bluuebunny/crossref_metadata_2025 huggingface dataset:
Orbital Mass in a Child With Acute Lymphoblastic Leukemia: A Case Report and Review of the Literature
Authors: Ramamoorthy Jaikumar , Jain Richa , Trehan Amita , Saxena Akshay K. , Ahluwalia Jasmina
Published: February 2016

Acute lymphoblastic leukemia arising from lymphoid precursor cells of the bone marrow, the lymphoreticular system, and the soft tissue can present with medullary and extramedullary involvement. Extramedullary involvement has the propensity to affect a multitude of organs. Presentation with proptosis secondary to orbital mass in childhood acute lymphoblastic leukemia (ALL) is very rare. We report a child with pre-B cell ALL with an extramedullary soft tissue mass involving both orbits presenting with proptosis, and give a brief overview of the literature about this unusual entity. Rapid investigation and timely initiation of treatment are needed to salvage the eye and the vision. Orbital involvement is considered to confer a poorer prognosis to children with ALL.
Characteristics of the Family Caregivers Who Did Not Benefit From a Successful Psychoeducational Group Intervention During Palliative Cancer Care
Authors: Holm Maja , Årestedt Kristofer , Carlander Ida , Wengström Yvonne , Öhlen Joakim , Alvariza Anette
Published: February 2016

Background:

Although there has been a steady increase in intervention studies aimed toward supporting family caregivers in palliative cancer care, they often report modest effect sizes and there is a lack of knowledge about possible barriers to intervention effectiveness.

Objective:

The aim of this study is to explore the characteristics of family caregivers who did not benefit from a successful psychoeducational group intervention compared with the characteristics of those who did.

Intervention/Methods:

A psychoeducational intervention for family caregivers was delivered at 10 palliative settings in Sweden. Questionnaires were used to collect data at baseline and following the intervention. The Preparedness for Caregiving Scale was the main outcome for the study and was used to decide whether or not the family caregiver had benefited from the intervention (Preparedness for Caregiving Scale difference score ≤ 0 vs ≥ 1).

Results:

A total of 82 family caregivers completed the intervention and follow-up. Caregivers who did not benefit from the intervention had significantly higher ratings of their preparedness and competence for caregiving and their health at baseline compared with the group who benefited. They also experienced lower levels of environmental burden and a trend toward fewer symptoms of depression.

Conclusions:

Family caregivers who did not benefit from the intervention tended to be less vulnerable at baseline. Hence, the potential to improve their ratings was smaller than for the group who did benefit.

Implications for Practice:

Determining family caregivers in cancer and palliative care who are more likely to benefit from an intervention needs to be explored further in research.
The Challenges, Emotions, Coping, and Gains of Family Caregivers Caring for Patients With Advanced Cancer in Singapore
Authors: Leow Mabel Q. H. , Chan Sally W. C.
Published: February 2016

Background:

Caring for a family member with advanced cancer at home is demanding as the ill family member is likely to have complex physical and emotional needs. There is a paucity of studies on the experience of home family caregivers of people with advanced cancer in the Asian region.

Objective:

The aim of this study was to describe the experiences of family caregivers caring for a person with advanced cancer at home in Singapore.

Methods:

This was a qualitative study; data were collected by semistructured interviews and analyzed using content analysis. A purposive sample of 19 family caregivers who were taking care of a family member with advanced cancer were recruited from home hospice care services in Singapore.

Results:

Most of the caregivers were female (n = 14), ranging in age from 21 to 64 years (mean, 46.4 [SD, 10.5] years). Four themes were generated from the data: (1) caregiving challenges, (2) negative emotions, (3) ways of coping, and (4) positive gains of caregiving.

Conclusions:

This study generated insights into the challenges, emotions, and coping of Asian family caregivers caring for patients with advanced cancer. Such understanding could help in developing appropriate intervention for caregivers to reduce their burden and stress.

Implications for Practice:

Caregivers require knowledge on resolving family conflicts and about communicating and enhancing closeness with the ill family member. Support from healthcare professionals is essential even if caregivers have support from family members and friends; nurses can make conscious efforts to show concern for caregivers as well as for patients.
Death Anxiety and Quality of Life in Iranian Caregivers of Patients With Cancer
Authors: Soleimani Mohammad Ali , Lehto Rebecca H. , Negarandeh Reza , Bahrami Nasim , Chan Yiong Huak
Published: February 2016

Background:

Concerns about death may alienate and negatively impact communication among family members of patients with life-threatening illness. Little is known about the relationship of death anxiety to quality of life in cancer family caregivers.

Objective:

The aim of this study was to examine relationships between sociodemographic and patient-related factors, social support, and religiosity with death anxiety and quality of life in Iranian cancer family caregivers.

Methods:

Three hundred thirty family caregivers from an urban regional cancer institute in Iran participated in a descriptive-correlational study that incorporated sociodemographic surveys and validated death anxiety (Templer Scale) and Quality of life (Family Version) instruments.

Results:

Caregivers reported moderate levels of death anxiety and decrements in QOL. Quality of life was inversely associated with death anxiety (r = −0.30, P < .001). Female caregivers who were daughters had higher death anxiety, whereas male caregivers who were sons reported higher quality of life.

Conclusions:

Death anxiety is associated with lowered quality of life in Iranian family caregivers. Multiple factors may impact death anxiety and quality of life relevant to the socioreligious milieu.

Implications for Practice:

Addressing concerns that increase death anxiety may improve quality of life and lower stress associated with adapting to the family caregiver role. Caregiving responsibilities, added to challenges associated with personal, family, and professional life, impact multiple aspects of QOL. As nurses increasingly care for patients from diverse backgrounds, it becomes more imperative that support for family caregivers that promotes psychological adaptation and quality of life is needed.
Exploration of Exercise Outcome Expectations Among Breast Cancer Survivors
Authors: Hirschey Rachel , Docherty Sharron L. , Pan Wei , Lipkus Isaac
Published: February 2016

Background:

Exercise is associated with decreased recurrence risk and improved survival and quality of life for breast cancer survivors. However, only an estimated 17% to 37% of survivors adhere to the American Cancer Society exercise guidelines. A critical first step to increase exercise among survivors is to understand how they believe exercise will affect them.

Objective:

The aim of this study is to explore common exercise outcome expectations among 20 female survivors of stage IA to IIB breast cancer who completed adjuvant treatment and an exercise intervention.

Methods:

A mixed-method descriptive study consisting of semistructured telephone interviews assessed exercise outcome expectations and how the experience of cancer and its treatment influenced the expected outcomes of exercise. The qualitative data were analyzed using a summative content analysis procedure; means were calculated for each item of the exercise outcome questionnaire. The qualitative and quantitative data were compared and contrasted.

Results:

The sample was 70% white and 30% African American, with a mean (SD) age of 62 (8.5) years, and mean (SD) time since treatment completion of 4.2 (1.3) years. Three themes emerged from the interviews: (1) prevalence of common expectations, (2) pervasive impact of fatigue, and (3) a brighter future. Overall, findings revealed that breast cancer survivors have low levels of agreement that exercise may mitigate late and long-term cancer and treatment effects.

Conclusions:

In general, breast cancer survivors (even those who are motivated to exercise) do not hold strong beliefs that exercise will decrease late and long-term treatment effects.

Implications for Practice:

Clinicians can educate survivors about exercise benefits.
Clinical Relevance of Different Papillary Growth Patterns of Pulmonary Adenocarcinoma
Authors: Warth Arne , Muley Thomas , Harms Alexander , Hoffmann Hans , Dienemann Hendrik , Schirmacher Peter , Weichert Wilko
Published: February 2016

Growth patterns of pulmonary adenocarcinoma (ADC) have high prognostic impact and are accepted as a novel classification system for this entity. However, specifically for the papillary pattern, divergent data with respect to prevalence, clinical associations, and prognostic impact have been reported. By evaluating 674 resected pulmonary ADCs containing 308 cases with a papillary component and 101 papillary predominant cases, we documented differences in the morphologic composition of papillary growth patterns and delineated 3 different types. The different types were correlated with pathologic and clinical data including survival. Type 3 papillary cases with any or predominant papillary growth were associated with extensive spread through alveolar spaces, high proliferation, higher stage, low rates of EGFR mutations, and smoking, whereas type 1 papillary tumors showed the opposite associations. The subclassification of papillary growth revealed type-specific associations for overall and disease-free survival (disease-free survival type 1: 67.1 mo, type 2: 56.8 mo, type 3: 49.9 mo, P=0.025). The presence of any papillary type 3 pattern was a predominant pattern independent predictor of worse overall survival (hazard ratio=2.5, P=0.02). For a future grading system of lung ADC, categorization of papillary growth in 1 single category might not be adequate, as this pattern contains a heterogenous mix of tumors with a divergent prognosis. We suggest that papillary pattern types should be separated to further improve the prognostic power of ADC growth pattern analysis.
Histologic Features Associated With Columnar-lined Esophagus in Distal Esophageal and Gastroesophageal Junction (GEJ) Biopsies From GERD Patients
Authors: Soucy Genevieve , Onstad Lynn , Vaughan Thomas L. , Odze Robert D.
Published: February 2016

There are inherent problems with the endoscopic and pathologic criteria for columnar-lined esophagus (CLE). Furthermore, the clinical and biological significance of an irregular squamocolumnar junction (SCJ) is unclear. The aim of this study was to evaluate the association between histologic features in SCJ biopsies and CLE and to gain insight into the significance of an irregular SCJ. The study was a cross-sectional analysis of 2176 mucosal biopsies of the SCJ from 544 patients in a large prospective community clinic-based study of gastroesophageal reflux disease in Washington State. Biopsy samples were evaluated blindly for a wide variety of histologic features, such as the presence and type of mucosal glands, submucosal glands and ducts, goblet cells, multilayered epithelium (ME), inflammation, and buried columnar epithelium. Histologic findings were correlated with the endoscopic findings (normal Z-line, irregular Z-line, or CLE) and evaluated by logistic regression and receiver operating characteristic analysis.Five histologic features were associated with CLE: pure mucous glands, ME, presence of goblet cells, ≥50% of crypts with goblet cells, and buried columnar epithelium. Pure oxyntic glands were inversely associated with CLE. The features most strongly related to CLE included biopsies with ≥50% of crypts with goblet cells, ME, and mucosal gland type (area under the curve=0.71; 95% confidence interval=0.66-0.76). Patients with an irregular Z-line were histologically similar to those with CLE. Certain histologic features in biopsies of the SCJ are associated with the presence of CLE. Irregularity of the Z-line is probably indicative of ultrashort segment CLE, instead of being a potential variation of normal.
Analysis of NAB2-STAT6 Gene Fusion in 17 Cases of Meningeal Solitary Fibrous Tumor/Hemangiopericytoma
Authors: Yuzawa Sayaka , Nishihara Hiroshi , Wang Lei , Tsuda Masumi , Kimura Taichi , Tanino Mishie , Tanaka Shinya
Published: February 2016

