Characteristics of the Ontario Neurodegenerative Disease Research Initiative cohort.

INTRODUCTION: Understanding synergies between neurodegenerative and cerebrovascular pathologies that modify dementia presentation represents an important knowledge gap. METHODS: This multi-site, longitudinal, observational cohort study recruited participants across prevalent neurodegenerative diseases and cerebrovascular disease and assessed participants comprehensively across modalities. We describe univariate and multivariate baseline features of the cohort and summarize recruitment, data collection, and curation processes. RESULTS: We enrolled 520 participants across five neurodegenerative and cerebrovascular diseases. Median age was 69 years, median Montreal Cognitive Assessment score was 25, median independence in activities of daily living was 100% for basic and 93% for instrumental activities. Spousal study partners predominated; participants were often male, White, and more educated. Milder disease stages predominated, yet cohorts reflect clinical presentation. DISCUSSION: Data will be shared with the global scientific community. Within-disease and disease-agnostic approaches are expected to identify markers of severity, progression, and therapy targets. Sampling characteristics also provide guidance for future study design.

Retinal nerve fiber layer in frontotemporal lobar degeneration and amyotrophic lateral sclerosis.

Purpose: Tauopathy and transactive response DNA binding protein 43 (TDP-43) proteinopathy are associated with neurodegenerative diseases. These proteinopathies are difficult to detect in vivo. This study examined if spectral-domain optical coherence tomography (SD-OCT) can differentiate in vivo the difference in peripapillary retinal nerve fibre layer (pRNFL) thickness and macular retinal thickness between participants with presumed tauopathy (progressive supranuclear palsy) and those with presumed TDP-43 proteinopathy (amyotrophic lateral sclerosis and semantic variant primary progressive aphasia). Study design: Prospective, multi-centre, observational study. Materials and methods: pRNFL and macular SD-OCT images were acquired in both eyes of each participant using Heidelberg Spectralis SD-OCT. Global and pRNFL thickness in 6 sectors were analyzed, as well as macular thickness in a central 1 mm diameter zone and 4 surrounding sectors. Linear mixed model methods adjusting for baseline differences between groups were used to compare the two groups with respect to pRNFL and macular thickness. Results: A significant difference was found in mean pRNFL thickness between groups, with the TDP-43 group (n = 28 eyes) having a significantly thinner pRNFL in the temporal sector than the tauopathy group (n = 9 eyes; mean difference = 15.46 µm, SE = 6.98, p = 0.046), which was not significant after adjusting for multiple comparisons. No other significant differences were found between groups for pRNFL or macular thickness. Conclusion: The finding that the temporal pRNFL in the TDP-43 group was on average 15.46 µm thinner could potentially have clinical significance. Future work with larger sample sizes, longitudinal studies, and at the level of retinal sublayers will help to determine the utility of SD-OCT to differentiate between these two proteinopathies.

A randomised controlled trial to evaluate the impact of indoor living space on dairy cow production, reproduction and behaviour.

As a global society, we have a duty to provide suitable care and conditions for farmed livestock to protect animal welfare and ensure the sustainability of our food supply. The suitability and biological impacts of housing conditions for intensively farmed animals is a complex and emotive subject, yet poorly researched, meaning quantitative evidence to inform policy and legislation is lacking. Most dairy cows globally are housed for some duration during the year, largely when climatic conditions are unfavourable. However, the impact on biology, productivity and welfare of even the most basic housing requirement, the quantity of living space, remains unknown. We conducted a long-term (1-year), randomised controlled trial (CONSORT 10 guidelines) to investigate the impact of increased living space (6.5 m2 vs 3 m2 per animal) on critical aspects of cow biology, behaviour and productivity. Adult Holstein dairy cows (n = 150) were continuously and randomly allocated to a high or control living space group with all other aspects of housing remaining identical between groups. Compared to cows in the control living space group, cows with increased space produced more milk per 305d lactation (primiparous: 12,235 L vs 11,592 L, P < 0.01; multiparous: 14,746 L vs 14,644 L, P < 0.01) but took longer to become pregnant after calving (primiparous: 155 d vs 83 d, P = 0.025; multiparous: 133 d vs 109 d). In terms of behaviour, cows with more living space spent significantly more time in lying areas (65 min/d difference; high space group: 12.43 h/day, 95% CI = 11.70-13.29; control space group: 11.42 h/day, 95% CI = 10.73-12.12) and significantly less time in passageways (64 min/d), suggesting enhanced welfare when more space was provided. A key physiological difference between groups was that cows with more space spent longer ruminating each day. This is the first long term study in dairy cows to demonstrate that increased living space results in meaningful benefits in terms of productivity and behaviour and suggests that the interplay between farmed animals and their housed environment plays an important role in the concepts of welfare and sustainability of dairy farming.

