bluuebunny/crossref_metadata_2025 huggingface dataset:
Schema.org: Evolution of Structured Data on the Web
Authors: Guha R. V. , Brickley Dan , MacBeth Steve
Published: December 2015

Separation between content and presentation has always been one of the important design aspects of the Web. Historically, however, even though most Web sites were driven off structured databases, they published their content purely in HTML. Services such as Web search, price comparison, reservation engines, etc. that operated on this content had access only to HTML. Applications requiring access to the structured data underlying these Web pages had to build custom extractors to convert plain HTML into structured data. These efforts were often laborious and the scrapers were fragile and error-prone, breaking every time a site changed its layout.
The role of cerebral oxygenation and regional cerebral blood flow on tolerance to central hypovolemia
Authors: Kay Victoria L. , Rickards Caroline A.
Published: December 2015

Tolerance to central hypovolemia is highly variable, and accumulating evidence suggests that protection of anterior cerebral blood flow (CBF) is not an underlying mechanism. We hypothesized that individuals with high tolerance to central hypovolemia would exhibit protection of cerebral oxygenation (ScO2), and prolonged preservation of CBF in the posterior vs. anterior cerebral circulation. Eighteen subjects (7 male/11 female) completed a presyncope-limited lower body negative pressure (LBNP) protocol (3 mmHg/min onset rate). ScO2 (via near-infrared spectroscopy), middle cerebral artery velocity (MCAv), posterior cerebral artery velocity (PCAv) (both via transcranial Doppler ultrasound), and arterial pressure (via finger photoplethysmography) were measured continuously. Subjects who completed ≥70 mmHg LBNP were classified as high tolerant (HT; n = 7) and low tolerant (LT; n = 11) if they completed ≤60 mmHg LBNP. The minimum difference in LBNP tolerance between groups was 193 s (LT = 1,243 ± 185 s vs. HT = 1,996 ± 212 s; P < 0.001; Cohen's d = 3.8). Despite similar reductions in mean MCAv in both groups, ScO2 decreased in LT subjects from −15 mmHg LBNP ( P = 0.002; Cohen's d=1.8), but was maintained at baseline values until −75 mmHg LBNP in HT subjects ( P < 0.001; Cohen's d = 2.2); ScO2 was lower at −30 and −45 mmHg LBNP in LT subjects ( P ≤ 0.02; Cohen's d ≥ 1.1). Similarly, mean PCAv decreased below baseline from −30 mmHg LBNP in LT subjects ( P = 0.004; Cohen's d = 1.0), but remained unchanged from baseline in HT subjects until −75 mmHg ( P = 0.006; Cohen's d = 2.0); PCAv was lower at −30 and −45 mmHg LBNP in LT subjects ( P ≤ 0.01; Cohen's d ≥ 0.94). Individuals with higher tolerance to central hypovolemia exhibit prolonged preservation of CBF in the posterior cerebral circulation and sustained cerebral tissue oxygenation, both associated with a delay in the onset of presyncope.
The effect of experimental low back pain on lumbar muscle activity in people with a history of clinical low back pain: a muscle functional MRI study
Authors: Danneels Lieven , Cagnie Barbara , D'hooge Roseline , De Deene Yves , Crombez Geert , Vanderstraeten Guy , Parlevliet Thierry , Van Oosterwijck Jessica
Published: December 2015

In people with a history of low back pain (LBP), structural and functional alterations have been observed at several peripheral and central levels of the sensorimotor pathway. These existing alterations might interact with the way the sensorimotor system responds to pain. We examined this assumption by evaluating the lumbar motor responses to experimental nociceptive input of 15 participants during remission of unilateral recurrent LBP. Quantitative T2 images (muscle functional MRI) were taken bilaterally of multifidus, erector spinae, and psoas at several segmental levels (L3 upper and L4 upper and lower endplate) and during several conditions: 1) at rest, 2) upon trunk-extension exercise without pain, and 3) upon trunk-extension exercise with experimental induced pain at the clinical pain-side (1.5-ml intramuscular hypertonic saline injections in erector spinae). Following experimental pain induction, muscle activity levels similarly reduced for all three muscles, on both painful and nonpainful sides, and at multiple segmental levels ( P = 0.038). Pain intensity and localization from experimental LBP were similar as during recalled clinical LBP episodes. In conclusion, unilateral and unisegmental experimental LBP exerts a generalized and widespread decrease in lumbar muscle activity during remission of recurrent LBP. This muscle response is consistent with previous observed patterns in healthy people subjected to the same experimental pain paradigm. It is striking that similar inhibitory patterns in response to pain could be observed, despite the presence of preexisting alterations in the lumbar musculature during remission of recurrent LBP. These results suggest that motor output can modify along the course of recurrent LBP.
Quantifying the spatial extent of the corollary discharge benefit to transsaccadic visual perception
Authors: Jayet Bray Laurence C. , Bansal Sonia , Joiner Wilsaan M.
Published: December 2015