Solitary fibrous tumor/hemangiopericytoma (SFT/HPC) is a mesenchymal tumor that can affect virtually any region of the body. SFT/HPC of the thoracic cavity and soft tissue has been histologically considered a single biological entity termed SFT; in fact, NAB2-STAT6 gene fusion was recently identified in both diseases. In contrast, meningeal SFT and HPC still need to be investigated in detail with regard to gene fusion variants. The aim of this study was to verify the frequency of NAB2-STAT6 fusion and the relationship between fusion variants and clinicopathologic findings of SFT/HPC, especially meningeal SFT/HPC. We examined the NAB2-STAT6 fusion by reverse transcription polymerase chain reaction with 4 cases of meningeal SFT and 13 cases of meningeal HPC. NAB2-STAT6 fusion transcripts were identified in 12 of 17 cases, including NAB2ex6-STAT6ex17 (4/17, 24%), NAB2ex6-STAT6ex16 and NAB2ex4-STAT6ex2 (3/17, 18%, respectively), and NAB2ex5-STAT6ex16 (2/17, 12%). Three cases showed a pseudopapillary pattern, and 2 of them carried NAB2ex6-STAT6ex17. In addition, our meta-analysis revealed that the major fusion variant in meningeal SFT/HPC was NAB2ex6-STAT6ex16/17 (29/54, 54%), which was also common in soft tissue and intraperitoneum/retroperitoneum but rare in thoracic SFT. Fusion variant significantly correlated with age and histologic diagnosis in meningeal SFT/HPC but not with prognosis. Our results represented that meningeal SFT and HPC were in a single biological spectrum with NAB2-STAT6 gene fusion as was nonmeningeal SFT and further confirmed the organ-specific tumorigenic process and morphologic differences on the basis of fusion variants in meningeal SFT/HPC.
Modes of Death in a Pediatric Cardiac ICU*
Authors: Polito Angelo , Garisto Cristiana , Pezzella Chiara , Iacoella Claudia , Cogo Paola E.
Published: February 2016

Objective:

To determine epidemiology and proximate causes of death in a pediatric cardiac ICU in Southern Europe.

Design:

Retrospective chart review.

Setting:

Single-center institution.

Patients:

We concurrently identified 57 consecutive patients who died prior to discharge from the cardiac ICU.

Interventions:

None.

Measurements and Main Results:

Over the study period, there were 57 deaths for a combined mortality rate of 2.4%. Four patients (7%) were declared brain dead, 25 patients (43.8%) died after a failed resuscitation attempt, and 28 patients (49.1%) died after withholding or withdrawal of life-sustaining treatment. Cardiorespiratory failure was the most frequent proximate cause of death (39, 68.4%) followed by brain injury (14, 24.6%) and septic shock (4, 7%). Older age at admission, presence of mechanical ventilation and/or device-dependent nutrition support, patients on a left-ventricular assist device and longer cardiac ICU stay were more likely to have life support withheld or withdrawn.

Conclusions:

Almost half of the deaths in the cardiac ICU are predictable, and they are anticipated by the decision to limit life-sustaining treatments. Brain injuries play a direct role in the death of 25% of patients who die in the cardiac ICU. Patients with left-ventricular assist device are associated with withdrawal of treatment.
A watershed model of individual differences in fluid intelligence
Authors: Kievit Rogier A. , Davis Simon W. , Griffiths John , Correia Marta , Cam-CAN  , Henson Richard N.
Published: February 2016

Fluid intelligence is a crucial cognitive ability that predicts key life outcomes across the lifespan. Strong empirical links exist between fluid intelligence and processing speed on the one hand, and white matter integrity and processing speed on the other. We propose a watershed model that integrates these three explanatory levels in a principled manner in a single statistical model, with processing speed and white matter figuring as intermediate endophenotypes. We fit this model in a large (N=555) adult lifespan cohort from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) using multiple measures of processing speed, white matter health and fluid intelligence. The model fit the data well, outperforming competing models and providing evidence for a many-to-one mapping between white matter integrity, processing speed and fluid intelligence. The model can be naturally extended to integrate other cognitive domains, endophenotypes and genotypes.
Contributions of hippocampus and striatum to memory-guided behavior depend on past experience
Authors: Ferbinteanu Janina
Published: February 2016

The hippocampal and striatal memory systems operate independently and in parallel in supporting spatial and response learning, respectively, when animals are explicitly trained in one task. Here, we investigated whether this principle continues to hold when animals are concurrently trained in two types of tasks. Rats were trained on a plus maze in either a spatial navigation or a cue response task (individual training), while a third set of rats acquired both (concurrent training). Subsequently, the rats underwent either sham surgery or neurotoxic lesions of the hippocampus (HPC), medial dorsal striatum (DSM) or lateral dorsal striatum (DSL), followed by retention testing. Finally, rats in the individual training condition also acquired the novel ‘other’ task. When rats learned one task, HPC and DSL selectively supported spatial navigation cue response, respectively. However, when rats learned both tasks, HPC and DSL additionally supported the behavior incongruent with the processing style of the corresponding memory system. DSM significantly contributed to performance regardless of task or training procedure. Experience with the cue response task facilitated subsequent spatial learning, while experience with spatial navigation delayed both simultaneous and subsequent response learning. These findings suggest that multiple principles govern the interactions among memory systems.

