The Anatomy of the bill Tip of Kiwi and Associated Somatosensory Regions of the Brain: Comparisons with Shorebirds

Three families of probe-foraging birds, Scolopacidae (sandpipers and snipes), Apterygidae (kiwi), and Threskiornithidae (ibises, including spoonbills) have independently evolved long, narrow bills containing clusters of vibration-sensitive mechanoreceptors (Herbst corpuscles) within pits in the bill-tip. These ‘bill-tip organs’ allow birds to detect buried or submerged prey via substrate-borne vibrations and/or interstitial pressure gradients. Shorebirds, kiwi and ibises are only distantly related, with the phylogenetic divide between kiwi and the other two taxa being particularly deep. We compared the bill-tip structure and associated somatosensory regions in the brains of kiwi and shorebirds to understand the degree of convergence of these systems between the two taxa. For comparison, we also included data from other taxa including waterfowl (Anatidae) and parrots (Psittaculidae and Cacatuidae), non-apterygid ratites, and other probe-foraging and non probe-foraging birds including non-scolopacid shorebirds (Charadriidae, Haematopodidae, Recurvirostridae and Sternidae). We show that the bill-tip organ structure was broadly similar between the Apterygidae and Scolopacidae, however some inter-specific variation was found in the number, shape and orientation of sensory pits between the two groups. Kiwi, scolopacid shorebirds, waterfowl and parrots all shared hypertrophy or near-hypertrophy of the principal sensory trigeminal nucleus. Hypertrophy of the nucleus basorostralis, however, occurred only in waterfowl, kiwi, three of the scolopacid species examined and a species of oystercatcher (Charadriiformes: Haematopodidae). Hypertrophy of the principal sensory trigeminal nucleus in kiwi, Scolopacidae, and other tactile specialists appears to have co-evolved alongside bill-tip specializations, whereas hypertrophy of nucleus basorostralis may be influenced to a greater extent by other sensory inputs. We suggest that similarities between kiwi and scolopacid bill-tip organs and associated somatosensory brain regions are likely a result of similar ecological selective pressures, with inter-specific variations reflecting finer-scale niche differentiation

Interaction of amyloid and tau on cortical microstructure in cognitively unimpaired adults

INTRODUCTION: Neurite orientation dispersion and density imaging (NODDI), a multi-compartment diffusion-weighted imaging (DWI) model, may be useful for detecting early cortical microstructural alterations in Alzheimer's disease prior to cognitive impairment. METHODS: Using neuroimaging (NODDI and T1-weighted magnetic resonance imaging [MRI]) and cerebrospinal fluid (CSF) biomarker data (measured using Elecsys® CSF immunoassays) from 219 cognitively unimpaired participants, we tested the main and interactive effects of CSF amyloid beta (Aβ)42/Aβ40 and phosphorylated tau (p-tau) on cortical NODDI metrics and cortical thickness, controlling for age, sex, and apolipoprotein E ε4. RESULTS: We observed a significant CSF Aβ42/Aβ40 × p-tau interaction on cortical neurite density index (NDI), but not orientation dispersion index or cortical thickness. The directionality of these interactive effects indicated: (1) among individuals with lower CSF p-tau, greater amyloid burden was associated with higher cortical NDI; and (2) individuals with greater amyloid and p-tau burden had lower cortical NDI, consistent with cortical neurodegenerative changes. DISCUSSION: NDI is a particularly sensitive marker for early cortical changes that occur prior to gross atrophy or development of cognitive impairment

A perturbation-based balance training program for older adults: study protocol for a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Previous research investigating exercise as a means of falls prevention in older adults has shown mixed results. Lack of specificity of the intervention may be an important factor contributing to negative results. Change-in-support (CIS) balance reactions, which involve very rapid stepping or grasping movements of the limbs, play a critical role in preventing falls; hence, a training program that improves ability to execute effective CIS reactions could potentially have a profound effect in reducing risk of falling. This paper describes: 1) the development of a perturbation-based balance training program that targets specific previously-reported age-related impairments in CIS reactions, and 2) a study protocol to evaluate the efficacy of this new training program.</p> <p>Methods/Design</p> <p>The training program involves use of unpredictable, multi-directional moving-platform perturbations to evoke stepping and grasping reactions. Perturbation magnitude is gradually increased over the course of the 6-week program, and concurrent cognitive and movement tasks are included during later sessions. The program was developed in accordance with well-established principles of motor learning, such as individualisation, specificity, overload, adaptation-progression and variability. Specific goals are to reduce the frequency of multiple-step responses, reduce the frequency of collisions between the stepping foot and stance leg, and increase the speed of grasping reactions. A randomised control trial will be performed to evaluate the efficacy of the training program. A total of 30 community-dwelling older adults (age 64–80) with a recent history of instability or falling will be assigned to either the perturbation-based training or a control group (flexibility/relaxation training), using a stratified randomisation that controls for gender, age and baseline stepping/grasping performance. CIS reactions will be tested immediately before and after the six weeks of training, using platform perturbations as well as a distinctly different method of perturbation (waist pulls) in order to evaluate the generalisability of the training effects.</p> <p>Discussion</p> <p>This study will determine whether perturbation-based balance training can help to reverse specific age-related impairments in balance-recovery reactions. These results will help to guide the development of more effective falls prevention programs, which may ultimately lead to reduced health-care costs and enhanced mobility, independence and quality of life.</p

