22 research outputs found
How are normal sleeping controls selected? A systematic review of cross-sectional insomnia studies, and a standardised method to select healthy controls for sleep research
There appears to be some inconsistency in how normal sleepers (controls) are selected and screened for participation in research studies for comparison with insomnia patients. The purpose of the current study is to assess and compare methods of identifying normal sleepers in insomnia studies, with reference to published standards. We systematically reviewed the literature on insomnia patients which included control subjects. The resulting 37 articles were systematically reviewed with reference to the five criteria for normal sleep specified by Edinger et al. (2004). In summary, these criteria are: evidence of sleep disruption; sleep scheduling; general health; substance/medication use; and other sleep disorders. We found sleep diaries, PSG, and clinical screening examinations to be widely used with both control subjects and insomnia participants. However, there are differences between research groups in the precise definitions applied to the components of normal sleep. We found that none of reviewed studies applied all of the Edinger et al. criteria, and 16% met four criteria. In general, screening is applied most rigorously at the level of a clinical disorder, whether physical, psychiatric, or sleep. While the Edinger et al. criteria seem to be applied in some form by most researchers, there is scope to improve standards and definitions in this area. Ideally, different methods such as sleep diaries and questionnaires would be used concurrently with objective measures to ensure normal sleepers are identified, and descriptive information for control subjects would be reported. Here, we have devised working criteria and methods to be used for assessment of normal sleepers. This would help clarify the nature of the control group, in contrast to insomnia subjects and other patient groups
Allogeneic haematopoietic cell transplantation for extranodal natural killer/Tâ cell lymphoma, nasal type: a CIBMTR analysis
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146342/1/bjh14879.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146342/2/bjh14879_am.pd
Interdisciplinary-driven hypotheses on spatial associations of mixtures of industrial air pollutants with adverse birth outcomes
Background: Adverse birth outcomes (ABO) such as prematurity and small for gestational age confer a high risk of mortality and morbidity. ABO have been linked to air pollution; however, relationships with mixtures of industrial emissions are poorly understood. The exploration of relationships between ABO and mixtures is complex when hundreds of chemicals are analyzed simultaneously, requiring the use of novel approaches. Objective: We aimed to generate robust hypotheses spatially linking mixtures and the occurrence of ABO using a spatial data mining algorithm and subsequent geographical and statistical analysis. The spatial data mining approach aimed to reduce data dimensionality and efficiently identify spatial associations between multiple chemicals and ABO. Methods: We discovered co-location patterns of mixtures and ABO in Alberta, Canada (2006–2012). An ad-hoc spatial data mining algorithm allowed the extraction of primary co-location patterns of 136 chemicals released into the air by 6279 industrial facilities (National Pollutant Release Inventory), wind-patterns from 182 stations, and 333,247 singleton live births at the maternal postal code at delivery (Alberta Perinatal Health Program), from which we identified cases of preterm birth, small for gestational age, and low birth weight at term. We selected secondary patterns using a lift ratio metric from ABO and non-ABO impacted by the same mixture. The relevance of the secondary patterns was estimated using logistic models (adjusted by socioeconomic status and ABO-related maternal factors) and a geographic-based assignment of maternal exposure to the mixtures as calculated by kernel density. Results: From 136 chemicals and three ABO, spatial data mining identified 1700 primary patterns from which five secondary patterns of three-chemical mixtures, including particulate matter, methyl-ethyl-ketone, xylene, carbon monoxide, 2-butoxyethanol, and n-butyl alcohol, were subsequently analyzed. The significance of the associations (odds ratio > 1) between the five mixtures and ABO provided statistical support for a new set of hypotheses. Conclusion: This study demonstrated that, in complex research settings, spatial data mining followed by pattern selection and geographic and statistical analyses can catalyze future research on associations between air pollutant mixtures and adverse birth outcomes
Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.
The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)
Geomorphology and Late Quaternary development of Middleton and Elizabeth Reefs
Middleton and Elizabeth Reefs are two mid-latitude, annular reefs within the Lord Howe linear chain of volcanic islands and seamounts in the southwestern Pacific Ocean. Drilling, vibrocoring, seismic profiling, and dating indicate that each has a rim of Holocene reef framework, enclosing a lagoon partly filled by prograding sand sheets composed of fragments of coral, coralline algae, foraminifers, and other skeletal debris. The reefs lie close to the latitudinal limits for coral growth and the reef framework is very porous, dominated by branching rather than massive corals. Coralline algae are the principal binding agent in the upper reef framework. Holocene reef growth began on a foundation of Pleistocene reefal limestone encountered at a depth of 8 m in cores on the windward side of Middleton Reef. Holocene corals became established on this foundation around 6,700 radiocarbon yr B.P., implying little if any lag after inundation of the platform by the post-glacial sea-level rise. Windward reef growth tracked sea-level rise (\u27keep-up\u27 mode), and a prominent reef crest was established on both reefs by 5,000 yr B.P. Leeward margins appear to have been characterized by \u27catch-up\u27 growth. Development of cays is limited, and has been restricted by the paucity of coarse coralline debris or cemented conglomerate on which islands could become established. The morphology and development of Middleton and Elizabeth Reefs has been similar to that of tropical atolls, although the rate of subsidence appears to have been relatively slow reflecting their position on the margin of the foundered continental crust of the Lord Howe Rise
Carbonate sedimentation on subtropical shelves around Lord Howe Island and Balls Pyramid, Southwest Pacific
Lord Howe Island and Balls Pyramid are mid-oceanic basaltic islands, 20 km apart, in the Tasman Sea. Subaerial carbonates dating back at least 350 ka and a Holocene fringing reef occur on Lord Howe Island. No reefs or subaerial carbonate deposits occur on Balls Pyramid. Both islands sit near the centre of wide shelves that are on average 40^50 m deep with a distinct break of slope, between 70 and 100 m depth. The Lord Howe shelf is characterised by a discontinuous drowned ridge, which rises to 30 m depth and is located between the mid-shelf and shelf edge. It is composed of limestone and is interpreted as a fossil reef being veneered by Holocene coralline algae. Early to Middle Holocene branching-coral gravel is found in the lee of the fossil reef, indicating limited give-up reef growth during the Postglacial transgression. The surface sediments across the shelf are calcareous, except in close proximity to the island where volcanic content is significant. Coralline algae represent the dominant grain type, with minor amounts of coral. Bryozoans, Halimeda and foraminifera are common; however, they are not volumetrically important. Rhodoliths and molluscs occur near the shelf edge, and appear to have accumulated at times of lower sea level. These subtropical shelves are mid-oceanic examples of the transition between tropical and temperate carbonate sedimentation. They indicate the potential for carbonate production on broad planated shelves outside reef-forming seas
Synthesis and expression of Escherichia coli of DNA encoding the murine lambda-1 chain of a monoclonal antibody specific for Salmonella serotype B O-antigen: Protein Eng.
NRC publication: Ye
Autologous transplant for relapsed follicular lymphoma: impact of pre-transplant rituximab sensitivity.
Patients with rituximab-refractory follicular lymphoma (FL) have limited options. Before the rituximab era, autologous stem cell transplant (ASCT) was shown to improve outcomes in chemotherapy-sensitive, relapsed FL, but the impact of rituximab-sensitivity on these results is unknown. We analyzed 194 consecutive relapsed patients with FL who underwent ASCT at out center and categorized them as rituximab-sensitive (RS, n = 35), rituximab-refractory (RR, n = 65) or no rituximab (NoR, n = 94) if transplanted before rituximab was used. Progression-free survival at 3 years was 85% in RS and 35% in RR patients (p = 0.0004). Only rituximab-sensitivity was significant on multivariate analysis with improved overall survival (OS) (hazard ratio [HR] 0.24, p = 0.01) and progression-free survival (PFS) (HR 0.35, p = 0.006) in RS patients and increased relapse in RR patients (HR 2.11, p = 0.01). Pre-transplant rituximab-sensitivity is a strong independent predictor of post-transplant outcomes in relapsed FL, although one-third of RR patients achieved a PFS of over 3 years with ASCT
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