bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic Ethanol Exposure Selectively Inhibits the Influenza‐Specific CD8 T Cell Response During Influenza A Virus Infection
Authors: Hemann Emily A. , McGill Jodi L. , Legge Kevin L. 
Published: August 2014

BackgroundIt is well established that chronic ethanol (EtOH) consumption is associated with increased incidence and disease severity of respiratory infections. Our recent work demonstrates this increase in disease severity to influenza A virus (IAV) infections is due, in part, to a failure to mount a robust IAV‐specific CD8 T cell response along with a specific impairment in the ability of these T cells to produce interferon γ (IFNγ). However, the full extent of the lesion in the effector CD8 T cell compartment during chronic EtOH consumption remains unknown.MethodsUtilizing the Meadows–Cook murine model of chronic alcohol consumption, mice received EtOH in their drinking water for 8 or 12 weeks. Mice were challenged intranasally with IAV, and the activation and effector functions of IAV‐specific CD8 T cells were determined in both the lung‐draining lymph nodes (dLN) and lungs.ResultsOur results confirm the defect in IFNγ production; however, the ability of IAV‐specific T cells to produce tumor necrosis factor α (TNFα) and interleukin‐2 (IL‐2) in EtOH‐consuming mice remains unaltered. In contrast, EtOH consumption significantly reduces the ability of CD8 T cells to degranulate and kill IAV‐specific targets. Finally, our findings suggest the lesion begins during the initial activation of CD8 T cells, as we observe early defects in proliferation in the dLN of IAV‐infected, EtOH‐consuming mice.ConclusionsThese findings highlight the previously unrecognized depth of the lesion in the IAV‐specific CD8 T cell response during chronic EtOH consumption. Given the important role CD8 T cell immunity plays in control of IAV, these findings may aid in the development of vaccination and/or therapeutic strategies to reverse these defects in the CD8 T cell response and reduce serious disease outcomes associated with IAV infections in alcoholics.
Nonalcoholic fatty liver disease (NAFLD) in the Veterans Administration population: development and validation of an algorithm for NAFLD using automated data
Authors: Husain N. , Blais P. , Kramer J. , Kowalkowski M. , Richardson P. , El‐Serag H. B. , Kanwal F. 
Published: August 2014

SummaryBackgroundIn practice, nonalcoholic fatty liver disease (NAFLD) is diagnosed based on elevated liver enzymes and confirmatory liver biopsy or abdominal imaging. Neither method is feasible in identifying individuals with NAFLD in a large‐scale healthcare system.AimTo develop and validate an algorithm to identify patients with NAFLD using automated data.MethodsUsing the Veterans Administration Corporate Data Warehouse, we identified patients who had persistent ALT elevation (≥2 values ≥40 IU/mL ≥6 months apart) and did not have evidence of hepatitis B, hepatitis C or excessive alcohol use. We conducted a structured chart review of 450 patients classified as NAFLD and 150 patients who were classified as non‐NAFLD by the database algorithm, and subsequently refined the database algorithm.ResultsThe sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) for the initial database definition of NAFLD were 78.4% (95% CI: 70.0–86.8%), 74.5% (95% CI: 68.1–80.9%), 64.1% (95% CI: 56.4–71.7%) and 85.6% (95% CI: 79.4–91.8%), respectively. Reclassifying patients as having NAFLD if they had two elevated ALTs that were at least 6 months apart but within 2 years of each other, increased the specificity and PPV of the algorithm to 92.4% (95% CI: 88.8–96.0%) and 80.8% (95% CI: 72.5–89.0%), respectively. However, the sensitivity and NPV decreased to 55.0% (95% CI: 46.1–63.9%) and 78.0% (95% CI: 72.1–83.8%), respectively.ConclusionsPredictive algorithms using automated data can be used to identify patients with NAFLD, determine prevalence of NAFLD at the system‐wide level, and may help select a target population for future clinical studies in veterans with NAFLD.
The performance of contemporary cystatin C‐based GFR equations in predicting gentamicin clearance
Authors: Chin Paul K. L. , Chew‐Harris Janice S. C. , Florkowski Christopher M. , Begg Evan J. 
Published: August 2014

AimsWe aimed to compare the performances of contemporary cystatin C (Cys)‐based GFR equations, and the creatinine only Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) equation for predicting gentamicin clearance.MethodsThe bias and imprecision of the CKD‐EPI, CKD‐EPI_Cys and creatinine‐cystatin C CKD‐EPI (CKD‐EPI_CrCys) equations for predicting gentamicin clearances, were assessed in 260 patients treated with gentamicin during 2012–2013. The creatinine‐cystatin C Berlin Initiative Study equation (BIS_CrCys) was examined in the ≥70 year subgroup. The reference gentamicin clearance was calculated using post‐dose plasma concentrations.ResultsThe CKD‐EPI_CrCys equation had the highest percentage of estimates within 30% of the reference gentamicin clearance (70%, P = 0.003) and lowest root mean square error (95% CI) of 29 (25, 23) ml min−1 of the three equations for the entire cohort. There was no significant improvement in the performances of the equations with the exclusion of 41 patients with abnormal thyroid function tests or steroid co‐prescription at the time of the index gentamicin dose. Of the remaining 219 patients, adjustment for individual BSA improved the performances of all GFR equations (P ≤ 0.003) in those with body mass indices (BMI) <18.5 or ≥30 kg m−2, but not those with BMI 18.5–29.9 kg m−2. There was no advantage of the BIS_CrCys over the CKD‐EPI_CrCys equation in the ≥70 year subgroup.ConclusionsThe CKD‐EPI_CrCys equation provided the best estimate of gentamicin clearance. If used for guiding gentamicin dosing, the results from GFR equations should be adjusted for individual BSA at the extremes of body size.
Deconstructing the binaries of spatial data production: Towards hybridity
Authors: Cinnamon Jonathan 
Published: August 2014

AbstractBinaries, the most reductive form of categorization, can be usefully invoked to characterize emerging phenomena; yet, they are widely critiqued for oversimplifying a complex world and for their use as tools of social and political influence. Through a literature review and content analysis this article traces the emergence of volunteered geographic information (VGI), and identifies the recurrent use of several related binaries to contrast this phenomenon with the conventional spatial data production activities of states and corporations. Using several key examples, these binaries are deconstructed by identifying a mismatch in how VGI is conceptualized (bottom‐up, amateur, asserted) in the literature and the reality of existing VGI projects. As an alternative to a binary conceptualization of spatial data production, a different representation is put forward that more accurately depicts what is in actuality a vast, shifting, and heterogeneous landscape of spatial data production approaches. Thinking about contemporary spatial data production not as a binary but as a continuum could encourage the development of hybridities that harness the benefits of different approaches—including the oversight and quality control of conventional methods, with the speed, low cost, and distributed nature of citizen‐based spatial data production.
An exploration of Indigenous‐settler relations in the Port Alberni Valley, British Columbia regarding implementation of the 2011 Maa‐nulth Treaty
Authors: Morgan Vanessa Sloan , Castleden Heather 
Published: August 2014

AbstractOn April 1, 2011, the Maa‐nulth Treaty went into effect; this treaty involves signatories from five First Nations, the Province of British Columbia, and Canada. Encompassing territories never before ceded—largely in the Port Alberni region of Vancouver Island—these First Nations have reclaimed a degree of self‐determination through the Treaty. Using it as a platform for analysis, this study sought to examine local Indigenous‐settler relations within a modern treaty context. During the week of Treaty celebrations and formal implementation, face‐to‐face semi‐structured surveys were administered to local residents of Port Alberni, asking their perspectives on the Treaty to determine the breadth and depth of comprehension—and tensions surrounding it. Our hypothesis was that in the heart of the region where impacts would be felt the strongest, there would be diverse (likely heated) opinions revealed through the data; to our surprise, however, over 40 percent were unaware of the Treaty's existence, let alone its implications. This resulted in some challenges in the extent to which our data could be interpreted but provided proof‐of‐concept for further exploration into why residents remain unaware of their own implication in modern treaty negotiations and their associated historical complexities.
Navigating jurisdiction: local and regional strategies to access economic benefits from mineral development
Authors: Heisler Karen G. , Markey Sean 
Published: August 2014

AbstractThis article examines how concepts of territory and scale are used to create places of benefit from resource activities in remote rural regions. Our case study of mineral development in northwest British Columbia compares the experiences of First Nation, municipal and regional governments in accessing economic benefits from mineral development. Territorial land claims are changing the multi‐scalar jurisdictional hierarchy and the socio‐spatial relations between senior levels of government, resource companies, and local communities. The territorial rights of First Nation governments provide the political leverage to negotiate with companies seeking to “earn a social license” to operate within their territories. Municipal and regional governments, however, are restricted by their role in the multi‐scalar jurisdictional hierarchy. In response, municipal and regional governments are devising strategies to capture economic benefits. We discuss three economic development strategies used to access benefits from mineral development activities: negotiating commitments during the environmental assessment process, investment attraction strategies, and lobbying the provincial government for a share of the resource revenues generated from mining. These strategies reflect the political and economic context for local government in remote resource‐dependent regions and the changing socio‐spatial relations between senior levels of government, resource companies, and First Nation, municipal and regional governments.
Relation between outcomes and expression of estrogen receptor‐α phosphorylated at Ser167 in endometrioid endometrial cancer
Authors: Kato Eiichi , Orisaka Makoto , Kurokawa Tetsuji , Chino Yoko , Fujita Yuko , Shinagawa Akiko , Yoshida Yoshio 
Published: August 2014

Both ligand‐dependent and ligand‐independent activation of estrogen receptor (ER)α is modulated by receptor phosphorylation and results in activation of the ERα‐dependent pathways that are involved in endometrioid endometrial cancer (EEC) pathogenesis. It is also known that the mammalian target of rapamycin (mTOR)/p70 S6 kinase 1 (S6K1) and MAPK/p90 ribosomal S6 kinase (RSK) signaling pathways coordinately regulate phosphorylated‐ERα at Ser167 (p‐Ser167‐ERα). However, the expression of p‐Ser167‐ERα in EEC and its prognostic role in ECC is largely unexplored. The purpose of the present study was to investigate the expression of p‐Ser167‐ERα in ECC and its relationship with prognosis. Immunohistochemical staining of primary EEC surgical specimens (n = 103) was carried out using antibodies specific for p‐Ser167‐ERα and for p‐mTOR/p‐S6K1 and p‐MAPK/p‐RSK. The correlation of p‐Ser167‐ERα expression with clinicopathological features and survival of ECC was studied. Patients that were positive for nuclear p‐Ser167‐ERα had significantly shorter relapse‐free survival, and although the result was not significant, levels of nuclear p‐Ser167‐ERα tended to be higher in advanced‐stage ECC patients. Nuclear p‐Ser167‐ERα was significantly positively correlated with p‐MAPK and p‐S6K1, and with significantly shorter relapse‐free survival in EEC.
Clinical significance of serum thymus and activation‐regulated chemokine in gastric cancer: Potential as a serum biomarker
Authors: Lim Jong‐Baeck , Kim Do‐Kyun , Chung Hye Won 
Published: August 2014

Thymus and activation‐regulated chemokine (TARC) can stimulate cancer cell proliferation and migration. The present study evaluated the clinical significance of serum TARC in gastric cancer (GC). We measured serum TARC, macrophage‐derived chemokine, monocyte chemotactic protein‐1 and stem cell factor (SCF) levels using a chemiluminescent immunoassay along the GC carcinogenesis (normal, high‐risk, early GC [EGC] and advanced GC [AGC]) in both training (N = 25 per group) and independent validation datasets (90 normal, 30 high‐risk, 50 EGC and 50 AGC). Serum levels were compared among groups using one‐way analysis of variance. To evaluate the diagnostic potential of serum TARC for GC, receiver operating characteristic curve and logistic regression analyses were performed. Correlations between serum TARC and GC clinicopathological features were analyzed using Spearman's correlation. In the training dataset, serum TARC correlated with serum MDC, MCP‐1 and SCF. However, only serum TARC and SCF were significantly higher in cancer groups than non‐cancer groups (P < 0.001). In the validation dataset, serum TARC also increased along the GC carcinogenesis; the AGC group (167.2 ± 111.1 ng/mL) had significantly higher levels than the EGC (109.1 ± 67.7 ng/mL), the high‐risk (66.2 ± 47.7 ng/mL) and the normal (67.5 ± 36.2 ng/mL) groups (Bonferroni, all P < 0.001). Receiver operating characteristic curves and logistic regression demonstrated the remarkable diagnostic potential of serum TARC as a single marker (72.0% sensitivity and 71.1% specificity; cutoff point, 0.37; logistic regression) and in a multiple‐marker panel (72.6% sensitivity and 88.2% specificity; cutoff point, 0.54). Spearman's correlation showed that serum TARC was closely correlated with tumor size (γs = 0.227, P = 0.028), T‐stage (γs = 0.340, P = 0.001), N‐stage (γs = 0.318, P = 0.002) and M‐stage (γs = 0.346, P = 0.001). Serum TARC is a promising serum biomarker for GC.
BRCA1 promoter methylation of normal breast epithelial cells as a possible precursor for BRCA1‐methylated breast cancer
Authors: Otani Yoko , Miyake Tomohiro , Kagara Naofumi , Shimoda Masafumi , Naoi Yasuto , Maruyama Naomi , Shimomura Atsuhi , Shimazu Kenzo , Kim Seung Jin , Noguchi Shinzaburo 
Published: August 2014