Extraretinal information, such as corollary discharge (CD), is hypothesized to help compensate for saccade-induced visual input disruptions. However, support for this hypothesis is largely for one-dimensional transsaccadic visual changes, with little comprehensive information on the spatial characteristics. Here we systematically mapped the two-dimensional extent of this compensation by quantifying the insensitivity to different displacement metrics. Human subjects made saccades to targets positioned at different amplitudes (4° or 8°) and directions (rightward, oblique, or upward). After the saccade the initial target disappeared and, after a blank period, reappeared at a shifted location—a collinear, diagonal, or orthogonal displacement. Subjects reported the perceived shift direction, and we determined the displacement detection based on the perceptual judgments. The two-dimensional insensitivity fields resulting from the perceptual thresholds had spatial features similar to the saccadic eye movement variability: 1) scaled with movement amplitude, 2) oriented (less sensitive to the change) along the saccade vector, and 3) approximately constant in shape when normalized by movement amplitude. In addition, comparing the postsaccadic perceptual estimate of the presaccadic target location to that based solely on the postsaccade visual error showed that overall the perceptual estimate was approximately 50% more accurate and 35% less variable than estimates based solely on this visual information. However, this relationship was not uniform: The benefit of extraretinal information was observed largely for displacements with a component parallel to the saccade vector. These results suggest a graded use of extraretinal information when forming the postsaccadic perceptual evaluation of transsaccadic environmental changes.
Pulsatility of Hypothalamo-Pituitary Hormones: A Challenge in Quantification
Authors: Keenan Daniel M. , Veldhuis Johannes D.
Published: December 2015

Neuroendocrine systems control many of the most fundamental physiological processes, e.g., reproduction, growth, adaptations to stress, and metabolism. Each such system involves the hypothalamus, the pituitary, and a specific target gland or organ. In the quantification of the interactions among these components, biostatistical modeling has played an important role. In the present article, five key challenges to an understanding of the interactions of these systems are illustrated and discussed critically.
Ubiquitin-Specific Protease 4-Mediated Deubiquitination and Stabilization of PRL-3 Is Required for Potentiating Colorectal Oncogenesis
Authors: Xing Cheng , Lu Xing-Xing , Guo Peng-Da , Shen Tong , Zhang Shen , He Xiao-Shun , Gan Wen-Juan , Li Xiu-Ming , Wang Jing-Ru , Zhao Yuan-Yuan , Wu Hua , Li Jian-Ming
Published: December 2015

Ubiquitin specific protease 4 (USP4) is a deubiquitinating enzyme with key roles in the regulation of p53 and TGFβ signaling, suggesting its importance in tumorigenesis. However, the mechanisms and regulatory roles of USP4 in cancer, including colorectal cancer, remain largely elusive. Here, we present the first evidence that USP4 regulates the growth, invasion, and metastasis of colorectal cancer. USP4 expression was significantly elevated in colorectal cancer tissues and was significantly associated with tumor size, differentiation, distant metastasis, and poor survival. Knockdown of USP4 diminished colorectal cancer cell growth, colony formation, migration, and invasion in vitro and metastasis in vivo. Importantly, we found that phosphatase of regenerating liver-3 (PRL-3) is indispensable for USP4-mediated oncogenic activity in colorectal cancer. Mechanistically, we observed that USP4 interacted with and stabilized PRL-3 via deubiquitination. This resulted in activation of Akt and reduction of E-cadherin, critical regulators of cancer cell growth and metastasis. Examination of clinical samples confirmed that USP4 expression positively correlates with PRL-3 protein expression, but not mRNA transcript levels. Taken together, our results demonstrate that aberrant expression of USP4 contributes to the development and progression of colorectal cancer and reveal a critical mechanism underlying USP4-mediated oncogenic activity. These observations suggest that the potential of harnessing proteolytic degradation processes for therapeutic manipulation may offer a much-needed new approach for improving colorectal cancer treatment strategies. Cancer Res; 76(1); 83–95. ©2015 AACR.
The New Antitumor Drug ABTL0812 Inhibits the Akt/mTORC1 Axis by Upregulating Tribbles-3 Pseudokinase
Authors: Erazo Tatiana , Lorente Mar , López-Plana Anna , Muñoz-Guardiola Pau , Fernández-Nogueira Patricia , García-Martínez José A. , Bragado Paloma , Fuster Gemma , Salazar María , Espadaler Jordi , Hernández-Losa Javier , Bayascas Jose Ramon , Cortal Marc , Vidal Laura , Gascón Pedro , Gómez-Ferreria Mariana , Alfón José , Velasco Guillermo , Domènech Carles , Lizcano Jose M.
Published: December 2015

Purpose: ABTL0812 is a novel first-in-class, small molecule which showed antiproliferative effect on tumor cells in phenotypic assays. Here we describe the mechanism of action of this antitumor drug, which is currently in clinical development.

Experimental Design: We investigated the effect of ABTL0812 on cancer cell death, proliferation, and modulation of intracellular signaling pathways, using human lung (A549) and pancreatic (MiaPaCa-2) cancer cells and tumor xenografts. To identify cellular targets, we performed in silico high-throughput screening comparing ABTL0812 chemical structure against ChEMBL15 database.

Results: ABTL0812 inhibited Akt/mTORC1 axis, resulting in impaired cancer cell proliferation and autophagy-mediated cell death. In silico screening led us to identify PPARs, PPARα and PPARγ as the cellular targets of ABTL0812. We showed that ABTL0812 activates both PPAR receptors, resulting in upregulation of Tribbles-3 pseudokinase (TRIB3) gene expression. Upregulated TRIB3 binds cellular Akt, preventing its activation by upstream kinases, resulting in Akt inhibition and suppression of the Akt/mTORC1 axis. Pharmacologic inhibition of PPARα/γ or TRIB3 silencing prevented ABTL0812-induced cell death. ABTL0812 treatment induced Akt inhibition in cancer cells, tumor xenografts, and peripheral blood mononuclear cells from patients enrolled in phase I/Ib first-in-human clinical trial.

Conclusions: ABTL0812 has a unique and novel mechanism of action, that defines a new and drugable cellular route that links PPARs to Akt/mTORC1 axis, where TRIB3 pseudokinase plays a central role. Activation of this route (PPARα/γ-TRIB3-Akt-mTORC1) leads to autophagy-mediated cancer cell death. Given the low toxicity and high tolerability of ABTL0812, our results support further development of ABTL0812 as a promising anticancer therapy. Clin Cancer Res; 22(10); 2508–19. ©2015 AACR.
Frontotemporal Dysfunction in Amyotrophic Lateral Sclerosis: A Discriminant Function Analysis
Authors: Nidos Andreas , Kasselimis Dimitrios S. , Simos Panagiotis G. , Rentzos Michael , Alexakis Theodoros , Zalonis Ioannis , Zouvelou Vassiliki , Potagas Constantin , Evdokimidis Ioannis , Woolley Susan C.
Published: December 2015

Background: There is growing evidence for extramotor dysfunction (EMd) in amyotrophic lateral sclerosis (ALS), with a reported prevalence of up to 52%. Objective: In the present study, we explore the clinical utility of a brief neuropsychological battery for the investigation of cognitive, behavioral, and language deficits in patients with ALS. Methods: Thirty-four consecutive ALS patients aged 44-89 years were tested with a brief neuropsychological battery, including executive, behavioral, and language measures. Patients were initially classified as EMd or non-EMd based on their scores on the frontal assessment battery (FAB). Results: Between-group comparisons revealed significant differences in all measures (p < 0.01). Discriminant analysis resulted in a single canonical function, with all tests serving as significant predictors. This function agreed with the FAB in 13 of 17 patients screened as EMd and identified extramotor deficits in 2 additional patients. Overall sensitivity and specificity estimates against FAB were 88.2%. Conclusions: We stress the importance of discriminant function analysis in clinical neuropsychological assessment and argue that the proposed neuropsychological battery may be of clinical value, especially when the option of extensive and comprehensive neuropsychological testing is limited. The psychometric validity of an ALS-frontotemporal dementia diagnosis using neuropsychological tests is also discussed.
Factors Affecting Adnexal Torsion Direction: A Retrospective Cohort Study
Authors: Krissi Haim , Hiersch Liran , Aviram Amir , Ashwal Eran , Goldschmit Chen , Peled Yoav
Published: December 2015

Aims: To investigate a trend for adnexal torsion direction and factors that may be associated with direction. Methods: We retrospectively reviewed the medical files of all women who underwent exploratory laparoscopy for suspected ovarian torsion in our center from August 2010 to December 2012. Results: Fifty-five women had laparoscopically proven torsion. Medial rotation, defined as clockwise rotation of the left adnexa or counterclockwise rotation of the right adnexa, with the proximal (lateral) segment of the infundibulopelvic ligament serving as the referral point was noted in most cases (n = 47, 85.5%). There was no statistically significant difference between the medial and lateral rotation groups. However, the proportion of pregnant women and mean parity were significantly higher in the lateral compared to the medial rotation group: 62.5 vs. 19.1%, p = 0.009 and 1.1 ± 1.2 vs. 0.1 ± 0.4, p < 0.001. Medial torsion was present in 64.3% of pregnant women vs. 92.7% of nonpregnant women, p = 0.009. Conclusion: The direction of ovarian or adnexal torsion is usually medially rotated, opposite to the psoas muscles and the great blood vessels on the same side. However, surgeons should be aware of an increased rate of lateral rotation among pregnant women.
Retinal Phenotype following Combined Deletion of the Chemokine Receptor CCR2 and the Chemokine CX3CL1 in Mice
Authors: Hagbi-Levi Shira , Grunin Michelle , Elbaz-Hayoun Sarah , Tal David , Obolensky Alexey , Hanhart Joel , Banin Eyal , Burstyn-Cohen Tal , Chowers Itay
Published: December 2015

Purpose: Conflicting data were reported with respect to the retinal phenotype of mice with dual perturbation of the CCL2 and CX3CR1 genes. We report the generation and retinal phenotype of mice with a reverse CCR2/CX3CL1 gene deficiency as a suggested model for age-related macular degeneration (AMD). Methods: Crossing of single-deficient mice generated CCR2/CX3CL1 DKO mice. DKO mice were compared with age-matched C57BL6J mice. Evaluation included color fundus photographs, electroretinography (ERG), histology and morphometric analysis. Immunohistochemistry for CD11b in retinal cross-sections and retinal pigment epithelium (RPE)-choroid flat mounts was performed to assess microglia and macrophage recruitment. Results: A minority of DKO mice showed yellowish subretinal deposits at 10 months. ERG recordings showed reduced cone sensitivity in young, but not older DKO mice. Compared to wild-type mice, DKO mice exhibited 11% reduction in the number of outer nuclear layer nuclei. Old DKO mice had an increased number of CD11b-positive cells across the retina, and on RPE-choroid flat mounts. Conclusions: In the absence of the rd8 allele, deficiency of CCR2 and CX3CL1 in mice leads to a mild form of retinal degeneration which is associated with the recruitment of macrophages, particularly to the subretinal space. This model enables to assess consequences of perturbed chemokine signaling, but it does not recapitulate cardinal AMD features.
Long-Term Management of RAP Lesions in Clinical Practice: Treatment Efficacy and Predictors of Functional Improvement
Authors: Marques Marco Frederico , Marques João Pedro , Gil João Quadrado , Costa José , Almeida Elisabete , Cachulo Maria da Luz , Pires Isabel , Figueira João , Silva Rufino
Published: December 2015

Purpose: To evaluate the long-term efficacy of ranibizumab in the treatment of retinal angiomatous proliferation (RAP) and to identify predictors of functional outcome. Methods: Retrospective case series comprised 79 eyes of 68 consecutive patients with RAP followed up ≥36 months. Primary end-points were best-corrected visual acuity (BCVA) and central macular thickness (CMT) variation at 36 months and at the last visit. Results: Mean follow-up time was 59.8 ± 16.0 months. All eyes were treated with pro re nata ranibizumab, with (n = 33) or without (n = 46) photodynamic therapy (PDT). Stabilization or improvement in BCVA was observed in 50.6% of the patients at 36 months, and in 40.5% at the end of the follow-up, where 20.3% preserved reading vision. A significant decrease in CMT was observed at 36 months (p < 0.001), but not at the end of the follow-up. Geographic atrophy (GA) was present in 59.5% of the eyes at the final visit. Baseline subretinal fluid was associated with better visual outcomes (p = 0.001). Results of combination treatment with intravitreal ranibizumab and PDT did not significantly differ from ranibizumab monotherapy. Conclusion: Modest functional outcomes can be expected from the long-term treatment of RAP lesions in clinical practice, most likely due to the advent of GA. Baseline subretinal fluid positively correlated with final BCVA.
Patterns and Mechanisms of Artificial Kidney Failure during Continuous Renal Replacement Therapy
Authors: Zhang Ling , Tanaka Aiko , Zhu Guijun , Baldwin Ian , Eastwood Glenn M. , Bellomo Rinaldo
Published: December 2015

Background: We aimed to describe the previously unstudied relationship between circuit pressures and circuit clotting, here labeled as ‘artificial kidney failure' (AKF), in patients receiving continuous renal replacement therapy (CRRT). Methods: We performed an observational study of CRRT-treated critically ill patients to continuously record the multiple CRRT circuit pressures. Results: Three patterns of access outflow dysfunction (AOD) were also noted: severe, moderate and mild. Compared with circuits without AOD, circuits experiencing at least one AOD episode had shorter lifespans (14.2 ± 12.7 vs. 21.3 ± 16.5 h, p = 0.057). This effect was more obvious with moderate or severe AOD (8.7 ± 4.6 vs. 20.6 ± 15.7 h, p = 0.007). If any AOD events occurred within the first 4 h, the sensitivity and specificity in predicting early-immediate AKF were 53.4 and 94.4%, respectively. Conclusions: Early and intermediate AKF during CRRT is most likely dependent on AOD, which is a frequent event with variable severity.
Characterization of a de novo Supernumerary Neocentric Ring Chromosome Derived from Chromosome 7
Authors: Louvrier Camille , Egea Grégory , Labalme Audrey , Des Portes Vincent , Gazzo Sophie , Callet-Bauchu Evelyne , Till Marianne , Sanlaville Damien , Edery Patrick , Schluth-Bolard Caroline
Published: December 2015

Supernumerary ring chromosomes (SRC) are usually derived from regions adjacent to the centromere. Their identification may be challenging, particularly in case of low mosaicism. Here, we report on a patient who was referred for major in utero growth retardation, severe developmental delay, facial dysmorphism, cleft palate, and hypospadias. The karyotype showed a small SRC in mosaic. The combination of FISH, M-FISH and array-CGH was necessary for a complete characterization of this SRC. M-FISH revealed that the SRC originated from chromosome 7. Array-CGH performed with a 400K oligonucleotide array showed a gain in region 7q22.1q31.1 present in low mosaic. This result was confirmed by FISH using BAC probes specific for chromosome 7. The SRC was a neocentric ring derived from 7q22.1q31.1 and was found in only 8% of the cells. This is the first patient carrying a mosaic neocentric SRC derived from the long arm of chromosome 7. Our study emphasizes the need to combine different techniques and to use adapted bioinformatic tools for low-mosaicism marker identification. It also contributes to the delineation of the partial trisomy 7q phenotype.
Do Early Seizures Indicate Survival of Patients with Nontraumatic Intracerebral Hemorrhage?
Authors: Brüning Toralf , Awwad Samer , Al-Khaled Mohamed
Published: December 2015

Background and Purpose: Early seizures (ESs) in patients with nontraumatic spontaneous intracerebral hemorrhage (sICH) are a frequent complication. The aims of this study were to determine the frequency of ESs in patients with sICH and to investigate the association of ESs with outcomes in a monocenter study. Methods: During a 5-year period (2009-2013), 484 consecutive patients (mean age 72.3 ± 12.6; female sex 51%) with sICH who were admitted to the Department of Neurology at the University of Lübeck, Germany were enrolled and prospectively evaluated. Results: A total of 52 patients (10.7%; 95% CI 8-14) experienced ESs during a mean hospitalization of 12 days. Patients with ESs were less affected on the National Institutes of Health Stroke Scale at admission than those without ESs (7 vs. 10; p = 0.02). With the exception of the localization of hemorrhage (p = 0.008), differences in the baseline characteristics between patients with ESs and those without ESs were not found. The logistic regression analysis revealed an increased ES rate in patients with cortical hemispheric sICH (OR 3.5; 95% CI 1.8-6.7; p < 0.001). During hospitalization, 109 patients (23%) died and the in-hospital mortality was lower in patients with ESs than those without (9.6 vs. 24.0%, respectively; p = 0.02). An association between ESs and good functional outcome on the modified Rankin Scale ≤2 was not found (p = 0.3). Conclusion: ESs appear to be correlated with hemorrhage localization and associated with survival of the sICH.
Multiple Simultaneous Spontaneous Intracerebral Hemorrhages: A Rare Entity
Authors: Chen Yaohua , Hénon Hilde , Bombois Stéphanie , Pasquier Florence , Cordonnier Charlotte
Published: December 2015

Background: In hospital databases, multiple simultaneous spontaneous intracerebral hemorrhages (ICH-m) account for 0.7-5.6% of all ICHs. Their long-term outcome has never been systematically and prospectively investigated. We aimed at identifying the long-term outcome of patients with ICH-m. Methods: We prospectively recruited consecutive adults with ICH-m and followed them up for at least 4.5 years. We classified patients into the following 3 groups: (i) definite or probable cerebral amyloid angiopathy (CAA), (ii) deep perforating vasculopathy (DPV) and (iii) unknown causes. Results: Of 562 consecutive patients with ICH, 32 had ICH-m (5.7%): 8 (25%) with probable CAA, 5 (16%) with DPV and 19 (59%) with ICH-m of undetermined cause. At the last visit (cumulative follow-up of 39.5 person-year), 27 patients (84%) had died, and 3 of the 5 survivors were independent. Late-onset seizures, recurrent ICH-m (symptomatic or not) and new brain microbleeds were mainly found in patients with probable CAA. Conclusions: ICH-m is a rare but extremely severe expression of ICH. Survivors with CAA are more likely to develop late seizures and new hemorrhagic lesions. Because of low survival rates, large multicenter cohort studies are needed for a better understanding of this rare condition.
Clinical Outcomes of Remote Peritoneal Dialysis Patients: A Retrospective Cohort Study from a Single Center in China
Authors: Yi Chunyan , Guo Qunying , Lin Jianxiong , Huang Fengxian , Yu Xueqing , Yang Xiao
Published: December 2015

Background/Aims: To investigate clinical outcomes of remote peritoneal dialysis (PD) patients in Southern China. Methods: In this retrospective cohort study, incident remote PD patients managed with a comprehensive follow-up program in our PD center were included and clinical outcomes were estimated. Results: One thousand and five remote PD patients with mean age 46.1 ± 14.6 years, of which 38.1% were women, were followed-up for a median of 35.7 months. Patient survival rates were 95.4, 84.7 and 71.8% and death-censored technique survival rates were 98.6, 92.3 and 83.4% at 1, 3 and 5 years, respectively. Peritonitis rate was 0.16 episodes per patient-year. Advanced age, diabetes mellitus, shorter peritonitis-free survival time, poor compliance for regular visiting nephrologists and lower hemoglobin predicted all-cause mortality of remote PD patients. Conclusion: The remote PD patients in Southern China managed with comprehensive follow-up program had favorable clinical outcomes, which indicated that home-based PD therapy could be an appropriate treatment option for remote end-stage kidney disease patients.
Branch Atheromatous Disease: A Clinically Meaningful, Yet Unproven Concept
Authors: Petrone Luca , Nannoni Stefania , Del Bene Alessandra , Palumbo Vanessa , Inzitari Domenico
Published: December 2015

Background: In 1989, Louis Caplan first used the term branch atheromatous disease (BAD) to describe an occlusion or stenosis at the origin of a deep penetrating artery of the brain, associated with a microatheroma or a junctional plaque, and leading to an internal capsule or pontine small infarct. BAD remained an understudied concept for decades. In recent years, the increasing diffusion of high-resolution magnetic resonance imaging (HRMRI) techniques brought new attention to the BAD debate. We have reviewed clinical studies dealing with BAD-related stroke checking whether a univocal definition of BAD existed, as well as to what extent were consistently associated clinical and imaging features reported. Summary: We conducted a search of the available literature published up to October 20, 2015 via PubMed using the following search terms: ‘branch atheromatous disease,' ‘intracranial branch atheromatous disease,' ‘cerebral branch atheromatous disease,' combined with ‘stroke.' Forty-six articles were included. We found discrepant definitions and a large variation among clinical features reported in BAD-related stroke patients: among others, a consistent association between BAD and any specific vascular risk factor profile was not detected. Despite this, early neurological deterioration (END) was consistently reported to occur frequently in such patients, although no clear-cut rate range or specific predictor or mechanism of progression was established. In a majority of the studies reporting imaging data, BAD diagnosis was not based on the selective site or type of arterial walls changes, but was inferred based on the vascular territory, size and/or shape of the ischemic lesion. Following the concept that these changes are seated proximally along the perforator artery, differently from to lipohyalinosis changes located distally, the consequent ischemic lesion was hypothesized to be larger in BAD than in lacunar infarcts. However, across reviewed studies, there was little consistency on the dimensional cutoff used to define BAD-related infarcts. In the last few years, a still limited number of studies using HRMRI techniques is providing preliminary proofs that atheromatous changes causing selective remodeling in the parent vessel and extending through the proximal segment of perforating vessel may subtend BAD. Key Messages: Our literature search showed the lack of a clear-cut definition of BAD, although BAD-related strokes were consistently considered a high risk of END. The use of high-resolution imaging techniques in the assessment of small subcortical strokes may represent the cornerstone in the perspective to better delimiting the boundaries of BAD as a nosological entity.
Extracellular Vesicles from Red Blood Cell Products Induce a Strong Pro-Inflammatory Host Response,  Dependent on Both Numbers and Storage Duration
Authors: Straat Marleen , Böing Anita N. , Tuip-De Boer Anita , Nieuwland Rienk , Juffermans Nicole P.
Published: December 2015

