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Prion diseases are rare dementias that most commonly occur sporadically, but can be inherited or acquired, and for which there is no cure. We sought to understand which prion disease symptoms are most problematic for carers, to inform the development of outcome measures.
Self-completed questionnaire with follow-up of a subset of participants by structured interview.
A nested study in the UK National Prion Monitoring Cohort, a longitudinal observational study.
Participants and measurements:
71 carers, of people with different prion diseases with a wide range of disease severity, identified 236 of their four most problematic symptoms by questionnaire which were grouped into ten domains. Structured interviews were then done to qualitatively explore these experiences. Eleven family carers of people with prion disease were selected, including those representative of a range of demographics and disease subtypes and those who cared for people with prion disease, living or recently deceased. Interviews were transcribed and formally studied.
The six most problematic symptom domains were: mobility and coordination; mood and behavior; personal care and continence; eating and swallowing; communication; and cognition and memory. The prevalence of these symptoms varied significantly by disease stage and type. A formal analysis of structured interviews to explore these domains is reported.
We make suggestions about how healthcare professionals can focus their support for people with prion disease. Clinical trials that aim to generate evidence regarding therapies that might confer meaningful benefits to carers should consider including outcome measures that monitor the symptomatic domains we have identified as problematic.
For fifty years now, historians have had at their disposal a coherent account of the law of arms applicable in the Court of the Constable and Marshal to cases concerned with the dividing of spoils and the ransoming of prisoners taken in wars.1 Disputes over these matters were resolved by reference to any contracts formed between the parties involved, failing which to any regulations issued in relation to the particular conflicts in which they fought, failing which to more general regulations or the customs of warfare. At the more general level especially, the law of arms had an international flavour, for the regulations introduced in one place were often influenced by those already in force elsewhere, and the communities that considered themselves obliged to conform to customary usages were not always nationally defined. It was of course important for the decisions delivered in the courts of one place to appear acceptable in the other places from which those despoiled or imprisoned came, and it was partly to this end that the practice of military tribunals was rationalised in terms of the legal theory expounded in broadly similar terms in universities throughout Europe. The learned doctrine of the law schools provided a framework of legitimacy within which courts in different parts of Europe were able to fashion versions of the law of arms that could be expected to receive recognition elsewhere. It follows that to understand the law of arms properly required – and still requires – familiarity with academic theory as well as forensic practice.5 It was not without cause that advice was taken on the application of the law of arms from ‘doctors of law’ or ‘iurisperiti’, a cadre of experts in the civil and canon laws whose advice was relied on in the specialised courts of the Constable and Marshal, the Admiral, and certain other officials.
To quantifying the interdependency within the regulatory environment governing human subject research, including Institutional Review Boards (IRBs), federally mandated Medicare coverage analysis and contract negotiations.
Over 8000 IRB, coverage analysis and contract applications initiated between 2013 and 2016 were analyzed using traditional and machine learning analytics for a quality improvement effort to improve the time required to authorize the start of human research studies.
Staffing ratios, study characteristics such as the number of arms, source of funding and number and type of ancillary reviews significantly influenced the timelines. Using key variables, a predictive algorithm identified outliers for a workflow distinct from the standard process. Improved communication between regulatory units, integration of common functions, and education outreach improved the regulatory approval process.
Understanding and improving the interdependencies between IRB, coverage analysis and contract negotiation offices requires a systems approach and might benefit from predictive analytics.
Transient Ischaemic Attack (TIA) is a neurologic event with symptom resolution within 24 hours. Early specialist assessment of TIA reduces risk of stroke and death. National United Kingdom (UK) guidelines recommend patients with TIA are seen in specialist clinics within 24 hours (high risk) or seven days (low risk).
We aimed to develop a complex intervention for patients with low risk TIA presenting to the emergency ambulance service. The intervention is being tested in the TIER feasibility trial, in line with Medical Research Council (MRC) guidance on staged development and evaluation of complex interventions.
We conducted three interrelated activities to produce the TIER intervention:
•Survey of UK Ambulance Services (n = 13) to gather information about TIA pathways already in use
•Scoping review of literature describing prehospital care of patients with TIA
•Synthesis of data and definition of intervention by specialist panel of: paramedics; Emergency Department (ED) and stroke consultants; service users; ambulance service managers.