The breast cancer susceptibility gene 1 (BRCA1) and glutathione S‐transferase P1 (GSTP1) promoters are reportedly often methylated in breast cancer tissues. Their methylation status in surrounding normal breast tissues has not been examined thoroughly although this may well be important for a better understanding of breast carcinogenesis. In this study, BRCA1 and GSTP1 promoter methylation was examined by methylation‐specific PCR assay. Patients with BRCA1‐methylated (n = 15) or BRCA1‐unmethylated (n = 15) tumors and those with GSTP1‐methylated (n = 9) or GSTP1‐unmethylated (n = 11) tumors were included in the present study. Methylation status of manually micro‐dissected normal epithelial cells from the formalin‐fixed paraffin‐embedded sections of normal breast tissues adjacent to and distant from the tumors was examined at multiple sites (n = 1–5). Of the 15 patients with BRCA1‐methylated tumors, 9 harbored BRCA1 promoter methylation in at least one site of the normal breast tissues. However, no BRCA1 promoter methylation was observed at any site of the normal tissues of the 15 patients with BRCA1‐unmethylated tumors. No GSTP1 promoter methylation was observed in the normal tissues regardless of the methylation status of the tumors. The presence of BRCA1 promoter methylation in the normal tissues was confirmed in the epithelial cells enriched with the magnetic‐activated cell sorting method. Our findings suggest that a small proportion of normal breast epithelial cells with BRCA1 promoter methylation can be precursor cells from which BRCA1‐methylated breast tumors may originate. This does not apply to GSTP1 promoter methylation.
Ileocaecal junction carcinoma: a clinicopathological study of 199 cases
Authors: Lee L. H. , MacLean A. R. , Falck V. G. , Gui X. 
Published: August 2014

AbstractAimThe ileocaecal junction (ICJ) region is an epithelial transition zone in which carcinomas are frequently diagnosed. However, it is currently unknown whether ICJ carcinomas (ICJ‐CAs) have distinctive features. This study aimed to characterize the clinicopathological features of ICJ‐CAs.MethodAll ileal and colorectal resections for carcinoma, performed in Calgary, Canada between January 2009 and June 2012, were reviewed. Carcinomas in which the epicentre was within 5 cm of the ileocaecal valve (ICV) were defined as ICJ‐CAs. Of 1003 carcinomas studied, 199 (19.8%) were ICJ‐CAs, including 93 (9.3%) that crossed the ICV. Comparison of clinicopathological features with carcinomas of the other ileo‐colorectal regions was made. Survival was also assessed.ResultsClinically, ICJ‐CAs were more common in female than male patients (56.3% female) compared with left‐colonic (42.9% female) and rectal (37.9% female) carcinomas, and were more common in older age‐groups of patients (71.8 ± 12.7 years) compared with appendiceal (62.6 ± 11.3 years), left‐colonic (69.4 ± 12.3 years) and rectal (67.1 ± 11.9 years) carcinomas. Macroscopically, ICJ‐CAs were similar to other colorectal carcinomas and were mostly described as ulcerated (63.3%). Histologically, ICJ‐CAs had more mucinous, signet‐ring cell and/or neuroendocrine features (39.7%, 8.0% and 7.5%, respectively) than did carcinomas of the left colon (16.8%, 1.6% and 1.1%, respectively) and the rectum (14.1%, 1.0% and 0.0%, respectively). They were higher grade (20.1% were high grade) than those of the left‐colon (10.3%) and the rectum (9.8%). ICJ‐CAs presented at a higher T‐stage (25.6% were T4) compared with rectal carcinomas (11.6%). Most significantly, ICJ‐CAs presented at a higher N‐stage (25.6% were N2) than did right‐colonic (14.1%) and rectal (16.2%) carcinomas. Although survival of patients with ICJ‐CAs did not differ from those with right‐colonic carcinomas, those with carcinomas directly involving the ICV did show a significantly decreased survival.ConclusionICJ‐CAs display several distinct clinicopathological features that may require special diagnostic, prognostic and management attention.
The Role of Family Involvement on CEO Turnover: Evidence from Colombian Family Firms
Authors: González Maximiliano , Guzmán Alexander , Pombo Carlos , Trujillo María‐Andrea 
Published: August 2014