Benchmarks for Needed Psychiatric Beds for the United States: A Test of a Predictive Analytics Model.

The ideal balanced mental health service system presupposes that planners can determine the need for various required services. The history of deinstitutionalization has shown that one of the most difficult such determinations involves the number of needed psychiatric beds for various localities. Historically, such assessments have been made on the basis of waiting and vacancy lists, expert estimates, or social indicator approaches that do not take into account local conditions. Specifically, this study aims to generate benchmarks or estimated rates of needed psychiatric beds for the 50 U.S. states by employing a predictive analytics methodology that uses nonlinear regression. Data used were secured primarily from the U.S. Census' American Community Survey and from the Substance Abuse and Mental Health Administration. Key predictors used were indicators of community mental health (CMH) service coverage, mental health disability in the adult population, longevity from birth, and the percentage of the 15+ who were married in 2018. The model was then used to calculate predicted bed rates based on the 'what-if' assumption of an optimal level of CMH service availability. The final model revealed an overall rate of needed beds of 34.9 per 100,000 population, or between 28.1 and 41.7. In total, 32% of the states provide inpatient psychiatric care at a level less than the estimated need; 28% at a level in excess of the need; with the remainder at a level within 95% confidence limits of the estimated need. These projections are in the low range of prior estimates, ranging from 33.8 to 64.1 since the 1980s. The study demonstrates the possibility of using predictive analytics to generate individualized estimates for a variety of service modalities for a range of localities.

An Analytic Model for Negative Obstacle Detection with Lidar and Numerical Validation Using Physics-Based Simulation.

Negative obstacles have long been a challenging aspect of autonomous navigation for ground vehicles. However, as terrestrial lidar sensors have become lighter and less costly, they have increasingly been deployed on small, low-flying UAV, affording an opportunity to use these sensors to aid in autonomous navigation. In this work, we develop an analytical model for predicting the ability of UAV or UGV mounted lidar sensors to detect negative obstacles. This analytical model improves upon past work in this area because it takes the sensor rotation rate and vehicle speed into account, as well as being valid for both large and small view angles. This analytical model is used to predict the influence of velocity on detection range for a negative obstacle and determine a limiting speed when accounting for vehicle stopping distance. Finally, the analytical model is validated with a physics-based simulator in realistic terrain. The results indicate that the analytical model is valid for altitudes above 10 m and show that there are drastic improvements in negative obstacle detection when using a UAV-mounted lidar. It is shown that negative obstacle detection ranges for various UAV-mounted lidar are 60-110 m, depending on the speed of the UAV and the type of lidar used. In contrast, detection ranges for UGV mounted lidar are found to be less than 10 m.

Impact of Virtual Reality-Generated Construction Environments at Different Heights on Postural Stability and Fall Risk.

