Central Iliac Arteriovenous Anastomosis for Hypertension: Targeting Mechanical Aspects of the Circulation

Dr. Lobo reports personal fees from ROX Medical, St Jude Medical, and Cardiosonic, and grants from Medtronic. Dr. Stanton reports that ROX Medical funded the ROX CONTROL HTN study. Dr. Sobotka reports personal fees and equity from ROX Medical; equity in Cibiem, Ablative Solutions, and Rainbow Medical; and personal fees from Abbott Ventures and Boston Scientific

Hypertriglyceridemic Pancreatitis: Conventional Treatment Versus Therapeutic Plasma Exchange

Introdução:A pancreatite aguda (PA) por hipertrigliceridemia (HTG) pode ser tratada com troca plasmática terapêutica (TPT), com redução rápida dos valores de triglicerídeos. Contudo, não existem estudos comparativos definitivos que comprovem o real benefício desta terapêutica. Objetivo: Comparação dos métodos de tratamento (troca plasmática terapêutica versus convencional) em doentes com PA HTG, durante um período de 12 anos (2000-2012). Métodos: Estudo retrospetivo descritivo e inferencial de 37 doentes, avaliando: sexo, idade, antecedentes pessoais, gravidade, valores de TG e evolução consoante o tratamento (“TPT” ou terapêutica convencional “C”). Resultados: Os dois grupos TPT e C mostraram-se homogéneos quanto ao sexo (p = 0,647), idade (43,5 ± 9,74 anos TPT versus 45,30 ± 9,90 anos C; p = 0.320), pancreatite prévia (40% TPT vs 40,7% C; p = 1,0) alcoolismo crónico (50% TPT vs 70,4% C; p = 0,275) e gravidade pelo score de APACHE II (p = 0,054) e Ranson às 48 horas (p = 0,258). Dos doentes 45,95% apresentava mais de um fator de risco secundário para HTG. O grupo TPT apresentou maiores valores de TG à admissão: 4850 ± 2802 mg/dL vs 1845 ± 1858 mg/dL (p = 0,001). Não se verificaram diferenças na duração do internamento 14,2 ± 6,8 dias vs 13,5 ± 9,0 dias (p = 0,56) ou na taxa de mortalidade (p = 0,47). À data de alta a redução dos TG foi superior no grupo TPT: 4433,70 ± 2896,08 mg/dL - 91,41% vs 1582,95 ± 2051,06 mg/dL – 83,92% (p = 0,002). De referir seis intercorrências minor durante a troca plasmática terapêutica. Discussão/Conclusões: Apesar do viés de seleção (estudo retrospetivo), foi constatada uma maior redução dos TG por esta técnica. As intercorrências inerentes à técnica de troca plasmática terapêutica foram de simples resolução.info:eu-repo/semantics/publishedVersio

Pancreatite Hipertrigliceridémica: Tratamento Convencional Versus Troca Plasmática Terapêutica

Introduction: Acute pancreatitis (AP) induced by hypertriglyceridemia (HTG) can be treated with therapeutic plasma exchange (TPE), resulting in rapid reduction of triglyceride level. However, there are no definitive comparative studies that prove the real benefits of this therapy. Objectives: Comparison of treatment methods (TPE versus conventional) in patients with HTG AP during a period of 12 years (2000-2012). Methods: Retrospective, descriptive and inferential analysis of 37 patients, evaluating: gender, age, personal pathologic history, severity of disease, HTG values and evolution depending on treatment with therapeutic plasma exchange (“TPE”) or with conventional therapy (“C”). Results: Both groups TPE and C demonstrated homogeneity considering gender (p = 0.647), age (43.5 ± 9.74 years TPE vs 45.30 ± 9.90 years C; p = 0.320), prior AP episode (40% TPE vs 40.7% C; p = 1.0), chronic alcohol consumption (50% TPE vs 70.4% C; p = 0.275) and severity disease scores: APACHE II (p = 0.054) and Ranson (p = 0.258). More than one secondary HTG risk factor was presented in 45.95% of patients . TPE group presented higher TG levels at admission: 4850 ± 2802 mg/dL vs 1845 ± 1858 mg/dL (p = 0.001). No significant statistical differences were observed considering length of hospital stay [14.2 ± 6.8 days vs 13.5 ± 9.0 days (p = 0.56)] or mortality rate (p = 0.47). At discharge, TG reduction was greater in TPE group: 4433.70 ± 2896.08 mg/dL – 91.41% vs 1582.95 ± 2051.06 mg/dL – 83,92% (p = 0.002). Six minor complications associated to TPE occurred. Discussion/Conclusion: Despite the selection bias (retrospective study), a greater TG reduction was observed with TPE technique. Complications associated with the technique were simple to resolveinfo:eu-repo/semantics/publishedVersio

