bluuebunny/crossref_metadata_2025 huggingface dataset:
A phase I study of TRC105 anti‐endoglin (CD105) antibody in metastatic castration‐resistant prostate cancer
Authors: Karzai Fatima H. , Apolo Andrea B. , Cao Liang , Madan Ravi A. , Adelberg David E. , Parnes Howard , McLeod David G. , Harold Nancy , Peer Cody , Yu Yunkai , Tomita Yusuke , Lee Min‐Jung , Lee Sunmin , Trepel Jane B. , Gulley James L. , Figg William D. , Dahut William L.
Published: November 2014

Objective

TRC105 is a chimeric immunoglobulin G1 monoclonal antibody that binds endoglin (CD105). This phase I open‐label study evaluated the safety, pharmacokinetics and pharmacodynamics of TRC105 in patients with metastatic castration‐resistant prostate cancer (mCRPC).

Patients and Methods

Patients with mCRPC received escalating doses of i.v. TRC105 until unacceptable toxicity or disease progression, up to a predetermined dose level, using a standard 3 + 3 phase I design.

Results

A total of 20 patients were treated. The top dose level studied, 20 mg/kg every 2 weeks, was the maximum tolerated dose. Common adverse effects included infusion‐related reaction (90%), low grade headache (67%), anaemia (48%), epistaxis (43%) and fever (43%). Ten patients had stable disease on study and eight patients had declines in prostate specific antigen (PSA). Significant plasma CD105 reduction was observed at the higher dose levels. In an exploratory analysis, vascular endothelial growth factor (VEGF) was increased after treatment with TRC105 and VEGF levels were associated with CD105 reduction.

Conclusion

TRC105 was tolerated at 20 mg/kg every other week with a safety profile distinct from that of VEGF inhibitors. A significant induction of plasma VEGF was associated with CD105 reduction, suggesting anti‐angiogenic activity of TRC105. An exploratory analysis showed a tentative correlation between the reduction of CD105 and a decrease in PSA velocity, suggestive of potential activity of TRC105 in the patients with mCRPC. The data from this exploratory analysis suggest that rising VEGF level is a possible compensatory mechanism for TRC105‐induced anti‐angiogenic activity.
Prognostic Relevance of Histomolecular Classification of Diffuse Adult High‐Grade Gliomas with Necrosis
Authors: Figarella‐Branger Dominique , Mokhtari Karima , Colin Carole , Uro‐Coste Emmanuelle , Jouvet Anne , Dehais Caroline , Carpentier Catherine , Villa Chiara , Maurage Claude‐Alain , Eimer Sandrine , Polivka Marc , Vignaud Jean‐Michel , Laquerriere Annie , Sevestre Henri , Lechapt‐Zalcman Emmanuelle , Quintin‐Roué Isabelle , Aubriot‐Lorton Marie‐Hélène , Diebold Marie‐Danièle , Viennet Gabriel , Adam Clovis , Loussouarn Delphine , Michalak Sophie , Rigau Valérie , Heitzmann Anne , Vandenbos Fanny , Forest Fabien , Chiforeanu Danchristian , Tortel Marie‐Claire , Labrousse François , Chenard Marie‐Pierre , Nguyen Anh Tuan , Varlet Pascale , Kemeny Jean Louis , Levillain Pierre‐Marie , Cazals‐Hatem Dominique , Richard Pomone , Delattre Jean‐Yves ,   POLA Network
Published: November 2014

Diffuse adult high‐grade gliomas (HGGs) with necrosis encompass anaplastic oligodendrogliomas (AOs) with necrosis (grade III), glioblastomas (GBM, grade IV) and glioblastomas with an oligodendroglial component (GBMO, grade IV). Here, we aimed to search for prognostic relevance of histological classification and molecular alterations of these tumors. About 210 patients were included (63 AO, 56 GBM and 91 GBMO). GBMO group was split into “anaplastic oligoastrocytoma (AOA) with necrosis grade IV/GBMO,” restricted to tumors showing intermingled astrocytic and oligodendroglial component, and “GBM/GBMO” based on tumors presenting oligodendroglial foci and features of GBM. Genomic arrays, IDH1 R132H expression analyses and IDH direct sequencing were performed. 1p/19q co‐deletion characterized AO, whereas no IDH1 R132H expression and intact 1p/19q characterized both GBM and GBM/GBMO. AOA with necrosis/GBMO mainly demonstrated IDH1 R132H expression and intact 1p/19q. Other IDH1 or IDH2 mutations were extremely rare. Both histological and molecular classifications were predictive of progression free survival (PFS) and overall survival (OS) (P < 10−4). Diffuse adult HGGs with necrosis can be split into three histomolecular groups of prognostic relevance: 1p/19q co‐deleted AO, IDH1 R132H‐GBM and 1p/19q intact IDH1 R132H+ gliomas that might be classified as IDH1 R132H+ GBM. Because of histomolecular heterogeneity, we suggest to remove the name GBMO.
What is the impact of bisphosphonate therapy upon dental implant survival? A systematic review and meta‐analysis
Authors: Ata‐Ali Javier , Ata‐Ali Fadi , Peñarrocha‐Oltra David , Galindo‐Moreno Pablo
Published: November 2014

Objective

A systematic review and meta‐analysis are carried out to assess the scientific evidence that bisphosphonate therapy can decrease the success rate of dental implants.

Material and methods

The PubMed (Medline) database was used to search for articles published up until February 22, 2014. The meta‐analysis was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta‐analysis (PRISMA). The Newcastle–Ottawa scale (NOS) was used to assess study quality.

Results

The combinations of search terms resulted in a list of 256 titles. Fourteen finally met the inclusion criteria and were thus selected for inclusion in the systematic review. Eight studies (six retrospective and two prospective) were included in the meta‐analysis, with a total of 1288 patients (386 cases and 902 controls) and 4562 dental implants (1090 dental implants in cases and 3472 in controls). The summary odds ratio (OR = 1.43, P = 0.156) indicates that there is not enough evidence that bisphosphonates have a negative impact upon implant survival. According to the number need to harm (NNH), over 500 dental implants are required in patients receiving bisphosphonate treatment to produce a single implant failure.

Conclusion

Our results show that dental implant placement in patients receiving bisphosphonates does not reduce the dental implant success rate. On the other hand, such patients are not without complications, and risk evaluation therefore must be established on an individualized basis, as one of the most serious though infrequent complications of bisphosphonate therapy is bisphosphonate‐related osteonecrosis of the jaws. Given the few studies included in our meta‐analysis, further prospective studies involving larger sample sizes and longer durations of follow‐up are required to confirm the results obtained.
Severity and functional disability of patients with occupational contact dermatitis: validation of the German version of the Occupational Contact Dermatitis Disease Severity Index
Authors: Ofenloch Robert F. , Diepgen Thomas L. , Popielnicki Ana , Weisshaar Elke , Molin Sonja , Bauer Andrea , Mahler Vera , Elsner Peter , Schmitt Jochen , Apfelbacher Christian
Published: November 2014

Background

The Occupational Contact Dermatitis Disease Severity Index (ODDI) was designed in Australia to measure severity and functional disability in patients with occupational contact dermatitis (OCD) of the hands. The ODDI was translated into the German language with a linguistic validation process. The psychometric properties of the German version of the ODDI are still unclear.

Objectives

To report the linguistic validation procedure and to perform a psychometric validation by investigating the validity and reliability of the German ODDI version in a sample of patients with OCD.

Methods

Data were drawn from the baseline assessment (T0) and first follow‐up (T1) of the German chronic hand eczema (CHE) registry (CARPE). Spearman correlations of the ODDI with reference measures were computed to assess validity. Cronbach's alpha was calculated as a measure of internal consistency, and the intraclass correlation coefficient (ICC) was calculated to assess retest reliability. The smallest real difference (SRD) and minimal clinically important difference (MCID) were calculated to assess sensitivity to change. Physician Global Assessment (PGA) was used as an anchor for the MCID.

Results

Four hundred and twenty‐two patients (54.5% female, mean age 45.1 years) were included for analysis. Cronbach's alpha was found to be 0.73. The ICC was 0.79. Correlations between the ODDI total and the Dermatology Life Quality Index (rho = 0.36), and between PGA (rho = 0.48) and patient‐assessed disease severity (rho = 0.40), were of moderate strength. The MCID (1.29) was found to be smaller than the SRD (1.87).

Conclusions

The German ODDI version is reliable and valid for the measurement of functional impairment and disease severity in patients suffering from OCD.
Association between cobalt allergy and dermatitis caused by leather articles – a questionnaire study
Authors: Bregnbak David , Thyssen Jacob P. , Zachariae Claus , Menné Torkil , Johansen Jeanne D.
Published: November 2014

Background

Cobalt is a strong skin sensitizer and a prevalent contact allergen. Recent studies have recognized exposure to leather articles as a potential cause of cobalt allergy.

Objectives

To examine the association between contact allergy to cobalt and a history of dermatitis resulting from exposure to leather.

Methods

A questionnaire case–control study was performed: the case group consisted of 183 dermatitis patients with a positive patch test reaction to cobalt chloride and a negative patch test reaction to potassium dichromate; the control group consisted of 621 dermatitis patients who did not react to either cobalt or chromium in patch testing. Comparisons were made by use of a χ2‐test, Fisher's exact, and the Mann–Whitney test. Logistic regression analyses were used to test for associations while taking confounding factors into consideration.

Results

Leather was observed as the most frequent exposure source causing dermatitis in the case group. Although the case group significantly more often reported non‐occupational dermatitis caused by leather exposure (p < 0.001), no association was found between cobalt allergy and dermatitis caused by work‐related exposure to leather.

Conclusions

Our study suggests a positive association between cobalt allergy and a history of dermatitis caused by non‐occupational exposure to leather articles.
Are gloves sufficiently protective when hairdressers are exposed to permanent hair dyes? An in vivo study
Authors: Antelmi Annarita , Young Ewa , Svedman Cecilia , Zimerson Erik , Engfeldt Malin , Foti Caterina , Bruze Magnus
Published: November 2014

Background

The use of permanent hair dyes exposes hairdressers to contact allergens such as p‐phenylenediamine (PPD), and the preventive measures are insufficient.

Objectives

To perform an in vivo test to study the protective effect of gloves commonly used by hairdressers.

Patients/materials/methods

Six gloves from Sweden, Italy and Germany were studied: two vinyl, one natural rubber latex, two nitrile, and one polyethylene. The hair dye used for the provocation was a dark shade permanent dye containing PPD. The dye was mixed with hydrogen peroxide, and 8 PPD‐sensitized volunteers were tested with the gloves as a membrane between the hair dye and the skin in a cylindrical open chamber system. Three exposure times (15, 30 and 60 min) were used.

Results

Eczematous reactions were found when natural rubber latex, polyethylene and vinyl gloves were tested with the dye. The nitrile gloves gave good protection, even after 60 min of exposure to the hair dye.

Conclusions

Many protective gloves used by hairdressers are unsuitable for protection against the risk of elicitation of allergic contact dermatitis caused by PPD.
Acute appendicitis can be treated with single‐incision laparoscopy: a systematic review of randomized controlled trials
Authors: Vettoretto N. , Cirocchi R. , Randolph J. , Morino M.
Published: November 2014

Aim

Single‐incision laparoscopic surgery (SILS) has been proposed as the next step in minimally invasive surgery for appendicectomy. Previous reviews have summarized the results of low‐evidence comparative studies, suggesting that the two approaches are comparable in terms of outcomes but showing the need for randomized controlled trials (RCTs). This review offers a meta‐analyses of RCTs on this topic to evaluate the safety and efficacy of single‐incision laparoscopic appendectomy (SILA).

Method

A comprehensive research of electronic databases was performed. Primary outcomes (overall and access‐specific morbidity) were designated as safety issues. Secondary outcomes were pain, cosmesis, operative time, conversion rate and length of hospital stay.

Results

After exclusions, five RCTs satisfied the inclusion criteria. They included a total of 761 patients [379 SILA and 382 conventional three‐port laparoscopic appendectomies (CLA)]. No significant differences were found in overall morbidity, early wound morbidity or length of stay between SILA and CLA. Cosmesis and pain were not comparable due to different scales and time records. Conclusions on the incisional hernia rate were not reliable due to short follow‐up periods.

Conclusion

SILA can be considered an acceptable alternative to CLA in the treatment of acute appendicitis, but an economic evaluation of the various techniques for single access must be performed before its widespread clinical introduction. Better‐designed RCTs are necessary to define a population in which SILA could have major benefits.
Assessing surgeon stress when operating using heart rate variability and the State Trait Anxiety Inventory: will surgery be the death of us?
Authors: Jones K. I. , Amawi F. , Bhalla A. , Peacock O. , Williams J. P. , Lund J. N.
Published: November 2014

Aim

Performance in the operating room is affected by a combination of individual, patient and environmental factors amongst others. Stress has a potential negative impact on performance with the quality of surgical practice and patient safety being affected as a result. In order to appreciate the level of stress encountered during surgical procedures both objective and subjective methods can be used. This study reports the use of a combined objective (physiological) and subjective (psychological) method for evaluating stress experienced by the operating surgeon.

Method

Six consultant colorectal surgeons were evaluated performing eighteen anterior resections. Heart rate was recorded using a wireless chest strap at eight pre‐determined operative steps. Heart Rate Variability indices were calculated offline using computerized software. Surgeon reported stress was collected using the State Trait Anxiety Inventory, a validated clinical stress scale.

Results

A significant increase in stress was demonstrated in all surgeons whilst operating as indicated by sympathetic tone (control: 4.02 ± 2.28 vs operative: 11.42 ± 4.63; P < 0.0001). Peaks in stress according to operative step were comparable across procedures and surgeons. There was a significant positive correlation with subjective reporting of stress across procedures (r = 0.766; P = 0.0005).

Conclusion

This study demonstrates a significant increase in sympathetic tone in consultant surgeons measured using heart rate variability during elective colorectal resections. A significant correlation can be demonstrated between HRV measurements and perceived stress using the State Trait Anxiety Inventory. A combined approach to assessing operative stress is required to evaluate any effect on performance and outcomes.
Desmoplastic trichoepithelioma with pseudocarcinomatous hyperplasia: a report of three cases
Authors: McFaddin Courtney , Sirohi Deepika , Castro‐Echeverry Eduardo , Fernandez Martin P.
Published: November 2014

We report three cases of desmoplastic trichoepithelioma (DTE) with overlying pseudocarcinomatous hyperplasia. All three cases developed on the face of patients in their second decade. In spite of their young age, a diagnosis of squamous cell carcinoma was considered for each case, given the unusual juxtaposition of these two well‐known simulators of malignancy. Awareness of this potential association may avert a misdiagnosis of malignancy.
Acneiform primary cutaneous CD4‐positive small/medium pleomorphic T‐cell lymphoma with prominent necrosis
Authors: Wang Lei , Wang Gang , Gao Tianwen
Published: November 2014

Primary cutaneous CD4‐positive small/medium pleomorphic T‐cell lymphoma (SMPTCL) is an indolent form of cutaneous lymphoma that usually presents in solitary fashion and is histopathologically characterized by nodular infiltration of small‐ to medium‐sized pleomorphic T‐cells. We report the case of a patient who presented with a 5‐year history of acneiform lesions on his face. Histopathologic examination of two lesions revealed a nodular infiltrate of small to medium‐sized lymphocytes with necrosis in the dermis. The proliferating cells were positive for CD2, CD3 and CD4 and negative for CD8, CD30 and CD56. They were positive for TIA‐1 and negative for perforin and granzyme B. The Ki67 proliferation index was approximately 10%. The neoplastic cells expressed programmed death‐1 and lacked expression of CXCL‐13, bcl‐6 and CD10. In situ hybridization for Epstein–Barr virus‐encoded RNA yielded a negative result. T‐cell receptor gene rearrangement showed identical T‐lymphocyte monoclonality in both lesions. In brief, we report a rare case of acneiform SMPTCL with prominent necrosis.
A primary melanoma and its asynchronous metastasis highlight the role of BRAF, CDKN2A, and TERT
Authors: Hosler Gregory A. , Davoli Teresa , Mender Ilgen , Litzner Brandon , Choi Jaehyuk , Kapur Payal , Shay Jerry W. , Wang Richard C.
Published: November 2014

Background

Alterations in pathways including BRAF, CDKN2A, and TERT contribute to the development of melanoma, but the sequence in which the genetic alterations occur and their prognostic significance remains unclear. To clarify the role of these pathways, we analyzed a primary melanoma and its metastasis.

Methods

Immunohistochemistry for BRAF‐V600E, Sanger sequencing of BRAF and the TERT promoter, fluorescence in‐situ hybridization, and telomere analyses were performed on a primary melanoma and its asynchronous cerebellar metastasis. Using the log‐rank test and Cox‐proportional model, the cancer genome atlas (TCGA) cohort of melanomas was analyzed for the effect of BRAF mutation and CDKN2A loss on survival.

Results

The primary melanoma expressed mutant BRAF‐V600E and possessed a homozygous deletion of CDKN2A. In addition to these early defects, the metastatic lesion also possessed evidence of aneuploidy and an activating mutation of the TERT promoter. In the TCGA melanoma cohort, there was a non‐significant trend toward poor prognosis in early stage cutaneous melanoma patients with concomitant BRAF mutation and CDKN2A loss.

Conclusion

BRAF mutation and CDKN2A loss occurred early and TERT promoter mutation later in a case of lethal metastatic melanoma. The effects of these pathways on survival warrant further investigation in early stage cutaneous melanoma patients.
Ossifying plexiform tumor
Authors: Lee Solomon S. , Baker Brian L. , Gapp Joshua D.G. , Rosenberg Andrew E. , Googe Paul B.
Published: November 2014

We report a rare case of ossifying plexiform tumor in a 64‐year‐old female. The patient had a 2‐year history of gradual hardening of the right thumb pad and pain that radiated up the forearm. Physical examination showed a tender, mobile 2‐cm subcutaneous nodule distending the tip of the right thumb. The biopsy specimen showed a well‐delineated tumor with multiple lobules of epithelioid and spindled cells arranged in a plexiform pattern separated by fibrous bands and having foci of bone formation. The neoplastic cells had scant‐to‐moderate amphophilic cytoplasm with mild nuclear pleomorphism in a myxocollagenous background. No necrosis, mitoses or cytological atypicia were seen. The osteocytes present in the bone islands were bland, with occasional rimming osteoblasts. X‐ray showed stippled calcification in the soft tissue of the distal thumb without involvement of the phalanx. The patient is tumor free for 1 year after complete local excision. Only three cases of ossifying plexiform tumor have been reported. All previous cases and the current case presented as subcutaneous nodules on hand digits of females, measuring 1–2 cm in greatest dimension. Ossifying plexiform tumor appears to be a benign neoplasm with no reports of progression or metastasis.
Lipomatous variant of angiomyofibroblastoma: a case report and review of the literature
Authors: Upreti Sheela , Morine Angela , Ng Daniel , Bigby Susan M.
Published: November 2014

Angiomyofibroblastoma represents a rare, benign mesenchymal tumor with a predilection for the vulvovaginal region. Lipomatous change may occur but rarely comprises a substantial component of the lesion. There are only eight reports in the English language literature describing the lipomatous variant of this tumor. We describe a further lipomatous angiomyofibroblastoma that occurred on the labium majus of a 49‐year‐old woman. The histopathologic and immunohistochemical features are described, and the collective experience in the literature is reviewed.
Exporting National Champions: China's Outward Foreign Direct Investment Finance in Comparative Perspective
Authors: Gallagher Kevin P. , Irwin Amos
Published: November 2014

We examine the extent to which Chinese development banks have financed the globalization of China's “national champion” firms: specifically, through outward foreign direct investment (OFDI). We create a database of Chinese finance for OFDI and compare our results to the existing literature and available data on Japan, Korea and other Asian nations. We estimate the total value of China's OFDI finance from 2002 to 2012 at US$140bn. As a percentage of total OFDI, China's lending is roughly three times higher than Japan's, the previous global leader in OFDI finance. We identify two major reasons for China's high (31 percent) ratio of OFDI lending to total OFDI. First, China has a greater incentive to give OFDI loans than Japan or Korea ever did because its borrowers are state‐owned so it can more easily channel funds to targeted areas. Second, China has a greater capacity to give OFDI loans because it has significantly higher savings and foreign exchange reserves than Japan and Korea.
Financial Imbalance Index as a New Early Warning Indicator: Methods and Applications in the Chinese Economy
Authors: Ma Yong , Chen Yulu
Published: November 2014

Based on the stylized facts of financial crises and systemic risk accumulation, this paper constructs a new financial imbalance index (FII) from the perspective of endogenous financial cycles and assesses its application in China's macro‐financial analysis. The results show that the FII is not only an effective index to detect financial imbalances in China's economic cycles, but is also more accurate than and plays more of a leading role than conventional indicators, such as the consumer price index, the financial conditions index and the purchasing managers indicator. Empirical analysis shows that the FII can be used as an effective indicator to measure systemic financial risk, and can provide policy‐makers and market participants with useful information to make appropriate decisions.
Bridging the Gap between Western and Chinese Evidence in the International Education Market
Authors: Wen Wen , Luo Yan , Hu Die
Published: November 2014

Using a sample of 1674 international students in China, the present study explores sociocultural adaptation and its determinants. The results indicate that sociocultural adaptation among international students in China is largely shaped by the nature of the interaction with host nationals. In particular, among international students, those who experienced higher levels of social interaction with host nationals and received more social support were better poised for sociocultural adaptation. Rather contrary to similar research in the Western context, the study finds that international students from East Asia actually experienced more sociocultural difficulties in China than their counterparts from Western countries. These findings suggest the possibility of China and other oriental countries with sound higher education systems playing more active roles in the global higher education market.
Gender Effect in Explaining Mobility Patterns in the Labor Market: A Case Study of Turkey
Authors: Eryar Değer , Tekgüç Hasan
Published: November 2014

This paper examines the importance of gender for different job mobility patterns using an extensive household survey data from İzmir, the third largest city in Turkey. The determinants of job‐to‐job and job‐to‐nonemployment transitions are analyzed with the help of a multinomial logit estimation method. The results indicate that there is a distinction regarding the probability of job mobility patterns based on gender. It is more likely for women to be engaged in job‐to‐nonemployment transition, whereas men tend to change jobs more often. Although gender plays a significant role in job mobility patterns, traditionally imposed social constraints associated with childcare and household duties provide us with mixed results considering the behavior of women in the job market. On the other hand, having highly paid and secure jobs decreases the probability of both patterns of job mobility.
The Growth Barriers of Informal Sector Enterprises: Evidence from India
Authors: Sasidharan Subash , Rajesh Raj S. N.
Published: November 2014

The present study investigates the growth barriers of informal sector enterprises in India. The empirical analysis is based on the National Sample Survey Organization's unit‐level data for three years, 2000–2001, 2005–6, and 2010–11. The results of the study reveal: proprietary and large firms survive and grow; enterprises managed by women are less likely to decline; inadequate power supply poses a severe growth obstacle to all categories of firms; and proprietary firms encounter capital shortage while large firms are constrained by the non‐availability of raw materials. We do not find evidence of sub‐contracting acting as an enabling factor in firm growth.
Changes in circulating adiponectin, leptin, glucose and C‐peptide in patients with ketosis‐prone diabetes
Authors: Gupta P. , Liu Y. , Lapointe M. , Yotsapon T. , Sarat S. , Cianflone K.
Published: November 2014

Aims

To evaluate circulating adipokines in people with ketosis‐prone diabetes, a heterogeneous disorder characterized by unprovoked ketoacidosis in people with previously unrecognized diabetes.

Methods

Patients presenting with ketoacidosis with no previous diabetes diagnosis were compared with patients with previously established Type 1 diabetes. Baseline assessments of autoimmune status (A+/A‐), and β‐cell function (B+/B‐), as well as leptin and adiponectin levels during a standardized mixed‐meal tolerance test of 120 min, were performed. In all, 20 patients with heterogeneous ketosis‐prone diabetes and 12 patients with Type 1 diabetes were evaluated at baseline, 12 and 24 months.

Results

At baseline, during a mixed‐meal tolerance test, glucose and adiponectin concentrations were lower in patients with ketosis‐prone diabetes than in those with Type 1 diabetes (P = 0.0023 and P < 0.0001, respectively), whereas C‐peptide concentrations were higher, with no significant difference in leptin concentrations. Within 12 months, 11 patients with ketosis‐prone diabetes (all A‐/B+) were discontinued from insulin treatment (ketosis‐prone diabetes ‐ insulin group), while nine patients (four A‐B‐, four A+B‐ and one A‐B+) were maintained on insulin (ketosis‐prone diabetes + insulin group). Fasting C‐peptide levels increased significantly over 24 months in the ketosis‐prone diabetes ‐ insulin group (P = 0.01), while HbA1c levels decreased (P < 0.0001). Overall, the ketosis‐prone diabetes ‐ insulin group had a higher BMI (P = 0.018), yet a lower fasting glucose concentration (P = 0.003) compared with the ketosis‐prone diabetes + insulin group. Over 24 months, the mixed‐meal tolerance test area‐under‐the‐curve of C‐peptide increased in the ketosis‐prone diabetes ‐ insulin group, with no change in ketosis‐prone diabetes + insulin (P < 0.0001). At 24 months, in spite of the higher BMI in the ketosis‐prone diabetes ‐ insulin group, mixed‐meal tolerance test glucose and leptin concentrations were significantly lower (P < 0.0001 and P = 0.017, respectively), while adiponectin levels were higher (P = 0.023) compared with the ketosis‐prone diabetes + insulin group.

Conclusions

In spite of the higher BMI in the ketosis‐prone diabetes ‐ insulin group, lower leptin and higher adiponectin levels may contribute to improved β‐cell function and insulin sensitivity, as evidenced by lower glucose and higher C‐peptide levels. This allows insulin therapy to be withdrawn.
The experiences and impact of transition from child to adult healthcare services for young people with Type 1 diabetes: a systematic review
Authors: Sheehan A. M. , While A. E. , Coyne I.
Published: November 2014

Introduction

Despite the transition between child and adult services for young people with Type 1 diabetes mellitus being a high‐risk period, little is known about the impact of healthcare transition upon young people.

Methods

A systematic review was conducted using PubMed, PsycINFO, CINAHL and EMBASE. Papers published between January 2001 and June 2014 that examined the impact or experiences of healthcare transition in young people with Type 1 diabetes were included. Data were extracted by two independent reviewers and integrated by narrative synthesis.

Results

A total of 8990 citations were reviewed and 43 studies were included in the review, 24 of which explored the impact of transition and 24 examined experiences of transition. There were mixed results in terms of the change in glycaemic control and diabetes‐related hospitalizations, but all studies assessing attendance found worse attendance post‐transition. Data regarding experiences reported that young people and parents experienced greater difficulty in accessing and maintaining diabetes health care. Young people were required to develop independent self‐management and self‐advocacy skills to navigate the transition and adult health care, but some were inadequately prepared for this.

