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.

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.

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.

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.

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.

PLX8394, a new generation BRAF inhibitor, selectively inhibits BRAF in colonic adenocarcinoma cells and prevents paradoxical MAPK pathway activation.

BRAF inhibitors (BRAFi) are standard of care for the treatment of BRAF V600 mutation-driven metastatic melanoma, but can lead to paradoxical activation of the mitogen-activated protein kinase (MAPK) signalling pathway. This can result in the promotion of precancerous lesions and secondary neoplasms, mainly (but not exclusively) associated with pre-existing mutations in RAS genes. We previously reported a patient with synchronous BRAF-mutated metastatic melanoma and BRAF wt /KRAS G12D-metastatic colorectal cancer (CRC), whose CRC relapsed and progressed when treated with the BRAF inhibitor dabrafenib (GSK2118436). We used tissue from the resected CRC metastasis to derive a cell line, LM-COL-1, which directly and reliably mimicked the clinical scenario including paradoxical activation of the MAPK signalling pathway resulting in increased cell proliferation upon dabrafenib treatment. Novel BRAF inhibitors (PLX8394 and PLX7904), dubbed as "paradox breakers", were developed to inhibit V600 mutated oncogenic BRAF without causing paradoxical MAPK pathway activation. In this study we used our LM-COL-1 model alongside multiple other CRC cell lines with varying mutational backgrounds to demonstrate and confirm that the paradox breaker PLX8394 retains on-target inhibition of mutated BRAF V600 without paradoxically promoting MAPK signalling.

Cerebral Oximetry Monitoring to Maintain Normal Cerebral Oxygen Saturation during High-risk Cardiac Surgery: A Randomized Controlled Feasibility Trial.

BACKGROUND: Cerebral oxygen desaturation during cardiac surgery has been associated with adverse perioperative outcomes. Before a large multicenter randomized controlled trial (RCT) on the impact of preventing desaturations on perioperative outcomes, the authors undertook a randomized prospective, parallel-arm, multicenter feasibility RCT to determine whether an intervention algorithm could prevent desaturations. METHODS: Eight Canadian sites randomized 201 patients between April 2012 and October 2013. The primary outcome was the success rate of reversing cerebral desaturations below 10% relative to baseline in the intervention group. Anesthesiologists were blinded to the cerebral saturation values in the control group. Intensive care unit personnel were blinded to cerebral saturation values for both groups. Secondary outcomes included the area under the curve of cerebral desaturation load, enrolment rates, and a 30-day follow-up for adverse events. RESULTS: Cerebral desaturations occurred in 71 (70%) of the 102 intervention group patients and 56 (57%) of the 99 control group patients (P = 0.04). Reversal was successful in 69 (97%) of the intervention group patients. The mean cerebral desaturation load (SD) in the operating room was smaller for intervention group patients compared with control group patients (104 [217] %.min vs. 398 [869] %.min, mean difference, -294; 95% CI, -562 to -26; P = 0.03). This was also true in the intensive care unit (P = 0.02). There were no differences in adverse events between the groups. CONCLUSIONS: Study sites were successful in reversal of desaturation, patient recruitment, randomization, and follow-up in cardiac surgery, supporting the feasibility of conducting a large multicenter RCT.

Cytomegalovirus infection does not impact on survival or time to first treatment in patients with chronic lymphocytic leukemia.

Human cytomegalovirus (HCMV) is a widely prevalent herpes virus which establishes a state of chronic infection. The establishment of CMV-specific immunity controls viral reactivation and leads to the accumulation of very large numbers of virus-specific T cells which come to dominate the immune repertoire. There is concern that this may reduce the immune response to heterologous infections and HCMV infection has been associated with reduced survival in elderly people. Patients with chronic lymphocytic leukemia (B-CLL) suffer from a state of immune suppression but have a paradoxical increase in the magnitude of the CMV-specific T cell and humoral immune response. As such, there is now considerable interest in how CMV infection impacts on the clinical outcome of patients with B-CLL. Utilizing a large prospective cohort of patients with B-CLL (n = 347) we evaluated the relationship between HCMV seropositivity and patient outcome. HCMV seropositive patients had significantly worse overall survival than HCMV negative patients in univariate analysis (HR = 2.28, 95% CI: 1.34-3.88; P = 0.002). However, CMV seropositive patients were 4 years older than seronegative donors and this survival difference was lost in multivariate modeling adjusted for age and other validated prognostic markers (P = 0.34). No significant difference was found in multivariate modeling between HCMV positive and negative patients in relation to the time to first treatment (HR = 1.12, 95% CI: 0.68-1.84; P = 0.65). These findings in a second independent cohort of 236 B-CLL patients were validated. In conclusion no evidence that HCMV impacts on the clinical outcome of patients with B-CLL was found. Am. J. Hematol. 91:776-781, 2016. © 2016 Wiley Periodicals, Inc.

