Visual contrast detection cannot be predicted from surrogate measures of retinal ganglion cell number and sampling density in healthy young adults

To establish whether a clinically exploitable relationship exists between surrogate measures of retinal ganglion cell number and functional sampling density and visual contrast sensitivity in healthy young eyes

Self-Organizing Service Ecosystems: Exploring a New Concept for Service Science

The rapid advancements on digital technologies have positioned digital transformation as a central topic of interest to information systems (IS) researchers. However, our understanding of the nature, extent and dynamics of digital service ecosystems remains limited. This short paper contributes to IS and service science research by introducing the conceptualization of self-organizing service ecosystem as an analytical lens for understanding digital transformative phenomena in service ecosystems. To achieve this, we draw on the most recent narrative of value co-creation from service-dominant logic and on key definitions from the theory of self-organization. This paper also discusses future research directions emphasizing on the role and impact of technology in self-organizing service ecosystems

Test–retest repeatability of the NX-16: a three-dimensional (3D) body scanner in a male cohort

© 2019, The Author(s). Purpose: Whole-body three-dimensional scanning is a tool utilised for the collection of body girths, volume, and surface area measurements. Few studies have investigated the validity and repeatability of this technology. The aim of the present study was to investigate the test retest variability of the NX-16 body scanner (NX-16, TC2, Cary, North Carolina, USA). Methods: Phase one involved the measurement of a mannequin on 300 occasions (30 scans over 10 sessions). In phase two, 13 apparently healthy male participants were recruited; each participant was scanned a total of four times (two scans over two sessions). Stature, body mass, and body fat % were obtained. Fourteen girth measurements were obtained (chest, underbust, stomach, waist, seat, hip, R/L bicep, R/L thigh, R/L mid-thigh, and R/L calf). Coefficient of variation was calculated for measurements obtained. Results: Coefficient of variation for phase one ranged from 0.0% for the R calf, to 3.3% for the L thigh measurement. For phase two, values were higher, ranging from 0.5% for calf and chest to 4.6% for thigh measurements. Conclusions: Test–retest variability of the measurements provided by the NX-16 body scanner varied according to body location. However, variability within measurements was low using a mannequin or human participant. The NX-16 body scanner (TC2, Cary, North Carolina, USA) may be a useful tool for tracking changes in body composition over time during large population studies

The proportion of individuals likely to benefit from customized optic nerve head structure-function mapping

yesPurpose: Inter-individual variance in optic nerve head (ONH) position, axial length and location of the temporal raphe suggest that customizing mapping between visual field locations and optic nerve head sectors for individuals may be clinically useful. Here we quantify the proportion of the population predicted to have structure-function mappings that markedly deviate from “average”, and thus would benefit from customized mapping. Design: Database study and case report Participants: Population database of 2836 eyes from the Beijing Eye Study; single case report of an individual with primary open angle glaucoma Methods: Using the morphometric fundus data of the Beijing Eye Study on 2836 eyes and applying a recently developed model based on axial length and ONH position relative to the fovea, we determined for each measurement location in the 24-2 Humphrey visual field the proportion of eyes for which, in the customized approach as compared to the generalized approach, the mapped ONH sector was shifted into a different sector. We determined the proportion of eyes for which the mapped ONH location was shifted by 15°, 30° or 60°. Main outcome measures: Mapping correspondence between locations in visual field space to localized sectors on the optic nerve head Results: The largest inter-individual differences in mapping are in the nasal step region where the same visual field location can map to either the superior or inferior ONH depending on other anatomical features. For these visual field locations, approximately 12% of eyes showed a mapping opposite to conventional expectations. Conclusions: Anatomically customised mapping shifts the map markedly in approximately 12% of the general population in the nasal step region where visual field locations can map to the opposite pole of the ONH than conventionally considered. Early glaucomatous damage commonly affects this region, hence individually matching structure to function may prove clinically useful for the diagnosis and monitoring of progression within individuals.Australian Research Council Linkage Project 130100055 (industry partner, Heidelberg Engineering, GmBH, Germany)

Structure-Function Mapping: Variability and Conviction in Tracing Retinal Nerve Fiber Bundles and Comparison to a Computational Model

