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Movement disorders associated with exposure to antipsychotic drugs are common and stigmatising but underdiagnosed.
To develop and evaluate a new clinical procedure, the ScanMove instrument, for the screening of antipsychotic-associated movement disorders for use by mental health nurses.
Item selection and content validity assessment for the ScanMove instrument were conducted by a panel of neurologists, psychiatrists and a mental health nurse, who operationalised a 31-item screening procedure. Interrater reliability was measured on ratings for 30 patients with psychosis from ten mental health nurses evaluating video recordings of the procedure. Criterion and concurrent validity were tested comparing the ScanMove instrument-based rating of 13 mental health nurses for 635 community patients from mental health services with diagnostic judgement of a movement disorder neurologist based on the ScanMove instrument and a reference procedure comprising a selection of commonly used rating scales.
Interreliability analysis showed no systematic difference between raters in their prediction of any antipsychotic-associated movement disorders category. On criterion validity testing, the ScanMove instrument showed good sensitivity for parkinsonism (90%) and hyperkinesia (89%), but not for akathisia (38%), whereas specificity was low for parkinsonism and hyperkinesia, and moderate for akathisia.
The ScanMove instrument demonstrated good feasibility and interrater reliability, and acceptable sensitivity as a mental health nurse-administered screening tool for parkinsonism and hyperkinesia.
We present a new distance determination to the Small Magellanic Cloud from the surface brightness technique applied to the Cepheid variable HV 829. Although this is a preliminary distance based on only one star, it illustrates the power of the surface brightness technique to extragalactic Cepheid distances, it develops the technique which we will apply to additional SMC and LMC Cepheids, and the distance is of intrinsic interest because of the current controvery concerning distances for the Magellanic Clouds.
For HV 829 itself we obtain a distance modulus of 18.91 ± 0.20 mag. From other evidence we infer that HV 829 is slightly in front of the SMC centroid distance. Correcting to the SMC centroid yields a distance to the SMC of 19.05 ± 0.20 mag. We stress that this distance modulus is fully independent of any other distance modulus for the SMC, including those based upon Cepheids. Even so, our result agrees more closely with other, independent Cepheid distances than with RR Lyrae distances and main sequence fitting distances.
The United States has been a leader in the creation of disability rights law, providing a policy template for other nations. Yet the social model, the animating philosophy behind the disability rights movement, has had little effect on the wide range of welfare programs that serve people with disabilities. These programs, whose creation preceded the modern disability rights movement, reflect a medical model of disability that is at odds with the social model. Analysing the Americans with Disabilities Act (which embodies the social model) and Social Security Disability Insurance (the largest welfare program for people with disabilities), we explore how and why this layering of contradictory disability rights and welfare programs developed and how it has been maintained. We argue that the tension between these policies engendered a series of patches, or ‘kludges’, that allow the policies to coexist without meaningful synthesis. We contend that the United States is particularly prone to this layering of ‘tense policies’, but that it is likely characteristic of disability policy in many nations. Finally we argue that accurate benchmarking of disability rights regimes across nations requires analysts to dig through all the layers of disability policy.
OBJECTIVES/SPECIFIC AIMS: The goal of this research is to use circulating tumor cells (CTC) enumeration and characterization to monitor anticancer treatment response. Emerging evidence strongly suggests the implications that epithelial-to-mesenchymal transition may have in cancer metastasis. Consequently, we hope to elucidate the significance of mesenchymal and stem-like CTCs in the peripheral blood of metastatic pancreatic cancer patients by analyzing the prevalence and frequency trends of CD133+ CTCs, as they relate to clinical events. We also hope to determine if there is a correlation between EpCAM+ CTCs and CD133+ CTCs numbers with tumor size, disease stage, and patient clinical outcome. METHODS/STUDY POPULATION: Blood samples of patients with metastatic pancreatic cancer (stage IV) were obtained from the University of Florida Health Cancer Center after informed consent through an IRB-approved protocol. CTC capture, characterization, and enumeration was performed on the blood of these cancer patients during their anticancer treatment. Patients had blood drawn for this purpose at time points aligned with clinical phlebotomy (every 2 weeks). CTC capture was performed by introducing treated patient blood samples into antibody-functionalized microdevices. The PDMS devices were functionalized by immobilizing either anti-EpCAM or anti-CD133, through an avidin-biotin complex. After capture, cells were fixated and permeabilized with 4% paraformaldehyde and 0.2% Triton X-100, respectively. Three-color immunocytochemistry (anti-cytokeratin-FITC, anti-CD45-PE, and DAPI) was performed to identify CTCs from nonspecifically captured blood cells. To be counted as a CTC, based on the FDA-approved technical definition, a cell with the appropriate cell size and morphology must be nucleated (DAPI+), express cytokeratin (CK+), and lack the leukocytic CD45 marker (CD45−). RESULTS/ANTICIPATED RESULTS: We tested the clinical utility of the device for monitoring the response of patients with advanced pancreatic cancer to a chemotherapy treatment consisting of anticancer drugs including 5-fluorouracil, leucovorin, oxaliplatin, and dasatinib. We have detected EpCAM+ CTCs in 47/47 (100%) and CD133+ CTCs in 41/47 (87.2%) of blood samples, coming from a cohort of 16 patients. We studied the correlation between the CTC numbers and the clinical result of patients in the study. We found that the size and changes in the size of the primary tumor (confirmed by CT scans) correlated with the frequency and increase/decrease trends in the number of CTCs detected. We expect to find some relationship between the number of detected CD133+ CTCs, or rather stem-like CTCs, and the clinical outcome of patients (eg, disease progression leading to withdrawal from study). DISCUSSION/SIGNIFICANCE OF IMPACT: Enumeration of patient CTCs and stem-like CTCs at different stages of a patient’s treatment may correlate with disease stage and prognosis, and prove useful in monitoring early recurrence, patient-specific treatment response, and newly acquired resistances; all of which would aid in providing guidance for the next step in clinical intervention. This type of liquid biopsy technology has great potential to make an impact in the future of personalized medicine and point-of-care diagnostics, as well as become a sturdy tool for translational research.