Impact of anesthetic handover on mortality and morbidity in cardiac surgery: a cohort study.

OBJECTIVE: Clinical handover is a critical moment in patient care. The authors tested the hypothesis that handover of anesthesia care is associated with increased mortality and morbidity in patients undergoing cardiac surgery. DESIGN: This was a single-center, retrospective cohort study of prospectively collected data. SETTING: The study was conducted in a quaternary care cardiac surgery center and university research hospital. PARTICIPANTS: All patients undergoing cardiac surgical procedures between April 1, 1999 and October 31, 2009 were included in the study. INTERVENTIONS: Propensity-score matching was used to adjust for differences between patients who received intraoperative handover of anesthesia care and those who did not, and in-hospital mortality and morbidity were compared using multivariate logistic modeling. MEASUREMENTS AND MAIN RESULTS: 14,421 patients met the inclusion criteria for this study; handover occurred in 966 cases (6.7%). After propensity-score matching, 7,137 patients were included for analysis. In-hospital mortality was 5.4% in the handover group and 4.0% in the non-handover group (match-adjusted odds ratio, 1.425; 95% confidence interval, 1.013-2.006; p = 0.0422); the incidence of major morbidity was 18.5% in the handover group and 15.6% in the non-handover group (match-adjusted odds ratio, 1.274; 95% confidence interval, 1.037-1.564; p = 0.0212). CONCLUSIONS: Handover of anesthetic care during cardiac surgery is associated with a 43% greater risk of in-hospital mortality and 27% greater risk of major morbidity. Further studies are required to explore this relationship and to systematically evaluate and improve the process of handover.

Impact of subglottic suctioning on the incidence of pneumonia after cardiac surgery: a retrospective observational study.

OBJECTIVE: Continuous aspiration of subglottic secretions (CASS) has been found to decrease the incidence of pneumonia in the general intensive care unit (ICU) population, but its benefit in cardiac surgery patients is unclear. The present study aimed to determine whether the routine use of CASS in cardiac surgical patients was associated with decreased pneumonia. DESIGN: A retrospective, single-center observational study. SETTING: The study was conducted in a quaternary care cardiac surgery center and university research hospital. PARTICIPANTS: 4,880 patients undergoing cardiac surgery were studied. INTERVENTIONS: The control group (no CASS) received a standard endotracheal tube and underwent surgery between April 1, 2007 and March 31, 2009. The intervention group (CASS) received a subglottic suctioning endotracheal tube and underwent surgery between June 1, 2009 and May 31, 2011. The primary outcome was the development of pneumonia, and the secondary outcomes were 30-day in-hospital mortality, ventilation time, need for tracheostomy, ICU length of stay (LOS), and hospital LOS. MEASUREMENTS AND MAIN RESULTS: The unadjusted incidence of pneumonia was 1.9% in the CASS group and 5.6% in the control group (p<0.0001). The CASS group also had lower 30-day in-hospital mortality (2.1% v 3.3%; p = 0.007), median ventilation time (8.42 v 7.3 hours; p<0.0001), and shorter median ICU LOS (1.77 v 1.17 days; p<0.0004) compared with the control group. Tracheostomy rates and median hospital LOS did not differ between groups. After adjusting using multivariable modeling, CASS remained an independent risk predictor for pneumonia (odds ratio [OR] 0.342, 95% confidence interval [CI] 0.239-0.490) and ICU LOS (OR 0.817, 95% CI 0.718-0.931). CONCLUSIONS: The universal implementation of CASS in a quaternary care cardiac surgical population was associated with a decreased incidence of pneumonia.

vanishing tassel2 encodes a grass-specific tryptophan aminotransferase required for vegetative and reproductive development in maize.

Auxin plays a fundamental role in organogenesis in plants. Multiple pathways for auxin biosynthesis have been proposed, but none of the predicted pathways are completely understood. Here, we report the positional cloning and characterization of the vanishing tassel2 (vt2) gene of maize (Zea mays). Phylogenetic analyses indicate that vt2 is a co-ortholog of TRYPTOPHAN AMINOTRANSFERASE OF ARABIDOPSIS1 (TAA1), which converts Trp to indole-3-pyruvic acid in one of four hypothesized Trp-dependent auxin biosynthesis pathways. Unlike single mutations in TAA1, which cause subtle morphological phenotypes in Arabidopsis thaliana, vt2 mutants have dramatic effects on vegetative and reproductive development. vt2 mutants share many similarities with sparse inflorescence1 (spi1) mutants in maize. spi1 is proposed to encode an enzyme in the tryptamine pathway for Trp-dependent auxin biosynthesis, although this biochemical activity has recently been questioned. Surprisingly, spi1 vt2 double mutants had only a slightly more severe phenotype than vt2 single mutants. Furthermore, both spi1 and vt2 single mutants exhibited a reduction in free auxin levels, but the spi1 vt2 double mutants did not have a further reduction compared with vt2 single mutants. Therefore, both spi1 and vt2 function in auxin biosynthesis in maize, possibly in the same pathway rather than independently as previously proposed.

Assessment of rabies exposure risk in a group of U.S. Air Force basic trainees - Texas, January 2014.

In January 2014, members of the Joint Base San Antonio (JBSA)-Lackland, Texas, preventive medicine and public health teams evaluated a U.S. Air Force basic training squadron for potential exposure in sleeping bays to rabies virus carried by Mexican free-tailed bats (Tadarida brasiliensis). Exposure to bats while asleep or otherwise unaware is an important risk factor for rabies in the United States. Over the past several decades, most indigenous human rabies infections in the United States have resulted from the bite of an infected bat, and the bite was not reported in more than half of the cases. Mexican free-tailed bats in Texas often carry rabies virus. Among 8,904 bats tested during 2001-2010, a total of 1,558 (18%) tested positive for rabies. To assess the risk to the Air Force trainees and identify those for whom rabies postexposure prophylaxis (PEP) might be indicated, Lackland preventive medicine and public health teams interviewed 922 persons (866 trainees and 56 instructors) and determined that PEP, consisting of human rabies immune globulin and the 4-dose vaccination series given over 14 days, was indicated for 200 persons (22%). This report describes the public health response to a mass indoor exposure to bats, including group-based rabies risk stratification, adverse reactions to PEP, and infestation remediation. These interventions can be considered for future mass exposures to bats.

Transesophageal echocardiography simulation is an effective tool in teaching psychomotor skills to novice echocardiographers.

BACKGROUND: Performance of transesophageal echocardiography (TEE) requires the psychomotor ability to obtain interpretable echocardiographic images. The purpose of this study was to determine the effectiveness of a simulation-based curriculum in which a TEE simulator is used to teach the psychomotor skills to novice echocardiographers and to compare instructor-guided with self-directed online delivery of the curriculum. METHODS: After institutional review board approval, subjects inexperienced in TEE completed an online review of TEE material prior to a baseline pre-test of TEE psychomotor skills using the simulator. Subjects were randomized to two groups. The first group received an instructor-guided lesson of TEE psychomotor skills with the simulator. The second group received a self-directed slide presentation of TEE psychomotor skills with the simulator. Both lessons delivered identical information. Following their respective training sessions, all subjects performed a post-test of their TEE psychomotor skills using the simulator. Two assessors rated the TEE performances using a validated scoring system for acquisition of images. RESULTS: Pre-test TEE simulator scores were similar between the two instruction groups (9.0 vs 5.0; P = 0.28). The scores in both groups improved significantly following training, regardless of the method of instruction (P < 0.0001). The improvement in scores (post-test scores minus pre-test scores) did not differ significantly between instruction groups (12.5 vs 14.5; P = 0.55). There was strong inter-rater reliability between assessors (α = 0.98; 95% confidence interval [CI]: 0.97 to 0.99). CONCLUSIONS: High-fidelity TEE simulators are an effective training adjunct for the acquisition of basic TEE psychomotor skills. There was no difference in improvement between the different modalities of instruction. Further research will examine the need for a faculty resource for a curriculum in which a simulator is used as an adjunct.

