bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Proliferative Capacity of Genetically-Engineered Pig and Human Corneal Endothelial Cells
Authors: Fujita Minoru , Mehra Ruhina , Lee Seung Eun , Roh Danny S. , Long Cassandra , Funderburgh James L. , Ayares David L. , Cooper David K.C. , Hara Hidetaka
Published: December 2012

Purpose: The possibility of providing cultured corneal endothelial cells (CECs) for clinical transplantation has gained much attention. However, the worldwide need for human (h) donor corneas far exceeds supply. The pig (p) might provide an alternative source. The aim of this study was to compare the proliferative capacity of CECs from wild-type (WT) pigs, genetically-engineered (GE) pigs, and humans. Methods: The following CECs were cultured: hCECs from donors (i) ≤36 years (young), (ii) ≥49 years (old), and WT pCECs from (iii) neonatal (<5 days), (iv) young (<2 months), and (v) old (>20 months) pigs, and CECs from young (vi) GE pigs (GTKO/CD46 and GTKO/CD46/CD55). Proliferative capacity of CECs was assessed by direct cell counting over 15 days of culture and by BrdU assay. Cell viability during culture was assessed by annexin V staining. The MTT assay assessed cell metabolic activity. Results: There was significantly lower proliferative capacity of old CECs than of young CECs (p < 0.01) in both pigs and humans. There was no significant difference in proliferative capacity/metabolic activity between young pCECs and young hCECs. However, there was a significantly higher percentage of cell death in hCECs compared to pCECs during culture (p < 0.01). Young GE pCECs showed similar proliferative capacity/cell viability/metabolic activity to young WT pCECs. Conclusions: Because of the greater availability of young pigs and the excellent proliferative capacity of cultured GE pCECs, GE pigs could provide a source of CECs for clinical transplantation.
Progenitor Cells for Ocular Surface Regenerative Therapy
Authors: Casaroli-Marano Ricardo P. , Nieto-Nicolau Nuria , Martínez-Conesa Eva M.
Published: December 2012

The integrity and normal function of the corneal epithelium are essential for maintaining the cornea’s transparency and vision. The existence of a cell population with progenitor characteristics in the limbus maintains a dynamic of constant epithelial repair and renewal. Currently, cell-based therapies for bio-replacement, such as cultured limbal epithelial transplantation and cultured oral mucosal epithelial transplantation, present very encouraging clinical results for treating limbal stem cell deficiencies. Another emerging therapeutic strategy consists of obtaining and implementing human progenitor cells of different origins using tissue engineering methods. The development of cell-based therapies using stem cells, such as human adult mesenchymal stromal cells, represents a significant breakthrough in the treatment of certain eye diseases and also offers a more rational, less invasive and more physiological approach to ocular surface regeneration.
High on-treatment platelet reactivity and P2Y12 antagonists in clinical trials
Authors: Kristensen Steen , Hochholzer Willibald , Neumann Franz-Josef , Trenk Dietmar
Published: December 2012

Dual antiplatelet therapy with aspirin and clopidogrel in patients undergoing percutaneous coronary intervention (PCI) and in patients with acute coronary syndromes (ACS) has substantially decreased the rate of cardiovascular events. Within the past decade, the variability in pharmacodynamic response as well as the moderate antiplatelet efficacy of clopidogrel has raised major concerns, since high on-clopidogrel platelet reactivity has consistently been associated with increased risk for ischaemic events in PCI patients. The variability in response could be linked to genetic polymorphisms impacting on activity of cytochrome P450 enzymes as well as clinical and demographic variables, but, taken together, factors identified so far can explain only up to approximately 12% of this variability in adenosine diphosphate-induced platelet aggregation on clopidogrel. Regulatory agencies as well as major cardiac societies suggest the use of other anti-platelet medications or alternative dosing strategies for clopidogrel in patients with reduced effectiveness of clopidogrel. This review will focus on the current status of alternate strategies for more sufficient suppression of high platelet reactivity.
The
ABCG8
G574R Variant, Serum Plant Sterol Levels, and Cardiovascular Disease Risk in the Old Order Amish
Authors: Horenstein Richard B. , Mitchell Braxton D. , Post Wendy S. , Lütjohann Dieter , von Bergmann Klaus , Ryan Kathleen A. , Terrin Michael , Shuldiner Alan R. , Steinle Nanette I.
Published: December 2012

Objective—

To determine whether long-term exposure to moderate elevations in plasma plant sterol levels increases risk for atherosclerosis.

Methods and Results—

In Old Order Amish participants aged 18 to 85 years, with (n=110) and without (n=181) 1 copy of the
ABCG8
G574R variant, we compared mean plasma levels of plant sterols and cholesterol precursors and carotid intima-media wall thickness. Carriers of a single 574R allele had increased plant sterol levels (eg, 35%–37% higher plasma levels of sitosterol, campesterol, and stigmasterol) and increased plant sterol/cholesterol ratios (
P
<0.001 for all). 574R carriers had significantly decreased levels of lathosterol and lanosterol, precursors in a pathway for endogenous cholesterol synthesis, suggesting that plant sterols may alter regulation of genes involved in cholesterol synthesis. The G574R variant was not associated with high-density lipoprotein cholesterol or low-density lipoprotein cholesterol levels. Compared with noncarriers, 574R carriers had decreased carotid intima-media wall thickness (0.62 versus 0.66 mm; age- and sex-adjusted
P
=0.03). Adjustment for body weight, blood pressure, and standard lipid measures (high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides) did not alter this association.

