Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

Neuroimaging-based classification of PTSD using data-driven computational approaches: a multisite big data study from the ENIGMA-PGC PTSD consortium

Background: Recent advances in data-driven computational approaches have been helpful in devising tools to objectively diagnose psychiatric disorders. However, current machine learning studies limited to small homogeneous samples, different methodologies, and different imaging collection protocols, limit the ability to directly compare and generalize their results. Here we aimed to classify individuals with PTSD versus controls and assess the generalizability using a large heterogeneous brain datasets from the ENIGMA-PGC PTSD Working group. Methods: We analyzed brain MRI data from 3,477 structural-MRI; 2,495 resting state-fMRI; and 1,952 diffusion-MRI. First, we identified the brain features that best distinguish individuals with PTSD from controls using traditional machine learning methods. Second, we assessed the utility of the denoising variational autoencoder (DVAE) and evaluated its classification performance. Third, we assessed the generalizability and reproducibility of both models using leave-one-site-out cross-validation procedure for each modality. Results: We found lower performance in classifying PTSD vs. controls with data from over 20 sites (60 % test AUC for s-MRI, 59 % for rs-fMRI and 56 % for D-MRI), as compared to other studies run on single-site data. The performance increased when classifying PTSD from HC without trauma history in each modality (75 % AUC). The classification performance remained intact when applying the DVAE framework, which reduced the number of features. Finally, we found that the DVAE framework achieved better generalization to unseen datasets compared with the traditional machine learning frameworks, albeit performance was slightly above chance. Conclusion: These results have the potential to provide a baseline classification performance for PTSD when using large scale neuroimaging datasets. Our findings show that the control group used can heavily affect classification performance. The DVAE framework provided better generalizability for the multi-site data. This may be more significant in clinical practice since the neuroimaging-based diagnostic DVAE classification models are much less site-specific, rendering them more generalizable.Stress-related psychiatric disorders across the life spa

Reach out and touch me: effects of four distinct haptic technologies on affective touch in virtual reality

Virtual reality presents an extraordinary platform for multimodal communication. Haptic technologies have been shown to provide an important contribution to this by facilitating co-presence and allowing affective communication. However, the findings of the affective influences rely on studies that have used myriad different types of haptic technology, making it likely that some forms of tactile feedback are more efficient in communicating emotions than others. To find out whether this is true and which haptic technologies are most effective, we measured user experience during a communication scenario featuring an affective agent and interpersonal touch in virtual reality. Interpersonal touch was simulated using two types of vibrotactile actuators and two types of force feedback mechanisms. Self-reports of subjective experience of the agent’s touch and emotions were obtained. The results revealed that, regardless of the agent’s expression, force feedback actuators were rated as more natural and resulted in greater emotional interdependence and a stronger sense of co-presence than vibrotactile touch

Deep and ongoing response of castrate-resistant prostate cancer on very low-dose enzalutamide in an elderly chemotherapy-naïve patient: a case report

BACKGROUND: Enzalutamide is an orally administered drug that blocks signaling in the androgen receptor with clinical activity in both chemotherapy-naive and post-chemotherapy patients with castrate-resistant prostate cancer (CRPC). Enzalutamide is generally well-tolerated, but dose reductions are nonetheless needed in case of side effects. CASE: An 82-year-old patient with chemotherapy-naive metastatic castration-resistant prostate cancer was treated with a very low dose of 40 mg enzalutamide once daily. The trough levels of enzalutamide and the active metabolite N-desmethylenzalutamide were 4.5 mg/L and 3.0 mg/L, respectively. This exposure provided a long-term response without any significant side effects. CONCLUSION: Low doses of enzalutamide may be efficacious, while also reducing the risk of side effects. Furthermore, employing a lower dose would reduce healthcare costs and increase access to enzalutamide. Studies exploring the efficacy of lower enzalutamide doses are warranted

Safety-licensing assessment of NASAP reactor concepts and fuel cycle facilities

Assessments are presented of the safety/licensability of reactor concepts based on information supplied by the Nonproliferation Alternative Systems Assessment Program (NASAP) characterization contractors in their updated responses to the data package for NASAP Rolling Report II. The assessment of the LMFBR includes information from a characterization contractor on alternate fuel cycles but does not include information provided by a characterization contractor on plant-related safety issues. The information provided by the characterization contractors was supplemented by assessments provided by the U. S. Nuclear Regulatory Commission

