bluuebunny/crossref_metadata_2025 huggingface dataset:
Incorporating opportunity costs in strategic management research: The value of diversification and payout as opportunities forgone when reinvesting in the firm
Authors: Mackey Tyson B , Barney Jay B
Published: May 2013

This article explores the theoretical and empirical implications of incorporating forgone opportunities in strategic management research. Drawing on the well-studied literature examining whether firms should reinvest in focused businesses or pursue alternatives of diversifying and/or paying out excess cash to shareholders, hypotheses are developed for when diversification and payout policy, as the opportunity costs of reinvesting in the firm’s original businesses, will present firms with higher and lower opportunity costs. Empirical results suggest that the value of reinvestment in existing businesses is higher for firms facing lower opportunity costs of forgoing other alternatives (e.g. diversification and paying out) than for firms that have much higher opportunity costs of forgoing these same alternatives. Implications for incorporating opportunity costs into the diversification literature and the broader strategic management literature are also explored.
Further Examination of Potential Discrimination Among MLB Umpires
Authors: Tainsky Scott , Mills Brian M. , Winfree Jason A.
Published: May 2013

We address potential racial bias by Major League Baseball umpires with respect to ball–strike calls. We offer a number of econometric specifications to test the robustness of the results, adding the role of implicit and explicit monitoring as well as pitch location. Our analysis shows mixed results regarding the matching of umpire and pitcher race. We conclude that evidence of own-race bias is sensitive to specification and methodology. How results can differ based on different data sets, specifications, time periods, and race classifications are discussed.
The Appearance of Data
Authors: St. Pierre Elizabeth Adams
Published: May 2013

This paper explores conditions that allow data to appear, to come into being, in both conventional and more radical approaches in empirical social science research. Conventional qualitative inquiry that uses a positivist ontology—even when it claims to be interpretive—treats qualitative data, words, as brute, existing independent of an interpretive frame, waiting to be “collected” by a human. However, a Deleuzo-Guattarian ontology that does not assume the subject/object binary might not think the concept data at all. The author resists recuperating data in the collapse of the old empiricism and is content to pause in the curious possibilities of a normative ontology that imagines a superior, affirmative, and experimental empiricism in which all concepts, including data, must be re-thought.
Robotic Hybrid Technique in Rectal Surgery for Deep Pelvic Endometriosis
Authors: Cassini Diletta , Cerullo Guido , Miccini Michelangelo , Manoochehri Farshad , Ercoli Alfredo , Baldazzi Gianandrea
Published: May 2013

Background. Deep pelvic endometriosis is a complex disorder that affects 6% to 12% of all women in childbearing age. The incidence of bowel endometriosis ranges between 5.3% and 12%, with rectum and sigma being the most frequently involved tracts, accounting for about 80% of cases. It has been reported that segmental colorectal resection is the best surgical option in terms of recurrence rate and improvement of symptoms. The aim of this study is to analyze indications, feasibility, limits, and short-term results of robotic (Da Vinci Surgical System)-assisted laparoscopic rectal sigmoidectomy for the treatment of deep pelvic endometriosis. Patients and Methods. Between January 2006 and December 2010, 19 women with bowel endometriosis underwent colorectal resection through the robotic-assisted laparoscopic approach. Intraoperative and postoperative data were collected. All procedures were performed in a single center and short-term complications were evaluated. Results. Nineteen robotic-assisted laparoscopic colorectal resections for infiltrating endometriosis were achieved. Additional procedures were performed in 7 patients (37%). No laparotomic conversion was performed. No intraoperative complications were observed. The mean operative time was 370 minutes (range = 250-720 minutes), and the estimated blood loss was 250 mL (range = 50-350 mL). The overall complication rate was 10% (2 rectovaginal fistulae). Conclusions. Deep pelvic endometriosis is a benign condition but may have substantial impact on quality of life due to severe pelvic symptoms. We believe that robotic-assisted laparoscopic colorectal resection is a feasible and relatively safe procedure in the context of close collaboration between gynecologists and surgeons for treatment of deep pelvic endometriosis with intestinal involvement, with low rates of complications and significant improvement of intestinal symptoms.
An analysis of historical agency in Québec history textbooks
Authors: Éthier Marc-André , Lefrançois David , Demers Stéphanie
Published: May 2013

In the 1980s, in Québec history textbooks, authors presented history through linear, monocausal designs and attributed most social, political or economic changes favourable to democracy to unstable external causes or to stable external causes. They seldom attributed the evolution of democracy to ‘unstable internal causes’. These textbooks presented citizens as having almost no active role in socio-historical changes. This invited students to analyse past controversial social issues from a fatalistic perspective or through subjective moral criteria, while reinforcing the assumption that people from the past had bad ideas that good people have fortunately refuted since. Québec history programmes were reformed, in the 2000s, for middle and high schools. This article presents the results of a content analysis of the new history textbooks used in Québec, to see whether they still present such a deterministic and relativist perspective of social change. The preliminary results show that they do.
Creating cohesive citizens in England? Exploring the role of diversity, deprivation and democratic climate at school
Authors: Keating Avril , Benton Tom
Published: May 2013