Conclusion—

Although the G574R variant is associated with moderately elevated plant sterol levels, carriers of the 574R allele had modestly lower levels of carotid wall thickness compared with noncarriers.
Angiogenesis Mediated by Toll-Like Receptor 4 in Ischemic Neural Tissue
Authors: He Chang , Sun Yuying , Ren Xiangrong , Lin Qing , Hu Xiao , Huang Xi , Su Shao-Bo , Liu Yizhi , Liu Xialin
Published: December 2012

Objective—

Activation of the immune system via toll-like receptors (TLRs) is implicated in atherosclerosis, microvascular complications, and angiogenesis. However, the involvement of TLRs in inflammation-associated angiogenesis in ischemic neural tissue has not been investigated. The goal of this study is to determine the role of TLR4 signaling in oxygen-induced neovascularization in retina, a neural tissue.

Methods and Results—

In oxygen-induced retinopathy model, we found that retinal neovascularization was significantly attenuated in TLR4
−/−
mice. The further study revealed that the absence of TLR4 led to downregulation of proinflammatory factors in association with the attenuated activation of glia in the ischemic retina, which was also associated with reduced expression of high-mobility group box-1, an endogenous ligand for TLR4. The application of high-mobility group box-1 to the ischemic retina promoted the production of proinflammatory factors in wild-type but not TLR4
−/−
mice. High-mobility group box-1 treatment in vitro also significantly promoted the production of proinflammatory factors in retinal glial cells from wild-type mice, but much less from TLR4
−/−
mice.

Conclusion—

Our results suggest that the release of high-mobility group box-1 in ischemic neural tissue initiates TLR4-dependent responses that contribute to neovascularization. These findings represented a previously unrecognized effect of TLR4 on angiogenesis in association with the activation of glia in ischemic neural tissue.
Cardiac MRI
Authors: Gerche Andre La , Claessen Guido , Van de Bruaene Alexander , Pattyn Nele , Van Cleemput Johan , Gewillig Marc , Bogaert Jan , Dymarkowski Steven , Claus Piet , Heidbuchel Hein
Published: December 2012

Background—

Accurate measures are critical when attempting to distinguish normal from pathological changes in cardiac function during exercise, yet imaging modalities have seldom been assessed against invasive exercise standards. We sought to validate a novel method of biventricular volume quantification by cardiac MRI (CMR) during maximal exercise.

Methods and Results—

CMR was performed on 34 subjects during exercise and free-breathing with the use of an ungated real-time (RT-ungated) CMR sequence. ECG and respiratory movements were retrospectively synchronized, enabling compensation for cardiac cycle and respiratory phase. Feasibility of RT-ungated imaging was compared with standard exercise CMR imaging with ECG gating (gated); accuracy of RT-ungated CMR was assessed against an invasive standard (direct Fick); and reproducibility was determined after a second bout of maximal exercise. Ventricular volumes were analyzed more frequently during high-intensity exercise with RT-ungated compared with gated CMR (100% versus 47%;
P
<0.0001) and with better interobserver variability for RT-ungated (coefficient of variation=1.9% and 2.0% for left and right ventricular stroke volumes, respectively) than gated (coefficient of variation=15.2% and 13.6%;
P
<0.01). Cardiac output determined by RT-ungated CMR proved accurate against the direct Fick method with excellent agreement (intraclass correlation coefficient,
R
=0.96), which was highly reproducible during a second bout of maximal exercise (
R
=0.98).

Conclusions—

When RT-ungated CMR is combined with post hoc analysis incorporating compensation for respiratory motion, highly reproducible and accurate biventricular volumes can be measured during maximal exercise.
The Rapid Distraction of Attentional Resources toward the Source of Incongruent Stimulus Input during Multisensory Conflict
Authors: Donohue Sarah E. , Todisco Alexandra E. , Woldorff Marty G.
Published: December 2012

Neuroimaging work on multisensory conflict suggests that the relevant modality receives enhanced processing in the face of incongruency. However, the degree of stimulus processing in the irrelevant modality and the temporal cascade of the attentional modulations in either the relevant or irrelevant modalities are unknown. Here, we employed an audiovisual conflict paradigm with a sensory probe in the task-irrelevant modality (vision) to gauge the attentional allocation to that modality. ERPs were recorded as participants attended to and discriminated spoken auditory letters while ignoring simultaneous bilateral visual letter stimuli that were either fully congruent, fully incongruent, or partially incongruent (one side incongruent, one congruent) with the auditory stimulation. Half of the audiovisual letter stimuli were followed 500–700 msec later by a bilateral visual probe stimulus. As expected, ERPs to the audiovisual stimuli showed an incongruency ERP effect (fully incongruent versus fully congruent) of an enhanced, centrally distributed, negative-polarity wave starting ∼250 msec. More critically here, the sensory ERP components to the visual probes were larger when they followed fully incongruent versus fully congruent multisensory stimuli, with these enhancements greatest on fully incongruent trials with the slowest RTs. In addition, on the slowest-response partially incongruent trials, the P2 sensory component to the visual probes was larger contralateral to the preceding incongruent visual stimulus. These data suggest that, in response to conflicting multisensory stimulus input, the initial cognitive effect is a capture of attention by the incongruent irrelevant-modality input, pulling neural processing resources toward that modality, resulting in rapid enhancement, rather than rapid suppression, of that input.
Increased Facilitatory Connectivity from the Pre-SMA to the Left Dorsal Premotor Cortex during Pseudoword Repetition
Authors: Hartwigsen Gesa , Saur Dorothee , Price Cathy J. , Baumgaertner Annette , Ulmer Stephan , Siebner Hartwig R.
Published: December 2012

Previous studies have demonstrated that the repetition of pseudowords engages a network of premotor areas for articulatory planning and articulation. However, it remains unclear how these premotor areas interact and drive one another during speech production. We used fMRI with dynamic causal modeling to investigate effective connectivity between premotor areas during overt repetition of words and pseudowords presented in both the auditory and visual modalities. Regions involved in phonological aspects of language production were identified as those where regional increases in the BOLD signal were common to repetition in both modalities. We thus obtained three seed regions: the bilateral pre-SMA, left dorsal premotor cortex (PMd), and left ventral premotor cortex that were used to test 63 different models of effective connectivity in the premotor network for pseudoword relative to word repetition. The optimal model was identified with Bayesian model selection and reflected a network with driving input to pre-SMA and an increase in facilitatory drive from pre-SMA to PMd during repetition of pseudowords. The task-specific increase in effective connectivity from pre-SMA to left PMd suggests that the pre-SMA plays a supervisory role in the generation and subsequent sequencing of motor plans. Diffusion tensor imaging-based fiber tracking in another group of healthy volunteers showed that the functional connection between both regions is underpinned by a direct cortico-cortical anatomical connection.
Development and Initial Validation of a Scale to Assess Sufi Beliefs
Authors: Joshanloo Mohsen , Rastegar Parviz
Published: December 2012

Although the beliefs that Sufis (Sūfī) have introduced and promoted in the Islamic world seem to have had far-reaching influence on the way Muslims think and act, neither theorizing nor empirical research in the psychological literature has as yet focused on such beliefs and their impact on Islamic societies. Furthermore, although intellectual controversies about the functionality of Sufi beliefs abound, there is no instrument to address the existing issues empirically. The purpose of the three studies presented here is to identify major domains of Sufi belief, to describe the development and factor structure of a scale used to assess them, and to test the internal consistency, temporal stability (Study 1), and the convergent validity of this scale's scores (Studies 2 and 3) in three samples of Iranian Shi'ite university students. The combined findings from the three studies reported here provide initial evidence that the Sufi Beliefs Scale is reliable, valid, and can be used in further studies.
Personality and Social Integration Factors Distinguishing Nonreligious from Religious Groups: The Importance of Controlling for Attendance and Demographics
Authors: Galen Luke W. , Kloet Jim
Published: December 2012

Previous studies linking personality and social integration with religiosity conflate the weakly religious with the completely nonreligious, and religious belief with group membership, leading to spurious associations. The present study characterizes the growing nonreligious population by comparing church and secular group members on personality characteristics and social integration. Although church members were higher in Agreeableness, Conscientiousness, and perceived social support, these differences were largely eliminated when controlling for demographics and group attendance. Secular group members were higher on Intellect/Openness. Many previously reported characteristics associated with religiosity are a function not of belief itself, but of strong convictions and group identification.
Refining Christian Religious Orientations through Cluster Analyses
Authors: Brown Scott R. , Westman Alida
Published: December 2012

To explore religious orientations, 163 Christians answered the Intrinsic and Extrinsic Religious Orientation and Quest Scales. Cluster analysis showed that Extrinsic Item 2 (“It doesn't matter so much what I believe so long as I lead a moral life”) did not fit in the two- or three-cluster model. One cluster of the two-cluster and one of the three-cluster models were exactly the same and reflected intrinsic, personal religion. The remaining clusters showed why a correlation is found between the Extrinsic and Quest scales and suggest refinements of the scales.
In Ordained Ministry there is Neither Male nor Female? The Personality Profile of Male and Female Anglican Clergy Engaged in Multi-parish Rural Ministry
Authors: Brewster Christine E. , Francis Leslie J. , Robbins Mandy
Published: December 2012

Robbins, Francis, and Rutledge (1997) documented the personality profile of Church of England clergymen and clergywomen prior to the ordination of the first women to the priesthood in 1994, drawing on Eysenck's three-dimensional model of personality. They found that the personality profiles of clergymen and clergywomen were indistinguishable. The present paper reports a comparable study conducted in 2004 among 182 clergywomen and 540 clergymen serving in similar parochial posts in order to examine whether the ordination of women to the priesthood had impacted the overall personality profile of Anglican clergy. The data suggest that little change had taken place between the two cohorts of clergy studied. Once again clergywomen and clergymen appeared to be formed in the same image.
Modeling the Post-9/11 Meaning-Laden Paradox: From Deep Connection and Deep Struggle to Posttraumatic Stress and Growth
Authors: Ai Amy L. , Tice Terrence N. , Lemieux Catherine M. , Huang Bu
Published: December 2012

The prospective study follows college students after the 9/11 attacks. Based on evidence and trauma-related theories, and guided by reports on positive and negative reactions and meaning-related actions among Americans after 9/11, we explored the seemingly contradictory, yet meaning-related pathways to posttraumatic growth (PTG) and posttraumatic stress disorder symptoms (PTGD), indicating the sense of deep interconnectedness and deep conflict. The final model showed that 9/11 emotional turmoil triggered processes of assimilation, as indicated in pathways between prayer coping and perceived spiritual and social support, and of accommodation, as indicated in the pathway of spiritual struggle. Both pathways were directly associated with PTG in the follow-up. Perceived spiritual and social support contributed to lower levels of PTSD symptoms, whereas spiritual struggle had an opposite impact on symptoms; both effects were mediated through optimism but in opposite directions. The study suggests the interplay of complex crisis-related phenomena following meaning-laden collective trauma that presented existential challenges, involving coping, optimism, deep conflict, and deep interconnectedness.
An Exploration of Religious Gender Differences amongst Jewish-American Emerging Adults of Different Socio-Religious Subgroups
Authors: Etengoff Chana
Published: December 2012

