Conducting unattended home sleep studies in children with narcolepsy and healthy matched controls: a feasibility study

Introduction: We investigated the technical feasibility and acceptability of conducting unattended home sleep studies for research purposes in children with and without narcolepsy. Methods: 23 children with narcolepsy (age: 8-15 years) and 23 healthy gender and age-matched controls were recruited. As part of a larger descriptive study called ‘The Paediatric Narcolepsy Project’, we aimed to investigate the differences in sleep architecture between children with and without narcolepsy. Children underwent home polysomnography (PSG) using a portable PSG system (Embla® Systems). A standard montage was used to measure sleep architecture with nine EEG channels (F3, F4, C3, Cz, C4, O1, O2, M1, M2), two electro-oculography (EOG) and two electromyography (EMG) channels. All children were set up in their own homes by the researcher. Study failure was defined as sleep recordings with less than four hours of interpretable sleep data. Four hours of sleep was deemed acceptable to capture two sleep cycles. Failed home studies were classified into three main areas of sensor removal, equipment failure or battery failure. Results: 22/23 children with narcolepsy (male=15, female=8) underwent home PSG. One child declined due to a previous negative PSG experience in hospital. Similarly, 22/23 matched controls underwent the sleep recording. One child became unwell during the set up, so did not proceed.16/22 (73%) of the children with narcolepsy were successfully studied and all of the control children were successfully studied. Discussion: This research has shown that conducting unattended home sleep studies to measure sleep architecture in children with narcolepsy and healthy controls for research purposes is feasible and is tolerated by the majority of children. However, our data show that unattended home sleep studies carry a risk of data loss, even when set up in the home by a trained researcher

Smectic Pair Density Wave Order in EuRbFe4As4

The pair density wave (PDW) is a novel superconducting state in which Cooper pairs carry center-of-mass momentum in equilibrium, leading to the breaking of translational symmetry. Experimental evidence for such a state exists in high magnetic field and in some materials that feature density wave orders that explicitly break translational symmetry. However, evidence for a zero-field PDW state that exists independent of other spatially ordered states has so far been elusive. Here, we show that such a state exists in the iron pnictide superconductor EuRbFe4As4 (Eu-1144), a material that features coexisting superconductivity (Tc ~ 37K) and magnetism (Tm ~ 15 K). We show from the Spectroscopic Imaging Scanning Tunneling Microscopy (SI-STM) measurements that the superconducting gap at low temperature has long-range, unidirectional spatial modulations with an incommensurate period of ~8 unit cells. Upon raising the temperature above Tm, the modulated superconductor disappears, but a uniform superconducting gap survives to Tc. When an external magnetic field is applied, gap modulations disappear inside the vortex halo. The SI-STM and bulk measurements show the absence of other density wave orders, showing that the PDW state is a primary, zero-field superconducting state in this compound. Both four-fold rotational symmetry and translation symmetry are recovered above Tm, indicating that the PDW is a smectic order

Cognitive dysfunction in naturally occurring canine idiopathic epilepsy

Globally, epilepsy is a common serious brain disorder. In addition to seizure activity, epilepsy is associated with cognitive impairments including static cognitive impairments present at onset, progressive seizure-induced impairments and co-morbid dementia. Epilepsy occurs naturally in domestic dogs but its impact on canine cognition has yet to be studied, despite canine cognitive dysfunction (CCD) recognised as a spontaneous model of dementia. Here we use data from a psychometrically validated tool, the canine cognitive dysfunction rating (CCDR) scale, to compare cognitive dysfunction in dogs diagnosed with idiopathic epilepsy (IE) with controls while accounting for age. An online cross-sectional study resulted in a sample of 4051 dogs, of which n = 286 had been diagnosed with IE. Four factors were significantly associated with a diagnosis of CCD (above the diagnostic cut-off of CCDR ≥50): (i) epilepsy diagnosis: dogs with epilepsy were at higher risk; (ii) age: older dogs were at higher risk; (iii) weight: lighter dogs (kg) were at higher risk; (iv) training history: dogs with more exposure to training activities were at lower risk. Impairments in memory were most common in dogs with IE, but progression of impairments was not observed compared to controls. A significant interaction between epilepsy and age was identified, with IE dogs exhibiting a higher risk of CCD at a young age, while control dogs followed the expected pattern of low-risk throughout middle age, with risk increasing exponentially in geriatric years. Within the IE sub-population, dogs with a history of cluster seizures and high seizure frequency had higher CCDR scores. The age of onset, nature and progression of cognitive impairment in the current IE dogs appear divergent from those classically seen in CCD. Longitudinal monitoring of cognitive function from seizure onset is required to further characterise these impairments

Probing the mass-loss history of AGB and red supergiant stars from CO rotational line profiles - II. CO line survey of evolved stars: derivation of mass-loss rate formulae

