bluuebunny/crossref_metadata_2025 huggingface dataset:
STRAPS: A Fully Data-Driven Spatio-Temporally Regularized Algorithm for M/EEG Patch Source Imaging
Authors: Liu Ke , Yu Zhu Liang , Wu Wei , Gu Zhenghui , Li Yuanqing
Published: March 2015

For M/EEG-based distributed source imaging, it has been established that the L2-norm-based methods are effective in imaging spatially extended sources, whereas the L1-norm-based methods are more suited for estimating focal and sparse sources. However, when the spatial extents of the sources are unknown a priori, the rationale for using either type of methods is not adequately supported. Bayesian inference by exploiting the spatio-temporal information of the patch sources holds great promise as a tool for adaptive source imaging, but both computational and methodological limitations remain to be overcome. In this paper, based on state-space modeling of the M/EEG data, we propose a fully data-driven and scalable algorithm, termed STRAPS, for M/EEG patch source imaging on high-resolution cortices. Unlike the existing algorithms, the recursive penalized least squares (RPLS) procedure is employed to efficiently estimate the source activities as opposed to the computationally demanding Kalman filtering/smoothing. Furthermore, the coefficients of the multivariate autoregressive (MVAR) model characterizing the spatial-temporal dynamics of the patch sources are estimated in a principled manner via empirical Bayes. Extensive numerical experiments demonstrate STRAPS's excellent performance in the estimation of locations, spatial extents and amplitudes of the patch sources with varying spatial extents.
A Programmer–Interpreter Neural Network Architecture for Prefrontal Cognitive Control
Authors: Donnarumma Francesco , Prevete Roberto , Chersi Fabian , Pezzulo Giovanni
Published: March 2015

There is wide consensus that the prefrontal cortex (PFC) is able to exert cognitive control on behavior by biasing processing toward task-relevant information and by modulating response selection. This idea is typically framed in terms of top-down influences within a cortical control hierarchy, where prefrontal-basal ganglia loops gate multiple input–output channels, which in turn can activate or sequence motor primitives expressed in (pre-)motor cortices. Here we advance a new hypothesis, based on the notion of programmability and an interpreter–programmer computational scheme, on how the PFC can flexibly bias the selection of sensorimotor patterns depending on internal goal and task contexts. In this approach, multiple elementary behaviors representing motor primitives are expressed by a single multi-purpose neural network, which is seen as a reusable area of "recycled" neurons (interpreter). The PFC thus acts as a "programmer" that, without modifying the network connectivity, feeds the interpreter networks with specific input parameters encoding the programs (corresponding to network structures) to be interpreted by the (pre-)motor areas. Our architecture is validated in a standard test for executive function: the 1-2-AX task. Our results show that this computational framework provides a robust, scalable and flexible scheme that can be iterated at different hierarchical layers, supporting the realization of multiple goals. We discuss the plausibility of the "programmer–interpreter" scheme to explain the functioning of prefrontal-(pre)motor cortical hierarchies.
An Efficient and Effective Algorithm for Large Scale Global Optimization Problems
Authors: Lian Kanchao , Peng Xu-Yu , Ouyang Aijia
Published: March 2015

Invasive weed optimization (IWO) algorithm and quantum-behaved particle swarm optimization (QPSO) algorithm are inclined to fall into local optimum with lower convergence accuracy when separately used to deal with large scale global optimization (LSGO) problems. In order to fully utilize the advantages of these two intelligent algorithms and complement each other, following the idea of portfolio optimization, this paper correspondingly adjusts and improves the quantum models of IWO and QPSO, organically integrates the two algorithms, and proposes the quantum-behaved invasive weed optimization (QIWO) algorithm. This mixed algorithm can achieve the purpose of information exchange and cooperative search through alternate search enables the make algorithm converge to the optimal solution quickly, properly overcoming the defects of falling into local optimum and premature convergence. Test results of 20 LSGO functions show that compared with other algorithms, QIWO has stronger global optimization capability, faster convergence speed and higher convergence accuracy.
Entropy, stability, and Yang–Mills flow
Authors: Kelleher Casey , Streets Jeffrey
Published: March 2015

Following [T. Colding and W. Minicozzi, II, Generic mean curvature flow I; generic singularities, Ann. of Math. 175(2) (2012) 755–833], we define a notion of entropy for connections over [Formula: see text] which has shrinking Yang–Mills solitons as critical points. As in [T. Colding and W. Minicozzi, II, Generic mean curvature flow I; generic singularities, Ann. of Math. 175(2) (2012) 755–833], this entropy is defined implicitly, making it difficult to work with analytically. We prove a theorem characterizing entropy stability in terms of the spectrum of a certain linear operator associated to the soliton. This leads furthermore to a gap theorem for solitons. These results point to a broader strategy of studying “generic singularities” of the Yang–Mills flow, and we discuss the differences in this strategy in dimension [Formula: see text] versus [Formula: see text].
Concentration analysis in Banach spaces
Authors: Solimini Sergio , Tintarev Cyril
Published: March 2015

The concept of a profile decomposition formalizes concentration compactness arguments on the functional-analytic level, providing a powerful refinement of the Banach–Alaoglu weak-star compactness theorem. We prove existence of profile decompositions for general bounded sequences in uniformly convex Banach spaces equipped with a group of bijective isometries, thus generalizing analogous results previously obtained for Sobolev spaces and for Hilbert spaces. Profile decompositions in uniformly convex Banach spaces are based on the notion of [Formula: see text]-convergence by Lim [Remarks on some fixed point theorems, Proc. Amer. Math. Soc. 60 (1976) 179–182] instead of weak convergence, and the two modes coincide if and only if the norm satisfies the well-known Opial condition, in particular, in Hilbert spaces and [Formula: see text]-spaces, but not in [Formula: see text], [Formula: see text]. [Formula: see text]-convergence appears naturally in the context of fixed point theory for non-expansive maps. The paper also studies the connection of [Formula: see text]-convergence with the Brezis–Lieb lemma and gives a version of the latter without an assumption of convergence a.e.
Zinc deficiency mediates alcohol-induced apoptotic cell death in the liver of rats through activating ER and mitochondrial cell death pathways
Authors: Sun Qian , Zhong Wei , Zhang Wenliang , Li Qiong , Sun Xiuhua , Tan Xiaobing , Sun Xinguo , Dong Daoyin , Zhou Zhanxiang
Published: March 2015

Hepatic zinc deficiency has been well documented in alcoholic patients, but the mechanisms by which zinc deficiency mediates cell death have not been well defined. The objectives of this study were to determine whether alcohol perturbs subcellular zinc homeostasis and how organelle zinc depletion may link with cell death pathways. Wistar rats were pair-fed with the Lieber-DeCarli control or ethanol diet for 5 mo. Chronic alcohol exposure significantly reduced zinc level in isolated hepatic endoplasmic reticulum (ER) and mitochondria. Among the detected zinc transporters, ER Zrt/Irt-like protein (ZIP)13 and mitochondrial ZIP8, which transport zinc from ER and mitochondria to cytosol, were significantly increased. Mitochondrial zinc transporter (ZnT) 4, which transports zinc from cytosol to mitochondria, was also increased. ER phosphorylated eukaryotic initiation factor 2α, activating transcription factor 4, and C/EBP homologous protein were significantly upregulated, and mitochondrial cytochrome c release and Bax insertion were detected in association with caspase-3 activation and apoptotic cell death. To define the role of zinc deficiency in ER and mitochondrial stress, H4IIEC3 cells were treated with 3 μM N,N,N′,N′-tetrakis (2-pyridylmethyl) ethylenediamine for 6 h with or without supplementation with zinc or N-acetylcysteine (NAC). The results demonstrated that zinc deprivation induced caspase-3 activation and apoptosis in association with ER and mitochondria dysfunction, which were inhibited by zinc as low as 10 μM but not by 2 mM NAC. These results suggest that chronic ethanol exposure induced in ER and mitochondrial zinc deficiency might activate intrinsic cell death signaling pathway, which could not be effectively rescued by antioxidant treatment.
Animal models of gastrointestinal and liver diseases. Animal models of visceral pain: pathophysiology, translational relevance, and challenges
Authors: Greenwood-Van Meerveld Beverley , Prusator Dawn K. , Johnson Anthony C.
Published: March 2015

Visceral pain describes pain emanating from the thoracic, pelvic, or abdominal organs. In contrast to somatic pain, visceral pain is generally vague, poorly localized, and characterized by hypersensitivity to a stimulus such as organ distension. Animal models have played a pivotal role in our understanding of the mechanisms underlying the pathophysiology of visceral pain. This review focuses on animal models of visceral pain and their translational relevance. In addition, the challenges of using animal models to develop novel therapeutic approaches to treat visceral pain will be discussed.
Restraint stress exacerbates cardiac and adipose tissue pathology via β-adrenergic signaling in rats with metabolic syndrome
Authors: Matsuura Natsumi , Nagasawa Kai , Minagawa Yuji , Ito Shogo , Sano Yusuke , Yamada Yuichiro , Hattori Takuya , Watanabe Shogo , Murohara Toyoaki , Nagata Kohzo
Published: March 2015

Restraint stress stimulates sympathetic nerve activity and can affect adiposity and metabolism. However, the effects of restraint stress on cardiovascular and metabolic disorders in metabolic syndrome (MetS) have remained unclear. We investigated the effects of chronic restraint stress and β-adrenergic receptor (β-AR) blockade on cardiac and adipose tissue pathology and metabolic disorders in a rat model of MetS. DahlS.Z- Leprfa/ Leprfa (DS/obese) rats, derived from a cross between Dahl salt-sensitive and Zucker rats. Rats were exposed to restraint stress (restraint cage, 2 h/day) for 4 wk from 9 wk of age with or without daily subcutaneous administration of the β-AR blocker propranolol (2 mg/kg). Age-matched homozygous lean littermates of DS/obese rats (DahlS.Z- Lepr+ /Lepr+ rats) served as control animals. Chronic restraint stress exacerbated hypertension as well as left ventricular hypertrophy, fibrosis, diastolic dysfunction, and oxidative stress in a manner sensitive to propranolol treatment. Restraint stress attenuated body weight gain in DS/obese rats, and this effect tended to be reversed by propranolol ( P = 0.0682). Restraint stress or propranolol did not affect visceral or subcutaneous fat mass. However, restraint stress potentiated cardiac and visceral adipose tissue inflammation in DS/obese rats, and these effects were ameliorated by propranolol. Restraint stress also exacerbated glucose intolerance, insulin resistance, and abnormal lipid metabolism in a manner sensitive to propranolol. In addition, restraint stress increased urinary norepinephrine excretion, and propranolol attenuated this effect. Our results thus implicate β-ARs in the exacerbation of cardiac and adipose tissue pathology and abnormal glucose and lipid metabolism induced by restraint stress in this model of MetS.
Proresolving actions of a new resolvin D1 analog mimetic qualifies as an immunoresolvent
Authors: Orr Sarah K. , Colas Romain A. , Dalli Jesmond , Chiang Nan , Serhan Charles N.
Published: March 2015

Resolution of inflammation is an active process driven by several new families of endogenous lipid mediators collectively coined specialized proresolving mediators (SPM). Here, we report a synthetic analog of resolvin D1 (RvD1) and aspirin-triggered RvD1, benzo-diacetylenic-17 R-RvD1-methyl ester (BDA-RvD1), which was prepared using fewer steps than required for total organic synthesis of natural SPM. BDA-RvD1 was resistant to further metabolism by human recombinant 15-prostaglandin dehydrogenase, a major inactivation pathway for RvD1. In ischemia-reperfusion-initiated second organ injury, BDA-RvD1 intravenously (1 μg) reduced neutrophil infiltration into the lungs by 58 ± 9% and was significantly more potent than native RvD1. BDA-RvD1 at 100 ng/mouse also shortened the resolution interval, Ri, of Escherichia coli peritonitis with a similar potency as RvD1, by ∼57%, from Ri 10.5 h to 4.5 h. With isolated human phagocytes, BDA-RvD1 at picomolar concentrations (10−12 M) stimulated phagocytosis of zymosan A particles. BDA-RvD1 activated human recombinant G protein-coupled receptor 32/DRV1, an RvD1 receptor, in a dose-dependent manner. These results indicate that, both in vivo in mice and with isolated human cells, BDA-RvD1 shares defining proresolving actions of RvD1, including inhibiting leukocyte infiltration and stimulating phagocytosis. Moreover, they provide evidence for a new analog mimetic and example of an immunoresolvent, namely an agent that stimulates active resolution of inflammation, for a potential new therapeutic class.
Can intradermal administration of angiotensin II influence human heat loss responses during whole body heat stress?
Authors: Fujii Naoto , Meade Robert D. , Paull Gabrielle , McGinn Ryan , Foudil-bey Imane , Akbari Pegah , Kenny Glen P.
Published: March 2015

It is unclear if angiotensin II, which can increase the production of reactive oxygen species (oxidative stress), modulates heat loss responses of cutaneous blood flow and sweating. We tested the hypothesis that angiotensin II-induced increases in oxidative stress impair cutaneous perfusion and sweating during rest and exercise in the heat. Eleven young (24 ± 4 yr) healthy adults performed two 30-min cycling bouts at a fixed rate of metabolic heat production (400 W) in the heat (35°C). The first and second exercises were followed by a 20- and 40-min recovery. Four microdialysis fibers were placed in the forearm skin for continuous administration of either: 1) lactated Ringer (control), 2) 10 μM angiotensin II, 3) 10 mM ascorbate (an antioxidant), or 4) a combination of 10 μM angiotensin II + 10 mM ascorbate. Cutaneous vascular conductance (CVC; laser-Doppler perfusion units/mean arterial pressure) and sweating (ventilated capsule) were evaluated at each skin site. Compared with control, angiotensin II reduced both CVC and sweating at baseline resting and during each recovery in the heat (all P < 0.05). However, during both exercise bouts, there were no differences in CVC or sweating between the treatment sites (all P > 0.05). When ascorbate was coinfused with angiotensin II, the effect of angiotensin II on sweating was abolished (all P > 0.05); however, its effect on CVC at baseline resting and during each recovery remained intact (all P < 0.05). We show angiotensin II impairs cutaneous perfusion independent of oxidative stress, while it impairs sweating through increasing oxidative stress during exposure to an ambient heat stress before and following exercise.
Torque decrease during submaximal evoked contractions of the quadriceps muscle is linked not only to muscle fatigue
Authors: Matkowski Boris , Lepers Romuald , Martin Alain
Published: March 2015

The aim of this study was to analyze the neuromuscular mechanisms involved in the torque decrease induced by submaximal electromyostimulation (EMS) of the quadriceps muscle. It was hypothesized that torque decrease after EMS would reflect the fatigability of the activated motor units (MUs), but also a reduction in the number of MUs recruited as a result of changes in axonal excitability threshold. Two experiments were performed on 20 men to analyze 1) the supramaximal twitch superimposed and evoked at rest during EMS ( Experiment 1, n = 9) and 2) the twitch response and torque-frequency relation of the MUs activated by EMS ( Experiment 2, n = 11). Torque loss was assessed by 15 EMS-evoked contractions (50 Hz; 6 s on/6 s off), elicited at a constant intensity that evoked 20% of the maximal voluntary contraction (MVC) torque. The same stimulation intensity delivered over the muscles was used to induce the torque-frequency relation and the single electrical pulse evoked after each EMS contraction ( Experiment 2). In Experiment 1, supramaximal twitch was induced by femoral nerve stimulation. Torque decreased by ∼60% during EMS-evoked contractions and by only ∼18% during MVCs. This was accompanied by a rightward shift of the torque-frequency relation of MUs activated and an increase of the ratio between the superimposed and posttetanic maximal twitch evoked during EMS contraction. These findings suggest that the torque decrease observed during submaximal EMS-evoked contractions involved muscular mechanisms but also a reduction in the number of MUs recruited due to changes in axonal excitability.
Does nebulized fentanyl relieve dyspnea during exercise in healthy man?
Authors: Kotrach Houssam G. , Bourbeau Jean , Jensen Dennis
Published: March 2015

Few therapies exist for the relief of dyspnea in restrictive lung disorders. Accumulating evidence suggests that nebulized opioids selective for the mu-receptor subtype may relieve dyspnea by modulating intrapulmonary opioid receptor activity. Our respective primary and secondary objectives were to test the hypothesis that nebulized fentanyl (a mu-opioid receptor agonist) relieves dyspnea during exercise in the presence of abnormal restrictive ventilatory constraints and to identify the physiological mechanisms of this improvement. In a randomized, double-blind, placebo-controlled crossover study, we examined the effect of 250 μg nebulized fentanyl, chest wall strapping (CWS), and their interaction on detailed physiological and perceptual responses to constant work rate cycle exercise (85% of maximum incremental work rate) in 14 healthy, fit young men. By design, CWS decreased vital capacity by ∼20% and mimicked the negative consequences of a mild restrictive lung disorder on exercise endurance time and on dyspnea, breathing pattern, dynamic operating lung volumes, and diaphragmatic electromyographic and respiratory muscle function during exercise. Compared with placebo under both unrestricted control and CWS conditions, nebulized fentanyl had no effect on exercise endurance time, integrated physiological response to exercise, sensory intensity, unpleasantness ratings of exertional dyspnea. Our results do not support a role for intrapulmonary opioids in the neuromodulation of exertional dyspnea in health nor do they provide a physiological rationale for the use of nebulized fentanyl in the management of dyspnea due to mild restrictive lung disorders, specifically those arising from abnormalities of the chest wall and not affiliated with airway inflammation.
Muscle-specific glucose and free fatty acid uptake after sprint interval and moderate-intensity training in healthy middle-aged men
Authors: Eskelinen Jari-Joonas , Heinonen Ilkka , Löyttyniemi Eliisa , Saunavaara Virva , Kirjavainen Anna , Virtanen Kirsi A. , Hannukainen Jarna C. , Kalliokoski Kari K.
Published: March 2015

We tested the hypothesis that sprint interval training (SIT) causes larger improvements in glucose and free fatty acid uptake (FFAU) in lower and upper body muscles than moderate-intensity training (MIT). Twenty-eight healthy, untrained, middle-aged men were randomized into SIT ( n = 14, 4–6 × 30 s of all-out cycling/4 min recovery) and MIT groups [ n = 14, 40–60 min cycling at 60% of peak O2 uptake (V̇o2 peak)] and completed six training sessions within 2 wk. Pre- and postmeasurements included V̇o2 peak, whole body (M-value), muscle-specific insulin-stimulated glucose uptake (GU), and fasting FFAU measured with positron emission tomography in thigh [quadriceps femoris (QF) and hamstrings] and upper body (deltoids, biceps, and triceps brachii) muscles. V̇o2 peak and M-value improved significantly by 6 and 12% in SIT, and 3 and 8% in MIT, respectively,. GU increased significantly only in the QF, and there was no statistically significant difference between the training modes. GU increased in all four heads of QF in response to SIT, but only in the vasti muscles in response to MIT, whereas in rectus femoris the response was completely lacking. Training response in FFAU in QF was smaller and nonsignificant, but it also differed between the training modes in the rectus femoris. In conclusion, SIT and MIT increased insulin-stimulated GU only in the main working muscle QF and not in the upper body muscles. In addition, the biarticular rectus femoris did not respond to moderate-intensity training, reflecting most probably poor activation of it during moderate-intensity cycling.
Phase I Study of a Bispecific Ligand-Directed Toxin Targeting CD22 and CD19 (DT2219) for Refractory B-cell Malignancies
Authors: Bachanova Veronika , Frankel Arthur E. , Cao Qing , Lewis Dixie , Grzywacz Bartosz , Verneris Michael R. , Ustun Celalettin , Lazaryan Aleksandr , McClune Brian , Warlick Erica D. , Kantarjian Hagop , Weisdorf Daniel J. , Miller Jeffrey S. , Vallera Daniel A.
Published: March 2015

Purpose: The novel bispecific ligand-directed toxin (BLT) DT2219 consists of a recombinant fusion between the catalytic and translocation enhancing domain of diphtheria toxin (DT) and bispecific single-chain variable fragments (scFV) of antibodies targeting human CD19 and CD22. We conducted a phase I dose-escalation study to assess the safety, maximum tolerated dose, and preliminary efficacy of DT2219 in patients with relapsed/refractory B-cell lymphoma or leukemia.

Experimental Design: DT2219 was administered intravenously over 2 hours every other day for 4 total doses. Dose was escalated from 0.5 μg/kg/day to 80 μg/kg/day in nine dose cohorts until a dose-limiting toxicity (DLT) was observed.

Results: Twenty-five patients with mature or precursor B-cell lymphoid malignancies expressing CD19 and/or CD22 enrolled to the study. Patients received median 3 prior lines of chemotherapy and 8 failed hematopoietic transplantation. All patients received a single course of DT2219; one patient was retreated. The most common adverse events, including weight gain, low albumin, transaminitis, and fever were transient grade 1–2 and occurred in patients in higher dose cohorts (≥40 μg/kg/day). Two subjects experienced DLT at dose levels 40 and 60 μg/kg. Durable objective responses occurred in 2 patients; one was complete remission after 2 cycles. Correlative studies showed a surprisingly low incidence of neutralizing antibody (30%).

Conclusions: We have determined the safety of a novel immunotoxin DT2219 and established its biologically active dose between 40 and 80 μg/kg/day ×4. A phase II study exploring repetitive courses of DT2219 is planned. Clin Cancer Res; 21(6); 1267–72. ©2015 AACR.
Absence of Four-and-a-Half LIM Domain Protein 2 Decreases Atherosclerosis in ApoE
−/−
Mice
Authors: Ebrahimian Talin , Simon David , Lemarié Catherine A. , Simeone Stefania , Heidari Maryam , Mann Koren K. , Wassmann Sven , Lehoux Stephanie
Published: March 2015

Objective—

Four-and-a-half LIM domain protein-2 (FHL2) is expressed in endothelial cells, vascular smooth muscle cells, and leukocytes. It regulates cell survival, migration, and inflammatory response, but its role in atherogenesis is unknown.

Approach and Results—

To investigate the role of FHL2 in atherosclerosis, FHL2-deficient mice were crossed with ApoE-deficient mice, to generate ApoE/FHL2−/− mice. After high-fat diet, ApoE/FHL2−/− mice had significantly smaller atherosclerotic plaques than ApoE−/− mice in the aortic sinus, the brachiocephalic artery, and the aorta. This was associated with enhanced collagen and smooth muscle cell contents and a 2-fold reduction in macrophage content within the plaques of ApoE/FHL-2−/− versus ApoE−/− mice. This could be explained, in part, by the reduction in aortic ICAM-1 (intracellular adhesion molecule) mRNA and VCAM-1 (vascular cell adhesion molecule) protein expression in the plaque. Aortic gene expression of the chemokines CX3CL1 and CCL5 was increased in ApoE/FHL2−/− versus ApoE−/− mice. Peritoneal thioglycollate injection elicited equivalent numbers of monocytes and macrophages in both groups, but a significantly lower number of proinflammatory Ly6C high monocytes were recruited in ApoE/FHL2−/− versus ApoE−/− mice. Furthermore, mRNA levels of CX3CR1 were 2-fold higher in monocytes from ApoE/FHL2−/− versus ApoE−/− mice. Finally, we investigated the potential importance of myeloid cell FHL2 deficiency in atherosclerosis. After being irradiated, ApoE−/− or ApoE/FHL2−/− mice were transplanted with ApoE−/− or ApoE/FHL2−/− bone marrow. After high-fat diet, both chimeric groups developed smaller plaques than ApoE−/− transplanted with ApoE−/− bone marrow.

Conclusions—

These results suggest that FHL2 in both myeloid and vascular cells may play an important role in atherosclerosis by promoting proinflammatory chemokine production, adhesion molecule expression, and proinflammatory monocyte recruitment.
Iron Homeostasis and Pulmonary Hypertension
Authors: Cotroneo Emanuele , Ashek Ali , Wang Lei , Wharton John , Dubois Olivier , Bozorgi Sophie , Busbridge Mark , Alavian Kambiz N. , Wilkins Martin R. , Zhao Lan
Published: March 2015

Rationale:

Iron deficiency without anemia is prevalent in patients with idiopathic pulmonary arterial hypertension and associated with reduced exercise capacity and survival.

Objectives:

We hypothesized that iron deficiency is involved in the pathogenesis of pulmonary hypertension and iron replacement is a possible therapeutic strategy.

Methods and Results:

Rats were fed an iron-deficient diet (IDD, 7 mg/kg) and investigated for 4 weeks. Iron deficiency was evident from depleted iron stores (decreased liver, serum iron, and ferritin), reduced erythropoiesis, and significantly decreased transferrin saturation and lung iron stores after 2 weeks IDD. IDD rats exhibited profound pulmonary vascular remodeling with prominent muscularization, medial hypertrophy, and perivascular inflammatory cell infiltration, associated with raised pulmonary artery pressure and right ventricular hypertrophy. IDD rat lungs demonstrated increased expression of hypoxia-induced factor-1α and hypoxia-induced factor-2α, nuclear factor of activated T cells and survivin, and signal transducers and activators of transcription-3 activation, which promote vascular cell proliferation and resistance to apoptosis. Biochemical examination showed reduced mitochondrial complex I activity and mitochondrial membrane hyperpolarization in mitochondria from IDD rat pulmonary arteries. Along with upregulation of the glucose transporter, glucose transporter 1, and glycolytic genes,
hk1
and
pdk1
, lung fluorine-18–labeled 2-fluoro-2-deoxyglucose ligand uptake was significantly increased in IDD rats. The hemodynamic and pulmonary vascular remodeling were reversed by iron replacement (ferric carboxymaltose, 75 mg/kg) and attenuated in the presence of iron deficiency by dichloroacetate and imatinib, 2 putative treatments explored for pulmonary arterial hypertension that target aerobic glycolysis and proliferation, respectively.

Conclusions:

These data suggest a major role for iron in pulmonary vascular homeostasis and support the clinical evaluation of iron replacement in patients with pulmonary hypertension.
Infarct Volume-Based Subgroup Selection in Acute Ischemic Stroke Trials
Authors: Kufner Anna , Wouters Anke , Bracoud Luc , Laage Rico , Schneider Armin , Schäbitz Wolf-Rüdiger , Hermier Marc , Thijs Vincent , Fiebach Jochen B.
Published: March 2015

Background and Purpose—

We investigated whether hyperintensities with a diameter of at least 3, 3.5, and 4 cm and visible on at least 3 slices on diffusion-weighted imaging enables patient selection with an infarct volume of ≥15 mL.

Methods—

Consecutive acute stroke patients were screened for the AXIS2 trial and examined according to a standardized magnetic resonance imaging protocol in 65 sites. Diffusion-weighted lesion diameters were measured and compared with volumetric assessments.

Results—

Out of 238 patients, 86.2% (N=206) had infarct diameter of at least 3 cm. Volumetric assessments showed infarct volume of ≥15 mL in 157 patients. A cut-off value of 3 cm led to 96.8% sensitivity and 33.3% specificity for predicting lesion volume of ≥15 mL. Analogously, a 3.5 cm cut-off led to 96.8% sensitivity and 50.6% specificity and a 4 cm cut-off led to 91.7% sensitivity and 61.7% specificity.

Conclusions—

Lesion diameter measures may enable multicentric patient recruitment with a prespecified minimal infarct volume.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00927836.
B-Type Natriuretic Peptides Help in Cardioembolic Stroke Diagnosis
Authors: Llombart Víctor , Antolin-Fontes Albert , Bustamante Alejandro , Giralt Dolors , Rost Natalia S. , Furie Karen , Shibazaki Kensaku , Biteker Murat , Castillo José , Rodríguez-Yáñez Manuel , Fonseca Ana Catarina , Watanabe Tetsu , Purroy Francisco , Zhixin Wu , Etgen Thorleif , Hosomi Naohisa , Jafarian Kerman Scott Reza , Sharma Jagdish C. , Knauer Carolin , Santamarina Estevo , Giannakoulas George , García-Berrocoso Teresa , Montaner Joan
Published: March 2015

Background and Purpose—

Determining the underlying cause of stroke is important to optimize secondary prevention treatment. Increased blood levels of natriuretic peptides (B-type natriuretic peptide/N-terminal pro-BNP [BNP/NT-proBNP]) have been repeatedly associated with cardioembolic stroke. Here, we evaluate their clinical value as pathogenic biomarkers for stroke through a literature systematic review and individual participants’ data meta-analysis.

Methods—

We searched publications in PubMed database until November 2013 that compared BNP and NT-proBNP circulating levels among stroke causes. Standardized individual participants’ data were collected to estimate predictive values of BNP/NT-proBNP for cardioembolic stroke. Dichotomized BNP/NT-proBNP levels were included in logistic regression models together with clinical variables to assess the sensitivity and specificity to identify cardioembolic strokes and the additional value of biomarkers using area under the curve and integrated discrimination improvement index.

Results—

From 23 selected articles, we collected information of 2834 patients with a defined cause. BNP/NT-proBNP levels were significantly elevated in cardioembolic stroke until 72 hours from symptoms onset. Predictive models showed a sensitivity >90% and specificity >80% when BNP/NT-proBNP were added considering the lowest and the highest quartile, respectively. Both peptides also increased significantly the area under the curve and integrated discrimination improvement index compared with clinical models. Sensitivity, specificity, and precision of the models were validated in 197 patients with initially undetermined stroke with final pathogenic diagnosis after ancillary follow-up.

Conclusions—

Natriuretic peptides are strongly increased in cardioembolic strokes. Future multicentre prospective studies comparing BNP and NT-proBNP might aid in finding the optimal biomarker, the best time point, and the optimal cutoff points for cardioembolic stroke identification.
Systolic Blood Pressure and Mortality After Stroke
Authors: Lin Michelle P. , Ovbiagele Bruce , Markovic Daniela , Towfighi Amytis
Published: March 2015

Background and Purpose—

Recent studies suggest a J-shaped association between systolic blood pressure (SBP) and cardiovascular events. The optimal SBP target after stroke remains unknown. We assessed the link between SBP and mortality after stroke.

Methods—

We included adults (≥20 years) with self-reported stroke who participated in the National Health and Nutrition Examination Surveys 1998 to 2004, with mortality assessment in 2006. Baseline SBP was categorized as low to normal (<120 mm Hg), normal (120–140 mm Hg), and high (≥140 mm Hg). Independent relationships between baseline SBP and all-cause and vascular mortality were assessed using Cox proportional hazards.

Results—

Of 31 126 adult participants, 455 had self-reported stroke and baseline BP readings: 19% had low to normal, 31% had normal, and 50% had high SBP. Two years after assessment, the low to normal SBP group tended to have the highest cumulative all-cause mortality (11.5%), compared with mortality rates of 8.5% and 7.5% in the normal and high SBP groups, respectively. Similar patterns were seen with vascular mortality. After adjusting for covariates, compared with the high SBP group, the low to normal group had higher all-cause mortality (adjusted hazard ratio, 1.96; 95% confidence interval, 1.13–3.39;
P
=0.017) and trended toward higher vascular mortality (adjusted hazard ratio, 2.08; 95% confidence interval, 0.93–4.68;
P
=0.075). Compared with the normal BP group, the risk of all-cause and vascular mortality trended higher in low to normal BP group but did not achieve statistical significance.

Conclusions—

After stroke, compared with SBP in the high range, low to normal SBP is associated with poorer mortality outcomes.
Motivations for Bilateral Aid Allocation in Korea: Humanitarian, Commercial, or Diplomatic?
Authors: Park Bokyeong , Lee Hongshik
Published: March 2015

This study investigates Korea's motivations for foreign aid allocation, analyzing panel data from over 180 countries for the last 20 years. The results show that Korea's aid allocation reflects both recipient needs and Korea's own national interests but does not consistently consider aid effectiveness. Korean aid is also characterized by its use as an instrument of both summit diplomacy and resource security. In addition, its commercial motivations appear to have shifted over time, from export promotion to overseas investment support. Despite internal and external pressures, there is no obvious evidence that Korea's allocation rule converges with international guidelines that recommend greater consideration of recipient needs and aid effectiveness and less consideration of donor interests.
Morphological comparisons of two pairs of easily confused species in subtribe Goodyerinae (Cranichideae; Orchidaceae)
Authors: Liu Xia Qiao , Cheng Quan Zhi , Tan Yun Hong , Hsu Chuan Tian , Tian Zhen Huai
Published: March 2015

Two yellow-lipped species of Zeuxine viz. Z. flava and Z. sakagutii and another pair of species of Rhomboda, R. moulmeinensis and R. fanjingensis, are so similar that they are frequently misidentified. In this paper, based on field observations, study of type specimens and protologues, illustrations and comparisons of these two pairs of confused species are provided to enable identification.
Attribution of the Recent Winter Sea Ice Decline over the Atlantic Sector of the Arctic Ocean
Authors: Park Doo-Sun R. , Lee Sukyoung , Feldstein Steven B.
Published: March 2015