This article explores gender differences in the religious experiences of 416 Jewish (Secular, Traditional, and Modern-Orthodox) emerging adults ( M Age = 23.16). Prior research has indicated that women are more religious than men cross-culturally. The purpose of this study was to investigate if such gender differences remain applicable to Jewish-American emerging adults given both the changing role of women in society and emerging adults’ prolonged search for identity. Findings reveal that most gender differences in the religious values and experiences of Jewish-American emerging adults are statistically insignificant and when significant, are specific to subgroup. Furthermore, it was found that gender analyses of composite scores do not necessarily accurately report the presence or lack thereof of gender differences in religious development. It is therefore suggested that future research may benefit from the analysis of individual religious items and that efforts be made to explore within-group and between-group differences.
Random Errors in Turbulence Measurements in the Atmospheric Surface Layer: Implications for Monin–Obukhov Similarity Theory
Authors: Salesky Scott T. , Chamecki Marcelo
Published: December 2012

An error propagation analysis is conducted to estimate random errors in the friction velocity u* and the Monin–Obukhov similarity theory (MOST) stability variable z/L from estimated random errors in the turbulent fluxes. Errors in the dimensionless mean wind shear φm and mean temperature gradient φh are also estimated. To the authors’ knowledge, this is the first time that errors in calculated values of z/L, φm, and φh have been systematically analyzed. Random errors in z/L are found to be large for unstable conditions, reaching values of 40% or greater. It is shown through statistical hypothesis tests that random errors cannot explain departures of calculated values of φm and φh from theory. The deviation of calculated values of φm from empirical curves is found to have a strong diurnal variation that increases with height; deviations of φh from theory are not found to have clear diurnal variation. These results support the findings of previous studies, which have suggested that additional dimensionless parameters representing additional physical processes need to be included in the set of governing parameters for surface layer similarity. Implications for atmospheric surface layer turbulence are also discussed.
Sensitivity of the Ocean State to the Vertical Distribution of Internal-Tide-Driven Mixing
Authors: Melet Angelique , Hallberg Robert , Legg Sonya , Polzin Kurt
Published: December 2012

The ocean interior stratification and meridional overturning circulation are largely sustained by diapycnal mixing. The breaking of internal tides is a major source of diapycnal mixing. Many recent climate models parameterize internal-tide breaking using the scheme of St. Laurent et al. While this parameterization dynamically accounts for internal-tide generation, the vertical distribution of the resultant mixing is ad hoc, prescribing energy dissipation to decay exponentially above the ocean bottom with a fixed-length scale. Recently, Polzin formulated a dynamically based parameterization, in which the vertical profile of dissipation decays algebraically with a varying decay scale, accounting for variable stratification using Wentzel–Kramers–Brillouin (WKB) stretching. This study compares two simulations using the St. Laurent and Polzin formulations in the Climate Model, version 2G (CM2G), ocean–ice–atmosphere coupled model, with the same formulation for internal-tide energy input. Focusing mainly on the Pacific Ocean, where the deep low-frequency variability is relatively small, the authors show that the ocean state shows modest but robust and significant sensitivity to the vertical profile of internal-tide-driven mixing. Therefore, not only the energy input to the internal tides matters, but also where in the vertical it is dissipated.
Embracing a Weight-of-Evidence Approach for Establishing NOAELs for Nanoparticle Inhalation Toxicity Studies
Authors: Warheit David B. , Reed Kenneth L. , DeLorme Michael P.
Published: December 2012

The goal of this article is to evaluate a recently published subchronic inhalation study with carbon nanofibers in rats and discuss the importance of a weight-of-evidence (WOE) framework for determining no adverse effect levels (NOAELs). In this Organization for Economic Cooperation and Development (OECD) 413 guideline inhalation study with VGCF™-H carbon nanofibers (CNFs), rats were exposed to 0, 0.54, 2.5 or 25 mg/m3 CNF for 13 weeks. The standard toxicology experimental design was supplemented with bronchoalveolar lavage (BAL) and respiratory cell proliferation (CP) endpoints. BAL fluid (BALF) recovery of inflammatory cells and mediators (i.e., BALF– lactate dehydrogenase [LDH], microprotein [MTP], and alkaline phosphatase [ALKP] levels) were increased only at 25 mg/m3, 1 day after exposure. No differences versus control values in were measured at 0.54 or 2.5 mg/m3 exposure concentrations for any BAL fluid endpoints. Approximately 90% (2.5 and 25 mg/m3) of the BAL-recovered macrophages contained CNF. CP indices at 25 mg/m3 were increased in the airways, lung parenchyma, and subpleural regions, but no increases in CP versus controls were measured at 0.54 or 2.5 mg/m3. Based upon histopathology criteria, the NOAEL was set at  0.54 mg/m3, because at 2.5 mg/m3, “minimal cellular inflammation” of the airways/lung parenchyma was noted by the study pathologist; while the 25 mg/m3 exposure concentration produced slight inflammation and occasional interstitial thickening. In contrast, none of the more sensitive pulmonary biomarkers such as BAL fluid inflammation/cytotoxicity biomarkers or CP turnover results at 2.5 mg/m3 were different from air-exposed controls. Given the absence of convergence of the histopathological observations versus more quantitative measures at 2.5 mg/m3, it is recommended that more comprehensive guidance measures be implemented for setting adverse effect levels in (nano)particulate, subchronic inhalation studies including a WOE approach for establishing no adverse effect levels; and a suggestion that some findings should be viewed as normal physiological adaptations (e.g., normal macrophage phagocytic responses—minimal inflammation) to long-term particulate inhalation exposures.
Hallmarks in the History of Enteral and Parenteral Nutrition
Authors: Vassilyadi Frank , Panteliadou Alkistis‐Kira , Panteliadis Christos
Published: December 2012

