Earlier papers introduced a method of accurately estimating the angular cosmic microwave background temperature power spectrum based on Gibbs sampling. Here we extend this framework to polarized ...data. All advantages of the Gibbs sampler still apply, and exact analysis of megapixel polarized data sets is thus feasible. These advantages may be even more important for polarization measurements than for temperature measurements. While approximate methods can alias power from the larger. E-mode spectrum into the weaker B-mode spectrum, the Gibbs sampler (or equivalently, exact likelihood evaluations) allows for a statistically optimal separation of these modes in terms of power spectra. To demonstrate the method, we analyze two simulated data sets: (1) a hypothetical fixture CMBPol mission, with the focus on B-mode estimation; and (2) a Planck-tike mission, to highlight the computational feasibility of the method.
We analyze the 3 yr Wilkinson Microwave Anisotropy Probe (WMAP) temperature anisotropy data seeking to confirm the power spectrum and likelihoods published by the WMAP team. We apply five independent ...implementations of four algorithms to the power spectrum estimation and two implementations to the parameter estimation. Our single most important result is that we broadly confirm the WMAP power spectrum and analysis. Still, we do find two small but potentially important discrepancies. On large angular scales there is a small power excess in the WMAP spectrum (5%-10% at 30) primarily due to likelihood approximation issues between 13 , 30. On small angular scales there is a systematic difference between the V- and W-band spectra (few percent at 300). Recently, the latter discrepancy was explained by Huffenberger et al. (2006) in terms of oversubtraction of unresolved point sources. As far as the low- bias is concerned, most parameters are affected by a few tenths of a a. The most important effect is seen in n sub(s). For the combination of WMAP, ACBAR, and BOOMERANG, the significance of n sub(s) 1 drops from 62.7 a to 62.3 a when correcting for this bias. We propose a few simple improvements to the low-1 WMAP likelihood code, and introduce two important extensions to the Gibbs sampling method that allows for proper sampling of the low signal-to-noise ratio regime. Finally, we make the products from the Gibbs sampling analysis publicly available, thereby providing a fast and simple route to the exact likelihood without the need of expensive matrix inversions.
A well-tested and validated Gibbs sampling code, that performs component separation and cosmic microwave background (CMB) power spectrum estimation, was applied to the WMAP five-year data. Using a ...simple model consisting of CMB, noise, monopoles, and dipoles, a 'per pixel' low-frequency power-law (fitting for both amplitude and spectral index), and a thermal dust template with a fixed spectral index, we found that the low- ( < 50) CMB power spectrum is in good agreement with the published WMAP5 results. Residual monopoles and dipoles were found to be small (3 Delta *mK) or negligible in the five-year data. We comprehensively tested the assumptions that were made about the foregrounds (e.g., dust spectral index, power-law spectral index prior, templates), and found that the CMB power spectrum was insensitive to these choices. We confirm the asymmetry of power between the north and south ecliptic hemispheres, which appears to be robust against foreground modeling. The map of low-frequency spectral indices indicates a steeper spectrum on average ( Delta *b = -2.97 +/- 0.21) relative to those found at low (~GHz) frequencies.
Hypoxia inducible factor 1 (HIF-1) represses the transcription of pro-apoptotic
bid
in colorectal cancer cells
in vitro
. To assess the clinical relevance of this observation, HIF-1
α
and Bid were ...assessed in serial sections of 39 human colorectal adenocarcinomas by immunohistochemistry. In high HIF-1
α
nuclear-positive cell subpopulations, there was a significant reduction in Bid expression (ANOVA,
P
=0.04). Given the role of Bid in drug-induced apoptosis, these data add impetus to strategies targeting HIF-1 for therapeutic gain.
Significant volumes of research over the past four decades has sought to elucidate the social, infrastructural, economic, and human health effects of climate change induced surface flooding. To date, ...epidemiological and public health studies of flooding events have focused on mental health effects, vector-borne diseases, and infectious enteric disease due to floodwater contact (i.e. typically low consumption rates). The inherent nature of groundwater (i.e. out of sight, out of mind) and the widely held belief that aquifers represent a pristine source of drinking water due to natural attenuation may represent the “perfect storm” causing direct consumption of relatively large volumes of surface flood-contaminated groundwater. Accordingly, the current study sought to systematically identify and synthesize all available peer-reviewed literature pertaining to the nexus between surface flooding, groundwater contamination and human gastroenteric outcomes. Just 14 relevant studies were found to have been published during the period 1980–2017, thus highlighting the fact that this potentially significant source of climate-related exposure to environmental infection has remained understudied to date. Studies differed significantly in terms of type and data reporting procedures, making it difficult to discern clear trends and patterns. Approximately 945 confirmed cases of flood-related enteric disease were examined across studies; these concurred with almost 10,000 suspected cases, equating to approximately 20 suspected cases per confirmed case. As such, no regional, national or global estimates are available for the human gastrointestinal health burden of flood-related groundwater contamination. In light of the demonstrable public health significance of the concurrent impacts of groundwater susceptibility and climate change exacerbation, strategies to increase awareness about potential sources of contamination and motivate precautionary behaviour (e.g. drinking water testing and treatment, supply interruptions) are necessary. Mainstreaming climate adaptation concerns into planning policies will also be necessary to reduce human exposure to waterborne sources of enteric infection.