Gait disorders are associated with non-cardiovascular falls in elderly people: a preliminary study

BACKGROUND: The association between unexplained falls and cardiovascular causes is increasingly recognized. Neurally mediated cardiovascular disorders and hypotensive syndromes are found in almost 20 percent of the patients with unexplained falls. However, the approach to these patients remains unclear. Gait assessment might be an interesting approach to these patients as clinical observations suggests that those with cardiovascular or hypotensive causes may not manifest obvious gait alterations. Our primary objective is to analyze the association between gait disorders and a non-cardiovascular cause of falls in patients with unexplained falls. A second objective is to test the sensitivity and specificity of a gait assessment approach for detecting non-cardiovascular causes when compared with intrinsic-extrinsic classification. METHODS: Cross-sectional study performed in a falls clinic at a university hospital in 41 ambulatory elderly participants with unexplained falls. Neurally mediated cardiovascular conditions, neurological diseases, gait and balance problems were assessed. Gait disorder was defined as a gait velocity < 0.8 m/s or Tinetti Gait Score <9. An attributable etiology of the fall was determined in each participant. Comparisons between the gait assessment approach and the attributable etiology regarding a neurally mediated cardiovascular cause were performed. Fisher exact test was used to test the association hypothesis. Sensitivity and specificity of gait assessment approach and intrinsic-extrinsic classification to detect a non-cardiovascular mediated fall was calculated with 95% confidence intervals (CI95%). RESULTS: A cardiovascular etiology (orthostatic and postprandial hypotension, vasovagal syndrome and carotid sinus hypersensitivity) was identified in 14% of participants (6/41). Of 35 patients with a gait disorder, 34 had a non-cardiovascular etiology of fall; whereas in 5 out of 6 patients without a gait disorder, a cardiovascular diagnosis was identified (p < 0.001). Sensitivity and specificity of the presence of gait disorder for identifying a non-cardiovascular mediated cause was 97.1% (CI95% = 85–99) and 83% (CI95% = 36–99), respectively. CONCLUSION: In community dwelling older persons with unexplained falls, gait disorders were associated with non-cardiovascular diagnosis of falls. Gait assessment was a useful approach for the detection of a non-cardiovascular mediated cause of falls, providing additional value to this assessment

The Common Representative Intermediates Mechanism Version 2 in the United Kingdom Chemistry and Aerosols Model

Funder: Met Office and the Natural Environment Research CouncilFunder: ESA Climate Change InitiativeAbstract: We document the implementation of the Common Representative Intermediates Mechanism version 2, reduction 5 into the United Kingdom Chemistry and Aerosol model (UKCA) version 10.9. The mechanism is merged with the stratospheric chemistry already used by the StratTrop mechanism, as used in UKCA and the UK Earth System Model, to create a new CRI‐Strat mechanism. CRI‐Strat simulates a more comprehensive treatment of non‐methane volatile organic compounds (NMVOCs) and provides traceability with the Master Chemical Mechanism. In total, CRI‐Strat simulates the chemistry of 233 species competing in 613 reactions (compared to 87 species and 305 reactions in the existing StratTrop mechanism). However, while more than twice as complex than StratTrop, the new mechanism is only 75% more computationally expensive. CRI‐Strat is evaluated against an array of in situ and remote sensing observations and simulations using the StratTrop mechanism in the UKCA model. It is found to increase production of ozone near the surface, leading to higher ozone concentrations compared to surface observations. However, ozone loss is also greater in CRI‐Strat, leading to less ozone away from emission sources and a similar tropospheric ozone burden compared to StratTrop. CRI‐Strat also produces more carbon monoxide than StratTrop, particularly downwind of biogenic VOC emission sources, but has lower burdens of nitrogen oxides as more is converted into reservoir species. The changes to tropospheric ozone and nitrogen budgets are sensitive to the treatment of NMVOC emissions, highlighting the need to reduce uncertainty in these emissions to improve representation of tropospheric chemical composition