Experimental evaluation of fission-gas release in LMFBR subassemblies using an electrically heated test section with sodium as coolant

A description is given of an out-of-pile experiment which simulated fission-gas release in current-design uranium-oxide fuel subassemblies of liquid- metal-cooled fast breeder reactors (LMFBR's) and which was performed to evaluate the potential for pin-to-pin failure propagation due to thermal transients induced in adjacent fuel pins. A sodium-cooled test section containing three electrically heated pins was used. Gas (angon or xenon), injected as a jet through a needle protruding into the flow cross-sectional area of the test section, was made to impinge on one of the heater pins. Data are presented regarding the measured cladding-temperature rise and the calculated local heat- transfer coefficient in the impingement area, with the following parameters: gas type, needle internal diameter, heat flux, coolant flow rate, gas-plenum pressure and temperature, and axial location with respect to the gas jet. The cladding- temperature rises measured represent upper values, since the conditions under which they were obtained are conservative. There are two reasons for this: (a) The gasrelease rates correspond to those that would prevail if the internal resistance to the flow of gas, between the gas plenum and the point of release of the fuel pin, were negligibly small; (b) the tests were performed under steady- state conditions, whereas, under actual reactor conditions, the gas-release rates would be decreasing with time because of the fixed fission-gas inventory. For a narrow range of gas-release rates under subsonic and near-subsonic conditions, cladding-temperature rises were found to occur in the impingement area, for the above conservative conditions, of up to approximates 240 deg C at a heat flux of 250 W/cm/sup 2/. (auth

Sleep apnea and sleep : diagnostic aspects

Background: Patients with sleep apnea have frequent apneas and hypopneas during sleep. Apneas can be either central or obstructive. The apnea-hypopnea index (AHI) is the mean number of apneas and hypopneas per hour of sleep. Aims: 1) To evaluate the effect of a mandibular advancement device on obstructive apneas and sleep; 2) to evaluate the influence of body position on central apnea frequency; 3) to investigate whether obstructive or central apnea is related to mortality in patients with stroke; and 4) to investigate sleep and sleeping positions in women. Methods: Subjects were investigated during whole-night sleep respiratory recordings, either polysomnography including continuous recordings of EEG, EOG, EMG, airflow, respiratory effort, ECG, pulse oximetry and body position, or simplified sleep apnea recordings without EEG, EOG and EMG. Results: The frequency of obstructive apneas, hypopneas and arousals decreased and rapid eye movement (REM) sleep increased in patients with mild, moderate and severe sleep apnea during treatment with a mandibular advancement device. Central apneas were more prevalent in the supine position compared with the non-supine position in patients with Cheyne-Stokes respiration. The mean ± SD central AHI was 41 ± 13 in the supine position and 26 ± 12 in the non-supine position, p<0.001. Stroke patients with obstructive sleep apnea ran an increased risk of death during 10 ± 0.6 years of follow-up with an adjusted hazard ratio of 1.76 (95% CI 1.05-2.95) compared with controls, independent of hypertension, age, body mass index, gender, smoking, diabetes mellitus, atrial fibrillation, Mini-Mental State Examination and Barthel-ADL. Central apnea was not related to early death. Total sleep time, sleep efficiency, rapid eye movement sleep, slow wave and time in the supine position decreased with age in women. Sleep quality in women was reduced with age, body mass index, obstructive sleep apnea, smoking, alcohol and hypertension. Conclusions: Obstructive sleep apneas and arousals are reduced and REM sleep is increased using a mandibular advancement device in patients with mild, moderate and severe sleep apnea. The frequency of central apneas and hypopneas is increased in the supine position in patients with Cheyne-Stokes respiration. Stroke patients with obstructive sleep apnea run an increased risk of early death. Central sleep apnea was not related to early death among the present patients. Normal values for sleep stages and sleeping positions are presented in a population-based sample of women. Age, body mass index, obstructive sleep apnea, smoking, alcohol and hypertension reduce sleep quality in women

Myelosuppression by sunitinib is flt-3 genotype dependent

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