Discreet element modeling of under sleeper pads using a box test

It has recently been reported that under sleeper pads (USPs) could improve ballasted rail track by decreasing the sleeper settlement and reducing particle breakage. In order to find out what happens at the particle-pad interface, discrete element modelling (DEM) is used to provide micro mechanical insight. The same positive effects of USP are found in the DEM simulations. The evidence provided by DEM shows that application of a USP allows more particles to be in contact with the pad, and causes these particles to transfer a larger lateral load to the adjacent ballast but a smaller vertical load beneath the sleeper. This could be used to explain why the USP helps to reduce the track settlement. In terms of particle breakage, it is found that most breakage occurs at the particle-sleeper interface and along the main contact force chains between particles under the sleeper. The use of USPs could effectively reduce particle abrasion that occurs in both of these regions

Perceived state of self during motion can differentially modulate numerical magnitude allocation.

Although a direct relationship between numerical-allocation and spatial-attention has been proposed, recent research suggests these processes are not directly coupled. In keeping with this, spatial attention shifts induced either via visual or vestibular motion can modulate numerical allocation in some circumstances but not in others. In addition to shifting spatial attention, visual or vestibular motion-paradigms also (i) elicit compensatory eye-movements which themselves can influence numerical-processing and (ii) alter the perceptual-state of-"self", inducing changes in bodily self-consciousness impacting upon cognitive mechanisms. Thus, the precise mechanism by which motion modulates numerical-allocation remains unknown. We sought to investigate the influence that different perceptual experiences of motion have upon numerical magnitude allocation whilst controlling for both eye-movements and task-related effects. We first used optokinetic visual-motion stimulation (OKS) to elicit the perceptual experience of either "visual world" or "self"-motion during which eye movements were identical. In a second experiment we used a vestibular protocol examining the effects of perceived and subliminal angular rotations in darkness, which also provoked identical eye movements. We observed that during the perceptual experience of "visual-world" motion, rightward OKS biased judgments towards smaller numbers, whereas leftward OKS biased judgments towards larger numbers. During the perceptual experience of "self-motion", judgments were biased towards larger numbers irrespective of the OKS direction. Contrastingly, vestibular motion perception was found not to modulate numerical magnitude allocation, nor was there any differential modulation when comparing "perceived" versus "subliminal" rotations. We provide a novel demonstration that magnitude-allocation can be differentially modulated by the perceptual state of-self during visual-motion. This article is protected by copyright. All rights reserved

Discrete element modelling of scaled railway ballast under triaxial conditions

The aim of this study is to demonstrate the use of tetrahedral clumps to model scaled railway ballast using the discrete element method (DEM). In experimental triaxial tests, the peak friction angles for scaled ballast are less sensitive to the confining pressure when compared to full-sized ballast. This is presumed to be due to the size effect on particle strength, whereby smaller particles are statistically stronger and exhibit less abrasion. To investigate this in DEM, the ballast is modelled using clumps with breakable asperities to produce the correct volumetric deformation. The effects of the quantity and properties of these asperities are investigated, and it is shown that the strength affects the macroscopic shear strength at both high and low confining pressures, while the effects of the number of asperities diminishes with increasing confining pressure due to asperity breakage. It is also shown that changing the number of asperities only affects the peak friction angle but not the ultimate friction angle by comparing the angles of repose of samples with different numbers of asperities

Folate catabolites in spot urine as non-invasive biomarkers of folate status during habitual intake and folic acid supplementation.

Folate status, as reflected by red blood cell (RCF) and plasma folates (PF), is related to health and disease risk. Folate degradation products para-aminobenzoylglutamate (pABG) and para-acetamidobenzoylglutamate (apABG) in 24 hour urine have recently been shown to correlate with blood folate. Since blood sampling and collection of 24 hour urine are cumbersome, we investigated whether the determination of urinary folate catabolites in fasted spot urine is a suitable non-invasive biomarker for folate status in subjects before and during folic acid supplementation. Immediate effects of oral folic acid bolus intake on urinary folate catabolites were assessed in a short-term pre-study. In the main study we included 53 healthy men. Of these, 29 were selected for a 12 week folic acid supplementation (400 µg). Blood, 24 hour and spot urine were collected at baseline and after 6 and 12 weeks and PF, RCF, urinary apABG and pABG were determined. Intake of a 400 µg folic acid bolus resulted in immediate increase of urinary catabolites. In the main study pABG and apABG concentrations in spot urine correlated well with their excretion in 24 hour urine. In healthy men consuming habitual diet, pABG showed closer correlation with PF (rs = 0.676) and RCF (rs = 0.649) than apABG (rs = 0.264, ns and 0.543). Supplementation led to significantly increased folate in plasma and red cells as well as elevated urinary folate catabolites, while only pABG correlated significantly with PF (rs = 0.574) after 12 weeks. Quantification of folate catabolites in fasted spot urine seems suitable as a non-invasive alternative to blood or 24 hour urine analysis for evaluation of folate status in populations consuming habitual diet. In non-steady-state conditions (folic acid supplementation) correlations between folate marker (RCF, PF, urinary catabolites) decrease due to differing kinetics

