Supraesophageal Reflux Disease: Solving a Riddle Wrapped in a Mystery Inside an Enigma

Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0

Early initiation of antiretroviral therapy and associated reduction in mortality, morbidity and defaulting in a nurse-managed, community cohort in Lesotho.

INTRODUCTION: The latest WHO guidelines recommend initiating antiretroviral therapy (ART) at CD4 cell counts less than 350 cells/μl. However, donors and national governments are reluctant to support implementation owing to uncertainty regarding feasibility and relative benefit. Lesotho has supported earlier initiation since 2008. We assessed outcomes comparing early (CD4 cell counts >200 cells/μl) and late (CD4 cell counts ≤200 cells/μl) initiation. METHODS: We describe survival probability among patients initiating ART at CD4 cell counts 200 or less and more than 200 cells/μl and assess associations between baseline CD4 cell counts and mortality, morbidity, loss to follow-up and hospitalization using Cox regression adjusting for confounders identified a priori. RESULTS: Our analysis included 1177 patients; median age was 38 years and the majority (67%) were women. Median time on ART for the overall cohort was 506 days (interquartile range 396-608). Five hundred and thirty eight patients initiated ART at a CD4 cell count 200 cells/μl or less (interquartile range 54-160) and 639 patients initiated at CD4 cell count more than 200 cells/μl (interquartile range 238-321). In multivariate analysis, we found that patients initiating at CD4 cell count more than 200 cells/μl were 68% less likely to die (adjusted hazard ratio 0.32, 95% confidence interval 0.20-0.50), and 39% less likely to be lost to follow-up (adjusted hazard ratio 0.61, 95% confidence interval 0.43-0.87). Initiating ART at CD4 cell count more than 200 cells/μl was also associated with a 27% reduction in the rate of incident morbidity (adjusted hazard ratio 0.73, 95% confidence interval 0.65-0.82) and a 63% decreased rate of hospitalization (adjusted hazard ratio 0.37, 95% confidence interval 0.19-0.73). CONCLUSION: Earlier initiation is feasible in a low resource, high HIV prevalence setting, and provides important benefits in terms of reduced mortality, morbidity, retention and hospitalization. Donors should fully support the implementation of the latest WHO recommendations

Nanoscale covariance magnetometry with diamond quantum sensors

Nitrogen vacancy (NV) centers in diamond are atom-scale defects with long spin coherence times that can be used to sense magnetic fields with high sensitivity and spatial resolution. Typically, the magnetic field projection at a single point is measured by averaging many sequential measurements with a single NV center, or the magnetic field distribution is reconstructed by taking a spatial average over an ensemble of many NV centers. In averaging over many single-NV center experiments, both techniques discard information. Here we propose and implement a new sensing modality, whereby two or more NV centers are measured simultaneously, and we extract temporal and spatial correlations in their signals that would otherwise be inaccessible. We analytically derive the measurable two-point correlator in the presence of environmental noise, quantum projection noise, and readout noise. We show that optimizing the readout noise is critical for measuring correlations, and we experimentally demonstrate measurements of correlated applied noise using spin-to-charge readout of two NV centers. We also implement a spectral reconstruction protocol for disentangling local and nonlocal noise sources, and demonstrate that independent control of two NV centers can be used to measure the temporal structure of correlations. Our covariance magnetometry scheme has numerous applications in studying spatiotemporal structure factors and dynamics, and opens a new frontier in nanoscale sensing

Beware of black swans: Taking stock of the description–experience gap in decision under uncertainty

Uncertainty pervades most aspects of life. From selecting a new technology to choosing a career, decision makers rarely know in advance the exact outcomes of their decisions. Whereas the consequences of decisions in standard decision theory are explicitly described (the decision from description (DFD) paradigm), the consequences of decisions in the recent decision from experience (DFE) paradigm are learned from experience. In DFD, decision makers typically overrespond to rare events. That is, rare events have more impact on decisions than their objective probabilities warrant (overweighting). In DFE, decision makers typically exhibit the opposite pattern, underresponding to rare events. That is, rare events may have less impact on decisions than their objective probabilities warrant (underweighting). In extreme cases, rare events are completely neglected, a pattern known as the “Black Swan effect.” This contrast between DFD and DFE is known as a description–experience gap. In this paper, we discuss several tentative interpretations arising from our interdisciplinary examination of this gap. First, while a source of underweighting of rare events in DFE may be sampling error, we observe that a robust description–experience gap remains when these factors are not at play. Second, the residual description–experience gap is not only about experience per se but also about the way in which information concerning the probability distribution over the outcomes is learned in DFE. Econometric error theories may reveal that different assumed error structures in DFD and DFE also contribute to the gap

The Implementation of Earth Jurisprudence through Substantive Constitutional Rights of Nature

To date, international processes associated with sustainable development have not led to an internationally legally binding framework that adequately addresses the challenges we face. Human influence on the planet has led to the adoption, although not universally accepted, of the term Anthropocene to define our new relationship with nature. This paper aims to look at the role and rule of law in the making of society and, more importantly, the arguments for a shift in the paradigm from an Anthropocentric ontology to a more Earth-centered one. We critique the current approach to sustainable development and environmental protection, review arguments on the Rights of Nature and explore the potential for the concept of Earth Jurisprudence building on current literature. In particular, the paper outlines that a constitutional right of nature is needed to address the challenges that we now face globally. To this end, we also examine in detail the case study of the constitution of Ecuador where the rights of nature have been codified. We outline some of the key issues involved in this proposed approach to new legal frameworks and make recommendations for future research

High efficacy of lopinavir/r-based second-line antiretroviral treatment after 24 months of follow up at ESTHER/Calmette Hospital in Phnom Penh, Cambodia

<p>Abstract</p> <p>Background</p> <p>The number of patients on second-line highly active antiretroviral therapy (HAART) regimens is increasing in resource-limited settings. We describe the outcomes after 24 months for patients on LPV/r-based second-line regimens followed up by the ESTHER programme in Phnom Penh, Cambodia.</p> <p>Methods</p> <p>Seventy patients who initiated second-line HAART regimens more than 24 months earlier were included, and immuno-virological data analyzed. HIV RNA viral load was determined by real-time RT-PCR. HIV-1 drug resistance was interpreted according to the ANRS algorithm.</p> <p>Results</p> <p>Of the 70 patients, two were lost to follow up, three died and 65 (92.8%) remained on second-line treatment after 24 months of follow up (median duration of treatment: 27.4 months). At switch to second-line, the median CD4 T cell count was 106 cells/mm³and the median viral load was 4.7 Log₁₀. Second-line regimens prescribed were ddI/3TC/LPV_/r(65.7%), ddI/TDF/LPV_/r(10.0%), ddI/AZT/LPV_/r(8.6%) and TDF/3TC/LPV_/r(7.1%). The median CD4 T cell gain was +258 cells/mm³at 24 months (n = 63). After 24 months of follow up, 92.3% (60/65) of the patients presented undetectable viral loads, giving an overall treatment success rate of 85.7% (CI: 75.6- 92.0) in intent-to-treat analysis.</p> <p>Conclusions</p> <p>These data suggest that a LPV_/r-based second-line regimen is associated with a high rate of virological suppression and immune reconstitution after 24 months of follow up in Cambodia.</p

Proliferating cell nuclear antigen acts as a cytoplasmic platform controlling human neutrophil survival

Cytosolic proliferating cell nuclear antigen (PCNA) binds to procaspases and protects human neutrophils from apoptosis

Homogenization Pressure and Temperature Affect Protein Partitioning and Oxidative Stability of Emulsions

The oxidative stability of 10 % fish oil-in-water emulsions was investigated for emulsions prepared under different homogenization conditions. Homogenization was conducted at two different pressures (5 or 22.5 MPa), and at two different temperatures (22 and 72 °C). Milk proteins were used as the emulsifier. Hence, emulsions were prepared with either a combination of α-lactalbumin and β-lactoglobulin or with a combination of sodium caseinate and β-lactoglobulin. Results showed that an increase in pressure increased the oxidative stability of emulsions with caseinate and β-lactoglobulin, whereas it decreased the oxidative stability of emulsions with α-lactalbumin and β-lactoglobulin. For both types of emulsions the partitioning of proteins between the interface and the aqueous phase appeared to be important for the oxidative stability. The effect of pre-heating the aqueous phase with the milk proteins prior to homogenization did not have any clear effect on lipid oxidation in either of the two types of emulsions. (Résumé d'auteur

Molecular Detection of Multiple Emerging Pathogens in Sputa from Cystic Fibrosis Patients

Background: There is strong evidence that culture-based methods detect only a small proportion of bacteria present in the respiratory tracts of cystic fibrosis (CF) patients. Methodology/Principal Findings: Standard microbiological culture and phenotypic identification of bacteria in sputa from CF patients have been compared to molecular methods by the use of 16S rDNA amplification, cloning and sequencing. Twenty-five sputa from CF patients were cultured that yield 33 isolates (13 species) known to be pathogens during CF. For molecular cloning, 760 clones were sequenced (7.263.9 species/sputum), and 53 different bacterial species were identified including 16 species of anaerobes (30%). Discrepancies between culture and molecular data were numerous and demonstrate that accurate identification remains challenging. New or emerging bacteria not or rarely reported in CF patients were detected including Dolosigranulum pigrum, Dialister pneumosintes, and Inquilinus limosus. Conclusions/Significance: Our results demonstrate the complex microbial community in sputa from CF patients, especially anaerobic bacteria that are probably an underestimated cause of CF lung pathology. Metagenomic analysis is urgentl

Risk factors and prognostic implications of diagnosis of cancer within 30 days after an emergency hospital admission (emergency presentation): an International Cancer Benchmarking Partnership (ICBP) population-based study

BACKGROUND: Greater understanding of international cancer survival differences is needed. We aimed to identify predictors and consequences of cancer diagnosis through emergency presentation in different international jurisdictions in six high-income countries. METHODS: Using a federated analysis model, in this cross-sectional population-based study, we analysed cancer registration and linked hospital admissions data from 14 jurisdictions in six countries (Australia, Canada, Denmark, New Zealand, Norway, and the UK), including patients with primary diagnosis of invasive oesophageal, stomach, colon, rectal, liver, pancreatic, lung, or ovarian cancer during study periods from Jan 1, 2012, to Dec 31, 2017. Data were collected on cancer site, age group, sex, year of diagnosis, and stage at diagnosis. Emergency presentation was defined as diagnosis of cancer within 30 days after an emergency hospital admission. Using logistic regression, we examined variables associated with emergency presentation and associations between emergency presentation and short-term mortality. We meta-analysed estimates across jurisdictions and explored jurisdiction-level associations between cancer survival and the percentage of patients diagnosed as emergencies. FINDINGS: In 857 068 patients across 14 jurisdictions, considering all of the eight cancer sites together, the percentage of diagnoses through emergency presentation ranged from 24·0% (9165 of 38 212 patients) to 42·5% (12 238 of 28 794 patients). There was consistently large variation in the percentage of emergency presentations by cancer site across jurisdictions. Pancreatic cancer diagnoses had the highest percentage of emergency presentations on average overall (46·1% [30 972 of 67 173 patients]), with the jurisdictional range being 34·1% (1083 of 3172 patients) to 60·4% (1317 of 2182 patients). Rectal cancer had the lowest percentage of emergency presentations on average overall (12·1% [10 051 of 83 325 patients]), with a jurisdictional range of 9·1% (403 of 4438 patients) to 19·8% (643 of 3247 patients). Across the jurisdictions, older age (ie, 75-84 years and 85 years or older, compared with younger patients) and advanced stage at diagnosis compared with non-advanced stage were consistently associated with increased emergency presentation risk, with the percentage of emergency presentations being highest in the oldest age group (85 years or older) for 110 (98%) of 112 jurisdiction-cancer site strata, and in the most advanced (distant spread) stage category for 98 (97%) of 101 jurisdiction-cancer site strata with available information. Across the jurisdictions, and despite heterogeneity in association size (I2=93%), emergency presenters consistently had substantially greater risk of 12-month mortality than non-emergency presenters (odds ratio >1·9 for 112 [100%] of 112 jurisdiction-cancer site strata, with the minimum lower bound of the related 95% CIs being 1·26). There were negative associations between jurisdiction-level percentage of emergency presentations and jurisdiction-level 1-year survival for colon, stomach, lung, liver, pancreatic, and ovarian cancer, with a 10% increase in percentage of emergency presentations in a jurisdiction being associated with a decrease in 1-year net survival of between 2·5% (95% CI 0·28-4·7) and 7·0% (1·2-13·0). INTERPRETATION: Internationally, notable proportions of patients with cancer are diagnosed through emergency presentation. Specific types of cancer, older age, and advanced stage at diagnosis are consistently associated with an increased risk of emergency presentation, which strongly predicts worse prognosis and probably contributes to international differences in cancer survival. Monitoring emergency presentations, and identifying and acting on contributing behavioural and health-care factors, is a global priority for cancer control. FUNDING: Canadian Partnership Against Cancer; Cancer Council Victoria; Cancer Institute New South Wales; Cancer Research UK; Danish Cancer Society; National Cancer Registry Ireland; The Cancer Society of New Zealand; National Health Service England; Norwegian Cancer Society; Public Health Agency Northern Ireland, on behalf of the Northern Ireland Cancer Registry; the Scottish Government; Western Australia Department of Health; and Wales Cancer Network