bluuebunny/crossref_metadata_2025 huggingface dataset:
Exception Handling in Message-Based Integration Systems and Modeling Using BPMN
Authors: Ritter Daniel , Sosulski Jan
Published: August 2016

Enterprise Integration Patterns (EIP) are a collection of widely used patterns for integrating enterprise applications and business processes. These patterns represent a “de-facto” standard for design decisions when integrating enterprise applications. For the specification of integration scenarios, the patterns’ control and data flow syntax and semantics have been expressed in the Business Process Model and Notation (BPMN). However, exceptions during message processing are left for further studies. In previous work, we specified common technical, exceptional situations in integration systems and derive exception types, for which we define a compliant representation in BPMN, resulting in general patterns for exception handling and compensation. In addition to the patterns, the Exception Flow was introduced, evaluated syntactically and semantically for representative integration scenarios. In this work, we complement these contributions by extending the exception strategies and patterns, and by adding an evaluation of pattern-based compilation from BPMN-based integration descriptions to an open source integration runtime system.
BIOMECHANICAL EFFECT OF DIFFERENT LAG SCREW LENGTHS WITH DIFFERENT BARREL LENGTHS IN DYNAMIC HIP SCREW SYSTEM: A FINITE ELEMENT ANALYSIS STUDY
Authors: TZENG CHUNG-YUH , HUANG KUI-CHUO , WU YUN-CHE , CHANG CHU-LING , LEE KUAN-RONG , SU KUO-CHIH
Published: August 2016

The dynamic hip screw (DHS) system is commonly used to treat intertrochanteric fracture of the hip joint. Breakage of the lag screw was noted in clinical practice and the length of lag screw as well as the length of the side plate in the DHS system appeared to play a role in the risk of breakage. Thus, the aim of this study was to investigate the biomechanical effect of different lag screw lengths and barrel plate lengths in the DHS implant system by finite element analysis (FEA). Four FEA simulation models were created according to different lengths of lag screw (79[Formula: see text]mm and 63[Formula: see text]mm) and different lengths of barrel side plate (43[Formula: see text]mm and 37[Formula: see text]mm). The von Mises stress was used as the observation indicator. The results showed that the maximum tensile stress on the long lag screw was slightly greater than that of the shorter lag screw. Use of a shorter barrel side plate may also cause high stress between the lag screw and the barrel side plate. This finding provides biomechanical reference data that may be of value to orthopedic surgeons with respect to choice of implant size and length in the treatment of intertrochanteric fracture with a DHS system to prevent complications such as implant failure caused by broken lag screws.
Substituted tetraphenyl porphyrin catalyzed oxidative N-dealkylation of tertiary amine using molecular oxygen
Authors: Agarwal Dau. D. , Bhat Daisy
Published: August 2016

Oxidative N-dealkylation of NN-dimethylaniline catalyzed by substituted tetraaryl porphyrin complexes of iron and manganese with molecular oxygen, gave a mixture of dealkylated, monooxygenated and dimerised compounds as products. Presence of substituents on the catalyst effects nature and yield of products formed. One electron transfer route [E T) predominated over H-atom abstraction [HAT] in most of the reactions.
Asymmetric epoxidation of alkenes catalyzed by novel chiral porphyrin metal complexes
Authors: Sakthipriya Pachiannan , Ananthi Nallamuthu
Published: August 2016

Novel chiral porphyrin ligands were synthesized from four different chiral aldehydes. In situ transition metal complexes of these novel chiral porphyrin ligands were found to catalyze asymmetric epoxidation reaction of styrene possessing various substituents. The chiral epoxides were formed in excellent yield and ee.
Effect of bulky meso-substituents on photoinduced twisted intramolecular charge transfer processes in meso-diarylamino subporphyrins
Authors: Lee Seung-Kyu , Kim Jun Oh , Shimizu Daiki , Osuka Atsuhiro , Kim Dongho
Published: August 2016

Photoexcited-state dynamics of meso-diarylamino subporphyrins 4–6 in cyclohexane, toluene, and acetonitrile have been studied by steady-state/time-resolved absorption and fluorescence experiments and quantum calculations. While 4 emits fluorescence from the locally excited state regardless of solvent polarity, the fluorescence of 5 and 6 are solvent-polarity dependent. The observed efficient fluorescent quenching of 5 and 6 has been ascribed to twisted intramolecular charge transfer (TICT), in which the two N–C[Formula: see text] bonds in 5 and the C[Formula: see text]–N bond in 6 are twisted to facilitate the intramolecular electron transfer. In 2-methyltetrahydrofuran (2-MeTHF), the fluorescence of 5 and 6 are both almost completely quenched at 297 K, but restored at 77 K (below the melting point of 2-MeTHF) because of the frozen molecular twisting. Furthermore, electrochemical studies also revealed the charge separation processes of 4–6 are thermally unfavorable in nonpolar toluene and cyclohexane unless their structures change contrary to the observed efficient fluorescence quenching. These observations support the TICT mechanism. In addition, the formation of TICT state is affected by steric effect as the size of the meso-substituents increases.
The lattice of primary ideals of orders in quadratic number fields
Authors: Peruginelli Giulio , Zanardo Paolo
Published: August 2016

Let [Formula: see text] be an order in a quadratic number field [Formula: see text] with ring of integers [Formula: see text], such that the conductor [Formula: see text] is a prime ideal of [Formula: see text], where [Formula: see text] is a prime. We give a complete description of the [Formula: see text]-primary ideals of [Formula: see text]. They form a lattice with a particular structure by layers; the first layer, which is the core of the lattice, consists of those [Formula: see text]-primary ideals not contained in [Formula: see text]. We get three different cases, according to whether the prime number [Formula: see text] is split, inert or ramified in [Formula: see text].
The evolution of BEAGLE
Authors: Forsyth Richard
Published: August 2016

EuroGP 2016 co-chair

James McDermott

describes the EvoStar opening keynote talk given by

Dr Richard Forsyth

. An early GP pioneer, Richard Forsyth's talk covered some interesting interesting historical pathways and included a description of his BEAGLE system developed in 1981.
Preterm infant gut microbiota affects intestinal epithelial development in a humanized microbiome gnotobiotic mouse model
Authors: Yu Yueyue , Lu Lei , Sun Jun , Petrof Elaine O. , Claud Erika C.
Published: August 2016

Development of the infant small intestine is influenced by bacterial colonization. To promote establishment of optimal microbial communities in preterm infants, knowledge of the beneficial functions of the early gut microbiota on intestinal development is needed. The purpose of this study was to investigate the impact of early preterm infant microbiota on host gut development using a gnotobiotic mouse model. Histological assessment of intestinal development was performed. The differentiation of four epithelial cell lineages (enterocytes, goblet cells, Paneth cells, enteroendocrine cells) and tight junction (TJ) formation was examined. Using weight gain as a surrogate marker for health, we found that early microbiota from a preterm infant with normal weight gain (MPI-H) induced increased villus height and crypt depth, increased cell proliferation, increased numbers of goblet cells and Paneth cells, and enhanced TJs compared with the changes induced by early microbiota from a poor weight gain preterm infant (MPI-L). Laser capture microdissection (LCM) plus qRT-PCR further revealed, in MPI-H mice, a higher expression of stem cell marker Lgr5 and Paneth cell markers Lyz1 and Cryptdin5 in crypt populations, along with higher expression of the goblet cell and mature enterocyte marker Muc3 in villus populations. In contrast, MPI-L microbiota failed to induce the aforementioned changes and presented intestinal characteristics comparable to a germ-free host. Our data demonstrate that microbial communities have differential effects on intestinal development. Future studies to identify pioneer settlers in neonatal microbial communities necessary to induce maturation may provide new insights for preterm infant microbial ecosystem therapeutics.
Hyperpolarization-activated cyclic nucleotide-gated channels in peripheral diaphragmatic lymphatics
Authors: Negrini Daniela , Marcozzi Cristiana , Solari Eleonora , Bossi Elena , Cinquetti Raffaella , Reguzzoni Marcella , Moriondo Andrea
Published: August 2016

Diaphragmatic lymphatic function is mainly sustained by pressure changes in the tissue and serosal cavities during cardiorespiratory cycles. The most peripheral diaphragmatic lymphatics are equipped with muscle cells (LMCs), which exhibit spontaneous contraction, whose molecular machinery is still undetermined. Hypothesizing that spontaneous contraction might involve hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in lymphatic LMCs, diaphragmatic specimens, including spontaneously contracting lymphatics, were excised from 33 anesthetized rats, moved to a perfusion chamber containing HEPES-Tyrode's solution, and treated with HCN channels inhibitors cesium chloride (CsCl), ivabradine, and ZD-7288. Compared with control, exposure to 10 mM CsCl reduced (−65%, n = 13, P < 0.01) the contraction frequency (FL) and increased end-diastolic diameter (DL-d, +7.3%, P < 0.01) without changes in end-systolic diameter (DL-s). Ivabradine (300 μM) abolished contraction and increased DL-d (−14%, n = 10, P < 0.01) or caused an incomplete inhibition of FL ( n = 3, P < 0.01), leaving DL-d and DL-s unaltered. ZD-7288 (200 μM) completely ( n = 12, P < 0.01) abolished FL, while DL-d decreased to 90.9 ± 2.7% of control. HCN gene expression and immunostaining confirmed the presence of HCN1-4 channel isoforms, likely arranged in different configurations, in LMCs. Hence, all together, data suggest that HCN channels might play an important role in affecting contraction frequency of LMCs.
Adaptation of the cerebrocortical circulation to carotid artery occlusion involves blood flow redistribution between cortical regions and is independent of eNOS
Authors: Polycarpou Andreas , Hricisák László , Iring András , Safar Daniel , Ruisanchez Éva , Horváth Béla , Sándor Péter , Benyó Zoltán
Published: August 2016

Cerebral circulation is secured by feed-forward and feed-back control pathways to maintain and eventually reestablish the optimal oxygen and nutrient supply of neurons in case of disturbances of the cardiovascular system. Using the high temporal and spatial resolution of laser-speckle imaging we aimed to analyze the pattern of cerebrocortical blood flow (CoBF) changes after unilateral (left) carotid artery occlusion (CAO) in anesthetized mice to evaluate the contribution of macrovascular (circle of Willis) vs. pial collateral vessels as well as that of endothelial nitric oxide synthase (eNOS) to the cerebrovascular adaptation to CAO. In wild-type mice CoBF reduction in the left temporal cortex started immediately after CAO, reaching its maximum (−26%) at 5–10 s. Thereafter, CoBF recovered close to the preocclusion level within 30 s indicating the activation of feed-back pathway(s). Interestingly, the frontoparietal cerebrocortical regions also showed CoBF reduction in the left (−17–19%) but not in the right hemisphere, although these brain areas receive their blood supply from the common azygos anterior cerebral artery in mice. In eNOS-deficient animals the acute CoBF reduction after CAO was unaltered, and the recovery was even accelerated compared with controls. These results indicate that 1) the Willis circle alone is not sufficient to provide an immediate compensation for the loss of one carotid artery, 2) pial collaterals attenuate the ischemia of the temporal cortex ipsilateral to CAO at the expense of the blood supply of the frontoparietal region, and 3) eNOS, surprisingly, does not play an important role in this CoBF redistribution.
CXCL16 regulates renal injury and fibrosis in experimental renal artery stenosis
Authors: Ma Zhiheng , Jin Xiaogao , He Liqun , Wang Yanlin
Published: August 2016

Recent studies have shown that inflammation plays a critical role in the initiation and progression of hypertensive kidney disease, including renal artery stenosis. However, the signaling mechanisms underlying the induction of inflammation are poorly understood. We found that CXCL16 was induced in the kidney in a murine model of renal artery stenosis. To determine whether CXCL16 is involved in renal injury and fibrosis, wild-type and CXCL16 knockout mice were subjected to renal artery stenosis induced by placing a cuff on the left renal artery. Wild-type and CXCL16 knockout mice had comparable blood pressure at baseline. Renal artery stenosis caused an increase in blood pressure that was similar between wild-type and CXCL16 knockout mice. CXCL16 knockout mice were protected from RAS-induced renal injury and fibrosis. CXCL16 deficiency suppressed bone marrow-derived fibroblast accumulation and myofibroblast formation in the stenotic kidneys, which was associated with less expression of extracellular matrix proteins. Furthermore, CXCL16 deficiency inhibited infiltration of F4/80+ macrophages and CD3+ T cells in the stenotic kidneys compared with those of wild-type mice. Taken together, our results indicate that CXCL16 plays a pivotal role in the pathogenesis of renal artery stenosis-induced renal injury and fibrosis through regulation of bone marrow-derived fibroblast accumulation and macrophage and T-cell infiltration.
Anthelmintic Niclosamide Disrupts the Interplay of p65 and FOXM1/β-catenin and Eradicates Leukemia Stem Cells in Chronic Myelogenous Leukemia
Authors: Jin Bei , Wang Chengyan , Li Juan , Du Xin , Ding Ke , Pan Jingxuan
Published: August 2016

Purpose: Leukemia stem cells (LSC), which are insensitive to tyrosine kinase inhibitors (TKI), are an important source of TKI resistance and disease relapse in chronic myelogenous leukemia (CML). Obstacles to eradicating LSCs include limited understanding of the regulation network of LSCs. The current study aimed to examine the interplay between NF-κB and FOXM1/β-catenin, and the effect of its chemical intervention on CML LSCs.

Experimental Design: The interplay between NF-κB and FOXM1/β-catenin was analyzed by reciprocal coimmunoprecipitation (co-IP) and chromatin immunoprecipitation (ChIP) assay in CML cells. The effect of disturbing NF-κB and FOXM1/β-catenin by niclosamide on the self-renewal capacity and survival of LSCs was evaluated in vitro in human primary CML CD34+ cells and in vivo in CML mice.

Results: Reciprocal co-IP experiments showed physical interaction of p65 and FOXM1. p65 promoted transcription of FOXM1 gene. ChIP assay revealed recruitment of p65 on the promoter of FOXM1 gene. Conversely, FOXM1 and β-catenin positively regulated the nuclear translocation and transcriptional activity of NF-κB in CML cells. Niclosamide disrupted the positive feedback loop between NF-κB and FOXM1/β-catenin, thereby impairing the self-renewal capacity and survival of CML LSCs. Niclosamide decreased the long-term engraftment of human CML LSCs in NOD-SCID IL2Rγ chain-deficient (NOG) mice, and prolonged the survival of CML mice.

Conclusions: Interaction of p65 with FOXM1/β-catenin is critical in CML and its disruption by niclosamide eradicates LSCs. These findings may improve the understanding of a self-renewal regulatory mechanism of LSCs and offer a rationale-based approach to eliminate LSCs in CML. Clin Cancer Res; 23(3); 789–803. ©2016 AACR.
Loss of SMAD4 Promotes Lung Metastasis of Colorectal Cancer by Accumulation of CCR1+ Tumor-Associated Neutrophils through CCL15-CCR1 Axis
Authors: Yamamoto Takamasa , Kawada Kenji , Itatani Yoshiro , Inamoto Susumu , Okamura Ryosuke , Iwamoto Masayoshi , Miyamoto Ei , Chen-Yoshikawa Toyofumi F. , Hirai Hideyo , Hasegawa Suguru , Date Hiroshi , Taketo Makoto M. , Sakai Yoshiharu
Published: August 2016

Purpose: We have reported loss of SMAD4 promotes expression of CCL15 from colorectal cancer to recruit CCR1+ myeloid cells through the CCL15-CCR1 axis, which contributes to invasion and liver metastasis. However, the molecular mechanism of lung metastasis is yet to be elucidated. Our purpose is to determine whether similar mechanism is involved in the lung metastasis of colorectal cancer.

Experimental Design: In a mouse model, we examined whether SMAD4 could affect the metastatic activity of colorectal cancer cells to the lung through the CCL15-CCR1 axis. We immunohistochemically analyzed expression of SMAD4, CCL15, and CCR1 with 107 clinical specimens of colorectal cancer lung metastases. We also characterized the CCR1+ myeloid cells using several cell-type–specific markers.

Results: In a mouse model, CCL15 secreted from SMAD4-deficient colorectal cancer cells recruited CCR1+ cells, promoting their metastatic activities to the lung. Immunohistochemical analysis of lung metastases from colorectal cancer patients revealed that CCL15 expression was significantly correlated with loss of SMAD4, and that CCL15-positive metastases recruited approximately 1.9 times more numbers of CCR1+ cells than CCL15-negative metastases. Importantly, patients with CCL15-positive metastases showed a significantly shorter relapse-free survival (RFS) than those with CCL15-negative metastases, and multivariate analysis indicated that CCL15 expression was an independent predictor of shorter RFS. Immunofluorescent staining showed that most CCR1+ cells around lung metastases were tumor-associated neutrophil, although a minor fraction was granulocytic myeloid-derived suppressor cell.

Conclusions: CCL15-CCR1 axis may be a therapeutic target to prevent colorectal cancer lung metastasis. CCL15 can be a biomarker indicating poor prognosis of colorectal cancer patients with lung metastases. Clin Cancer Res; 23(3); 833–44. ©2016 AACR.
Sulforaphane Prevents Neuronal Apoptosis and Memory Impairment in Diabetic Rats
Authors: Wang Gengyin , Fang Hui , Zhen Yanfeng , Xu Gang , Tian Jinli , Zhang Yazhong , Zhang Dandan , Zhang Guyue , Xu Jing , Zhang Zhiyue , Qiu Mingyue , Ma Yijia , Zhang Hongrui , Zhang Xinxin
Published: August 2016

Background/Aims: To explore the effects of sulforaphane (SFN) on neuronal apoptosis in hippocampus and memory impairment in diabetic rats. Methods: Thirty male rats were randomly divided into normal control, diabetic model and SFN treatment groups (N = 10 in each group). Streptozotocin (STZ) was applied to establish diabetic model. Water Morris maze task was applied to test learning and memory. Tunel assaying was used to detect apoptosis in hippocampus. The expressions of Caspase-3 and myeloid cell leukemia 1(MCL-1) were detected by western blotting. Neurotrophic factor levels and AKT/GSK3β pathway were also detected. Results: Compared with normal control, learning and memory were apparently impaired, with up-regulation of Caspase-3 and down-regulation of MCL-1 in diabetic rats. Apoptotic neurons were also found in CA1 region after diabetic modeling. By contrast, SFN treatment prevented the memory impairment, decreased the apoptosis of hippocampal neurons. SFN also attenuated the abnormal expression of Caspase-3 and MCL-1 in diabetic model. Mechanically, SFN treatment reversed diabetic modeling-induced decrease of p-Akt, p-GSK3β, NGF and BDNF expressions. Conclusion: SFN could prevent the memory impairment and apoptosis of hippocampal neurons in diabetic rat. The possible mechanism was related to the regulation of neurotropic factors and Akt/GSK3β pathway.
Triggering of Suicidal Erythrocyte Death by Psammaplin A
Authors: Al Mamun Bhuyan Abdulla , Signoretto Elena , Lang Florian
Published: August 2016

Background/Aims: Psammaplin A, a natural product isolated from marine sponges, triggers apoptosis of tumor cells and is thus considered for the treatment of malignancy. In analogy to apoptosis of nucleated tumor cells, erythrocytes may enter eryptosis, a suicidal death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Cellular mechanisms stimulating eryptosis include increase of cytosolic Ca2+ activity ([Ca2+]i), oxidative stress and ceramide. The present study explored, whether Psammaplin A induces eryptosis and to possibly shed some light on the underlying mechanisms. Methods: Phosphatidylserine exposing erythrocytes were identified utilizing annexin-V-binding, cell volume was estimated from forward scatter, [Ca2+]i determined utilizing Fluo3-fluorescence, the abundance of reactive oxygen species (ROS) quantified with DCFDA dependent fluorescence, and ceramide abundance at the erythrocyte surface detected with specific antibodies. Results: A 48 hours exposure of human erythrocytes to Psammaplin A (2-8 µg/ml) significantly decreased forward scatter and significantly increased the percentage of annexin-V-binding cells. Psammaplin A significantly increased Fluo3-fluorescence, the effect of Psammaplin A on annexin-V-binding and forward scatter was, however, not significantly blunted by removal of extracellular Ca2+. Psammaplin A significantly increased DCFDA fluorescence and ceramide abundance. Conclusions: Psammaplin A triggers cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect paralleled by increase of [Ca2+]i, induction of oxidative stress and enhanced appearance of ceramide.
Cytogenetics of the Thorny Catfish Trachydoras paraguayensis (Eigenmann & Ward, 1907), (Siluriformes, Doradidae): Evidence of Pericentric Inversions and Chromosomal Fusion
Authors: Baumgärtner Lucas , Paiz Leonardo M. , Margarido Vladimir P. , Portela-Castro Ana L.B.
Published: August 2016

The karyotype and chromosomal characteristics of Trachydorasparaguayensis, a representative of the South American catfish family Doradidae, were analyzed by conventional (Giemsa staining, silver staining, C-banding) and molecular (FISH with rDNA and telomeric probes) cytogenetic techniques. The diploid chromosome number was 2n = 56, with 36 metacentric, 16 submetacentric, and 4 subtelocentric chromosomes in both sexes; however, a remarkable heteromorphism in pair 22 (submetacentric and metacentric elements) was detected in 6 individuals. Compared to other representatives of Doradidae which mostly have 58 chromosomes, the karyotype of T. paraguayensis suggests a reduction in 2n due to chromosomal fusion, as could be deduced from the presence of an interstitial telomere sequence in the submetacentric pair 19. Pale heterochromatic blocks were present in the terminal regions of some chromosomes, very similar to other species of Doradidae. The interstitial position of the NORs observed in the karyotype of T. paraguayensis differs from those reported for most Doradidae species, indicating that it is a derived character. FISH with 5S rDNA revealed 2 interstitial fluorescent signals in the submetacentric pair 22, and the polymorphism of these sites likely resulted from a pericentric inversion.
Incidence, Risk Factors and a Novel Prevention Technique for Inguinal Hernia after Robot-Assisted Radical Prostatectomy
Authors: Shimbo Masaki , Endo Fumiyasu , Matsushita Kazuhito , Iwabuchi Toshihisa , Fujisaki Akiko , Kyono Yoko , Hishiki Kohsuke , Muraishi Osamu , Hattori Kazunori
Published: August 2016

Introduction: To evaluate the incidence and risk factors for postoperative inguinal hernia (IH) after robot-assisted radical prostatectomy (RARP) and to assess whether a newly developed prevention technique reduces the incidence of IH after RARP. Methods: We included 161 consecutive patients (322 groins) who underwent RARP between September 2011 and October 2013. The prevention technique was as follows: (1) sufficient incision of peritoneum around the internal inguinal ring; (2) separation of spermatic vessels; (3) dissection of vas deferens. Results: Postoperative IH occurred in 14 cases (19.4%) occurring in the observation group compared to 2 cases (2.2%) in the prevention group. Patent processus vaginalis (PPV) was the only risk factor. Time-to-event analysis demonstrated a significant decrease in IH incidence in the IH prevention group (p = 0.005). Conclusion: Our data reveal a higher incidence of IH after RARP, with the existence of PPV as the only identified risk factor. Our simple IH-prevention technique, which does not involve the use of artificial materials, appears safe and effective.
Negros candidatos e candidatos negros: partidos políticos e campanhas eleitorais na cidade de São Paulo após o fim do Estado Novo
Authors: Sotero Edilza Correia
Published: August 2016

A abertura política após o fim do Estado Novo estimulou a organização e atuação de grupos com diversas demandas. No caso de ativistas negros, um dos cursos de ação para resolução de problemas relacionados à população negra visava a participação nas esferas de decisões do Estado, via política partidária. Em São Paulo, as estratégias de inserção política desenvolvidas por líderes do “meio negro” foram construídas com base no argumento de legitimidade de representação, em um momento que diferentes grupos políticos começavam a se valer de um discurso antirracista, centrado no combate ao “preconceito de cor”.
Probucol in Albuminuric Type 2 Diabetes Mellitus Patients on Renin–Angiotensin System Blockade
Authors: Jin Sang-Man , Han Kyung Ah , Yu Jae Myung , Sohn Tae Seo , Choi Sung Hee , Chung Choon Hee , Park Ie Byung , Rhee Eun Jung , Baik Sei Hyun , Park Tae Sun , Lee In-Kyu , Ko Seung-Hyun , Hwang You-Cheol , Cha Bong Soo , Lee Hyoung Woo , Nam Moon-Suk , Lee Moon-Kyu
Published: August 2016

Objective—

To determine the effect of probucol on urine albumin excretion in type 2 diabetes mellitus patients with albuminuria using angiotensin-converting enzyme inhibitors or angiotensin receptor blockers.

Approach and Results—

This was a 16-week, phase II, randomized, placebo-controlled, parallel-group study in type 2 diabetes mellitus patients with a urinary albumin/creatinine ratio of ≥300 mg/g using angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, conducted in 17 tertiary referral hospitals. Eligible patients were randomized to probucol 250 mg/d (n=44), probucol 500 mg/d (n=41), and placebo (n=41) groups in a ratio of 1:1:1 after block randomization procedures, keeping the treatment assignment blinded to the investigators, patients, and study assistants. The primary end point was change in the geometric mean of urinary albumin/creatinine ratio from baseline to week 16 (
ClinicalTrials.gov
identifier NCT01726816). The study was started on November 8, 2012, and completed on March 24, 2014. The least squares mean change±SE from baseline in urinary albumin/creatinine ratio at week 16 was −7.2±639.5 mg/g in the probucol 250 mg/d group (n=43;
P
=0.2077 versus placebo group), 9.3±587.4 mg/g in the probucol 500 mg/d group (n=40;
P
=0.1975 versus placebo group), and 259.0±969.1 mg/g in the placebo group (n=41). Although the majority of subjects were on statins, probucol treatment significantly lowered total cholesterol and low-density lipoprotein cholesterol levels. QT prolongation occurred in one and two subjects in control and probucol 250 mg/d groups, respectively.

Conclusions—

Four months of probucol up to 500 mg/d failed to reduce urinary albumin excretion.
Sex and Race/Ethnicity Differences in Implantable Cardioverter-Defibrillator Counseling and Use Among Patients Hospitalized With Heart Failure
Authors: Hess Paul L. , Hernandez Adrian F. , Bhatt Deepak L. , Hellkamp Anne S. , Yancy Clyde W. , Schwamm Lee H. , Peterson Eric D. , Schulte Phillip J. , Fonarow Gregg C. , Al-Khatib Sana M.
Published: August 2016

Background:

Previous studies have found that women and black patients eligible for a primary prevention implantable cardioverter-defibrillator (ICD) are less likely than men or white patients to receive one.

Methods:

We performed an observational analysis of the Get With The Guidelines-Heart Failure Program from January 1, 2011, to March 21, 2014. Patients admitted with heart failure and an ejection fraction ≤35% without an ICD were included. Rates of ICD counseling among eligible patients and ICD receipt among counseled patients were examined by sex and race/ethnicity.

Results:

Among 21 059 patients from 236 sites, 4755 (22.6%) received predischarge ICD counseling. Women were counseled less frequently than men (19.3% versus 24.6%,
P
<0.001, adjusted odds ratio [OR], 0.84; 95% confidence interval [CI], 0.78–0.91). Racial and ethnic minorities were less likely to receive counseling than white patients (black 22.6%, Hispanic 18.6%, other race/ethnic group 14.4% versus white 24.3%,
P
<0.001 for each): adjusted OR versus white, 0.69; 95% CI, 0.63 to 0.76 for black patients; adjusted OR, 0.62; 95% CI, 0.55 to 0.70 for Hispanic patients; adjusted OR, 0.53; 95% CI, 0.43 to 0.65 for other patients. Among the 4755 counseled patients, 2977 (62.6%) received an ICD or had one planned for placement after hospital stay. Among those counseled, women and men were similarly likely to receive an ICD (adjusted OR, 1.13; 95% CI, 0.99–1.29). However, black (adjusted OR, 0.70; 95% CI, 0.56–0.88) and Hispanic patients (adjusted OR, 0.68; 95% CI, 0.46–1.01) were less likely to receive an ICD.

Conclusions:

Up to 4 of 5 hospitalized patients with heart failure eligible for ICD counseling did not receive it, particularly women and minority patients. Among counseled patients, ICD use differences by race and ethnicity persisted.
Dynamic Predictive Scores for Cardiac Surgery–Associated Acute Kidney Injury
Authors: Jiang Wuhua , Teng Jie , Xu Jiarui , Shen Bo , Wang Yimei , Fang Yi , Zou Zhouping , Jin Jifu , Zhuang Yamin , Liu Lan , Luo Zhe , Wang Chunsheng , Ding Xiaoqiang
Published: August 2016

Background

Cardiac surgery–associated acute kidney injury (
CSA
‐
AKI
) is a common complication with a poor prognosis. In order to identify modifiable perioperative risk factors for
AKI
, which existing risk scores are insufficient to predict, a dynamic clinical risk score to allow clinicians to estimate the risk of
CSA
‐
AKI
from preoperative to early postoperative periods is needed.

Methods and Results

A total of 7233 cardiac surgery patients in our institution from January 2010 to April 2013 were enrolled prospectively and distributed into 2 cohorts. Among the derivation cohort, logistic regression was used to analyze
CSA
‐
AKI
risk factors preoperatively, on the day of
ICU
admittance and 24 hours after
ICU
admittance. Sex, age, valve surgery combined with coronary artery bypass grafting, preoperative
NYHA
score >2, previous cardiac surgery, preoperative kidney (without renal replacement therapy) disease, intraoperative cardiopulmonary bypass application, intraoperative erythrocyte transfusions, and postoperative low cardiac output syndrome were identified to be associated with
CSA
‐
AKI
. Among the other 1152 patients who served as a validation cohort, the point scoring of risk factor combinations led to area under receiver operator characteristics curves (
AUROC
) values for
CSA
‐
AKI
prediction of 0.74 (preoperative), 0.75 (on the day of
ICU
admission), and 0.82 (postoperative), and Hosmer–Lemeshow goodness‐of‐fit tests revealed a good agreement of expected and observed
CSA
‐
AKI
rates.

Conclusions

The first dynamic predictive score system, with Kidney Disease: Improving Global Outcomes (KDIGO) AKI definition, was developed and predictive efficiency for
CSA
‐
AKI
was validated in cardiac surgery patients.
The Capillary Index Score as a Marker of Viable Cerebral Tissue
Authors: Al-Ali Firas , Berkhemer Olvert A. , Yousman Wina P. , Elias John J. , Bender Evin N. , Lingsma Hester F. , van der Lugt Aad , Dippel Diederik W.J. , Roos Yvo B.W.E.M. , van Oostenbrugge Robert J. , van Zwam Wim H. , Dillon William P. , Majoie Charles B.L.M.
Published: August 2016

Background and Purpose—

The capillary index score (CIS) is based on the hypothesis that areas lacking capillary blush on pretreatment cerebral digital subtraction angiograms correspond to nonviable cerebral tissue.

Methods—

Pretreatment digital subtraction angiograms and post-treatment noncontrast enhanced computed tomographic scans from the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) trial were evaluated for areas lacking capillary blush and with tissue hypodensity, respectively. Because the superior and middle zones of the CIS correspond to the 7 cerebral cortex regions of the Alberta Stroke Program Early CT (ASPECT) score, capillary blush was scored in these 2 zones (0–2), called sub-CIS, and compared with the ASPECT score in these 7 regions (0–7), called hypodensity score. The presence and extent of hypodensity were compared between sub-CIS zones with contingency tables and nonparametric comparisons between groups, respectively.

Results—

On the basis of a sample size of 50 subjects, 100% with sub-CIS <2 had the presence of hypodensity (hypodensity score ≥1) versus 57% for sub-CIS=2 (
P
=0.004). The extent of hypodensity (numeric hypodensity score) was significantly lower for sub-CIS=2 than 0 or 1 (
P
=0.02). For 42 subjects with revascularization data, the presence and extent of hypodensity were significantly lower for sub-CIS=2 plus good revascularization than for other combinations of sub-CIS and revascularization (
P
=0.02 and 0.01, respectively).

Conclusions—

The absence of capillary blush on pretreatment digital subtraction angiogram seems to correspond to nonviable cerebral tissue. Successful revascularization reduces the chance of tissue hypodensity (infarction), when capillary blush is present.

Clinical Trial Registration—

URL:
http://www.trialregister.nl
. Unique identifier: NTR number 1804. URL:
http://www.isrctn.com
. Unique identifier: ISRCTN10888758.
FABS
Authors: Goyal Nitin , Tsivgoulis Georgios , Male Shailesh , Metter E. Jeffrey , Iftikhar Sulaiman , Kerro Ali , Chang Jason J. , Frey James L. , Triantafyllou Sokratis , Papadimitropoulos Georgios , Abedi Vida , Alexandrov Anne W. , Alexandrov Andrei V. , Zand Ramin
Published: August 2016

Background and Purpose—

A large number of patients with symptoms of acute cerebral ischemia are stroke mimics (SMs). In this study, we sought to develop a scoring system (FABS) for screening and stratifying SM from acute cerebral ischemia and to identify patients who may require magnetic resonance imaging to confirm or refute a diagnosis of stroke in the emergency setting.

Methods—

We designed a scoring system: FABS (6 variables with 1 point for each variable present): absence of Facial droop, negative history of Atrial fibrillation, Age <50 years, systolic Blood pressure <150 mm Hg at presentation, history of Seizures, and isolated Sensory symptoms without weakness at presentation. We evaluated consecutive patients with symptoms of acute cerebral ischemia and a negative head computed tomography for any acute finding within 4.5 hours after symptom onset in 2 tertiary care stroke centers for validation of FABS.

Results—

A total of 784 patients (41% SMs) were evaluated. Receiver operating characteristic curve (C statistic, 0.95; 95% confidence interval [CI], 0.93–0.98) indicated that FABS≥3 could identify patients with SM with 90% sensitivity (95% CI, 86%–93%) and 91% specificity (95% CI, 88%–93%). The negative predictive value and positive predictive value were 93% (95% CI, 90%–95%) and 87% (95% CI, 83%–91%), respectively.

Conclusions—

FABS seems to be reliable in stratifying SM from acute cerebral ischemia cases among patients in whom the head computed tomography was negative for any acute findings. It can help clinicians consider advanced imaging for further diagnosis.
Protective Effects and Magnetic Resonance Imaging Temperature Mapping of Systemic and Focal Hypothermia in Cerebral Ischemia
Authors: Vieites-Prado Alba , Iglesias-Rey Ramón , Fernández-Susavila Héctor , da Silva-Candal Andrés , Rodríguez-Castro Emilio , Gröhn Olli H.J. , Wellmann Sven , Sobrino Tomás , Castillo José , Campos Francisco
Published: August 2016

Background and Purpose—

Hypothermia is potentially the most effective protective therapy for brain ischemia; however, its use is limited because of serious side effects. Although focal hypothermia (FH) has a significantly lower stress profile than systemic hypothermia (SH), its efficacy in ischemia has been poorly studied. We aimed to compare the therapeutic effects of each treatment on various short- and long-term clinically relevant end points.

Methods—

Sprague–Dawley rats were subjected to transient (45 minutes) occlusion of the middle cerebral artery. One hour after arterial reperfusion, animals were randomly assigned to groups for treatment with SH or FH (target temperature: 32°C) for 4 or 24 hours. Lesion volume, edema, functional recovery, and histological markers of cellular injury were evaluated for 1 month after ischemic injury. Effects of SH and FH on cerebral temperature were also analyzed for the first time by magnetic resonance thermometry, an approach that combines spectroscopy with gradient-echo–based phase mapping.

Results—

Both therapeutic approaches reduced ischemic lesion volume (
P
<0.001), although a longer FH treatment (24 hours) was required to achieve similar protective effects to those induced by 4 hours of SH. In addition, magnetic resonance thermometry demonstrated that systemic hypothermia reduced whole-brain temperature, whereas FH primarily reduced the temperature of the ischemic region.

Conclusions—

Focal brain hypothermia requires longer cooling periods to achieve the same protective efficacy as SH. However, FH mainly affects the ischemic region, and therefore represents a promising and nonstressful alternative to SH.
Leukoaraiosis, Cerebral Hemorrhage, and Outcome After Intravenous Thrombolysis for Acute Ischemic Stroke
Authors: Charidimou Andreas , Pasi Marco , Fiorelli Marco , Shams Sara , von Kummer Rüdiger , Pantoni Leonardo , Rost Natalia
Published: August 2016

Background and Purpose—

We performed a meta-analysis to assess whether leukoaraiosis on brain computed tomographic scans of acute ischemic stroke patients treated with intravenous thrombolysis is associated with an increased risk of symptomatic intracerebral hemorrhage (sICH) or poor functional outcome at 3 to 6 months after stroke, or both.

Methods—

We searched PubMed and pooled relevant data in meta-analyses using random effects models. Using odds ratios (OR), we quantified the strength of association between the presence and severity of leukoaraiosis and post-thrombolysis sICH or 3- to 6-month modified Rankin Score >2.

Results—

Eleven eligible studies (n=7194) were pooled in meta-analysis. The risk of sICH was higher in patients with leukoaraiosis (OR, 1.55; 95% confidence interval [CI], 1.17–2.06;
P
=0.002) and severe leukoaraiosis (OR, 2.53; 95% CI, 1.92–3.34;
P
<0.0001) compared with patients without leukoaraiosis. Leukoaraiosis was an independent predictor of sICH in 6 included studies (n=4976; adjusted OR, 1.75; 95% CI, 1.35–2.27;
P
<0.0001). OR for leukoaraiosis and poor 3- to 6-month outcome was 2.02 (95% CI, 1.54–2.65;
P
<0.0001), with significant statistical heterogeneity (
I
2
, 75.7%;
P
=0.002). In adjusted analyses, leukoaraiosis was an independent predictor of poor outcome (n=3688; adjusted OR, 1.61; 95% CI, 1.44–1.79;
P
<0.0001). In post hoc analyses, including only leukoaraiosis patients in randomized controlled trials (IST-3 [third International Stroke Trial], NINDS [National Institute of Neurological Disorders and Stroke], ECASS-1–2 [European Cooperative Acute Stroke Study]; n=2234), tissue-type plasminogen activator versus control was associated with higher sICH risk (OR, 5.50; 95% CI, 2.49–12.13), but lower poor outcome risk (OR, 0.75; 95% CI, 0.60–0.95).

Conclusions—

Leukoaraiosis might increase post-intravenous thrombolysis sICH risk and poor outcome poststroke. Despite increased sICH risk, intravenous tissue-type plasminogen activator treatment has net clinical benefit in patients with leukoaraiosis. Given the risk of bias/confounding, these results should be considered hypothesis-generating and do not justify withholding intravenous thrombolysis.
In-Transit Telemedicine Speeds Ischemic Stroke Treatment
Authors: Belt Gary H. , Felberg Robert A. , Rubin Jane , Halperin John J.
Published: August 2016

Background and Purpose—

Time to treatment is critically important in ischemic stroke. We compared the efficacy and cost of teleneurology evaluation during patient transport with that of mobile stroke transport units.

Methods—

Using cellular-connected telemedicine devices, we assessed 89 presumptive stroke patients in ambulances in transit. Paramedics assisted remote teleneurologists in obtaining a simplified history and examination, then coordinating care with the receiving emergency department. We prospectively assessed door-to-needle and last-known-well-to-needle times for all intravenous alteplase–treated stroke patients brought to our emergency departments by emergency medical services’ transport, comparing those with and without in-transit telestroke.

Results—

From January 2015 through March 2016, 111 stroke patients received intravenous alteplase at study emergency departments. Mean door to needle was 13 minutes less with in-transit telestroke (28 versus 41;
P
=0.02). Although limitations in cellular communication degraded transmission quality, this did not prevent the completion of satisfactory patient evaluations.

Conclusions—

Improvement in time to treat seems comparable with in-transit telestroke and mobile stroke transport units. The low cost/unit makes this approach scalable, potentially providing rapid management of more patients.
Mass Instruction or Higher Learning? The Impact of College Class Size on Student Retention and Graduation
Authors: Bettinger Eric P. , Long Bridget Terry
Published: August 2016

This paper measures the effects of collegiate class size on college retention and graduation. Class size is a perennial issue in research on primary and secondary schooling. Few researchers have focused on the causal impacts of collegiate class size, however. Whereas college students have greater choice of classes, selection problems and nonrandom sorting make it difficult to estimate causal impacts. Using unique data and exogenous variation in class size, we estimate the impacts of class size using a sample of nearly 60,000 four-year college students. Using an instrumental variables approach to control for selection bias, the results suggest an increase in collegiate class size leads to an increase in dropout rates and a reduction in on-time degree completion, but no change in long-run degree completion.
Minority Nations and Self-determination: A Proposal for the Regulation of Sovereignty Processes
Authors: Ruiz Vieytez Eduardo J.
Published: August 2016

Basque and Catalan demands for legitimising political accommodation, solely on the basis of the democratic will of their residents, poses a significant challenge to the Spanish constitutional system. The core of the debate in this kind of conflict revolves around the so-called “right to decide” which commonly finds its expression in the capacity to hold a referendum over sovereignty matters. The path opened by Quebec, Scotland and other minority nations are considered by some to constitute evidence of the democratic need to include this right as a new accommodation formula. Incorporating a “sovereigntist proceeding” into the legal system(s) may pave the way to a new framework aimed at solving the significant constitutional problems that exist in Spain and other countries. I suggest that such a procedure could be incorporated and regulated in the existing legal systems and provide some guidelines that could be adopted when drafting the aforementioned regulation.
Two new Gomphonema species (Bacillariophyta) from the Maritime Antarctic Region
Authors: VIJVER BART VAN DE , KOPALOVÁ KATEŘINA , ZIDAROVA RALITSA , KOCIOLEK J. PATRICK
Published: August 2016

Two new diatom taxa belonging to the genus Gomphonema were recorded during a survey of the Maritime Antarctic freshwater and limno-terrestrial diatom flora: Gomphonema jamesrossense sp. nov. and G.maritimo-antarcticum sp. nov. Detailed light (LM) and scanning electron microscope (SEM) observations are used to characterize the morphology and ultrastructure of the two new Gomphonema taxa. Comparisons with similar taxa and the ecological preferences of each species are added. The revision of these species confirmed the endemic nature of the Antarctic diatom flora.
A new species of Ptilagrostis (Stipeae, Poaceae) from Qinghai-Tibet Plateau
Authors: ZHANG ZHONG-SHUAI , LI LING-LU , CHEN WEN-LI
Published: August 2016

A new species, Ptilagrostis arcuata, from Qinghai-Tibet Plateau is described and illustrated. It is easily distinguished from the similar P. concinna by its arcuate or heliciform awns with golden yellow or pale yellow hairs, narrower basal leaves, and absence of bracts below the panicles. The chromosome number of the new species is 2n=22, karyotype 2n=22=14m+6sm+2st.
Response of Marine Boundary Layer Cloud Properties to Aerosol Perturbations Associated with Meteorological Conditions from the 19-Month AMF-Azores Campaign
Authors: Liu Jianjun , Li Zhanqing , Cribb Maureen
Published: August 2016

This study investigates the response of marine boundary layer (MBL) cloud properties to aerosol loading by accounting for the contributions of large-scale dynamic and thermodynamic conditions and quantifies the first indirect effect (FIE). It makes use of 19-month measurements of aerosols, clouds, and meteorology acquired during the Atmospheric Radiation Measurement Mobile Facility field campaign over the Azores. Cloud droplet number concentrations and cloud optical depth (COD) significantly increased with increasing aerosol number concentration . Cloud droplet effective radius (DER) significantly decreased with increasing . The correlations between cloud microphysical properties [, liquid water path (LWP), and DER] and were stronger under more stable conditions. The correlations between , LWP, DER, and were stronger under ascending-motion conditions, while the correlation between COD and was stronger under descending-motion conditions. The magnitude and corresponding uncertainty of the FIE ranged from 0.060 ± 0.022 to 0.101 ± 0.006 depending on the different LWP values. Under more stable conditions, cloud-base heights were generally lower than those under less stable conditions. This enabled a more effective interaction with aerosols, resulting in a larger value for the FIE. However, the dependence of the response of cloud properties to aerosol perturbations on stability varied according to whether ground- or satellite-based DER retrievals were used. The magnitude of the FIE had a larger variation with changing LWP under ascending-motion conditions and tended to be higher under ascending-motion conditions for clouds with low LWP and under descending-motion conditions for clouds with high LWP. A contrasting dependence of FIE on atmospheric stability estimated from the surface and satellite cloud properties retrievals reported in this study underscores the importance of assessing all-level properties of clouds in aerosol–cloud interaction studies.