Over the past decade, cohesion and integration have been a key concern for policymakers in countries across Europe and North America. The rapid increase in immigration, coupled with the perception of rapid social change and instability, is seen to have presented communities and governments with a range of ‘new’ challenges. In the attendant debates, schools are often presented as part of the solution to these challenges, but much remains unknown about the relationship between schools and community cohesion. This article therefore explores the role of schools as a site of socialisation for children and young people and their role in fostering the attitudes, behaviours and norms that are typically associated with citizens in a cohesive society. This article focuses in particular on the role of school demographics and school climate and uses longitudinal data from students in England to examine these relationships.
Anterior Cruciate Ligament Reconstruction and Osteoarthritis
Authors: Magnussen Robert A. , Duthon Victoria , Servien Elvire , Neyret Philippe
Published: May 2013

Objective:

The goals of this study are to address several questions, the answers to which are key to the understanding and eventually to the prevention of this frequent source of morbidity. These questions include the following: (1) What is the natural history of anterior cruciate ligament (ACL) deficiency? (2) How important is the status of the meniscus at the time of reconstruction? (3) Does ACL reconstruction prevent the development of osteoarthritis in the long term? (4) Can we predict which patients will develop osteoarthritis? (5) What can be done?

Design:

This study addresses the key questions above through the long-term follow-up of a cohort of patients treated with ACL reconstruction by Professor Henri Dejour in Lyon, France, supplemented with a review of the relevant literature.

Results:

The prevalence of osteoarthritis in ACL-deficient knees is about 40% after 15 years and close to 90% after 25 to 35 years. It remains unclear whether reconstruction of the ACL significantly reduces this risk. The status of the meniscus at the time of ACL reconstruction is a strong predictor of the risk of osteoarthritis: Patients who undergo total meniscectomy are at 2- to 10-fold increased risk of developing osteoarthritis relative to those with intact menisci. Patients showing early evidence of arthritis at short- to medium-term follow-up are at high risk for progression over subsequent years. Numerous emerging techniques may provide tools to more effectively prevent and treat osteoarthritis following ACL injury in the future.

Conclusion:

Osteoarthritis following ACL injury continues to be a major problem requiring further research.
At the Heart of a Conflict
Authors: Kouzakova Marina , Harinck Fieke , Ellemers Naomi , Scheepers Daan
Published: May 2013

Value-based conflicts are prone to escalation and rather insensitive to standard conflict resolution techniques. To understand why this is the case, we assessed self-regulatory and cardiovascular (CV) responses to test how people cope with conflict, depending on whether values versus resources are at stake. Our results show that a value conflict induces a CV threat profile and raises a prevention focus. Conversely, a resource conflict induces a CV challenge profile and decreases prevention focus. These results suggest that value conflicts are linked to more prevention-focused motivational profiles than resource conflicts. This knowledge can foster the development of specific strategies to facilitate resolution of value conflicts.
Comparing Brand Awareness Levels of In-Game Advertising in Sport Video Games Featuring Visual and Verbal Communication Cues
Authors: Walsh Patrick , Zimmerman Matthew H. , Clavio Galen , Williams Antonio S.
Published: May 2013

As technology advances, new forms of in-game advertising (IGA) executions continue to be developed. What was once simply a static advertisement has expanded to include verbal mentions of the brands placed within the games. While research has examined brand awareness of IGA, what has yet to be determined is the effectiveness of IGA which features these verbal cues. Therefore, this study examined the brand awareness levels of IGA which featured a visual brand placement (e.g., company logo placed within the game) versus those that have the visual placement accompanied by a verbal mention of the brand name. The results indicate that brand awareness levels were significantly higher for advertisements that contained both the visual and the verbal cues.
The level of residual disease based on mutant NPM1 is an independent prognostic factor for relapse and survival in AML
Authors: Shayegi Nona , Kramer Michael , Bornhäuser Martin , Schaich Markus , Schetelig Johannes , Platzbecker Uwe , Röllig Christoph , Heiderich Caroline , Landt Olfert , Ehninger Gerhard , Thiede Christian
Published: May 2013

Key Points

NPM1 RT-PCR levels >1% are associated with poor overall and disease-free survival in AML patients treated with chemotherapy. NPM1 MRD levels >10% are associated with poor overall and disease-free survival in AML patients after allogeneic transplantation.
Survival of the weak (signalers): anergy in CLL
Authors: Woyach Jennifer A.
Published: May 2013

In this issue of Blood, Apollonio et al report on a subset of chronic lymphocytic leukemia (CLL) characterized by molecular anergy and demonstrate how this phenotype could potentially be targeted therapeutically.1
Better BMT for Hurler syndrome—on the level?
Authors: Pulsipher Michael A.
Published: May 2013

In this issue of Blood, Boelens et al report transplantation outcomes for the largest cohort assembled to date of patients with Hurler syndrome, demonstrating key associations with survival and outlining approaches that result in higher levels of α-l-iduronidase, the enzyme missing in this devastating disorder.1
Distinct position-specific sequence features of hexa-peptides that form amyloid-fibrils: application to discriminate between amyloid fibril and amorphous β-aggregate forming peptide sequences
Authors: Thangakani A Mary , Kumar Sandeep , Velmurugan D , Gromiha M Michael
Published: May 2013

Background

Comparison of short peptides which form amyloid-fibrils with their homologues that may form amorphous β-aggregates but not fibrils, can aid development of novel amyloid-containing nanomaterials with well defined morphologies and characteristics. The knowledge gained from the comparative analysis could also be applied towards identifying potential aggregation prone regions in proteins, which are important for biotechnology applications or have been implicated in neurodegenerative diseases. In this work we have systematically analyzed a set of 139 amyloid-fibril hexa-peptides along with a highly homologous set of 168 hexa-peptides that do not form amyloid fibrils for their position-wise as well as overall amino acid compositions and averages of 49 selected amino acid properties.

Results

Amyloid-fibril forming peptides show distinct preferences and avoidances for amino acid residues to occur at each of the six positions. As expected, the amyloid fibril peptides are also more hydrophobic than non-amyloid peptides. We have used the results of this analysis to develop statistical potential energy values for the 20 amino acid residues to occur at each of the six different positions in the hexa-peptides. The distribution of the potential energy values in 139 amyloid and 168 non-amyloid fibrils are distinct and the amyloid-fibril peptides tend to be more stable (lower total potential energy values) than non-amyloid peptides. The average frequency of occurrence of these peptides with lower than specific cutoff energies at different positions is 72% and 50%, respectively. The potential energy values were used to devise a statistical discriminator to distinguish between amyloid-fibril and non-amyloid peptides. Our method could identify the amyloid-fibril forming hexa-peptides to an accuracy of 89%. On the other hand, the accuracy of identifying non-amyloid peptides was only 54%. Further attempts were made to improve the prediction accuracy via machine learning. This resulted in an overall accuracy of 82.7% with the sensitivity and specificity of 81.3% and 83.9%, respectively, in 10-fold cross-validation method.

Conclusions

Amyloid-fibril forming hexa-peptides show position specific sequence features that are different from those which may form amorphous β-aggregates. These positional preferences are found to be important features for discriminating amyloid-fibril forming peptides from their homologues that don't form amyloid-fibrils.
Antibacterial activities of almond skins on cagA-positive and-negative clinical isolates of Helicobacter pylori
Authors: Bisignano Carlo , Filocamo Angela , La Camera Erminia , Zummo Sebastiana , Fera Maria Teresa , Mandalari Giuseppina
Published: May 2013

Background

Helicobacter pylori is known to be a gastric pathogen of humans. Eradication regimens for H. pylori infection have some side effects, compliance problems, relapses, and antibiotic resistance. Therefore, the need for alternative therapies for H. pylori infections is of special interest. We have previously shown that polyphenols from almond skins are active against a range of food-borne pathogens. The aim of this study was to evaluate the antibacterial effects of natural almond skins before and after simulated human digestion and the pure flavonoid compounds epicatechin, naringenin and protocatechuic acid against H. pylori.

Results

H. pylori strains were isolated from gastric biopsy samples following standard microbiology procedures. Also, cagA and vacA genes were identified using PCR. Susceptibility studies on 34 strains of H. pylori, including two reference strains (ATCC 43504, ATCC 49503), were performed by the standard agar dilution method.

Natural almond skin was the most effective compound against H. pylori (MIC range, 64 to 128 μg/ml), followed by natural skin post gastric digestion (MIC range, 128 to 512 μg/ml), and natural almond skin post gastric plus duodenal digestion (MIC range, 256 to 512 μg/ml). Amongst the pure flavonoid compounds, protocatechuic acid showed the greatest activity (MIC range, 128 to 512 μg/ml) against H. pylori strains.

Conclusions

Polyphenols from almond skins were effective in vitro against H. pylori, irrespective of genotype status and could therefore be used in combination with antibiotics as a novel strategy for antibiotic resistance.
Age dependence of tumor genetics in unfavorable neuroblastoma: arrayCGH profiles of 34 consecutive cases, using a Swedish 25-year neuroblastoma cohort for validation
Authors: Cetinkaya Cihan , Martinsson Tommy , Sandgren Johanna , Träger Catarina , Kogner Per , Dumanski Jan , Díaz de Ståhl Teresita , Hedborg Fredrik
Published: May 2013

Background

Aggressive neuroblastoma remains a significant cause of childhood cancer death despite current intensive multimodal treatment protocols. The purpose of the present work was to characterize the genetic and clinical diversity of such tumors by high resolution arrayCGH profiling.

Methods

Based on a 32K BAC whole-genome tiling path array and using 50-250K Affymetrix SNP array platforms for verification, DNA copy number profiles were generated for 34 consecutive high-risk or lethal outcome neuroblastomas. In addition, age and MYCN amplification (MNA) status were retrieved for 112 unfavorable neuroblastomas of the Swedish Childhood Cancer Registry, representing a 25-year neuroblastoma cohort of Sweden, here used for validation of the findings. Statistical tests used were: Fisher’s exact test, Bayes moderated t-test, independent samples t-test, and correlation analysis.