Parenteral nutrition (PN) and enteral nutrition (EN) have a very long history, emerging in the ancient world and developing throughout the common epoch. This history dates back as far as 3500 bc to the ancient Egyptians, Indians, and Chinese. Their medical practices were the first reports of enteral feeding therapy, provided via rectum with enemas of wine, milk, whey, wheat, and barley. Hippocrates and Plato, in ancient Greece, were the first personalities to emphasize the importance of diet on health. In the following centuries, Erasistratus and Herophilus described the first notion of the circulatory system, and Oribasius and Celsus described the role of nutrition and disease. There is a great historical gap between the times of Galen (2nd century), who elaborated on the circulatory system; Ibn Zuhr (12th century), who constructed the first model of PN; and Capivacceus (16th century), who placed the first tube for EN. The 17th–19th centuries showed major developments in modern nutrition elements. Steps toward artificial nutrition began in 1628 with the detailed description of blood circulation by William Harvey; however, most of the advances in enteral and parenteral feeding techniques, solutions, and formulas took place in the 20th century. Over the last decade of the 20th century, research focused on metabolic control, multitude formulas, timing and the combination of EN and PN for intensive care patients.
Influence of clamp band joint on dynamic behavior of launching system in ascent flight
Authors: Qin ZY , Yan SZ , Chu FL
Published: December 2012

A dynamic model for the launching system incorporating the influence of the clamp band joint is developed using the finite element method, where both of the launch vehicle and the spacecraft are modeled as Timoshenko beams. The clamp band joint is represented by a massless beam element, of which the element stiffness matrix is developed based on the expressions for the axial and bending stiffnesses of the joint deduced by the authors in the previous works. Dynamic analyses are performed to evaluate the joint influence on the launching system, where the variations of the mass and length of the launching system due to the fuel combustion and stage jettisons during the ascent flight are considered. The dynamic model presented here can be applied to investigate dynamics of launching systems involving the influence of clamp band joints conveniently.
Flutter of a two-dimensional wing with asymmetry at low Mach numbers
Authors: Shao Song , Zhu Qing-Hua , Huang Yu-Xin , Zhang Cheng-Lin , Ni Xian-Ping
Published: December 2012

A two-dimensional wing aeroelastic model with a modified Leishman–Beddoes model in state-space form is performed to investigate the flutter behavior at low Mach numbers. The two-dimensional wing aeroelastic system employs highly aerodynamic non-linear features. The modifications to the Leishman–Beddoes model are validated by comparing with the experimental results of airfoil airloads at low Mach numbers, and the wing flutter experimental results also verify the model of the two-dimensional wing aeroelastic system. Results demonstrate that a fold bifurcation, which is related to the high-amplitude limit cycle oscillation, stems from the phenomenon of dynamic stall and the emergence of the period-2 limit cycle oscillation is due to the asymmetry of the aeroelastic system.
Morphological and vegetation changes on tidal flats of the Amazon Coast during the last 5000 cal. yr BP
Authors: Guimarães José Tasso Felix , Cohen Marcelo Cancela Lisboa , França Marlon Carlos , Pessenda Luiz Carlos Ruiz , Behling Hermann
Published: December 2012

The analysis of morphology, sedimentary facies, palynology, carbon and nitrogen isotopes, C/N ratio and radiocarbon data from tidal flats sediments influenced by the Amazon River indicates that vegetation development during the last 5000 cal. yr BP was controlled by morphological changes associated with marine and fluvial process. The proximal portion of the tidal flat corresponds to abandoned channels surrounded by terrestrial vegetation since 5280–5160 cal. yr BP. During the last 2840–2750 cal. yr BP, autochthonous organic material became prevalent as well as the increase in contribution of terrestrial organic matter mainly from ‘várzea’ vegetation. Herbaceous plants already colonized the tidal flat before 3170–2970 cal. yr BP, and after 2630–2310 cal. yr BP and 1350–1290 cal. yr BP they were replaced by mangrove vegetation following the development of secondary channels connected to the sea with brackish water influence. Furthermore, the erosion of the herbaceous field to form chenier ridges/tidal mixed flat after 3170–2970 cal. yr BP and before 220–140 cal. yr BP in the distal portion of the tidal flat suggests an overall interpretation of a retrogradation cycle. This process was driven by a relative sea-level rise influenced by the increase of Amazon discharge during the late Holocene.
Some recommendations for multi-arm multi-stage trials
Authors: Wason James , Magirr Dominic , Law Martin , Jaki Thomas
Published: December 2012