BACKGROUND: Falls due to postural instability are common in construction environments especially from a height. The purpose of the study was to investigate the impact of virtual reality (VR)-generated environments at different virtual heights on postural stability. METHODS: Nineteen adults were analyzed for postural stability, tested in real (No VR) environment and in three VR environments, randomly assigned, at virtual heights of 0 ft. (VR0), 40 ft. (VR40), and 120 ft. (VR120). Postural stability was quantified using center of pressure postural sway variables and analyzed using a repeated measures analysis of variance (ANOVA). Participants also completed a simulation sickness questionnaire (SSQ) before and after VR exposure and a presence questionnaire (PQ) after VR exposure. FINDINGS: Significant postural instability (p < .05) was identified between VR and No VR, in which increased postural instability was evident in all VR conditions compared with No VR. Scores from SSQ were within a pre-post score difference of five and the PQ score was (104.21 ± 14.03). CONCLUSION/APPLICATION TO PRACTICE: Findings suggest that VR environments, regardless of virtual height, induced increased postural instability, which can be attributed to visual sensory conflicts to the postural control system created by VR exposure. Participants' subjective responses on SSQ and PQ confirmed the feasibility of using VR to represent realistic immersions in virtual heights. However, objectively, VR could potentially lead to postural instability, stressing caution. VR can be a potential tool for providing virtual high-altitude environment exposure for fall prevention training, however, more research is needed on postural adaptation with acute and chronic exposure to VR.

Butyrophilin 2A1 is essential for phosphoantigen reactivity by γδ T cells.

Gamma delta (γδ) T cells are essential to protective immunity. In humans, most γδ T cells express Vγ9Vδ2+ T cell receptors (TCRs) that respond to phosphoantigens (pAgs) produced by cellular pathogens and overexpressed by cancers. However, the molecular targets recognized by these γδTCRs are unknown. Here, we identify butyrophilin 2A1 (BTN2A1) as a key ligand that binds to the Vγ9+ TCR γ chain. BTN2A1 associates with another butyrophilin, BTN3A1, and these act together to initiate responses to pAg. Furthermore, binding of a second ligand, possibly BTN3A1, to a separate TCR domain incorporating Vδ2 is also required. This distinctive mode of Ag-dependent T cell activation advances our understanding of diseases involving pAg recognition and creates opportunities for the development of γδ T cell-based immunotherapies.

Virtual-Reality-Induced Visual Perturbations Impact Postural Control System Behavior.

BACKGROUND: Virtual reality (VR) is becoming a widespread tool in rehabilitation, especially for postural stability. However, the impact of using VR in a "moving wall paradigm" (visual perturbation), specifically without and with anticipation of the perturbation, is unknown. METHODS: Nineteen healthy subjects performed three trials of static balance testing on a force plate under three different conditions: baseline (no perturbation), unexpected VR perturbation, and expected VR perturbation. The statistical analysis consisted of a 1 × 3 repeated-measures ANOVA to test for differences in the center of pressure (COP) displacement, 95% ellipsoid area, and COP sway velocity. RESULTS: The expected perturbation rendered significantly lower (p < 0.05) COP displacements and 95% ellipsoid area compared to the unexpected condition. A significantly higher (p < 0.05) sway velocity was also observed in the expected condition compared to the unexpected condition. CONCLUSIONS: Postural stability was lowered during unexpected visual perturbations compared to both during baseline and during expected visual perturbations, suggesting that conflicting visual feedback induced postural instability due to compensatory postural responses. However, during expected visual perturbations, significantly lowered postural sway displacement and area were achieved by increasing the sway velocity, suggesting the occurrence of postural behavior due to anticipatory postural responses. Finally, the study also concluded that VR could be used to induce different postural responses by providing visual perturbations to the postural control system, which can subsequently be used as an effective and low-cost tool for postural stability training and rehabilitation.

Validation of Optical Coherence Tomography Retinal Segmentation in Neurodegenerative Disease.

PURPOSE: This study assessed agreement between an automated spectral-domain optical coherence tomography (SD-OCT) retinal segmentation software and manually corrected segmentation to validate its use in a prospective clinical study of neurodegenerative diseases (NDD). METHODS: The sample comprised 30 subjects with NDD, including vascular cognitive impairment, frontotemporal dementia, Parkinson's disease, and Alzheimer's disease. Macular SD-OCT scans were acquired and segmented using Heidelberg Spectralis. For the central foveal B scan of each eye, eight segmentation lines were examined to determine the proportion of each line that the software erroneously delineated. Errors in four lines were manually corrected in all B scans spanning a 6-mm circle centered on the foveola. Mean volume and thickness measurements for four retinal layers (total retina, retinal nerve fiber layer [RNFL], inner retinal layers, and outer retinal layers) were obtained before and after correction. RESULTS: The outer plexiform layer line had one of the lowest mean error ratios (2%), while RNFL had the highest (23%). Agreement between automated software and trained observer was excellent (ICC > 0.98) for retinal thickness and volume of all layers. Mean volume differences between software and observers for the four layers ranged from -0.003 to 0.006 mm3. Mean thickness differences ranged from -1.855 to 1.859 µm. CONCLUSIONS: Despite occasional small errors in software-generated retinal sublayer segmentation, agreement was excellent between software-derived and observer-corrected mean volume and thickness sublayer measurements. TRANSLATIONAL RELEVANCE: Automated SD-OCT segmentation software generates valid measurements of retinal layer volume and thickness in NDD subjects, thereby avoiding the need to manually correct nonobvious delineation errors.

The impact of geographic isolation on mental disability in the United States.

Geographic isolation has long been hypothesized to have a role in the origins and development of mental disabilities. A considerable body of research has established such a correlation. However, study designs have limited researchers' ability to establish a causal connection and rule out rival hypotheses. This study, therefore, aims to assess the strength of the geographic isolation - mental disability relationship and to disentangle it from alternative possibilities, namely that it reflects socioeconomic status, social isolation, economic inequality, or reverse causation. The study employs an analysis of variations in the rates of mental disability throughout 2960 U.S. counties using both Census and CDC data. In addition to partial correlation and ordinary least square analyses, the study employs two-stage least squares regression with instrumental variables (2SLS-IV), a procedure that permits resolution of the problem of endogeneity involving the potential effects of unmeasured variables and reverse causation. Results reveal that the initial bivariate effects of geographic isolation on rates of mental disability are robust after controls for socioeconomic status, income inequality, social isolation, and other predictors are introduced and when tested with the 2SLS-IV procedure. Most variation (54.4%) in county mental disability rates is accounted for by the independent effects of geographic isolation, socioeconomic status, income inequality, and other variables. The results presented, although not conclusive, supports more targeted service planning and more equitable resource investments in rural parts of the United States and other nations.

Evaluation of an Internet-based intervention for ICD patients with elevated symptoms of posttraumatic stress disorder.

BACKGROUND: To date, treatment to reduce posttraumatic stress disorder (PTSD) symptoms in implantable cardioverter defibrillator (ICD) patients has been limited by lack of symptom recognition, lack of provider referrals, barriers to treatment access, and inadequate evidence base of treatment effectiveness in this population. METHODS: Participants were 46 patients with ICDs (17 paired) with elevated PTSD symptoms who were recruited in electrophysiology clinics at community and university hospitals as well as ICD support forums. Participants were provided the Web-based, brief psychosocial intervention, which was tailored to ICD patients and contained elements of evidence-based cognitive-behavioral protocols for PTSD. Pretest and posttest measurement assessed participants' trauma experiences, mental health, and device-specific distress (device acceptance and shock anxiety). RESULTS: Postintervention scores on the PTSD Checklist (PCL; M = 35.5, SD = 10.09) were significantly lower than preintervention scores (M = 46.31, SD = 9.88), t (16) = 3.51, P = 0.003, d = 1.08. CONCLUSIONS: Preliminary results indicate that future research with a more robust design is warranted. Given limitations in accessibility of mental health providers to manage cardiac-related psychological sequelae, brief, Web-based intervention may be an effective, supplemental, clinical modality to offer treatment to this population.

Deinstitutionalization of mental hospitals and rates of psychiatric disability: An international study.

This study tests several hypotheses regarding the impact of deinstitutionalization of inpatient care on levels of psychiatric disability. It employs a secondary analysis of existing datasets from the World Health Organization's mental health program, the Global Burden of Disease study, as well as supplemental datasets on the national environments examined. The primary model accounts for 87.1% of the variation in global disability levels, but only a quarter or 28.3% of the recent changes in these levels between 1990 and 2015. One of the most important predictors of declines in mental disability is the proportion of a nation's health budget that is invested in mental health services.

Retinal blood oxygen saturation and aqueous humour biomarkers in early diabetic retinopathy.

PURPOSE: The aim of this study was to assess the relationship between retinal blood oxygen saturation (SO2 ) and specific aqueous humour (AH) concentrations of proangiogenic biomarkers in diabetic patients with nonproliferative diabetic retinopathy (NPDR) and to compare them with those of matched control subjects. METHODS: The sample comprised 14 participants with mild-to-moderate NPDR (69.1 ± 6.6 years) and 17 age-matched healthy controls (69.7 ± 6.3 years); all participants were previously scheduled for routine cataract extraction with intraocular lens implantation. Multiplex cytokine analyses of specific biomarkers, including vascular endothelial growth factor A (VEGF-A), angiopoietin2 (Ang2), epidermal growth factor (EGF), hepatocyte growth factor (HGF) and interleukin-8 (IL-8) were performed by BioPlex 200 system. Six non-invasive hyperspectral retinal images were acquired. RESULTS: Mean SO2 was significantly higher in both arterioles (94.4 ± 1.9 versus 93.0 ± 1.6) and venules (64.4 ± 5.6 versus 55.9 ± 4.8) of NPDR than in the healthy controls (p < 0.001). AH levels of HGF (p = 0.018), Ang2 (p = 0.005) and IL-8 (p = 0.034) were significantly higher, and EGF (p = 0.030) was significantly lower in NPDR subjects. The study demonstrated a correlation between venular retinal blood oxygen saturation and proangiogenic factors HGF (r = 0.558, p = 0.038), Ang2 (r = 0.556, p = 0.039) and EGF (r = -0.554, p = 0.040), but did not find any correlation for IL-8 (r = 0.330, p = 0.249) even though this biomarker was significantly higher in the diabetic group. CONCLUSION: To our knowledge, the present study is the first report considering the association between SO2 and AH concentrations of protein biomarkers in diabetic retinopathy. The biomarkers of interest have been shown to participate in cell death, which may explain higher oxygen saturation in NPDR.

Formation of metallacarboxylic acids through Hieber base reaction. A density functional theory study.

Using density functional theory (B97-D/ECP2/PCM//RI-BP86/ECP1 level), we have studied the effects of ligand variation on OH- uptake by transition-metal carbonyls (Hieber base reaction), i.e., LnM(CO) + OH- → [LnM(CO2H)]-, M = Fe, Ru, Os, L = CO, PMe3, PF3, py, bipy, Cl, H. The viability of this step depends notably on the nature of the co-ligands, and a large span of driving forces is predicted, ranging from ΔG = -144 kJ/mol to +122 kJ/mol. Based on evaluation of atomic charges from natural population analysis, it is the ability of the co-ligands to delocalize the additional negative charge (through their π-acidity) that is the key factor affecting the driving force for OH- uptake. Implications for the design of new catalysts for water gas shift reaction are discussed. Graphical abstract ᅟ.

Five-year rehospitalization experience of a state-wide cohort of persons with schizophrenia.

PURPOSE: This study has the objective of assessing the psychiatric rehospitalization experience of a large cohort of persons with schizophrenia and modeling the effects of personal and systemic conditions on rehospitalization risk. METHODS: The study employs a secondary analysis of US data from Massachusetts' casemix database of all patients discharged from acute general hospital units. It focuses on 11,291 patients during 1994-2000 who were discharged from acute adult psychiatric units. Predictors used include basic demographics, length of stay, continuity of care with doctors and facilities, diagnoses, discharge referral, type of insurance, and distance to and selected socioeconomic characteristics of the patient's home zip code. Data are analyzed with descriptive statistics and modeled with the Cox proportional hazard model. The model was assessed through split-half reliability testing, the generalized R2, and Harrell's Concordance Index. RESULTS: Overall, 13.4% of patients were rehospitalized within 1 month; 38.9% within 1 year; and 64.1% within 5 years. Predictors that are most strongly associated with lower rehospitalization rates include continuity of care, discharge to a chronic hospital, and density of home zipcode, whereas discharge to another acute psychiatric unit had the greatest effect on increasing risk of rehospitalization. Overall the Cox model has generalized R2 of 0.343 and a Concordance Index of 0.734. CONCLUSIONS: The results highlight the need to enhance the continuity of the relationships with providers, whether these are with the assigned psychiatrists or other therapists and case managers, as well as workplace issues involving staff turnover and hospital assignment and admitting policies.

