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Objectives:To identify the risk factors of neonatal sepsisduring the period from January 2017 to December 2019. Methods:A cross-sectional, retrospective study, observational, descriptive; the record of 106 newborns diagnosed with sepsis were reviewed. We excluded 15 were included in the data collection, diagnosis of early and late neonatal sepsis, maternal age, number of gestation, prenatal care, premature birth, diagnosis of UTI diagnosis of chorioamnionitis, premature rupture of membrane (s RPM ), sex product, invasive procedures, product weight and route of obtaining the product. Results:Of the 1401 patients obtained alive, 191 obtained diagnosis of neonatal sepsis and an incidence of 6.49% of early neonatal sepsis was obtained. The main risk factor associated with early neonatal sepsis has been the way of obtaining caesarean with 52.74%, the low birth weight with 32.96% and multiparity an incidence of 34.06% and there were no significant differences between sexes as the man / femalerelationship was 1.02.However if a significant importance in the delivery / caesarean relationship was obtained0.89. There was only one death recorded. Conclusions:The main risk factors associated with early neonatal sepsis are obtained via caesarean section, low birth weight and multiparity, male sex was the most affected but with no significant differences, the IVU, PROM, maternal age less to 18 years and the lack of prenatal care they had similar incidence. Only one late neonatal sepsis and death was obtained. I do not chorioamnionitis data was obtained.

The benign prostatic hyperplasia (BPH) is a (noncancerous) malignant growth in the size of the prostate. This enlargement of the prostate gland is produced by a relative increase in estrogen (female hormones) on testosterone (male hormone), which appears in men with age. Objective:To determine the relationship of PSA, with the size of the prostate in patients with benign prostatic hyperplasia admitted to General Hospital of Escarcega, Campeche Dr. Janel Aguilar during the period from August 2019 to January 2020. Method:patients were studied with the diagnosis of benign prostatic hyperplasia 50 years of age and older and excluded those who had other diseases that may alter prostate specific antigen, subsequently classified by age determined through PSA ultrasound prostate-specific and the average size of the prostate in grams and the average PSA for each age range and the relationship between them, while describes how it affects their self-esteem was determined. Results:Of the patients studied, 22 belong to the range of 50 to 59 years old (51.16%), 14 to range from 60 to 69 years old (32.55%) and 7 to range from 70 to 79 years old ( 16.27%). 44.1% of patients presented a prostate of 50 grams, the 51.16% prostates 60 grams and 4.6% a prostate gland of 70 grams. The average size of the prostate in grams was 50 grams in the range 50 to 59 years old, 60 g in the range 60 to 69 years old and 60 grams in the range of 70 to 79 years, and the average value of PSA was 5.5 ng / ml, 6 ng / ml and 7.5 ng / ml respectively. In the range 50 to 59 years of age every gram prostate equivalent to 0.11 ng / ml of PSA in the range 60 to 69 years of age every gram prostate equivalent to 0.1 ng / ml of PSA and the range 70 to 79 years old every gram of prostate equivalent to 0.125 ng / ml of PSA. Similarly we find that the entire population 72% have low self-esteem and problems with its image. Conclusions:In our environment in the group of 50-59 years old is the highest number of patients with benign prostatic hyperplasia.

The paper seeks to evaluate OYO Homes & Hotels, an Indian Hotel chain that holds the position of the third-largest hospitality chain in the world. The purpose of this paper is to evaluate how job satisfaction affects the performance of employees in OYO as a service provider company. The research will be based on secondary information gathered from databases, Internet and relevant information provided on OYO's official website. To fulfill the objective, the project aims to analyze the employees' main causes of job satisfaction, strategies in dealing with job dissatisfaction, and changes in performance. Finally, with the analysis, the project will establish recommendations for OYO to maximize employee performance in relation to job satisfaction.

After laparoscopic sleeve gastrectomy (LSG), several studies have reported an increase in the incidence of gastroesophageal reflux (GERD). The etiopathogenesis of GERD post-LSG is multifactorial, and hiatal hernia (HH) is one of them. The primary objective was to measure the incidence of de novo HH post-LSG. The secondary objectives were to relate the presence of HH with GERD, the chronic use of proton pump inhibitors (PPI), and the time elapsed from LSG.A surgical evaluation of the crura after LSG was performed. A retrospective cohort study of 74 consecutive patients with history of LSG submitted to an intra-abdominal surgery that allowed the evaluation of the crura.Of a total of 74 patients, 51 were included. At the time of surgery, 37 patients (72.5%) had a HH; 24 patients (47.1%) had GERD, and 23 patients (45.1%) were frequently using PPI. When patients with HH and those without HH were compared, GERD was observed in 56.8% versus 21.4% (p = 0.01) and frequent consumption on PPI was found in 54.1% versus 21.4% (p = 0.02). According to the data of LSG, with a follow-up of 18 months, 60% presented HH; meanwhile, with a follow-up of 18 months, 84.6% presented HH (p = 0.02).Patients submitted to LSG showed a high incidence of de novo HH. HH was associated with a higher incidence of GERD and PPI dependence. The longer the time elapsed from the LSG, the greater the incidence of HH.

Sparsely labeled NMR samples provide opportunities to study larger biomolecular assemblies than is traditionally done by NMR. This requires new computational tools that can handle the sparsity and ambiguity in the NMR datasets. The MELD (modeling employing limited data) Bayesian approach was assessed to be the best performing in predicting structures from sparsely labeled NMR data in the 13th edition of the Critical Assessment of Structure Prediction (CASP) event—and limitations of the methodology were also noted. In this report, we evaluate the nature and difficulty in modeling unassigned sparsely labeled NMR datasets and report on an improved methodological pipeline leading to higher-accuracy predictions. We benchmark our methodology against the NMR datasets provided by CASP 13.

Left ventricular aneurysms (LVA) occur after an infarcted area of the myocardium necrotizes, fibroses, and expands, forming a dyskinetic cavity. Most ventricular aneurysms are asymptomatic and go unrecognized unless found incidentally. Symptoms commonly reported include angina, heart failure, syncope, and even sudden cardiac death. Late complications from left ventricular aneurysms are infrequently reported. This case reports an elderly woman who presented with new-onset angina from an expanding 18-year-old true left ventricular aneurysm that was successfully treated with surgical repair.