Significance Statement

Currently, we distinguish among several types of memories, each supported by a distinct neural circuit. The memory systems are thought to operate independently and in parallel. Here, we demonstrate that the hippocampus and the dorsal striatum memory systems indeed operate independently and in parallel when rats learn one type of task at a time, but interact co-operatively and in synergism when rats concurrently learn two types of tasks. Furthermore, new learning is modulated by past experiences. These results can be explained by a model in which independent and parallel information processing that occurs in the separate memory-related neural circuits is supplemented by information transfer between the memory systems at the level of the cortex.
Recurrent selection explains parallel evolution of genomic regions of high relative but low absolute differentiation in greenish warblers
Authors: Irwin Darren E. , Alcaide Miguel , Delmore Kira E. , Irwin Jessica H. , Owens Gregory L.
Published: February 2016

Recent technological developments allow investigation of the repeatability of evolution at the genomic level. Such investigation is particularly powerful when applied to a ring species, in which spatial variation represents changes during the evolution of two species from one. We examined genomic variation among three subspecies of the greenish warbler ring species, using genotypes at 13,013,950 nucleotide sites along a new greenish warbler consensus genome assembly. Genomic regions of low within-group variation are remarkably consistent between the three populations. These regions show high relative differentiation but low absolute differentiation between populations. Comparisons with outgroup species show the locations of these peaks of relative differentiation are not well explained by phylogenetically-conserved variation in recombination rates or selection. These patterns are consistent with a model in which selection in an ancestral form has reduced variation at some parts of the genome, and those same regions experience recurrent selection that subsequently reduces variation within each subspecies. The degree of heterogeneity in nucleotide diversity is greater than explained by models background selection, but are consistent with selective sweeps. Given the evidence that greenish warblers have had both population differentiation for a long period of time and periods of gene flow between those populations, we propose that some genomic regions underwent selective sweeps over a broad geographic area followed by within-population selection-induced reductions in variation. An important implication of this “sweep-before-differentiation” model is that genomic regions of high relative differentiation may have moved among populations more recently than other genomic regions.
Genomic prediction of coronary heart disease
Authors: Abraham Gad , Havulinna Aki S. , Bhalala Oneil G. , Byars Sean G. , De Livera Alysha M. , Yetukuri Laxman , Tikkanen Emmi , Perola Markus , Schunkert Heribert , Sijbrands Eric J. , Palotie Aarno , Samani Nilesh J. , Salomaa Veikko , Ripatti Samuli , Inouye Michael
Published: February 2016

Background

Genetics plays an important role in coronary heart disease (CHD) but the clinical utility of a genomic risk score (GRS) relative to clinical risk scores, such as the Framingham Risk Score (FRS), is unclear.

Methods

We generated a GRS of 49,310 SNPs based on a CARDIoGRAMplusC4D Consortium meta-analysis of CHD, then independently tested this using five prospective population cohorts (three FINRISK cohorts, combined n=12,676, 757 incident CHD events; two Framingham Heart Study cohorts (FHS), combined n=3,406, 587 incident CHD events).

Results

The GRS was strongly associated with time to CHD event (FINRISK HR=1.74, 95% CI 1.61-1.86 per S.D. of GRS; Framingham HR=1.28, 95% CI 1.18-1.38), and was largely unchanged by adjustment for clinical risk scores or individual risk factors, including family history. Integration of the GRS with clinical risk scores (FRS and ACC/AHA13 score) improved prediction of CHD events within 10 years (meta-analysis C-index: +1.5-1.6%,P<0.001), particularly for individuals ≥60 years old (meta-analysis C-index: +4.6-5.1%,P<0.001). Men in the top 20% of the GRS had 3-fold higher risk of CHD by age 75 in FINRISK and 2-fold in FHS, and attaining 10% cumulative CHD risk 18y earlier in FINRISK and 12y earlier in FHS than those in the bottom 20%. Furthermore, high genomic risk was partially compensated for by low systolic blood pressure, low cholesterol level, and non-smoking.

Conclusions

A GRS based on a large number of SNPs substantially improves CHD risk prediction and encodes decades of variation in CHD risk not captured by traditional clinical risk scores.
Increased pollination specialization did not increase corolla shape constraints in Antillean plants
Authors: Joly Simon , Lambert François , Alexandre Hermine , Clavel Julien , Léveillé-Bourret Étienne , Clark John L.
Published: February 2016

Flowers show important structural variation as reproductive organs but the evolutionary forces underlying this diversity are still poorly understood. In animal-pollinated species, flower shape is strongly fashioned by selection imposed by pollinators, which is expected to vary according to guilds of effective pollinators. Using the Antillean subtribe Gesneriinae (Gesneriaceae), we tested the hypothesis that pollination specialists pollinated by one functional type of pollinator have maintained more similar corolla shapes through time due to stronger selection constraints compared to species with more generalist pollination strategies. Using geometric morphometrics and evolutionary models, we showed that the corolla of hummingbird specialists, bat specialists, and species with a mixed-pollination strategy (pollinated by hummingbirds and bats; thus a more generalist strategy) have distinct shapes and that these shapes have evolved under evolutionary constraints. However, we did not find support for smaller disparity in corolla shape for hummingbird specialists compared to more generalist species. This could be because the corolla shape of more generalist species in subtribe Gesneriinae, which has evolved multiple times, is finely adapted to be effectively pollinated by both bats and hummingbirds. These results suggest that pollination generalization is not necessarily associated with relaxed selection constraints.
Cell fate-decision as high-dimensional critical state transition
Authors: Mojtahedi Mitra , Skupin Alexander , Zhou Joseph , Castaño Ivan G. , Leong-Quong Rebecca Y. Y. , Chang Hannah , Giuliani Alessandro , Huang Sui
Published: February 2016

