Risk models and scores for type 2 diabetes: Systematic review

This article is published under a Creative Commons Attribution Non Commercial (CC BY-NC 3.0) licence that allows reuse subject only to the use being non-commercial and to the article being fully attributed (http://creativecommons.org/licenses/by-nc/3.0).Objective - To evaluate current risk models and scores for type 2 diabetes and inform selection and implementation of these in practice. Design - Systematic review using standard (quantitative) and realist (mainly qualitative) methodology. Inclusion - criteria Papers in any language describing the development or external validation, or both, of models and scores to predict the risk of an adult developing type 2 diabetes. Data sources - Medline, PreMedline, Embase, and Cochrane databases were searched. Included studies were citation tracked in Google Scholar to identify follow-on studies of usability or impact. Data extraction - Data were extracted on statistical properties of models, details of internal or external validation, and use of risk scores beyond the studies that developed them. Quantitative data were tabulated to compare model components and statistical properties. Qualitative data were analysed thematically to identify mechanisms by which use of the risk model or score might improve patient outcomes. Results - 8864 titles were scanned, 115 full text papers considered, and 43 papers included in the final sample. These described the prospective development or validation, or both, of 145 risk prediction models and scores, 94 of which were studied in detail here. They had been tested on 6.88 million participants followed for up to 28 years. Heterogeneity of primary studies precluded meta-analysis. Some but not all risk models or scores had robust statistical properties (for example, good discrimination and calibration) and had been externally validated on a different population. Genetic markers added nothing to models over clinical and sociodemographic factors. Most authors described their score as “simple” or “easily implemented,” although few were specific about the intended users and under what circumstances. Ten mechanisms were identified by which measuring diabetes risk might improve outcomes. Follow-on studies that applied a risk score as part of an intervention aimed at reducing actual risk in people were sparse. Conclusion - Much work has been done to develop diabetes risk models and scores, but most are rarely used because they require tests not routinely available or they were developed without a specific user or clear use in mind. Encouragingly, recent research has begun to tackle usability and the impact of diabetes risk scores. Two promising areas for further research are interventions that prompt lay people to check their own diabetes risk and use of risk scores on population datasets to identify high risk “hotspots” for targeted public health interventions.Tower Hamlets, Newham, and City and Hackney primary care trusts and National Institute of Health Research

GASPS—A Herschel Survey of Gas and Dust in Protoplanetary Disks: Summary and Initial Statistics

We describe a large-scale far-infrared line and continuum survey of protoplanetary disk through to young debris disk systems carried out using the ACS instrument on the Herschel Space Observatory. This Open Time Key program, known as GASPS (Gas Survey of Protoplanetary Systems), targeted ∼250 young stars in narrow wavelength regions covering the [OI] fine structure line at 63 μm the brightest far-infrared line in such objects. A subset of the brightest targets were also surveyed in [OI]145 μm, [CII] at 157 μm, as well as several transitions of H_2O and high-excitation CO lines at selected wavelengths between 78 and 180 μm. Additionally, GASPS included continuum photometry at 70, 100 and 160 μm, around the peak of the dust emission. The targets were SED Class II–III T Tauri stars and debris disks from seven nearby young associations, along with a comparable sample of isolated Herbig AeBe stars. The aim was to study the global gas and dust content in a wide sample of circumstellar disks, combining the results with models in a systematic way. In this overview paper we review the scientific aims, target selection and observing strategy of the program. We summarise some of the initial results, showing line identifications, listing the detections, and giving a first statistical study of line detectability. The [OI] line at 63 μm was the brightest line seen in almost all objects, by a factor of ∼10. Overall [OI]63 μm detection rates were 49%, with 100% of HAeBe stars and 43% of T Tauri stars detected. A comparison with published disk dust masses (derived mainly from sub-mm continuum, assuming standard values of the mm mass opacity) shows a dust mass threshold for [OI]63 μm detection of ∼10^(-5) M_⊙. Normalising to a distance of 140 pc, 84% of objects with dust masses ≥10^(-5) M_⊙ can be detected in this line in the present survey; 32% of those of mass 10^(-6)–10^(-5) M_⊙, and only a very small number of unusual objects with lower masses can be detected. This is consistent with models with a moderate UV excess and disk flaring. For a given disk mass, [OI] detectability is lower for M stars compared with earlier spectral types. Both the continuum and line emission was, in most systems, spatially and spectrally unresolved and centred on the star, suggesting that emission in most cases was from the disk. Approximately 10 objects showed resolved emission, most likely from outflows. In the GASPS sample, [OI] detection rates in T Tauri associations in the 0.3–4 Myr age range were ∼50%. For each association in the 5–20 Myr age range, ∼2 stars remain detectable in [OI]63 μm, and no systems were detected in associations with age >20 Myr. Comparing with the total number of young stars in each association, and assuming a ISM-like gas/dust ratio, this indicates that ∼18% of stars retain a gas-rich disk of total mass ∼1 M_(Jupiter) for 1–4 Myr, 1–7% keep such disks for 5–10 Myr, but none are detected beyond 10–20 Myr. The brightest [OI] objects from GASPS were also observed in [OI]145 μm, [CII]157 μm and CO J = 18 - 17, with detection rates of 20–40%. Detection of the [CII] line was not correlated with disk mass, suggesting it arises more commonly from a compact remnant envelope