Objective The primary objective of this research was to explore the link between sleep and flare pain associated with chikungunya virus (CHIKV) infection. The secondary objective was to investigate if cytokines and T regulatory (Treg) cells have an influence on this relationship. Methods A cross-sectional study was performed using data collected in Barranquilla, Colombia, which enrolled patients with and without chronic arthritis with a history of chikungunya infection. Flare severity was measured by a version of the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) flare questionnaire adapted for CHIKV arthritis, including metrics for pain, difficulty with physical activity, fatigue, stiffness and difficulty maintaining social activities due to arthritis that contribute to flare severity. In addition, four sleep disturbance items, five inflammatory cytokine levels, four anti-inflammatory cytokine levels, and six Treg levels were measured. Then, multivariable linear regression models were used to test the direct and indirect effects of flare-pain on sleep disturbance, and to determine whether this relationship was mediated by cytokines or Tregs. Finally, the SAS CALIS procedure was used to test path models showing possible causal effects with mediators and confounds. Results The analysis showed that sleep disturbance is positively correlated with CHIKV arthritis flare pain, and that it is a significant predictor of flare severity after adjusting for demographic variables, cytokine, and T cell levels. Further, neither T cells nor cytokines mediate the pain/sleep relationship in CHIKV arthritis. Conclusion There is a strong association between sleep disturbance and arthritis flare pain and severity; however, this relationship is not mediated by cytokines or T cells. Since this study is unable to determine causation, further research is needed to determine the mechanism underlying the relationship between sleep disturbances and CHIKV arthritis flares.

Point of care ultrasound has emerged as useful tool in cardiac arrest situations in adult population. Despite of these, there is not a protocol for cardiopulmonary resuscitation in the delivery room for newborns. We describe two case were ultrasound helped to rule out the cardiopulmonary arrest case and we propose and algorithm were ultrasound is integrated in the newborn resuscitation and may help to diagnose the cardiac arrest cause.

Objectives To correlate the ultrasound (US) measurements of the median nerve cross-sectional area (CSA) and the measurements of its stiffness by shear wave elastography (SWE) with the severity grade of carpal tunnel syndrome (CTS) using electrodiagnostic testing (EDT) and to determine the cutoff points for CSA and SWE measurements to allow us to discriminate patients with moderate and severe CTS from those with mild or negative EDT findings. Methods Seventy-three patients with 105 hands with a clinical suspicion of CTS were studied with US and SWE. We measured the median nerve CSA and elasticity (E) at the tunnel inlet (CSAu and Eu), in the quadratus pronator (CSAo and Eo), and the differences (CSAu - CSAo and Eu - Eo). Results The nerve area and stiffness increased according to the EDT severity of CTS; the CSA increased proportionally as CTS increased from negative to severe according to EDT, and the stiffness was not different between patients with negative and mild EDT findings but was higher in patients with moderate and severe EDT findings versus negative and mild EDT findings. The cutoff points of a CSAu of 14 mm2 or greater and an Eu - Eo of 57 kPa or greater together allowed the discrimination of moderate and severe CTS from the rest. Conclusions The joint use of US and SWE is an alternative to EDT in the clinical management and treatment of patients with a clinical suspicion of CTS.

This paper describes outcomes of the 2019 Cryo-EM Model Challenge. The goals were to (1) assess the quality of models that can be produced from cryogenic electron microscopy (cryo-EM) maps using current modeling software, (2) evaluate reproducibility of modeling results from different software developers and users and (3) compare performance of current metrics used for model evaluation, particularly Fit-to-Map metrics, with focus on near-atomic resolution. Our findings demonstrate the relatively high accuracy and reproducibility of cryo-EM models derived by 13 participating teams from four benchmark maps, including three forming a resolution series (1.8 to 3.1 Å). The results permit specific recommendations to be made about validating near-atomic cryo-EM structures both in the context of individual experiments and structure data archives such as the Protein Data Bank. We recommend the adoption of multiple scoring parameters to provide full and objective annotation and assessment of the model, reflective of the observed cryo-EM map density., A multi-laboratory study in the form of a community challenge assesses the quality of models that can be produced from cryo-EM maps using different software tools, the reproducibility of models generated by different users and the performance of metrics used for model validation.

Third-order non-linearities are important because they allow control over light pulses in ubiquitous high-quality centro-symmetric materials like silicon and silica. Degenerate four-wave mixing provides a direct measure of the third-order non-linear sheet susceptibility χ(3)L (where L represents the material thickness) as well as technological possibilities such as optically gated detection and emission of photons. Using picosecond pulses from a free electron laser, we show that silicon doped with P or Bi has a value of χ(3)L in the THz domain that is higher than that reported for any other material in any wavelength band. The immediate implication of our results is the efficient generation of intense coherent THz light via upconversion (also a χ(3) process), and they open the door to exploitation of non-degenerate mixing and optical nonlinearities beyond the perturbative regime., Light: Science & Applications, 10 (1), ISSN:2047-7538

This paper describes outcomes of the 2019 Cryo-EM Map-based Model Metrics Challenge sponsored by EMDataResource (www.emdataresource.org). The goals of this challenge were (1) to assess the quality of models that can be produced using current modeling software, (2) to check the reproducibility of modeling results from different software developers and users, and (3) compare the performance of current metrics used for evaluation of models. The focus was on near-atomic resolution maps with an innovative twist: three of four target maps formed a resolution series (1.8 to 3.1 Å) from the same specimen and imaging experiment. Tools developed in previous challenges were expanded for managing, visualizing and analyzing the 63 submitted coordinate models, and several novel metrics were introduced. The results permit specific recommendations to be made about validating near-atomic cryo-EM structures both in the context of individual laboratory experiments and holdings of structure data archives such as the Protein Data Bank. Our findings demonstrate the relatively high accuracy and reproducibility of cryo-EM models derived from these benchmark maps by 13 participating teams, representing both widely used and novel modeling approaches. We also evaluate the pros and cons of the commonly used metrics to assess model quality and recommend the adoption of multiple scoring parameters to provide full and objective annotation and assessment of the model, reflective of the observed density in the cryo-EM map.

Proyecto FAPA, Universidad de Los Andes (Bogota, Colombia). Centro Nacional de Pesquisa em Energia e Materiais, Brazilian Synchrotron Light Laboratory (LNLS), proposal n. XAFS1 – 17105. CARIPARO (Cassa di Risparmio di Padova e Rovigo) project MAKEARTH. European Union's Horizon 2020 research and innovation programme, under the Marie Sklodowska-Curie grant agreement No. 654606

The autosomal dominant polycystic kidney disease (ADPKD) accounts for one out of 400-1000 live births, being a hereditary disorder with cystic and noncystic manifestations as well as extrarenal involvement. The pericardial effusion (PE) in the context of a patient with ADPKD is complex, and it is not entirely defined. Several theories have been proposed. The most accepted, so far, is linked to mutations in the PKD1 gene which can entail an abnormal production of matrix components, matrix-degrading enzymes, and inhibitors of metalloproteinases, and defects in connective tissue which would lead to an abnormal distensibility of the connective tissue. We report the case of a 35-year-old female Moroccan patient with the diagnosis of ADPKD associated with arterial hypertension who came into the Emergency Department with lower abdominal pain lasting for five days being diagnosed as salpingitis. Abdominal computed tomography scan with contrast showed both kidneys with several cystic images with a thin wall. A transthoracic echocardiogram revealed the presence of moderate PE more in the anterior aspect. A greater set of standard tests to rule out collagen vascular disease, rheumatoid diseases, autoimmune disorders, and malignancies was ordered. These tests yielded no abnormality. The association of ADPKD with PE is rare. The awareness of this connection by the emergency physicians is key to prevent misplaced concern.

As the evolution of new cutting-edge energy technologies gain more and more momentum, modern power systems require higher capability in controlling all the devices and equipment that are able to handle processes for smartening the typical usage of the energy resources. This is the case of Renewable Energy Sources and Distributed Generation, innovative energy storage systems, electromobility programs, etc. The inteGRIDy project aims to offer a unique approach and an integrated software solution for managing all the energy processes within a smart modern energy context, from the measurement and collection of data from the field, to the smart elaboration of the information related to these data, ending with the graphical representation and interface with the human actors interacting with this framework. The management of the data exchanged and data storage are handled as well. In this paper, the methodology adopted to design the inteGRIDy Reference Architecture and the layered structure of the Architecture itself are presented. All the different processes entailed by the management approach provided are described and detailed layer by layer, as their benefits for the energy system under control.

The use of Millimeter-wave (mmWave) spectrum in cellular communications has recently attracted growing interest to support the expected massive increase in traffic demands. However, the high path-loss at mmWave frequencies poses severe challenges. In this paper, we analyze the potential coverage gains of using unmanned aerial vehicles (UAVs), as hovering relays, in integrated access and backhaul (IAB) mmWave cellular scenarios. Specifically, we utilize the WinProp software package, which employs ray tracing methodology, to study the propagation characteristics of outdoor mmWave channels at 30 and 60 GHz frequency bands in a Manhattan-like environment. In doing so, we propose the implementation of amplify-and-forward (AF) and decode-and-forward (DF) relaying mechanisms in the WinProp software. We show how the 3D deployment of UAVs can be defined based on the coverage ray tracing maps at access and backhaul links. Furthermore, we propose an adaptive UAV transmission power for the AF relaying. We demonstrate, with the aid of ray tracing simulations, the performance gains of the proposed relaying modes in terms of downlink coverage, and the received signal to interference and noise ratio (SINR)., Comment: in Proc. IEEE WoWMoM Workshop Wireless Netw. Planning Comput. UAV Swarms, Washington, DC, USA, Jun.2019

SECCION IV. Diagnóstico de los casos de infección por SARS-CoV-2/COVID-19

Background and study aims: Hereditary diffuse gastric cancer (HGGC), an autosomal dominant tumor-syndrome, accounts for 1 % to 3 % of gastric cancers worldwide. Presumably 30 % to 40 % of all patients fulfilling the clinical guidelines for HDGC are carriers of a pathogenic mutation in the CDH1 gene. Patients often show multiple foci of signet ring cell carcinoma at early age and are advised to undergo prophylactic total gastrectomy (PTG). Our aim was to improve the endoscopic detection of HDGC by using an enhanced endoscopic protocol. Patient and methods: Patients with a proven CDH1 germline mutation identified in our institute were prospectively included. Patients were advised to undergo PTG and offered a baseline endoscopic examination prior surgery. Examination was performed by using high-resolution white-light endoscopy and pan-gastric chromoendoscopy with indigo carmine as dye combined with targeted and multiple random biopsies assessed by an expert histopathologist. Postoperative histopathology was compared with results from endoscopic biopsies. Results: Between September 2012 and November 2014 8 patients with a proven CDH1 germline mutation were included. We conducted 44 targeted (6.3/patient) and 225 random (32.1/patient) biopsies in 7 patients. We detected 1 gastric cancer by random biopsy (14 %). All other examinations showed no signs of cancer. Histopathology of gastrectomy specimen revealed multiple foci of gastric carcinoma in 6 patients (86 %) with a total number of 27 cancer foci. Conclusions: Examination with targeted and random biopsies combined with chromoendoscopy is not able to detect small foci of gastric cancer in CDH1 mutation carriers. Therefore PTG is advocated in these patients.

Author(s): Okhunov, Zhamshid; Yoon, Renai; Perez Lanzac, Alberto; Sgroi, Michael; Lau, Wei Ling; Del Junco, Michael; Ordon, Michael; Drysch, Austin; Hwang, Christina; Vernez, Simone L; Fujitani, Roy; Kabutey, Nii-Kabu; Kalantar-Zadeh, Kamyar; Landman, Jaime | Abstract: ObjectivesWe attempted to create a surgical model to evaluate the retroperitoneal space for the ability to transfer solutes through the retroperitoneal membrane. Our dual objectives were to develop a technique to assess the feasibility of retroperitoneal dialysis (RPD) in a porcine model.MethodsWe incorporated two 35-kg Yorkshire pigs for this pilot study. In the first animal, we clamped renal vessels laparoscopically. In the second animal, we embolized renal arteries. In both animals, we dilated the retroperitoneal space bilaterally and deployed dialysis catheters. We measured serum creatinine (Cr), urea, and electrolytes at baseline 6 hours before the dialysis and every 4 hours after.ResultsWe successfully created retroperitoneal spaces bilaterally and deployed dialysis catheters in both animals. In the first animal, dialysate and plasma Cr ratio (D/P) on the left and right side were 0.43 and 0.3, respectively. Cr clearance by 40 minutes of dialysis treatment was 6.3 mL/min. The ratio of dialysate glucose at 4 hours dwell time to dialysate glucose at 0 dwell time (D/D0) for left/rights sides were 0.02 and 0.02, respectively. kt/Vurea was 0.43. In the second animal, D/P Cr for left/right sides were 0.34 and 0.33, respectively. kt/Vurea was 0.17. We euthanized the pigs due to fluid collection in the peritoneal space and rapid increase of serum Cr, urea, and electrolytes.ConclusionsWe demonstrated the feasibility of creation of a functionally anephric porcine model with successful development of retroperitoneal spaces using balloon inflation. Notwithstanding minimal clearance and limited diffusion capacity in this experiment, additional studies are needed to examine potential use of retroperitoneal space for peritoneal dialysis.

In this article we propose an optimal sizing of WSN network, the network required for the location of Universal Data aggregation UDAP. These allow data exchange between the UDAP and the smart meter. We consider a georeferenced stage for randomly placed points on the map, getting potential candidates sites to be activated by a UDAP. There are several problems when we consider the coverage, capacity and interference. But we have parameters that we can control and some we can not control parameters, then to solve the problems presented. We assume some parameters as a constant radius depending on the technology used, as we assume a scenario without interference. When we take into account the capacity we consider to each UDAP has limited capacity so that He can serve multiple users simultaneously, then this is an important parameter for dimensioning. In addition to the network may have scalability in the future, we try to minimize the number of channels used. Interference is a very important aspect to consider, that parameter appears when you have two UDAP functioning at a very short distance from each other. For all inconvenienced, we propose an algorithm that optimizes the number of UDAP used, using a MILP to cover at least a percentage N of users, but considering all the problems described.

Bivalirudin is an alternative to unfractionated heparin (UFH) anticoagulation during percutaneous coronary intervention. Previously, we have reported clinical benefit on major bleeding in favor of bivalirudin compared with UFH monotherapy but inconclusive results on mortality. Controversial data have been reported in the last 2 years. We conducted an updated meta-analysis including randomized trials and observational studies, which evaluated ischemic and bleeding outcomes for bivalirudin compared with UFH-only during percutaneous coronary intervention. We included 18 observational studies and 12 randomized trials published from 2003 to 2015. Primary outcomes were major adverse cardiovascular events within 30 days including death, myocardial infarction, and urgent revascularization and stent thrombosis, major bleeding, and transfusion. Overall, we found a significant risk reduction with bivalirudin for major bleeding (odds ratio [OR] 0.59, 95% confidence interval [CI] 0.49 to 0.71, p0.0001) and for transfusion (OR 0.79, 95% CI 0.66 to 0.95, p = 0.01) and similar risk for major adverse cardiovascular events (OR 0.98, 95% CI 0.86 to 1.12, p = 0.80). However, there was a substantial increased risk of stent thrombosis associated with bivalirudin (OR 1.52, 95% CI 1.11 to 2.08, p = 0.009). No impact on mortality was found. Meta-regression analyses on major bleeding suggested that bivalirudin was more effective than UFH at doses60 IU/kg and independent of radial access. In conclusion, compared with UFH monotherapy, bivalirudin remains associated with less bleeding risk but higher stent thrombosis risk. Further study remains required to define its role in current antithrombotic armamentarium.

3138 Background: Clinical effective multi-antigen active immunotherapy for colorectal cancer (CRC) is still limited and most studies have failed. We consider this is because the targets in some of the studies are not oncogenic drivers. This is especially important for patients that progressed to standard of care treatment. Also, most of the studies with Immune checkpoint inhibitors (ICH) have failed in CRC but potentially may impact and provide better outcomes if used as combination therapies. We treated CRC patients with progressive disease in a pilot study n = 15 and found clinical responses that correlate with the CD8, delayed-type hypersensitivity (DTH) and Th1 parameters. After patients achieved remission we used the same peptides to prevent relapse with clinical and statistics significance. Methods: N = 15 CRC patients were enrolled in this pilot trial after approval for the ethic IRB committee from CICS Mexico. Patients were treated with an intradermal vaccine every week for four weeks, every two weeks four times in axillary and inguinal lymph nodes (LN) areas, and finally subcutaneously every month six times in the sites with tumor activity. Previously to the treatment we perform Granzyme B ELISPOT, ELISA, DTH and CT scan as initial controls. We delivered intradermal four peptides from sixteen peptides predicted from four proteins such as Fascin-1, Ape-1, VCP and RCAS1. Results: 86% of the patients had an objective clinical responses and 14% stable disease. All the patients had a correlation with the immunological assays as following. 58% of patients had an increased in the CD8 cells demonstrated by Granzyme B; DTH reactions were gradually increasing and by the first month of treatment the DTH were positive for Fascin-1 (78%), Ape-1 (85%), VCP (95%) and RCAS1 (83%) peptides. The more immunogenic peptides by ELISA were Fascin-1 A (P = 0.001), Fascin-1 D (P = 0.005), Ape-1 C (p = 0.001), VCP A (P = 0.003), RCAS1 A (p = 0.001) and RCAS1 B (P = 0.01). Conclusions: The treatment was effective with CR and SD responses. Once we validate this data we are planning a clinical study combining the treatment with low dose of ICH. Currently all the patients with CR are now under relapse prevention. We are still treating the patients with SD until disease progression. Importantly we believe that this data may impact the PFS and OS in CRC patients who have Karnoksky > to 80% despite progressive disease to standard of care.

The Pacific Alliance (PA) is one of the most dynamic economic liberalization processes among Latin American nations. The objective of this group is to advance towards regional integration through the liberalization of trade, services, investment and the freer movement of people among its members (Chile, Colombia, Mexico and Peru). This chapter aims to answer the question of whether the PA is a World Trade Organization-plus (WTO+) (i.e. it goes beyond the normal provisions of the WTO agreements) or a WTOx agreement (i.e. it covers issues for which there are no WTO agreements) within specific areas. The areas included in this assessment are: market access for goods, services and foreign direct investment; trade facilitation, government procurement, competition and intellectual property. The chapter concludes that the PA is a new-generation agreement that could be considered a WTO+ agreement in areas such as trade in goods and services, public procurement, trade facilitation and customs cooperation, and it is likely to reach WTO+ in terms of its provisions on intellectual property. The scope of the commitments in areas such as competition, investment and movement of capital, which are WTOx, represents this group’s longstanding commitment towards deeper regional economic integration.

This article reviews antithrombotic strategies for percutaneous coronary interventions according to the access site and the current evidence with the aim of limiting ischemic complications and preventing radial artery occlusion (RAO). Prevention of RAO should be part of the quality control of any radial program. The incidence of RAO postcatheterization and interventions should be determined initially using the echo-duplex and then frequently assessed using the more cost-effective pulse oximetry technique. Any evidence of higher risk of RAO should prompt internal analysis and multidisciplinary mechanisms to be put in place.

BackgroundLower esophageal sphincter (LES) electrical stimulation therapy (EST) has been shown to improve outcome in gastroesophageal reflux disease (GERD) patients at 1 year. The aim of this open-label extension trial (NCT01578642) was to study the 2-year safety and efficacy of LES-EST in GERD patients.MethodsGERD patients responsive partially to proton pump inhibitors (PPI) with off-PPI GERD health-related quality of life (HRQL) of ≥20, 24-hour esophageal pH ≤4.0 for >5% of the time, hiatal hernia ≤3 cm, and esophagitis LA grade C or lower participated in this trial. Bipolar stitch electrodes and a pulse generator (EndoStim BV, The Hague, The Netherlands) were implanted laparoscopically. LES-EST at 20 Hz, 215 μs, 3-8 mAmp was delivered over 30-minute sessions, 6-12 sessions per day, starting on day 1 after implantation. Patients were evaluated using GERD-HRQL, symptom diaries, Short Form-12, and esophageal pH testing at regular intervals. Stimulation sessions were optimized based on residual symptoms and esophageal pH at follow-up.ResultsTwenty-five patients (mean age [SD] = 52 [12] years; 14 men) were implanted successfully; 23 patients participated in the 2-year extension trial, and 21 completed their 2-year evaluation. At 2 years, there was improvement in their median GERD-HRQL on LES-EST compared with both their on-PPI (9 vs 0; P = .001) and off-PPI (23.5 vs 0; P

Background Intensity-modulated radiation therapy (IMRT) uses solid compensators or multileaf collimators to modulate the intensity of radiation in each field, delivering highly conformal dose distributions. This technique allows treating volumes with concave shapes when the target is close to a critical structure. The movement of multileaf collimator under computer control can modulate the dose in 3 main ways: IMRT with static field with segments, IMRT with dynamic delivery, and IMRT rotational therapy. Volumetric modulated arc therapy (VMAT) is a novel radiation technique that creates conformal distributions with variable gantry speed, dynamic movements of multileaf collimator, and variations in dose rate. The purpose of this study was to review the basis of VMAT, highlighting the differences with other IMRT techniques. © 2014 Wiley Periodicals, Inc. Head Neck 37: 909–914, 2015

The autonomic nervous supply to the kidneys is involved in the development of several diseases including hypertension. The neural distribution at the segmental vessels and intrarenal vasculature has not been well characterized. Thus, we evaluated the autonomic nerve distribution from the great vessels to the renal cortex in a cadaveric model.We performed a detailed anatomical nerve dissection from the inferior mesenteric artery to the renal operculum in 2 human cadaveric torsos. Autonomic nerve fibers were verified by dissecting the greater splanchnic, sympathetic trunk and ganglia. We then systematically cross-sectioned the kidneys in 12, 1 mm slices across 3.6 cm, and stained the slices for histopathological analysis of neural tissue in relation to segmental arteries and other anatomical landmarks. Advanced reconstructive software was used to create a 3-dimensional computer image.Autonomic nerve fibers are located almost exclusively anteriorly on the main renal arteries and segmental arteries, and are absent from veins. Histopathology revealed that the intrarenal nerves continued to track exclusively with the arteries but were more circumferentially distributed. There is minimal nerve tissue around the veins. Many nerves were within a few millimeters of the renal collecting system.The autonomic nerves supplying the kidney maintain their distribution almost exclusively along the anterior surface of arteries as they pass from the aorta to the segmental arteries. Once inside the renal parenchyma, the nerves are circumferentially distributed around the renal arteries and are in close proximity to the renal collecting system.

e17079 Background: There are several reports of increased of SUV in the lymph nodes of cancer patients after immune manipulation such as the administration of vaccines and checkpoint inhibitors. However the clinical importance of these phenomena is poorly understood. The administration of two immunogenic drugs and eight peptides in HGSOC induced atypical bright zones in multiple lymph nodes and, in areas with microscopic disease where potentially we can have cancer stem cells (CSC’s). Methods: We enrolled N = 10 HGSOC after the local IRB ethic committee approval. All the patients had 3 recurrences with mPFS = 8 months of the third relapse. The last FDG-PET scan was used as basal image for the study. Blood was collected for cellular and humoral immunology analysis such as Granzyme B ELISPOT and ELISA. Tissue was used for IHC analysis for the evaluation of CD8, FOXP3, Th1, and proteins related with CSC’s. The patients received 50 mg of oxaliplatin and 30 mg of doxorubicin total dose every week four times simultaneously with multi peptide immunotherapy. A second FDG-PET scan was performed after the termination of the treatment. Results: After the treatment 100% of the patients showed intense atypical bright uptake areas in lymph nodes and in the peritoneum. There was a correlation between the brightness intensity (SUV), and the Granzyme B production (p = 0.001). We found multiple bright small lesions in the peritoneum that were not visible before treatment. We demonstrated the presence of proteins related with CSC’s in the original tumor tissue and an antibody immune response against EGFR (P = 0.005), Ape-1 (p = 0.003) and Bcl-2 (p = 0.05). Conclusions: Immunotherapy may produce hypermetabolic activity that could lead to overtreatment when evaluated by FDG-PET in HGSOC. Vaccination may activate lymph nodes and anti-cancer immune interventions may also activate CD8 and Th1 cells able to accumulate in CSC’s clusters and increased notably the SUV, which may lead to false relapse interpretation by the radiologists and oncologists.

There are many risk factors for developing hypertension. In the XXI century, smarter ways to investigate are needed, so preventing the turning of an adolescent into a hypertensive adult must be a priority. Objective: The aim of this paper is to predict the risk of high blood pressure onset in

Mounting a T helper 1 (Th1) type of response is required for the successful priming of antigen specific CD8 T-cells which ultimately lead to effective antitumoral responses. Several cellular components of the immune system participate of the Th1 decision-making process. They include innate cells sensing the transformed cells, mainly dendritic cells (DCs), and the further involvement of antigen specific CD4 T-cells promoting direct activation of CD8 T-cells through cross-presentation (1). The correct stimulation of DCs by type I interferons and molecular pattern sensors as STING is required to drive their differentiation to conventional DC 1 (cDC1) which through the secretion of large amounts of IL-12 and the expression of CD40 skew the CD4 T-cells differentiation to Th1 (2). However, this system is sensitive to modifications of the tumor cytokine microenvironmen,t leading to failure. Adoptive cell transfer (ACT) cancer immunotherapies are promising treatments for advanced malignancies. These therapies attempt to supply key cellular actors missing and induce proper antitumoral immunity. They include mainly the in vitro modification of autologous cells, from DCs loaded with tumor antigens to the expression of chimeric antigen receptor (CAR) on T and NK cells. Constant development of these technologies has given successful results as clinical trials have already showed up to 90 % of complete remission in relapsed/refractory B cell acute lymphoid leukemia (B-ALL) (3), treatment now approved for commercial use. However, there is still lack of consistency in the responses obtained from different individuals and in different trials. Previously our laboratory has already shown that modulation of the JAK-STAT inhibitory protein tyrosine phosphatases (PTPs), PTPN1 and PTP-N2, enhance proinflammatory type I interferon signalling while decreases the effects of immunosuppressive cytokines acting through STAT3 signaling (4, 5). Specifically, we have demonstrated that partial inhibition of these phosphatases in immune cells enhances the secretion of IL-12p70 by DCs[6] and increases the cytotoxic activity of antigen specific CD8 T-cells [Pérez-Quintero LA, Tremblay ML, unpublished results]. Moreover, the partial inhibition of these phosphatases in CD8 T-cells enhance the acquisition of a central memory (Tcm) phenotype, which has been found to be associated with better remission in CAR-T-cells therapies. Nevertheless, alternative methods to enrich this phenotype, as cytokine cocktails, have proven expensive and ineffective. Having this in mind, we propose here the use of small-molecule inhibitors specific for PTPN1 and PTPN2 as a simple and cost-effective method to enhance antitumoral responses. By treating ex vivo the cellular products in animal models for DCs and CD8 ACT therapies we show, as a proof of concept, a marked improvement on the reduction of tumor burden and remission, with the late goal of translating these findings into a clinical setup. References: 1. Gajewski TF, Schreiber H, Fu YX. Innate and adaptive immune cells in the tumor microenvironment. Nature Immunology 2013;14:1014. 2. Theisen D,Murphy K. The role of cDC1s in vivo: CD8 T-cell priming through cross-presentation [version 1]. 2017;6. 3. Oluwole OO,Davila ML. At The Bedside: Clinical review of chimeric antigen receptor (CAR) T-cell therapy for B cell malignancies. Journal of Leukocyte Biology 2016. 4. Pike KA, et al. Protein tyrosine phosphatase 1B is a regulator of the interleukin-10–induced transcriptional program in macrophages. Science Signaling 2014;7(324): ra43-ra43. 5. Pike KA, et al. TC-PTP regulates the IL-7 transcriptional response during murine early T-cell development. Scientific Reports 2017;7(1):13275. 6. Penafuerte C, et al. Downregulation of PTP1B and TC-PTP phosphatases potentiate dendritic cell-based immunotherapy through IL-12/IFNγ signaling. OncoImmunology 2017;6(6):e1321185. Citation Format: Luis Alberto Perez-Quintero, Kelly Anne Pike, Penafuerte Claudia, Michel Tremblay. Enhancing antitumoral activity of cell-based immunotherapies by modulating the JAK-STAT axis [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B035.

To assess the reliability of the S.T.O.N.E. (stone size [S], tract length [T], obstruction [O], number of involved calices [N], and essence or stone density [E]) nephrolithometry scoring system by testing its reproducibility between different observers.Preoperative images of 58 patients who underwent percutaneous nephrolithotomy (PCNL) were reviewed. Medical students, urology residents, one fellow, and a urology attending independently reviewed all images and scored the renal stones. Interobserver reliabilities of the total score for all categories and each component were evaluated by the intraclass correlation (ICC) and a κ coefficient.The interobserver reliability for the total score demonstrated high correlations for all components and total score (ICC=S, T, O, N, E and total 0.80, 0.97, 0.89, 0.84, 0.91, and 0.87, respectively). κ rates for individual components between two medical students were 0.36, 1, 0.31, 0.45, 0.33, and 0.30 for the S, T, O, N, E components and total score, respectively. κ values between the two urology residents were 0.71, 1, 0.92, 0.79, 0.93, and 0.67 for S, T, O, N, E components and total score, respectively. κ values between the urology fellow and an attending physician were 0.95, 1, 0.88, 0.94, 0.89, and 0.87 for S, T, O, N, E components and total score, respectively. P value for all the scoring components was0.05, indicating that the estimated κ was not a result of chance.The S.T.O.N.E. nephrolithometry has excellent interobserver reliability. Quantifying the S and N metrics was the most challenging and least reliable. Standardized protocols to measure these components should be considered to improve accuracy and reproducibility of the scoring system.

The late-stage clinical course, histopathologic analysis, and surgical salvage procedures after eventful cosmetic injection of hydroxyethylmethacrylate particles suspended in hyaluronic acid (DermaLive, marketed through Dermatech, Paris, France and Novamedical GmbH, Langenfeld, Germany) have been studied. The study was designed to present modified treatment guidelines, report results, and draw conclusions regarding the future management of patients with late-stage DermaLive complications.The study consulted and reviewed 21 patients with late-stage complications after facial implantation of DermaLive. Histology samples from excisional biopsies followed by radical surgical excision procedures were obtained and analyzed for nine patients.The treated zones included nasolabial folds, forehead and glabella, lips, and the perioral and zygoma regions. The late-onset period between injection and first symptoms averaged 17.5 months. Lesions were mostly symptomatic, with discomfort, pain, swelling, and edema. Clinical aspects included bulging, palpable nodules, erythema, and scar formation. A positive correlation between patient age and the delay period was found. All surgically treated patients recovered well. The initial conservative measures achieved only partial success, whereas all nine surgically treated patients (43 %) demonstrated complete relief of their clinical symptoms.Soft tissue augmentation with DermaLive led to a series of severe delayed adverse reactions. Sclerosing DermaLive granulomas demonstrated low success rates with conservative measures, whereas early radical surgical excision achieved good results.This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

One of the clinical situations linked to the use of warfarin is the skin necrosis occurring in approximately 0.01 to 0.1% of all patients receiving warfarin. Typically, lesions develop during the first days after initiation of warfarin therapy (usually around the tenth day) and are often associated with the administration of a loading dose. The pathophysiological mechanisms for warfarin-induced skin necrosis, despite several theories, remain uncertain. For the diagnosis, along with a high degree of suspicion, a rapid recognition and management is required.

Nowadays, risk prediction is being focused as a key element in identifying risk factors for cardiovascular disease (CVD).1 The publication of the Third Report of the National Cholesterol Education Program's Adult Treatment Panel (ATP-III)2 in 2001, among other work,3 was paramount for risk prediction becoming the cornerstone in the field of CVD prevention, particularly in adulthood. However, considering the title of the present publication, the author puts forward the following question: where do we stand in relation to the prediction of CVD that is focused on the early stages of life, i.e., childhood or adolescence? An extensive search on the subject in Medline yielded little evidence to suggest the development of models aimed to predict CVD in adulthood on the basis of cardiovascular risks in the early stages of life. Nevertheless, prediction of cardiovascular risks since childhood and adolescence is essential and constitutes a key issue in cardiovascular epidemiology. There are conditions such as arterial hypertension (HTN) for which the former statement can be fully justified, taking into consideration its increasing prevalence in the early stages of life.4 The author of this letter published one scientific paper,5 where two risk scores were proposed to assess the likelihood of hypertension in adulthood after analyzing cardiac risk factors in Cuban adolescents. It is thus justifiable to give a wake-up call to the medical community to go to the root of the problem (childhood and adolescence) where the genesis of hypertension occurs. A management strategy should then be adopted to prevent the increased chances of developing hypertension in adulthood. This can also apply to other conditions such as familial hyperlipidemia, diabetes and obesity, involving the broad class of CVD. This demonstrates the importance of developing a new model of CVD risk factors to predict CVD from childhood and adolescence. The benefit will be far less when addressing these risk factors once damage is already established. I strongly believe that the correct identification and management of risks in terms of prediction is decisive in preventing clinical vascular events in adult life. Keywords: prediction, cardiovascular disease

Myopodin is a cytoskeleton protein that shuttles to the nucleus depending on the cellular differentiation and stress. It has shown tumor suppressor functions. Myopodin methylation status was useful for staging bladder and colon tumors and predicting clinical outcome. To our knowledge, myopodin has not been tested in kidney cancer to date. The purpose of this study was to evaluate whether myopodin methylation status could be clinically useful in renal cancer (1) as a prognostic biomarker and 2) as a predictive factor of response to antiangiogenic therapy in patients with metastatic disease. Methylation-specific polymerase chain reactions (MS-PCR) were used to evaluate myopodin methylation in 88 kidney tumors. These belonged to patients with localized disease and no evidence of disease during follow-up (n = 25) (group 1), and 63 patients under antiangiogenic therapy (sunitinib, sorafenib, pazopanib, and temsirolimus), from which group 2 had non-metastatic disease at diagnosis (n = 32), and group 3 showed metastatic disease at diagnosis (n = 31). Univariate and multivariate Cox analyses were utilized to assess outcome and response to antiangiogenic agents taking progression, disease-specific survival, and overall survival as clinical endpoints. Myopodin was methylated in 50 out of the 88 kidney tumors (56.8 %). Among the 88 cases analyzed, 10 of them recurred (11.4 %), 51 progressed (57.9 %), and 40 died of disease (45.4 %). Myopodin methylation status correlated to MSKCC Risk score (p = 0.050) and the presence of distant metastasis (p = 0.039). Taking all patients, an unmethylated myopodin identified patients with shorter progression-free survival, disease-specific survival, and overall survival. Using also in univariate and multivariate models, an unmethylated myopodin predicted response to antiangiogenic therapy (groups 2 and 3) using progression-free survival, disease-specific, and overall survival as clinical endpoints. Myopodin was revealed hypermethylated in kidney cancer. Myopodin methylation status identified which patients showed a more aggressive clinical behavior and predicted antiangiogenic response. These observations support the clinical utility of an unmethylated myopodin as a prognostic and predictive biomarker in kidney cancer.

Background Electrical stimulation of the lower esophageal sphincter (LES) improves LES pressure without interfering with LES relaxation. The aim of this open-label pilot trial was to evaluate the safety and efficacy of long-term LES stimulation using a permanently implanted LES stimulator in patients with gastroesophageal reflux disease (GERD). Methods GERD patients who were at least partially responsive to proton pump inhibitors (PPI) with abnormal esophageal pH, hiatal hernia ≤3 cm, and esophagitis ≤LA grade C were included. Bipolar stitch electrodes were placed in the LES and an IPG was placed in a subcutaneous pocket. Electrical stimulation was delivered at 20 Hz, 215 μs, 3–8 mA in 30 min sessions. The number and timing of sessions was tailored to each patient’s GERD profile. Patients were evaluated using GERD-HRQL, daily symptom and medication diaries, SF-12, esophageal pH, and high-resolution manometry. Results 24 patients (mean age = 53 years, SD = 12 years; 14 men) were implanted; 23 completed their 6-month evaluation. Median GERD-HRQL scores at 6 months was 2.0 (IQR = 0–5.5) and was significantly better than both baseline on-PPI [9.0 (range = 6.0–10.0); p p p p Conclusions Electrical stimulation of the LES is safe and effective for treating GERD. There is a significant and sustained improvement in GERD symptoms, esophageal pH, and reduction in PPI usage without any side effects with the therapy. Furthermore, the therapy can be optimized to address an individual patient’s disease.

Chromaffin cells have been widely used to study neurosecretion since they exhibit similar calcium dependence of several exocytotic steps as synaptic terminals do, but having the enormous advantage of being neither as small or fast as neurons, nor as slow as endocrine cells. In the present study, secretion associated to experimental measurements of the exocytotic dynamics in human chromaffin cells of the adrenal gland was simulated by using a model that combines stochastic and deterministic approaches for short and longer depolarizing pulses, respectively. Experimental data were recorded from human chromaffin cells, obtained from healthy organ donors, using the perforated patch configuration of the patch-clamp technique. We have found that in human chromaffin cells, secretion would be mainly managed by small pools of non-equally fusion competent vesicles, slowly refilled over time. Fast secretion evoked by brief pulses can be predicted only when 75% of one of these pools (the "ready releasable pool" of vesicles, abbreviated as RRP) are co-localized to Ca2?+? channels, indicating an immediately releasable pool in the range reported for isolated cells of bovine and rat (Alvarez and Marengo, J Neurochem 116:155---163, 2011). The need for spatial correlation and close proximity of vesicles to Ca2?+? channels suggests that in human chromaffin cells there is a tight control of those releasable vesicles available for fast secretion.

Angiosarcomas are a rare type of malignant vascular tumour characterised by proliferation of tumour cells with vascular endothelial features. These tumours are usually very aggressive and overall mortality is very high. Pulmonary angiosarcomas are usually secondary tumours, and only a few primary cases have been reported. We present a case of a 56 year-old male with persistent haemoptysis secondary to lung epithelioid angiosarcoma with pleural metastases.

Eur J Clin Invest 2010; 40 (12): 1122–1130 Abstract Background Elderly patients with suspected or known coronary artery disease are often referred for pharmacological stress testing. Data on the value of exercise echocardiography (ExEcho) for predicting outcome (particularly all-cause mortality) in these patients are scarce. Methods Peak treadmill ExEcho was performed in 2159 patients ≥ 70 years of age with known or suspected coronary artery disease. Left ventricular wall motion was evaluated at baseline and with exercise, and the increase in wall motion score index from rest to peak exercise (ΔWMSI) was calculated. Ischaemia was diagnosed when new or worsening wall motion abnormalities developed with exercise. The end points were all-cause mortality and major cardiac events (cardiac death or myocardial infarction). Results Ischaemia developed in 844 patients (38·6%) during exercise. Over a mean follow-up of 3·5 ± 3·1 years, 439 deaths occurred. The cumulative 5-year mortality rate was 29·3% in patients with ischaemia versus 16·8% in those without ischaemia (P

e14066Background: Little is known about the immunogenicity of pediatric medulloblastomas and DIPG in order to rationally develop immunotherapies. We performed a systematic review of putative biolog...

The association of atrial fibrillation (AF) with coronary artery disease (CAD) remains controversial. In addition, the relation of AF to myocardial ischemia and outcomes in patients with known or suspected CAD referred for exercise stress testing has been poorly explored. In this study, 17,100 patients agedor = 50 years with known or suspected CAD who underwent exercise electrocardiography (n = 11,911) or exercise echocardiography (n = 5,189) were evaluated. End points were all-cause mortality, nonfatal myocardial infarction, and coronary revascularization. Overall, 619 patients presented with AF at the time of the tests. Patients with AF who had interpretable electrocardiograms had a lower likelihood of exercise-induced ischemic ST-segment abnormalities (adjusted odds ratio 0.51, 95% confidence interval 0.34 to 0.76, p = 0.001), and those with AF who underwent exercise echocardiography had a lower likelihood of new or worsening exercise-induced wall motion abnormalities (adjusted odds ratio 0.62, 95% confidence interval 0.44 to 0.87, p = 0.006). During a mean follow-up period of 6.5 + or - 3.9 years, 2,364 patients died, 1,311 had nonfatal myocardial infarctions, 1,615 underwent percutaneous coronary intervention, and 922 underwent coronary artery bypass surgery. The 10-year mortality rate was 43% in patients with AF compared to 19% in those without AF (p0.001). In multivariate analysis, AF remained an independent predictor of all-cause mortality (adjusted hazard ratio 1.45, 95% confidence interval 1.20 to 1.76, p0.001), but not of nonfatal myocardial infarction or coronary revascularization. In conclusion, despite being associated with an apparently lower likelihood of myocardial ischemia, AF was an independent predictor of all-cause mortality in patients with known or suspected CAD referred for exercise stress testing.

In addition to lymphomas, vascular tumors represent the most common neoplasms of the spleen. Littoral cell angiomas are benign vascular tumors originating from the littoral cells lining the splenic sinuses. In this report, we describe the case of a 63-year-old patient who developed night sweats 16 months after renal transplantation. Diagnostic workup showed multiple splenic masses believed to represent lymphoma infiltration to the spleen. Lymph nodes and bone marrow were unaffected, and diagnostic splenectomy was performed. Histological examination of the pathological specimen from the splenectomy specimen showed multiple littoral cell angiomas of the spleen. We recommend that physicians involved in the area of organ transplantation, especially kidneys, remain alert for other rarer splenic lesions in transplant recipients than posttransplantation lymphoma. More specific tools need to be developed to aid in the differential diagnosis of splenic masses to avoid splenectomy in patients with littoral cell angiomas.

Objective The aim of this study was the development of an experimental cardiomyopathy induced with Adriamycin (Pharmacia & Upjohn, Erlangen, Germany) with selective toxic damage of the left ventricular myocardium that avoided an ischemic component. Methods An intracoronary catheter was implanted directly into the left main stem in pigs and connected to a percutaneous access port that was used for repetitive Adriamycin administration (3–5 × 25 mg weekly over a 1-hour period). Hemodynamic and echocardiographic variables were measured before Adriamycin administration, 1 week after, and at 4 weeks. Thereafter, all hearts were autopsied for detailed histologic examination. Statistical analysis was done by an analysis of variance for multiple parameters. Results All pigs had normal baseline cardiac function. Measurements after Adriamycin administration and 4 weeks later demonstrated a continued increase of the central venous pressure, pulmonary artery pressure, pulmonary wedge pressure, and pulmonary vascular resistance, whereas cardiac output, stroke volume index, and left ventricular stroke work index decreased. These results were supported by the echocardiographic data depicting an increase of left ventricular diameters and volumes, accompanied by a decrease of intraventricular and left ventricular posterior wall thickness as well as left ventricular ejection fraction. Right ventricular volumes and function did not change during the trial. The histologic examination of the hearts revealed a selective toxic damage of the left ventricular myocardium with multifocal necroses and advanced tissue reorganization. Conclusion This animal model creates a selective left ventricular damage that avoids ischemic damage of the myocardium. Both aspects can improve research on Adriamycin-induced cardiomyopathy, especially preventive or therapeutic strategies.

Efficient produced water management has been a growing concern in the oil and gas industry over the last decades. Water cuts have risen and more oil fields are maturing. Therefore growing volumes of produced water have to be handled every year. The most common disposal option is reinjection into the reservoir. In order to reinject produced water it has to be treated. Produced water tanks (PWT) are usually applied as first stage separators in water treatment plants. The oil-water separation efficiency of PWTs can be improved by optimizing tank internals to reduce the load on downstream treatment units. This study shows the results of a Computational Fluid Dynamics (CFD) based optimization approach for various water tanks in mature oil field environments. The concept centers on the induction of a tangential liquid movement in PWTs to maximize residence time for a given volume of water and to reduce short-circuiting. In order to show the benefits of such a setup, an existing tank was upgraded with CFD designed internals. The separation efficiency of the tank was recorded prior to and after installing the internals. The results showed that the average residence time could be extended eightfold. Based on the initial experience and additional simulation work, the internals concept was adapted and improved for several new tanks. These tanks are currently under construction and first field results will become available in 2016.

Atomistic molecular dynamics (MD) simulations of protein molecules are too computationally expensive to predict most native structures from amino acid sequences. Here, we integrate "weak" external knowledge into folding simulations to predict protein structures, given their sequence. For example, we instruct the computer "to form a hydrophobic core," "to form good secondary structures," or "to seek a compact state." This kind of information has been too combinatoric, nonspecific, and vague to help guide MD simulations before. Within atomistic replica-exchange molecular dynamics (REMD), we develop a statistical mechanical framework, modeling using limited data with coarse physical insight(s) (MELD + CPI), for harnessing weak information. As a test, we apply MELD + CPI to predict the native structures of 20 small proteins. MELD + CPI samples to within less than 3.2 Å from native for all 20 and correctly chooses the native structures (

Dendritic spines may be tiny in volume, but are of major importance for neuroscience. They are the main receivers for excitatory synaptic connections, and their constant changes in number and in shape reflect the dynamic connectivity of the brain. Two-photon microscopy allows following the fate of individual spines in brain slice preparations and in live animals. The diffraction-limited and non-isotropic resolution of this technique, however, makes detection of such tiny structures rather challenging, especially along the optical axis (z-direction). Here we present a novel spine detection algorithm based on a statistical dendrite intensity model and a corresponding spine probability model. To quantify the fidelity of spine detection, we generated correlative datasets: Following two-photon imaging of live pyramidal cell den- drites, we used serial block-face scanning electron microscopy (SBEM) to reconstruct dendritic ultrastruc- ture in 3D. Statistical models were trained on synthetic fluorescence images generated from SBEM datasets via point spread function (PSF) convolution. After the training period, we tested automatic spine detection on real two-photon datasets and compared the result to ground truth (correlative SBEM data). The performance of our algorithm allowed tracking changes in spine volume automatically over several hours. Using a second fluorescent protein targeted to the endoplasmic reticulum, we could analyze the motion of this organelle inside individual spines. Furthermore, we show that it is possible to distinguish activated spines from non-stimulated neighbors by detection of fluorescently labeled presynaptic vesicle clusters. These examples illustrate how automatic segmentation in 5D (x, y, z, t, k) allows us to investigate brain dynamics at the level of individual synaptic connections.

Background B-type natriuretic peptide (BNP) is valuable in diagnosing heart failure (HF), but its utility in obese patients is unknown. Studies have suggested a cut-point of BNP ≥100 pg/mL for the diagnosis of HF; however, there is an inverse relation between BNP levels and body mass index. We evaluated differential cut-points for BNP in diagnosing acute HF across body mass index levels to determine whether alternative cut-points can improve diagnosis. Methods The Breathing Not Properly Multinational Study was a 7-center, prospective study of 1586 patients who presented to the Emergency Department with acute dyspnea. B-type natriuretic peptide was measured on arrival. Height and weight data were available for 1368 participants. The clinical diagnosis of HF was adjudicated by 2 independent cardiologists who were blinded to BNP results. Results Heart failure was the final diagnosis in 46.1%. Mean BNP levels (pg/mL) in lean, overweight/obese, and severely/morbidly obese patients were 643, 462, and 247 for patients with acute HF, and 52, 35, and 25 in those without HF, respectively ( P Conclusions Body mass index influences the selection of cut-points for BNP in diagnosing acute HF. A lower cut-point (BNP ≥54 pg/mL) should be used in severely obese patients to preserve sensitivity. A higher cut-point in lean patients (BNP ≥170 pg/mL) could be used to increase specificity.

We examined the relation between B-type natriuretic peptide (BNP) levels and a history of stable angina pectoris and/or healed myocardial infarction in 1,240 patients who were evaluated in the emergency department for possible heart failure. In patients who had heart failure, there was no relation between BNP levels and previous stable angina pectoris and/or healed myocardial infarction. However, in patients who did not have heart failure, there was a relation between BNP levels and previous stable angina pectoris and/or healed myocardial infarction but no significant independent relation in multiple regression analysis.