Multi-arm multi-stage designs can improve the efficiency of the drug-development process by evaluating multiple experimental arms against a common control within one trial. This reduces the number of patients required compared to a series of trials testing each experimental arm separately against control. By allowing for multiple stages experimental treatments can be eliminated early from the study if they are unlikely to be significantly better than control. Using the TAILoR trial as a motivating example, we explore a broad range of statistical issues related to multi-arm multi-stage trials including a comparison of different ways to power a multi-arm multi-stage trial; choosing the allocation ratio to the control group compared to other experimental arms; the consequences of adding additional experimental arms during a multi-arm multi-stage trial, and how one might control the type-I error rate when this is necessary; and modifying the stopping boundaries of a multi-arm multi-stage design to account for unknown variance in the treatment outcome. Multi-arm multi-stage trials represent a large financial investment, and so considering their design carefully is important to ensure efficiency and that they have a good chance of succeeding.
Developing the Market for Land
Authors: Gangopadhyay Shubhashis
Published: December 2012

Government’s land acquisition has come increasingly under fire from both the courts and the people whose lands are being acquired. This article argues that the way land is being acquired in India is contrary to the principles that govern a market-based society. It shows the close similarities in how land was acquired in two examples, one in USA and one in India. Both had implications for how the practice of land acquisition has evolved. The article also suggests a method of resolving the problem.
Bureaucracy, Its Reform and Development
Authors: Dixit Avinash
Published: December 2012

Few aspects of economic policy elicit more conflicting opinions than the role of bureaucracy in policy making and implementation. These range from Max Weber’s picture of a rule-governed efficient institution to the ‘Yes, Minister’ caricature of one bound in complex red tape, operating inefficiently and serving the interests of its own officials. In this article, I attempt a better understanding guided by the economics of incentives and organisations. I emphasise the multidimensional complexity of government bureaucracies—they are answerable to multiple political principals, must handle multiple tasks, have multiple levels of hierarchy and so on—and suggest some institutional and organisational reforms that seem relevant for India and other less-developed countries that wish to sustain growth and progress to and beyond a middle-income level.
Identification of protoxins and a microbial basis for red maple (Acer rubrum) toxicosis in equines
Authors: Agrawal Karan , Ebel Joseph G. , Altier Craig , Bischoff Karyn
Published: December 2012

The leaves of Acer rubrum (red maple), especially when wilted in the fall, cause severe oxidative damage to equine erythrocytes, leading to potentially fatal methemoglobinemia and hemolytic anemia. Gallic acid and tannins from A. rubrum leaves have been implicated as the toxic compounds responsible for red maple toxicosis, but the mechanism of action and toxic principle(s) have not been elucidated to date. In order to investigate further how red maple toxicosis occurs, aqueous solutions of gallic acid, tannic acid, and ground dried A. rubrum leaves were incubated with contents of equine ileum, jejunum, cecum, colon, and liver, and then analyzed for the metabolite pyrogallol, as pyrogallol is a more potent oxidizing agent. Gallic acid was observed to be metabolized to pyrogallol maximally in equine ileum contents in the first 24 hr. Incubation of tannic acid and A. rubrum leaves, individually with ileum contents, produced gallic acid and, subsequently, pyrogallol. Ileum suspensions, when passed through a filter to exclude microbes but not enzymes, formed no pyrogallol, suggesting a microbial basis to the pathway. Bacteria isolated from ileum capable of pyrogallol formation were identified as Klebsiella pneumoniae and Enterobacter cloacae. Therefore, gallotannins and free gallic acid are present in A. rubrum leaves and can be metabolized by K. pneumoniae and E. cloacae found in the equine ileum to form pyrogallol either directly or through a gallic acid intermediate (gallotannins). Identification of these compounds and their physiological effects is necessary for the development of effective treatments for red maple toxicosis in equines.
New autoimmune diseases after cord blood transplantation: a retrospective study of EUROCORD and the Autoimmune Disease Working Party of the European Group for Blood and Marrow Transplantation
Authors: Daikeler Thomas , Labopin Myriam , Ruggeri Annalisa , Crotta Alessandro , Abinun Mario , Hussein Ayad Ahmed , Carlson Kristina , Cornillon Jérôme , Diez-Martin Jose L. , Gandemer Virginie , Faraci Maura , Lindemans Caroline , O'Meara Anne , Mialou Valerie , Renard Marleen , Sedlacek Petr , Sirvent Anne , Socié Gérard , Sora Federica , Varotto Stefania , Sanz Jaime , Voswinkel Jan , Vora Ajay , Yesilipek M. Akif , Herr Andree-Laure , Gluckman Eliane , Farge Dominique , Rocha Vanderson
Published: December 2012

Key Points

Autoimmune diseases do occur after CBT in approximately 5% of patients. Of these, AIHA or ITP were observed the most often and were treated with prednisone, CSA, and RTX.
Anti–IFN-γ autoantibodies in adults with disseminated nontuberculous mycobacterial infections are associated with HLA-DRB1*16:02 and HLA-DQB1*05:02 and the reactivation of latent varicella-zoster virus infection
Authors: Chi Chih-Yu , Chu Chen-Chung , Liu Jing-Pei , Lin Chia-Hao , Ho Mao-Wang , Lo Wen-Jyi , Lin Po-Chang , Chen Hung-Jen , Chou Chia-Huei , Feng Jia-Yih , Fung Chang-Phone , Sher Yuh-Pyng , Li Chi-Yuan , Wang Jen-Hsien , Ku Cheng-Lung
Published: December 2012