Background: Transfusion of red blood cells (RBCs) is associated with adverse outcome, but the causative factor is unknown. Extracellular vesicles (EVs) have pro-inflammatory properties. We hypothesized that EVs released from both fresh and stored RBC products can induce a host inflammatory response in a dose-dependent manner. Methods: Whole blood was incubated with supernatant from RBC units stored for different time periods, either containing (different numbers of) EVs or depleted from EVs. Results: Incubation with both fresh and stored supernatant containing EVs induced a strong host response with production of TNF, IL-6 and IL-8. In supernatant depleted from EVs, this host response was completely abrogated. IL-10 levels were not affected. EV-induced host response was both dependent on the number of EVs as well as on storage time. Conclusions: EVs from both fresh and stored RBC units illicit a strong inflammatory host response in recipients and may therefore contribute to adverse outcome of RBC transfusion.
Living Long and Well: Prospects for a Personalized Approach to the Medicine of Ageing
Authors: Fuellen Georg , Schofield Paul , Flatt Thomas , Schulz Ralf-Joachim , Boege Fritz , Kraft Karin , Rimbach Gerald , Ibrahim Saleh , Tietz Alexander , Schmidt Christian , Köhling Rüdiger , Simm Andreas
Published: December 2015

Research into ageing and its underlying molecular basis enables us to develop and implement targeted interventions to ameliorate or cure its consequences. However, the efficacy of interventions often differs widely between individuals, suggesting that populations should be stratified or even individualized. Large-scale cohort studies in humans, similar systematic studies in model organisms as well as detailed investigations into the biology of ageing can provide individual validated biomarkers and mechanisms, leading to recommendations for targeted interventions. Human cohort studies are already ongoing, and they can be supplemented by in silico simulations. Systematic studies in animal models are made possible by the use of inbred strains or genetic reference populations of mice. Combining the two, a comprehensive picture of the various determinants of ageing and ‘health span' can be studied in detail, and an appreciation of the relevance of results from model organisms to humans is emerging. The interactions between genotype and environment, particularly the psychosocial environment, are poorly studied in both humans and model organisms, presenting serious challenges to any approach to a personalized medicine of ageing. To increase the success of preventive interventions, we argue that there is a pressing need for an individualized evaluation of interventions such as physical exercise, nutrition, nutraceuticals and calorie restriction mimetics as well as psychosocial and environmental factors, separately and in combination. The expected extension of the health span enables us to refocus health care spending on individual prevention, starting in late adulthood, and on the brief period of morbidity at very old age.
N‐Terminal Pro–Brain Natriuretic Peptide (NT‐proBNP) Levels are Increased in Patients With Transient Ischemic Attack Accompanied by Nonfocal Symptoms
Authors: Plas Gerben J. J. , Jurg Susanne D. , Brusse‐Keizer Marjolein , Dippel Diederik W. J. , Koudstaal Peter J. , den Hertog Heleen M.
Published: December 2015

Background

Transient nonfocal neurological symptoms may serve as markers of cardiac dysfunction. We assessed whether serum N‐terminal pro–brain natriuretic peptide (
NT
‐pro
BNP)
levels, a biomarker of cardiac disease, are increased in patients with transient ischemic attack
(TIA)
accompanied by nonfocal symptoms and in patients with attacks of nonfocal symptoms (transient neurological attack [
TNA]
).

Methods and Results

We included 15 patients with
TNA
, 69 with
TIA
accompanied by nonfocal symptoms, 58 with large‐vessel
TIA
, 32 with cardioembolic
TIA
, and 46 age‐ and sex‐matched healthy control participants. Serum
NT
‐pro
BNP
levels were determined within 1 week after the attack. We compared log‐transformed
NT
‐pro
BNP
levels of patients with cardioembolic
TIA
s and mixed or nonfocal
TNA
s, with those of patients with noncardioembolic
TIA
s as a reference group. Adjustments for age, sex, atrial fibrillation, and a history of nonischemic heart disease were made with a multiple linear regression model. Compared with large‐vessel
TIA
(mean 14.2 pmol/L), mean
NT
‐pro
BNP
levels were significantly higher in patients with
TIA
accompanied by nonfocal symptoms (40.5 pmol/L,
P
=0.049) and with cardioembolic
TIA
(123.5 pmol/L;
P
=0.004) after adjustments for age, sex, atrial fibrillation, and a history of nonischemic heart disease. Patients with
TNA
also had higher mean
NT
‐pro
BNP
levels (20.8 pmol/L,
P
=0.38) than those with large‐vessel
TIA
, but this difference was not statistically significant.

Conclusion

NT
‐pro
BNP
levels are increased in patients with
TIA
accompanied by nonfocal symptoms.
Disparities in Temporal and Geographic Patterns of Declining Heart Disease Mortality by Race and Sex in the United States, 1973–2010
Authors: Vaughan Adam S. , Quick Harrison , Pathak Elizabeth B. , Kramer Michael R. , Casper Michele
Published: December 2015

Background

Examining small‐area differences in the strength of declining heart disease mortality by race and sex provides important context for current racial and geographic disparities and identifies localities that could benefit from targeted interventions. We identified and described temporal trends in declining county‐level heart disease mortality by race, sex, and geography between 1973 and 2010.

Methods and Results

Using a Bayesian hierarchical model, we estimated age‐adjusted mortality with diseases of the heart listed as the underlying cause for 3099 counties. County‐level percentage declines were calculated by race and sex for 3 time periods (1973–1985, 1986–1997, 1998–2010). Strong declines were statistically faster or no different than the total national decline in that time period. We observed county‐level race–sex disparities in heart disease mortality trends. Continual (from 1973 to 2010) strong declines occurred in 73.2%, 44.6%, 15.5%, and 17.3% of counties for white men, white women, black men, and black women, respectively. Delayed (1998–2010) strong declines occurred in 15.4%, 42.0%, 75.5%, and 76.6% of counties for white men, white women, black men, and black women, respectively. Counties with the weakest patterns of decline were concentrated in the South.

