Development of Level 1b Calibration and Validation Readiness, Implementation and Management Plans for GOES-R

A complement of Readiness, Implementation and Management Plans (RIMPs) to facilitate management of post-launch product test activities for the official Geostationary Operational Environmental Satellite (GOES-R) Level 1b (L1b) products have been developed and documented. Separate plans have been created for each of the GOES-R sensors including: the Advanced Baseline Imager (ABI), the Extreme ultraviolet and X-ray Irradiance Sensors (EXIS), Geostationary Lightning Mapper (GLM), GOES-R Magnetometer (MAG), the Space Environment In-Situ Suite (SEISS), and the Solar Ultraviolet Imager (SUVI). The GOES-R program has implemented these RIMPs in order to address the full scope of CalVal activities required for a successful demonstration of GOES-R L1b data product quality throughout the three validation stages: Beta, Provisional and Full Validation. For each product maturity level, the RIMPs include specific performance criteria and required artifacts that provide evidence a given validation stage has been reached, the timing when each stage will be complete, a description of every applicable Post-Launch Product Test (PLPT), roles and responsibilities of personnel, upstream dependencies, and analysis methods and tools to be employed during validation. Instrument level Post-Launch Tests (PLTs) are also referenced and apply primarily to functional check-out of the instruments

Reduced GABAergic Neuron Excitability, Altered Synaptic Connectivity, and Seizures in a KCNT1 Gain-of-Function Mouse Model of Childhood Epilepsy.

Gain-of-function (GOF) variants in K+ channels cause severe childhood epilepsies, but there are no mechanisms to explain how increased K+ currents lead to network hyperexcitability. Here, we introduce a human Na+-activated K+ (KNa) channel variant (KCNT1-Y796H) into mice and, using a multiplatform approach, find motor cortex hyperexcitability and early-onset seizures, phenotypes strikingly similar to those of human patients. Although the variant increases KNa currents in cortical excitatory and inhibitory neurons, there is an increase in the KNa current across subthreshold voltages only in inhibitory neurons, particularly in those with non-fast-spiking properties, resulting in inhibitory-neuron-specific impairments in excitability and action potential (AP) generation. We further observe evidence of synaptic rewiring, including increases in homotypic synaptic connectivity, accompanied by network hyperexcitability and hypersynchronicity. These findings support inhibitory-neuron-specific mechanisms in mediating the epileptogenic effects of KCNT1 channel GOF, offering cell-type-specific currents and effects as promising targets for therapeutic intervention

Validation of Reference Genes for the Relative Quantification of Gene Expression in Human Epicardial Adipose Tissue

BACKGROUND: Relative quantification is a commonly used method for assessing gene expression, however its accuracy and reliability is dependent upon the choice of an optimal endogenous control gene, and such choice cannot be made a priori. There is limited information available on suitable reference genes to be used for studies involving human epicardial adipose tissue. The objective of the current study was to evaluate and identify optimal reference genes for use in the relative quantification of gene expression in human epicardial fat depots of lean, overweight and obese subjects. METHODOLOGY/PRINCIPAL FINDINGS: Some of the commonly used reference genes including 18S, ACTB, RPL27, HPRT, CYCA, GAPDH, RPLPO, POLR2A and B2M were quantified using real-time PCR analysis. The expression stability of these genes was evaluated using Genorm, Normfinder and Bestkeeper algorithms. In addition, the effect of sample size on the validation process was studied by randomly categorizing subjects in two cohorts of n = 2 and n = 33. CONCLUSIONS/SIGNIFICANCE: CYCA, GAPDH and RPL27 were identified as the most stable genes common to all three algorithms and both sample sizes. Their use as reference gene pairs might contribute to the enhanced robustness of relative quantification in the studies involving the human epicardial adipose tissue

NeuroGrid: recording action potentials from the surface of the brain.