Cell fate choice and commitment of multipotent progenitor cells to a differentiated lineage requires broad changes of their gene expression profile. However, how progenitor cells overcome the stability of their robust gene expression configuration (attractor) and exit their state remains elusive. Here we show that commitment of blood progenitor cells to the erythroid or the myeloid lineage is preceded by the destabilization of their high-dimensional attractor state and that cells undergo a critical state transition. Single-cell resolution analysis of gene expression in populations of differentiating cells affords a new quantitative index for predicting critical transitions in a high-dimensional state space: decrease of correlation between cells with concomitant increase of correlation between genes as cells approach a tipping point. The detection of “rebellious cells” which enter the fate opposite to the one intended corroborates the model of preceding destabilization of the progenitor state. Thus, “early-warning signals” associated with critical transitions can be detected in statistical ensembles of high-dimensional systems, offering a formal tool for analyzing single-cell’s molecular profiles that goes beyond computational pattern recognition but is based on dynamical systems theory and can predict impending major shifts in cell populations in development and disease.
Socially mediated effects of climate change decrease survival of hibernating Alpine marmots
Authors: Rézouki Célia , Tafani Marion , Cohas Aurélie , Loison Anne , Gaillard Jean‐Michel , Allainé Dominique , Bonenfant Christophe
Published: February 2016

In the context of global change, an increasing challenge is to understand the interaction between weather variables and life histories. Species‐specific life histories should condition the way climate influences population dynamics, particularly those that are associated with environmental constraints, such as lifestyles like hibernation and sociality. However, the influence of lifestyle in the response of organisms to climate change remains poorly understood.

Based on a 23‐year longitudinal study on Alpine marmots, we investigated how their lifestyle, characterized by a long hibernation and a high degree of sociality, interacts with the ongoing climate change to shape temporal variation in age‐specific survival.

As generally reported in other hibernating species, we expected survival of Alpine marmots to be affected by the continuous lengthening of the growing season of plants more than by changes in winter conditions. We found, however, that Alpine marmots displayed lower juvenile survival over time. Colder winters associated with a thinner snow layer lowered juvenile survival, which in turn was associated with a decrease in the relative number of helpers in groups the following years, and therefore lowered the chances of over‐winter survival of juveniles born in the most recent years.

Our results provide evidence that constraints on life‐history traits associated with hibernation and sociality caused juvenile survival to decrease over time, which might prevent Alpine marmots coping successfully with climate change.
Neighbour Effects in the Provision of Public Goods in a Young Democracy: Evidence from China
Authors: Agostini Claudio A. , Brown Philip , Zhang Xiaobo
Published: February 2016

Fiscal mimicking and yardstick competition among neighbouring jurisdictions have been widely documented in developed countries with long histories of democracy. However, there is very little empirical evidence concerning these practices in developing countries with young democracies. Using a primary panel of 86 rural Chinese administrative villages that have undergone transitions to democracy over the past two decades, we show that the neighbourhood effect also exists in a young democracy, albeit at a lower magnitude than in a mature democracy. Elected chairs of village committees who have served more than one term respond positively to the provision of public projects in neighbouring villages by increasing both the number of public projects and the funding allocated to undertake them. In contrast, appointed party secretaries with more than 1 year of service are insensitive to neighbours' performance. In addition, village leaders are strategic in timing the arrival of public projects to increase the probability of re‐election: in the year preceding elections, both the number and budget of public projects increase significantly. In this sense, politicians in young and old democracies behave alike.
Gains from Trade Under Monopolistic Competition
Authors: Feenstra Robert C.
Published: February 2016

The monopolistic competition model in international trade predicts three sources of gains from trade that are not present in traditional models: consumer gains from having access to new import varieties of differentiated products; gains from a reduction in firm markups due to import competition; and gains from the self‐selection of more efficient firms into export markets, provided that firms are heterogeneous in their productivities. With the added assumption that the distribution of firms’ productivity is Pareto, and with a support that is unbounded above, we argue that only the third source of gains from trade, due to the self‐selection of firms, operates. This result helps to explain the simple formula for the gains from trade found by Arkolakis et al. (2012). If the Pareto distribution is bounded above, however, then all three sources of gains from trade operate once again.
China's Global Influence: A Survey through the Lens of International Trade
Authors: Qiu Larry D. , Zhan Chaoqun
Published: February 2016

One of the most impressive changes in the global economy in the past half‐century has been China's high and sustained growth and its integration into the global economy. This phenomenal change not only brings huge benefits to the Chinese people, but also exerts a tremendous influence on the rest of the world. How large is China's influence on the global economy? How are various countries/regions affected differently? How are various industries in a country affected differently? Answering these questions is not simple. In this paper, we review the recent literature that attempts to answer these questions. The findings of the survey conducted in this study aim to provide a complete picture of China's global influence and to identify issues that require further analysis.
Outward Direct Investment, Firm Productivity and Credit Constraints: Evidence from Chinese Firms
Authors: Wang Bijun , Tan Yuyan , Yu Miaojie , Huang Yiping
Published: February 2016

