2,975 research outputs found
A spatial scan statistic for zero-inflated Poisson process
The scan statistic is widely used in spatial cluster detection applications
of inhomogeneous Poisson processes. However, real data may present substantial
departure from the underlying Poisson process. One of the possible departures
has to do with zero excess. Some studies point out that when applied to data
with excess zeros, the spatial scan statistic may produce biased inferences. In
this work, we develop a closed-form scan statistic for cluster detection of
spatial zero-inflated count data. We apply our methodology to simulated and
real data. Our simulations revealed that the Scan-Poisson statistic steadily
deteriorates as the number of zeros increases, producing biased inferences. On
the other hand, our proposed Scan-ZIP and Scan-ZIP+EM statistics are, most of
the time, either superior or comparable to the Scan-Poisson statistic
Evolution of production of Astatine-211 in Orléans Cyclotron
Introduction
Since 2005, we produce, at academic scale in Orleans, 211At for needs of chemistry and physicians teams of Nantes in research project of alpha immunotherapy. Between 2005 and 2014, several modifications were been made on preparation of target, targetry and radiation to protect personnel.
Material and Methods
The first target was a molten Bi metal onto a Cu support pre-treated with acid attack. The wished thickness (up to 100 ”m) was obtained by mechanical treatment of target. The target is irradiated at 32MeV alpha particle beam for around 2 hours and then delivered by road transport to users. Only a measure of radiation dose was made to evaluate target activity. The second target we have used since 2010 is a electrodeposition of Bi (thickness of around 30 ”m) onto AlN backing. We used a beam of 30.5 MeV for reaction 207Bi(α,n)211At (2 h with a current intensity of 2”A). Activity has measured with a detector Ge at 687 keV (γ-branching fraction = 0.26 %) before to be delivered. For all targets, beam energy on target was around 28.7 Mev in order not to produce too much 210At.
Results and Conclusion
138 productions with the first target were delivered with an estimated activity of less than 100 MBq. Difficulties with wet extraction1, low yield of radiolabelling (metallic impurities and activation of copper resulting in 66Ga and 67Ga) made necessary to change process of extraction. With support of AlN, dry extraction was used with good yield (75â80 %) and without activation of support. Until today, 46 batchs were delivered with activity of 44 ± 12 MBq/”Ah. Yield activity of 211At has been almost doubled compared to first target (25MBq/”Ah). The dose burden to personnel was decreased with modification of targetry (outside of blockhouse of cyclotron, in a specific line beam to radionuclide production, cf. FIG. 1).
In the case of 211At production, energy of reaction is of major impact. With our versatile accelerator (range of energy in alpha between 10 and 50 MeV) and a low thickness of metal, itâs easy to reach the right energy. This radionuclide production will be continued until ARRONAX, Nantes cyclotron, could take over from us for bigger activity of 211At
The Extracellular Matrix of the Lateral Pharyngeal Wall in Obstructive Sleep Apnea
Study Objectives: To compare the components of the extracellular matrix in the lateral pharyngeal muscular wall in patients with and without obstructive sleep apnea (OSA). This may help to explain the origin of the increased collapsibility of the pharynx in patients with OSA. Design: Specimens from the superior pharyngeal constrictor muscle, obtained during pharyngeal surgeries, were evaluated using histochemical and immunohistochemical analyses to determine the fractional area of collagen types I and II, elastic fibers, versican, fibronectin, and matrix metalloproteinases 1 and 2 in the endomysium. Setting: Academic tertiary center. Patiens: A total of 51 nonobese adult patients, divided into 38 patients with OSA and 13 nonsnoring control subjects without OSA. Interventions: Postintervention study performed on tissues from patients after elective surgery. Measurements and Results: Pharyngeal muscles of patients with OSA had significantly more collagen type I than pharyngeal muscles in control subjects. Collagen type I was correlated positively and independently with age. The other tested components of the extracellular matrix did not differ significantly between groups. In a logistic regression, an additive effect of both the increase of collagen type I and the increase in age with the presence of OSA was observed (odds ratio (OR), 2.06; 95% confidence interval (CI), 1.17-3.63), when compared with the effect of increased age alone (OR, 1.11; 95% CI, 1.03-1.20). Conclusion: Collagen type I in the superior pharyngeal constrictor muscle was more prevalent in patients with OSA and also increased with age. It was hypothesized that this increase could delay contractile-relaxant responses in the superior pharyngeal constrictor muscle at the expiratory-inspiratory phase transition, thus increasing pharyngeal collapsibility.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [06/50630-7
