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Tuberous sclerosis complex (TSC) is associated with intellectual disability, but the risk pathways are poorly understood.
The Tuberous Sclerosis 2000 Study is a prospective longitudinal study of the natural history of TSC. One hundred and twenty-five UK children age 0–16 years with TSC and born between January 2001 and December 2006 were studied. Intelligence was assessed using standardized measures at ≥2 years of age. The age of onset of epilepsy, the type of seizure disorder, the frequency and duration of seizures, as well as the response to treatment was assessed at interview and by review of medical records. The severity of epilepsy in the early years was estimated using the E-Chess score. Genetic studies identified the mutations and the number of cortical tubers was determined from brain scans.
TSC2 mutations were associated with significantly higher cortical tuber count than TSC1 mutations. The extent of brain involvement, as indexed by cortical tuber count, was associated with an earlier age of onset and severity of epilepsy. In turn, the severity of epilepsy was strongly associated with the degree of intellectual impairment. Structural equation modelling supported a causal pathway from genetic abnormality to cortical tuber count to epilepsy severity to intellectual outcome. Infantile spasms and status epilepticus were important contributors to seizure severity.
The findings support the proposition that severe, early onset epilepsy may impair intellectual development in TSC and highlight the potential importance of early, prompt and effective treatment or prevention of epilepsy in tuberous sclerosis.
Growing evidence supports the use of Western therapies for the treatment of depression, trauma, and stress delivered by community health workers (CHWs) in conflict-affected, resource-limited countries. A recent randomized controlled trial (Bolton et al. 2014a) supported the efficacy of two CHW-delivered interventions, cognitive processing therapy (CPT) and brief behavioral activation treatment for depression (BATD), for reducing depressive symptoms and functional impairment among torture survivors in the Kurdish region of Iraq.
This study describes the adaptation of the CHW-delivered BATD approach delivered in this trial (Bolton et al. 2014a), informed by the Assessment–Decision–Administration-Production–Topical experts–Integration–Training–Testing (ADAPT–ITT) framework for intervention adaptation (Wingood & DiClemente, 2008). Cultural modifications, adaptations for low-literacy, and tailored training and supervision for non-specialist CHWs are presented, along with two clinical case examples to illustrate delivery of the adapted intervention in this setting.
Eleven CHWs, a study psychiatrist, and the CHW clinical supervisor were trained in BATD. The adaptation process followed the ADAPT–ITT framework and was iterative with significant input from the on-site supervisor and CHWs. Modifications were made to fit Kurdish culture, including culturally relevant analogies, use of stickers for behavior monitoring, cultural modifications to behavioral contracts, and including telephone-delivered sessions to enhance feasibility.
BATD was delivered by CHWs in a resource-poor, conflict-affected area in Kurdistan, Iraq, with some important modifications, including low-literacy adaptations, increased cultural relevancy of clinical materials, and tailored training and supervision for CHWs. Barriers to implementation, lessons learned, and recommendations for future efforts to adapt behavioral therapies for resource-limited, conflict-affected areas are discussed.
This paper describes the system architecture of a newly constructed radio telescope – the Boolardy engineering test array, which is a prototype of the Australian square kilometre array pathfinder telescope. Phased array feed technology is used to form multiple simultaneous beams per antenna, providing astronomers with unprecedented survey speed. The test array described here is a six-antenna interferometer, fitted with prototype signal processing hardware capable of forming at least nine dual-polarisation beams simultaneously, allowing several square degrees to be imaged in a single pointed observation. The main purpose of the test array is to develop beamforming and wide-field calibration methods for use with the full telescope, but it will also be capable of limited early science demonstrations.
Intellectual disability (ID) is highly prevalent in tuberous sclerosis (TS). Putative neurobiological risk factors include indices of cortical tuber (CT) load and epilepsy. We have used univariate and multivariate analyses, including both CT and epilepsy measures as predictors, in an attempt to clarify the pattern of cross-sectional associations between these variables and ID in TS.
Forty-eight children, adolescents and young adults with TS were identified through regional specialist clinics. All subjects underwent thorough history taking and examination, and had brain magnetic resonance imaging (MRI) scans. The number and regional distribution of CTs was recorded. Subjects were assigned to one of nine ordered intellectual quotient (IQ) categories (range <25 to >130) using age-appropriate tests of intelligence.
On univariate analyses, ID was significantly associated with both a history of infantile spasm (IS) (Z=−2·49, p=0·01) and total CT count (Spearman's ρ=−0·30, p=0·04). When controlling for total CT count, the presence of CTs in frontal (regression coefficient=−2·43, p=0·02) and temporal (regression coefficient=−1·60, p=0·02) lobes was significantly associated with ID. In multivariate analyses the association between IS and ID was rendered insignificant by the inclusion of the presence of CTs in temporal and frontal lobes, both of which remained associated (p=0·05 and p=0·06 respectively) with ID.
The presence of CTs in specific brain regions as opposed to a history of IS was associated with ID in TS. The significance of these findings is discussed in relation to previous work in TS, and the neural basis of intelligence.
Five siblings with autosomal dominant oculopharyngeal muscular dystrophy (OPMD) underwent P-31 Nuclear Magnetic Resonance Spectroscopy studies of forearm flexor muscles. Mean values of PCr/(PCr + Pi) in the patients were reduced (p = 0.01) and pH elevated (p = 0.02) in resting muscle when compared to controls. During exercise PCr/(PCr + Pi) fell quickly to values less than controls (p < 0.0001) despite submaximal exercise output and developed exercise-induced acidosis which exceeded that of controls (p = 0.05). Acidosis recovered slowly despite relatively normal recovery of PCr/(PCr + Pi) following exercise. Within the patient group, however, one member had normal resting, exercise and recovery values. The studies suggest that OPMD is a more widespread disorder of striated muscle than clinically appreciated. The pattern of findings observed in OPMD differs from those identified in denervation, disuse and mitochondrial myopathy.
HR 6469 consists of an evolved G5 star and a close pair of fainter stars, probably both on the main sequence. The period of the close pair is just over two days, and shallow eclipses have been detected (Boyd et al. 1985), although no analysis of the light curve has been published. The wide system has a period of about 5.5 years, and has been resolved by speckle interferometry (McAlister et al. 1983). The G5 star and the primary of the close pair are detectable in the spectrum, with the latter showing modest rotational broadening. Spectral types and rotational velocities for the evolved star and the brighter component of the close pair have been published by Strassmeier & Fekel (1990).
The increasing interest in the possible role of antioxidant vitamins in many disease states means that methods of assessing vitamin intakes which are suitable for large-scale investigations are now required. The suitability of the food-frequency questionnaire, which was developed by the Medical Research Council – Cardiff Group, for determining dietary intake of antioxidant vitamins in epidemiological studies was investigated in 196 Scottish men. The validity of the dietary data was assessed by comparison with serum vitamin concentrations, and separate analyses were performed for current smokers and non-smokers. The results showed that total energy intake and the percentage of energy derived from sugar were higher in smokers, and that both dietary and serum values of vitamin C, β-carotene and vitamin E were lower in smokers than non-smokers. After adjustment for serum lipids, energy intake and body mass index, correlation coefficients between dietary and serum vitamins C and E were similar for smokers (r 0.555 and 0.25 respectively) and non-smokers (r 0.58 and 0.32 respectively). Correlation between dietary and serum carotenes was reduced from 0.28 in non-smokers to 0.09 in smokers and correlations for retinol and total vitamin A were weakly significant only for non-smokers. The food-frequency questionnaire assigned > 70% of subjects correctly into the upper or lower plus adjacent tertiles of serum vitamin values, with the exception of β-carotene and total vitamin A for smokers. Thus, the food-frequency questionnaire appeared to be an adequate tool for assigning individuals into tertiles of serum antioxidant vitamins with the main exception of β-carotene for smokers. Marked differences do occur between the vitamins and between the smoking groups which may reflect reduced accuracy of reporting on the food-frequency questionnaire or differential absorption and metabolism of the vitamins.
The analysis of the instabilities of convection rolls in a fluid layer heated from below with no-slip boundaries exhibits a close competition between various oscillatory modes in the range 2 [lsim ] P [lsim ] 12 of the Prandtl number P. In addition to the even-oscillatory instability known from earlier work two new instabilities have been found, each of which is responsible for a small section of the stability boundary of steady rolls. The most interesting property of the new instabilities is their close relationship to the hot-blob oscillations known from experimental studies of convection. In the lower half of the Prandtl-number range considered the B02-mode dominates, which is characterized by two blobs each of slightly hotter and colder fluid circulating around in the convection roll in a spatially and time-periodic fashion. At higher Prandtl numbers the BE 1-mode dominates, which possesses one hot blob (and one cold blob) circulating with the convection velocity. Just outside the stability boundary there exist other growing modes exhibiting three or four blobs which may be observable in experiments.