Retinal perfusion changes in radiation retinopathy.

PURPOSE: To investigate retinal blood flow and oxygen saturation changes in patients diagnosed with retinopathy following plaque radiation treatment to treat choroidal melanoma. METHODS: Eight patients (mean age 55.75 years, SD 12.58 years) who have developed unilateral ischaemic radiation-related retinopathy as confirmed by wide-field fluorescein angiography were recruited for the study. The fellow eye with no other ocular or retinal pathology was used as control. Both eyes underwent measurement of total retinal blood flow (TRBF) and retinal blood oxygen saturation using prototype methodologies of Doppler Spectral Domain Optical Coherence Tomography (OCT) and Hyperspectral Retinal Camera, respectively. RESULTS: The average TRBF in the retinopathy eye was significantly lower compared to the fellow eye (33.48 ± 12.73 µl/min versus 50.37 ± 15.26 µl/min; p = 0.013). The arteriolar oxygen saturation (SaO2 ) and venular oxygen saturation (SvO2 ) were higher in the retinopathy eye compared to the fellow eye (101.11 ± 4.26%, versus 94.45 ± 5.79%; p = 0.008) and (62.96 ± 11.05% versus 51.24 ± 6.88%, p = 0.051), respectively. CONCLUSION: The ionizing radiation seems to have an impact on the TRBF, SaO2 and SvO2 , clinically presenting similar to a rapidly developing diabetic retinopathy. The results show an altered retinal vascular physiology in patients with radiation-related retinopathy.

Transfusion Requirements in Cardiac Surgery III (TRICS III): Study Design of a Randomized Controlled Trial.

OBJECTIVES: To determine if a restrictive transfusion threshold is noninferior to a higher threshold as measured by a composite outcome of mortality and serious morbidity. DESIGN: Transfusion Requirements in Cardiac Surgery (TRICS) III was a multicenter, international, open-label randomized controlled trial of two commonly used transfusion strategies in patients having cardiac surgery using a noninferiority trial design (ClinicalTrials.gov number, NCT02042898). SETTING: Eligible patients were randomized prior to surgery in a 1:1 ratio. PARTICIPANTS: Potential participants were 18 years or older undergoing planned cardiac surgery using cardiopulmonary bypass (CPB) with a preoperative European System for Cardiac Operative Risk Evaluation (EuroSCORE I) of 6 or more. INTERVENTIONS: Five thousand patients; those allocated to a restrictive transfusion group received a red blood cell (RBC) transfusion if the hemoglobin concentration (Hb) was less than 7.5 g/dL intraoperatively and/or postoperatively. Patients allocated to a liberal transfusion strategy received RBC transfusion if the Hb was less than 9.5 g/dL intraoperatively or postoperatively in the intensive care unit or less than 8.5 g/dL on the ward. MEASUREMENTS AND MAIN RESULTS: The primary outcome was a composite of all-cause mortality, myocardial infarction, stroke, or new onset renal dysfunction requiring dialysis at hospital discharge or day 28, whichever comes first. The primary outcome was analyzed as a per-protocol analysis. The trial monitored adherence closely as adherence to the transfusion triggers is important in ensuring that measured outcomes reflect the transfusion strategy. CONCLUSION: By randomizing prior to surgery, the TRICS III trial captured the most acute reduction in hemoglobin during cardiopulmonary bypass.

Behavioral Mental Health: An Emerging Field of Service or an Oxymoron?

