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Two common approaches to identify subgroups of patients with bipolar disorder are clustering methodology (mixture analysis) based on the age of onset, and a birth cohort analysis. This study investigates if a birth cohort effect will influence the results of clustering on the age of onset, using a large, international database.
The database includes 4037 patients with a diagnosis of bipolar I disorder, previously collected at 36 collection sites in 23 countries. Generalized estimating equations (GEE) were used to adjust the data for country median age, and in some models, birth cohort. Model-based clustering (mixture analysis) was then performed on the age of onset data using the residuals. Clinical variables in subgroups were compared.
There was a strong birth cohort effect. Without adjusting for the birth cohort, three subgroups were found by clustering. After adjusting for the birth cohort or when considering only those born after 1959, two subgroups were found. With results of either two or three subgroups, the youngest subgroup was more likely to have a family history of mood disorders and a first episode with depressed polarity. However, without adjusting for birth cohort (three subgroups), family history and polarity of the first episode could not be distinguished between the middle and oldest subgroups.
These results using international data confirm prior findings using single country data, that there are subgroups of bipolar I disorder based on the age of onset, and that there is a birth cohort effect. Including the birth cohort adjustment altered the number and characteristics of subgroups detected when clustering by age of onset. Further investigation is needed to determine if combining both approaches will identify subgroups that are more useful for research.
In 2011 the Incidence Assay Critical Path Working Group reviewed the current state of HIV incidence assays and helped to determine a critical path to the introduction of an HIV incidence assay. At that time the Consortium for Evaluation and Performance of HIV Incidence Assays (CEPHIA) was formed to spur progress and raise standards among assay developers, scientists and laboratories involved in HIV incidence measurement and to structure and conduct a direct independent comparative evaluation of the performance of 10 existing HIV incidence assays, to be considered singly and in combinations as recent infection test algorithms. In this paper we report on a new framework for HIV incidence assay evaluation that has emerged from this effort over the past 5 years, which includes a preliminary target product profile for an incidence assay, a consensus around key performance metrics along with analytical tools and deployment of a standardized approach for incidence assay evaluation. The specimen panels for this evaluation have been collected in large volumes, characterized using a novel approach for infection dating rules and assembled into panels designed to assess the impact of important sources of measurement error with incidence assays such as viral subtype, elite host control of viraemia and antiretroviral treatment. We present the specific rationale for several of these innovations, and discuss important resources for assay developers and researchers that have recently become available. Finally, we summarize the key remaining steps on the path to development and implementation of reliable assays for monitoring HIV incidence at a population level.
In this work we present an experimental study where energetic ions were produced in an underdense 2.5 × 1019 cm−3 plasma created by a 50 fs Ti:Sapphire laser with 5 TWs of power. The plasma comprises 95% He and 5% N2 gases. Ionization-induced trapping of nitrogen K-shell electrons in the laser-induced wakefield generates an electron beam with a mean energy of 40 MeV and ~1 nC of charge. Some of the helium ions at the wake–vacuum interface are accelerated with a measured minimum ion energy of He1+ ions of 1.2 MeV and He2+ ions of 4 MeV. The physics of the interaction is studied with 2D particle-in-cell simulations. These reveal the formation of an ion filament on the axis of the plasma due to space charge attraction of the wakefield-accelerated high-charge electron bunch. Some of these high-energy electrons escape the plasma to form a sheath at the plasma–vacuum boundary that accelerates some of the ions in the filament in the forward direction. Electrons with energy less than the sheath potential cannot escape and return to the plasma boundary in a vortex-like motion. This in turn produces a time-varying azimuthal magnetic field, which generates a longitudinal electric field at the interface that further accelerates and collimates the ions.
The cognitive profile of early onset Parkinson’s disease (EOPD) has not been clearly defined. Mutations in the parkin gene are the most common genetic risk factor for EOPD and may offer information about the neuropsychological pattern of performance in both symptomatic and asymptomatic mutation carriers. EOPD probands and their first-degree relatives who did not have Parkinson’s disease (PD) were genotyped for mutations in the parkin gene and administered a comprehensive neuropsychological battery. Performance was compared between EOPD probands with (N = 43) and without (N = 52) parkin mutations. The same neuropsychological battery was administered to 217 first-degree relatives to assess neuropsychological function in individuals who carry parkin mutations but do not have PD. No significant differences in neuropsychological test performance were found between parkin carrier and noncarrier probands. Performance also did not differ between EOPD noncarriers and carrier subgroups (i.e., heterozygotes, compound heterozygotes/homozygotes). Similarly, no differences were found among unaffected family members across genotypes. Mean neuropsychological test performance was within normal range in all probands and relatives. Carriers of parkin mutations, whether or not they have PD, do not perform differently on neuropsychological measures as compared to noncarriers. The cognitive functioning of parkin carriers over time warrants further study. (JINS, 2011, 17, 1–10)
Susceptibility to coeliac disease involves HLA and non-HLA-linked genes. The CTLA4/CD28 gene region encodes immune regulatory T-cell surface molecules and is a strong candidate as a susceptibility locus. We evaluated CTLA4/CD28 in coeliac disease by genetic linkage and association and combined our findings with published studies through a meta-analysis. 116 multiplex families were genotyped across CTLA4/CD28 using eight markers. The contribution of CTLA4/CD28 to coeliac disease was assessed by non-parametric linkage and association analyses. Seven studies were identified that had evaluated the relationship between CTLA4/CD28 and coeliac disease and a pooled analysis of data undertaken. In our study there was evidence for a relationship between variation in the CTLA4/CD28 region and coeliac disease by linkage and association analyses. However, the findings did not attain formal statistical significance (p = 0·004 and 0·039, respectively). Pooling findings with published results showed significant evidence for linkage (504 families) and association (940 families): p values, 0·0001 and 0·0014 at D2S2214, respectively, and 0·0008 and 0·0006 at D2S116, respectively. These findings suggest that variation in the CD28/CTLA4 gene region is a determinant of coeliac disease susceptibility. Dissecting the sequence variation underlying this relationship will depend on further analyses utilising denser sets of markers.
The ALFA mission is designed to map the entire sky at frequencies between approximately 0.3 and 30 MHz with angular resolution limited by interstellar and interplanetary scattering. Most of this region of the spectrum is inaccessible from the ground because of absorption and refraction by the Earth’s ionosphere. A wide range of astrophysical questions concerning solar system, galactic, and extragalactic objects could be answered with high resolution images at low frequencies, where absorption effects and coherent emission processes become important and the synchrotron lifetimes of electrons are comparable to the age of the universe.
A brief description of a set of processes and materials to make printed circuit panels will be given. Then we will discuss the multi-disciplines required for forming a scientific base and provide examples where the fundamentalist and often times specialist is providing the scientific data needed by the packaging engineer. Control techniques, characterization or otherwise basic information helpful in decision making is provided to the development and production groups. Specifically, the state of resin cure at critical steps in the process is used to demonstrate the inter-relation between cure, flow, and mechanical properties in affecting printed circuit board integrity. Finally, the complex role of moisture solubility and diffusion from the process environment in perturbing the chemical and mechanical state is discussed.
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