Putative DHHC-Cysteine-Rich Domain S-Acyltransferase in Plants

Protein S-acyltransferases (PATs) containing Asp-His-His-Cys within a Cys-rich domain (DHHC-CRD) are polytopic transmembrane proteins that are found in eukaryotic cells and mediate the S-acylation of target proteins. S-acylation is an important secondary and reversible modification that regulates the membrane association, trafficking and function of target proteins. However, little is known about the characteristics of PATs in plants. Here, we identified 804 PATs from 31 species with complete genomes. The analysis of the phylogenetic relationships suggested that all of the PATs fell into 8 groups. In addition, we analysed the phylogeny, genomic organization, chromosome localisation and expression pattern of PATs in Arabidopsis, Oryza sative, Zea mays and Glycine max. The microarray data revealed that PATs genes were expressed in different tissues and during different life stages. The preferential expression of the ZmPATs in specific tissues and the response of Zea mays to treatments with phytohormones and abiotic stress demonstrated that the PATs play roles in plant growth and development as well as in stress responses. Our data provide a useful reference for the identification and functional analysis of the members of this protein family

First-line, Fixed-Duration Nivolumab plus Ipilimumab Followed by Nivolumab in Clinically Diverse Patient Populations With Unresectable Stage III or IV Melanoma: CheckMate 401

PURPOSETo address the paucity of data in patients with historically poor outcomes, we conducted the single-arm phase IIIb CheckMate 401 study to evaluate the safety and efficacy of nivolumab plus ipilimumab followed by nivolumab monotherapy in clinically diverse patient populations with advanced melanoma.METHODSTreatment-naive patients with unresectable stage III-IV melanoma received nivolumab 1 mg/kg plus ipilimumab 3 mg/kg once every 3 weeks (four doses) followed by nivolumab 3 mg/kg (240 mg following a protocol amendment) once every 2 weeks for 24 months. The primary end point was the incidence of grade 3-5 select treatment-related adverse events (TRAEs). Overall survival (OS) was a secondary end point. Outcomes were evaluated in subgroups defined by Eastern Cooperative Oncology Group performance status (ECOG PS), brain metastasis status, and melanoma subtype.RESULTSIn total, 533 patients received at least one dose of study drug. Grade 3-5 select TRAEs affecting the GI (16%), hepatic (15%), endocrine (11%), skin (7%), renal (2%), and pulmonary (1%) systems occurred in the all-treated population; similar incidence rates were observed across all subgroups. At 21.6 months' median follow-up, 24-month OS rates were 63% in the all-treated population, 44% in the ECOG PS 2 subgroup (including patients with cutaneous melanoma only), 71% in the brain metastasis subgroup, 36% in the ocular/uveal melanoma subgroup, and 38% in the mucosal melanoma subgroup.CONCLUSIONNivolumab plus ipilimumab followed by nivolumab monotherapy was tolerable in patients with advanced melanoma and poor prognostic characteristics. Efficacy was similar between the all-treated population and patients with brain metastases. Reduced efficacy was observed in patients with ECOG PS 2, ocular/uveal melanoma, and/or mucosal melanoma, highlighting the continued need for novel treatment options for these difficult-to-treat patients

malERA: An updated research agenda for insecticide and drug resistance in malaria elimination and eradication

Resistance to first-line treatments for Plasmodium falciparum malaria and the insecticides used for Anopheles vector control are threatening malaria elimination efforts. Suboptimal responses to drugs and insecticides are both spreading geographically and emerging independently and are being seen at increasing intensities. Whilst resistance is unavoidable, its effects can be mitigated through resistance management practices, such as exposing the parasite or vector to more than one selective agent. Resistance contributed to the failure of the 20th century Global Malaria Eradication Programme, and yet the global response to this issue continues to be slow and poorly coordinated—too often, too little, too late. The Malaria Eradication Research Agenda (malERA) Refresh process convened a panel on resistance of both insecticides and antimalarial drugs. This paper outlines developments in the field over the past 5 years, highlights gaps in knowledge, and proposes a research agenda focused on managing resistance. A deeper understanding of the complex biological processes involved and how resistance is selected is needed, together with evidence of its public health impact. Resistance management will require improved use of entomological and parasitological data in decision making, and optimisation of the useful life of new and existing products through careful implementation, combination, and evaluation. A proactive, collaborative approach is needed from basic science and the development of new tools to programme and policy interventions that will ensure that the armamentarium of drugs and insecticides is sufficient to deal with the challenges of malaria control and its elimination