bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum microRNA levels in patients with Crohn's disease during induction therapy by infliximab
Authors: Fujioka Shin , Nakamichi Ikuo , Esaki Motohiro , Asano Kouichi , Matsumoto Takayuki , Kitazono Takanari
Published: January 2014

Background and Aim

microRNAs (miRNAs) have been suggested to be candidates for biomarkers in various diseases including Crohn's disease (CD). To identify possible biomarkers predictive of the therapeutic effect of infliximab in CD, we investigated serum miRNA levels during the induction therapy by the medication.

Methods

Nineteen CD patients who were applied to the induction therapy by infliximab were enrolled. Serum samples for miRNA analyses were obtained at weeks 0 and 6, and the therapeutic efficacy by infliximab was assessed according to the Crohn's disease activity index value at week 14. Exploratory miRNA profiling by low‐density array was initially performed in three patients. The levels of candidate miRNA were subsequently determined by real‐time polymerase chain reaction (PCR) assays in the remaining 16 patients. The miRNA levels during the induction therapy were compared between the two groups classified by the clinical response to infliximab at week 14.

Results

Low‐density array analysis identified 14 miRNAs that showed twofold or more altered expression during the induction therapy by infliximab. Subsequent analysis by real‐time PCR demonstrated significantly increased levels of five miRNAs (let‐7d, let‐7e, miR‐28‐5p, miR‐221, and miR‐224) at week 6 when compared with those at week 0 (P < 0.05 each). In addition, miRNA levels of let‐7d and let‐7e were significantly increased in the group of patients who achieved clinical remission by infliximab (P = 0.001 and P = 0.002, respectively).

Conclusion

let‐7d and let‐7e might be possible therapeutic biomarkers in patients with CD, who are treated by infliximab.
Profiling the genes affected by pathogenic TDP‐43 in astrocytes
Authors: Huang Cao , Huang Bo , Bi Fangfang , Yan Linda H. , Tong Jianbin , Huang Jufang , Xia Xu‐Gang , Zhou Hongxia
Published: January 2014

Mutation in TAR DNA binding protein 43 (TDP‐43) is a causative factor of amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Neurodegeneration may not require the presence of pathogenic TDP‐43 in all types of relevant cells. Rather, expression of pathogenic TDP‐43 in neurons or astrocytes alone is sufficient to cause cell‐autonomous or non‐cell‐autonomous neuron death in transgenic rats. How pathogenic TDP‐43 in astrocytes causes non‐cell‐autonomous neuron death, however, is not clear. Here, we examined the effect of pathogenic TDP‐43 on gene expression in astrocytes. Microarray assay revealed that pathogenic TDP‐43 in astrocytes preferentially altered expression of the genes encoding secretory proteins. Whereas neurotrophic genes were down‐regulated, neurotoxic genes were up‐regulated. Representative genes Lcn2 and chitinase‐3‐like protein 1 were markedly up‐regulated in astrocytes from primary culture and intact transgenic rats. Furthermore, synthetic chitinase‐3‐like protein 1 induced neuron death in a dose‐dependent manner. Our results suggest that TDP‐43 pathogenesis is associated with the simultaneous induction of multiple neurotoxic genes in astrocytes, which may synergistically produce adverse effects on neuronal survival and contribute to non‐cell‐autonomous neuron death.

image

Restricted expression of pathogenic TDP‐43 in astrocytes causes non‐cell‐autonomous motor neuron death in transgenic rats. As revealed by microarray assay, pathogenic TDP‐43 in astrocytes preferentially altered expression of the genes encoding secretory proteins. Whereas neurotrophic genes were down‐regulated, neurotoxic genes were up‐regulated. Therefore, TDP‐43 pathogenesis is associated with simultaneous induction of neurotoxic genes and repression of neurotrophic genes in astrocytes.
Inhibition of interleukin‐1β production by extracellular acidification through the TDAG8/cAMP pathway in mouse microglia
Authors: Jin Ye , Sato Koichi , Tobo Ayaka , Mogi Chihiro , Tobo Masayuki , Murata Naoya , Ishii Satoshi , Im Dong‐Soon , Okajima Fumikazu
Published: January 2014

Interleukin‐1β (IL‐1β) is released from activated microglia and involved in the neurodegeneration of acute and chronic brain disorders, such as stroke and Alzheimer's disease, in which extracellular acidification has been shown to occur. Here, we examined the extracellular acidic pH regulation of IL‐1β production, especially focusing on TDAG8, a major proton‐sensing G‐protein‐coupled receptor, in mouse microglia. Extracellular acidification inhibited lipopolysaccharide ‐induced IL‐1β production, which was associated with the inhibition of IL‐1β cytoplasmic precursor and mRNA expression. The IL‐1β mRNA and protein responses were significantly, though not completely, attenuated in microglia derived from TDAG8‐deficient mice compared with those from wild‐type mice. The acidic pH also stimulated cellular cAMP accumulation, which was completely inhibited by TDAG8 deficiency. Forskolin and a cAMP derivative, which specifically stimulates protein kinase A (PKA), mimicked the proton actions, and PKA inhibitors reversed the acidic pH‐induced IL‐1β mRNA expression. The acidic pH‐induced inhibitory IL‐1β responses were accompanied by the inhibition of extracellular signal‐related kinase and c‐Jun N‐terminal kinase activities. The inhibitory enzyme activities in response to acidic pH were reversed by the PKA inhibitor and TDAG8 deficiency. We conclude that extracellular acidic pH inhibits lipopolysaccharide‐induced IL‐1β production, at least partly, through the TDAG8/cAMP/PKA pathway, by inhibiting extracellular signal‐related kinase and c‐Jun N‐terminal kinase activities, in mouse microglia.

image

A number of studies have shown that extracellular acidification in brain is observed in ischemia and neurodegenerative disorders. However, the molecular mechanism by which extracellular acidification regulates the biological activities of microglia remains uncharacterized. Here, we examined the extracellular acidic pH regulation of IL‐1β production, especially focusing on TDAG8, a member of OGR1 family receptors. Our results suggest that extracellular acidic pH inhibited lipopolysaccharide ‐induced IL‐1β production at least partly through the TDAG8/cAMP pathway, by inhibiting ERK and JNK activities.
Incidence and Correlates in the Development of Iatrogenic Femoral Pseudoaneurysm after Percutaneous Coronary Interventions
Authors: BADR SALEM , KITABATA HIRONORI , TORGUSON REBECCA , CHEN FANG , SUDDATH WILLIAM O. , SATLER LOWELL F. , PICHARD AUGUSTO D. , WAKSMAN RON , BERNARDO NELSON L.
Published: January 2014

Objective

We aimed to identify the correlates in the development of post‐percutaneous coronary intervention (PCI) iatrogenic femoral pseudoaneurysm (IFP).

Background

IFP is one of the more common vascular complications of PCI.

Methods

From February 2008 to June 2012, 10,169 consecutive patients who underwent PCI were retrospectively studied. Patients who developed postprocedural IFP were identified at a single, large tertiary PCI center.

Results

One hundred thirty‐nine patients developed IFP (1.38%) and were compared to the cohort that did not. Baseline characteristics were comparable, although patients in the IFP group were older and had a higher incidence of insulin‐requiring diabetes mellitus and chronic renal insufficiency (68.4 ± 12.9 vs. 65.4 ± 12.3 years, P = 0.004; 23.9% vs. 14.6%, P = 0.002; and 26.6% vs. 17.3%, P = 0.004, respectively). The non‐IFP group had more men and a higher use of vascular closure devices, respectively (64.7% vs. 49.6%, P < 0.001; and 54.1% vs. 26.5%, P < 0.001). There was no significant difference in the use of dual antiplatelet or anticoagulation therapies between the 2 cohorts. Univariable correlates for the development of IFP were female gender, insulin‐requiring diabetes mellitus, chronic renal insufficiency, and use of manual compression to achieve hemostasis. On multivariable analysis, the successful deployment of vascular closure device for hemostasis reduced the occurrence of IFP (odds ratio 0.31, 95% confidence interval 0.21–0.46, P < 0.0001).

Conclusion

The development of IFP following PCI is not uncommon and the appropriate use of vascular closure devices to achieve hemostasis should be encouraged to minimize this vascular complication. (J Interven Cardiol 2014;27:212–216)
Volitional chewing with a conscious effort alters and facilitates swallowing during feeding sequence
Authors: Furuya J. , Hara A. , Nomura T. , Kondo H.
Published: January 2014

The key objective of mastication is to form a food bolus suitable for smooth swallowing. However, chewing is usually performed without a conscious effort. Poor bolus formation can cause pharyngeal residue and suffocation in elderly individuals with reduced swallowing function. Therefore, chewing with a conscious effort may help the bolus to more easily pass the pharynx. This study aimed to clarify the impact of mastication with a conscious effort on the feeding sequence. Subjects included 25 dentulous volunteers who were informed and provided written consent. Lateral videofluoroscopy was performed during the feeding of solid agar jelly under two conditions: chewing naturally in their usual manner (without volition) and chewing with a conscious effort (with volition). Temporal evaluation was performed for mastication, stage II transport (STII), swallow onset and oropharyngeal transit time. Moreover, bolus volume at swallow onset and subjective evaluation of swallowing easiness were measured. Volitional chewing with a conscious effort lengthened the duration of the chewing sequence before and after STII and delayed the swallow onset despite the fact that the bolus volume in the vallecula and hypopharynx (HYP) had significantly increased. Furthermore, with volition, the bolus transit time from swallow onset in the oral cavity, upper oropharynx and HYP was reduced, and subjective evaluation of swallowing easiness demonstrated significant improvement. These results suggest that volitional chewing with a conscious effort can alter bolus transport and swallowing, resulting in easier swallowing.
Genetic and phenotypic divergence in an island bird: isolation by distance, by colonization or by adaptation?
Authors: Spurgin Lewis G. , Illera Juan Carlos , Jorgensen Tove H. , Dawson Deborah A. , Richardson David S.
Published: January 2014

Discerning the relative roles of adaptive and nonadaptive processes in generating differences among populations and species, as well as how these processes interact, is a fundamental aim in biology. Both genetic and phenotypic divergence across populations can be the product of limited dispersal and gradual genetic drift across populations (isolation by distance), of colonization history and founder effects (isolation by colonization) or of adaptation to different environments preventing migration between populations (isolation by adaptation). Here, we attempt to differentiate between these processes using island populations of Berthelot's pipit (Anthus berthelotii), a passerine bird endemic to three Atlantic archipelagos. Using microsatellite markers and approximate Bayesian computation, we reveal that the northward colonization of this species ca. 8500 years ago resulted in genetic bottlenecks in the colonized archipelagos. We then show that high levels of genetic structure exist across archipelagos and that these are consistent with a pattern of isolation by colonization, but not with isolation by distance or adaptation. Finally, we show that substantial morphological divergence also exists and that this is strongly concordant with patterns of genetic structure and bottleneck history, but not with environmental differences or geographic distance. Overall, our data suggest that founder effects are responsible for both genetic and phenotypic changes across archipelagos. Our findings provide a rare example of how founder effects can persist over evolutionary timescales and suggest that they may play an important role in the early stages of speciation.
Formation of Microvascular Networks: Role of Stromal Interactions Directing Angiogenic Growth
Authors: Hoying James B. , Utzinger Urs , Weiss Jeffrey A.
Published: January 2014

In the adult, angiogenesis leads to an expanded microvascular network as new vessel segments are added to an existing microcirculation. Necessarily, growing neovessels must navigate through tissue stroma as they locate and grow toward other vessel elements. We have a growing body of evidence demonstrating that angiogenic neovessels reciprocally interact with the interstitial matrix of the stroma resulting in directed neovascular growth during angiogenesis. Given the compliance and the viscoelastic properties of collagen, neovessel guidance by the stroma is likely due to compressive strain transverse to the direction of primary tensile forces present during active tissue deformation. Similar stromal strains control the final network topology of the new microcirculation, including the distribution of arterioles, capillaries, and venules. In this case, stromal‐derived stimuli must be present during the post‐angiogenesis remodeling and maturation phases of neovascularization to have this effect. Interestingly, the preexisting organization of vessels prior to the start of angiogenesis has no lasting influence on the final, new network architecture. Combined, the evidence describes interplay between angiogenic neovessels and stroma that is important in directed neovessel growth and invasion. This dynamic is also likely a mechanism by which global tissue forces influence vascular form and function.
Post‐transcriptional silencing of UIS4 in Plasmodium berghei sporozoites is important for host switch
Authors: Silvie Olivier , Briquet Sylvie , Müller Katja , Manzoni Giulia , Matuschewski Kai
Published: January 2014

Plasmodium sporozoites are transmitted by mosquitoes and first infect hepatocytes of their mammalian host, wherein they develop as liver stages, surrounded by the parasitophorous vacuole membrane (PVM). The parasite must rapidly adapt to its changing environment after switching host. Shortly after invasion, the PVM is remodelled by insertion of essential parasite proteins of the early transcribed membrane protein family such as UIS4. Here, using the rodent malaria model Plasmodium berghei, we show that transcripts encoding UIS4 are stored in a translationally repressed state in sporozoites, allowing UIS4 protein synthesis only after host cell invasion. Using a series of reporter transgenic parasite lines we could demonstrate that the open reading frame of UIS4 mRNA is critical for gene silencing, whereas the 5′ and 3′ untranslated regions are dispensable. Our data further indicate that the UIS4 translational repression machinery is present only in mature sporozoites in the mosquito salivary glands, and that premature expression of UIS4 protein results in a loss of parasite infectivity. Our findings reveal the importance of specific post‐transcriptional control in sporozoites, and establish that host switch requires high levels of translationally silent UIS4 RNA, which permits stage conversion, yet avoids premature expression of this liver stage‐specific protein.
Sexual dimorphism and developmental patterns in the external morphology of the vaquita, Phocoena sinus
Authors: Torre Jorge , Vidal Omar , Brownell Robert L.
Published: January 2014

A total of 56 vaquitas (Phocoena sinus) were examined to evaluate their sexual dimorphism and isometric and/or allometric growth in 35 external characteristics. Absolute and relative (to total length) measurements and growth rates were compared between sexually immature and mature females and males. T‐tests and analysis of variance (ANOVA) and covariance (ANCOVA) were used to evaluate sexual dimorphism. Sexual dimorphism in the vaquita was detected in the total length, head region (from blowhole to tip of upper jaw), anterior section of the body (from dorsal fin to tip of upper jaw), dorsal fin and the genital and anal regions. Fluke width is relatively larger in mature males than immature males, but in females this relative metric does not change during their development. In addition, males present a higher dorsal fin. These somatic changes are probably related to the swimming capacity (speed, agility, maneuvering) during the breeding season and/or foraging activities. A linear model of growth was used to determine possible proportional changes with respect to total body length through the development of 33 external characteristics. The anterior region of the body and the flippers were relatively larger in immature individuals than in mature ones.
Neutralizing Unethical Negotiating Tactics: An Empirical Investigation of Approach Selection and Effectiveness
Authors: Fleck Denise , Volkema Roger , Pereira Sergio , Levy Barbara , Vaccari Lara
Published: January 2014

Negotiation is integral to business success, and information is the lifeblood of the negotiation process. When invalid information is disseminated via manipulation or deceit, one or more parties can suffer. Nonetheless, many studies have shown that the use of questionable or unethical tactics is commonplace. This article reports on a study of twelve behaviors that can neutralize a counterpart's tendencies to employ questionable or unethical tactics, improving the chances for an integrative (win–win) outcome. The results suggest that while nearly two thirds of participants employed neutralizing behaviors, they used many of these behaviors later in the negotiation process than anticipated and simultaneously alongside questionable or unethical tactics. While we found some evidence that the twelve neutralizing behaviors were viewed differently from questionable or unethical tactics, the expected attenuating effects were not found. The implications of these findings, including opportunities for future research, are discussed.
Teaching Negotiations in the New Millennium: Evidence‐Based Recommendations for Online Course Delivery
Authors: Parlamis Jennifer D. , Mitchell Lorianne D.
Published: January 2014

Traditional methods for teaching negotiation have required both instructor and student to be physically present in the same location. With the advent of the Internet and associated technological advances, however, instructors may now transcend geographical barriers and effectively deliver the same content virtually. In this article, we present an exploratory study comparing two masters‐level negotiation courses: one taught using a traditional in‐person method and the other taught online. Results showed no significant difference in knowledge acquisition as quantified by objective measures, including mean grades. In addition, self‐report data indicate that, although students' skill and mastery of negotiation improved in both courses, online students reported that they experienced less interaction and social engagement with their classmates and instructor. Several course development strategies and best practices are discussed.
Vascular calcification in long‐term kidney transplantation
Authors: Vipattawat Kotcharat , Kitiyakara Chagriya , Phakdeekitcharoen Bunyong , Kantachuvesiri Surasak , Sumethkul Vasant , Jirasiritham Sophon , Stitchantrakul Wasana , Disthabanchong Sinee
Published: January 2014

Aim

Vascular calcification (VC) is common among patients with chronic kidney disease (CKD) due to the strong prevalence of cardiovascular and CKD‐related risk factors such as diabetes mellitus (DM), hypertension and phosphate retention. Kidney transplantation improves kidney function and abnormal mineral metabolism at the same time. It remains unclear whether kidney transplantation favourably impacts VC in the long‐term.

Methods

The present study examined VC in 132 kidney transplant (KT) recipients who had been transplanted for longer than one year. The severity of VC was compared to 129 CKD stages 5‐5D patients on a kidney transplant (KT) waiting list.

Results

The median KT vintage was 88 months. The prevalence of VC among KT and CKD patients were 54.5% and 62.8%, respectively, (P = 0.2). There were no differences in age, gender, body mass index (BMI), the prevalence of DM or CVD between the two groups. Among patients with calcification, a more severe degree was observed in KT recipients (P = 0.01). Aging, DM, CVD and dialysis vintage were associated with significant VC in both groups. The degree of VC in KT recipients was more pronounced than that in CKD patients among those who experienced prolonged dialysis vintage (>2 years) (P = 0.04). Among KT recipients, the severity of VC increased with the length of time after transplantation and became more substantial after 5 years.

Conclusions

Long‐term KT recipients demonstrated a more severe degree of VC compared to matched CKD stages 5‐5D patients. The severity of VC became more pronounced among those with longer transplant vintage and was in part influenced by past dialysis experience.
Looking in the Porphyromonas gingivalis cabinet of curiosities: the microbium, the host and cancer association
Authors: Atanasova K.R. , Yilmaz Ö.
Published: January 2014

The past decades of biomedical research have yielded massive evidence for the contribution of the microbiome in the development of a variety of chronic human diseases. There is emerging evidence that Porphyromonas gingivalis, a well‐adapted opportunistic pathogen of the oral mucosa and prominent constituent of oral biofilms, best known for its involvement in periodontitis, may be an important mediator in the development of a number of multifactorial and seemingly unrelated chronic diseases, such as rheumatoid arthritis and orodigestive cancers. Orodigestive cancers represent a large proportion of the total malignancies worldwide, and include cancers of the oral cavity, gastrointestinal tract and pancreas. For prevention and/or enhanced prognosis of these diseases, a good understanding of the pathophysiological mechanisms and the interaction between P. gingivalis and host is much needed. With this review, we introduce the currently accumulated knowledge on P. gingivalis's plausible association with cancer as a risk modifier, and present the putative cancer‐promoting cellular and molecular mechanisms that this organism may influence in the oral mucosa.
Plasticity in latitudinal patterns of leaf N and P of Oryza rufipogon in China
Authors: Zhou W. , Wang Z. , Xing W. , Liu G.
Published: January 2014

