months. Results Fifteen of the 46 participants declined over the year (≥ 3 points lost on ACE-III). Four-week verbal memory predicted cognitive decline in healthy older people better than clinical gold standard memory tests and hippocampal MRI. The best single-test predictor of cognitive decline was the 4-week delayed recall on the world list (R 2 = .123, p = .018, β = .418). Combined with hippocampal subfield volumetry, 4-week verbal recall identifies those at risk of cognitive decline with 93% sensitivity and 86% specificity (AUC = .918, p

Abstract Background Early Alzheimer’s disease (AD) diagnosis is vital for development of disease-modifying therapies. Prior to significant brain tissue atrophy, several microstructural changes take place as a result of Alzheimer’s pathology. These include deposition of amyloid, tau and iron, as well as altered water homeostasis in tissue and some cell death. T2 relaxation time, a quantitative MRI measure, is sensitive to these changes and may be a useful non-invasive, early marker of tissue integrity which could predict conversion to dementia. We propose that different microstructural changes affect T2 in opposing ways, such that average ‘midpoint’ measures of T2 are less sensitive than measuring distribution width (heterogeneity). T2 heterogeneity in the brain may present a sensitive early marker of AD pathology. Methods In this cohort study, we tested 97 healthy older controls, 49 people with mild cognitive impairment (MCI) and 10 with a clinical diagnosis of AD. All participants underwent structural MRI including a multi-echo sequence for quantitative T2 assessment. Cognitive change over 1 year was assessed in 20 participants with MCI. T2 distributions were modelled in the hippocampus and thalamus using log-logistic distribution giving measures of log-median value (midpoint; T2μ) and distribution width (heterogeneity; T2σ). Results We show an increase in T2 heterogeneity (T2σ; p

Abstract Background Frailty refers to the reduction in homeostatic reserve resulting from an accumulation of physiological deficits over a lifetime. Frailty is common in older patients undergoing surgery and is an independent risk factor for post-operative mortality, morbidity and increased length of hospital stay. In frail individuals, stressors, such as surgery, can precipitate an acute deterioration in health, manifesting as delirium, falls, reduction in mobility or continence, rendering these individuals at an increased risk of adverse perioperative outcomes. However, little is known about how frailty affects the patient experience, functional ability and quality of life (QoL) after surgery. In addition, the distribution of frailty in this population is unknown. Methods We will conduct a multi-centre observational trial to investigate the relationship between patient reported outcome measures and preoperative frailty. We aim to recruit approximately two-hundred patients with operable, potentially curative colorectal cancer. Eligible patients will be identified at three hospital sites. QoL and functional ability (measured using EORTC QLQ-C30 and WHO-DAS 2.0 respectively) will be recorded at the pre-operative assessment clinic, and at 6 and 12 weeks postoperatively. Frailty scores including the Edmonton Frail Scale (EFS) and Rockwood clinical frailty scale (CFS) will be calculated both preoperatively, and at 12 weeks post-operatively. Secondary outcome measures including post-operative morbidity and mortality will be measured using Clavien Dindo classification and 90-day mortality. Discussion This observational feasibility study seeks to define the prevalence of frailty in older (> 65 years) colorectal cancer patients and understand how frailty impacts on patient reported outcome measures. This information will help to inform larger studies relating to treatment decision algorithms and promote shared decision making in this population.

Background During adolescence, deselection from sport occurs during team try-outs when month of birth, stage of growth and maturation may influence selection. Aim The purpose of this study was to identify differences in growth and maturity related factors between those selected and deselected in youth sports teams and identify short-term associations with continued participation. Subjects and methods Eight hundred and seventy participants, aged 11–17 years, were recruited from six sports try-outs in Saskatchewan, Canada: baseball, basketball, football, hockey, soccer and volleyball. Two hundred and forty-four of the initial 870 (28%) returned for follow-up at 36 months. Chronological (years from birth), biological (years from age at peak height velocity (APHV)) and relative (month of birth as it relates to the selection band) ages were calculated from measures of date of birth, date of test, height, sitting height and weight. Parental heights were measured or recalled and participant’s adult height predicted. Reference standards were used to calculate z-scores. Sports participation was self-reported at try-outs and at 36-month follow-up. Results There was an over-representation of players across all sports born in the first and second quartiles of the selection bands (p

