Diagnostic challenges and psychosocial impacts of hypersomnia in a Nigerian adolescent: A case report

Hypersomnia, a disorder of sleep characterized by excessive quantity of sleep and excessive daytime sleepiness (EDS), could adversely affect health outcomes in childhood. To highlight diagnostic challenges and the impact of childhood hypersomnia in a resource limited setting, a 14year old Nigerian who presented with a seven year history of hypersomnia was studied. Screening for sleep disorder using BEARS sleep algorithm and assessment for EDS using the Epworth Sleepiness Scale were both positivefor EDS. The assessment of sleep hygiene using the Adolescent Sleep Hygiene Scale was normal and the use of Raven’s Progressive Matrices to assess intelligence was also normal. There was no contributory pastmedical history or demonstrable etiology. Magnetic Resonance Imaging (MRI) of the brain, Electro Encephalogram (EEG), assay of serum electrolytes were all normal while screening test for trypanosomiasis was negative. Poor level of awareness, high cost of evaluation and limited facilities for diagnosis of sleep disorder were the major diagnostic challenges. Depression, poor academic performance, suicidal ideation andstigmatization were all associated with hypersomnia in the patient.Keywords: Hypersomnia, adolescence, depression, sleep disorders, diagnostic challenges

Terahertz Security Image Quality Assessment by No-reference Model Observers

To provide the possibility of developing objective image quality assessment (IQA) algorithms for THz security images, we constructed the THz security image database (THSID) including a total of 181 THz security images with the resolution of 127*380. The main distortion types in THz security images were first analyzed for the design of subjective evaluation criteria to acquire the mean opinion scores. Subsequently, the existing no-reference IQA algorithms, which were 5 opinion-aware approaches viz., NFERM, GMLF, DIIVINE, BRISQUE and BLIINDS2, and 8 opinion-unaware approaches viz., QAC, SISBLIM, NIQE, FISBLIM, CPBD, S3 and Fish_bb, were executed for the evaluation of the THz security image quality. The statistical results demonstrated the superiority of Fish_bb over the other testing IQA approaches for assessing the THz image quality with PLCC (SROCC) values of 0.8925 (-0.8706), and with RMSE value of 0.3993. The linear regression analysis and Bland-Altman plot further verified that the Fish__bb could substitute for the subjective IQA. Nonetheless, for the classification of THz security images, we tended to use S3 as a criterion for ranking THz security image grades because of the relatively low false positive rate in classifying bad THz image quality into acceptable category (24.69%). Interestingly, due to the specific property of THz image, the average pixel intensity gave the best performance than the above complicated IQA algorithms, with the PLCC, SROCC and RMSE of 0.9001, -0.8800 and 0.3857, respectively. This study will help the users such as researchers or security staffs to obtain the THz security images of good quality. Currently, our research group is attempting to make this research more comprehensive.Comment: 13 pages, 8 figures, 4 table

Circulating endothelial cell-derived extracellular vesicles mediate the acute phase response and sickness behaviour associated with CNS inflammation.

Brain injury elicits a systemic acute-phase response (APR), which is responsible for co-ordinating the peripheral immunological response to injury. To date, the mechanisms responsible for signalling the presence of injury or disease to selectively activate responses in distant organs were unclear. Circulating endogenous extracellular vesicles (EVs) are increased after brain injury and have the potential to carry targeted injury signals around the body. Here, we examined the potential of EVs, isolated from rats after focal inflammatory brain lesions using IL-1β, to activate a systemic APR in recipient naïve rats, as well as the behavioural consequences of EV transfer. Focal brain lesions increased EV release, and, following isolation and transfer, the EVs were sequestered by the liver where they initiated an APR. Transfer of blood-borne EVs from brain-injured animals was also enough to suppress exploratory behaviours in recipient naïve animals. EVs derived from brain endothelial cell cultures treated with IL-1β also activated an APR and altered behaviour in recipient animals. These experiments reveal that inflammation-induced circulating EVs derived from endothelial cells are able to initiate the APR to brain injury and are sufficient to generate the associated sickness behaviours, and are the first demonstration that EVs are capable of modifying behavioural responses

IFNβ Protects Neurons from Damage in a Murine Model of HIV-1 Associated Brain Injury.