Proliferation in the use of the terminology around behavioral mental health suggests, on one hand, an emerging field of service that integrates psychiatric, substance abuse, and related services. On the other hand, this development also raises questions about the coherence of this approach. This review explores the history, definitional issues, current trends, and available data on the impact of this field. It considers a variety of critiques of behavioral mental health, such as possibility that the field attempts to integrate fundamentally incompatible domains, that the term "behavioral mental health" is thus an oxymoron, and that it represents a co-optation by the insurance industry of traditional ideals of mental health and of behavioral medicine or as code for the implementation of a medical model that emphasizes short-term, behavioral, and psychopharmacological treatments at the expense of a truly biopsychosocial orientation. Other concerns include the focus on individual change and the effectiveness of behavioral health as a strategy for destigmatizing mental health. Recommendations for addressing the various barriers to realizing the ideals of behavioral mental health include revamping the role of managed care in oversight of treatment decisions, broadening the implementation of evidence-based treatment, and the development of treatment models that build on traditional social work practice models.

Quantitative analysis of antimicrobial use on British dairy farms.

Antimicrobial resistance has been reported to represent a growing threat to both human and animal health, and concerns have been raised around levels of antimicrobial usage (AMU) within the livestock industry. To provide a benchmark for dairy cattle AMU and identify factors associated with high AMU, data from a convenience sample of 358 dairy farms were analysed using both mass-based and dose-based metrics following standard methodologies proposed by the European Surveillance of Veterinary Antimicrobial Consumption project. Metrics calculated were mass (mg) of antimicrobial active ingredient per population correction unit (mg/PCU), defined daily doses (DDDvet) and defined course doses (DCDvet). AMU on dairy farms ranged from 0.36 to 97.79 mg/PCU, with a median and mean of 15.97 and 20.62 mg/PCU, respectively. Dose-based analysis ranged from 0.05 to 20.29 DDDvet, with a median and mean of 4.03 and 4.60 DDDvet, respectively. Multivariable analysis highlighted that usage of antibiotics via oral and footbath routes increased the odds of a farm being in the top quartile (>27.9 mg/PCU) of antimicrobial users. While dairy cattle farm AMU appeared to be lower than UK livestock average, there were a selection of outlying farms with extremely high AMU, with the top 25 per cent of farms contributing greater than 50 per cent of AMU by mass. Identification of these high use farms may enable targeted AMU reduction strategies and facilitate a significant reduction in overall dairy cattle AMU.

Motor Phenotype in Neurodegenerative Disorders: Gait and Balance Platform Study Design Protocol for the Ontario Neurodegenerative Research Initiative (ONDRI).

BACKGROUND: The association of cognitive and motor impairments in Alzheimer's disease and other neurodegenerative diseases is thought to be related to damage in the common brain networks shared by cognitive and cortical motor control processes. These common brain networks play a pivotal role in selecting movements and postural synergies that meet an individual's needs. Pathology in this "highest level" of motor control produces abnormalities of gait and posture referred to as highest-level gait disorders. Impairments in cognition and mobility, including falls, are present in almost all neurodegenerative diseases, suggesting common mechanisms that still need to be unraveled. OBJECTIVE: To identify motor-cognitive profiles across neurodegenerative diseases in a large cohort of patients. METHODS: Cohort study that includes up to 500 participants, followed every year for three years, across five neurodegenerative disease groups: Alzheimer's disease/mild cognitive impairment, frontotemporal degeneration, vascular cognitive impairment, amyotrophic lateral sclerosis, and Parkinson's disease. Gait and balance will be assessed using accelerometers and electronic walkways, evaluated at different levels of cognitive and sensory complexity, using the dual-task paradigm. RESULTS: Comparison of cognitive and motor performances across neurodegenerative groups will allow the identification of motor-cognitive phenotypes through the standardized evaluation of gait and balance characteristics. CONCLUSIONS: As part of the Ontario Neurodegenerative Research Initiative (ONDRI), the gait and balance platform aims to identify motor-cognitive profiles across neurodegenerative diseases. Gait assessment, particularly while dual-tasking, will help dissect the cognitive and motor contribution in mobility and cognitive decline, progression to dementia syndromes, and future adverse outcomes including falls and mortality.