The visual surface brightness relation is applied to the determination of parallaxes of white dwarfs on the assumption, borne out by previous studies of white dwarfs of known parallax, that these show only a small range of linear diameters.
Archaeological tunneling is a standard excavation strategy in Mesoamerica. The ancient Maya built new structures atop older ones that were no longer deemed usable, whether for logistical or ideological reasons. This means that as archaeologists excavate horizontal tunnels into ancient Maya structures, they are essentially moving back in time. As earlier constructions are encountered, these tunnels may deviate in many directions in order to document architectural remains. The resultant excavations often become intricate labyrinths, extending dozens of meters. Traditional forms of archaeological documentation, such as photographs, plan views, and profile drawings, are limited in their ability to convey the complexity of tunnel excavations. Terrestrial Lidar (light detection and ranging) instruments are able to generate precise 3D models of tunnel excavations. This article presents the results of a model created with a Faro™ Focus 3D 120 Scanner of tunneling excavations at the site of El Zotz, Guatemala. The lidar data document the excavations inside a large mortuary pyramid, including intricately decorated architecture from an Early Classic (A.D. 300–600) platform buried within the present form of the structure. Increased collaboration between archaeologists and scholars with technical expertise maximizes the effectiveness of 3D models, as does presenting digital results in tandem with traditional forms of documentation.
We have examined the uncertainties involved in using the visual surface brightness technique on Galactic Cepheid variables. The random error in a single Cepheid distance measurement is well determined to be ±8%. An upper limit to the systematic uncertainty is shown to be ±6% in distance. These combine for a single Cepheid to a typical uncertainty of ±10% and, for samples larger than ten Cepheids, to a typical uncertainty of less than ±6% in distance.
We have determined quasi-geometric distances to the Magellanic Clouds, M31 and M33. Our analysis uses a Bayesian statistical method to provide mathematically rigorous and objective solutions for individual Cepheids. We combine the individual distances with a hierarchical Bayesian model to determine the galactic distances. We obtain distance moduli 18.87 ± 0.07 mag (LMC, 12 stars), 19.14 ± 0.10 (SMC, 8 stars), 23.83 ± 0.35 mag (M33, 1 star) and 25.2 ± 0.6 mag (M31, 1 star) – all uncorrected for metallicity. The M31 and M33 distances are very preliminary. If the PL relations of the LMC, SMC and Galaxy are identical, our results exclude the metallicity effect in the V, (V – R) surface brightness method predicted by Hindsley & Bell (1989) at the 5σ level. Alternately, if Hindsley & Bell’s prediction is adopted as true, we find a metallicity effect intrinsic to the Cepheid PL relation requiring a correction Δ(V – Mv) = (0.36 ± 0.07)Δ[A/H] mag. The latter has the opposite sign to other observational estimates of the Cepheid metallicity effect.
A new orbit has been derived for the binary Cepheid S Sagittae = HD 188727 = BD+16°4067, using both extant data and new radial velocities derived from radial velocity spectrometer observations at McDonald Observatory and the Dominion Astrophysical Observatory. We deconvoled both the pulsational and orbital components from the observed velocities in order to fit a truncated Fourier series to the pulsation velocities and to derive orbital elements respectively. We confirm the orbital elements given in Herbig and Moore (1952) and speculate that the secular trend evident in the orbital (O-C) diagram may be interpreted as evidence for a third component. (See Evans, Slovak and Welch, this volume, for IUE observations supporting this interpretation.)