The panel used results to define the TIER intervention, to include:
1.Protocol for paramedics to assess patients presenting with TIA and identify and refer low risk patients for prompt (< 7day) specialist review at TIA clinic
2.Patient Group Directive and information pack to allow paramedic administration of aspirin to patients left at home with referral to TIA clinic
3.Referral process via ambulance control room
4.Training package for paramedics
5.Agreement with TIA clinic service provider including rapid review of referred patients
We followed MRC guidance to develop a clinical intervention for assessment and referral of low risk TIA patients attended by emergency ambulance paramedic. We are testing feasibility of implementing and evaluating this intervention in the TIER feasibility trial which may lead to fully powered multicentre randomized controlled trial (RCT) if predefined progression criteria are met.
The Advanced Camera for Surveys was installed on the Hubble Space Telescope in March 2002. The instrument science team will search for planets using direct imaging with the ACS coronagraph and with precise astrometric and photometric measurement of suitable stars and disks. The camera is operational and performing to expectation.
The Advanced Camera for Surveys (ACS) offers a coronagraphic imaging mode with angular resolution of 0.026″pixel−1. In combination with with the appropriate subtraction of reference star point spread functions (PSF) the coronagraph is capable of achieving contrast ratios of ∼1000. We present some of the first ACS observations of the optically thin debris disk HD141569A and discuss new results from these observations.
Giant ragweed has been increasing as a major weed of row crops in the last 30 yr, but quantitative data regarding its pattern and mechanisms of spread in crop fields are lacking. To address this gap, we conducted a Web-based survey of certified crop advisors in the U.S. Corn Belt and Ontario, Canada. Participants were asked questions regarding giant ragweed and crop production practices for the county of their choice. Responses were mapped and correlation analyses were conducted among the responses to determine factors associated with giant ragweed populations. Respondents rated giant ragweed as the most or one of the most difficult weeds to manage in 45% of 421 U.S. counties responding, and 57% of responding counties reported giant ragweed populations with herbicide resistance to acetolactate synthase inhibitors, glyphosate, or both herbicides. Results suggest that giant ragweed is increasing in crop fields outward from the east-central U.S. Corn Belt in most directions. Crop production practices associated with giant ragweed populations included minimum tillage, continuous soybean, and multiple-application herbicide programs; ecological factors included giant ragweed presence in noncrop edge habitats, early and prolonged emergence, and presence of the seed-burying common earthworm in crop fields. Managing giant ragweed in noncrop areas could reduce giant ragweed migration from noncrop habitats into crop fields and slow its spread. Where giant ragweed is already established in crop fields, including a more diverse combination of crop species, tillage practices, and herbicide sites of action will be critical to reduce populations, disrupt emergence patterns, and select against herbicide-resistant giant ragweed genotypes. Incorporation of a cereal grain into the crop rotation may help suppress early giant ragweed emergence and provide chemical or mechanical control options for late-emerging giant ragweed.
We describe an on-going HST program aimed at determining the relationship between the nuclear black hole mass and bulge mass in spiral galaxies. We have selected a volume limited sample of 54 nearby spiral galaxies for which we already have ground based emission line rotation curves, CCD surface photometry and radio maps. We are now obtaining HST/STIS longslit observations of each of the galaxies in the sample in order to determine the nuclear Hα rotation curve at high (∼ 0.1) spatial resolution. We will use these data to measure the unresolved dark mass concentration at the nucleus of each object. Here we show the first results from observations of objects in the sample.
The tropopause, typically at 16 to 18 km altitude at the lower latitudes, dips down to only 8 km in the polar regions, allowing access to the cold, dry and nonturbulent lower stratosphere by tethered aerostats. These can float as high as 12 km, have long operating lifetimes, and are extremely reliable. In contrast to free-flying balloons, they can stay on station for weeks at a time, and payloads can be safely recovered for maintenance and adjustment and relaunched in a matter of hours. We propose to use such a platform, located first near Fairbanks, Alaska, and later in the Antarctic, to operate a new-technology 4 m telescope with diffraction-limited performance in the near infrared. Thanks to the low ambient temperature (~200 K), thermal emission from the optics is of the same order as that of the zodiacal light in the 2–3 μm band. Since this wavelength interval is the darkest part of the zodiacal light spectrum from optical wavelengths to 100 μm, the combination of high-resolution images and a very dark sky make it the spectral region of choice for observing galaxies, QSOs and clusters of galaxies at the formation epoch of galaxies.