The impact of topical mydriatic ophthalmic solutions on retinal vascular reactivity and blood flow.

The impact of mydriatic agents on the standardized provocation of retinal vascular reactivity has not been systematically investigated. Our aim was to investigate the effect of commonly used mydriatic agents on the provoked vascular response of retinal arterioles. One eye was randomly selected for mydriasis from 10 healthy volunteers (age 23.3 ± 4.9 years). A single drop of: 1% tropicamide (T), or a combination of 0.8% tropicamide and 5% phenylephrine (TP), or 1% cyclopentolate (C) were instilled into the volunteers lower fornix at each of three visits. Volunteers underwent a standardized isocapnic hyperoxic provocation. Four retinal hemodynamic measurements were acquired with the Canon Laser Blood Flowmeter at equivalent positions on the superior temporal arteriole (STA) and inferior temporal arteriole (ITA) at baseline, during provocation and after recovery. Statistical analysis was performed using linear mixed-effect models. Pre- and post-dilation measurements indicated that pupil diameter increased with use of T, TP, C (all <0.001), while systolic blood pressure, diastolic blood pressure and intraocular pressure did not change significantly (all >0.05). In response to a standardized isocapnic hyperoxic challenge, blood vessel diameter, blood velocity and flow decreased in both the STA and ITA relative to baseline. Comparison between the change elicited by isocapnic hyperoxic gas stimuli with respect to blood vessel diameter, blood velocity, blood flow, were equivalent for each mydriatic agent in the STA (p = 0.66, p = 0.99, p = 0.99, respectively) and the ITA (p = 0.85, p = 0.80, p = 0.66, respectively). Furthermore, comparison between the change in the STA and ITA with respect to the above parameters showed equivalent responses in both vessels for each mydriatic agent: T (p = 0.92, p = 0.99, p = 0.35; respectively), TP (p = 0.89, p = 0.96, p = 0.62; respectively), and C (p = 0.87, p = 0.35, p = 0.56; respectively). The provoked retinal vascular reactivity response to standardized isocapnic hyperoxia was equivalent irrespective of the agent used to achieve mydriasis.

Measuring aortic valve coaptation surface area using three-dimensional transesophageal echocardiography.

BACKGROUND: As aortic valve (AV) repairs become more sophisticated, surgeons need increasingly detailed information about the structure and function of this valve. Unlike two-dimensional transesophageal echocardiography (2D-TEE), using three-dimensional (3D)-TEE makes it possible to image the entire AV. We hypothesized that measuring coaptation surface area (CoapSA) would be feasible and reproducible, and CoapSA would decrease in patients with aortic insufficiency. METHODS: We developed a new technique to calculate the AV-CoapSA using 3D-TEE. We measured the coaptation surfaces between the right coronary cusp/left coronary cusp, right coronary cusp/non-coronary cusp, and left coronary cusp/non-coronary cusp in ten normal AVs and ten AVs with moderate-severe aortic insufficiency (AI). Since computer models have previously shown that CoapSA is trapezoidal, we used the formula: trapezoid area = length × (medial coaptation height + lateral coaptation height)/2. The total CoapSA was calculated by adding all three areas. To adjust for valve size, we indexed the value to the diameter of the ventricular aortic junction (VAJ). Measurements were performed by two observers. RESULTS: The intra-observer correlation was 0.84 for one observer (P < 0.0001) and 0.93 for the other (P < 0.0001). The inter-observer correlation was 0.87 (P < 0.0001). In normal valves, the CoapSA [mean total (standard deviation)] was significantly greater than in the insufficient valves [1.61 (0.31) cm(2) vs 1.03 (0.22) cm(2), respectively; P < 0.001]. After indexing for the VAJ diameter, the total CoapSA remained significantly greater in normal valves than in insufficient valves. CONCLUSION: In this proof of concept study, we present a new and innovative technique to measure AV-CoapSA using 3D-TEE. It is reproducible and shows decreased CoapSA in patients with AI. Coaptation surface area may provide insight into mechanisms of AI and may have predictive value following AV repair.

Modeling the geographic distribution of serious mental illness in New Zealand.