CO and CI maps of the starburst galaxy M82

The first map of an external galaxy in the 3P₁ - 3P0 fine-structure line of atomic carbon (CI) is presented towards the nucleus of the starbuster M82, and compared with the distinction of the CO J = 4 - 3 molecular emission. The CI traces features that are seen in lower transition CO maps, and shows that CI and the CO are well mixed and have similar spatial distributions. There are small differences between the CO J = 4 - 3 line and lower transition CO data towards the NE part of the molecular ring, where the emission is less prominent. The abundance ratio [CI]/[CO] across M82 is very high, with an average value ~ 0.5 across most of the nucleus, a factor at least 5 times that which is typical of dense molecular cloud cores seen in our own Galaxy. This means that on average, CI is overabundant towards M82. This result can be explained using models which provide enhancements to the CI abundance above normal Interstellar Medium values, a result of a greater cosmic ray flux in M82, or where there is substantial mixing of the gas

Evidence for a non-genomic action of testosterone in skeletal muscle which may improve athletic performance: Implications for the female athlete

This review will focus on the proposed second mode of testosterone action (now termed non-genomic) that appears to occur independently of the traditional transcriptional mechanism in mammalian skeletal muscle cells which may enhance skeletal muscle contractile properties. This mechanism of testosterone action differs from the traditional pathway, originating at the cell membrane, having a rapid onset of action, requiring second messengers to execute its effects and is insensitive to inhibitors of traditional androgen receptor action, transcription and protein synthesis. Importantly, unlike the traditional action of testosterone in skeletal muscle, this non-genomic pathway is shown to have a direct acute effect on calcium-dependent components important for the contractile process. The changes within the contractile apparatus may enhance the ability of the muscle to produce explosive power during athletic performance. Rapid increases in Inositol triphosphate mass and calcium release from the sarcoplasmic reticulum have been reported in rodent skeletal muscle cells, and a rapid androgen (dihydrotestosterone)- induced increase in peak force production has been recorded in intact rodent skeletal muscle fibre bundles while showing increases in the activity of the Ras/MAP/ERK mediated pathway. Because the non-genomic action of testosterone is enhanced during increases in exposure to testosterone and is acute in its action, implications for athletic performance are likely greater in females than males due to natural fluctuations in circulating testosterone levels during the female menstrual cycle, reproductive pathology, and changes induced by hormonal contraceptive methods. Research should be undertaken in humans to confirm a pathway for non-genomic testosterone action in human skeletal muscle. Specifically, relationships between testosterone fluctuations and physiological changes within skeletal muscle cells and whole muscle exercise performance need to be examined

Water depletion in the disk atmosphere of Herbig AeBe stars

We present high resolution (R = 100,000) L-band spectroscopy of 11 Herbig AeBe stars with circumstellar disks. The observations were obtained with the VLT/CRIRES to detect hot water and hydroxyl radical emission lines previously detected in disks around T Tauri stars. OH emission lines are detected towards 4 disks. The OH P4.5 (1+,1-) doublet is spectrally resolved as well as the velocity profile of each component of the doublet. Its characteristic double-peak profile demonstrates that the gas is in Keplerian rotation and points to an emitting region extending out to ~ 15-30 AU. The OH, emission correlates with disk geometry as it is mostly detected towards flaring disks. None of the Herbig stars analyzed here show evidence of hot water vapor at a sensitivity similar to that of the OH lines. The non-detection of hot water vapor emission indicates that the atmosphere of disks around Herbig AeBe stars are depleted of water molecules. Assuming LTE and optically thin emission we derive a lower limit to the OH/H2O column density ratio > 1 - 25 in contrast to T Tauri disks for which the column density ratio is 0.3 -- 0.4.Comment: Accepted for publication in Ap

A Keplerian Disk around the Herbig Ae star HD169142

We present Submillimeter Array observations of the Herbig Ae star HD169142 in 1.3 millimeter continuum emission and 12CO J=2-1 line emission at 1.5 arcsecond resolution that reveal a circumstellar disk. The continuum emission is centered on the star position and resolved, and provides a mass estimate of about 0.02 solar masses for the disk. The CO images show patterns in position and velocity that are well matched by a disk in Keplerian rotation with low inclination to the line-of-sight. We use radiative transfer calculations based on a flared, passive disk model to constrain the disk parameters by comparison to the spectral line emission. The derived disk radius is 235 AU, and the inclination is 13 degrees. The model also necessitates modest depletion of the CO molecules, similar to that found in Keplerian disks around T Tauri stars.Comment: 10 pages, 2 figures, accepted by A