Cognitive Function of Children and Adolescents with Attention-Deficit/Hyperactivity Disorder in a 2-Year Open-Label Study of Lisdexamfetamine Dimesylate

BACKGROUND: SPD489-404 was the first 2-year safety study of lisdexamfetamine dimesylate in the treatment of attention-deficit/hyperactivity disorder in children and adolescents. In accordance with advice from the European Medicines Agency, assessment of cognitive function was a predefined safety outcome in SPD489-404. OBJECTIVE: The objective of this study was to assess cognitive function over 2 years in study SPD489-404, using the Cambridge Neuropsychological Test Automated Battery (CANTAB). METHODS: Participants aged 6-17 years received dose-optimised open-label lisdexamfetamine dimesylate (30, 50 or 70 mg/day) for 104 weeks. Cognition was assessed using four CANTAB tasks; Delayed Matching to Sample (DMS), Spatial Working Memory (SWM), Stop Signal Task (SST) and Reaction Time (RTI). Key and additional variables were pre-specified for each CANTAB task; groupwise mean percentage changes in key variables from baseline of > 5% were considered potentially clinically significant. RESULTS: All 314 enrolled participants received lisdexamfetamine dimesylate and were included in the safety population, and 191 (60.8%) completed the study. No potentially clinically significant deteriorations from baseline were observed in any key CANTAB variable over the 2 years of the study. Based on predefined thresholds, potentially clinically significant improvements from baseline were observed at 6 months (DMS median reaction time, mean per cent change, - 6.6%; SWM total between-search errors, - 22.8%; SST stop signal reaction time, -18.9%), and at the last on-treatment assessment (DMS median reaction time, - 6.5%; SWM total between-search errors, - 32.6%; SST stop signal reaction time, - 25.7%). CONCLUSIONS: Lisdexamfetamine dimesylate treatment for 2 years was not associated with deterioration of cognitive function in children and adolescents with attention-deficit/hyperactivity disorder. Although improvements in some cognitive measures were observed, lack of a control group makes interpretation of the findings difficult. Further studies of the impact of stimulants on cognition are required

Common Variants at 10 Genomic Loci Influence Hemoglobin A(1C) Levels via Glycemic and Nonglycemic Pathways

OBJECTIVE-Glycated hemoglobin (HbA(1c)), used to monitor and diagnose diabetes, is influenced by average glycemia over a 2- to 3-month period. Genetic factors affecting expression, turnover, and abnormal glycation of hemoglobin could also be associated with increased levels of HbA(1c). We aimed to identify such genetic factors and investigate the extent to which they influence diabetes classification based on HbA(1c) levels.RESEARCH DESIGN AND METHODS-We studied associations with HbA(1c) in up to 46,368 nondiabetic adults of European descent from 23 genome-wide association studies (GWAS) and 8 cohorts with de novo genotyped single nucleotide polymorphisms (SNPs). We combined studies using inverse-variance meta-analysis and tested mediation by glycemia using conditional analyses. We estimated the global effect of HbA(1c) loci using a multilocus risk score, and used net reclassification to estimate genetic effects on diabetes screening.RESULTS-Ten loci reached genome-wide significant association with HbA(1c), including six new loci near FN3K (lead SNP/P value, rs1046896/P = 1.6 x 10(-26)), HFE (rs1800562/P = 2.6 x 10(-20)), TMPRSS6 (rs855791/P = 2.7 x 10(-14)), ANK1 (rs4737009/P = 6.1 x 10(-12)), SPTA1 (rs2779116/P = 2.8 x 10(-9)) and ATP11A/TUBGCP3 (rs7998202/P = 5.2 x 10(-9)), and four known HbA(1c) loci: HK1 (rs16926246/P = 3.1 x 10(-54)), MTNR1B (rs1387153/P = 4.0 X 10(-11)), GCK (rs1799884/P = 1.5 x 10(-20)) and G6PC2/ABCB11 (rs552976/P = 8.2 x 10(-18)). We show that associations with HbA(1c) are partly a function of hyperglycemia associated with 3 of the 10 loci (GCK, G6PC2 and MTNR1B). The seven nonglycemic loci accounted for a 0.19 (%HbA(1c)) difference between the extreme 10% tails of the risk score, and would reclassify similar to 2% of a general white population screened for diabetes with HbA(1c).CONCLUSIONS-GWAS identified 10 genetic loci reproducibly associated with HbA(1c). Six are novel and seven map to loci where rarer variants cause hereditary anemias and iron storage disorders. Common variants at these loci likely influence HbA(1c) levels via erythrocyte biology, and confer a small but detectable reclassification of diabetes diagnosis by HbA(1c) Diabetes 59: 3229-3239, 201

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty