bluuebunny/crossref_metadata_2025 huggingface dataset:
Crizotinib Response in a Late Relapse of ALK-positive Lung Adenocarcinoma
Authors: Zito Marino Federica , Morabito Alessandro , Gridelli Cesare , Rocco Gaetano , Liguori Giuseppina , De Rosa Nicla , Botti Gerardo , Franco Renato
Published: March 2016

Anaplastic lymphoma kinase (ALK) rearrangement is a therapeutic target in non–small cell lung cancer. To date, few reports have been provided related to ALK-rearranged late recurrence and sensitivity to the treatment with specific ALK inhibitors. We report a case of a 35-year-old man who underwent a right lower lobe lobectomy for lung adenocarcinoma, and treated with the platinum-based chemotherapy regimen. After 10 healthy years, he developed a lung nodule in the same site as the previous. Cytopathologic diagnosis was lung adenocarcinoma. Furthermore, the pulmonary nodule was considered a late recurrence in relation to the lymph node involvement, the same histotype and the site, ALK fluorescence in situ hybridization test and epidermal growth factor receptor analysis were performed on the formalin-fixed paraffin-embedded specimens of the previous resected tumor, because of inadequacity cytologic sample. Being positive for ALK rearrangement, the patient was treated with crizotinib with a good response. To the best of our knowledge, it is the first case of a late relapse of ALK-positive lung adenocarcinoma sensitive to crizotinib in the literature.
Immunohistochemical Expression of MCM-2 in Oral Epithelial Dysplasias
Authors: Zakaria Samar H. , Farag Heba A. , Khater Dina S.
Published: March 2016

Background:

Oral cancer is one of the most frequent cancers in the world. It arises from epithelial dysplasia. Hence, identifying these lesions in an early stage could prevent their malignant transformation. The aim of the present work was to assess the cell proliferative activity of minichromosome maintenance protein (MCM-2) in oral epithelial dysplastic lesions and to correlate the results with different grades of epithelial dysplasia in an attempt to use MCM-2 in the early detection of malignancy.

Methods:

MCM-2 expression was determined by the nuclear count in a total of 30 oral epithelial dysplastic specimens roughly classified into 10 cases of mild, moderate, and severe dysplasia. Five cases of early invasive squamous-cell carcinomas and 5 cases of epithelial hyperplasia were also included.

Results:

The MCM-2 immunostaining was found to increase gradually from mild to moderate to severe dysplasia and reached its maximum value in early invasive squamous cell carcinoma.

Conclusion:

MCM-2 is of prognostic value in cases of oral dysplasia that have a tendency to undergo malignant transformation.
Flat Intraurothelial Neoplasia Exhibiting Diffuse Immunoreactivity for CD44 and Cytokeratin 5 (Urothelial Stem Cell/Basal Cell Markers): A Variant of Intraurothelial Neoplasia Commonly Associated With Muscle-invasive Urothelial Carcinoma
Authors: Mai Kien T. , Busca Aurelia , Belanger Eric C.
Published: March 2016

Background:

Immunoreactivity for CD44 and cytokeratin (CK)5 (urothelial stem/basal cell markers) are decreased/negative in the common type of intraurothelial neoplasia including urothelial carcinomas (UC) in situ. Recent studies also reveal that a majority of muscle-invasive UC are basal-like UC with large areas of positive CD44/CK5 immunoreactivity. In addition, approximately 80% of muscle-invasive UC develop de novo as nonpapillary invasive UC. In this study, we investigate the CD44/CK5 immunoreactivity of the flat intraurothelial neoplasia (FIUN) associated with nonpapillary invasive UC.

Materials and Methods:

Consecutive cases of nonpapillary UC were submitted for immunostaining. Immunostaining for CK5/CD44 was scored as high for staining of >25% thickness of urothelium and low for lesser immunoreactivity.

Results:

In total, 109 consecutive cases were grouped into: in situ UC [carcinoma in situ (CIS)] (n=11), pT1 (n=14), and pT2-4 (n=84) with surface urothelium available for study. Forty-four cases including CIS (n=9), pT1 (n=12), and pT2-4 (n=23) showed FIUN with low/negative CD44/CK5 reactivity; 40 cases showed strong CK20 reactivity. Sixty-two cases including CIS (n=2), pT1 (n=2), and pT2-4 (n=58) showed extensive FIUN exhibiting high CD44/CK5 reactivity; 30 cases showed reactive CK20. FIUN lesions with high CD44/CK5 reactivity scores were associated with mild (urothelial dysplasia) to moderate atypia (CIS) and were rarely preceded by papillary UC. Most invasive UC associated with FIUN with high CD44/CK5 reactivity also exhibited extensive CD44/CK5 reactivity. The remaining 3 cases showed only reactive urothelium. Of interest, 4 cases with FIUN showed negative CD44/CK5/CK20 reactivity.

Conclusions:

Existence of CD44/CK5-immunoreactive (or basal-like) FIUN is consistent with the recent distinction of basal and luminal subtypes of UC. This type of FIUN is often associated with UC with progression to high-stage disease not preceded by recurrent papillary UC.
Renal Cell Carcinoma Occurring in Patients With Prior Neuroblastoma
Authors: Falzarano Sara M. , McKenney Jesse K. , Montironi Rodolfo , Eble John N. , Osunkoya Adeboye O. , Guo Juan , Zhou Shengmei , Xiao Hong , Dhanasekaran Saravana M. , Shukla Sudhanshu , Mehra Rohit , Magi-Galluzzi Cristina
Published: March 2016

Renal cell carcinoma (RCC) associated with neuroblastoma (NB) was included as a distinct entity in the 2004 World Health Organization classification of kidney tumors. A spectrum of RCC subtypes has been reported in NB survivors. We herein describe a series of 8 RCCs diagnosed in 7 patients with a history of NB. Microscopic evaluation, immunohistochemical staining for PAX8, cathepsin K, and succinate dehydrogenase subunit B (SDHB), and fluorescence in situ hybridization (FISH) forTFE3andTFEBwere performed. Four distinct morphologic subtypes were identified: 3 tumors were characterized by cells with abundant oncocytoid cytoplasm and irregular nuclei; 3 showed features of microphthalmia transcription factor family translocation RCC (MiTF-RCC); 1 had features of hybrid oncocytic-chromophobe tumor; 1 had papillary RCC histology. All RCCs expressed PAX8 and retained SDHB expression. Cathepsin K was positive in 2 MiTF-RCCs, 1 wasTFEBFISH positive, and the other was indeterminate. Cathepsin K was negative in a third MiTF-RCC withTFE3rearrangement.TFE3FISH was negative in 4 and insufficient in 1 of the other 5 RCCs. While a subset of RCCs associated with NB is characterized by cells with prominent oncocytoid cytoplasm, other RCC subtypes also occur in post-NB patients. Renal neoplasms occurring in patients with a history of NB do not represent a single entity but a heterogenous group of RCCs.SDHBmutations do not explain the subset of nontranslocation RCCs with oncocytoid features; therefore, further studies are needed to clarify whether they may represent a distinct entity with unique molecular abnormalities or may belong to other emerging RCC subtypes.
Clinicopathologic Characterization of Aggressive Natural Killer Cell Leukemia Involving Different Tissue Sites
Authors: Gao Li-Min , Zhao Sha , Liu Wei-Ping , Zhang Wen-Yan , Li Gan-Di , Küçük Can , Hu Xiao-Zhou , Chan Wing C. , Tang Yuan , Ding Wen-Shuang , Yan Jia-Qi , Yao Wen-Qing , Wang Jian Chao
Published: March 2016

Aggressive natural killer cell leukemia (ANKL) is a rare disease with an extremely aggressive clinical course. The etiology of ANKL is unclear with few genetic/epigenetic aberrations described to date. Moreover, misdiagnosis of ANKL is a frequent problem. Clinicopathologic characteristics of 35 retrospective cases of ANKL were investigated with the aim of improving diagnosis and to find the genetic/epigenetic aberrations associated with ANKL etiology. Because of the relatively low number of leukemic cells in the peripheral blood and bone marrow, diagnosis of ANKL can be missed; therefore, it is important to perform biopsy on solid tissues, if necessary. We describe the pathology of ANKL in the lymph nodes, bone marrow, spleen, liver, and skin, with focus on diagnosis and differentiated diagnosis. We observed young male predominance in our cohort, and the clinical course was more aggressive than reported previously. Low lactate dehydrogenase (<712 IU/L), chemotherapy or l-asparaginase administration were found to be associated with more favorable outcomes. SH2 domains of STAT5B and STAT3 also were screened for the presence of activating mutations. Moreover, CpG island methylation status of HACE1, a candidate tumor-suppressor gene, was determined in ANKL samples. We observed activating STAT5B mutations (1/5) and hypermethylation of HACE1 (3/4) in ANKL cases, suggesting that these aberrations may contribute to ANKL pathogenesis.
Interlaboratory Variability in the Histologic Grading of Colorectal Adenocarcinomas in a Nationwide Cohort
Authors: Kuijpers Chantal C.H.J. , Sluijter Caro E. , von der Thüsen Jan H. , Grünberg Katrien , van Oijen Martijn G.H. , van Diest Paul J. , Jiwa Mehdi , Nagtegaal Iris D. , Overbeek Lucy I.H. , Willems Stefan M.
Published: March 2016

Differentiation grade of colorectal adenocarcinoma (CRC) is a prognostic factor and important for therapy selection. In patients with stage II colon cancer, poor differentiation is an indication for adjuvant chemotherapy. The variability in daily practice in the grading of CRC was assessed in a nationwide cohort. Using the Dutch Pathology Registry (PALGA), all synoptically reported CRC resections from 2010 to 2013 were identified. Proportions of poorly differentiated (PD) adenocarcinomas were determined and compared between 35 laboratories by univariable and multivariable logistic regression analyses. In total, 11,719 resections of 11,681 patients were included, of which 1427 (12.2%) were PD (range between 35 laboratories: 5.0% to 33.2%). After adjustment for case mix, 4 (11%) laboratories still reported a significantly lower (n=2) or higher (n=2) proportion of PD adenocarcinoma compared with the reference laboratory. Seven of 8 investigated laboratories showed considerable intralaboratory variation between pathologists as well. In a subgroup of 2812 patients (2813 tumors) who could have been eligible for adjuvant chemotherapy solely on the basis of the differentiation grade (stage II colon cancer patients without other high-risk factors [ie, T4, <10 lymph nodes evaluated, perforation, ileus, or angioinvasion]), 258 (9.2%) were PD (range between laboratories: 0% to 22.7%). In this subgroup, 4 laboratories still diagnosed significantly more PD adenocarcinomas after multivariable logistic regression analysis, increasing the number of colon cancer patients eligible for adjuvant therapy. In conclusion, this large nationwide cohort demonstrates considerable interlaboratory and intralaboratory variation in differentiation grading of CRC. Better standardization of grading criteria is needed for optimal determination of prognosis and treatment selection.
Diagnostic Challenges Caused by Endoscopic Biopsy of Colonic Polyps
Authors: Panarelli Nicole C. , Somarathna Thusitha , Samowitz Wade S. , Kornacki Susan , Sanders Scott A. , Novelli Marco R. , Shepherd Neil A. , Yantiss Rhonda K.
Published: March 2016

Endoscopic mucosal biopsy may misplace mucosal elements into the submucosa of colonic adenomas, mimicking invasive adenocarcinoma. Biopsy-related misplacement can be more challenging to recognize than typical misplaced epithelium (pseudoinvasion) in pedunculated polyps. We compared the features of 16 polyps with biopsy-related misplaced epithelium with those of 10 adenomas with pseudoinvasion and 10 adenomas with invasive adenocarcinoma and performed Ki67 and p53 immunostaining on all cases. Features of misplaced epithelium in polyps referred to the Bowel Cancer Screening Program Expert Board in the United Kingdom were also evaluated for the same morphologic features. Biopsy-related epithelial misplacement occurred in adenomas throughout the colon and often appeared infiltrative (69%), including epithelial cells singly dispersed within reactive fibroinflammatory stroma or granulation tissue (44%). Misplaced epithelium displayed only low-grade cytologic features and was associated with extruded mucin (75%), tattoo pigment (63%), and misplaced normal glands (38%); scant lamina propria and muscularis mucosae were often present (88% and 44%, respectively). Cases referred to the Bowel Cancer Screening Program Expert Board also contained infiltrative-appearing misplaced epithelium (91%) that was cytologically low grade (72%), contained nondysplastic glands (11%), and showed other signs of injury. In contrast, misplaced epithelium in pedunculated polyps always had a lobular contour with a rim of lamina propria, hemorrhage, and/or hemosiderin. Invasive carcinomas showed malignant cytology and desmoplasia; most (70%) lacked features of trauma. Ki67 and p53 staining was patchy and weak in the misplaced epithelium, whereas invasive carcinomas showed increased staining for one or both markers. Pathologists should be aware that endoscopically manipulated adenomas may contain misplaced epithelium that simulates malignancy.
CD1a Reactivity in Non-neoplastic Adenohypophysis
Authors: Pisapia David J. , Rosenblum Marc K. , Lavi Ehud
Published: March 2016

Within the differential diagnosis of patients presenting with sellar or suprasellar lesions is Langerhans cell histiocytosis (LCH). CD1a staining is frequently used to identify the presence of an abnormal proliferation of Langerhans cells on histologic sections and contributes to the diagnosis of LCH. Here, we report that the MTB-1 monoclonal antibody against the CD1a antigen reacts to native adenohypophyseal epithelial cells. We show that immunohistochemistry for CD1a exhibits strong positivity in all autopsy and surgically resected non-neoplastic adenohypophysis tested. Thus, CD1a positivity by itself should be interpreted with caution, and we recommend the routine use of a panel of stains including CD1a, Langerin, and synaptophysin in conjunction with morphologic analysis before a diagnosis of LCH is rendered. In addition, we find that pituitary adenomas fail to stain for CD1a prompting consideration of the utility of this stain as a marker for non-neoplastic gland.
On Shaky Ground
Authors: Whitney Rachel E. , Burke Rita V. , Lehman-Huskamp Kathy , Arora Gitanjli , Park Daniel B. , Cicero Mark X.
Published: March 2016

Objective

The aim of this study was to evaluate residents' confidence and attitudes related to management of earthquake victims during a tabletop simulation and 6 months after the intervention.

Methods

Pediatric residents from 4 training programs were recruited via e-mail. The tabletop simulation involved 3 pediatric patients (crush injury, head injury, and a nonverbal patient with minor injuries). A facilitated debriefing took place after the simulation. The same simulation was repeated 6 months later. A survey was administered before the simulation, immediately after, and after the 6-month repeat simulation to determine participants' self-rated confidence and willingness to respond in the event of a disaster. A 5-point Likert scale that ranged through novice, advanced beginner, competent, proficient, and expert was used.

Results

Ninety-nine participants completed the survey before the initial simulation session. Fifty-one residents completed the immediate postsurvey, and 75 completed the 6-month postsurvey. There was a statistically significant improvement in self-rated confidence identifying and managing victims of earthquake disasters after participating in the simulation, with 3% rating themselves as competent on the presurvey and 33% rating themselves as competent on the postsurvey (P < 0.05). There was a nonstatistically significant improvement in confidence treating suspected traumatic head injury as well as willingness to deploy to both domestic and international disasters.

Conclusions

Tabletop simulation can improve resident comfort level with rare events, such as caring for children in the aftermath of an earthquake. Tabletop can also be easily integrated into resident curriculum and may be an effective way to provide disaster medical response training for trainees.
Involvement of Chromosome 8 in Müllerian Adenosarcoma
Authors: Howitt Brooke E. , Dal Cin Paola , Nucci Marisa R. , Quade Bradley J.
Published: March 2016

Müllerian adenosarcoma (MA) is an uncommon biphasic neoplasm of the female genital tract, composed of malignant stroma and benign epithelium. Little is known about the molecular and cytogenetic aberrations in MA pathogenesis, including those with progression to sarcomatous overgrowth (SO). Herein, we report all cases of MA in which karyotyping was attempted at our institution. Twenty-one samples from 20 subjects consisted of 15 primary (7 without SO, 8 with SO) and 6 metastatic MA, were cytogenetically investigated in our institution. Karyotypes were successfully obtained in 14/21 (67%) cases and 9 (45%) had cytogenetic aberrations. Two (1 MA with SO and 1 metastatic MA) were markedly complex, displaying extreme aneuploidy with numerous rearrangements. Seven (2 MA without SO, 3 MA with SO, and 2 metastatic MA) demonstrated noncomplex clonal aberrations, of which 5 (71%) included an abnormality involving chromosome 8. Two tumors had rearrangements at 8q13 and another 3 tumors had extra copies of chromosome 8. In 5 cases, a normal karyotype (46,XX) was obtained (2 MA without SO, 2 MA with SO, and 1 metastatic MA). Further study is warranted to explore the genetic mechanism by which chromosome abnormalities, particularly those at 8q13, contribute to MA tumorigenesis.
The Effect of Dolutegravir on the Pharmacokinetics of Metformin in Healthy Subjects
Authors: Song Ivy H. , Zong Jian , Borland Julie , Jerva Fred , Wynne Brian , Zamek-Gliszczynski Maciej J. , Humphreys Joan E. , Bowers Gary D. , Choukour Mike
Published: March 2016

Background:

Dolutegravir is an integrase strand transfer inhibitor (INSTI) licensed for use in HIV-1 infection and is an inhibitor of organic cation transporter 2 (OCT2). This study assessed the effect of dolutegravir on the pharmacokinetics of metformin, an OCT2 substrate.

Design:

This was an open-label, parallel-group, 3-period crossover study in healthy adult subjects. Subjects were enrolled into 1 of 2 treatment cohorts (15 subjects/cohort) receiving metformin 500 mg q12h for 5 days in period 1; metformin 500 mg q12h plus dolutegravir 50 mg q24h (cohort 1) or 50 mg q12h (cohort 2) for 7 days in period 2; and metformin 500 mg q12h for 10 days in period 3. There were no washout periods between treatments. Effects of dolutegravir on metformin transport and paracellular permeability were evaluated in vitro.

Results:

Co-administration of dolutegravir 50 mg q24h increased metformin area under the curve(0–τ) by 79% and Cmax by 66%, whereas dolutegravir 50 mg q12h increased metformin area under the curve(0–τ) and Cmax by 145% and 111%, respectively. Metformin t(1/2) remained unchanged. Increased metformin exposure during dolutegravir co-administration returned to period 1 levels after dolutegravir discontinuation in period 3. Co-administration of dolutegravir and metformin was well tolerated. In vitro, dolutegravir was not a clinically relevant inhibitor of OCT1, OCT3, multidrug and toxin extrusion protein 1, multidrug and toxin extrusion protein 2-K, or plasma membrane monoamine transporter, and it did not affect metformin paracellular permeability or uptake into an intestinal cell line.

Conclusions:

Dolutegravir significantly increased metformin plasma exposure, which can be partially explained by OCT2 inhibition. It is recommended that dose adjustments of metformin be considered to maintain optimal glycemic control when patients are starting/stopping dolutegravir while taking metformin.
Implementation and Operational Research: A Cost-Effective, Clinically Actionable Strategy for Targeting HIV Preexposure Prophylaxis to High-Risk Men Who Have Sex With Men
Authors: Ross Eric L. , Cinti Sandro K. , Hutton David W.
Published: March 2016

Background:

Preexposure prophylaxis (PrEP) is effective at preventing HIV infection among men who have sex with men (MSM), but there is uncertainty about how to identify high-risk MSM who should receive PrEP.

Methods:

We used a mathematical model to assess the cost-effectiveness of using the HIV Incidence Risk Index for MSM (HIRI-MSM) questionnaire to target PrEP to high-risk MSM. We simulated strategies of no PrEP, PrEP available to all MSM, and eligibility thresholds set to HIRI-MSM scores between 5 and 45, in increments of 5 (where a higher score predicts greater HIV risk). Based on the iPrEx, IPERGAY, and PROUD trials, we evaluated PrEP efficacies from 44% to 86% and annual costs from $5900 to 8700. We designate strategies with incremental cost-effectiveness ratio (ICER) ≤$100,000/quality-adjusted life-year (QALY) as “cost-effective.”

Results:

Over 20 years, making PrEP available to all MSM is projected to prevent 33.5% of new HIV infections, with an ICER of $1,474,000/QALY. Increasing the HIRI-MSM score threshold reduces the prevented infections, but improves cost-effectiveness. A threshold score of 25 is projected to be optimal (most QALYs gained while still being cost-effective) over a wide range of realistic PrEP efficacies and costs. At low cost and high efficacy (IPERGAY), thresholds of 15 or 20 are optimal across a range of other input assumptions; at high cost and low efficacy (iPrEx), 25 or 30 are generally optimal.

Conclusions:

The HIRI-MSM provides a clinically actionable means of guiding PrEP use. Using a score of 25 to determine PrEP eligibility could facilitate cost-effective use of PrEP among high-risk MSM who will benefit from it most.
The Risk of Cardiovascular Disease Is Not Increasing Over Time Despite Aging and Higher Comorbidity Burden of Kidney Transplant Recipients
Authors: Lam Ngan N. , Kim S. Joseph , Knoll Gregory A. , McArthur Eric , Lentine Krista L. , Naylor Kyla L. , Li Alvin H. , Shariff Salimah Z. , Ribic Christine M. , Garg Amit X.
Published: March 2016

Background

Cardiovascular death remains the leading cause of mortality in kidney transplant recipients. Cardiovascular events are associated with significant morbidity. However, current trends in cardiovascular events after kidney transplantation are poorly understood.

Methods

We conducted a retrospective study using healthcare databases in Ontario, Canada, to determine whether the incidence of cardiovascular events after kidney transplantation has changed from 1994 to 2009. Our primary endpoint was a 3-year composite outcome of posttransplant death or major cardiovascular event (myocardial infarction, coronary angioplasty, coronary artery bypass graft surgery, stroke).

Results

Recipients (n = 4954) were older and had more baseline comorbidity in recent years. A total of 445 recipients (9.0%) died or experienced a major cardiovascular event within 3 years of transplantation. There was no significant change in the incidence of the composite outcome or death-censored cardiovascular events over time (P = 0.41 and 0.92, respectively). After adjusting for age, sex, and comorbidities, the risk of death or major cardiovascular event steadily declined across the years of transplant (2006-2009 adjusted hazard ratio, 0.70; P = 0.009; referent 1994-1997). When recipients were matched on age, sex, and date of cohort entry to members of the general population and to the chronic kidney disease population, the risk was lowest in the general population and highest in the chronic kidney disease population.

Conclusion

Despite transplant centers accepting recipients who are older with more comorbidities in recent years, the 3-year cumulative incidence of death or major cardiovascular event has remained stable over time.
Probing the causal role of prestimulus interregional synchrony for perceptual integration via tACS
Authors: Stonkus Rolandas , Braun Verena , Kerlin Jess , Volberg Gregor , Hanslmayr Simon
Published: March 2016

The phase of prestimulus oscillations at 7-10 Hz has been shown to modulate perception of briefly presented visual stimuli. Specifically, a recent combined EEG-fMRI study suggested that a prestimulus oscillation at around 7 Hz represents open and closed windows for perceptual integration by modulating connectivity between lower order occipital and higher order parietal brain regions. We here utilized brief event-related transcranial alternating current stimulation (tACS) to specifically modulate this prestimulus 7 Hz oscillation, and the synchrony between parietal and occipital brain regions. To this end we tested for a causal role of this particular prestimulus oscillation for perceptual integration. The EEG was acquired at the same time allowing us to investigate frequency specific after effects phase-locked to stimulation offset. On a behavioural level our results suggest that the tACS did modulate perceptual integration, however, in an unexpected manner. On an electrophysiological level our results suggest that brief tACS does induce oscillatory entrainment, as visible in frequency specific activity phase-locked to stimulation offset. Together, our results do not strongly support a causal role of prestimulus 7 Hz oscillations for perceptual integration. However, our results suggest that brief tACS is capable of modulating oscillatory activity in a temporally sensitive manner.
Epidemiological analysis of psoriatic arthritis patients in Japan
Authors: Yamamoto Toshiyuki , Ohtsuki Mamitaro , Sano Shigetoshi , Igarashi Atsuyuki , Morita Akimichi , Okuyama Ryuhei , Kawada Akira ,   the Working Group of the Epidemiological Survey in the Japanese Society for Psoriasis Research
Published: March 2016

To determine the current status of psoriatic arthritis, we conducted a retrospective survey by sending questionnaires. The newly visited psoriatic arthritis patients accounted for 10.5% (95% confidence interval, 7.9–13%) of all newly visited psoriasis patients (n = 2581) between April 2014 and March 2015 in 73 institutes. Additionally, questionnaires on detailed patients’ information were returned by 92 institutes (response rate, 70.8%), where 1282 patients with psoriatic arthritis were identified. There was a male predominance. The mean onset age of psoriatic arthritis was 44.9 years, and mean onset age for cutaneous psoriasis (36.4 years) was lower than that for arthritis (45.1 years). The mean duration in patients who developed psoriasis prior to arthritis was 11.2 years, while that in patients preceded by arthritis was 4.4 years. According to the Moll and Wright criteria, polyarthritis type was most common (36%), followed by distal interphalangeal type (26%) and oligoarthritis type (22%). Peripheral joint pain was 61.5%, back pain such as lumbago and neck pain was 34.3%. Enthesitis and dactylitis were observed in 28.3% and 59.2%, respectively. Biologics were used in 55.5% of psoriatic arthritis patients, and 31% used disease‐modifying antirheumatic drugs. In conclusion, the ratio of psoriatic arthritis in Japan is increasing, and nearly 10% of new psoriasis patients had psoriatic arthritis. This study shows the current status of psoriatic arthritis in Japan, including several unexpected findings such as male predominance, longer duration between the onset of cutaneous psoriasis and arthritis, and dominance of polyarthritis.
Variation and association of fibronectin‐binding protein genes fnbA and fnbB in Staphylococcus aureus Japanese isolates
Authors: Murai Miyo , Moriyama Hideaki , Hata Eiji , Takeuchi Fumihiko , Amemura‐Maekawa Junko
Published: March 2016