Results

MNA or segmental 11q loss (11q-) was found in 28/34 tumors. With two exceptions, these aberrations were mutually exclusive. Children with MNA tumors were diagnosed at significantly younger ages than those with 11q- tumors (mean: 27.4 vs. 69.5 months; p=0.008; n=14/12), and MNA tumors had significantly fewer segmental chromosomal aberrations (mean: 5.5 vs. 12.0; p<0.001). Furthermore, in the 11q- tumor group a positive correlation was seen between the number of segmental aberrations and the age at diagnosis (Pearson Correlation 0.606; p=0.037). Among nonMNA/non11q- tumors (n=6), one tumor displayed amplicons on 11q and 12q and three others bore evidence of progression from low-risk tumors due to retrospective evidence of disease six years before diagnosis, or due to tumor profiles with high proportions of numerical chromosomal aberrations. An early age at diagnosis of MNA neuroblastomas was verified by registry data, with an average of 29.2 months for 43 cases that were not included in the present study.

Conclusion

MNA and segmental 11q loss define two major genetic variants of unfavorable neuroblastoma with apparent differences in their pace of tumor evolution and in genomic integrity. Other possible, but less common, routes in the development of aggressive tumors are progression of low-risk infant-type lesions, and gene amplifications other than MYCN. Knowledge on such nosological diversity of aggressive neuroblastoma might influence future strategies for therapy.
Higher rate of skin rash in a phase II trial with weekly nanoparticle albumin-bound paclitaxel and cisplatin combination in Chinese breast cancer patients
Authors: Tang Li Chen , Wang Bi Yun , Sun Si , Zhang Jian , Jia Zhen , Lu Yun Hua , Di Geng Hong , Shao Zhi Ming , Hu Xi Chun
Published: May 2013

Abstracts

Background

The aim of this sub-study is to explore the incidence of skin rash among advanced breast cancer(ABC) patients in a phase II trial treated with weekly nab-paclitaxel and cisplatin combination.

Methods

Nab-paclitaxel(125 mg/m2) was administered on days 1, 8, 15, followed by cisplatin(75 mg/m2) on day 1 every 28 day cycle until disease progression, intolerable toxicities or the maximum of 6 cycles. Patients who received at least one injection of the study drug were included in this analysis of the incidence of skin rash among Chinese patients. Toxicity was graded using the CTCAE4.0 criteria. Statistical analysis was carried out by using SPSS 16.0 (SPSS Inc, Chicago, IL).

Results

Seventy three patients were enrolled and eligible for analysis. A total of 384 cycles were administered at the time of this analysis. Rash was presented in 27 patients (37.0%). The most common sites involved were face (14/27), neck (14/27), limbs (18/27) and frictional parts of the trunk (10/27). Macular and papular rash with pruritus commonly occurred 2 (95% CI: 1–7) days after the first day of chemotherapy. Only one patient developed Grade 3 skin toxicity with generalized erythroderma and disfigurement of the face requiring dose reduction. The rash gradually regressed 2 (95% CI: 1–10) days after antihistamines used, but pigmentation remained in 13/27 cases. The incidence rate of skin rash was significantly higher than what has been described for western patients (approximate 4%, P < 0.0001).

Conclusion

A higher rate of maculo-papular rash occurred in Chinese breast cancer patients treated with weekly nab-paclitaxel compared to western patients. The albumin component of nab-paclitaxel might be the cause of the skin disorder.

Trial registration

NCT01149798
Details acquired from medical history and patients’ experience of empathy – two sides of the same coin
Authors: Ohm Friedemann , Vogel Daniela , Sehner Susanne , Wijnen-Meijer Marjo , Harendza Sigrid
Published: May 2013

Background

History taking and empathetic communication are two important aspects in successful physician-patient interaction. Gathering important information from the patient’s medical history is needed for effective clinical decision making while empathy is relevant for patient satisfaction. We wanted to investigate whether medical students near graduation are able to combine both skills as required in daily medical practice.

Methods

Thirty near graduates from Hamburg Medical School participated in an assessment for clinical competences including a consultation hour with five standardized patients. Each patient interview was videotaped and standardized patients rated participants with the CARE questionnaire for consultation and relational empathy. All videotaped interviews were rated with a checklist based on the number of important medical aspects for each case. Data were analysed with the linear mixed model to correct for random effects. Regression analysis was performed to look for correlations between the number of questions asked by a participant and their respective empathy rating.

Results

Of the 123 aspects that could have been gathered in total, students only requested 56.4% (95% CI 53.5-59.3). While no difference between male and female participants was found, a significant difference (p < .001) was observed between the two parts of the checklist with 61.1% (95% CI 57.9-64.3) of aspects asked for in part 1 (patient’s symptoms) versus 52.0 (95 47.4-56.7) in part 2 (further history). All female standardized patients combined rated female participants (mean score 14.2, 95% CI 12.3-16.3) to be significantly (p < .01) more empathetic than male participants (mean score 19.2, 95% CI 16.3-22.6). Regression analysis revealed no correlation between the number of medical aspects gathered by a participant and his or her respective empathy score given by the standardized patient in the CARE questionnaire.

Conclusion

Gathering sufficient medical data from a patient’s history and empathetic communication are two completely separate sides of the coin of history taking. While both skills have to be acquired during medical school training with particular focus on their respective learning objectives, medical students need to be provided with additional learning and feedback opportunities where they can be observed exercising both skills combined as required in physicians’ daily practice.
Use of V(D)J recombination excision circles to identify T- and B-cell defects and to monitor the treatment in primary and acquired immunodeficiencies
Authors: Serana Federico , Chiarini Marco , Zanotti Cinzia , Sottini Alessandra , Bertoli Diego , Bosio Andrea , Caimi Luigi , Imberti Luisa
Published: May 2013

T-cell receptor excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs) are circular DNA segments generated in T and B cells during their maturation in the thymus and bone marrow. These circularized DNA elements persist in the cells, are unable to replicate, and are diluted as a result of cell division, thus are considered markers of new lymphocyte output. The quantification of TRECs and KRECs, which can be reliably performed using singleplex or duplex real-time quantitative PCR, provides novel information in the management of T- and B-cell immunity-related diseases. In primary immunodeficiencies, when combined with flow cytometric analysis of T- and B-cell subpopulations, the measure of TRECs and KRECs has contributed to an improved characterization of the diseases, to the identification of patients’ subgroups, and to the monitoring of stem cell transplantation and enzyme replacement therapy. For the same diseases, the TREC and KREC assays, introduced in the newborn screening program, allow early disease identification and may lead to discovery of new genetic defects. TREC and KREC levels can also been used as a surrogate marker of lymphocyte output in acquired immunodeficiencies. The low number of TRECs, which has in fact been extensively documented in untreated HIV-infected subjects, has been shown to increase following antiretroviral therapy. Differently, KREC number, which is in the normal range in these patients, has been shown to decrease following long-lasting therapy. Whether changes of KREC levels have relevance in the biology and in the clinical aspects of primary and acquired immunodeficiencies remains to be firmly established.
A possible role for CCR5 in the progression of atherosclerosis in HIV-infected patients: a cross-sectional study
Authors: Fernández-Sender Laura , Alonso-Villaverde Carlos , Rull Anna , Rodríguez-Gallego Esther , Riera-Borrull Marta , Hernández-Aguilera Anna , Camps Jordi , Beltrán-Debón Raúl , Aragonès Gerard , Menendez Javier A , Joven Jorge
Published: May 2013

Background

Chemokines can block viral entry by interfering with HIV co-receptors and are recognised mediators of atherosclerosis development. A number of experimental drugs that inhibit HIV entry arrest the development of atherosclerosis in animal models. We hypothesised that the expression of chemokine receptors in circulating leukocytes is associated with the rate of atherosclerosis progression in HIV-infected patients.

Methods

The increase in intima-media thickness during a 2-year follow-up was used to classify HIV-infected patients (n = 178) as progressors (n = 142) or non-progressors (n = 36) with respect to atherosclerosis. Logistic regression was used to assess variables associated with atherosclerosis progression. Mutations in the CCR5Δ32, CCR2 64I, and CX3CR1 (T280M and V249I) co-receptors as well as the levels of CCR5, CXCR4, CX3CR1, and CCR2 mRNA expression in circulating leukocytes were analysed as independent variables.

Results

Among the baseline variables, only genetic variants explained the dichotomous outcome. The expression of CCR2 and CXCR4 did not discriminate between progressors and non-progressors. Conversely, CCR5 and CX3CR1 expression was higher in not only progressors but also patients with detectable viral load. The logistic regression, however, demonstrated a significant role for CCR5 expression as a predictor of atherosclerosis progression (B = 2.1, OR = 8.1, p = 0.04) and a negligible effect for CXC3R1 and CCR2 expression.

Conclusions

Available CCR5 antagonists should be investigated for their potential to delay the course of atherosclerosis in HIV-infected patients.
HER2 expression and relevant clinicopathological features in gastric and gastroesophageal junction adenocarcinoma in a Chinese population
Authors: Shan Ling , Ying Jianming , Lu Ning
Published: May 2013

Background

With varied immunohistochemistry scoring criteria and patient cohorts, HER2-positivity rates in gastric cancer (GC) and gastroesophageal junction (GEJ) adenocarcinoma have been reported with a wide range. Recently standardized scoring criteria for GC and GEJ cancer has been established and recommended. In this study, the frequency of HER2 expression and the relationship between HER2 expression and clinicopathological features were examined in a large cohort of Chinese GC and GEJ cancer patients.

Methods

A total of 1463 patients, including 929 primary GCs and 534 primary GEJ adenocarcinomas, was retrospectively analyzed for HER2 overexpression by immunohistochemistry (IHC). Fluorescence in situ hybridization (FISH) analysis was used in 308 GCs and GEJ adenocarcinoma cases to assess HER2 gene amplification.

Results

HER2 overexpression (3+) was detected in 9.8% of carcinomas and more frequently observed in GEJ cancer cases, in the intestinal type, and in the well or moderately differentiated type (P=0.003, 0.000, and 0.000, respectively). HER2 equivocal (2+) was detected in 14.4% of cases. As for the 308 cases analyzed by FISH, 39 (of 40, 97.5%) IHC 3+ cases, 11 (of 38, 28.9%) IHC 2+ cases, and 3 (of 230, 1.3%) IHC 1+/0 cases showed HER2 gene amplification. A high concordance rate (98.5%) between IHC and FISH was demonstrated.

Conclusions

Approximately 10% of Chinese patients with primary GC and GEJ adenocarcinoma were HER2-positive on IHC. HER2 overexpression was associated with GEJ site, intestinal cancer subtype, and well or moderately differentiated carcinomas.

Virtual slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1935951199941072.
Clinico- pathological profile of patients with breast diseases
Authors: Aslam Hafiz Muhammad , Saleem Shafaq , Shaikh Hiba Arshad , Shahid Nazish , Mughal Anum , Umah Ribak
Published: May 2013

Background

To evaluate the spectrum of breast diseases and their association with presenting complains of patients.

Methodology

It was a cross sectional study conducted from 1stJanuary 2010 – 30thDecember 2012. A total of 254 breast specimens of patients, who were admitted in Civil Hospital Karachi with breast complaints, were included. Specimens were collected either from mastectomy, lumpectomy or needle biopsy from the admitted patients. Informed written consent was taken from all the patients. All patients with primary breast diseases were included. Patients undergoing chemotherapy or with secondary breast disease and slides with insufficient specimen were excluded. All data was entered and analyzed through SPSS 19.

Result

There were 254 breast lesions, histologically diagnosed in 3 year review period. The overall mean age of patients with breast lesion was 25.18, SD ± 11.73 with a wide age range of 12–74 years. Most common cases identified are benign 191(75.3%), followed by inflammatory 30(11.8%) and malignant lesions 30(11.8%). Most patients presenting with the complain of pain have diagnosis of fibroadenoma 24 (63.2%) while patient with complain of lump also have the most common diagnosis of fibroadenoma 147 (72.8%).

Conclusions

Study shows that in Pakistani females, mostly encountered breast lesion was fibroadenoma. Due to lack of awareness breast diseases present lately. Awareness must be created among women to reduce the mortality and morbidity with breast lesions.

Virtual slides

The virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/1037059088969395.
The wooly mutation (wly) on mouse chromosome 11 is associated with a genetic defect in Fam83g
Authors: Radden Legairre A , Child Kevin M , Adkins Elisabeth B , Spacek Damek V , Feliciano Aaron M , King Thomas R
Published: May 2013

Background

Mice homozygous for the spontaneous wooly mutation (abbreviated wly) are recognized as early as 3–4 weeks of age by the rough or matted appearance of their coats. Previous genetic analysis has placed wly in a 5.9 Mb interval on Chromosome 11 that contains over 200 known genes. Assignment of wly to one of these genes is needed in order to provide probes that would ultimately facilitate a complete molecular analysis of that gene’s role in the normal and disrupted development of the mammalian integument.

Results

Here, a large intraspecific backcross family was used to genetically map wly to a smaller (0.8 Mb) span on mouse Chromosome 11 that includes fewer than 20 genes. DNA sequencing of the coding regions in two of these candidates known to be expressed in skin has revealed a 955 bp, wly-specific deletion. This deletion, which lies within the coordinates of both Slc5a10 [for solute carrier family 5 (sodium/glucose cotransporter), member 10] and Fam83g (for family with sequence similarity 83, member G), alters the splicing of mutant Fam83g transcripts only, and is predicted to result in a severely truncated (probably non-functional) protein product.

Conclusion

We suggest that this mutation in Fam83g is the likely basis of the mouse wooly phenotype.
Chimeric antigen receptor containing ICOS signaling domain mediates specific and efficient antitumor effect of T cells against EGFRvIII expressing glioma
Authors: Shen Chan-Juan , Yang Yu-Xiu , Han Ethan Q , Cao Na , Wang Yun-Fei , Wang Yi , Zhao Ying-Ying , Zhao Li-Ming , Cui Jian , Gupta Puja , Wong Albert J , Han Shuang-Yin
Published: May 2013

Background

Adoptive transfer of chimeric antigen receptor (CAR)-modified T cells appears to be a promising immunotherapeutic strategy. CAR combines the specificity of antibody and cytotoxicity of cytotoxic T lymphocytes, enhancing T cells’ ability to specifically target antigens and to effectively kill cancer cells. Recent efforts have been made to integrate the costimulatory signals in the CAR to improve the antitumor efficacy. Epidermal growth factor receptor variant III (EGFRvIII) is an attractive therapeutic target as it frequently expresses in glioma and many other types of cancers. Our current study aimed to investigate the specific and efficient antitumor effect of T cells modified with CAR containing inducible costimulator (ICOS) signaling domain.

Methods

A second generation of EGFRvIII/CAR was generated and it contained the EGFRvIII single chain variable fragment, ICOS signaling domain and CD3ζ chain. Lentiviral EGFRvIII/CAR was prepared and human CD3+ T cells were infected by lentivirus encoding EGFRvIII/CAR. The expression of EGFRvIII/CAR on CD3+ T cells was confirmed by flow cytometry and Western blot. The functions of EGFRvIII/CAR+ T cells were evaluated using in vitro and in vivo methods including cytotoxicity assay, cytokine release assay and xenograft tumor mouse model.

Results

Chimeric EGFRvIIIscFv-ICOS-CD3ζ (EGFRvIII/CAR) was constructed and lentiviral EGFRvIII/CAR were made to titer of 106 TU/ml. The transduction efficiency of lentiviral EGFRvIII/CAR on T cells reached around 70% and expression of EGFRvIII/CAR protein was verified by immunoblotting as a band of about 57 kDa. Four hour 51Cr release assays demonstrated specific and efficient cytotoxicity of EGFRvIII/CAR+ T cells against EGFRvIII expressing U87 cells. A robust increase in the IFN-γ secretion was detected in the co-culture supernatant of the EGFRvIII/CAR+ T cells and the EGFRvIII expressing U87 cells. Intravenous and intratumor injection of EGFRvIII/CAR+ T cells inhibited the in vivo growth of the EGFRvIII expressing glioma cells.

Conclusions

Our study demonstrates that the EGFRvIII/CAR-modified T cells can destroy glioma cells efficiently in an EGFRvIII specific manner and release IFN-γ in an antigen dependent manner. The specific recognition and effective killing activity of the EGFRvIII-directed T cells with ICOS signaling domain lays a foundation for us to employ such approach in future cancer treatment.
ATP13A2 (PARK9) protein levels are reduced in brain tissue of cases with Lewy bodies
Authors: Murphy Karen E , Cottle Louise , Gysbers Amanda M , Cooper Antony A , Halliday Glenda M
Published: May 2013

Background

ATP13A2 (PARK9) loss of function mutations are a genetic cause of an early-onset form of Parkinson’s disease (PD), with in vitro studies showing that ATP13A2 deficits lead to lysosomal and mitochondrial dysfunction and α-synuclein accumulation, while elevated ATP13A2 expression reduces α-synuclein toxicity. The three human brain tissue studies assessing changes in ATP13A2 expression in PD produced divergent results; mRNA is increased while protein levels were observed to be either increased or decreased. This apparent conflict in protein levels might have arisen from examining Lewy body disease cases with coexisting Alzheimer-type pathologies.

To assess whether ATP13A2 levels in Lewy body disease are modified by Alzheimer-type β-amyloid deposition, we evaluated cases of pure PD and pure dementia with Lewy bodies (DLB) for changes in ATP13A2, α-synuclein and β-amyloid protein levels in cortical regions with and without Lewy bodies.

Results

In all Lewy body disease cases, we identified decreased ATP13A2 protein levels that correlated with increases in both α-synuclein and β-amyloid. Partial colocalization was observed between ATP13A2 and α-synuclein in Lewy bodies, whereas ATP13A2 did not colocalize with pathological β-amyloid deposition.

Conclusions

Our data show that patients with Lewy body diseases have an overall deficit in ATP13A2 protein levels, with the remaining protein being more insoluble and partially redistributing towards Lewy bodies. This supports the concept that increasing ATP13A2 levels may offer potential therapeutic benefits to patients with Lewy body diseases.
Extensive aggregation of α-synuclein and tau in juvenile-onset neuroaxonal dystrophy: an autopsied individual with a novel mutation in the PLA2G6 gene-splicing site
Authors: Riku Yuichi , Ikeuchi Takeshi , Yoshino Hiroyo , Mimuro Maya , Mano Kazuo , Goto Yoji , Hattori Nobutaka , Sobue Gen , Yoshida Mari
Published: May 2013

Background

Infantile neuroaxonal dystrophy (INAD) is a rare autosomal-recessive neurodegenerative disorder. Patients with INAD usually show neurological symptoms with infant onset and die in childhood. Recently, it was reported that mutations in the PLA2G6 gene cause INAD, but neuropathological analysis of genetically confirmed individuals with neuroaxonal dystrophy has been limited.

Results

Here, we report a Japanese individual with neuroaxonal dystrophy associated with compound heterozygous mutations in the PLA2G6 gene. A novel splice-site mutation resulting in skipping and missense mutations (p.R538C) in exon 9 was identified in the patient. This patient initially presented with cerebellar ataxia at the age of 3 years, which was followed by symptoms of mental retardation, extrapyramidal signs, and epileptic seizure. The patient survived until 20 years of age. Neuropathological findings were characterized by numerous axonal spheroids, brain iron deposition, cerebellar neuronal loss, phosphorylated alpha-synuclein-positive Lewy bodies (LBs), and phosphorylated-tau-positive neurofibrillary tangles. In particular, LB pathology exhibited a unique distribution with extremely severe cortical involvement.

Conclusions

Our results support a genetic clinical view that compound heterozygous mutations with potential residual protein function are associated with a relatively mild phenotype. Moreover, the severe LB pathology suggests that dysfunction of the PLA2G6 gene primarily contributes to LB formation.
Filamentous white matter prion protein deposition is a distinctive feature of multiple inherited prion diseases
Authors: Reiniger Lilla , Mirabile Ilaria , Lukic Ana , Wadsworth Jonathan DF , Linehan Jacqueline M , Groves Michael , Lowe Jessica , Druyeh Ronald , Rudge Peter , Collinge John , Mead Simon , Brandner Sebastian
Published: May 2013

Background

Sporadic, inherited and acquired prion diseases show distinct histological patterns of abnormal prion protein (PrP) deposits. Many of the inherited prion diseases show striking histological patterns, which often associate with specific mutations. Most reports have focused on the pattern of PrP deposition in the cortical or cerebellar grey matter.

Results

We observed that the subcortical white matter in inherited prion diseases frequently contained filamentous depositions of abnormal PrP, and we have analysed by immunohistochemistry, immunofluorescence and electron microscopy 35 cases of inherited prion disease seen at the UK National Prion Clinic. We report here that filamentous PrP is abundantly deposited in myelinated fibres in inherited prion diseases, in particular in those with N-terminal mutations.