Key Points

Anti–IFN-γ autoantibodies are associated with HLA-DRB1*16:02 and DQB1*05:02.
Willingness to use a rapid diagnostic test for malaria in a rural area of central Côte d’Ivoire
Authors: Comoé Colombe Coffie , Ouattara Allassane F , Raso Giovanna , Tanner Marcel , Utzinger Jürg , Koudou Benjamin G
Published: December 2012

Background

Malaria mortality is mainly a direct consequence of inadequate and/or delayed diagnosis and case management. Some important control interventions (e.g. long-lasting insecticidal nests) have contributed to reduce malaria morbidity and mortality in different parts of the world. Moreover, the development and effective use of rapid diagnostic tests (RDTs) hold promise to further enhance the control and elimination of malaria, particularly in areas where health services are deficient. The aim of this study was to determine knowledge, attitudes, practices and beliefs in relation to RDTs for malaria in rural Côte d’Ivoire.

Methods

One hundred individuals from Bozi and Yoho who sought care at the health centre in Bozi and were offered an RDT for malaria were interviewed in April 2010 using a pre-tested questionnaire on practice and perceptions in relation to RDTs for malaria. The relationships between acceptance of RDTs and factors related to opinions were identified, using generalized linear mixed models. Qualitative data from open-ended questions complemented the quantitative analysis.

Results

Only 34 out of 100 patients who were offered an RDT for malaria were willing to undergo the test. People who perceived blood as a sacred body fluid were less likely to comply with an RDT. The concurrent availability and use of RDTs for HIV and malaria was associated with an unwilling attitude towards RDTs for malaria (Fisher’s exact test, p <0.001). The initial willingness of patients to accept malaria testing with RDTs was significantly related to general fear and wanting to know malaria infection status. For further and regular use of RDTs, a strong relationship was observed between acceptance and the idea that an RDT is a pretext used by health worker to know HIV status (odds ratio (OR) = 16.61, 95% confidence interval (CI) = 1.03-268.5). Those thinking that blood samples were useful for medical diagnoses were 8.31-times (95% CI = 2.22-31.1) more likely to undergo an RDT compared to those rejecting blood sampling as a diagnostic strategy.

Conclusion

Socio-cultural factors might be barriers for accepting RDTs in general health services. There are social representations of malaria and HIV/AIDS, symbolic for blood or experiences in relation to blood taking and blood-related diseases in relation to the introduction and routine use of RDTs. Special attention should be given to these barriers as otherwise the promotion of RDTs for prompt and effective diagnosis and subsequent management of malaria is hampered.
Common sequence variants in CD36 gene and the levels of triglyceride and high-density lipoprotein cholesterol among ethnic Chinese in Taiwan
Authors: Chien Kuo-Liong , Hsu Hsiu-Ching , Liu Pi-Hua , Lin Hung-Ju , Chen Ming-Fong
Published: December 2012

Background

Evidence of the genetic association betweenCD36candidate gene and the risk of metabolic syndrome and its components has been inconsistent. This case–control study assessed the haplotype-tagged SNPs fromCD36on the risk of metabolic syndrome and components.

Methods and results

We recruited 1,000 cases and age, gender-matched controls were randomly selected from the participants with metabolic syndrome defined by International Diabetes Federation. Overall, the haplotype tagged SNPs of CD36 gene were not related to the risk of metabolic syndrome. For individuals with normal lipid levels, several SNPs were significantly associated with the triglycerides and HDL-cholesterol levels: Subjects with rs3211848 homozygote had a higher triglyceride level (99.16 ± 2.61 mg/dL), compared with non-carriers (89.27 ± 1.45 mg/dL,P = 0.001). In addition, compared with non-carriers, individuals with rs1054516 heterozygous and homozygous genotypes had a significantly lower HDL-cholesterol (46.6 ± 0.46 mg/dL for non-carrier, 44.6 ± 0.36 mg/dL for heterozygous, and 44.3 ± 0.56 mg/dL for homozygous,P = 0.0008).

Conclusion

TheCD36gene variants were significantly associated with triglycerides and HDL-cholesterol concentrations among ethnic Chinese in Taiwan.
Analysis of the tumor length and other prognosis factors in pT1-2 node-negative esophageal squamous cell carcinoma in a Chinese population
Authors: Song Zhengbo , Wang Jiwen , Lin Baochai , Zhang Yiping
Published: December 2012

Background

Tumor length is an important prognostic factor for many carcinomas, but its role in esophageal cancer remained undetermined. The aim of this study was to investigate the effect of tumor length on survival for patients with confined tumors (grade pT1-2) without lymph-node metastases in esophageal squamous cell carcinoma.

Methods

We enrolled 201 patients with esophageal squamous cell carcinoma (SCC) who had undergone surgical resection and been confirmed as pT1-2N0M0. The relationship of tumor length with overall survival was assessed and compared with other factors detailed in the American Joint Committee on Cancer (AJCC) tumor, node, metastasis (TNM) staging system published in 2009.

Results

The overall survival (OS) rates at 1, 3, and 5 years were 93.0%, 83.7%, and 69.2%, respectively. The tumor length adversely affected OS, with the 5-year rate being 93.5%, 82.0%, 68.6%, 67.9%, 55.3% and 41.1%, respectively for tumor lengths of less than 10 mm, 10 to 20 mm, 20 to 30 mm, 30 to 40 mm, 40 to 50 mm, and greater than 50 mm (P< 0.001). Multivariate analyses showed that the pathologic T classification and grade of tumor was significantly associated with OS. Tumor length of 30 mm or more remained an independent prognostic factor (P = 0.04), as did the other current TNM factors.