Display omitted
•Review of the nexus between flooding, groundwater contamination and enteric infection.•Low number of studies identified from 1980 to 2017 (n = 14).•Mechanisms of flood-triggered groundwater contamination under-investigated.•Need for interdisciplinary collaboration when studying public health impacts of flood events.•Significant work required to inform timely, spatially-specific mitigation strategies.
BackgroundOverweight and obesity are increasing in prevalence worldwide In Ireland, their prevalence makes up over 60% of the population. The incidence of many chronic diseases, and some cancers, is ...increased in those who are overweight and obese. This places pressure on the health service, financially and otherwise. There is also a cost on society in terms of productivity loss. Many countries have studied the costs involved, but as each country has a unique profile of risk prevalence and health service, the costs are country specific. In order to inform prevention policies and ignite political will in the public health battle against obesity, the measurement of direct and indirect costs of overweight and obesity is a useful exercise. This study was a collaborative effort to enumerate these costs for the island of Ireland.MethodsA comprehensive literature review was performed examining the international evidence on cost of overweight and obesity. Regression analyses of data from SLAN and TILDA in the Republic of Ireland, and The 2010/11 Health Survey for Northern Ireland were performed to give estimates of direct health care costs in both jurisdictions, and of indirect costs due to absenteeism. In addition, Population Attributable Fractions were applied to hospital activity, drug reimbursement, social welfare and mortality data for both jurisdictions to give additional information where no survey data were available, and to triangulate results. Adjustments were made for inflation and purchasing power parity to allow for the production of an estimate in one currency for a single year.ResultsThe literature review yielded 45 studies and showed heterogeneity of methodology between studies. However, in almost all cases there was a positive correlation between obesity and increased healthcare costs, and indirect costs were in all cases greater than direct costs. The cost of overweight and obesity for the Republic of Ireland was estimated to be Euro1,166,050,482 and for Northern Ireland it was Euro510,323,754 for the year 2009. Direct healthcare costs represented 38% of the total, and 2.9% of total healthcare spend in the Republic of Ireland and, in Northern Ireland, 25% of the total and 2.8% of total healthcare spend.ConclusionUrgent public health action is required in Ireland to address the problem of increasing prevalence of overweight and obesity. The cost of associated chronic disease is substantial, and if prevalence rates continue to rise, will cause unsustainable health service cost escalation, and productivity losses to the wider economy.
Current data suggest that chemotherapy combinations may be superior to single agents in biliary tract cancer. The epidermal growth factor receptor (EGFR) pathway appears to be associated with tumor ...stage, prognosis and response to therapy. This trial was designed to evaluate the tolerability and efficacy of the combination of panitumumab, a monoclonal anti-EGFR antibody, with gemcitabine and irinotecan.
Patients with advanced (unresectable or metastatic) cholangiocarcinoma, ECOG PS 0–2, and adequate organ function were treated with panitumumab (9 mg/kg) on day 1, and gemcitabine (1000 mg/m2) and irinotecan (100 mg/m2) on days 1 and 8 of a 21-day cycle. The primary objective was to evaluate the 5-month progression-free survival (PFS). Secondary objectives included overall response rate (ORR) and overall survival (OS). Mutational analyses of EGFR, KRAS and BRAF were carried out when feasible.
Thirty-five patients received a median of 7 (0–30) cycles. The most common grade 3/4 toxic effects were neutropenia (10 patients, 29%), thrombocytopenia (10 patients, 29%), skin rash (13 patients, 37%) and dehydration (9 patients, 26%). Two patients had CR, 9 had partial response (PR), and 15 had SD for a disease-control rate of 74% (by RECIST) in 28 assessable patients. Two patients went on to have surgical resection. The 5-month PFS was 69%. The median PFS was 9.7 months and the median OS was 12.9 months. In 17 testable samples, no EGFR or BRAF mutations were identified; there were 7 KRAS mutations, with no difference in OS by KRAS status.
This study showed encouraging efficacy of this regimen with good tolerability. Further study in this area is warranted.
Clinical Trials Number: The trial was registered with the National Cancer Institute (www.clinicaltrials.gov identifier NCT00948935).
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