AbstractManuscript TypeEmpiricalResearch Question/IssueWe analyze CEO turnover in closely held firms with some level of ownership dispersion in a context of low investor protection. In particular, we examine the impact of family involvement on CEO turnover and CEO turnover/performance sensitivity. We argue that family involvement in management, ownership, and control has both a direct effect on CEO turnover from the family presence itself, and a moderating effect over CEO turnover/performance sensitivity attributable to the agency tensions between majority and minority shareholders (whether other family blocks or non‐family shareholders).Research Findings/InsightsUsing data from 1996–2006 for 523 Colombian firms, we find direct and moderating effects, depending on the type of family involvement. Family involvement in management and boards reduces CEO turnover, but family involvement in ownership increases it. Regarding moderating effects, family involvement in ownership reduces CEO turnover/performance sensitivity, while the opposite occurs with family directors.Theoretical/Academic ImplicationsOur results show that closely held firms in emerging markets exhibit a strong negative CEO turnover/performance sensitivity, which is a somewhat counterintuitive result, and also contribute to a better understanding of agency conflicts within family firms by highlighting the different ways families affect CEO turnover.Practitioner/Policy ImplicationsOur findings suggest that even benevolently entrenched family CEOs are not immune to poor financial performance. Families that are majority or controlling shareholders may support CEOs even when the firm performs poorly because of potential benefits from control. Family boards are very sensitive to financial performance even when the CEO is a family member.
Which Executive Characteristics Create Value in Banking? Evidence from Appointment Announcements
Authors: Nguyen Duc Duy (Louis) , Hagendorff Jens , Eshraghi Arman 
Published: August 2014

AbstractManuscript TypeEmpiricalResearch Question/IssueThis study seeks to understand how the characteristics of executive directors affect the market performance of US banks. To explore the expected performance effects linked to executive characteristics, we measure any changes in the market valuation of banks linked to announcements of executive appointments.Research Findings/InsightsOur study has two important findings. First, we show that age, education, and the prior work experience of executives create shareholder wealth while gender is not linked to measurable value effects. Second, these wealth effects are moderated by the level of influence of incoming executives, with their magnitude diminished under independent boards and higher if the incoming executive is also appointed as CEO. Our results are robust to the treatment of selection bias.Theoretical/Academic ImplicationsBy illustrating the wealth effects linked to executive appointments, our study contributes to the current debate on whether and how individual executives matter for firm performance and behavior. The findings also shed light on the value of human capital in the banking industry.Practitioner/Policy ImplicationsThis study offers important insights to policymakers charged with ensuring the competency of executives in banking. Our findings advocate policies that mandate banks to appoint highly qualified executives with relevant banking experience.
The development of race‐based perceptual categorization: skin color dominates early category judgments
Authors: Dunham Yarrow , Stepanova Elena V. , Dotsch Ron , Todorov Alexander 
Published: August 2014

AbstractPrior research on the development of race‐based categorization has concluded that children understand the perceptual basis of race categories from as early as age 4 (e.g. Aboud, 1988). However, such work has rarely separated the influence of skin color from other physiognomic features considered by adults to be diagnostic of race categories. In two studies focusing on Black–White race categorization judgments in children between the ages of 4 and 9, as well as in adults, we find that categorization decisions in early childhood are determined almost entirely by attention to skin color, with attention to other physiognomic features exerting only a small influence on judgments as late as middle childhood. We further find that when skin color cues are largely eliminated from the stimuli, adults readily shift almost entirely to focus on other physiognomic features. However, 6‐ and 8‐year‐old children show only a limited ability to shift attention to facial physiognomy and so perform poorly on the task. These results demonstrate that attention to ‘race’ in younger children is better conceptualized as attention to skin color, inviting a reinterpretation of past work focusing on children's race‐related cognition.