Conclusions

Since 1973, heart disease mortality has declined substantially for these race–sex groups. Patterns of decline differed by race and geography, reflecting potential disparities in national and local drivers of these declines. Better understanding of racial and geographic disparities in the diffusion of heart disease prevention and treatment may allow us to find clues to progress toward racial and geographic equity in heart disease mortality.
Socio-environmental Disputes within mercosur: Lack of a More Meaningful Cooperation
Authors: de Almeida Bruno Rodrigues , de Vasconcelos Raphael Carvalho
Published: December 2015

Global environmental degradation is but one aspect of a crisis in human rationality, resulting from anthropocentric and unsustainable paradigms. Increasing awareness towards the need for sustainability promotes rationality standards founded in holistic and interdisciplinary approaches that encourage participatory governance at various levels. Within this context, the peaceful settlement of cross-border, socio-environmental conflicts represents a challenge to the unilateral exercise of jurisdiction, owing to issues such as enforceability, effectiveness and the granting of provisional measures. Hence, international, regional and/or sub-regional entities must become meaningful vehicles for institutional environmental cooperation, in order to establish higher levels of participatory governance among relevant local, regional and global players. mercosur’s Environmental Framework Agreement (Decision cmc nº 2 of June 22, 2001), its Additional Protocol on Cooperation on Environmental Emergencies (Decision cmc nº 4 of July 8, 2004) and the Summit of Environmental Ministers of mercosur (Decision cmc nº 19 of December 15, 2003) represent important steps towards the promotion of socio-environmental, cultural, political, economic, ecological and geographical sustainability. However, its dispute settlement system is still lacking in additional institutional cooperation principles and rules to achieve these goals. It can be argued that Member States should engender the additional regulatory framework to reduce asymmetries between local socio-environmental public policies and, thus, inspire stronger confidence in the effectiveness of its dispute settlement system.
Procedural Developments at the International Criminal Court (2014)
Authors: Le Floch Guillaume , Lemey Marie , Paiola Lucie
Published: December 2015

The current column covers some selected procedural developments at the International Criminal Court (“icc”) in 2014. During the reporting period, the caseload of the Court continued to increase. The Court delivered numerous decisions on many subjects, several of which have contributed to the clarification of certain aspects of proceedings before the Court.
Abkhaz Personal Names
Authors: Chirikba Viacheslav A.
Published: December 2015

The paper presents a study of the Abkhaz personal names. Traditionally, Abkhazians, a Caucasian people living in the Republic of Abkhazia (many Abkhazians live also in Turkey and in some Middle Eastern countries), used a two-name system, consisting, as a rule, of the surname plus the postposed first name. The Abkhaz personal names are analysed with regard to their origin, structure, semantics, and social status. The onomastic system in general, as well as the tradition of naming among the Abkhazians are outlined as well.
Forty centimeter long transverse and radial sections cut from fresh increment cores
Authors: Ivanova Albena , Dolezal Jiri , Gärtner Holger , Schweingruber Fritz
Published: December 2015

The analysis of anatomical variations within annual rings of trees and shrubs has great potential for reconstructing past environmental conditions. However, detailed wood anatomical analysis has rarely been applied to long-term reconstructions mostly because of methodological constraints and time-consuming procedures of data collection. We developed a new technique to prepare long, 15–20 μm thick sections for wood anatomical analyses cut from fresh increment cores with a length of up to 40 cm. We used an improved version of the WSL core-microtome and tested the method by sectioning 400 cores from 6 conifer and 25 deciduous species. Standardly used staining and dehydration procedures were successfully applied. This simple, easily applicable and fast technique opens a vast field of possible research by allowing anatomical analysis of long tree-ring cores. In this way long and well-replicated chronologies of cell structures can be developed.
A new species and a new combination of Phalaenopsis (Orchidaceae: Epidendroideae: Aeridinae): evidence from morphological and DNA analysis
Authors: DENG HUA , ZHANG GUO-QIANG , Liu Zhong-Jian , WANG YAN
Published: December 2015

A new species of Phalaenopsis, P. pingxiangensis, from Guangxi, China, is described and illustrated. Detailed morphological comparison between the newly discovered orchid and other members of Phalaenopsis s.l. indicate that P. pingxiangensis is similar to P. marriottiana. The new species differs from the latter in its small stature, short inflorescence with two flowers, smaller and pink flower with pale yellow sepals abaxially, orbicular petals, purple-red, flabellate lip and terete column without wings. The molecular analyses of Phalaenopsis indicate that P. pingxiangensis is a distinct species nested in P. subgenus Hygrochilus. In addition, Hygrochilus tsii is transferred to Phalaenopsis.
Cytological status of Viola kitaibeliana (Section Melanium, Violaceae) in Europe
Authors: Magrini Sara , Scoppola Anna
Published: December 2015

Viola kitaibeliana Schultes in Roemer & Schultes (1819: 383) was described for “Pannonia” as a small pansy with “caule erecto simplicissimo, foliis grosse crenatis, inferioribus subrotundis glabris, superioribus obovatis, stipulis similibus subintegerrimis, basive subpinnatis, petalo cornuto calycem glabrum aequante, reliquis brevioribus. Arvensi proxima, hac praecocior multo, (Aprili florens!) tenerior, et notis indicatis satis distincta. Flores 2, vel unicus, raro tres, oblique erecti in pedunculis folia excedentibus.” (Typus: M0112803; Fig. 1). Thereafter, many other names have been assigned to similar pansies described outside the Pannonian region: e.g. V. tricolor Linneus (1753: 935) var. nana De Candolle (1824: 304) and V. nemausensis Jordan (1846: 18) in France, V. tricolor subsp. minima Gaudin (1828: 210) in Switzerland, V. tricolor var. trimestris De Candolle (1824: 304), V. tricolor var. henriquesii Willk. ex Coutinho (1892: 36) and V. tricolor var. machadeana Coutinho (1892: 36) in the Iberian Peninsula. None of these taxa have been reported in Flora Europaea by Valentine et al. (1968) and later they have been included in V. kitaibeliana or placed in synonymy with it in the main floras (e.g. Muñoz Garmendia et al. 1993). According to Valentine et al. (1968) and to the updates of Magrini & Scoppola (2015b), in Europe V. kitaibeliana is widespread from Southwest to East, extending to Ukraine (Fig. 2).
New earthworms of the Amynthas morrisi-group (Oligochaeta, Megascolecidae) from Hainan Island, China
Authors: SUN JING , JIANG JI-BAO , ZHAO QI , QIU JIANG-PING
Published: December 2015

This paper describes two new species of earthworms belonging to the Amynthas morrisi-group from Hainan Island, China: Amynthas zonarius sp. nov. and Amynthas wuzhimontis sp. nov. Both have two pairs of spermathecal pores in 5/6–6/7, and simple intestinal caeca. Amynthas zonarius sp. nov. has a pad-like male porophore, with flat-topped tubercle surrounded by 5 skin folds distal half of the spermathecal diverticulum dilated into band-shaped seminal chamber. Amynthas wuzhimontis sp. nov. has a seminal chamber constricted into moniliform subchambers and a glandular pad-like elliptical male pore porophore surrounded by the tumid area. Partial COI sequences of the holotypes of the two new species have been submitted to GenBank as DNA barcodes to enable molecular species identification.
Satellite and In Situ Salinity: Understanding Near-Surface Stratification and Subfootprint Variability
Authors: Boutin J. , Chao Y. , Asher W. E. , Delcroix T. , Drucker R. , Drushka K. , Kolodziejczyk N. , Lee T. , Reul N. , Reverdin G. , Schanze J. , Soloviev A. , Yu L. , Anderson J. , Brucker L. , Dinnat E. , Santos-Garcia A. , Jones W. L. , Maes C. , Meissner T. , Tang W. , Vinogradova N. , Ward B.
Published: December 2015

Remote sensing of salinity using satellite-mounted microwave radiometers provides new perspectives for studying ocean dynamics and the global hydrological cycle. Calibration and validation of these measurements is challenging because satellite and in situ methods measure salinity differently. Microwave radiometers measure the salinity in the top few centimeters of the ocean, whereas most in situ observations are reported below a depth of a few meters. Additionally, satellites measure salinity as a spatial average over an area of about 100 × 100 km2. In contrast, in situ sensors provide pointwise measurements at the location of the sensor. Thus, the presence of vertical gradients in, and horizontal variability of, sea surface salinity complicates comparison of satellite and in situ measurements. This paper synthesizes present knowledge of the magnitude and the processes that contribute to the formation and evolution of vertical and horizontal variability in near-surface salinity. Rainfall, freshwater plumes, and evaporation can generate vertical gradients of salinity, and in some cases these gradients can be large enough to affect validation of satellite measurements. Similarly, mesoscale to submesoscale processes can lead to horizontal variability that can also affect comparisons of satellite data to in situ data. Comparisons between satellite and in situ salinity measurements must take into account both vertical stratification and horizontal variability.
Assessment and Implications of NCEP Stage IV Quantitative Precipitation Estimates for Product Intercomparisons
Authors: Nelson Brian R. , Prat Olivier P. , Seo D.-J. , Habib Emad
Published: December 2015

The National Centers for Environmental Prediction (NCEP) stage IV quantitative precipitation estimates (QPEs) are used in many studies for intercomparisons including those for satellite QPEs. An overview of the National Weather Service precipitation processing system is provided here so as to set the stage IV product in context and to provide users with some knowledge as to how it is developed. Then, an assessment of the stage IV product over the period 2002–12 is provided. The assessment shows that the stage IV product can be useful for conditional comparisons of moderate-to-heavy rainfall for select seasons and locations. When evaluating the product at the daily scale, there are many discontinuities due to the operational processing at the radar site as well as discontinuities due to the merging of data from different River Forecast Centers (RFCs) that use much different processing algorithms for generating their precipitation estimates. An assessment of the daily precipitation estimates is provided based on the cumulative distribution function for all of the daily estimates for each RFC by season. In addition it is found that the hourly estimates at certain RFCs suffer from lack of manual quality control and caution should be used.
The Crucifixion Scene as the Climax of Lukan Inclusivity
Authors: Wilson Benjamin R.
Published: December 2015

Many interpreters have noted that Luke’s gospel emphasizes the inclusive parameters of Jesus’ ministry, as figures from a wide range of social locations are characterized positively as the surprising recipients of divine favour and models of a faithful perspective toward Jesus. The present article considers Luke’s passion narrative in light of this prominent Lukan theme, finding that Luke’s special interest in the universality of Jesus’ ministry reaches its climax at the cross. The article outlines the inclusive parameters of Jesus’ ministry throughout Luke’s gospel and then shows how this theme is developed through the characterization of a series of figures within the passion narrative.
Kingship and Thrones for All Christians: Paul’s Inaugurated Eschatology in 1 Corinthians 4–6
Authors: Wenkel David H.
Published: December 2015

The central argument presented here is that 1 Corinthians 4–6 reflects a single eschatological vision of the identity of the Corinthians. This single vision works itself out in two separate references as Paul addresses them as both ‘kings’ and ‘judges’. This conclusion is based on a fresh reading of Paul’s identification of the Corinthians as ‘kings’ in 1 Cor. 4 and ‘judges’ in 1 Cor. 6. This study proposes that these labels actually reflect a single reality based on Paul’s inaugurated eschatology.