Infection with human immunodeficiency virus-1 (HIV-1) causes brain injury. Type I interferons (IFNα/β) are critical mediators of any anti-viral immune response and IFNβ has been implicated in the temporary control of lentiviral infection in the brain. Here we show that transgenic mice expressing HIV-1 envelope glycoprotein 120 in their central nervous system (HIVgp120tg) mount a transient IFNβ response and provide evidence that IFNβ confers neuronal protection against HIVgp120 toxicity. In cerebrocortical cell cultures, neuroprotection by IFNβ against gp120 toxicity is dependent on IFNα receptor 1 (IFNAR1) and the β-chemokine CCL4, as IFNAR1 deficiency and neutralizing antibodies against CCL4, respectively, abolish the neuroprotective effects. We find in vivo that IFNβ mRNA is significantly increased in HIVgp120tg brains at 1.5, but not 3 or 6 months of age. However, a four-week intranasal IFNβ treatment of HIVgp120tg mice starting at 3.5 months of age increases expression of CCL4 and concomitantly protects neuronal dendrites and pre-synaptic terminals in cortex and hippocampus from gp120-induced damage. Moreover, in vivo and in vitro data suggests astrocytes are a major source of IFNβ-induced CCL4. Altogether, our results suggest exogenous IFNβ as a neuroprotective factor that has potential to ameliorate in vivo HIVgp120-induced brain injury

Cell-type specific RNA-Seq reveals novel roles and regulatory programs for terminally differentiated Dictyostelium cells

Abstract Background A major hallmark of multicellular evolution is increasing complexity by the evolution of new specialized cell types. During Dictyostelid evolution novel specialization occurred within taxon group 4. We here aim to retrace the nature and ancestry of the novel “cup” cells by comparing their transcriptome to that of other cell types. Results RNA-Seq was performed on purified mature spore, stalk and cup cells and on vegetative amoebas. Clustering and phylogenetic analyses showed that cup cells were most similar to stalk cells, suggesting that they share a common ancestor. The affinity between cup and stalk cells was also evident from promoter-reporter studies of newly identified cell-type genes, which revealed late expression in cups of many stalk genes. However, GO enrichment analysis reveal the unexpected prominence of GTPase mediated signalling in cup cells, in contrast to enrichment of autophagy and cell wall synthesis related transcripts in stalk cells. Combining the cell type RNA-Seq data with developmental expression profiles revealed complex expression dynamics in each cell type as well as genes exclusively expressed during terminal differentiation. Most notable were nine related hssA-like genes that were highly and exclusively expressed in cup cells. Conclusions This study reveals the unique transcriptomes of the mature cup, stalk and spore cells of D. discoideum and provides insight into the ancestry of cup cells and roles in signalling that were not previously realized. The data presented in this study will serve as an important resource for future studies into the regulation and evolution of cell type specialization

Prospective validation of the 4C prognostic models for adults hospitalised with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol

Purpose: To prospectively validate two risk scores to predict mortality (4C Mortality) and in-hospital deterioration (4C Deterioration) among adults hospitalised with COVID-19. // Methods: Prospective observational cohort study of adults (age ≥18 years) with confirmed or highly suspected COVID-19 recruited into the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK) study in 306 hospitals across England, Scotland and Wales. Patients were recruited between 27 August 2020 and 17 February 2021, with at least 4 weeks follow-up before final data extraction. The main outcome measures were discrimination and calibration of models for in-hospital deterioration (defined as any requirement of ventilatory support or critical care, or death) and mortality, incorporating predefined subgroups. // Results: 76 588 participants were included, of whom 27 352 (37.4%) deteriorated and 12 581 (17.4%) died. Both the 4C Mortality (0.78 (0.77 to 0.78)) and 4C Deterioration scores (pooled C-statistic 0.76 (95% CI 0.75 to 0.77)) demonstrated consistent discrimination across all nine National Health Service regions, with similar performance metrics to the original validation cohorts. Calibration remained stable (4C Mortality: pooled slope 1.09, pooled calibration-in-the-large 0.12; 4C Deterioration: 1.00, –0.04), with no need for temporal recalibration during the second UK pandemic wave of hospital admissions. // Conclusion: Both 4C risk stratification models demonstrate consistent performance to predict clinical deterioration and mortality in a large prospective second wave validation cohort of UK patients. Despite recent advances in the treatment and management of adults hospitalised with COVID-19, both scores can continue to inform clinical decision making