Recording from neural networks at the resolution of action potentials is critical for understanding how information is processed in the brain. Here, we address this challenge by developing an organic material-based, ultraconformable, biocompatible and scalable neural interface array (the 'NeuroGrid') that can record both local field potentials(LFPs) and action potentials from superficial cortical neurons without penetrating the brain surface. Spikes with features of interneurons and pyramidal cells were simultaneously acquired by multiple neighboring electrodes of the NeuroGrid, allowing for the isolation of putative single neurons in rats. Spiking activity demonstrated consistent phase modulation by ongoing brain oscillations and was stable in recordings exceeding 1 week's duration. We also recorded LFP-modulated spiking activity intraoperatively in patients undergoing epilepsy surgery. The NeuroGrid constitutes an effective method for large-scale, stable recording of neuronal spikes in concert with local population synaptic activity, enhancing comprehension of neural processes across spatiotemporal scales and potentially facilitating diagnosis and therapy for brain disorders

Diagnostic and economic evaluation of new biomarkers for Alzheimer's disease: the research protocol of a prospective cohort study

Doc number: 72 Abstract Background: New research criteria for the diagnosis of Alzheimer's disease (AD) have recently been developed to enable an early diagnosis of AD pathophysiology by relying on emerging biomarkers. To enable efficient allocation of health care resources, evidence is needed to support decision makers on the adoption of emerging biomarkers in clinical practice. The research goals are to 1) assess the diagnostic test accuracy of current clinical diagnostic work-up and emerging biomarkers in MRI, PET and CSF, 2) perform a cost-consequence analysis and 3) assess long-term cost-effectiveness by an economic model. Methods/design: In a cohort design 241 consecutive patients suspected of having a primary neurodegenerative disease are approached in four academic memory clinics and followed for two years. Clinical data and data on quality of life, costs and emerging biomarkers are gathered. Diagnostic test accuracy is determined by relating the clinical practice and new research criteria diagnoses to a reference diagnosis. The clinical practice diagnosis at baseline is reflected by a consensus procedure among experts using clinical information only (no biomarkers). The diagnosis based on the new research criteria is reflected by decision rules that combine clinical and biomarker information. The reference diagnosis is determined by a consensus procedure among experts based on clinical information on the course of symptoms over a two-year time period. A decision analytic model is built combining available evidence from different resources among which (accuracy) results from the study, literature and expert opinion to assess long-term cost-effectiveness of the emerging biomarkers. Discussion: Several other multi-centre trials study the relative value of new biomarkers for early evaluation of AD and related disorders. The uniqueness of this study is the assessment of resource utilization and quality of life to enable an economic evaluation. The study results are generalizable to a population of patients who are referred to a memory clinic due to their memory problems. Trial registration: NCT0145089

Hybrid and global kitchens - first and third world intersections (part 2)

Post-colonial movements for independence are voices of autonomy and independence before the onslaught of global organizations and cultures. This paper introduces the second set of themed papers in Gender, Place and Culture (see 13.2) which contains some of these voices, emanating from intensely private as well as communal and street kitchens; where women proclaim their visibility, economic value as food producers and transformers. The essays by Christie on the fiesta kitchens of central Mexico, Schroeder on the community kitchens of Bolivia and Peru, Robson on Islamic kitchens in rural Nigeria, Wardrop on the street vendors of south Durban and Pascali on Italian migrant kitchens in North East America, all acknowledge the vital contexts of \u27development\u27, urbanization, migration and industrialization to their stories, while also highlighting powerful elements of resistance and autonomy within the kitchen. As such the Western gaze records not so much the impacts of globalization as its cooking and transformation into something new, a hybrid dish, customized for local consumption. <br /

Adolescent self-harm in Ghana: a qualitative interview-based study of first-hand accounts

Background: Recent prevalence studies suggest that self-harm among adolescents in sub-Saharan Africa is as common as it is in high income countries. However, very few qualitative studies exploring first-person accounts of adolescent self-harm are available from sub-Saharan Africa. We sought to explore the experiences and first-person perspectives of Ghanaian adolescents reporting self-harm - for deeper reflections on the interpretive repertoires available in their cultural context for making sense of self-harm in adolescents. Methods: Guided by a semi-structured interview protocol, we interviewed one-to-one 36 adolescents (24 in-school adolescents and 12 street-connected adolescents) on their experiences of self-harm. We applied experiential thematic analysis to the data. Results: Adolescents’ description of the background to their self-harm identified powerlessness in the family context and unwanted adultification in the family as key factors leading up to self-harm among both in-school and street-connected adolescents. Adolescents’ explanatory accounts identified the contradictory role of adultification as a protective factor against self-harm among street-connected adolescents. Self-harm among in-school adolescents was identified as a means of “enactment of tabooed emotions and contestations”, as a “selfish act and social injury”, as “religious transgression”, while it was also seen as improving social relations. Conclusions: The first-person accounts of adolescents in this study implicate familial relational problems and interpersonal difficulties as proximally leading to self-harm in adolescents. Self-harm in adolescents is interpreted as an understandable response, and as a strong communicative signal in response to powerlessness and family relationship difficulties. These findings need to be taken into consideration in the planning of services in Ghana and are likely to be generalisable to many other countries in sub-Saharan Africa