Collisional Cascades in Planetesimal Disks I. Stellar Flybys

We use a new multiannulus planetesimal accretion code to investigate the evolution of a planetesimal disk following a moderately close encounter with a passing star. The calculations include fragmentation, gas and Poynting-Robertson drag, and velocity evolution from dynamical friction and viscous stirring. We assume that the stellar encounter increases planetesimal velocities to the shattering velocity, initiating a collisional cascade in the disk. During the early stages of our calculations, erosive collisions damp particle velocities and produce substantial amounts of dust. For a wide range of initial conditions and input parameters, the time evolution of the dust luminosity follows a simple relation, L_d/L_{\star} = L_0 / [alpha + (t/t_d)^{beta}]. The maximum dust luminosity L_0 and the damping time t_d depend on the disk mass, with L_0 proportional to M_d and t_d proportional to M_d^{-1}. For disks with dust masses of 1% to 100% of the `minimum mass solar nebula' (1--100 earth masses at 30--150 AU), our calculations yield t_d approx 1--10 Myr, alpha approx 1--2, beta = 1, and dust luminosities similar to the range observed in known `debris disk' systems, L_0 approx 10^{-3} to 10^{-5}. Less massive disks produce smaller dust luminosities and damp on longer timescales. Because encounters with field stars are rare, these results imply that moderately close stellar flybys cannot explain collisional cascades in debris disk systems with stellar ages of 100 Myr or longer.Comment: 33 pages of text, 12 figures, and an animation. The paper will appear in the March 2002 issue of the Astronmomical Journal. The animation and a copy of the paper with full resolution figures are at S. Kenyon's planet formation website: http://cfa-www.harvard.edu/~kenyon/p

Gravitational Stirring in Planetary Debris Disks

We describe gravitational stirring models of planetary debris disks using a new multi-annulus planetesimal evolution code. The current code includes gravitational stirring and dynamical friction; future studies will include coagulation, fragmentation, Poynting-Robertson drag, and other physical processes. We use the results of our calculations to investigate the physical conditions required for small bodies in a planetesimal disk to reach the shattering velocity and begin a collisional cascade. Our results demonstrate that disks composed primarily of bodies with a single size will not undergo a collisional cascade which produces small dust grains at 30-150 AU on timescales of 1 Gyr or smaller. Disks with a size distribution of bodies reach conditions necessary for a collisional cascade in 10 Myr to 1 Gyr if the disk is at least as massive as a minimum mass solar nebula and if the disk contains objects with radii of 500 km or larger. The estimated 500 Myr survival time for these disks is close to the median age of roughly 400 Myr derived for nearby stars with dusty disks.Comment: 23 pages of text + 16 Figures; to appear in the Astronomical Journal, January 200

Spectroscopy of Brown Dwarf Candidates in the rho Ophiuchi Molecular Core

We present an analysis of low resolution infrared spectra for 20 brown dwarf candidates in the core of the $\rho$ Ophiuchi molecular cloud. Fifteen of the sources display absorption-line spectra characteristic of late-type stars. By comparing the depths of water vapor absorption bands in our candidate objects with a grid of M dwarf standards, we derive spectral types which are independent of reddening. Optical spectroscopy of one brown dwarf candidate confirms the spectral type derived from the water bands. Combining their spectral types with published near-infrared photometry, effective temperatures and bolometric stellar luminosities are derived enabling us to place our sample on the Hertzsprung-Russell diagram. We compare the positions of the brown dwarf candidates in this diagram with two sets of theoretical models in order to estimate their masses and ages. Considering uncertainties in placing the candidates in the H-R diagram, six objects consistently lie in the brown dwarf regime and another five objects lie in the transition region between stellar and substellar objects. The ages inferred for the sample are consistent with those derived for higher mass association members. Three of the newly identified brown dwarfs display infrared excesses at $\lambda$=2.2 $\mu$m suggesting that young brown dwarfs can have active accretion disks. Comparing our mass estimates of the brown dwarf candidates with those derived from photometric data alone suggests that spectroscopy is an essential component of investigations of the mass functions of young clusters.Comment: Astronomical Journal, in press: 25 pages, latex, 5 tables and 6 figures (separate

Combined assessment (aspiration cytology and mammography) of clinically suspicious breast masses

We examined the safety and utility of the combined assessment of aspiration cytology and mammography in 705 women who had clinically suspicious or malignant palpable breast masses. Histological assessment confirmed 176 benign and 529 malignant lesions. There were no incorrect (false positive) diagnoses made in the 176 benign masses when combined assessment was used (specificity 1,0; predictive value 0,86); in isolation, however, there was a false positive cytological diagnosis («papillary carcinoma») and 3 false positive mammographic diagnoses. Benign disease (false negative) was incorrectly diagnosed by combined assessment in 4 of the 529 malignant masses (sensitivity 0,99; predictive value 0,98): cytological diagnoses were of fat necrosis (2) and benign cells on cytospin (1) and aspiration biopsy (1); mammographic diagnoses were of benign disease (2) and normality (2). Indeterminate («atypical», «suspicious») diagnoses were problematic and frequent (overall 223 (31,6%), malignant masses 137 (25,9%), benign masses 86 (48,9%); cytology 117 (16,6%), mammography 141 (20%). Thus, with the combined assessment of mammography and cytology in clinically suspicious breast masses, a decisive diagnosis was made in about two-thirds of cases allowing the safe commencement of therapy; the balance of patients required cone or excision biopsy