Summary of Investigation: Assisted reproduction technologies (ART) are now commonly used to conceive. ART is associated with higher incidence of negative birth outcomes which may be due to altered cytokine signaling. Materials and Methods: This pilot study evaluated the suppressors of cytokine signaling SOCS and levels of proinflammatory cytokines ART and non-ART placentas (n=14 each) matched for maternal and gestational age, delivery method, pregnancy weight gain, and body mass index. Comparisons of advanced maternal age (AMA), with or without pre-term birth (PTB) were included. SOCS1, 2, and 3 levels were evaluated with immunohistochemistry and IFN-γ, IL1-β, IL-6, IL-8, IL-10, and TNF-α with ELISA. Results: ART was associated with significantly lower SOCS3. Although SOCS1/IL-10 and SOCS2 and 3/IFN-γ significantly associated in normal conception, associations were lost in ART. In AMA, placental SOCS1 and 2 were associated with IFN-γ, and SOCS3 with IL-6, but under 35 these associations were lost. Term birth was associated with placental SOCS1 inhibition of IL-8 and SOCS2 induction of IL-10, but PTB was not. Conclusion: Cytokine signaling is dysregulated in human placentas by ART which might be a cause of negative reproductive outcomes in ART.

The acquisition of sensory information about the world is a dynamic and interactive experience, yet the majority of sensory research focuses on perception without action and is conducted with participants who are passive observers with very limited control over their environment. This approach allows for highly controlled, repeatable experiments and has led to major advances in our understanding of basic sensory processing. Typical human perceptual experiences, however, are far more complex than conventional action-perception experiments and often involve bi-directional interactions between perception and action. Innovations in virtual reality (VR) technology offer an approach to close this notable disconnect between perceptual experiences and experiments. VR experiments can be conducted with a high level of empirical control while also allowing for movement and agency as well as controlled naturalistic environments. New VR technology also permits tracking of fine hand movements, allowing for seamless empirical integration of perception and action. Here, we used VR to assess how multisensory information and cognitive demands affect hand movements while reaching for virtual targets. First, we manipulated the visibility of the reaching hand to uncouple vision and proprioception in a task measuring accuracy while reaching toward a virtual target (n = 20, healthy young adults). The results, which as expected revealed multisensory facilitation, provided a rapid and a highly sensitive measure of isolated proprioceptive accuracy. In the second experiment, we presented the virtual target only briefly and showed that VR can be used as an efficient and robust measurement of spatial memory (n = 18, healthy young adults). Finally, to assess the feasibility of using VR to study perception and action in populations with physical disabilities, we showed that the results from the visual-proprioceptive task generalize to two patients with recent cerebellar stroke. Overall, we show that VR coupled with hand-tracking offers an efficient and adaptable way to study human perception and action.

Abstract Introduction: Ensuring equitable access to health care is a widely agreed-upon goal in medicine, yet access to care is a multidimensional concept that is difficult to measure. Although frameworks exist to evaluate access to care generally, the concept of “access to genomic medicine” is largely unexplored and a clear framework for studying and addressing major dimensions is lacking. Methods: Comprised of seven clinical genomic research projects, the Clinical Sequencing Evidence-Generating Research consortium (CSER) presented opportunities to examine access to genomic medicine across diverse contexts. CSER emphasized engaging historically underrepresented and/or underserved populations. We used descriptive analysis of CSER participant survey data and qualitative case studies to explore anticipated and encountered access barriers and interventions to address them. Results: CSER’s enrolled population was largely lower income and racially and ethnically diverse, with many Spanish-preferring individuals. In surveys, less than a fifth (18.7%) of participants reported experiencing barriers to care. However, CSER project case studies revealed a more nuanced picture that highlighted the blurred boundary between access to genomic research and clinical care. Drawing on insights from CSER, we build on an existing framework to characterize the concept and dimensions of access to genomic medicine along with associated measures and improvement strategies. Conclusions: Our findings support adopting a broad conceptualization of access to care encompassing multiple dimensions, using mixed methods to study access issues, and investing in innovative improvement strategies. This conceptualization may inform clinical translation of other cutting-edge technologies and contribute to the promotion of equitable, effective, and efficient access to genomic medicine.