Study protocol: EXERcise and Cognition In Sedentary adults with Early-ONset dementia (EXERCISE-ON)

<p>Abstract</p> <p>Background</p> <p>Although the development of early-onset dementia is a radical and invalidating experience for both patient and family there are hardly any non-pharmacological studies that focus on this group of patients. One type of a non-pharmacological intervention that appears to have a beneficial effect on cognition in older persons without dementia and older persons at risk for dementia is exercise. In view of their younger age early-onset dementia patients may be well able to participate in an exercise program. The main aim of the EXERCISE-ON study is to assess whether exercise slows down the progressive course of the symptoms of dementia.</p> <p>Methods/Design</p> <p>One hundred and fifty patients with early-onset dementia are recruited. After completion of the baseline measurements, participants living within a 50 kilometre radius to one of the rehabilitation centres are randomly assigned to either an <it>aerobic exercise program in a rehabilitation centre</it> or a <it>flexibility and relaxation program in a rehabilitation centre</it>. Both programs are applied three times a week during 3 months. Participants living outside the 50 kilometre radius are included in a feasibility study where participants join in a <it>daily physical activity program set at home making use of pedometers</it>. Measurements take place at baseline (entry of the study), after three months (end of the exercise program) and after six months (follow-up). Primary outcomes are cognitive functioning; psychomotor speed and executive functioning; (instrumental) activities of daily living, and quality of life. Secondary outcomes include physical, neuropsychological, and rest-activity rhythm measures.</p> <p>Discussion</p> <p>The EXERCISE-ON study is the first study to offer exercise programs to patients with early-onset dementia. We expect this study to supply evidence regarding the effects of exercise on the symptoms of early-onset dementia, influencing quality of life.</p> <p>Trial registration</p> <p>The present study is registered within The Netherlands National Trial Register (ref: NTR2124)</p

A development study and randomised feasibility trial of a tailored intervention to improve activity and reduce falls in older adults with mild cognitive impairment and mild dementia

Background: People with dementia progressively lose abilities and are prone to falling. Exercise- and activity-based interventions hold the prospect of increasing abilities, reducing falls, and slowing decline in cognition. Current falls prevention approaches are poorly suited to people with dementia, however, and are of uncertain effectiveness. We used multiple sources, and a co-production approach, to develop a new intervention, which we will evaluate in a feasibility randomised controlled trial (RCT), with embedded adherence, process and economic analyses. Methods: We will recruit people with mild cognitive impairment or mild dementia from memory assessment clinics, and a family member or carer. We will randomise participants between a therapy programme with high intensity supervision over 12 months, a therapy programme with moderate intensity supervision over 3 months, and brief falls assessment and advice as a control intervention. The therapy programmes will be delivered at home by mental health specialist therapists and therapy assistants. We will measure activities of daily living, falls and a battery of intermediate and distal health status outcomes, including activity, balance, cognition, mood and quality of life. The main aim is to test recruitment and retention, intervention delivery, data collection and other trial processes in advance of a planned definitive RCT. We will also study motivation and adherence, and conduct a process evaluation to help understand why results occurred using mixed methods, including a qualitative interview study and scales measuring psychological, motivation and communication variables. We will undertake an economic study, including modelling of future impact and cost to end-of-life, and a social return on investment analysis. Discussion: In this study, we aim to better understand the practicalities of both intervention and research delivery, and to generate substantial new knowledge on motivation, adherence and the approach to economic analysis. This will enable us to refine a novel intervention to promote activity and safety after a diagnosis of dementia, which will be evaluated in a definitive randomised controlled trial.\ud Trial registration: ClinicalTrials.gov: NCT02874300; ISRCTN 10550694