Development and operation of a pixel segmented liquid-filled linear array for radiotherapy quality assurance

A liquid isooctane (C$_{8}$H$_{18}$) filled ionization linear array for radiotherapy quality assurance has been designed, built and tested. The detector consists of 128 pixels, each of them with an area of 1.7 mm $\times$ 1.7 mm and a gap of 0.5 mm. The small pixel size makes the detector ideal for high gradient beam profiles like those present in Intensity Modulated Radiation Therapy (IMRT) and radiosurgery. As read-out electronics we use the X-Ray Data Acquisition System (XDAS) with the Xchip developed by the CCLRC. Studies concerning the collection efficiency dependence on the polarization voltage and on the dose rate have been made in order to optimize the device operation. In the first tests we have studied dose rate and energy dependences, and signal reproducibility. Dose rate dependence was found lower than 2.5 % up to 5 Gy min$^{-1}$, and energy dependence lower than 2.1 % up to 20 cm depth in solid water. Output factors and penumbras for several rectangular fields have been measured with the linear array and were compared with the results obtained with a 0.125 cm$^{3}$ air ionization chamber and radiographic film, respectively. Finally, we have acquired profiles for an IMRT field and for a virtual wedge. These profiles have also been compared with radiographic film measurements. All the comparisons show a good correspondence. Signal reproducibility was within a 2% during the test period (around three months). The device has proved its capability to verify on-line therapy beams with good spatial resolution and signal to noise ratio.Comment: 16 pages, 12 figures Submitted to Phys. Med. Bio

Intervention in acute coronary syndromes:do patients undergo intervention on the basis of their risk characteristics? The Global Registry of Acute Coronary Events (GRACE)

OBJECTIVE: To determine whether revascularisation is more likely to be performed in higher-risk patients and whether the findings are influenced by hospitals adopting more or less aggressive revascularisation strategies. METHODS: GRACE (Global Registry of Acute Coronary Events) is a multinational, observational cohort study. This study involved 24,189 patients enrolled at 73 hospitals with on-site angiographic facilities. RESULTS: Overall, 32.5% of patients with a non-ST elevation acute coronary syndrome (ACS) underwent percutaneous coronary intervention (PCI; 53.7% in ST segment elevation myocardial infarction (STEMI)) and 7.2% underwent coronary artery bypass grafting (CABG; 4.0% in STEMI). The cumulative rate of in-hospital death rose correspondingly with the GRACE risk score (variables: age, Killip class, systolic blood pressure, ST segment deviation, cardiac arrest at admission, serum creatinine, raised cardiac markers, heart rate), from 1.2% in low-risk to 3.3% in medium-risk and 13.0% in high-risk patients (c statistic = 0.83). PCI procedures were more likely to be performed in low- (40% non-STEMI, 60% STEMI) than medium- (35%, 54%) or high-risk patients (25%, 41%). No such gradient was apparent for patients undergoing CABG. These findings were seen in STEMI and non-ST elevation ACS, in all geographical regions and irrespective of whether hospitals adopted low (4.2-33.7%, n = 7210 observations), medium (35.7-51.4%, n = 7913 observations) or high rates (52.6-77.0%, n = 8942 observations) of intervention. CONCLUSIONS: A risk-averse strategy to angiography appears to be widely adopted. Proceeding to PCI relates to referral practice and angiographic findings rather than the patient\u27s risk status. Systematic and accurate risk stratification may allow higher-risk patients to be selected for revascularisation procedures, in contrast to current international practice

Complete revascularization with multivessel PCI for myocardial infarction

BACKGROUND In patients with ST-segment elevation myocardial infarction (STEMI), percutaneous coronary intervention (PCI) of the culprit lesion reduces the risk of cardiovascular death or myocardial infarction. Whether PCI of nonculprit lesions further reduces the risk of such events is unclear. METHODS We randomly assigned patients with STEMI and multivessel coronary artery disease who had undergone successful culprit-lesion PCI to a strategy of either complete revascularization with PCI of angiographically significant nonculprit lesions or no further revascularization. Randomization was stratified according to the intended timing of nonculprit-lesion PCI (either during or after the index hospitalization). The first coprimary outcome was the composite of cardiovascular death or myocardial infarction; the second coprimary outcome was the composite of cardiovascular death, myocardial infarction, or ischemia-driven revascularization. RESULTS At a median follow-up of 3 years, the first coprimary outcome had occurred in 158 of the 2016 patients (7.8%) in the complete-revascularization group as compared with 213 of the 2025 patients (10.5%) in the culprit-lesion-only PCI group (hazard ratio, 0.74; 95% confidence interval [CI], 0.60 to 0.91; P=0.004). The second coprimary outcome had occurred in 179 patients (8.9%) in the complete-revascularization group as compared with 339 patients (16.7%) in the culprit-lesion-only PCI group (hazard ratio, 0.51; 95% CI, 0.43 to 0.61; P<0.001). For both coprimary outcomes, the benefit of complete revascularization was consistently observed regardless of the intended timing of nonculprit-lesion PCI (P=0.62 and P=0.27 for interaction for the first and second coprimary outcomes, respectively). CONCLUSIONS Among patients with STEMI and multivessel coronary artery disease, complete revascularization was superior to culprit-lesion-only PCI in reducing the risk of cardiovascular death or myocardial infarction, as well as the risk of cardiovascular death, myocardial infarction, or ischemia-driven revascularization. (Funded by the Canadian Institutes of Health Research and others; COMPLETE ClinicalTrials.gov number, NCT01740479. opens in new tab.

Using the present to interpret the past: the role of ethnographic studies in Andean archaeology

Within Andean research it is common to use ethnographic analogies to aid the interpretation of archaeological remains, and ethnographers and archaeologists have developed shared research in technology, material culture and material practice. Although most of this research does not follow the detailed recording methods of spatial patterning envisioned in earlier formulations of ethnoarchaeology, it has had a profound effect on how archaeology in the region has been interpreted. This paper uses examples from the study of pottery production to address earlier debates about the use of ethnographic analogy, discusses the dangers of imposing an idealised or uniform vision of traditional Andean societies onto earlier periods (‘Lo Andino’) but stresses the benefits of combining ethnographic and archaeological research to explore continuities and changes in cultural practice and regional variations

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Something old, something new: Educational inclusion and head teachers as policy actors and subjects in the City of Buenos Aires

In Argentina, "inclusion" has become a central target of national and provincial educational policy since the mid-2000s. Unlike in other countries, inclusion has been associated with the transformation of upper secondary schooling into a compulsory level of education, together with the effective integration of pupils from socio-economically deprived families. This article examines how policy on inclusion is "done by" and "done to" head teachers in two Escuelas de Reingreso (Returning Schools) in the City of Buenos Aires. It scrutinises the usefulness of Ball and colleagues´ approach to policy in a very different context from their own. It argues that the head teachers are both policy actors and subjects. As policy actors, they creatively interpret and translate their schools´ policy mandates within specific contexts. In so doing, they produce antagonistic versions of "inclusion": the "educational" and "socio-educational" approaches. As policy subjects, they are spoken by competing policy discourses (in a Foucaultian sense) on schooling: the "selection and homogenisation" and the "inclusion and personalisation" discourses. They demarcate the limits to which head teachers are able to imagine, think and do. In different ways, they contribute to the misrecognition of the centrality of teachers` views and practices in pupils´ learning.Fil: Meo, Analía Inés. Universidad de Buenos Aires. Facultad de Ciencias Sociales. Instituto de Investigaciones ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin