Soil-transmitted helminth parasites and allergy: Observations from Ecuador.

There is considerable interest as to potential protective effects of soil-transmitted helminths (STH) against allergy and allergic diseases. Here, we discuss findings of studies done of the effects of STH parasites on atopy and allergic diseases in Ecuador. While cross-sectional studies have consistently shown a reduced prevalence of allergen skin prick test (SPT) reactivity among infected schoolchildren, the removal of these infections by repeated deworming did not affect SPT prevalence over the short-term (ie, 12 months) but may have increased SPT prevalence over the long-term (ie, 15-17 years). In the case of allergic symptoms, cross-sectional studies have generally not shown associations with STH and intervention studies showed no impact on prevalence. However, a birth cohort suggested that early STH infections might reduce wheeze by 5 years. Allergic sensitization to Ascaris, however, explained a significant proportion of wheezing among rural schoolchildren. Studies of the effects of STH on immune and inflammatory responses indicated a potential role of STH in contributing to more robust regulation. The effects of STH on allergy are likely to be determined by history of exposure over the life-course and by interactions with a wide variety of other infectious and non-infectious factors

Predictors of total morbidity burden on days 3, 5 and 8 after cardiac surgery.

BACKGROUND: Post-operative morbidity affects up to 36% of cardiac surgical patients. However, few countries reliably record morbidity outcome data, despite patients wanting to be informed of all the risks associated with surgery. The Cardiac Post-Operative Morbidity Score (C-POMS) is a new tool for describing and scoring (0-13) total morbidity burden after cardiac surgery, derived by noting the presence/absence of 13 morbidity domains on days 3, 5, 8 and 15. Identifying modifiable C-POMS risk factors may suggest targets for intervention to reduce morbidity and healthcare costs. Thus, we explored the association of C-POMS with previously identified predictors of post-operative morbidity. METHODS: A systematic literature review of pre-operative risk assessment models for post-operative morbidity was conducted to identify variables associated with post-operative morbidity. The association of those variables with C-POMS was explored in patients drawn from the original C-POMS study (n = 444). RESULTS: Seventy risk factors were identified, of which 56 were available in the study and 49 were suitable for analysis. Numbers were too few to analyse associations on D15. Thirty-three (67.3%) and 20 (40.8%) variables were associated with C-POMS on at least 1 or 2 days, respectively. Pre-operative albumin concentration, left ventricular ejection fraction and New York Heart Association functional class were associated with C-POMS on all days. Of the 16 independent risk factors, pre-operative albumin and haemoglobin concentrations and weight are potentially modifiable. CONCLUSIONS: Different risk factors are associated with total morbidity burden on different post-operative days. Pre-operative albumin and haemoglobin concentrations and weight were independently predictive of post-operative total morbidity burden suggesting therapeutic interventions aimed at these might reduce both post-operative morbidity risk and health-care costs in patients undergoing cardiac surgery

Rural to urban migration is associated with increased prevalence of childhood wheeze in a Latin-American city.

INTRODUCTION: The urbanisation process has been associated with increases in asthma prevalence in urban and rural areas of low-income and middle-income countries (LMICs). However, although rural to urban migration and migration between cities are considered important determinants of this process, few studies have evaluated the effects of internal migration on asthma in urban populations of LMICs. The present study evaluated the effects of internal migration on the prevalence of wheeze in an urban area of Latin America. METHODS: We did a cross-sectional analysis of 2510 schoolchildren living in the city of Esmeraldas, Ecuador. Logistic regression was used to analyse associations between childhood wheeze and different aspects of migration among schoolchildren. RESULTS: 31% of schoolchildren were migrants. Rural to urban migrants had a higher prevalence of wheeze, (adj.OR=2.01,95% CI1.30 to 3.01, p=0.001) compared with non-migrants. Age of migration and time since migration were associated with wheeze only for rural to urban migrants but not for urban to urban migrants. Children who had migrated after 3 years of age had a greater risk of wheeze (OR 2.51, 95% CI 1.56 to 3.97, p=0.001) than non-migrants while migrants with less than 5 years living in the new residence had a higher prevalence of wheeze than non-migrants (<3 years: OR=2.34, 95% CI 1.26 to 4.33, p<0.007 and 3-5 years: OR=3.03, 95% CI 1.49 to 6.15, p<0.002). CONCLUSIONS: Our study provides evidence that rural to urban migration is associated with an increase in the prevalence of wheeze among schoolchildren living in a Latin-American city. Age of migration and time since migration were important determinants of wheeze only among migrants from rural areas. A better understanding of the social and environmental effects of internal migration could improve our understanding of the causes of the increase in asthma and differences in prevalence between urban and rural populations

CD4 cell responses to combination antiretroviral therapy in patients starting therapy at high CD4 cell counts

Objective: To examine CD4 cell responses to combination antiretroviral therapy (cART) in patients enrolled in the Australian HIV Observational Database who commenced cART at CD4 cell counts >350 cells per microliter. Methods: CD4 cell counts were modelled using random effects, repeated measurement models in 432 HIV-infected adults from Australian HIV Observational Database who commenced their first cART regimen and had a baseline CD4 count >350 cells per microliter. Using published AIDS and/or death incidence rates combined with the data summarized by time and predicted CD4 cell count, we calculated the expected reduction in risk of an event for different starting baseline CD4 strata. Results: Mean CD4 counts increased above 500 cells per microliter in all baseline CD4 strata by 12 months (means of 596, 717, and 881 cells/μL in baseline CD4 strata 351-500, 501-650, and >650 cells/μL, respectively) and after 72 months since initiating cART, mean CD4 cell counts (by increasing baseline CD4 strata) were 689, 746, 742 cells per microliter. The expected reduction in risk of mortality for baseline CD4 counts >650 cells per microliter relative to 351-500 cells per microliter was approximately 8%, an absolute risk reduction 0.33 per 1000 treated patient-years. Conclusions: Patients starting cART at high CD4 cell counts (>650 cells/μL) tend to maintain this immunological level over 6 years of follow-up. Patients starting from 351 to 500 CD4 cells per microliter achieve levels of >650 cells per microliter after approximately 3 years of cART. Initiating cART with a baseline CD4 count 501-650 or >650 cells per microliter relative to 351-500 cells per microliter indicated a minimal reduction in risk of AIDS incidence and/or death. Copyright © 2011 Lippincott Williams & Wilkins

Learning and Matching Multi-View Descriptors for Registration of Point Clouds

Critical to the registration of point clouds is the establishment of a set of accurate correspondences between points in 3D space. The correspondence problem is generally addressed by the design of discriminative 3D local descriptors on the one hand, and the development of robust matching strategies on the other hand. In this work, we first propose a multi-view local descriptor, which is learned from the images of multiple views, for the description of 3D keypoints. Then, we develop a robust matching approach, aiming at rejecting outlier matches based on the efficient inference via belief propagation on the defined graphical model. We have demonstrated the boost of our approaches to registration on the public scanning and multi-view stereo datasets. The superior performance has been verified by the intensive comparisons against a variety of descriptors and matching methods

<i>C-elegans</i> model identifies genetic modifiers of alpha-synuclein inclusion formation during aging

Inclusions in the brain containing alpha-synuclein are the pathological hallmark of Parkinson's disease, but how these inclusions are formed and how this links to disease is poorly understood. We have developed a &lt;i&gt;C-elegans&lt;/i&gt; model that makes it possible to monitor, in living animals, the formation of alpha-synuclein inclusions. In worms of old age, inclusions contain aggregated alpha-synuclein, resembling a critical pathological feature. We used genome-wide RNA interference to identify processes involved in inclusion formation, and identified 80 genes that, when knocked down, resulted in a premature increase in the number of inclusions. Quality control and vesicle-trafficking genes expressed in the ER/Golgi complex and vesicular compartments were overrepresented, indicating a specific role for these processes in alpha-synuclein inclusion formation. Suppressors include aging-associated genes, such as sir-2.1/SIRT1 and lagr-1/LASS2. Altogether, our data suggest a link between alpha-synuclein inclusion formation and cellular aging, likely through an endomembrane-related mechanism. The processes and genes identified here present a framework for further study of the disease mechanism and provide candidate susceptibility genes and drug targets for Parkinson's disease and other alpha-synuclein related disorders

Cooper pairing near charged black holes

We show that a quartic contact interaction between charged fermions can lead to Cooper pairing and a superconducting instability in the background of a charged asymptotically Anti-de Sitter black hole. For a massless fermion we obtain the zero mode analytically and compute the dependence of the critical temperature T_c on the charge of the fermion. The instability we find occurs at charges above a critical value, where the fermion dispersion relation near the Fermi surface is linear. The critical temperature goes to zero as the marginal Fermi liquid is approached, together with the density of states at the Fermi surface. Besides the charge, the critical temperature is controlled by a four point function of a fermionic operator in the dual strongly coupled field theory.Comment: 1+33 pages, 4 figure

Thermoelastic properties of magnesiowustite, (Mg1-xFex)O: determination of the Anderson-Gruneisen parameter by time-of-flight neutron powder diffraction at simultaneous high pressures and temperatures

The ability to perform neutron diffraction studies at simultaneous high pressures and high temperatures is a relatively recent development. The suitability of this technique for determining P-V-T equations of state has been investigated by measuring the lattice parameters of Mg1-xFexO ( x = 0.2, 0.3, 0.4), in the range P < 10.3 GPa and 300 < T < 986 K, by time-of-flight neutron powder diffraction. Pressures were determined using metallic Fe as a marker and temperatures were measured by neutron absorption resonance radiography. Within the resolution of the experiment, no evidence was found for any change in the temperature derivative of the isothermal incompressibility, partial derivative K-T/partial derivative T, with composition. By assuming that the equation-of-state parameters either varied linearly or were invariant with composition, the 60 measured state points were fitted simultaneously to a P-V-T-x equation of state, leading to values of partial derivative K-T/partial derivative T = -0.024 (9) GPa K-1 and of the isothermal Anderson-Gruneisen parameter delta(T) = 4.0 (16) at 300 K. Two designs of simultaneous high-P/T cell were employed during this study. It appears that, by virtue of its extended pressure range, a design using toroidal gaskets is more suitable for equation-of-state studies than is the system described by Le Godec, Dove, Francis, Kohn, Marshall, Pawley, Price, Redfern, Rhodes, Ross, Schofield, Schooneveld, Syfosse, Tucker & Welch [Mineral. Mag. (2001), 65, 737-748]. (c) 2008 International Union of Crystallography Printed in Singapore - all rights reserved

Postoperative Concurrent Chemoradiotherapy Versus Postoperative Radiotherapy in High-Risk Cutaneous Squamous Cell Carcinoma of the Head and Neck: The Randomized Phase III TROG 05.01 Trial

© 2018 by American Society of Clinical Oncology Purpose To report the results of the Trans Tasman Radiation Oncology Group randomized phase III trial designed to determine whether the addition of concurrent chemotherapy to postoperative radiotherapy (CRT) improved locoregional control in patients with high-risk cutaneous squamous cell carcinoma of the head and neck. Patients and Methods The primary objective was to determine whether there was a difference in freedom from locoregional relapse (FFLRR) between 60 or 66 Gy (6 to 6.5 weeks) with or without weekly carboplatin (area under the curve 2) after resection of gross disease. Secondary efficacy objectives were to compare disease-free survival and overall survival. Results Three hundred twenty-one patients were randomly assigned, with 310 patients commencing allocated treatment (radiotherapy [RT] alone, n = 157; CRT, n = 153). Two hundred thirty-eight patients (77%) had high-risk nodal disease, 59 (19%) had high-risk primary or in-transit disease, and 13 (4%) had both. Median follow-up was 60 months. Median RT dose was 60 Gy, with 84% of patients randomly assigned to CRT completing six cycles of carboplatin. The 2- and 5-year FFLRR rates were 88% (95% CI, 83% to 93%) and 83% (95% CI, 77% to 90%), respectively, for RT and 89% (95% CI, 84% to 94%) and 87% (95% CI, 81% to 93%; hazard ratio, 0.84; 95% CI, 0.46 to 1.55; P = .58), respectively, for CRT. There were no significant differences in disease-free or overall survival. Locoregional failure was the most common site of first treatment failure, with isolated distant metastases as the first site of failure seen in 7% of both arms. Treatment was well tolerated in both arms, with no observed enhancement of RT toxicity with carboplatin. Grade 3 or 4 late toxicities were infrequent. Conclusion Although surgery and postoperative RT provided excellent FFLRR, there was no observed benefit with the addition of weekly carboplatin

Macrophage-derived human resistin is induced in multiple helminth infections and promotes inflammatory monocytes and increased parasite burden.

Parasitic helminth infections can be associated with lifelong morbidity such as immune-mediated organ failure. A better understanding of the host immune response to helminths could provide new avenues to promote parasite clearance and/or alleviate infection-associated morbidity. Murine resistin-like molecules (RELM) exhibit pleiotropic functions following helminth infection including modulating the host immune response; however, the relevance of human RELM proteins in helminth infection is unknown. To examine the function of human resistin (hResistin), we utilized transgenic mice expressing the human resistin gene (hRetnTg+). Following infection with the helminth Nippostrongylus brasiliensis (Nb), hResistin expression was significantly upregulated in infected tissue. Compared to control hRetnTg- mice, hRetnTg+ mice suffered from exacerbated Nb-induced inflammation characterized by weight loss and increased infiltration of inflammatory monocytes in the lung, along with elevated Nb egg burdens and delayed parasite expulsion. Genome-wide transcriptional profiling of the infected tissue revealed that hResistin promoted expression of proinflammatory cytokines and genes downstream of toll-like receptor signaling. Moreover, hResistin preferentially bound lung monocytes, and exogenous treatment of mice with recombinant hResistin promoted monocyte recruitment and proinflammatory cytokine expression. In human studies, increased serum resistin was associated with higher parasite load in individuals infected with soil-transmitted helminths or filarial nematode Wuchereria bancrofti, and was positively correlated with proinflammatory cytokines. Together, these studies identify human resistin as a detrimental factor induced by multiple helminth infections, where it promotes proinflammatory cytokines and impedes parasite clearance. Targeting the resistin/proinflammatory cytokine immune axis may provide new diagnostic or treatment strategies for helminth infection and associated immune-mediated pathology