PURPOSE: This study aims to estimate, apply, and validate a model of the risk of serious mental illness (SMI) in local service areas throughout New Zealand. METHODS: The study employs a secondary analysis of data from the Te Rau Hinengaro Mental Health Survey of 12,992 adults aged 16 years and over from the household population. It uses small area estimation (SAE) methods involving: (1) estimation of a logistic model of risk of SMI; (2) use of the foregoing model for computing estimates, using census data, for District Board areas; (3) validation of estimates against an alternative indicator of SMI prevalence. RESULTS: The model uses age, ethnicity, marital status, employment, and income to predict 92.2 % of respondents' SMI statuses, with a specificity of 95.9 %, sensitivity of 16.9 %, and an AUC of 0.73. The resulting estimates for the District Board areas ranged between 4.1 and 5.7 %, with confidence intervals from ±0.3 to ±1.1 %. The estimates demonstrated a correlation of 0.51 (p = 0.028) with rates of psychiatric hospitalization. CONCLUSIONS: The use of SAE methods demonstrated the capacity for deriving local prevalence rates of SMI, which can be validated against an available indicator.

Relative magnitude of vascular reactivity in the major arterioles of the retina.

The relative magnitude of vascular reactivity to inhaled gas stimuli in the major retinal arterioles has not been systematically investigated. The purpose of this study was to compare the magnitude of retinal vascular reactivity in response to inhaled gas provocation at equivalent measurement sites in the superior-, and inferior-, temporal retinal arterioles (STA, ITA). One randomly selected eye of each of 17 healthy volunteers (age 24.4 ± 4.7) was prospectively enrolled. Volunteers were connected to a sequential gas delivery circuit and a computer-controlled gas blender (RespirAct™, Thornhill Research Inc., Canada) and underwent an isocapnic hyperoxic challenge i.e. P(ET)O(2) of 500 mm Hg with P(ET)CO(2) maintained at 38 mm Hg during baseline and hyperoxia. Four retinal hemodynamic measurements were acquired using bi-directional laser Doppler velocimetry and simultaneous vessel densitometry (Canon Laser Blood Flowmeter, CLBF-100, Japan) at equivalent positions on the STA and ITA. Statistical analysis was performed using linear mixed-effect models. During the hyperoxic phase, the vessel diameter (STA p=0.004; ITA p=0.003), blood velocity (STA p<0.001; ITA p<0.001) and flow (STA p<0.001; ITA p<0.001) decreased in both the STA and the ITA relative to baseline. The diameter, velocity and flow were equivalent between STA and ITA at baseline and during hyperoxia; and their magnitude of change remained comparable with hyperoxia (p>0.05). The magnitude of retinal arteriolar vascular reactivity in response to isocapnic hyperoxic inhaled gas challenge was not significantly different between the STA and ITA. However, the correlation analysis did not reveal a significant relationship between the percentage changes in diameter, velocity and flow of the STA and ITA and did not demonstrate equal responses from the STA and ITA to gas provocation.

Declines in mental illness over the adult years: an enduring finding or methodological artifact?

OBJECTIVES: Epidemiological surveys have revealed dramatic declines in the prevalence of serious mental illness (SMI) as adults age. Analyses of these datasets have not determined whether this is attributable, on one hand, to declining incidence, shorter duration of condition, and lesser severity with age, or on the other hand, confounding variables and methodological biases. This study, thus, aims to test several such competing hypotheses. METHODS: This study employs a secondary analysis of data from the 2001/2002 US National Comorbidity Replication Survey of 9282 adults, 18 and older, living in the household population of the 48 contiguous states, as well as supplemental datasets from Israel, New Zealand, and other sources. RESULTS: One-year SMI prevalence rates in the US drop from 8.0% of adults 18-29 to 1.4% of the 65+, and to similar degrees in Israel and New Zealand. The drop in the US can be explained by the early onset of most mental illnesses, and declines in both incidence and duration of condition with age. Comorbidity also drops with age; however, the remaining diagnoses show a gradually increasing severity. Institutionalization explains a small portion of the declines, as does premature mortality of the seriously mentally ill that accounts for 16.3% of the decline. CONCLUSION: The results reveal that a substantial portion of the declines are explainable in terms of declining incidence and improving recovery rates, with some reduction also attributable to institutionalization and premature mortality which removes some older and more seriously disabled adults from the epidemiological survey populations.

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.

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.