Fibronectin‐binding proteins A and B (FnBPA and FnBPB) mediate adhesion of Staphylococcus aureus to fibrinogen, elastin and fibronectin. FnBPA and FnBPB are encoded by two closely linked genes, fnbA and fnbB, respectively. With the exception of the N‐terminal regions, the amino acid sequences of FnBPA and FnBPB are highly conserved. To investigate the genetics and evolution of fnbA and fnbB, the most variable regions, which code for the 67th amino acids of the A through B regions (A67–B) of fnbA and fnbB, were focused upon. Eighty isolates of S. aureus in Japan were sequenced and 19 and 18 types in fnbA and fnbB, respectively, identified. Although the phylogeny of fnbA and fnbB were found to be quite different, each fnbA type connected with a specific fnbB type, indicating that fnbA and fnbB mutate independently, whereas the combination of both genes after recombination is stable. Hence those fnbA–fnbB combinations were defined as FnBP sequence types (FnSTs). Representative isolates of each FnST were assigned distinct STs by multilocus sequence typing, suggesting correspondence of FnST with genome lineage. Linkage disequilibrium (LD) analysis of the A67–B region revealed that subdomains N2, N3 and FnBR1 form a LD block in fnbA, whereas N2 and N3 form two independent LD blocks in fnbB. N2–N3 three‐dimensional structural models indicated that not only the variable amino acid residues, but also well‐conserved amino acid residues between FnBPA and FnBPB, are located on the surface of the protein. These results highlight a molecular process of the FnBP that has evolved by mingled mutation and recombination with retention of functions.
Food availability and predation risk, rather than intrinsic attributes, are the main factors shaping the reproductive decisions of a long‐lived predator
Authors: Hoy Sarah R. , Millon Alexandre , Petty Steve J. , Whitfield D. Philip , Lambin Xavier
Published: March 2016

Deciphering the causes of variation in reproductive success is a fundamental issue in ecology, as the number of offspring produced is an important driver of individual fitness and population dynamics. Little is known, however, about how different factors interact to drive variation in reproduction, such as whether an individual's response to extrinsic conditions (e.g. food availability or predation) varies according to its intrinsic attributes (e.g. age, previous allocation of resources towards reproduction).

We used 29 years of reproductive data from marked female tawny owls and natural variation in food availability (field vole) and predator abundance (northern goshawk) to quantify the extent to which extrinsic and intrinsic factors interact to influence owl reproductive traits (breeding propensity, clutch size and nest abandonment).

Extrinsic and intrinsic factors appeared to interact to affect breeding propensity (which accounted for 83% of the variation in owl reproductive success). Breeding propensity increased with vole density, although increasing goshawk abundance reduced the strength of this relationship. Owls became slightly more likely to breed as they aged, although this was only apparent for individuals who had fledged chicks the year before.

Owls laid larger clutches when food was more abundant. When owls were breeding in territories less exposed to goshawk predation, 99·5% of all breeding attempts reached the fledging stage. In contrast, the probability of breeding attempts reaching the fledging stage in territories more exposed to goshawk predation depended on the amount of resources an owl had already allocated towards reproduction (averaging 87·7% for owls with clutches of 1–2 eggs compared to 97·5% for owls with clutches of 4–6 eggs).

Overall, our results suggested that changes in extrinsic conditions (predominantly food availability, but also predator abundance) had the greatest influence on owl reproduction. In response to deteriorating extrinsic conditions (fewer voles and more goshawks), owls appeared to breed more frequently, but allocated fewer resources per breeding attempt. However, intrinsic attributes also appeared to have a relatively small influence on how an individual responded to variation in extrinsic conditions, which indicates that owl reproductive decisions were shaped by a complex series of extrinsic and intrinsic trade‐offs.
Overwintering strategies of migratory birds: a novel approach for estimating seasonal movement patterns of residents and transients
Authors: Ruiz‐Gutierrez Viviana , Kendall William L. , Saracco James F. , White Gary C.
Published: March 2016

Our understanding of movement patterns in wildlife populations has played an important role in current ecological knowledge and can inform landscape conservation decisions. Direct measures of movement can be obtained using marked individuals, but this requires tracking individuals across a landscape or multiple sites.

We demonstrate how movements can be estimated indirectly using single‐site, capture–mark–recapture (CMR) data with a multi‐state open robust design with state uncertainty model (MSORD‐SU). We treat residence and transience as two phenotypic states of overwintering migrants and use time‐ and state‐dependent probabilities of site entry and persistence as indirect measures of movement. We applied the MSORD‐SU to data on eight species of overwintering Neotropical birds collected in 14 countries between 2002 and 2011. In addition to entry and persistence probabilities, we estimated the proportions of residents at a study site and mean residence times.

We identified overwintering movement patterns and residence times that contrasted with prior categorizations of territoriality. Most species showed an evidence of residents entering sites at multiple time intervals, with transients tending to enter between peak resident movement times. Persistence and the proportion of residents varied by latitude, but were not always positively correlated for a given species.