China is currently the third largest country in terms of outward direct investment (ODI), with the investors mainly being state‐owned enterprises. This presents a question: What inhibits private enterprises from increasing ODI? Using a firm‐level panel data set for Zhejiang Province in China, we examine the impact of firm heterogeneity on private firm ODI. We have three main findings: first, a higher productivity level contributes to better access to ODI, and increases ODI value as well; second, lowering a firm's financial constraint level can increase both the probability and volume of ODI; third, productivity cannot offset the negative effect of financial constraint on private firm ODI.
Research into employee trust: epistemological foundations and paradigmatic boundaries
Authors: Siebert Sabina , Martin Graeme , Bozic Branko
Published: February 2016

This article explores the epistemological roots and paradigmatic boundaries of research into employee trust, a growing field in human resource management. Drawing on Burrell and Morgan's well‐known sociological paradigms and their epistemological foundations, we identify the dominant approaches to employee trust research to examine its strengths and limitations. Our review of the literature on employee trust revealed that the majority of the most cited papers were written from a psychological perspective, characterised by positivistic methodologies, variance theory explanations and quantitative data collection methods. We also found that most of the studies can be located in the functionalist paradigm, and while accepting that functionalism and psychological positivism have their merits, we argue that research in these traditions sometimes constrains our understanding of employee trust in their organisations. We conclude that trust researchers would benefit from a better understanding of the ontological, epistemological and axiological assumptions underlying of HRM research and should embrace greater epistemic reflexivity.
The pregnane X receptor down‐regulates organic cation transporter 1 (SLC22A1) in human hepatocytes by competing for (“squelching”) SRC‐1 coactivator
Authors: Hyrsova Lucie , Smutny Tomas , Carazo Alejandro , Moravcik Stefan , Mandikova Jana , Trejtnar Frantisek , Gerbal‐Chaloin Sabine , Pavek Petr
Published: February 2016

Background and Purpose

The organic cation transporter 1 (OCT1) transports cationic drugs into hepatocytes. The high hepatic expression of OCT1 is controlled by the HNF4α and USF transcription factors. Pregnane X receptor (PXR) mediates induction of the principal xenobiotic metabolizing enzymes and transporters in the liver. Here, we have assessed the down‐regulation of OCT1 expression by PXR activation.

Experimental Approach

We used primary human hepatocytes and related cell lines to measure OCT1 expression and activity, by assaying MPP+ accumulation. Western blotting, qRT‐PCR, the OCT1 promoter gene reporter constructs and chromatin immunoprecipitation assays were also used.

Key Results

OCT1 mRNA in human hepatocytes was down‐regulated along with reduced [3H]MPP+ accumulation in differentiated HepaRG cells after treatment with rifampicin. Rifampicin and hyperforin as well as the constitutively active PXR mutant T248D suppressed activity of the 1.8 kb OCT1 promoter construct in gene reporter assays. Silencing of both PXR and HNF4α in HepaRG cells blocked the PXR ligand‐mediated down‐regulation of OCT1 expression. The mutation of HNF4α and USF1 (E‐box) responsive elements reversed the PXR‐mediated inhibition in gene reporter assays. Chromatin immunoprecipitation assays indicated that PXR activation sequestrates the SRC‐1 coactivator from the HNF4α response element and E‐box of the OCT1 promoter. Consistent with these findings, exogenous overexpression of the SRC‐1, but not the PGC1α coactivator, relieved the PXR‐mediated repression of OCT1 transactivation.

Conclusions and Implications

PXR ligands reduced the HNF4α‐mediated and USF‐mediated transactivation of OCT1 gene expression by competing for SRC‐1 and decreased delivery of a model OCT1 substrate into hepatocytes.
Gemcitabine enhances rituximab‐mediated complement‐dependent cytotoxicity to B cell lymphoma by CD20 upregulation
Authors: Hayashi Kazumi , Nagasaki Eijiro , Kan Shin , Ito Masaki , Kamata Yuko , Homma Sadamu , Aiba Keisuke
Published: February 2016

Although rituximab, a chimeric monoclonal antibody that specifically binds to CD20, has significantly improved the prognosis for diffuse large B cell lymphoma (DLBCL), one‐third of DLBCL patients demonstrate resistance to rituximab or relapse after rituximab treatment. Thus, a novel approach to rituximab‐based treatment is likely to be required to improve the efficacy of DLBCL treatment. As complement dependent cytotoxicity (CDC) is a key mechanism mediating rituximab's tumoricidal activity, rituximab binding to CD20 on tumor cells is a critical factor for effective rituximab‐based treatments against DLBCL. We found that gemcitabine (GEM), but not lenalidomide (LEN) or azacitidine (AZA), can upregulate CD20 expression in TK and KML‐1 cells, two human DLBCL cell lines. Treatment of TK and KML‐1 cells with GEM enhanced CD20 expression at both the mRNA and protein levels. CD20 upregulation by GEM treatment was accompanied by increased rituximab binding to CD20. In TK cells, GEM treatment synergistically increased rituximab‐mediated CDC activity in a dose‐dependent manner. In KML cells, GEM treatment also induced upregulation of complement regulatory proteins, possibly leading to resistance to CDC. Treatment with LEN, a drug that did not upregulate CD20, did not enhance rituximab‐mediated CDC activity. GEM treatment activated nuclear factor‐kappa B (NF‐kB) signaling in these cells. Furthermore, a specific inhibitor to NF‐kB suppressed GEM‐induced CD20 upregulation, indicating that GEM‐induced NF‐kB activation is closely associated with CD20 upregulation. These results suggest that when used in combination, GEM might enhance the antitumor efficacy of rituximab against DLBCL due to its unique ability to upregulate CD20.
Phase I study of a new cancer vaccine of ten mixed peptides for advanced cancer patients
Authors: Iwasa Satoru , Yamada Yasuhide , Heike Yuji , Shoji Hirokazu , Honma Yoshitaka , Komatsu Nobukazu , Matsueda Satoko , Yamada Akira , Morita Michi , Yamaguchi Rin , Tanaka Natsuki , Kawahara Akihiko , Kage Masayoshi , Shichijo Shigeki , Sasada Tetsuro , Itoh Kyogo
Published: February 2016

A phase I study of a new cancer vaccine (KRM‐10), consisting of a mixture of 10 different short peptides, was conducted for patients with advanced gastrointestinal cancers. Primary or secondary endpoints included the dose‐limiting toxicity (DLT), or safety and immune responses, respectively. Peptide‐specific cytotoxic T lymphocytes (CTL) and immunoglobulin G (IgG), together with soluble inflammatory factors, were measured before and after vaccination. Twenty‐one patients were vaccinated with KRM‐10 at dose levels of 10 (n = 6), 20 (n = 8) or 30 mg (n = 7) of peptides every week for 6 weeks. No DLT were observed in the dose range evaluated. Common treatment‐related adverse events were a grade 1 injection site reaction in 15 patients, and fever in three patients (grade 1 in two patients and grade 2 in one patient). CTL activity to at least one peptide at the time of the third and sixth vaccination increased in 2 and 3 of 6 (10 mg), 2 of 8 and 4 of 6 (20 mg), or 2 and 1 of 6 (30 mg) patients, respectively. IgG levels, at the third and sixth vaccination, were also increased in 1 and 1 of 6 (10 mg), 2 of 8 and 4 of 6 (20 mg), or 1 and 3 of 6 (30 mg) patients, respectively. The KRM‐10 vaccine consisting of 20 mg of peptides was determined as the optimal dose for a coming phase II trial because of its safety, and also for demonstrating the most potent activity for augmenting the immune response of the three doses tested. This trial was registered at the UMIN Clinical Trials Registry as UMIN000008820.
Ridge Preservation Using Composite Alloplastic Materials: A Randomized Control Clinical and Histological Study in Humans
Authors: Mayer Yaniv , Zigdon‐Giladi Hadar , Machtei Eli E.
Published: February 2016

Aim

To evaluate (clinically, histologically, and histo‐morphometrically) the use of composite materials (Biphasic calcium sulphate [BCS] with β Tri‐Calcium Phosphate (β‐TCP) and Hydroxyapatite [HA]) in extraction socket sites and compare it to un‐disturbed natural healing.

Material and Methods

Prospective clinical trial of 36 patients (40 extraction sockets) were randomly assigned to either test or control group. Alveolar ridge horizontal dimension was measured in the middle of the socket at crest and 3 and 6 mm subcrestally. Crestal vertical height was measured at baseline surgery and at 4 month re‐entry, at which time bone core biopsies were harvested from the center of the edentulous ridge. Histo‐morphometric evaluation of the samples was performed using hematoxylin & eosin stains and morphometric software.

Results

The change in horizontal ridge width was higher in the control compared to the experimental group: 2.28 ± 2.36 mm versus 0.03 ± 2.32 mm (p = .007) at −3 mm and 2.28 ± 2.43 versus 0.035 ± 3.05 (p = .02) at −6 mm, for the experimental and control sites, respectively. The vertical distance form bone crest to neighboring horizontal line interconnecting the neighboring teeth was minimal in both groups (0.307 ± 2.01 mm versus 0.14 ± 2.03 mm [p = 0.41]). Residual scaffolds occupied 15.99 ± 11.4% of the volume in the grafted (test) sites while bone area fraction was not statistically different among the groups (47.7 ± 10.6% versus 52.6 ± 11.6%, test versus control, respectively p = .39). The percentage of connective tissue in the control group was significantly higher that test group (36.3 ± 19.4% versus 46.7 ± 10.6% test versus control, respectively, p = .013).

Conclusion

Ridge preservation technique using a combination of two synthetic bone grafts β‐TCP and HA with BCS resulted in greater stability in the horizontal dimension after 4 months.
Guided bone regeneration in osteoporotic conditions following treatment with zoledronic acid
Authors: Mardas Nikos , Busetti Juliano , de Figueiredo José Antonio Poli , Mezzomo Luis André , Scarparo Roberta Kochenborger , Donos Nikolaos
Published: February 2016

Objectives

To evaluate new bone formation in calvarial critical size defects (CSD) under dense polytetrafluoroethylene (d‐PTFE), microporous membranes for guided bone regeneration (GBR) in healthy, osteoporotic and osteoporotic treated with zoledronic acid (ZA) rats.

Methods

Forty‐eight, female, 6‐month old Wistar rats were included in the study. Osteoporosis was induced by ovariectomy (OVX) and calcium‐deficient diet in 32 rats. Sixteen OVX rats were treated with a single dose of Zolendronic Acid (ZA) (OZ), while 16 OVX rats received no treatment (O). The remaining 16 rats were sham‐operated and used as healthy controls (C). At 6 weeks following osteoporosis induction, two 5 mm CSD were created in the parietal bones and one of them was treated with a double d‐PTFE membrane. The healing periods were 30 and 60 days. New bone formation (NB) was assessed by qualitative and quantitative histological analysis.

Results

After 30 days of healing, NB (mean% (95% CI)) was 78.9% (21), 93.1% (9.3) and 84.2% (26.9) in the membrane treated defects and 18.8% (24.1), 27.1% (7.9) and 31% (38.8) in the untreated defects of group O, OZ and C, respectively. After 60 days of healing, NB was 78.3% (14.4), 95.8% (9) and 90.1% (26.1) in the membrane treated defects and 10.8% (17.4), 51.6% (39.4) and 15.7% (12.1) in the untreated defects of group O, OZ and C, respectively. Hierarchical analysis of variance showed that treatment with ZA (P = 0.001) and the use of membrane (P = 0.000) significantly increased new bone formation while presence of osteoporosis may have reduced new bone formation (P = 0.028).

Conclusion

d‐PTFE membranes for GBR promote bone healing in osteoporotic and healthy rats. Treatment with ZA may improve new bone formation in osteoporotic rats.
MiR‐150 Regulates Poststroke Cerebral Angiogenesis via Vascular Endothelial Growth Factor in Rats
Authors: He Quan‐Wei , Li Qian , Jin Hui‐Juan , Zhi Fang , Suraj Baral , Zhu Yi‐Yi , Xia Yuan‐Peng , Mao Ling , Chen Xiao‐Lu , Hu Bo
Published: February 2016

Aims

Angiogenesis is a harmonized target for poststroke recovery. Therefore, exploring the mechanisms involved in angiogenesis after stroke is vitally significant. In this study, we are reporting a miR‐150‐based mechanism underlying cerebral poststroke angiogenesis.

Methods

Rat models of middle cerebral artery occlusion (MCAO) and cell models of oxygen–glucose deprivation were conducted. Capillary density, tube formation, cell proliferation, and cell migration were measured byFITC‐dextran assay, matrigel assay, Ki‐67 staining, and wound healing assay, respectively. The expression of miR‐150 and vascular endothelial growth factor (VEGF) was, respectively, measured byRT‐PCRand Western blotting. Dual‐luciferase assay was conducted to confirm the binding sites between miR‐150 andVEGF.

Results

We found that miR‐150 expression in the brain and serum of rats subjected to cerebral ischemia, and in oxygen–glucose‐deprived brain microvascular endothelial cells (BMVECs) and astrocytes. Upregulation of miR‐150 expression could decrease vascular density of infarct border zone in rat afterMCAOand decrease tube formation, proliferation, and migration ofBMVECs. We also found that miR‐150 could negatively regulate the expression ofVEGF, andVEGFwas confirmed to be a direct target of miR‐150. Moreover,VEGFmediated the function of miR‐150 on tube formation, proliferation, and migration ofBMVECs.

Conclusions

Our data suggested that miR‐150 could regulate cerebral poststroke angiogenesis in rats throughVEGF.
What is the likelihood of colorectal cancer when surgery for ulcerative‐colitis‐associated dysplasia is deferred?
Authors: Murphy J. , Kalkbrenner K. A. , Blas J. V. , Pemberton J. H. , Landmann R. G. , Young‐Fadok T. M. , Etzioni D. A.
Published: February 2016

Aim

Surgery aims to prevent cancer‐related morbidity for patients with ulcerative colitis (UC) associated dysplasia. The literature varies widely regarding the likelihood of dysplastic progression to higher grades of dysplasia or cancer. The aim of this study was to characterize the likelihood of the development of colorectal cancer (CRC) of patients with UC‐associated dysplasia who chose to defer surgery.

Method

A retrospective review was carried out of patients undergoing surgery for UC at the Mayo Clinic, who were diagnosed to have dysplasia between August 1993 and July 2012. The relationships between grade of dysplasia, time to surgery and the detection of unsuspected carcinoma were investigated.

Results

In all, 175 patients underwent surgery at a median of 4.9 (interquartile range 2.5–8.9) months after a diagnosis of dysplasia. Their median age was 52 (interquartile range 43−59) years. An initial diagnosis of indeterminate dysplasia was not associated with CRC [0/23; 17.7 (8.1−29.6) months]. Thirty‐six patients who had an initial diagnosis of dysplasia progressed from indeterminate to low‐grade dysplasia [24.2 (11.0−30.4) months]. Low‐grade dysplasia was associated with a 2% (1/56; T2N0M0) risk of CRC when present in random surveillance biopsies and a 3% (2/61; T1N0M0, T4N0M0) risk if detected in endoscopically visible lesions [7.4 (5.2−33.3) months]. Eighteen patients progressed from indeterminate to high‐grade dysplasia [19.1 (9.2−133.9) months]. Seventeen patients progressed from low to high‐grade dysplasia [11.0 (5.8−30.1) months]. None of the patients with high‐grade dysplasia (0/35) progressed to CRC [4.5 (1.7−9.9) months].

Conclusion

Dysplasia was associated with a low incidence of node negative CRC if surgery was deferred for up to 5 years. These findings may help inform the decision‐making process for asymptomatic patients who are having to decide between intensive surveillance or surgery for UC‐associated dysplasia.