bluuebunny/crossref_metadata_2025 huggingface dataset:
Scalable computation of high-order optimization queries
Authors: Brucato Matteo , Abouzied Azza , Meliou Alexandra
Published: January 2019

Constrained optimization problems are at the heart of significant applications in a broad range of domains, including finance, transportation, manufacturing, and healthcare. Modeling and solving these problems has relied on application-specific solutions, which are often complex, error-prone, and do not generalize. Our goal is to create a domain-independent, declarative approach, supported and powered by the system where the data relevant to these problems typically resides: the database. We present a complete system that supports
package queries
, a new query model that extends traditional database queries to handle complex constraints and preferences over answer sets, allowing the declarative specification and efficient evaluation of a significant class of constrained optimization problems---integer linear programs (ILP)---within a database.
Distributed strategies for computational sprints
Authors: Fan Songchun , Zahedi Seyed Majid , Lee Benjamin C.
Published: January 2019

Computational sprinting is a class of mechanisms that boost performance but dissipate additional power. We describe a sprinting architecture in which many, independent chip multiprocessors share a power supply and sprints are constrained by the chips' thermal limits and the rack's power limits. Moreover, we present the computational sprinting game, a multi-agent perspective on managing sprints. Strategic agents decide whether to sprint based on application phases and system conditions. The game produces an equilibrium that improves task throughput for data analytics workloads by 4--6x over prior greedy heuristics and performs within 90% of an upper bound on throughput from a globally optimized policy.
The october 2018 issue
Authors: Bonaventure Olivier
Published: January 2019

SIGCOMM'18 was held in Hungary and the participants were pleased with both the technical program and the social interactions with all the members of the community. During her keynote on
Networks Capable of Change,
Jennifer Rexford mentioned two papers published in CCR that have had an important impact on our community :
OpenFlow: enabling innovation in campus networks and P4: programming protocol-independent packet processors.
These two editorial notes paved the way for Software-Defined Networks and then programmable switches. They are a good illustration of the benefits of having a venue like CCR that is open to other types of papers than the scientific papers that usually appear in our conferences and workshops.
SIGCSE top ten symposium papers of all time award
Authors: Decker Adrienne , Weiss Mark Allen
Published: January 2019

Following approval by the ACM SIG Governing Board and then the ACM Awards Committee, the SIGCSE Board is pleased to announce the creation of an ACM approved SIG award to commemorate the 50th SIGCSE Technical Symposium to be held in Minneapolis, MN February 27-March 1, 2019.
Postpartum Depression: Pathophysiology, Treatment, and Emerging Therapeutics
Authors: Stewart Donna E. , Vigod Simone N.
Published: January 2019

Postpartum depression (PPD) is common, disabling, and treatable. The strongest risk factor is a history of mood or anxiety disorder, especially having active symptoms during pregnancy. As PPD is one of the most common complications of childbirth, it is vital to identify best treatments for optimal maternal, infant, and family outcomes. New understanding of PPD pathophysiology and emerging therapeutics offer the potential for new ways to add to current medications, somatic treatments, and evidence-based psychotherapy. The benefits and potential harms of treatment, including during breastfeeding, are presented.
Progress in Understanding and Treating Idiopathic Pulmonary Fibrosis
Authors: Kropski Jonathan A. , Blackwell Timothy S.
Published: January 2019

This is a time of substantial progress in the evaluation and care of patients with idiopathic pulmonary fibrosis (IPF). In addition to the approval and widespread availability of the first IPF-specific therapies, there have been improvements in imaging interpretation and lung biopsy methods to enable more expeditious and more accurate diagnosis. Recent advances in identifying genetic factors that underlie susceptibility to IPF and affect prognosis have raised the possibility of personalized therapeutic approaches in the future. Further, evolving work is elucidating novel mechanisms influencing epithelial, mesenchymal, and inflammatory cell responses during the injury-repair process, thus advancing understanding of disease pathogenesis. As analytic approaches mature, the field is now poised to harness the power of rapidly advancing “omics” technologies to further accelerate progress.
Harnessing Tumor Mutations for Truly Individualized Cancer Vaccines
Authors: Vormehr Mathias , Türeci Özlem , Sahin Ugur
Published: January 2019

T cells are key effectors of anticancer immunity. They are capable of distinguishing tumor cells from normal ones by recognizing major histocompatibility complex–bound cancer-specific peptides. Accumulating evidence suggests that peptides associated with T cell–mediated tumor rejection arise predominantly from somatically mutated proteins and are unique to every patient's tumor. Knowledge of an individual's cancer mutanome (the entirety of cancer mutations) allows harnessing this enormous tumor cell–specific repertoire of highly immunogenic antigens for individualized cancer vaccines. This review outlines the preclinical and clinical state of individualized cancer vaccine development and the challenges ahead.
DNA Methylation and Susceptibility to Autism Spectrum Disorder
Authors: Tremblay Martine W. , Jiang Yong-hui
Published: January 2019

The prevalence of autism spectrum disorder (ASD) has been increasing steadily over the last 20 years; however, the molecular basis for the majority of ASD cases remains unknown. Recent advances in next-generation sequencing and detection of DNA modifications have made methylation-dependent regulation of transcription an attractive hypothesis for being a causative factor in ASD etiology. Evidence for abnormal DNA methylation in ASD can be seen on multiple levels, from genetic mutations in epigenetic machinery to loci-specific and genome-wide changes in DNA methylation. Epimutations in DNA methylation can be acquired throughout life, as global DNA methylation reprogramming is dynamic during embryonic development and the early postnatal period that corresponds to the peak time of synaptogenesis. However, technical advances and causative evidence still need to be established before abnormal DNA methylation and ASD can be confidently associated.
Abbreviated Magnetic Resonance Imaging (MRI) for Breast Cancer Screening: Rationale, Concept, and Transfer to Clinical Practice
Authors: Kuhl Christiane K.
Published: January 2019

Given the increasing understanding of cancer as a heterogeneous group of diseases, detection methods should offer a sensitivity profile that ensures perfect sensitivity for biologically important cancers while screening out self-limiting pseudocancers. However, mammographic screening is biased toward detection of ductal carcinoma in situ and slowly growing cancers—and thus frequently fails to detect biologically aggressive cancers. This explains the persistently high rates of interval cancers and high rates of breast cancer mortality observed in spite of decades of mammographic screening. Magnetic resonance imaging (MRI), in contrast, has a sensitivity profile that matches clinical needs. Conventional MRI is not suitable for population-wide screening due to high cost, limited tolerability, and lack of availability. We introduced abbreviated MRI in 2014. Abbreviated MRI will change the way MRI is used in clinical medicine. This article describes the rationale to use MRI in general, and abbreviated MRI in particular, for breast cancer screening.
Remember to breathe: teaching respiratory physiology in a clinical context using simulation
Authors: Bintley Helen L. , Bell Alexander , Ashworth Rachel
Published: January 2019

Evidence shows that biomedical knowledge is more effectively taught within the medical curriculum by teaching in context, to facilitate learning transfer. The purpose of the present study was to evaluate the effect of combining high-technology simulation and physiology teaching on medical student learning and experience. First-year medical students received respiratory physiology teaching in the form of lectures, problem-based learning, and practical sessions. These students were then given the opportunity to apply their knowledge and problem solve using respiratory-related clinical case scenarios in simulated patients. Student understanding was assessed using a short quiz performed immediately before and after the session. Results revealed that the session significantly improved the mean score on tests (6.97 ± 0.29 vs. 8.22 ± 0.19, P < 0.001). Student evaluation was collected in focus groups, and recurring concepts were extracted from the data. Students reported that the sessions helped to bridge the gap between theory and practice, which aided their learning. In addition, this teaching methodology (simulation) was reportedly patient centered and added to the realism of the simulated scenario, with students stating that this teaching improved their confidence with managing real patients and clinical uncertainty. Simulation has been used extensively to teach clinical skills; however, research regarding its potential for teaching biomedical science within a clinical context is limited. Our study shows that combining high-technology simulation and physiology teaching contributed to an immediate improvement in medical student knowledge and enhanced their ability to make connections between theoretical knowledge and the world of practice.
Numerical and Experimental Analysis of the Dynamic Behavior of Piezoelectric Stiffened Composite Plates Subjected to Airflow
Authors: Chung Nguyen Thai , Thuy Nguyen Ngoc , Thu Duong Thi Ngoc , Chau Le Hai
Published: January 2019

In this paper, the authors present results on dynamic behavior analysis of the stiffened composite plate with piezoelectric patches under airflow by finite element method and experimental study. The first‐order shear deformation plate theory and nine‐noded isoparametric piezoelectric laminated plate finite element with five elastic degrees of freedom at each node and one electric degree of freedom per element per piezoelectric layer were used in the dynamic analysis of plates by finite element method. The modern equipment was used in the dynamic behaviors analysis of plates subjected to airflow load by experimental method. In this study, the results of the theoretical method have been compared with experimental studies.
Effects of Multihollow Surface Dielectric Barrier Discharge Plasma on Chemical and Antioxidant Properties of Peanut
Authors: Gebremical Gebremedhin Gebremariam , Emire Shimelis Admassu , Berhanu Tarekegn
Published: January 2019

An experiment was conducted to investigate the effects of atmospheric pressure plasma generated by multihollow surface dielectric barrier discharge on chemical and antioxidant properties of peanut. Multihollow surface dielectric barrier discharge is a novel plasma device applicable in food industry applications due to the capacity of the generated plasma to treat the surface of food without changing the quality. Peanut seeds were exposed to the multihollow plasma for different plasma power (10–40 W), air flow rate (0.5–20 l/min), and time (1–15 min). The fatty acid profile, peroxide value, acid value, moisture content, total polyphenols, and antioxidant activity were evaluated during cold plasma treatment. The result revealed that, due to the variation plasma power, treatment time and air flow rate caused a decrease in unsaturated fatty acid and moisture content and increased saturated fatty acids, peroxide value, acid value, and total polyphenols of the peanut.
Electronic Structural and Optical Properties of Multilayer Blue Phosphorus: A First-Principle Study
Authors: Li Bing , Ren Ceng-Ceng , Zhang Shu-Feng , Ji Wei-Xiao , Zhang Chang-Wen , Li Ping , Wang Pei-Ji
Published: January 2019

Using the density functional theory, we systematically calculated the stability, electronic, and optical properties of monolayer and multilayer blue phosphorus. The results show the structures are all dynamically stable, and the gaps decrease with an increase of the number of layers. An unexpected transformation from indirect to direct band gaps is also observed as the tensile strain increases. In addition, the optical properties indicate the optical absorption peak of the material is in the ultraviolet region.
Real-World Treatment Patterns, Outcomes, and Healthcare Resource Utilization in Relapsed or Refractory Multiple Myeloma: Evidence from a Medical Record Review in France
Authors: Lin Huamao Mark , Davis Keith L. , Kaye James A. , Luptakova Katarina , Nagar Saurabh P. , Mohty Mohamad
Published: January 2019

Background. Limited data are available from real-world practices in Europe describing prevailing treatment patterns and outcomes in relapsed/refractory multiple myeloma (RRMM), particularly by cytogenetic risk. Methods. A retrospective medical record review was conducted in 200 RRMM patients in France. From first relapse, patients were assessed on second-/third-line treatments, progression-free survival (PFS), overall survival (OS), and healthcare utilization. Results. Fifty-five high risk and 113 standard risk patients were identified. Overall, 192 patients (96%) received second-line therapy after relapse. Lenalidomide-based regimens were most common (>50%) in second line. Hospitalization incidence in high risk patients was approximately twice that of standard risk patients. From Kaplan-Meier estimation, median (95% CI) second-line PFS was 21.4 (17.5, 25.0) months (by high versus standard risk: 10.6 [6.4, 17.0] versus 28.7 [22.1, 37.3] months). Among second-line recipients, 47.4% were deceased at data collection. Median second-line OS was 59.4 (38.8, NE) months (by high versus standard risk: 36.5 [17.4, 50.6] versus 73.6 [66.5, NE] months). Conclusions. The prognostic importance of cytogenetic risk in RRMM was apparent, whereby high (versus standard) risk patients had decidedly shorter PFS and OS. Frequent hospitalizations indicated potentially high costs associated with RRMM, particularly for high risk patients. These findings may inform economic evaluations of RRMM therapies.
Automatic Segmentation of Ulna and Radius in Forearm Radiographs
Authors: Gou Xiaofang , Rao Yuming , Feng Xiuxia , Yun Zhaoqiang , Yang Wei
Published: January 2019

Automatic segmentation of ulna and radius (UR) in forearm radiographs is a necessary step for single X-ray absorptiometry bone mineral density measurement and diagnosis of osteoporosis. Accurate and robust segmentation of UR is difficult, given the variation in forearms between patients and the nonuniformity intensity in forearm radiographs. In this work, we proposed a practical automatic UR segmentation method through the dynamic programming (DP) algorithm to trace UR contours. Four seed points along four UR diaphysis edges are automatically located in the preprocessed radiographs. Then, the minimum cost paths in a cost map are traced from the seed points through the DP algorithm as UR edges and are merged as the UR contours. The proposed method is quantitatively evaluated using 37 forearm radiographs with manual segmentation results, including 22 normal-exposure and 15 low-exposure radiographs. The average Dice similarity coefficient of our method reached 0.945. The average mean absolute distance between the contours extracted by our method and a radiologist is only 5.04 pixels. The segmentation performance of our method between the normal- and low-exposure radiographs was insignificantly different. Our method was also validated on 105 forearm radiographs acquired under various imaging conditions from several hospitals. The results demonstrated that our method was fairly robust for forearm radiographs of various qualities.
Current Practice and Barriers to an Early Antimicrobial Conversion from Intravenous to Oral among Hospitalized Patients at Jimma University Specialized Hospital: Prospective Observational Study
Authors: Beyene Berha Alemseged , Kassie Gizat Molla
Published: January 2019

Objective. The aim of the present study was to explore the current practice and its barriers to an early antimicrobial conversion from intravenous (IV) to oral (PO) therapy among hospitalized patients.Method. Hospital based prospective observational study was conducted to assess the practice of an early antimicrobial IV to PO conversion and its barriers using medical chart and case-specific physicians’ interviews, respectively, from February to September, 2014. Patient charts and medication records were reviewed for appropriateness of IV to PO conversion program every 24hrs using a pretested data collection abstraction format. Independent samplest-test was used to compare the duration of therapy and time to clinical stability between converted and nonconverted patients. Two-tailed P values of < 0.05 were regarded as statistically significant.Results. One hundred forty-two patients were included in the study, of whom two-thirds (67.6%) of the patients were eligible for IV to PO antimicrobial conversion. However, only 20.9% of patients’ timely conversion was made. A shorter duration of IV therapy was recorded for converted (2.80±1.87) versus nonconverted patients (8.50±6.32), (P=0.009). The most important barriers of not converting IV to PO in clinically stable patients were presence of comorbidity; clinicians perceived that the patient should always complete IV course of antimicrobials as a standard practice.Conclusion. Conversion from IV to PO antimicrobials was found to be unnecessarily delayed in a significant proportion of patients hospitalized with moderate to severe infection due to a range of different barriers. Addressing these issues has the potential to reduce inappropriate antimicrobial use and resistance.
Hydrogen Sulfide Oxidation: Adaptive Changes in Mitochondria of SW480 Colorectal Cancer Cells upon Exposure to Hypoxia
Authors: Malagrinò Francesca , Zuhra Karim , Mascolo Ludovica , Mastronicola Daniela , Vicente João B. , Forte Elena , Giuffrè Alessandro
Published: January 2019

Hydrogen sulfide (H2S), a known inhibitor of cytochrome c oxidase (CcOX), plays a key signaling role in human (patho)physiology. H2S is synthesized endogenously and mainly metabolized by a mitochondrial sulfide-oxidizing pathway including sulfide:quinone oxidoreductase (SQR), whereby H2S-derived electrons are injected into the respiratory chain stimulating O2 consumption and ATP synthesis. Under hypoxic conditions, H2S has higher stability and is synthesized at higher levels with protective effects for the cell. Herein, working on SW480 colon cancer cells, we evaluated the effect of hypoxia on the ability of cells to metabolize H2S. The sulfide-oxidizing activity was assessed by high-resolution respirometry, measuring the stimulatory effect of sulfide on rotenone-inhibited cell respiration in the absence or presence of antimycin A. Compared to cells grown under normoxic conditions (air O2), cells exposed for 24 h to hypoxia (1% O2) displayed a 1.3-fold reduction in maximal sulfide-oxidizing activity and 2.7-fold lower basal O2 respiration. Based on citrate synthase activity assays, mitochondria of hypoxia-treated cells were 1.8-fold less abundant and displayed 1.4-fold higher maximal sulfide-oxidizing activity and 2.6-fold enrichment in SQR as evaluated by immunoblotting. We speculate that under hypoxic conditions mitochondria undergo these adaptive changes to protect cell respiration from H2S poisoning.
Effect of Participation with Accompanying Household Member in the Complete Health Improvement Program in Appalachia
Authors: Kotekal Dhatri , Worley Melanie , Patel Hemal , Jensen Laura , Dogbey Godwin Y. , Drozek David
Published: January 2019

Intensive therapeutic lifestyle modification programs, such as the Complete Health Improvement Program (CHIP), reduce cardiovascular disease (CVD) risk factors. However, there are little data on how participation in CHIP with a household member can affect CVD biomarkers. This study focuses on the benefit of joint participation of household members in CHIP in order to have a better outcome in improving CVD risk factors compared with lone or individual participation. Data from 20 CHIP classes offered from 2011 to 2015 in Athens, Ohio, where each class was conducted over 2-4 months, consisting of 16-18 sessions, were collected. Body mass index (BMI), blood pressure, fasting glucose, and lipid profiles were measured before and near the completion of each class. A statistically significant greater reduction in BMI (p = 0.003) in those who attended with a household member compared to those who attended as individuals was found. CHIP has some effect on various CVD risk factors for those who attend intensive therapeutic lifestyle modification programs with an accompanying household member. Hence, encouragement of participation with a family member or a “buddy” may be prudent, especially if weight reduction is a key program participation goal. Further evaluation of the “buddy effect” involving both of those residing in the same household and those who do not but nevertheless provide mutual support is warranted.
Pomalidomide Alters Pancreatic Macrophage Populations to Generate an Immune-Responsive Environment at Precancerous and Cancerous Lesions
Authors: Bastea Ligia I. , Liou Geou-Yarh , Pandey Veethika , Fleming Alicia K. , von Roemeling Christina A. , Doeppler Heike , Li Zhimin , Qiu Yushi , Edenfield Brandy , Copland John A. , Tun Han W. , Storz Peter
Published: January 2019

During development of pancreatic cancer, alternatively activated macrophages contribute to fibrogenesis, pancreatic intraepithelial neoplasia (PanIN) lesion growth, and generation of an immunosuppressive environment. Here, we show that the immunomodulatory agent pomalidomide depletes pancreatic lesion areas of alternatively activated macrophage populations. Pomalidomide treatment resulted in downregulation of interferon regulatory factor 4, a transcription factor for M2 macrophage polarization. Pomalidomide-induced absence of alternatively activated macrophages led to a decrease in fibrosis at PanIN lesions and in syngeneic tumors; this was due to generation of an inflammatory, immune-responsive environment with increased expression of IL1α and presence of activated (IFNγ-positive) CD4+ and CD8+ T-cell populations. Our results indicate that pomalidomide could be used to decrease fibrogenesis in pancreatic cancer and may be ideal as a combination treatment with chemotherapeutic drugs or other immunotherapies.

Significance:

These findings reveal new insights into how macrophage populations within the pancreatic cancer microenvironment can be modulated, providing the means to turn the microenvironment from immunosuppressive to immune-responsive.
Nod1 Imprints Inflammatory and Carcinogenic Responses toward the Gastric Pathogen Helicobacter pylori
Authors: Suarez Giovanni , Romero-Gallo Judith , Piazuelo Maria B. , Sierra Johanna C. , Delgado Alberto G. , Washington M. Kay , Shah Shailja C. , Wilson Keith T. , Peek Richard M.
Published: January 2019

Helicobacter pylori (H. pylori) is the strongest known risk for gastric cancer. The H. pylori cag type IV secretion system is an oncogenic locus that translocates peptidoglycan into host cells, where it is recognized by NOD1, an innate immune receptor. Beyond this, the role of NOD1 in H. pylori–induced cancer remains undefined. To address this knowledge gap, we infected two genetic models of Nod1 deficiency with the H. pylori cag+ strain PMSS1: C57BL/6 mice, which rarely develop cancer, and INS-GAS FVB/N mice, which commonly develop cancer. Infected C57BL/6Nod1–/− and INS-GASNod1−/− mice acutely developed more severe gastritis, and INS-GASNod1−/− mice developed gastric dysplasia more frequently compared with Nod1+/+ mice. Because Nod1 genotype status did not alter microbial phenotypes of in vivo–adapted H. pylori, we investigated host immunologic responses. H. pylori infection of Nod1−/− mice led to significantly increased gastric mucosal levels of Th1, Th17, and Th2 cytokines compared with Nod1 wild-type (WT) mice. To define the role of specific innate immune cells, we quantified cytokine secretion from H. pylori–infected primary gastric organoids generated from WT or Nod1−/− mice that were cocultured with or without WT or Nod1−/− macrophages. Infection increased cytokine production from gastric epithelial cells and macrophages and elevations were significantly increased with Nod1 deficiency. Furthermore, H. pylori infection altered the polarization status of Nod1−/− macrophages compared with Nod1+/+ macrophages. Collectively, these studies demonstrate that loss of Nod1 augments inflammatory and injury responses to H. pylori. Nod1 may exert its restrictive role by altering macrophage polarization, leading to immune evasion and microbial persistence.

Significance:

These findings suggest that manipulation of NOD1 may represent a novel strategy to prevent or treat pathologic outcomes induced by H. pylori infection.
Challenges with Novel Clinical Trial Designs: Master Protocols
Authors: Cecchini Michael , Rubin Eric H. , Blumenthal Gideon M. , Ayalew Kassa , Burris Howard A. , Russell-Einhorn Michele , Dillon Hildy , Lyerly H. Kim , Reaman Gregory H. , Boerner Scott , LoRusso Patricia M.
Published: January 2019

The 2018 Accelerating Anticancer Agent Development (AAADV) Workshop assembled a panel of experts for an in-depth discussion session to present “Challenges with Novel Clinical Trial Designs.” This panel offered assessments of the challenges faced by industry, the FDA, investigators, institutional review boards, and patients. The panel focused on master protocols, which include umbrella trials, platform trials, and basket trials. Umbrella trials and platform trials share many commonalities, whereas basket trials are more distinct. Umbrella and platform trials are generally designed with multiple arms where patients of the same histology or other unifying characteristics are enrolled into different arms and multiple investigational agents are evaluated in a single protocol. In contrast, basket studies generally enroll patients with different tumor types based on the presence of a specific mutation or biomarker regardless of histology; these trials may include expansion cohorts. These novel designs offer the promise of expedited drug assessment and approval, but they also place new challenges on all the stakeholders involved in the drug development process. Only by identifying the challenges of these complex, innovative clinical trial designs and highlighting challenges from each perspective can we begin to address these challenges. The 2018 AAADV Workshop convened a panel of experts from relevant disciplines to highlight the challenges that are created by master protocols, and, where appropriate, offer strategies to address these challenges.
Effect of Verapamil on Kidney Function Using Radionuclide Imaging
Authors: Mustafa Seham , Elgazzar Abdelhamid H. , Kamal Nabil
Published: January 2019

Background and Objective: Calcium channel blockers (CCBs) are among the most widely used prescribed drugs for the treatment of cardiovascular diseases. The present study investigates the effect of verapamil, which is most commonly used as a CCB, on kidney function using radionuclide imaging. Methods: Ten New Zealand white rabbits were used in vitro (4) and in vivo (6) studies. Isometric tensions were recorded for isolated renal artery ring segments, while renographic studies were performed using Technetium-99m mercaptoacetyltriglycine and Gamma camera. Time to peak activity (Tmax) and time from peak to 50% activity (T1/2), were calculated from the renograms for control and treated rabbits with verapamil. Results: In vitro, verapamil shifted the curve of phenylephrine concentration-dependent contraction on renal artery to the right, and decrease the highest contraction by 30 ± 3%. In vivo, the average values of Tmax for control and treated rabbits were 2.8 ± 0.1 and 2.2 ± 0.2 min respectively. The T1/2 for control and treated rabbits were 4.7 ± 0.05 and 4.2 ± 0.08 min respectively. The differences were statistically significant: p < 0.05. There is 30 ± 4% decrease in the 2 values. This indicates that there is a rapid renal uptake of the tracer and clearance of the radioactivity after verapamil. Conclusion: Verapamil dilates the renal artery and accelerates both the Tmax and T1/2 in the renogram. It increases renal blood perfusion and protects kidney function and therefore improves its work. However, verapamil should not be used while performing renograms to avoid misleading results.
Non-Invasive Brain Stimulation in Dementia: A Complex Network Story
Authors: Pini Lorenzo , Manenti Rosa , Cotelli Maria , Pizzini Francesca B. , Frisoni Giovanni B. , Pievani Michela
Published: January 2019

Non-invasive brain stimulation (NIBS) is emerging as a promising rehabilitation tool for a number of neurodegenerative diseases. However, the therapeutic mechanisms of NIBS are not completely understood. In this review, we will summarize NIBS results in the context of brain imaging studies of functional connectivity and metabolites to gain insight into the possible mechanisms underlying recovery. We will briefly discuss how the clinical manifestations of common neurodegenerative disorders may be related with aberrant connectivity within large-scale neural networks. We will then focus on recent studies combining resting-state functional magnetic resonance imaging with NIBS to delineate how stimulation of different brain regions induce complex network modifications, both at the local and distal level. Moreover, we will review studies combining magnetic resonance spectroscopy and NIBS to investigate how microscale changes are related to modifications of large-scale networks. Finally, we will re-examine previous NIBS studies in dementia in light of this network perspective. A better understanding of NIBS impact on the functionality of large-scale brain networks may be useful to design beneficial treatments for neurodegenerative disorders.
Mauriac Syndrome: A Rare Hepatic Glycogenosis in Poorly Controlled Type 1 Diabetes
Authors: Patita Marta , Nunes Gonçalo , Alves de Matos António , Coelho Hélder , Fonseca Cristina , Fonseca Jorge
Published: January 2019

Background: Hepatic glycogenosis (HG) is a complication of poorly controlled type 1 diabetes mellitus (T1DM), characterized by glycogen accumulation in hepatocytes. Mauriac syndrome (MS) is a glycogenic hepatopathy, initially described in 1930, characterized by growth failure, delayed puberty, cushingoid appearance, hepatomegaly with abnormal liver enzymes, and hypercholesterolemia. HG is a condition with good prognosis and fast resolution after adequate glycemic control (although it has potential for relapse), with no case of evolution to end-stage liver disease described. Case: We describe a 26-year-old female, with T1DM complicated by severe retinopathy. The patient maintained poor glycemic control since childhood, presenting glycated hemoglobin persistently higher than 10% and recurrent episodes of ketoacidosis. In adolescence, she developed hepatomegaly and fluctuating elevation of aminotransferases and triglycerides. A small, nonrepresentative hepatic biopsy suggested macrovacuolar steatosis and mild fibrosis. After 15 years of diabetes, the patient was referred for gastroenterology clinic due to chronic diarrhea and exuberant hepatomegaly. Laboratory showed persistent elevation of aminotransferases and triglycerides. Bilirubin, iron metabolism, and coagulation were normal; viral serologies and autoimmune study were negative. Upper endoscopy, ileocolonoscopy, and enteroscopy presented no lesions. Abdominal magnetic resonance imaging displayed massive hepatomegaly. Liver biopsy was repeated showing marked nuclear glycogenization, mild steatosis, and no fibrosis; electron microscopy revealed very large deposits of glycogen and pleomorphic mitochondria with an unusually dense matrix, described for the first time in this entity. The diagnosis of MS variant and diarrhea due to autonomic neuropathy were assumed. Conclusion: Currently, HG is a well-recognized disease that occurs at any age and can be present without the full spectrum of features initially described for MS. In the era of insulin therapy, this entity represents a rare complication, caused by low therapeutic compliance.
Biosimilar Trastuzumab in Clinical Trials: Differences or Not?
Authors: Thill Marc
Published: January 2019

In the last decade, cancer therapies have increasingly taken the form of combination treatments in which biologic agents play a crucial role. In breast cancer, the treatment strategy is adjusted to intrinsic subtypes such as human epidermal growth factor receptor-2(HER2)-positive. With the introduction of trastuzumab, a monoclonal antibody against HER2, survival has significantly improved in early and metastatic breast cancer. Trastuzumab's patent has now expired and biosimilars are moving into the market. Several clinical trials have led to the approval of 5 different biosimilar trastuzumabs. Results proved similarity between the proposed biosimilar and the reference product without significant differences in efficacy and safety, although follow-up has been short. However, the shorter drug development process with its goal of showing similarity rather than patient benefit uses surrogate endpoints such as pathologic complete response and overall response rate, not survival endpoints in terms of the ‘gold standard' in evaluating cancer therapies. The aim of this article is to give insight into how to plan and perform a clinical trial to prove equivalence between a biosimilar trastuzumab and its reference product and to elucidate the setup and outcome of published clinical trials.
Han, Byung-Chul. Sociedade do cansaço
Authors: Corbanezi Elton Rogerio
Published: January 2019

Resenha do livro de Byung-Chul Han, Sociedade do cansaço. Petrópolis, Vozes, 2017
Estática e dinâmica do capitalismo tardio na teoria crítica
Authors: Vasconcellos Caio , Puzone Vladimir
Published: January 2019

O objetivo deste artigo é uma interpretação da teoria social de Theodor Adorno e Herbert Marcuse. Para tanto, reconstruímos aspectos de seus diagnósticos de época em dois momentos históricos, o nazismo e o pós-guerra europeu. Apesar de suas particularidades, Adorno e Marcuse partilham a pretensão de compreender a dialética entre aspectos dinâmicos e certa invariância estática, que caracteriza as sociedades burguesas. O desenvolvimento da teoria crítica deve ser entendido, então, como o exame dos traços permanentes da sociabilidade capitalista ao mesmo tempo em que esta se transforma no curso da história. Como conclusão, apresentamos uma breve reflexão sobre a atualidade da teoria crítica para interpretar fenômenos sociais contemporâneos.
Unfettered capitalism: on rackets, cronies and mafiosi
Authors: Klein Stefan , Pagliuso Regatieri Ricardo
Published: January 2019

In the early 1940s, critical theory borrowed the term racket from the urban crime underworld and applied it to criticize monopoly capitalism, which was regarded as a constellation ruled in a mafia-like manner. Decades later, after the experiences of the welfare state in the core counties and catch-up modernizations in the periphery, concepts such as cronyism and mafioso state were proposed. What these three approaches have in common is the fact that they highlight the mafia-like nature of capitalism and do so for different social and historical contexts. This article suggests that rackets, cronies or mafias have more recently, and increasingly, become structural elements of capitalism, as was first envisaged by critical theory during World War ii. We combine theoretical critique and insights with references to empirical expressions of this phenomenon to shed light on this development.
O ensino do modelo clássico de regressão linear por meio de simulação de Monte Carlo
Authors: Pagliarussi Marcelo Sanches
Published: January 2019

Este trabalho apresenta um conjunto de estudos de Monte Carlo, usando softwares de planilha eletrônica, que pode ser usado para facilitar a aprendizagem do conceito de distribuição amostral em um contexto de aprendizagem do modelo clássico de regressão linear. A partir da construção de duas planilhas básicas, uma para regressão simples e outra para regressão múltipla, outras planilhas podem ser facilmente obtidas com pequenas alterações no processo gerador de dados. As alterações que podem ser introduzidas incluem variações no tamanho das amostras e em diversas características do termo de erro, como sua variância, valor médio e função de probabilidade. Também podem ser introduzidas correlações entre os regressores no modelo de regressão múltipla. Um professor de econometria introdutória pode usar o conjunto de planilhas de modo a obter figuras e tabelas que facilitam a visualização do desempenho dos estimadores de mínimos quadrados ordinários para diferentes situações. Deste modo, os estudantes podem compreender na prática como as violações nas premissas do modelo clássico de regressão linear afetam om desempenho dos estimadores de mínimos quadrados ordinários e dos testes de hipóteses usualmente empregados no contexto da análise de regressão. As violações trabalhadas no presente trabalho incluem heterocedasticidade, omissão de variáveis relevantes, erros não normais e multicolinearidade.
"O poeta", de Mikhail Iúrevitch Lérmontov
Authors: Pinto Pedro Augusto , Lérmontov Mikhail Iúrevitch
Published: January 2019

Apesar de muito pouco conhecido no Brasil, Lérmontov é considerado na Rússia e no mundo um dos autores russos mais importantes do século XIX, tendo influenciado diretamente, apesar de sua curtíssima vida, figuras do porte de Dostoiévski, Tolstói e Maiakóvski. O poema que aqui apresentamos em uma tradução poética, absolutamente inédito na língua portuguesa, introduz alguns temas e tópicos essenciais à sua obra, como a paisagem do Cáucaso, a nostalgia romântica e condenação moral de seu próprio tempo, constituindo uma crítica singular à figura do poeta romântico nos próprios termos do Romantismo.
Sugarcane cutting work, risks, and health effects
Authors: Leite Marceli Rocha , Zanetta Dirce Maria Trevisan , Trevisan Iara Buriola , Burdmann Emmanuel de Almeida , Santos Ubiratan de Paula
Published: January 2019

Describe the main work risks for sugarcane cutters and their effects on workers’ health. METHODS: Critical review of articles, with bibliographic research carried out in the PubMed, SciELO Medline, and Lilacs databases. The following keywords were used: sugarcane workers, sugarcane cutters, sugarcane harvesting, cortadores de cana-de-açúcar, and colheita de canade-açúcar. The inclusion criteria were articles published between January 1997 and June 2017, which evaluated working conditions and health effects on sugarcane cutters. Those that did not deal with the work impact of cutting burned and unburnt sugarcane in the cutter’s health were excluded. The final group of manuscripts was selected by the lead author of this study and reviewed by a co-author. Disagreements were resolved by consensus using the predefined inclusion and exclusion criteria and, where necessary, the final decision was made by consulting a third co-author. RESULTS: From the 89 articles found, 52 met the selection criteria and were evaluated. Studies have shown that cutters work under conditions of physical and mental overload, thermal overload, exposure to pollutants, and are subject to accidents. The main effects observed were respiratory, cardiovascular, renal, musculoskeletal, heat stress, dehydration, genotoxic, and those due to accidents. CONCLUSIONS: Work on the manual cutting of sugarcane, especially of burned sugarcane, exposes workers to various risks, with different health impacts. Risk reduction for exposure to pollution and thermal and physical overload is required as a measure to preserve the health of the worker.
Sampling plan in health surveys, city of São Paulo, Brazil, 2015
Authors: Alves Maria Cecilia Goi Porto , Escuder Maria Mercedes Loureiro , Goldbaum Moises , Barros Marilisa Berti de Azevedo , Fisberg Regina Mara
Published: January 2019

OBJECTIVE: To evaluate the sampling plan of the Health Survey of the City of São Paulo (ISA-Capital 2015) regarding the accuracy of estimates and the conformation of domains of study by the Health Coordinations of the city of São Paulo, Brazil. METHODS: We have described the population, domains of study, and sampling procedures, including stratification, calculation of sample size, and random selection of sample units, of the Health Survey of the City of São Paulo, 2015. The estimates of proportions were analyzed in relation to precision using the coefficient of variation and the design effect. We considered suitable the coefficients below 30% at the regional level and 20% at the city level and the estimates of the design effect below 1.5. We considered suitable the strategy of establishing the Health Coordinations as domains after verifying that, within the coordinations, the estimates of proportions for the age and sex groups had the minimum acceptable precision. The estimated parameters were related to the subjects of use of services, morbidity, and self-assessment of health. RESULTS: A total of 150 census tracts were randomly selected, 30 in each Health Coordination, 5,469 households were randomly selected and visited, and 4,043 interviews were conducted. Of the 115 estimates made for the domains of study, 97.4% presented coefficients of variation below 30%, and 82.6% were below 20%. Of the 24 estimates made for the total of the city, 23 presented coefficient of variation below 20%. More than two-thirds of the estimates of the design effect were below 1.5, which was estimated in the sample size calculation, and the design effect was below 2.0 for 88%. CONCLUSIONS: The ISA-Capital 2015 sample generated estimates at the predicted levels of precision at both the city and regional levels. The decision to establish the regional health coordinations of the city of São Paulo as domains of study was adequate.
Active health Ombudsman service
Authors: Almeida Karlo Jozefo Quadros de , Roure Francis Nakle de , Bittencourt Roberto José , Santos Regina Maria Dias Buani dos , Bittencourt Fernanda Viana , Gottems Leila Bernarda Bernarda Donato , Amorim Fábio Ferreira
Published: January 2019

OBJECTIVE: To evaluate the active health Ombudsman service as an instrument to evaluate the quality of delivery and birth care in the Cegonha Network of the Federal District of Brazil. METHODS: This is a cross-sectional study of the telephone survey type carried out with 1,007 mothers with deliveries between October 15, 2013 and November 19, 2013 in the twelve public maternity hospitals that make up the Cegonha Network of the Federal District of Brazil. The instrument has 25 multiple choice or Likert scale questions, including sociodemographic data and acceptability evaluation in five domains: accessibility, relationship between the patient and health professionals, conditions of the structure of the service, information to the patient, and equity and opinion of the patient. We have studied qualitative or categorical variables according to the frequency and distribution of proportions. We have used the score transformed into a scale from zero to 100 for the analysis of the Likert-type scale questions. Results have been expressed as mean and standard deviation. RESULTS: Access to prenatal appointments was evaluated as good or excellent by 86.1% of the participants and laboratory tests was evaluated as good or excellent by 85.2% of them. The access to imaging tests was evaluations as good or excellent by 45.7% of the women; 79.5% of the interviewees had their delivery in the maternity hospital where they sought initial care and 18.3% received a home visit by a community health agent after discharge. Most women reported that newborns were placed skin-to-skin immediately after birth, 48.9% had a companion at the time of the delivery, 76.3% were advised about the first appointment of the newborn, and 94.8% were advised on breastfeeding in the maternity hospital. Regarding the evaluation of health professionals, 85.9% of the women considered reception and cordiality as good or excellent at the prenatal care and 94.8% considered it as good or excellent at the maternity hospital. CONCLUSIONS: The active health Ombudsman service has contributed to evaluate the quality of public management by allowing the incorporation of the perspective of users of the health service in the evaluation of the acceptability of the Cegonha Network in the Federal District of Brazil.
Prior Anticoagulation and Short‐ or Long‐Term Clinical Outcomes in Ischemic Stroke or Transient Ischemic Attack Patients With Nonvalvular Atrial Fibrillation
Authors: Tokunaga Keisuke , Koga Masatoshi , Itabashi Ryo , Yamagami Hiroshi , Todo Kenichi , Yoshimura Sohei , Kimura Kazumi , Sato Shoichiro , Terasaki Tadashi , Inoue Manabu , Shiokawa Yoshiaki , Takagi Masahito , Kamiyama Kenji , Tanaka Kanta , Takizawa Shunya , Shiozawa Masayuki , Okuda Satoshi , Okada Yasushi , Kameda Tomoaki , Nagakane Yoshinari , Hasegawa Yasuhiro , Shibuya Satoshi , Ito Yasuhiro , Matsuoka Hideki , Takamatsu Kazuhiro , Nishiyama Kazutoshi , Kario Kazuomi , Yagita Yoshiki , Fujita Kyohei , Ando Daisuke , Kumamoto Masaya , Arihiro Shoji , Toyoda Kazunori , Takasugi Junji , Higashida Kyoko , Sakamoto Yuki , Hirano Teruyuki , Suzuki Rieko , Nakagawara Jyoji , Homma Kazunari , Tanaka Eijirou , Akiyama Hisanao , Mochizuki Hiroshi , Nakashima Takahiro , Shibazaki Kensaku , Furui Eisuke , Maeda Koichiro , Endo Kaoru , Miyagi Tetsuya , Osaki Masato , Kobayashi Junpei , Okata Takuya , Takizawa Hotake , Matsuki Takayuki , Kinoshita Naoto , Matsubara Soichiro , Ide Toshihiro , Yoshimoto Takeshi , Kamimura Teppei , Kikuno Muneaki , Mizoguchi Tadataka , Sato Takeo , Nagatsuka Kazuyuki , Minematsu Kazuo
Published: January 2019

Background

We aimed to clarify associations between prior anticoagulation and short‐ or long‐term clinical outcomes in ischemic stroke or transient ischemic attack patients with nonvalvular atrial fibrillation.

Methods and Results

A total of 1189 ischemic stroke or transient ischemic attack patients with nonvalvular atrial fibrillation who were hospitalized within 7 days after onset were analyzed. Of these, 813 patients (68.4%) received no prior anticoagulation, 310 (26.1%) received prior warfarin treatment with an international normalized ratio (
INR
) <2 on admission, 28 (2.4%) received prior warfarin treatment with an
INR
≥2 on admission, and the remaining 38 (3.2%) received prior direct oral anticoagulant treatment. Prior warfarin treatment was associated with a lower risk of death or disability at 3 months compared with no prior anticoagulation (
INR
<2: adjusted odds ratio: 0.58; 95% CI, 0.42–0.81;
P
=0.001;
INR
≥2: adjusted odds ratio: 0.40; 95% CI, 0.16–0.97;
P
=0.043) but was not associated with a lower risk of death or disability at 2 years. Prior warfarin treatment with an
INR
≥2 on admission was associated with a higher risk of ischemic events within 2 years compared with no prior anticoagulation (adjusted hazard ratio: 2.94; 95% CI, 1.20–6.15;
P
=0.021).

Conclusions

Prior warfarin treatment was associated with a lower risk of death or disability at 3 months but was not associated with a lower risk of death or disability at 2 years in ischemic stroke or transient ischemic attack patients with nonvalvular atrial fibrillation. Prior warfarin treatment with an
INR
≥2 on admission was associated with a higher risk of ischemic events within 2 years.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
01581502.