We aim to (1) set up simple and general analytical expressions to estimate mass-loss rates of evolved stars, and (2) from those calculate estimates for the mass-loss rates of asymptotic giant branch (AGB), red supergiant (RSG), and yellow hypergiant stars in our galactic sample. Rotationally excited lines of CO are a very robust diagnostic in the study of circumstellar envelopes (CSEs). When sampling different layers of the CSE, observations of these molecular lines lead to detailed profiles of kinetic temperature, expansion velocity, and density. A state-of-the-art, nonlocal thermal equilibrium, and co-moving frame radiative transfer code that predicts CO line intensities in the CSEs of late-type stars is used in deriving relations between stellar and molecular-line parameters, on the one hand, and mass-loss rate, on the other. We present analytical expressions for estimating the mass-loss rates of evolved stellar objects for 8 rotational transitions of the CO molecule, apply them to our extensive CO data set covering 47 stars, and compare our results to those of previous studies. Our expressions account for line saturation and resolving of the envelope, thereby allowing accurate determination of very high mass-loss rates. We argue that, for estimates based on a single rotational line, the CO(2-1) transition provides the most reliable mass-loss rate. The mass-loss rates calculated for the AGB stars range from 4x10^-8 Msun/yr up to 8x10^-5 Msun/yr. For RSGs they reach values between 2x10^-7 Msun/yr and 3x10^-4 Msun/yr. The estimates for the set of CO transitions allow time variability to be identified in the mass-loss rate. Possible mass-loss-rate variability is traced for 7 of the sample stars. We find a clear relation between the pulsation periods of the AGB stars and their derived mass-loss rates, with a levelling off at approx. 3x10^-5 Msun/yr for periods exceeding 850 days.Comment: Accepted for publication by Astronomy and Astrophysics, 24 pages + 28 pages appendix, 20 figure

Of cattle, sand flies and men : a systematic review of risk factor analyses for South Asian visceral leishmaniasis and implications for elimination

Background: Studies performed over the past decade have identified fairly consistent epidemiological patterns of risk factors for visceral leishmaniasis (VL) in the Indian subcontinent. Methods and Principal Findings: To inform the current regional VL elimination effort and identify key gaps in knowledge, we performed a systematic review of the literature, with a special emphasis on data regarding the role of cattle because primary risk factor studies have yielded apparently contradictory results. Because humans form the sole infection reservoir, clustering of kala-azar cases is a prominent epidemiological feature, both at the household level and on a larger scale. Subclinical infection also tends to show clustering around kala-azar cases. Within villages, areas become saturated over a period of several years; kala-azar incidence then decreases while neighboring areas see increases. More recently, post kalaazar dermal leishmaniasis (PKDL) cases have followed kala-azar peaks. Mud walls, palpable dampness in houses, and peridomestic vegetation may increase infection risk through enhanced density and prolonged survival of the sand fly vector. Bed net use, sleeping on a cot and indoor residual spraying are generally associated with decreased risk. Poor micronutrient status increases the risk of progression to kala-azar. The presence of cattle is associated with increased risk in some studies and decreased risk in others, reflecting the complexity of the effect of bovines on sand fly abundance, aggregation, feeding behavior and leishmanial infection rates. Poverty is an overarching theme, interacting with individual risk factors on multiple levels. Conclusions: Carefully designed demonstration projects, taking into account the complex web of interconnected risk factors, are needed to provide direct proof of principle for elimination and to identify the most effective maintenance activities to prevent a rapid resurgence when interventions are scaled back. More effective, short-course treatment regimens for PKDL are urgently needed to enable the elimination initiative to succeed

Associations of HLA-DP Variants with Hepatitis B Virus Infection in Southern and Northern Han Chinese Populations: A Multicenter Case-Control Study

) locus has been reported to be associated with hepatitis B virus (HBV) infection in populations of Japan and Thailand. We aimed to examine whether the association can be replicated in Han Chinese populations. = 0.097∼0.697 and 0.198∼0.615 in northern Chinese population, respectively). loci were strongly associated with HBV infection in southern and northern Han Chinese populations, but not with HBV progression

A Granulin-Like Growth Factor Secreted by the Carcinogenic Liver Fluke, Opisthorchis viverrini, Promotes Proliferation of Host Cells

The human liver fluke, Opisthorchis viverrini, infects millions of people throughout south-east Asia and is a major cause of cholangiocarcinoma, or cancer of the bile ducts. The mechanisms by which chronic infection with O. viverrini results in cholangiocarcinogenesis are multi-factorial, but one such mechanism is the secretion of parasite proteins with mitogenic properties into the bile ducts, driving cell proliferation and creating a tumorigenic environment. Using a proteomic approach, we identified a homologue of human granulin, a potent growth factor involved in cell proliferation and wound healing, in the excretory/secretory (ES) products of the parasite. O. viverrini granulin, termed Ov-GRN-1, was expressed in most parasite tissues, particularly the gut and tegument. Furthermore, Ov-GRN-1 was detected in situ on the surface of biliary epithelial cells of hamsters experimentally infected with O. viverrini. Recombinant Ov-GRN-1 was expressed in E. coli and refolded from inclusion bodies. Refolded protein stimulated proliferation of murine fibroblasts at nanomolar concentrations, and proliferation was inhibited by the MAPK kinase inhibitor, U0126. Antibodies raised to recombinant Ov-GRN-1 inhibited the ability of O. viverrini ES products to induce proliferation of murine fibroblasts and a human cholangiocarcinoma cell line in vitro, indicating that Ov-GRN-1 is the major growth factor present in O. viverrini ES products. This is the first report of a secreted growth factor from a parasitic worm that induces proliferation of host cells, and supports a role for this fluke protein in establishment of a tumorigenic environment that may ultimately manifest as cholangiocarcinoma

The MCL-1 BH3 helix is an exclusive MCL-1 inhibitor and apoptosis sensitizer

available in PMC 2011 February 3.MCL-1 has emerged as a major oncogenic and chemoresistance factor. A screen of stapled peptide helices identified the MCL-1 BH3 domain as selectively inhibiting MCL-1 among the related anti-apoptotic Bcl-2 family members, providing insights into the molecular determinants of binding specificity and a new approach for sensitizing cancer cells to apoptosis.National Institutes of Health (U.S.) (NIH award 5RO1GM084181)National Institutes of Health (U.S.) (NIH grant 5P01CA92625)National Institutes of Health (U.S.) (Ruth L. Kirschstein National Research Service Award 1F31CA144566)Burroughs Wellcome Fund (Career Award