A voz dos bandos: colectivos de justiça e ritos da palavra portuguesa em Timor Leste colonial
Este artigo examina as relaçÔes entre o discurso da justiça e a prĂĄtica do ritual nos bandos do governo colonial portuguĂȘs em Timor Leste, entre a segunda metade do sĂ©culo XIX e as primeiras dĂ©cadas do sĂ©culo XX. Os bandos consistiam em ordens e instruçÔes de comando emanadas pelo governador portuguĂȘs em DĂli, e comunicadas de forma cerimonial por oficiais Ă s populaçÔes dos diversos reinos timorenses dispersos pelo paĂs. Bandos eram um instrumento por excelĂȘncia de governação colonial dos assuntos indĂgenas, servindo para arbitrar conflitos, punir transgressĂ”es e, em geral, instituir realidades no mundo timorense. Contudo, esta instituição assumiu igualmente uma singular expressĂŁo nos usos timorenses, servindo bandos para comunicar tambĂ©m as ordens de autoridades tradicionais, os liurais. O artigo acompanha as variaçÔes coloniais e indĂgenas que os bandos adquiriram em Timor Leste, conceptualizando-os enquanto colectivos de justiça. Ao considerar assim os bandos como colectivos â formaçÔes heterogĂ©neas em que elementos linguĂsticos e nĂŁo linguĂsticos se combinam na produção de efeitos de poder sobre as populaçÔes â o artigo propĂ”e uma via conceptual alternativa Ă s perspectivas linguĂsticas e literĂĄrias de anĂĄlise do discurso colonial
Parameterization Effects in the analysis of AMI Sunyaev-Zel'dovich Observations
Most Sunyaev--Zel'dovich (SZ) and X-ray analyses of galaxy clusters try to
constrain the cluster total mass and/or gas mass using parameterised models and
assumptions of spherical symmetry and hydrostatic equilibrium. By numerically
exploring the probability distributions of the cluster parameters given the
simulated interferometric SZ data in the context of Bayesian methods, and
assuming a beta-model for the electron number density we investigate the
capability of this model and analysis to return the simulated cluster input
quantities via three rameterisations. In parameterisation I we assume that the
T is an input parameter. We find that parameterisation I can hardly constrain
the cluster parameters. We then investigate parameterisations II and III in
which fg(r200) replaces temperature as a main variable. In parameterisation II
we relate M_T(r200) and T assuming hydrostatic equilibrium. We find that
parameterisation II can constrain the cluster physical parameters but the
temperature estimate is biased low. In parameterisation III, the virial theorem
replaces the hydrostatic equilibrium assumption. We find that parameterisation
III results in unbiased estimates of the cluster properties. We generate a
second simulated cluster using a generalised NFW (GNFW) pressure profile and
analyse it with an entropy based model to take into account the temperature
gradient in our analysis and improve the cluster gas density distribution. This
model also constrains the cluster physical parameters and the results show a
radial decline in the gas temperature as expected. The mean cluster total mass
estimates are also within 1 sigma from the simulated cluster true values.
However, we find that for at least interferometric SZ analysis in practice at
the present time, there is no differences in the AMI visibilities between the
two models. This may of course change as the instruments improve.Comment: 19 pages, 13 tables, 24 figure
Kidney function in tenofovir disoproxil fumarate-based oral pre-exposure prophylaxis users: a systematic review and meta-analysis of published literature and a multi-country meta-analysis of individual participant data
BACKGROUND: Previous WHO guidance on tenofovir disoproxil fumarate-based oral pre-exposure prophylaxis (PrEP) suggests measuring creatinine levels at PrEP initiation and regularly afterwards, which might represent barriers to PrEP implementation and uptake. We aimed to systematically review published literature on kidney toxicity among tenofovir disoproxil fumarate-based oral PrEP users and conducted an individual participant data meta-analysis (IPDMA) on kidney function among PrEP users in a global implementation project dataset.
METHODS: In this systematic review and meta-analysis we searched PubMed up to June 30, 2021, for randomised controlled trials (RCTs) or cohort studies that reported on graded kidney-related adverse events among oral PrEP users (tenofovir disoproxil fumarate-based PrEP alone or in combination with emtricitabine or lamivudine). We extracted summary data and conducted meta-analyses with random-effects models to estimate relative risks of grade 1 and higher and grade 2 and higher kidney-related adverse events, measured by elevated serum creatinine or decline in estimated creatinine clearance or estimated glomerular filtration rate. The IPDMA included (largely unpublished) individual participant data from 17 PrEP implementation projects and two RCTs. Estimated baseline creatinine clearance and creatinine clearance change after initiation were described by age, gender, and comorbidities. We used random-effects regressions to estimate the risk in decline of creatinine clearance to less than 60 mL/min.