Steady finite-amplitude solutions for two-dimensional convection in a layer heated from below with stress-free boundaries are obtained numerically by a Galerkin method. The stability of the steady convection rolls with respect to arbitrary three-dimensional infinitesimal disturbances is investigated. Stability is found only in a small fraction of the Rayleigh-number-wavenumber space where steady solutions exist. The cross-roll instability and the oscillatory and monotonic skewed varicose instabilities are most important in limiting the stability of steady convection rolls. The Prandtlnumbers P = 0.71, 7, 104 areemphasized, but the stability boundaries are sufficiently smoothly dependent on the parameters of the problem to permit qualitative extrapolations to other Prandtl numbers.
The stability properties of steady two-dimensional solutions describing convection in a horizontal fluid layer heated from below with stress-free boundaries are investigated in the neighbourhood of the critical Rayleigh number. The region of stable convection rolls as a function of the wavenumber α and the Rayleigh number R is bounded towards higher α by the monotonic skewed varicose instability, while towards low wavenumbers stability is limited by the zigzag instability or by the oscillatory skewed varicose instability. Only for a limited range of Prandtl numbers, 0·543 < P < ∞, does a finite domain of stability exist. In particular, convection rolls with the critical wavenumber αc are always unstable.
The ATLAS programme has been corrected and modified for use at low effective temperatures. A grid of unblanketed model atmospheres has been generated for the region G5-K5, V-II. A spectrum synthesis programme has been written for the calculation of flux vs wavelength for selected regions of the spectrum. Temperature distributions from the grid of continuum models and from published blanketed models will be used along with published oscillator strengths as input data for the spectral synthesis programme.
Spectrograms of MK standards have been taken at 12 Å mm−1 and 120 Å mm−1. The University of Toronto PDS microdensitometer system has been programmed to allow comparison between the synthesized spectra and the observed spectra to determine the effects of effective temperature, surface gravity, microturbulence, and abundance on classification criteria.
An infinitely long circular cylinder is fixed with its generators horizontal so that it is half-immersed, with its axis lying in the free surface of water. A regular train of water waves is incident on the cylinder from an arbitrary horizontal direction, and is partly reflected and partly transmitted under the cylinder. In the present paper we are concerned with the vertical component of the wave acting on the cylinder. It is assumed that the fluid is inviscid, that the fluid motion is irrotational, and that the depth of water is infinite. The equations of motion are linearized, and surface tension is neglected.
We shall find it convenient to use the fact that the required vertical force component can be inferred from the solution of a related problem, which we shall call the generalized heaving problem. In this latter problem a certain normal velocity is prescribed on the cylinder so that water waves which travel obliquely outwards are generated. There are no waves incident from infinity. When the prescribed velocity has the same phase everywhere on the cylinder the waves travel normally outwards, and in this case the generalized heaving problem reduces to the ordinary heaving problem, on which much information is already available. The generalized problem is solved here by a method which is a generalization of the known method (Ursell 1949) for ordinary heaving (when the wave crests are parallel to the cylinder axis). Generalized-added-mass coefficients and generalized-wave-making parameters for generalized heaving are computed for a range of wavenumbers and angles of travel, and are extended to larger wave-numbers by means of asymptotic analysis. Reciprocity relations (the Haskind relations) are then used to obtain the vertical force component in the original transmission problem from the wave-making parameters of the generalized heaving problem.
The following checklist includes work published in the quarter-century between 1935, the twelve-hundreth anniversary of Bede's death, and 1960, inclusive. It lists editions, studies and translations into Modern English of his Latin works; it omits translations into other languages, including Old English, and studies of these, as well as the Old English poems sometimes attributed to Bede. Most reviews of the listed books have also been omitted, although some which make substantial modifications have not. A universal writer like Bede is mentioned in many studies; only those that deal directly with him, or that seem to make real contributions to Bede scholarship, are in this checklist, which would otherwise have been many times its present length. The grouping is by topic, chronologically within each topic, alphabetically within each year. An asterisk marks those works which I have not been able to see.
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