Wintertime Arctic sea ice extent has been declining since the late twentieth century, particularly over the Atlantic sector that encompasses the Barents–Kara Seas and Baffin Bay. This sea ice decline is attributable to various Arctic environmental changes, such as enhanced downward infrared (IR) radiation, preseason sea ice reduction, enhanced inflow of warm Atlantic water into the Arctic Ocean, and sea ice export. However, their relative contributions are uncertain. Utilizing ERA-Interim and satellite-based data, it is shown here that a positive trend of downward IR radiation accounts for nearly half of the sea ice concentration (SIC) decline during the 1979–2011 winter over the Atlantic sector. Furthermore, the study shows that the Arctic downward IR radiation increase is driven by horizontal atmospheric water flux and warm air advection into the Arctic, not by evaporation from the Arctic Ocean. These findings suggest that most of the winter SIC trends can be attributed to changes in the large-scale atmospheric circulations.
Observing and Simulating the Summertime Low-Level Jet in Central Iowa
Authors: Vanderwende Brian J. , Lundquist Julie K. , Rhodes Michael E. , Takle Eugene S. , Irvin Samantha L.
Published: March 2015

In the U.S. state of Iowa, the increase in wind power production has motivated interest into the impacts of low-level jets on turbine performance. In this study, two commercial lidar systems were used to sample wind profiles in August 2013. Jets were systematically detected and assigned an intensity rating from 0 (weak) to 3 (strong). Many similarities were found between observed jets and the well-studied Great Plains low-level jet in summer, including average jet heights between 300 and 500 m above ground level, a preference for southerly wind directions, and a nighttime bias for stronger jets. Strong vertical wind shear and veer were observed, as well as veering over time associated with the LLJs. Speed, shear, and veer increases extended into the turbine-rotor layer during intense jets. Ramp events, in which winds rapidly increase or decrease in the rotor layer, were also commonly observed during jet formation periods. The lidar data were also used to evaluate various configurations of the Weather Research and Forecasting Model. Jet occurrence exhibited a stronger dependence on the choice of initial and boundary condition data, while reproduction of the strongest jets was influenced more strongly by the choice of planetary boundary layer scheme. A decomposition of mean model winds suggested that the main forcing mechanism for observed jets was the inertial oscillation. These results have implications for wind energy forecasting and site assessment in the Midwest.
Verifying Forecast Precipitation Type with mPING*
Authors: Elmore Kimberly L. , Grams Heather M. , Apps Deanna , Reeves Heather D.
Published: March 2015

In winter weather, precipitation type is a pivotal characteristic because it determines the nature of most preparations that need to be made. Decisions about how to protect critical infrastructure, such as power lines and transportation systems, and optimize how best to get aid to people are all fundamentally precipitation-type dependent. However, current understanding of the microphysical processes that govern precipitation type and how they interplay with physics-based numerical forecast models is incomplete, degrading precipitation-type forecasts, but by how much? This work demonstrates the utility of crowd-sourced surface observations of precipitation type from the Meteorological Phenomena Identification Near the Ground (mPING) project in estimating the skill of numerical model precipitation-type forecasts and, as an extension, assessing the current model performance regarding precipitation type in areas that are otherwise without surface observations. In general, forecast precipitation type is biased high for snow and rain and biased low for freezing rain and ice pellets. For both the North American Mesoscale Forecast System and Global Forecast System models, Gilbert skill scores are between 0.4 and 0.5 and from 0.35 to 0.45 for the Rapid Refresh model, depending on lead time. Peirce skill scores for individual precipitation types are 0.7–0.8 for both rain and snow, 0.2–0.4 for freezing rain and freezing rain, and 0.25 or less for ice pellets. The Rapid Refresh model displays somewhat lower scores except for ice pellets, which are severely underforecast, compared to the other models.
Do Women Suffer from Network Closure? The Moderating Effect of Social Capital on Gender Inequality in a Project-Based Labor Market, 1929 to 2010
Authors: Lutter Mark
Published: March 2015

That social capital matters is an established fact in the social sciences. Less clear, however, is how different forms of social capital affect gender disadvantages in career advancement. Focusing on a project-based type of labor market, namely the U.S. film industry, this study argues that women suffer a “closure penalty” and face severe career disadvantages when collaborating in cohesive teams. At the same time, gender disadvantages are reduced for women who build social capital in open networks with higher degrees of diversity and information flow. Using large-scale longitudinal data on career profiles of about one million performances by 97,657 film actors in 369,099 film productions between the years 1929 and 2010, I analyze career survival models and interaction effects between gender and different measures of social capital and information openness. Findings reveal that female actors have a higher risk of career failure than do their male colleagues when affiliated in cohesive networks, but women have better survival chances when embedded in open, diverse structures. This study contributes to the understanding of how and what type of social capital can be either a beneficial resource for otherwise disadvantaged groups or a constraining mechanism that intensifies gender differences in career advancement.
Cystatin C- and creatinine-based equations in the assessment of renal function in HIV-positive patients prior to commencing Highly Active Antiretroviral Therapy
Authors: Seape Tebogo , Gounden Verena , van Deventer Hendrick E , Candy Geoffrey P , George Jaya A
Published: March 2015

Background

We evaluated the accuracy and precision of creatinine- and cystatin C-based prediction equations for estimating glomerular filtration rate compared to measured glomerular filtration rate in an antiretroviral-naive human immunodeficiency virus population.