Characterising the adaptability in nature of plant stoichiometric patterns across geographic or environmental gradients is important in advancing our understanding of the organisation of plant–nutrient relationships. We examined correlations between plant nutrient traits, latitude, longitude, climate and soil variables in 34 populations of Oryza rufipogon across its range. We further compared the responses of population transplants at two experimental gardens: one beyond its northern natural range and another near the southern limit, to assess the nature of geographic variation in plant nutrients. The study showed that leaf P of O. rufipogon in the field was negatively correlated with latitude and largely depended on temperature and soil P availability. Leaf N was not related to latitude but was significantly correlated with precipitation and soil N concentration. Leaf N:P ratio was largely determined by absorption efficiency of P. Transplantation revealed that there were no significant associations of leaf nutrients with geographic, climatic or soil variables of origin in either of the experimental gardens, indicating phenotypic plasticity. However, examination of relationships between response ratios of leaf nutrients and change ratio of climate and soil environments, as well as norms of reaction in the transplantation experiment, revealed more complexity, suggesting both substantial genotypic diversity and the existence of genotype × environment interactions in these populations of O. rufipogon. These data indicate that adaptive plasticity response of plants to temperature and soil P availability significantly explain the observed shifts in leaf N, P and N:P of O. rufipogon along latitudinal gradients.
Optimal Procurement Design of an Assembly Supply Chain with Information Asymmetry
Authors: Fang Xiang , Ru Jun , Wang Yunzeng
Published: January 2014

We study a decentralized assembly supply chain in which an assembler (she) assembles a set of n components, each produced by a different supplier (he), into a final product to satisfy an uncertain market demand. Each supplier holds private cost information to himself, for which the assembler only has a subjective estimate. Furthermore, the assembler believes that the suppliers' costs follow a joint discrete probability distribution. The assembler aims to design an optimal menu of contracts to maximize her own expected profit. The assembler's problem is a complex multi‐dimensional constrained optimization problem. We prove that there exists a unique optimal menu of contracts for the assembler, and we further develop an efficient algorithm with a complexity of O( n) to compute the optimal contract. In addition, we conduct a comprehensive sensitivity analysis to analyze how environmental parameters affect individual firm's performance and the value of information to the assembler, to each supplier, and to the supply chain. Our results suggest that each supplier's private cost information becomes more valuable to the assembler and each supplier when the average market demand increases or when the final product unit revenue increases. Surprisingly, when a supplier's cost volatility increases and its mean remains the same, the value of information to the assembler or to each supplier does not necessarily increase. Furthermore, we show that when the suppliers' cost distributions become more positively correlated, the suppliers are always worse off, but the assembler is better off. However, the value of information for the assembler might increase or decrease.
Networks, Contexts, and the Combinatorial Dynamics of Democratic Politics
Authors: Huckfeldt Robert
Published: January 2014

Democratic politics inevitably stimulates a socially imbedded process of communication among citizens, and thus individuals experience politics by way of ongoing forms of social interaction and communication with others. Within this context, it is thus both ironic and problematic that political scientists, journalists, campaign consultants, and others typically conceive of political behavior in terms of individually independent actors rather than as the socially contingent outcome of interdependent citizens located within distinctive ongoing streams of socially communicated information. This state of affairs is less a consequence of theoretically articulated models of behavior than it is an unintentional methodological byproduct. Powerful, productive, and creative methods of analysis, based on the observational platforms of both sample surveys and laboratory experiments, tend to separate interdependent actors from one another. These practices often generate, by default, an atomistic view of public opinion and political behavior. This article addresses several lines of research, based both on laboratory and survey studies, that attempt to reintroduce political interdependence among citizens within the normal scope of political analysis. In this way, political analysis carries the potential to unify micro and macro analyses of democratic politics.
Political Parties, Motivated Reasoning, and Public Opinion Formation
Authors: Leeper Thomas J. , Slothuus Rune
Published: January 2014

A key characteristic of democratic politics is competition between groups, first of all political parties. Yet, the unavoidably partisan nature of political conflict has had too little influence on scholarship on political psychology. Despite more than 50 years of research on political parties and citizens, we continue to lack a systematic understanding of when and how political parties influence public opinion. We suggest that alternative approaches to political parties and public opinion can be best reconciled and examined through a richer theoretical perspective grounded in motivated reasoning theory. Clearly, parties shape citizens' opinions by mobilizing, influencing, and structuring choices among political alternatives. But the answer to when and how parties influence citizens' reasoning and political opinions depends on an interaction between citizens' motivations, effort, and information generated from the political environment (particularly through competition between parties). The contribution of motivated reasoning, as we describe it, is to provide a coherent theoretical framework for understanding partisan influence on citizens' political opinions. We review recent empirical work consistent with this framework. We also point out puzzles ripe for future research and discuss how partisan‐motivated reasoning provides a useful point of departure for such work.
Introduction to causal diagrams for confounder selection
Authors: Williamson Elizabeth J. , Aitken Zoe , Lawrie Jock , Dharmage Shyamali C. , Burgess John A. , Forbes Andrew B.
Published: January 2014

In respiratory health research, interest often lies in estimating the effect of an exposure on a health outcome. If randomization of the exposure of interest is not possible, estimating its effect is typically complicated by confounding bias. This can often be dealt with by controlling for the variables causing the confounding, if measured, in the statistical analysis. Common statistical methods used to achieve this include multivariable regression models adjusting for selected confounding variables or stratification on those variables. Therefore, a key question is which measured variables need to be controlled for in order to remove confounding. An approach to confounder‐selection based on the use of causal diagrams (often called directed acyclic graphs) is discussed. A causal diagram is a visual representation of the causal relationships believed to exist between the variables of interest, including the exposure, outcome and potential confounding variables. After creating a causal diagram for the research question, an intuitive and easy‐to‐use set of rules can be applied, based on a foundation of rigorous mathematics, to decide which measured variables must be controlled for in the statistical analysis in order to remove confounding, to the extent that is possible using the available data. This approach is illustrated by constructing a causal diagram for the research question: ‘Does personal smoking affect the risk of subsequent asthma?’. Using data taken from the Tasmanian Longitudinal Health Study, the statistical analysis suggested by the causal diagram approach was performed.
Is India Shining?
Authors: Banerjee Anurag , Banik Nilanjan
Published: January 2014

The popular perception about economic reforms having benefitted only the richer districts of India between 1999/2000 and 2004/2005 is investigated. Using the spatial dynamics of district‐level per‐capita income it was found that income distribution did not change between the years examined. It is argued that this is because of per‐capita income across districts being spatially positively correlated. Physical infrastructure, human capital, and factories are identified as factors responsible for increase in income for both the rich as well as the poor districts. Infrastructure, physical or social, is a key component of growth in India. A policy impact analysis shows development of better drainage and potable water systems has a large impact on income. For the year 2001/02, it was found that for every 1% increase in closed drainage system and potable water, district‐level median income increases by 1.39% and 0.21%, respectively.
Bank Ownership and Efficiency in the Aftermath of Financial Crises: Evidence from Indonesia
Authors: Parinduri Rasyad A. , Riyanto Yohanes E.
Published: January 2014

This paper examines the relationship between types of ownership of banks and their efficiency in the aftermath of a financial crisis using Greene's “true” panel data stochastic frontier model, which takes into account unobserved heterogeneity among banks. The Indonesian banking sector is analyzed using financial data of 144 banks operating in Indonesia over the period of 2000Q4–2005Q2. In the aftermath of the 1997 Asian financial crisis, the cost efficiency of all banks improves over time on average. However, there is some evidence that, as these banks improve their efficiency, state‐owned banks are the least efficient banks while joint‐venture and foreign‐owned banks are the most efficient.
Adaptor Protein2 (AP2) Orchestrates CXCR2‐Mediated Cell Migration
Authors: Raman Dayanidhi , Sai Jiqing , Hawkins Oriana , Richmond Ann
Published: January 2014

The chemokine receptor CXCR2 is vital for inflammation, wound healing, angiogenesis, cancer progression and metastasis. Adaptor protein 2 (AP2), a clathrin binding heterotetrameric protein comprised of α, β2, μ2 and σ2 subunits, facilitates clathrin‐mediated endocytosis. Mutation of the LLKIL motif in the CXCR2 carboxyl‐terminal domain (CTD) results in loss of AP2 binding to the receptor and loss of ligand‐mediated receptor internalization and chemotaxis. AP2 knockdown also results in diminished ligand‐mediated CXCR2 internalization, polarization and chemotaxis. Using knockdown/rescue approaches with AP2‐μ2 mutants, the binding domains were characterized in reference to CXCR2 internalization and chemotaxis. When in an open conformation, μ2 Patch 1 and Patch 2 domains bind tightly to membrane PIP2 phospholipids. When AP2‐μ2, is replaced with μ2 mutated in Patch 1 and/or Patch 2 domains, ligand‐mediated receptor binding and internalization are not lost. However, chemotaxis requires AP2‐μ2 Patch 1, but not Patch 2. AP2‐σ2 has been demonstrated to bind dileucine motifs to facilitate internalization. Expression of AP2‐σ2 V88D and V98S dominant negative mutants resulted in loss of CXCR2 mediated chemotaxis. Thus, AP2 binding to both membrane phosphatidylinositol phospholipids and dileucine motifs is crucial for directional migration or chemotaxis. Moreover, AP2‐mediated receptor internalization can be dissociated from AP2‐mediated chemotaxis.
The natural killer–activating receptor, NKG2D, on CD3+CD8+ T cells plays a critical role in identifying and killing autologous myeloma cells
Authors: Talebian Laleh , Fischer Dawn A. , Wu Jillian , Channon Jacqueline Y. , Sentman Charles L. , Ernstoff Marc S. , Meehan Kenneth R.
Published: January 2014

Background

The NKG2D receptor, one of the natural killer (NK) cell–activating receptors, is expressed on the surface of CD3+CD8+ T cells, γδ+ T cells, NK cells, NKT cells, and a few CD4+ T cells. We show, for the first time, a critical role for the NKG2D receptor on CD3+CD8+ T cells isolated from myeloma patients, in identifying and killing autologous myeloma cells isolated from the same patients’ marrow. We also show that blocking NKG2D using anti‐NKG2D reverses the cytotoxicity while blocking HLA‐I using antibodies does not have the same effect, showing that the autologous cytotoxicity is NKG2D dependent and major histocompatibility complex (MHC)‐I independent. We further confirmed the NKG2D specificity by small interfering RNA (siRNA) down regulation of NKG2D receptor.

Study Design and Methods

Using ex vivo expansion methods that enrich for NKG2D+CD3+CD8+ T cells, we investigated whether these ex vivo expanded NKG2D+CD3+CD8+ T cells would recognize and lyse autologous and allogeneic myeloma cells, independent of T‐cell receptor or MHC‐I expression.

Results

Myeloma cell lysis by the NKG2D+CD3+CD8+ T cells correlated with the amount of NKG2D ligand expression. With receptor–ligand interaction, interferon‐γ and tumor necrosis factor‐α were released. Blocking the NKG2D receptor by using either monoclonal antibodies or siRNAs inhibited the receptor's function and prevented myeloma cell lysis.

Conclusion

Clinical trials are ongoing to determine a correlation with the number and function of NKG2D+CD3+CD8+ T cells and clinical outcomes in transplanted myeloma patients, including lymphocyte recovery following transplant and overall survival.
Vector variational inequalities and their relations with vector optimization
Authors: Suneja Surjeet Kaur , Kohli Bhawna
Published: January 2014

In this paper, K- quasiconvex, K- pseudoconvex and other related functions have been introduced in terms of their Clarke subdifferentials, where   is an arbitrary closed convex, pointed cone with nonempty interior. The (strict, weakly) -pseudomonotonicity, (strict) K- naturally quasimonotonicity and K- quasimonotonicity of Clarke subdifferential maps have also been defined. Further, we introduce Minty weak (MVVIP) and Stampacchia weak (SVVIP) vector variational inequalities over arbitrary cones. Under regularity assumption, we have proved that a weak minimum solution of vector optimization problem (VOP) is a solution of (SVVIP) and under the condition of K- pseudoconvexity we have obtained the converse for MVVIP (SVVIP). In the end we study the interrelations between these with the help of strict K-naturally quasimonotonicity of Clarke subdifferential map.
Mond-Weir type second order multiobjective mixed symmetric duality with square root term under generalized univex function
Authors: Tripathy Arun Kumar
Published: January 2014

In this paper, a new class of second order (Φ,ρ)-univex and second order (Φ,ρ)-pseudo univex function are introduced with example. A pair Mond-Weir type second order mixed symmetric duality for multiobjective nondifferentiable programming is formulated and the duality results are established under the mild assumption of second order (∅,ρ) univexity and second order pseudo univexity. Special cases are discussed to show that this study extends some of the known results in related domain..
A class of semilocal E-preinvex maps in Banach spaces with applications to nondiï¬€erentiable vector optimization
Authors: Jiao Hehua
Published: January 2014

In this paper, a new class of semilocal E-preinvex and related maps in Banach spaces is introduced for a nondiï¬€erentiable vector optimization problem with restrictions of inequalities and some of its basic properties are studied. Furthermore, as its applications, some optimality conditions and duality results are established for a nondiï¬€erentiable vector optimization under the aforesaid maps assumptions.
Adolescent Performers’ Perspectives on Mental Toughness and Its Development: The Utility of the Bioecological Model
Authors: Mahoney John W. , Gucciardi Daniel F. , Mallett Clifford J. , Ntoumanis Nikos
Published: January 2014

In light of the extant literature, the aim of the current study was to compare adolescents’ perspectives on mental toughness and its development across performance contexts, and to explore if such perspectives align with Bronfenbrenner’s (2001) bioecological model. Eighteen mentally tough adolescents (9 boys, 9 girls, Mage = 15.6 years) from three performance contexts (i.e., sport, academia, and music) participated in focus groups, 7 of whom also participated in follow-up one-to-one interviews. Inductive analyses revealed that mental toughness was conceptualized by 9 personal characteristics, and that while similar across performance contexts, some difference between previous mental toughness conceptualization and the current study existed. Analyses also revealed that mental toughness development was predicated on significant others, supportive social processes, critical incidents, and curiosity. These findings resonated with the properties of the bioecological model. Future research into how bioecological factors combine to facilitate mental toughness development during critical stages of life was suggested.
Lessons Learned Consulting at Olympic Trials: Swimming Through Growing Pains
Authors: Christensen Dolores A. , Aoyagi Mark W.
Published: January 2014

The literature on the practice of sport and performance psychology (SPP) is lacking in recent contributions from student practitioners despite previous calls for additional contributions (Holt & Strean, 2001; Tonn & Harmison, 2004). A recent graduate from a master’s degree program in SPP was invited to attend USA Swimming 2012 Olympic Team Trials as a member of the support staff for the club swim team she had been consulting with for the duration of her graduate training. The focus of this paper is to expand upon this gap in the literature by providing a first-hand account of a young practitioner’s experiences at a high-performance meet. The neophyte consultant’s use of supervision for personal and professional preparation for Olympic trials, her experiences there, including ethical dilemmas encountered, and the lessons learned from attending such an event so early in her career will be discussed. Future implications are also offered for graduate students and early career professionals in SPP.
Bilateral axillary arterial obstruction
Authors: van der Matten Beatrice , Zandbergen Adrienne Anne Marie , Dees Adriaan
Published: January 2014

A 74-year-old patient with longstanding diabetes mellitus and hypertension presented with obstruction in both axillary arteries. Although atherosclerotic obstructive disease would have been the most likely diagnosis in this patient, clinical findings were highly suggestive of extracranial giant-cell arteritis. Prompt treatment with systemic corticosteroids resulted in an excellent clinical response, avoiding the risks of endovascular or surgical intervention.
Real-ear acoustical characteristics of impulse sound generated by golf drivers and the estimated risk to hearing: a cross-sectional study
Authors: Zhao Fei , Bardsley Barry
Published: January 2014

Objectives

This study investigated real-ear acoustical characteristics in terms of the sound pressure levels (SPLs) and frequency responses in situ generated from golf club drivers at impact with a golf ball. The risk of hearing loss caused by hitting a basket of golf balls using various drivers was then estimated.