Background: T 2 relaxation-based magnetic resonance imaging (MRI) signals may provide onset time for acute ischemic strokes with an unknown onset. The ability of visual and quantitative MRI-based methods in a cohort of hyperacute ischemic stroke patients was studied. Methods: A total of 35 patients underwent 3T (3 Tesla) MRI (

The data presented in this article relates to the manuscript entitled ‘Engineering of Chinese hamster ovary cell lipid metabolism results in an expanded ER and enhanced recombinant biotherapeutic protein production’, published in the Journal Metabolic Engineering [1]. In the article here, we present data examining the overexpression of the lipid metabolism modifying genes SCD1 and SREBF1 in CHO cells by densitometry of western blots and by using mass spectrometry to investigate the impact on specific lipid species. We also present immunofluorescence data at the protein level upon SCD1 and SREBF1 overexpression. The growth profile data during batch culture of control CHO cells and CHO cells engineered to overexpress SCD1 and SREBF1 during batch culture are also reported. Finally, we report data on the yields of model secretory recombinant proteins produced from control, SCD1 or SREBF1 engineered cells using a transient expression systems. Keywords: Chinese hamster ovary (CHO) cells, Lipid metabolism engineering, Cell line engineering, Difficult to express protein, Recombinant protein, Endoplasmic reticulum, Transcription factor engineering

Background: Patients with Major Depressive Disorder experience significantly reduced subjective Quality of Life (QOL), including impaired social and emotional functioning and greater fatigue and physical pain. Mounting evidence suggests that cognitive dysfunction (e.g., deficits in memory, executive function) contributes independently to the onset of reduced QOL, however the domain-specific nature of this relationship has not been investigated. The present study examined the relationship between specific cognitive domains (e.g., attention, spatial cognition) and specific deficits in mental and physical QOL in subjects with lifetime MDD, as well as acutely depressed, remitted and healthy participants. Methods: Data were obtained (N = 387) from the Cognitive Function and Mood Study (COFAMS), a cross-sectional study of emotional, functional and cognitive status in individuals with mood disorders. Participants' (acutely depressed n = 93, remitted n = 170, and healthy control n = 124) QOL was assessed with the 36-Item Short Form Health Survey (SF-36) and cognitive functioning was evaluated with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), the Colorado Assessment Tests (CATs) and the Psychology Experiment Building Language (PEBL). Results: Analyses revealed that poor immediate and delayed memory were associated with reduced mental QOL in individuals with lifetime MDD, acutely depressed, and healthy controls. In contrast, cognitive functioning was not associated with mental QOL in remitted patients. No cognitive domains were significantly related to physical QOL in any participant group. Conclusions: The result suggests that deficits in immediate and delayed memory may contribute to reduced mental QOL in acute MDD, whereas cognition does not appear to play a role in physical QOL. Memory should be considered important cognitive treatment targets for MDD patients suffering specifically from reduced mental QOL. Keywords: Quality of Life (QOL), Cognition, Major Depressive Disorder

The purpose of this study was to examine the relationships between athletic motor skill competencies (AMSC), maturation, sex, body mass index, physical performance, and psychological constructs (motivation to exercise, physical self-efficacy, and global self-esteem). Two-hundred and twenty-four children aged 11–13 years old were included in the study and sub-divided by sex. The athlete introductory movement screen (AIMS) and tuck jump assessment (TJA) were used to assess AMSC, while standing long jump distance assessed physical performance. Online surveys examined participants’ motivation to exercise, physical self-efficacy, and self-esteem. Trivial to moderate strength relationships were evident between AMSC and BMI (boys: rs = −0.183; girls: rs = −0.176), physical performance (boys: rs = 0.425; girls: rs = 0.397), and psychological constructs (boys: rs = 0.130–0.336; girls rs = 0.030–0.260), with the strength of relationships different between the sexes. Higher levels of AMSC were related to significantly higher levels of physical performance (d = 0.25), motivation to exercise (d = 0.17), and physical self-efficacy (d = 0.15–0.19) in both boys and girls. Enhancing AMSC may have mediating effects on levels of physical performance and psychological constructs in school-aged children, which may hold important implications for physical activity levels and the development of physical literacy.

The variational determination of the two-fermion reduced density matrix (2-RDM) is described for harmonically trapped, ultracold few-fermion systems in one dimension with equal spin populations. This is accomplished by formulating the problem as a semi-definite program, with the 2-RDM being subject to well-known N -representability conditions. The ground-state energies, as well as the density, pair-correlation function, and lower-order eigenvalues of the 2-RDM of various fermionic systems are found by utilising an augmented Lagrangian method for semi-definite programming. The ground-state energies are found to match well to those determined by full-configuration interaction and coupled-cluster calculations and the density, pair-correlation function, and eigenvalue results demonstrate that the salient features of these systems are well-described by this method. These results collectively demonstrate the utility of the reduced density matrix method firstly in describing strong correlation arising from short-range interactions, suggesting that the well-known N -representability conditions are sufficient to model ultracold fermionic systems, and secondly in illustrating the prospect of treating larger systems currently out of the reach of established methods.