Conclusions

It is possible that the presence of filamentous PrP is related to the pathogenesis of inherited forms, which is different from those sporadic and acquired forms.
Liver X receptor activation inhibits osteoclastogenesis by suppressing NF-κB activity and c-Fos induction and prevents inflammatory bone loss in mice
Authors: Kim Hyun-Ju , Yoon Kyung-Ae , Yoon Hye-Jin , Hong Jung Min , Lee Min-Jung , Lee In-Kyu , Kim Shin-Yoon
Published: May 2013

LXRs are nuclear receptors that function as important regulators of lipid homeostasis and inflammatory responses. LXR activation has been shown to suppress RANKL-induced osteoclast differentiation, but its underlying mechanisms and its influence on inflammatory bone destruction remain unclear. In this study, we report that the LXR agonists T0901317 and GW3965 inhibit osteoclastogenesis from primary BMMs in a dose-dependent manner. LXR activation suppressed RANKL-induced transcriptional activity of NF-κB without affecting IκBα degradation and the phosphorylation of p38. LXR agonists significantly suppressed RANKL-induced expression of c-Fos and NFATc1, which are crucial transcription factors for osteoclastogenesis. The activation of LXRs also inhibited RANKL-mediated AP-1 transcriptional activity. Furthermore, LXR activation attenuated PPARγ ligand-induced c-Fos expression, and LXR suppressed AP-1 promoter activity by PPARγ. The inhibitory effect of LXR activation on osteoclastogenesis was reversed by overexpression of c-Fos, suggesting that c-Fos is a downstream target of the antiosteoclastogenic action of LXRs. In addition to osteoclast differentiation, LXR activation accelerated apoptosis in mature osteoclasts by the induction of caspase-3 and -9 activity and Bim expression. Consistent with the in vitro effects we observed, the administration of a LXR agonist protected from bone loss induced by LPS in vivo. Together, our data provide evidence that LXRs may have potential as therapeutic targets for bone resorption-associated diseases.
Insulinoma presenting as refractory seizure disorder
Authors: Correia Pamela , Panchani Roopal , Ranjan Rajeev , Agrawal Chandrashekhar
Published: May 2013

Hypoglycaemia can lead to acute disorders of cognition, consciousness, epilepsy, transient ischemia, psychosis and chronic disorders of dementia and neuropathy. Misdiagnosis and delay in treatment are common and prolonged hypoglycemia can lead to permanent neurological deficit or fatal coma. Hypoglycemia caused by an insulinoma is a readily treatable condition that should be considered in the differential diagnosis of intractable seizures. The following case report highlights the need for careful reassessment of all seizures that are atypical and refractory to medication.
Identifying spatial priorities for protecting ecosystem services
Authors: Luck Gary W , Chan Kai MA , Klien Carissa J
Published: May 2013

Priorities for protecting ecosystem services must be identified to ensure future human well-being. Approaches to broad-scale spatial prioritization of ecosystem services are becoming increasingly popular and are a vital precursor to identifying locations where further detailed analyses of the management of ecosystem services is required (e.g., examining trade-offs among management actions). Prioritization approaches often examine the spatial congruence between priorities for protecting ecosystem services and priorities for protecting biodiversity; therefore, the spatial prioritization method used is crucial because it will influence the alignment of service protection and conservation goals. While spatial prioritization of ecosystem services and prioritization for conservation share similarities, such as the need to document threats and costs, the former differs substantially from the latter owing to the requirement to measure the following components: supply of services; availability of human-derived alternatives to service provision; capacity to meet beneficiary demand; and site dependency in and scale of service delivery. We review studies that identify broad-scale spatial priorities for managing ecosystem services and demonstrate that researchers have used different approaches and included various measures for identifying priorities, and most studies do not consider all of the components listed above. We describe a conceptual framework for integrating each of these components into spatial prioritization of ecosystem services and illustrate our approach using a worked example for water provision. A fuller characterization of the biophysical and social context for ecosystem services that we call for should improve future prioritization and the identification of locations where ecosystem-service management is especially important or cost effective.
Local indigenous knowledge about medicinal plants in and around Kakamega forest in western Kenya
Authors: Otieno Nickson Erick , Analo Caleb
Published: May 2013

Kakamega forest is Kenya’s only rainforest and is distinguishably rich in biodiversity but threatened by agricultural encroachment and other forms of human activity. It is also one of Kenya’s Important Bird Areas and a significant source of natural products to neighboring rural communities, such as medicinal plants, food, wood and other fibers. By using structured questionnaires for direct interviews, local indigenous knowledge was tapped through involvement of a focal group of elderly key informants in three blocks of the forest. Forty key species of medicinal plants used by local people were identified and recorded. Fifty-five percent of these were shrubs, thirty-two percent trees, seven-and-a-half percent lower plants such as herbs or forbs while five percent were climbers. About seventy percent of the medicinal plants occurred inside the forest itself and thirty percent around the edge and the immediate surroundings outside the forest. Thirty-eight (95%) of the plants were indigenous to Kenya and two (5%) exotic. Such extensive indigenous knowledge of the medicinal uses of the plants, including their distribution trends in the forest, may be tapped for decision support in rural health service planning, policy formulation for conserving the forest, tracking and mitigation of climate change impacts.