FINDINGS: We identified 62 unique records and included 17 articles reporting on 11 RCTs with 13â523 participants in meta-analyses. PrEP use was associated with increased risk of grade 1 and higher kidney adverse events (pooled odds ratio [OR] 1·49, 95% CI 1·22-1·81; I2=25%) and grade 2 and higher events (OR 1·75, 0·68-4·49; I2=0%), although the grade 2 and higher association was not statistically significant and events were rare (13 out of 6764 in the intervention group vs six out of 6782 in the control group). The IPDMA included 18â676 individuals from 15 countries (1453 [7·8%] from RCTs) and 79 (0·42%) had a baseline estimated creatinine clearance of less than 60 mL/min (increasing proportions with increasing age). Longitudinal analyses included 14â368 PrEP users and 349 (2·43%) individuals had a decline to less than 60 mL/min creatinine clearance, with higher risks associated with increasing age and baseline creatinine clearance of 60·00-89·99 mL/min (adjusted hazard ratio [aHR] 8·49, 95% CI 6·44-11·20) and less than 60 mL/min (aHR 20·83, 12·83-33·82).
INTERPRETATION: RCTs suggest that risks of kidney-related adverse events among tenofovir disoproxil fumarate-based oral PrEP users are increased but generally mild and small. Our global PrEP user analysis found varying risks by age and baseline creatinine clearance. Kidney function screening and monitoring might focus on older individuals, those with baseline creatinine clearance of less than 90 mL/min, and those with kidney-related comorbidities. Less frequent or optional screening among younger individuals without kidney-related comorbidities may reduce barriers to PrEP implementation and use.
FUNDING: Unitaid, Bill & Melinda Gates Foundation, WHO
Probenecid Blocks Human P2X7 Receptor-Induced Dye Uptake via a Pannexin-1 Independent Mechanism
P2X7 is a ligand-gated ion channel which is activated by ATP and displays secondary permeability characteristics. The mechanism of development of the secondary permeability pathway is currently unclear, although a role for the hemichannel protein pannexin-1 has been suggested. In this study we investigated the role of pannexin-1 in P2X7-induced dye uptake and ATP-induced IL-1ÎČ secretion from human monocytes. We found no pharmacological evidence for involvement of pannexin-1 in P2X7-mediated dye uptake in transfected HEK-293 cells with no inhibition seen for carbenoxolone and the pannexin-1 mimetic inhibitory peptide, 10Panx1. However, we found that probenecid inhibited P2X7-induced cationic and anionic dye uptake in stably transfected human P2X7 HEK-293 cells. An IC50 value of 203 ÎŒM was calculated for blockade of ATP-induced responses at human P2X7. Probenecid also reduced dye uptake and IL-1ÎČ secretion from human CD14+ monocytes whereas carbenoxolone and 10Panx1 showed no inhibitory effect. Patch clamp and calcium indicator experiments revealed that probenecid directly blocks the human P2X7 receptor
Whole-genome sequencing of 1,171 elderly admixed individuals from Brazil
As whole-genome sequencing (WGS) becomes the gold standard tool for studying population genomics and medical applications, data on diverse non-European and admixed individuals are still scarce. Here, we present a high-coverage WGS dataset of 1,171 highly admixed elderly Brazilians from a census-based cohort, providing over 76 million variants, of which ~2 million are absent from large public databases. WGS enables identification of ~2,000 previously undescribed mobile element insertions without previous description, nearly 5âMb of genomic segments absent from the human genome reference, and over 140 alleles from HLA genes absent from public resources. We reclassify and curate pathogenicity assertions for nearly four hundred variants in genes associated with dominantly-inherited Mendelian disorders and calculate the incidence for selected recessive disorders, demonstrating the clinical usefulness of the present study. Finally, we observe that whole-genome and HLA imputation could be significantly improved compared to available datasets since rare variation represents the largest proportion of input from WGS. These results demonstrate that even smaller sample sizes of underrepresented populations bring relevant data for genomic studies, especially when exploring analyses allowed only by WGS
Author Correction: Whole-genome sequencing of 1,171 elderly admixed individuals from Brazil (vol 13, 1004, 2022)
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