PURPOSE. We evaluated variability and conviction in tracing paths of retinal nerve fiber bundles (RNFBs) in retinal images, and compared traced paths to a computational model that produces anatomically-customized structure-function maps. METHODS. Ten retinal images were overlaid with 24-2 visual field locations. Eight clinicians and 6 naïve observers traced RNFBs from each location to the optic nerve head (ONH), recording their best estimate and certain range of insertion. Three clinicians and 2 naïve observers traced RNFBs in 3 images, 3 times, 7 to 19 days apart. The model predicted 108 ONH sectors relating to each location. Variability and repeatability in best estimates, certain range width, and differences between best estimates and model-predictions were evaluated. RESULTS. Median between-observer variability in best estimates was 278 (interquartile range [IQR] 208-388) for clinicians and 338 (IQR 228-508) for naïve observers. Median certain range width was 308 (IQR 148-458) for clinicians and 758 (IQR 458-1808) for naïve observers. Median repeatability was 108 (IQR 58-208) for clinicians and 158 (IQR 108-298) for naïve observers. All measures were worse further from the ONH. Systematic differences between model predictions and best estimates were negligible; median absolute differences were 178 (IQR 98-308) for clinicians and 208 (IQR 108-368) for naïve observers. Larger departures from the model coincided with greater variability in tracing. CONCLUSIONS. Concordance between the model and RNFB tracing was good, and greatest where tracing variability was lowest. When RNFB tracing is used for structure-function mapping, variability should be considered

National innovation systems, developing countries, and the role of intermediaries: a critical review of the literature

Developed over the past three decades, the national innovation system concept (NIS) has been widely used by both scholars and policy makers to explain how interactions between a set of distinct, nationally bounded institutions supports and facilitates technological change and the emergence and diffusion of new innovations. This concept provides a framework by which developing countries can adopt for purposes of catching up. Initially conceived on structures and interactions identified in economically advanced countries, the application of the NIS concept to developing countries has been gradual and has coincided – in the NIS literature – with a move away from overly macro-interpretations to an emphasis on micro-level interactions and processes, with much of this work questioning the nation state as the most appropriate level of analysis, as well as the emergence of certain intermediary actors thought to facilitate knowledge exchange between actors and institutions. This paper reviews the NIS literature chronologically, showing how this shift in emphasis has diminished somewhat the importance of both institutions, particularly governments, and the process of institutional capacity building. In doing so, the paper suggests that more recent literature on intermediaries such as industry associations may offer valuable insights to how institutional capacity building occurs and how it might be directed, particularly in the context of developing countries where governance capacities are often lacking, contributing to less effective innovation systems, stagnant economies, and unequal development

Atlantic Ocean Observing Networks: Cost and feasibility study

Results of a cost and feasibility study of the present and planned integrated Atlantic Ocean Observing System, including assessing the readiness and feasibility of implementation of different observing technologie

Immuno-transcriptomic profiling of extracranial pediatric solid malignancies.

We perform an immunogenomics analysis utilizing whole-transcriptome sequencing of 657 pediatric extracranial solid cancer samples representing 14 diagnoses, and additionally utilize transcriptomes of 131 pediatric cancer cell lines and 147 normal tissue samples for comparison. We describe patterns of infiltrating immune cells, T cell receptor (TCR) clonal expansion, and translationally relevant immune checkpoints. We find that tumor-infiltrating lymphocytes and TCR counts vary widely across cancer types and within each diagnosis, and notably are significantly predictive of survival in osteosarcoma patients. We identify potential cancer-specific immunotherapeutic targets for adoptive cell therapies including cell-surface proteins, tumor germline antigens, and lineage-specific transcription factors. Using an orthogonal immunopeptidomics approach, we find several potential immunotherapeutic targets in osteosarcoma and Ewing sarcoma and validated PRAME as a bona fide multi-pediatric cancer target. Importantly, this work provides a critical framework for immune targeting of extracranial solid tumors using parallel immuno-transcriptomic and -peptidomic approaches

Abnormal cardiovascular sympathetic and parasympathetic responses to physical and emotional stimuli in depersonalization disorder

BACKGROUND: Depersonalization disorder (DPD) is characterized by a subjective sense of unreality, disembodiment, emotional numbing and reduced psychogenic (sudomotor) sympathoexcitation. AIMS: Three related experiments utilized escalating physical and emotional challenges in 14 DPD participants and 16 controls aimed to elucidate (i) whether the cardiovascular sympathetic (SNS) and parasympathetic (PNS) nervous systems are implicated in DPD pathophysiology and (ii) if possible, to determine whether the blunted sympathoexcitation in DPD is peripherally or centrally mediated. METHOD: Participants completed the Beck Anxiety Inventory (BAI), Dissociative Experience Scale (DES), and Cambridge Depersonalization Scale (CDS). Study I recorded heart rate (HR) and blood pressure (BP) during 5 min supine baseline, 3 min sustained handgrip (HG), 3 min cold pressor (CP) and 5 min 60° head-up tilt (HUT). In study II, HR, BP, and heart rate variability (HRV) were recorded during 5 min simultaneous 60° HUT and continuous presentation of unpleasant images (5 s per image). Study III examined HR and BP orienting responses (ORs) to simultaneous 60° HUT and pseudorandom presentation of unpleasant, neutral and pleasant images (5 s per image 3 min 25 s). OR data was grouped by image valence post hoc. RESULTS: DPD BAI (p = 0.0004), DES (p = 0.0002), and CDS (p ≤ 0.0001) scores were higher than controls. The DPD group produced diminished diastolic BP (DBP) (p = 0.045) increases to HG. Other indices were comparable between groups. DPD participants produced diminished systolic BP (SBP) (p = 0.003) and DBP (p = 0.002) increases, but greater (p = 0.004) HR increases to CP. In study II, DPD high frequency HRV (HF-HRV)-indicating parasympathetic vagal activity-was reduced (p = 0.029). In study III, DPD DBP was higher throughout the 5 s duration of HUT/pseudorandom unpleasant image presentation (1 s, p = 0.002, 2 s p = 0.033, 3 s p = 0.001, 4 s p = 0.009, 5 s p = 0.029). CONCLUSIONS: Study I's BP pressor data supports previous findings of suppressed sympathoexcitation in DPD. The greater HR increases to CP, decreased HF-HRV in study II, and increased DBP during unpleasant ORs in study III implicates the SNS and PNS in DPD pathophysiology. These studies suggest the cardiovascular autonomic dysregulation in DPD is likely to be centrally-mediated

Effect of Deutetrabenazine on Chorea Among Patients With Huntington Disease A Randomized Clinical Trial

Importance Deutetrabenazine is a novel molecule containing deuterium, which attenuates CYP2D6 metabolism and increases active metabolite half-lives and may therefore lead to stable systemic exposure while preserving key pharmacological activity. Objective To evaluate efficacy and safety of deutetrabenazine treatment to control chorea associated with Huntington disease. Design, Setting, and Participants Ninety ambulatory adults diagnosed with manifest Huntington disease and a baseline total maximal chorea score of 8 or higher (range, 0-28; lower score indicates less chorea) were enrolled from August 2013 to August 2014 and randomized to receive deutetrabenazine (n = 45) or placebo (n = 45) in a double-blind fashion at 34 Huntington Study Group sites. Interventions Deutetrabenazine or placebo was titrated to optimal dose level over 8 weeks and maintained for 4 weeks, followed by a 1-week washout. Main Outcomes and Measures Primary end point was the total maximal chorea score change from baseline (the average of values from the screening and day-0 visits) to maintenance therapy (the average of values from the week 9 and 12 visits) obtained by in-person visits. This study was designed to detect a 2.7-unit treatment difference in scores. The secondary end points, assessed hierarchically, were the proportion of patients who achieved treatment success on the Patient Global Impression of Change (PGIC) and on the Clinical Global Impression of Change (CGIC), the change in 36-Item Short Form– physical functioning subscale score (SF-36), and the change in the Berg Balance Test. Results Ninety patients with Huntington disease (mean age, 53.7 years; 40 women [44.4%]) were enrolled. In the deutetrabenazine group, the mean total maximal chorea scores improved from 12.1 (95% CI, 11.2-12.9) to 7.7 (95% CI, 6.5-8.9), whereas in the placebo group, scores improved from 13.2 (95% CI, 12.2-14.3) to 11.3 (95% CI, 10.0-12.5); the mean between-group difference was –2.5 units (95% CI, –3.7 to –1.3) (P < .001). Treatment success, as measured by the PGIC, occurred in 23 patients (51%) in the deutetrabenazine group vs 9 (20%) in the placebo group (P = .002). As measured by the CGIC, treatment success occurred in 19 patients (42%) in the deutetrabenazine group vs 6 (13%) in the placebo group (P = .002). In the deutetrabenazine group, the mean SF-36 physical functioning subscale scores decreased from 47.5 (95% CI, 44.3-50.8) to 47.4 (44.3-50.5), whereas in the placebo group, scores decreased from 43.2 (95% CI, 40.2-46.3) to 39.9 (95% CI, 36.2-43.6), for a treatment benefit of 4.3 (95% CI, 0.4 to 8.3) (P = .03). There was no difference between groups (mean difference of 1.0 unit; 95% CI, –0.3 to 2.3; P = .14), for improvement in the Berg Balance Test, which improved by 2.2 units (95% CI, 1.3-3.1) in the deutetrabenazine group and by 1.3 units (95% CI, 0.4-2.2) in the placebo group. Adverse event rates were similar for deutetrabenazine and placebo, including depression, anxiety, and akathisia. Conclusions and Relevance Among patients with chorea associated with Huntington disease, the use of deutetrabenazine compared with placebo resulted in improved motor signs at 12 weeks. Further research is needed to assess the clinical importance of the effect size and to determine longer-term efficacy and safety