Methods

The study population consisted of 100 treatment-naive HIV patients. Glomerular filtration rate was estimated using the Cockcroft–Gault, Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, as well as cystatin C-based equations (CKD-EPIcystatin C, cystatin Cvan Deventer and CKD-EPIcombined)) compared to 51Cr-EDTA plasma clearance-measured glomerular filtration rate. We calculated percentage bias, standard deviation of the differences, accuracy within 15 and 30% of measured glomerular filtration rate and sensitivity and specificity for predicting measured glomerular filtration rate <60 mL/min/1.73 m2.

Results

Bias for all estimating glomerular filtration rate equations ranged from −9.4% to 38.4%. The CKD-EPIcombined without ethnicity correction factor equation had the least bias, 2.9% (−2.9 to 8.8). Bias was higher for the Modification of Diet in Renal Disease and CKD-EPI equation with the African–American ethnicity factor (38.4 and 33.7%) than without (14.2 and 15.3%). Standard deviation of the differences ranged from 29.2% (CKD-EPIcombined without ethnicity factor) to 54.0% (Modification of Diet in Renal Disease with ethnicity factor). Accuracy within 30% of measured glomerular filtration rate ranged from 78% for CKD-EPIcombined without ethnicity factor to 56.7% for the Cockcroft–Gault equation. Sensitivity for creatinine-based equations was less than 50% and for the CKD-EPIcystatin C equation was 75%.

Conclusion

Sensitivity of creatinine-based equations for predicting glomerular filtration rate was poor in this group of patients. The CKD-EPIcombined equation performed better than creatinine-based equations.
Narrative, time, and the archive in an African Second World War memoir: Isaac Fadoyebo’s A Stroke of Unbelievable Luck
Authors: Coates Oliver
Published: March 2015

This article will argue that Isaac Fadoyebo’s memoir A Stroke of Unbelievable Luck deserves recognition as a work of life-writing and a unique literary account of an African soldier’s military service in Nigeria, Sierra Lone, India, and Burma. While previous discussions of Fadoyebo’s memoir have approached it either as historical source material or as a documentary proof of an otherwise lost history, this article will demonstrate that Fadoyebo’s text must also be understood, in its own right, as a complex narrative. Critically, it will show how privileging historical experience in Fadoyebo’s text can marginalize its other qualities. In particular, it will draw attention to the spiritual, mystical, and philosophical dimensions of the memoir, and the discursive subjectivity associated with it. It will argue that this more abstract material is pivotal to our understanding of historical experience in the memoir. In doing so, it will demonstrate that Fadoyebo’s memoir actively situates and archives experience by writing, both helping the reader to interpret this experience, and by allowing the reader to invest affectively in it.
Frommelt Attitudes Toward Care of the Dying Scale Form B
Authors: Mastroianni Chiara , Piredda Michela , Taboga Chiara , Mirabella Fiorino , Marfoli Elisabetta , Casale Giuseppe , Matarese Maria , Murray Frommelt Katherine H. , De Marinis Maria Grazia
Published: March 2015

Nurses' attitudes toward caring for dying patients have an impact on the quality of the care provided. Education can improve knowledge and attitudes toward end-of-life care. No validated tool that measures such attitudes is available for Italian nursing students. The aim of this study was to translate the Frommelt Attitudes Toward Care of the Dying Scale (FATCOD) Form B from English into Italian and to establish its validity and reliability within an Italian population of students. A two-stage design was used. Stage 1 adapted the original version of the tool and tested it for content validity through a multistep process. Stage 2 tested its psychometric properties by analyzing internal consistency, test–retest reliability, and construct validity. The convenience sample consisted of 465 nursing students from all the universities of one Italian region. Measures of stability showed a very good overall (0.87) intraclass correlation coefficient (ICC). The discriminating capacity of the scale was adequate with good values of asymmetry and kurtosis for most of the items. Good internal consistency was found. The six factors derived from the factor analysis are the following: Fear/Malaise, Communication, Relationship, Care of the family, Family as Caring, and Active Care. FATCOD Form B-I is a valid, reliable, and acceptable tool for evaluation of attitudes toward end-of-life care in Italian students. It measures six specific dimensions that should be highlighted during health care student education and training.
A Cost Analysis of Kidney Replacement Therapy Options in Palestine
Authors: Younis Mustafa , Jabr Samer , Al-Khatib Abdallah , Forgione Dana , Hartmann Michael , Kisa Adnan
Published: March 2015

This study provides a cost analysis of kidney replacement therapy options in Palestine. It informs evidence-based resource allocation decisions for government-funded kidney disease services where transplant donors are limited, and some of the common modalities, i.e., peritoneal dialysis (PD) and home hemodialysis (HD), are not widely available due to shortages of qualified staff, specialists, and centers to follow the patient cases, provide training, make home visits, or provide educational programs for patients. The average cost of kidney transplant was US$16 277 for the first year; the estimated cost of HD per patient averaged US$16 085 per year—nearly as much as a transplant. Consistent with prior literature and experience, while live, related kidney donors are scarce, we found that kidney transplant was more adequate and less expensive than HD. These results have direct resource allocation implications for government-funded kidney disease services under Palestinian Ministry of Health. Our findings strongly suggest that investing in sufficient qualified staff, equipment, and clinical infrastructure to replace HD services with transplantation whenever medically indicated and suitable kidney donors are available, as well as deploying PD programs and Home HD programs, will result in major overall cost savings. Our results provide a better understanding of the costs of kidney disease and will help to inform Ministry of Health and related policy makers as they develop short- and long-term strategies for the population, in terms of both cost savings and enhanced quality of life.