To determine the frequency, risk factors, and outcomes for vancomycin-resistant Enterococcus (VRE) colonization and infection in patients with newly diagnosed acute leukemia.
Retrospective clinical study with VRE molecular strain typing.
A regional referral center for acute leukemia.
Two hundred fourteen consecutive patients with newly diagnosed acute leukemia between 2006 and 2012.
All patients had a culture of first stool and weekly surveillance for VRE. Clinical data were abstracted from the Intermountain Healthcare electronic data warehouse. VRE molecular typing was performed utilizing the semi-automated DiversiLab System.
The rate of VRE colonization was directly proportional to length of stay and was higher in patients with acute lymphoblastic leukemia. Risk factors associated with colonization include administration of corticosteroids (P=0.004) and carbapenems (P=0.009). Neither a colonized prior room occupant nor an increased unit colonization pressure affected colonization risk. Colonized patients with acute myelogenous leukemia had an increased risk of VRE bloodstream infection (BSI, P=0.002). Other risk factors for VRE BSI include severe neutropenia (P=0.04) and diarrhea (P=0.008). Fifty-eight percent of BSI isolates were identical or related by molecular typing. Eighty-nine percent of bloodstream isolates were identical or related to stool isolates identified by surveillance cultures. VRE BSI was associated with increased costs (P=0.0003) and possibly mortality.
VRE colonization has important consequences for patients with acute myelogenous leukemia undergoing induction therapy. For febrile neutropenic patients with acute myelogenous leukemia, use of empirical antibiotic regimens that avoid carbapenems and include VRE coverage may be helpful in decreasing the risks associated with VRE BSI.
The graphics processing unit has become an integral part of astronomical instrumentation, enabling high-performance online data reduction and accelerated online signal processing. In this paper, we describe a wide-band reconfigurable spectrometer built using an off-the-shelf graphics processing unit card. This spectrometer, when configured as a polyphase filter bank, supports a dual-polarisation bandwidth of up to 1.1 GHz (or a single-polarisation bandwidth of up to 2.2 GHz) on the latest generation of graphics processing units. On the other hand, when configured as a direct fast Fourier transform, the spectrometer supports a dual-polarisation bandwidth of up to 1.4 GHz (or a single-polarisation bandwidth of up to 2.8 GHz).
To assess the relative validity and repeatability of a sixty-four-item FFQ for estimating dietary intake of Zn and its absorption modifiers in Saudi adults. In addition, we used the FFQ to investigate the effect of age and gender on these intakes.
To assess validity, all participants completed the FFQ (FFQ1) and a 3 d food record. After 1 month, the FFQ was administered for a second time (FFQ2) to assess repeatability.
Jeddah, Saudi Arabia.
One hundred males and females aged 20–30 years and 60–70 years participated.
Mean intakes of Zn and protein from FFQ1 were significantly higher than those from the food record while there were no detectable differences between tools for measurement of phytic acid intake. Estimated intakes of Zn, protein and phytate by both approaches were strongly correlated (P<0·001). Bland–Altman analysis showed for protein that the difference in intake as measured by the two methods was similar across the range of intakes while for Zn and phytic acid, the difference increased with increasing mean intake. Zn and protein intakes from FFQ1 and FFQ2 were highly correlated (r>0·68, P<0·001) but were significantly lower at the second measurement (FFQ2). Older adults consumed less Zn and protein compared with young adults. Intakes of all dietary components were lower in females than in males.
The FFQ developed and tested in the current study demonstrated reasonable relative validity and high repeatability and was capable of detecting differences in intakes between age and gender groups.
Alzheimer's disease (AD) is considered to be a disorder predominantly affecting memory. It is increasingly recognized that the cognitive profile may be heterogeneous. We hypothesized that it would be possible to define distinct “cognitive phenotypes” in older people with AD.
Participants from three individual studies were included, consisting of 109 patients with a diagnosis of probable AD, and 91 age- and gender-matched control participants. All had demographic and cognitive assessment data available, including the Cambridge Cognitive Examination of the Elderly (CAMCOG). The CAMCOG scores and sub-scores were further analyzed using hierarchical cluster analysis and factor analysis.