Kerr/CFT, dipole theories and nonrelativistic CFTs

We study solutions of type IIB supergravity which are SL(2,R) x SU(2) x U(1)^2 invariant deformations of AdS_3 x S^3 x K3 and take the form of products of self-dual spacelike warped AdS_3 and a deformed three-sphere. One of these backgrounds has been recently argued to be relevant for a derivation of Kerr/CFT from string theory, whereas the remaining ones are holographic duals of two-dimensional dipole theories and their S-duals. We show that each of these backgrounds is holographically dual to a deformation of the DLCQ of the D1-D5 CFT by a specific supersymmetric (1,2) operator, which we write down explicitly in terms of twist operators at the free orbifold point. The deforming operator is argued to be exactly marginal with respect to the zero-dimensional nonrelativistic conformal (or Schroedinger) group - which is simply SL(2,R)_L x U(1)_R. Moreover, in the supergravity limit of large N and strong coupling, no other single-trace operators are turned on. We thus propose that the field theory duals to the backgrounds of interest are nonrelativistic CFTs defined by adding the single Schroedinger-invariant (1,2) operator mentioned above to the original CFT action. Our analysis indicates that the rotating extremal black holes we study are best thought of as finite right-moving temperature (non-supersymmetric) states in the above-defined supersymmetric nonrelativistic CFT and hints towards a more general connection between Kerr/CFT and two-dimensional non-relativistic CFTs.Comment: 48+8 pages, 4 figures; minor corrections and references adde

Development and validation of the ISARIC 4C Deterioration model for adults hospitalised with COVID-19: a prospective cohort study

BACKGROUND: Prognostic models to predict the risk of clinical deterioration in acute COVID-19 cases are urgently required to inform clinical management decisions. METHODS: We developed and validated a multivariable logistic regression model for in-hospital clinical deterioration (defined as any requirement of ventilatory support or critical care, or death) among consecutively hospitalised adults with highly suspected or confirmed COVID-19 who were prospectively recruited to the International Severe Acute Respiratory and Emerging Infections Consortium Coronavirus Clinical Characterisation Consortium (ISARIC4C) study across 260 hospitals in England, Scotland, and Wales. Candidate predictors that were specified a priori were considered for inclusion in the model on the basis of previous prognostic scores and emerging literature describing routinely measured biomarkers associated with COVID-19 prognosis. We used internal-external cross-validation to evaluate discrimination, calibration, and clinical utility across eight National Health Service (NHS) regions in the development cohort. We further validated the final model in held-out data from an additional NHS region (London). FINDINGS: 74 944 participants (recruited between Feb 6 and Aug 26, 2020) were included, of whom 31 924 (43·2%) of 73 948 with available outcomes met the composite clinical deterioration outcome. In internal-external cross-validation in the development cohort of 66 705 participants, the selected model (comprising 11 predictors routinely measured at the point of hospital admission) showed consistent discrimination, calibration, and clinical utility across all eight NHS regions. In held-out data from London (n=8239), the model showed a similarly consistent performance (C-statistic 0·77 [95% CI 0·76 to 0·78]; calibration-in-the-large 0·00 [-0·05 to 0·05]); calibration slope 0·96 [0·91 to 1·01]), and greater net benefit than any other reproducible prognostic model. INTERPRETATION: The 4C Deterioration model has strong potential for clinical utility and generalisability to predict clinical deterioration and inform decision making among adults hospitalised with COVID-19. FUNDING: National Institute for Health Research (NIHR), UK Medical Research Council, Wellcome Trust, Department for International Development, Bill & Melinda Gates Foundation, EU Platform for European Preparedness Against (Re-)emerging Epidemics, NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool, NIHR HPRU in Respiratory Infections at Imperial College London

Asthma prescribing, ethnicity and risk of hospital admission: an analysis of 35,864 linked primary and secondary care records in East London

This work was partly supported by funding from the Asthma UK Centre for Applied Research

Actigraphy in Human African Trypanosomiasis as a Tool for Objective Clinical Evaluation and Monitoring: A Pilot Study

The clinical picture of the parasitic disease human African trypanosomiasis (HAT, also called sleeping sickness) is dominated by sleep alterations. We here used actigraphy to evaluate patients affected by the Gambiense form of HAT. Actigraphy is based on the use of battery-run, wrist-worn devices similar to watches, widely used in middle-high income countries for ambulatory monitoring of sleep disturbances. This pilot study was motivated by the fact that the use of polysomnography, which is the gold standard technology for the evaluation of sleep disorders and has greatly contributed to the objective identification of signs of disease in HAT, faces tangible challenges in resource-limited countries where the disease is endemic. We here show that actigraphy provides objective data on the severity of sleep-wake disturbances that characterize HAT. This technique, which does not disturb the patient's routine activities and can be applied at home, could therefore represent an interesting, non-invasive tool for objective HAT clinical assessment and long-term monitoring under field conditions. The use of this method could provide an adjunct marker of HAT severity and for treatment follow-up, or be evaluated in combination with other disease biomarkers in body fluids that are currently under investigation in many laboratories