Cepheid variable stars are fundamental to the calibration of the extragalactic distance scale. We present radial velocities, preliminary metallicities, and preliminary surface brightness distances of Cepheids in Local Group galaxies M31 and M33 using data obtained with the High Resolution Spectrograph on the Hobby-Eberly Telescope at McDonald Observatory. These data are the first step toward surface brightness distance measurements and metallicity calibrations of these extragalactic Cepheids.
The BVRI light-curve parameters of 112 galactic Cepheids are determined by Fourier analysis using over 4,000 differential photoelectric observations. This catalog is similar to Schaltenbrand and Tammann's except that it is based on a homogeneous data set and the Fourier coefficients are given.
We have applied an approximately Bayesian and a fully Bayesian analysis to the calculation of Cepheid distances, radii and absolute magnitudes using the surface brightness (Baade–Wesselink) method. Both methods successfully account for errors in the data, provide unbiased distance estimates, and provide objective model selection for the radial velocity curve. In addition, the fully Bayesian analysis objectively selects a model for the magnitude curve; averages over models of various Fourier orders, properly weighted by the posterior probabilities of the individual models; and includes a Lutz–Kelker correction.
The approximately Bayesian method is that described by Jefferys & Barnes (1999) and Barnes & Jefferys (1999). It is a maximum likelihood approach with objective selection of the order of the Fourier series model of the radial velocities.
Suppose one of the current high angular resolution instruments were capable of measuring the instantaneous angular diameter of a Cepheid throughout its pulsation cycle. By comparing the angular diameter variation to the linear displacement variation, obtained from the integrated radial velocity curve, one could determine both the linear radius and the distance of the variable. This distance would be independent of all other astrophysical distance scales and would be geometric, i.e. independent of the effects of interstellar obscuration.
Although none of the current instruments has this capability, the same result can be accomplished indirectly through use of the stellar surface brightness. Recall that the visual surface brightness can be expressed in terms of the apparent visual magnitude and the stellar angular diameter. At any phase in the Cepheid pulsation, knowledge of the visual surface brightness and the apparent magnitude permits inference of the angular diameter.
From stars with measured angular diameters it is known that the visual surface brightness parameter Fv correlates remarkably well with the Johnson V-R color index (Barnes and Evans 1976; Barnes, Evans and Parsons 1976; Barnes, Evans and Moffett 1978). Johnson VR photometry may thus be used to determine the visual surface brightness and hence the stellar angular diameter. As shown in the referenced works, such angular diameters are essentially independent of the choice of interstellar obscuration corrections. This approach to stellar angular diameters and then to variable star distances is therefore nearly equivalent to direct measurements.
Knowledge on the ecology of humpback whales in the eastern North Atlantic is lacking by comparison with most other ocean basins. Humpback whales were historically over-exploited in the region and are still found in low relative abundances. This, coupled with their large range makes them difficult to study. With the aim of informing more effective conservation measures in Ireland, the Irish Whale and Dolphin Group began recording sightings and images suitable for photo-identification of humpback whales from Irish waters in 1999. Validated records submitted by members of the public and data from dedicated surveys were analysed to form a longitudinal study of individually recognizable humpback whales. The distribution, relative abundance and seasonality of humpback whale sighting records are presented, revealing discrete important areas for humpback whales in Irish coastal waters. An annual easterly movement of humpback whales along the southern coast of Ireland is documented, mirroring that of their preferred prey: herring and sprat. Photo-identification images were compared with others collected throughout the North Atlantic (N = 8016), resulting in matches of two individuals between Ireland and Iceland, Norway and the Netherlands but no matches to known breeding grounds (Cape Verde and West Indies). This study demonstrates that combining public records with dedicated survey data is an effective approach to studying low-density, threatened migratory species over temporal and spatial scales that are relevant to conservation and management.
In this communication, the author offers remarks on journals kept by Dr Carlyle, in the city of Carlisle, from 1757 to 1783 inclusive; by the Rev. Joseph Golding, at Aikbank, near Wigton, Cumberland, from 1792 to 1810 inclusive; and by himself at Bunkers Hill, two and a half miles west of Carlisle, which is situate 184 feet above the sea-level. The author gave tables showing the quantity of rain of each month and year included in these periods. From the averages, it appears that about twice as much rain falls in each of the latter months of the table as in the month of April; and about one-third less rain falls in the first six months of the year than in the last six months, and that April is the driest month of the year.
Audit is an important tool for quality improvement. The collection of data on clinical performance against evidence-based and clinically relevant standards, which are considered by clinicians to be realistic in routine practice, can usefully prompt reflective practice and the implementation of change. Evidence of participation in clinical audit is required to achieve intended learning outcomes for trainees in psychiatry and revalidation for those who are members of the Royal College of Psychiatrists. This article addresses some of the practical steps involved in conducting an audit project, and, to illustrate key points, draws on lessons learnt from a national, audit-based, quality improvement programme of lithium prescribing and monitoring conducted through the Prescribing Observatory for Mental Health.