Synthesis and applications. Our results suggest that migratory songbirds commonly move among habitats during the overwintering period. Substantial proportions of populations appear to be comprised of transient individuals, and residents tend to persist at specific sites for relatively short periods of time. This information on persistence and movement patterns should be explored for specific habitats to guide landscape management on the wintering grounds, such as determining which habitats are conserved or restored as part of certification programmes of tropical agroforestry crops. We suggest that research and conservation efforts on Neotropical migrant songbirds focus on identifying landscape configurations and regional habitat networks that support these diverse overwintering strategies to secure full life cycle conservation.
Where, why and how? Explaining the low‐temperature range limits of temperate tree species
Authors: Körner Christian , Basler David , Hoch Günter , Kollas Chris , Lenz Armando , Randin Christophe F. , Vitasse Yann , Zimmermann Niklaus E.
Published: March 2016

Attempts at explaining range limits of temperate tree species still rest on correlations with climatic data that lack a physiological justification. Here, we present a synthesis of a multidisciplinary project that offers mechanistic explanations. Employing climatology, biogeography, dendrology, population and reproduction biology, stress physiology and phenology, we combine results from in situ elevational (Swiss Alps) and latitudinal (Alps vs. Scandinavia) comparisons, from reciprocal common garden and phytotron studies for eight European broadleaf tree species.

We show that unlike for low‐stature plants, tree canopy temperatures can be predicted from weather station data, and that low‐temperature extremes in winter do not explain range limits. At the current low‐temperature range limit, all species recruit well. Transplants revealed that the local environment rather than elevation of seed origin dominates growth and phenology. Tree ring width at the range limit is not related to season length, but to growing season temperature, with no evidence of carbon shortage. Bud break and leaf emergence in adults trees are timed in such a way that the probability of freezing damage is almost zero, with a uniform safety margin across elevations and taxa. More freezing‐resistant species flush earlier than less resistant species.

Synthesis: we conclude that the range limits of the examined tree species are set by the interactive influence of freezing resistance in spring, phenology settings, and the time required to mature tissue. Microevolution of spring phenology compromises between demands set by freezing resistance of young, immature tissue and season length requirements related to autumnal tissue maturation.
Inhibition of platelet aggregation by vanilloid‐like agents is not mediated by transient receptor potential vanilloid‐1 channels or cannabinoid receptors
Authors: Almaghrabi Safa , Geraghty Dominic , Ahuja Kiran , Adams Murray
Published: March 2016

Vanilloid‐like agents, including capsaicin, N‐arachidonoyl‐dopamine and N‐oleoyldopamine inhibit platelet aggregation, however little is known about the precise mechanism(s) of action. The authors have previously shown that blocking of the capsaicin receptor, transient receptor potential vanilloid‐1 (TRPV1), does not interfere with capsaicin action during adenosine diphosphate (ADP)‐induced aggregation. This research is extended to investigate the effect of these vanilloid‐like‐agents on platelet count, and to test whether the effect of these agents is mediated through TRPV1 and/or cannabinoid (CB1 and CB2) receptors in the presence of other agonists, including collagen and arachidonic acid. Incubation of platelets with each of the individual vanilloids, or with receptor antagonists of TRPV1 (SB452533), CB1 (AM251) and CB2 (AM630), for up to 2 h did not significantly affect the platelet count. Similarly, the effect of individual vanilloids on the inhibition of platelet aggregation was not significantly different in the presence of receptor agonists compared to control, irrespective of the agonist used, suggesting that the inhibitory effect of vanilloids on platelet aggregation is independent of TRPV1, CB1 and CB2 receptors. Further research on the antiplatelet activity of vanilloids should focus on mechanisms other than those associated with vanilloid receptors.
The Impact of Funding Modalities on the Performance of Indigenous Organisations
Authors: Moran Mark , Porter Doug , Curth‐Bibb Jodie
Published: March 2016

Governments’ choice of funding modality can produce powerful incentives for organisations to perform in preferred ways, but it can also divert limited resources, narrow accountability, and undermine capability. Through literature review and interviews, the research explored the international literature on public finance management in developing country contexts, and compared this to case studies of Indigenous organisations. The situation in Australia was found to differ in three ways: (1) performance indicators are imposed, rather than negotiated; (2) few existing public funding modalities reward performance or provide incentives; and (3) funding arrangements do not generally require receiving organisations to be accountable to their constituents. Stability and durability of funding modalities, and clarity in functions and jurisdictional boundaries, were also found to positively influence performance. Further research is required to design new performance frameworks that build around the organisation, rather than the grant, with indicators of governance capability and downward accountability to constituents.
Gender-Based Violence and Young Homeless Women: Femininity, Embodiment and Vicarious Physical Capital
Authors: Watson Juliet
Published: March 2016

This article discusses how the gender-based violence of homelessness contributes to young women engaging in bodily alliances with men as a strategy for physical protection. The embedding of individualized and postfeminist discourses through the conditions of neoliberalism and the structural disadvantage of homelessness have meant that young women are required to adopt self-regulatory practices and take personal responsibility for their physical safety. Drawing on Bourdieu's social capital theory and its development by Skeggs and Shilling, and based on qualitative research undertaken with fifteen young women who had experienced homelessness in Australia, I suggest that feminine capital is mobilized through necessity by young homeless women through the formation and maintenance of intimate relationships with men to access a sense of safety in an environment that is hostile to the female body. However, as the narratives presented here demonstrate, the value and privilege ascribed to (certain) male bodies is only accessible vicariously to young women, it is inherently precarious, it can undermine access to other types of capital and these intimate relationships can also be a source of gender-based violence.
Reduction in remoteness distinctions and reconfiguration in the Bemba past tense
Authors: Kula Nancy C.
Published: March 2016

Bantu languages are well‐known for having multiple remoteness distinctions in both the past and the future. This paper looks at the 4‐way remoteness distinction of Bemba (central Bantu) showing that the system is undergoing change that is resulting in the loss of an intermediate past tense, by merger with the remote past. Two factors are central in driving this change; a merger of forms by tone loss and neutralisation and a shift in the scope of semantic function. Because the Bemba tense‐aspect system manifests the so‐called conjoint‐disjoint alternation, there is also some reconfiguration of theTAsystem that accompanies the merger. The different factors involved in this change are unified under a cognitive multi‐dimensional approach to tense, which is here extended to account for language change in tense systems.
Internationalisation of the Renminbi as an Investing and a Funding Currency: Analytics and Prospects
Authors: He Dong , Luk Paul , Zhang Wenlang
Published: March 2016

This paper develops a three‐currency model to study the determinants of the demand for assets and liabilites denominated in an international currency and to shed light on the prospects for the renminbi as a budding international currency. We show that interest rate differentials would be only one of the factors shaping the renminbi's position, while other factors, including the correlation between foreign countries' economic growth and their bilateral exchange rates against the renminbi, and the correlation between exchange rates of the renminbi with other international currencies, would also be important. A broad interpretation of these findings is that the renminbi will likely be attractive to investors from high‐income economies and fund‐raisers from emerging market economies.
Potentially Avoidable Hospitalizations among People at Different Activity of Daily Living Limitation Stages
Authors: Schüssler‐Fiorenza Rose Sophia Miryam , Stineman Margaret G. , Pan Qiang , Bogner Hillary , Kurichi Jibby E. , Streim Joel E. , Xie Dawei
Published: March 2016

Objective

To determine whether higher activity of daily living (ADL) limitation stages are associated with increased risk of hospitalization, particularly for ambulatory care sensitive (ACS) conditions.

Data Source

Secondary data analysis, including 8,815 beneficiaries from 2005 to 2006 Medicare Current Beneficiary Survey (MCBS).

Study Design

ADLlimitation stages (0‐IV) were determined at the end of 2005. Hospitalization rates were calculated for 2006 and age adjusted using direct standardization. Multivariate negative binomial regression, adjusting for baseline demographic and health characteristics, with the outcome hospitalization count was performed to estimate the adjusted rate ratio of ACS and non‐ACS hospitalizations for beneficiaries with ADL stages > 0 compared to beneficiaries without limitations.

Data Collection

BaselineADLstage and health conditions were assessed using 2005MCBSdata and count of hospitalization determined using 2006MCBSdata.

Principal Findings

Referenced to stage 0, the adjusted rate ratios (95 percent confidence interval) for stage I to stageIVranged from 1.9 (1.4–2.5) to 4.1 (2.2–7.8) forACShospitalizations compared with from 1.6 (1.3–1.9) to 1.8 (1.4–2.5) for non‐ACShospitalizations.

Conclusions

Hospitalization rates forACSconditions increased more dramatically withADLlimitation stage than did rates for non‐ACSconditions. Adults withADLlimitations appear particularly vulnerable to potentially preventable hospitalizations for conditions typically manageable in ambulatory settings.
Has Interprofessional Education Changed Learning Preferences? A National Perspective
Authors: Kashner T. Michael , Hettler Debbie L. , Zeiss Robert A. , Aron David C. , Bernett David S. , Brannen Judy L. , Byrne John M. , Cannon Grant W. , Chang Barbara K. , Dougherty Mary B. , Gilman Stuart C. , Holland Gloria J. , Kaminetzky Catherine P. , Wicker Annie B. , Keitz Sheri A.
Published: March 2016

Objective

To assess how changes in curriculum, accreditation standards, and certification and licensure competencies impacted how medical students and physician residents value interprofessional team and patient‐centered care.

Primary Data Source

The Department of Veterans Affairs Learners’ Perceptions Survey (2003–2013). The nationally administered survey asked a representative sample of 56,569 U.S. medical students and physician residents, with a comparison group of 78,038 nonphysician trainees, to rate satisfaction with 28 elements, in two overall domains, describing their clinical learning experiences at VA medical centers.

Study Design

Value preferences were scored as independent adjusted associations between an element (interprofessional team, patient‐centered preceptor) and the respective overall domain (clinical learning environment, faculty, and preceptors) relative to a referent element (quality of clinical care, quality of preceptor).

Principal Findings

Physician trainees valued interprofessional (14 percent vs. 37 percent, p < .001) and patient‐centered learning (21 percent vs. 36 percent, p < .001) less than their nonphysician counterparts. Physician preferences for interprofessional learning showed modest increases over time (2.5 percent/year, p < .001), driven mostly by internal medicine and surgery residents. Preferences did not increase with trainees’ academic progress.

Conclusions

Despite changes in medical education, physician trainees continue to lag behind their nonphysician counterparts in valuing experience with interprofessional team and patient‐centered care.
Bank Competition: Measurement, Decision‐Making, and Risk‐Taking
Authors: BUSHMAN ROBERT M. , HENDRICKS BRADLEY E. , WILLIAMS CHRISTOPHER D.
Published: March 2016

This paper investigates whether greater competition increases or decreases individual bank and banking system risk. Using a new text‐based measure of competition, and an instrumental variables analysis that exploits exogenous variation in bank deregulation, we provide robust evidence that greater competition increases both individual bank risk and a bank's contribution to system‐wide risk. Specifically, we find that higher competition is associated with lower underwriting standards, less timely loan loss recognition, and a shift toward noninterest revenue. Further, we find that higher competition is associated with higher stand‐alone risk of individual banks, greater sensitivity of a bank's downside equity risk to system‐wide distress, and a greater contribution by individual banks to downside risk of the banking sector.