Conclusion

Tumor length appears to affect the OS of patients with early-stage esophageal squamous cell carcinoma. It may provide additional prognostic information for the current TNM staging system.
Prognosis significance of HER-2/neu overexpression/amplification in Chinese patients with curatively resected gastric cancer after the ToGA clinical trial
Authors: Zhou Fei , Li Ning , Jiang Weihua , Hua Zhaolai , Xia Lin , Wei Qingyi , Wang Liwei
Published: December 2012

Background

HER-2/neu-targeted therapy has been successfully used in advanced gastric cancer, but the role of HER-2/neu in the prognosis of gastric cancer is not yet clear. In this study, we investigated the correlation between HER-2/neu expression and amplification as well as their association with clinic outcomes in patients with curatively resected gastric cancer.

Methods

We constructed tissue microarray blocks containing >70% of gastric cancer tissue and matched adjacent normal gastric tissue for 227 patients. Expression of the HER-2/neu protein in these specimens was analyzed using immunohistochemical staining. Amplification of HER-2/neu was also analyzed for the same samples using fluorescence in situ hybridization. Data on clinicopathological features and relevant prognostic factors in these patients were analyzed.

Results

Of the 227 gastric cancer samples, 11.89% were positive for HER-2/neu overexpression/amplification under the new scoring system. HER-2/neu overexpression/amplification was closely correlated to the Lauren type, degree of differentiation, tumor size and lymph node metastasis. HER-2/neu overexpression/amplification predicted poor survival in univariate analysis but not in a Cox proportional hazards model.

Conclusion

HER-2/neu overexpression/amplification was not an independent predictor for survival in patients with curatively resected gastric cancer.
Expression of CXCL12 receptors in B cells from Mexican Mestizos patients with systemic lupus erythematosus
Authors: Biajoux Vincent , Bignon Alexandre , Freitas Christelle , Martinez Valérie , Thelen Marcus , Lima Guadalupe , Jakez-Ocampo Juan , Emilie Dominique , Llorente Luis , Balabanian Karl
Published: December 2012

Background

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease characterized by B-cell hyper-reactivity and the production of pathogenic anti-nuclear-directed auto-antibodies (Abs). B-cell ontogeny is partly dependent on the CXCL12/CXCR4 axis for which the contribution to SLE pathogenesis remains unclear. CXCR7, the novel receptor for CXCL12, is differentially expressed among memory B-cell subsets. However, its biological role in SLE remains to be explored.

Methods

Relative CXCR4 and CXCR7 expression levels were compared by quantitative PCR in leukocytes from blood samples of 41 Mexican Mestizos patients with SLE and 45 ethnicity-matched healthy subjects. Intracellular and membrane expression of both receptors was analyzed by flow cytometry in naive and Ab-secreting B cells. B-cell responsiveness to CXCL12 was investigated using Transwell-based chemotaxis assays. Data were analyzed using the Kruskal-Wallis test for comparisons of values amongst healthy controls and patients with inactive or active SLE, and non-parametrically using the Mann–Whitney U-test for multiple comparisons and unpaired samples. Correlations were determined by Spearman’s ranking.

Result

SLE leukocytes displayed reduced levels of CXCR4 and CXCR7 transcripts. In SLE patients, a significant defect in CXCR4 expression was detected at the surface of naive and Ab-secreting B cells, associated with an abnormal intracellular localization of the receptor. CXCR7 predominantly localized in cytosolic compartments of B cells from healthy and SLE individuals. Disease activity did not impact on these expression patterns. Altered receptor compartmentalization correlated with an impaired CXCL12-promoted migration of SLE B cells.

Conclusions

Our data highlight a down-regulation of CXCL12 receptors on circulating B cells from SLE patients that likely influences their migratory behavior and distribution.
The role of dislocation-induced scattering in electronic transport in GaxIn1-xN alloys
Authors: Donmez Omer , Gunes Mustafa , Erol Ayse , Arikan Cetin M , Balkan Naci , Schaff William J
Published: December 2012

Electronic transport in unintentionally doped GaxIn1-xN alloys with various Ga concentrations (x = 0.06, 0.32 and 0.52) is studied. Hall effect measurements are performed at temperatures between 77 and 300 K. Temperature dependence of carrier mobility is analysed by an analytical formula based on two-dimensional degenerate statistics by taking into account all major scattering mechanisms for a two-dimensional electron gas confined in a triangular quantum well between GaxIn1-xN epilayer and GaN buffer. Experimental results show that as the Ga concentration increases, mobility not only decreases drastically but also becomes less temperature dependent. Carrier density is almost temperature independent and tends to increase with increasing Ga concentration. The weak temperature dependence of the mobility may be attributed to screening of polar optical phonon scattering at high temperatures by the high free carrier concentration, which is at the order of 1014 cm−2. In our analytical model, the dislocation density is used as an adjustable parameter for the best fit to the experimental results. Our results reveal that in the samples with lower Ga compositions and carrier concentrations, alloy and interface roughness scattering are the dominant scattering mechanisms at low temperatures, while at high temperatures, optical phonon scattering is the dominant mechanism. In the samples with higher Ga compositions and carrier concentrations, however, dislocation scattering becomes more significant and suppresses the effect of longitudinal optical phonon scattering at high temperatures, leading to an almost temperature-independent behaviour.