Design

Cross-sectional study.

Setting

The three driver clubs were chosen on the basis of reflection of the commonality and modern technology of the clubs. The participants were asked to choose the clubs in a random order and hit six two-piece range golf balls with each club. The experiment was carried out at a golf driving range in South Wales, UK.

Participants

19 male amateur golfers volunteered to take part in the study, with an age range of 19–54 years.

Outcome measures

The frequency responses and peak SPLs in situ of the transient sound generated from the club at impact were recorded bilaterally and simultaneously using the GN Otometric Freefit wireless real-ear measurement system. A swing speed radar system was also used to investigate the relationship between noise level and swing speed.

Results

Different clubs generated significantly different real-ear acoustical characteristics in terms of SPL and frequency responses. However, they did not differ significantly between the ears. No significant correlation was found between the swing speed and noise intensity. On the basis of the SPLs measured in the present study, the percentage of daily noise exposure for hitting a basket of golf balls using the drivers described above was less than 2%.

Conclusions

The immediate danger of noise-induced hearing loss for amateur golfers is quite unlikely. However, it may be dangerous to hearing if the noise level generated by the golf clubs exceeded 116 dBA.
Diffusion of an evidence-based smoking cessation intervention through Facebook: a randomised controlled trial study protocol
Authors: Cobb Nathan K , Jacobs Megan A , Saul Jessie , Wileyto E Paul , Graham Amanda L
Published: January 2014

Introduction

Online social networks represent a potential mechanism for the dissemination of health interventions including smoking cessation; however, which elements of an intervention determine diffusion between participants is unclear. Diffusion is frequently measured using R, the reproductive rate, which is determined by the duration of use (t), the ‘contagiousness’ of an intervention (β) and a participant's total contacts (z). We have developed a Facebook ‘app’ that allows us to enable or disable various components designed to impact the duration of use (expanded content, proactive contact), contagiousness (active and passive sharing) and number of contacts (use by non-smoker supporters). We hypothesised that these elements would be synergistic in their impact on R, while including non-smokers would induce a ‘carrier’ state allowing the app to bridge clusters of smokers.

Methods and analysis

This study is a fractional factorial, randomised control trial of the diffusion of a Facebook application for smoking cessation. Participants recruited through online advertising are randomised to 1 of 12 cells and serve as ‘seed’ users. All user interactions are tracked, including social interactions with friends. Individuals installing the application that can be traced back to a seed participant are deemed ‘descendants’ and form the outcome of interest. Analysis will be conducted using Poisson regression, with event count as the outcome and the number of seeds in the cell as the exposure.

Results

The results will be reported as a baseline R0 for the reference group, and incidence rate ratio for the remainder of predictors.

Ethics and Dissemination

This study uses an abbreviated consent process designed to minimise barriers to adoption and was deemed to be minimal risk by the Institutional Review Board (IRB). Results will be disseminated through traditional academic literature as well as social media. If feasible, anonymised data and underlying source code are intended to be made available under an open source license.

ClinicalTrials.gov registration number

NCT01746472.
Improving time to antibiotics and implementing the "Sepsis 6"
Authors: McGregor Calum
Published: January 2014

It has been shown that completion of the "Sepsis 6" within 1 hour reduces mortality (1). This project aims to assess compliance with this standard and evaluate the effectiveness of a sepsis improvement plan in a district general hospital in the UK.

A baseline audit was performed, examining case notes of “septic patients” retrospectively (those on intravenous antibiotics). Compliance with each element of the sepsis six plus time to first antibiotic (TTFA) was assessed. A sepsis improvement plan was introduced consisting of staff education, reinforcing vigilance, regular multidisciplinary meetings and incorporating a standardised approach through the use of a sepsis proforma. Following the introduction of this, and after some refinement, the average time to antibiotic fell from 6 hours to 1.4 hours.

In conclusion, an educational drive along with a systematic change in processes has seen reduced TTFA along with enhanced compliance with most elements of the sepsis 6. Through continued assessment and further improving upon systematic processes with continued education we would anticipate consistent improvement in the management of septic patients.
The importance of placebo effects in enhancing palliative care interventions
Authors: Lucas V , Booth S
Published: January 2014

In this narrative review, we examine evidence that may help to explain how placebo effects contribute to the effectiveness of palliative care interventions for the relief of symptoms such as pain, breathlessness and depression, and how they may underlie the impact of complementary therapies. We discuss the different ways of conceptualising placebo phenomena, including the importance of the therapeutic relationship, the context of care and the significance of meaning. There is increasing evidence from neuroscience that the term ‘placebo effect’ describes a number of phenomena that may explain the effectiveness of therapeutic interventions that affect the perception of symptoms. A greater appreciation of placebo effects emphasises the importance of addressing social, psychological, and spiritual factors with equal rigour. Commissioning bodies, rightly concerned about the evidence base for clinical interventions, need to recognise the multifaceted nature of symptom control measures and to realise that the focus for palliative care research needs to be on the specialty as a complex integrated intervention rather than on a series of individually evaluated measures.