Three clusters were identified. The scores loaded onto three factors representing the domains of attention, praxis, calculation, and perception; memory; and language comprehension and executive function. The main difference between the clusters related to degree of memory impairment. The composite score for memory between the clusters remained significantly different despite adjustment for illness duration and age of onset (p < 0.001).
These data suggest clinical heterogeneity within an older group of people with AD. This may have implications for diagnosis, prognosis, response to currently available treatments, and the development of novel therapies.
A survey of the Milky Way disk and the Magellanic System at the wavelengths of the 21-cm atomic hydrogen (H i) line and three 18-cm lines of the OH molecule will be carried out with the Australian Square Kilometre Array Pathfinder telescope. The survey will study the distribution of H i emission and absorption with unprecedented angular and velocity resolution, as well as molecular line thermal emission, absorption, and maser lines. The area to be covered includes the Galactic plane (|b| < 10°) at all declinations south of δ = +40°, spanning longitudes 167° through 360°to 79° at b = 0°, plus the entire area of the Magellanic Stream and Clouds, a total of 13 020 deg2. The brightness temperature sensitivity will be very good, typically σT≃ 1 K at resolution 30 arcsec and 1 km s−1. The survey has a wide spectrum of scientific goals, from studies of galaxy evolution to star formation, with particular contributions to understanding stellar wind kinematics, the thermal phases of the interstellar medium, the interaction between gas in the disk and halo, and the dynamical and thermal states of gas at various positions along the Magellanic Stream.
The discovery of a pulsar or pulsars orbiting near the Galactic Center (GC) could offer an unprecedented probe of strong-field gravity, the properties of our galaxy's supermassive black hole and insights into the paradoxical star formation history of the region. However, searching for pulsars near the GC is severely hampered by the large electron densities along our line of sight and the scattering-induced pulse broadening of the pulsar emission observed through it. As the broadened pulse length approaches the pulsar period, the periodicity in pulsar emission becomes nearly undetectable. Searches extended to higher frequencies, in an effort to reduce scattering, suffer from reduced intrinsic flux, higher system temperatures and increased atmospheric opacity. We are currently attempting to mitigate the challenges associated with searching for pulsars near the GC by employing new wide bandwidth receivers, upgraded IF distribution systems and novel digital spectrometers in a GC pulsar search campaign at the Green Bank Telescope in West Virginia, USA.
Our search will cover two frequency bands, from 12-15 GHz (Ku Band) and 18-26 GHz (K Band), during a total of approximately 30 hours of observations, with expected characteristic 10-sigma sensitivities between 5-10 micro-Jy. Our first observations are scheduled for mid-March 2012. Here we will present the status of our observations and initial results.
APSA is pleased to announce the next editorial team for the American Political Science Review. The new team, to be located at the University of North Texas, will begin their term on July 1, 2012. Their Editorial Statement follows.
Background: Elevated plasma homocysteine concentrations have been associated with both cognitive impairment and dementia. However, it is unclear whether some cognitive domains are more affected than others, or if this relationship is independent of B12 and folate levels, which can also affect cognition. We examined the relationship between plasma homocysteine and cognitive decline in an older hypertensive population.
Methods: 182 older people (mean age 80 years) with hypertension and without dementia, were studied at one center participating in the Study on COgnition and Prognosis in the Elderly (SCOPE). Annual cognitive assessments were performed using a computerized assessment battery and executive function tests, over a 3–5 year period (mean 44 months). Individual rates of decline on five cognitive domains were calculated for each patient. End of study plasma homocysteine, folate and B12 concentrations were measured. The relationship between homocysteine levels and cognitive decline was studied using multivariate regression models, and by comparing high versus low homocysteine quartile groups.
Results: Higher homocysteine showed an independent association with greater cognitive decline in three domains: speed of cognition (β = −27.33, p = 0.001), episodic memory (β = −1.25, p = 0.02) and executive function (β = −0.05, p = 0.04). The association with executive function was no longer significant after inclusion of folate in the regression model (β = −0.032, p = 0.22). Change in working memory and attention were not associated with plasma homocysteine, folate or B12. High homocysteine was associated with greater decline with a Cohen's d effect size of approximately 0.7 compared to low homocysteine.
Conclusions: In a population of older hypertensive patients, higher plasma homocysteine was associated with cognitive decline.