Conclusions

Although the impact of healthcare transition on outcomes for young people with Type 1 diabetes is unclear due to the paucity of high‐quality studies, transition appears to be associated with decreased clinic attendance. There is some preliminary evidence of a positive impact of structured transition programmes. Experiences of healthcare transition illuminate the barriers to smooth transitions and the need for better integration and continuity of care.
Circulating markers of inflammation and endothelial function, and their relationship to diabetic retinopathy
Authors: Sasongko M. B. , Wong T. Y. , Jenkins A. J. , Nguyen T. T. , Shaw J. E. , Wang J. J.
Published: November 2014

Aim

To examine the relationships of serum markers of inflammation and endothelial function to diabetic retinopathy.

Methods

We recruited 224 patients with diabetes (85 with Type 1 and 139 with Type 2 diabetes) aged 18–70 years. Serum markers of inflammation (high‐sensitivity C‐reactive protein) and endothelial function (soluble intercell adhesion molecule‐1, vascular cell adhesion molecule‐1, E‐selectin, endothelin‐1 and total nitrite) were assessed using nephelometry, immunoassays and spectroscopy. Diabetic retinopathy was graded from two‐field fundus photographs according to the Airlie House Classification system and was categorized into no diabetic retinopathy, mild non‐proliferative diabetic retinopathy, moderate non‐proliferative diabetic retinopathy and vision‐threatening diabetic retinopathy, the latter comprising severe non‐proliferative diabetic retinopathy, proliferative diabetic retinopathy or clinically significant macular oedema. Multinomial logistic regression was used to assess the associations between serum markers and diabetic retinopathy.

Results

In the study, 64% of patients (144/224) had diabetic retinopathy and 25% (57/244) had vision‐threatening diabetic retinopathy. After controlling for age, gender, diabetes duration, HbA1c, systolic blood pressure, total and HDL cholesterol, smoking, the use of insulin or oral hypoglycaemic agents, nephropathy and cardiovascular disease, a positive association was found between increasing high‐sensitivity C‐reactive protein levels and the presence of vision‐threatening diabetic retinopathy (odds ratio 1.26; 95% CI 1.05–1.51, per sd increase in high‐sensitivity C‐reactive protein). After stratifying by BMI ( ≥ 30 and < 30 kg/m2), this association was found to be more pronounced in people with a BMI ≥ 30 kg/m2 (odds ratio 2.9; P for interaction = 0.019). No associations were found between serum markers of endothelial activation and diabetic retinopathy.

Conclusions

Higher C‐reactive protein levels, but not markers of endothelial function, may be related to more severe diabetic retinopathy. This finding suggests that inflammatory processes are involved in severe diabetic retinopathy, particularly in patients with a BMI ≥ 30 kg/m2.
Topographic, latitudinal and climatic distribution of Pinus coulteri: geographic range limits are not at the edge of the climate envelope
Authors: Chardon Nathalie I. , Cornwell William K. , Flint Lorraine E. , Flint Alan L. , Ackerly David D.
Published: November 2014

With changing climate, many species are projected to move poleward or to higher elevations to track suitable climates. The prediction that species will move poleward assumes that geographically marginal populations are at the edge of the species' climatic range. We studied Pinus coulteri from the center to the northern (poleward) edge of its range, and examined three scenarios regarding the relationship between the geographic and climatic margins of a species' range. We used herbarium and iNaturalist.org records to identify P. coulteri sites, generated a species distribution model based on temperature, precipitation, climatic water deficit, and actual evapotranspiration, and projected suitability under future climate scenarios. In fourteen populations from the central to northern portions of the range, we conducted field studies and recorded elevation, slope and aspect (to estimate solar insolation) to examine relationships between local and regional distributions. We found that northern populations of P. coulteri do not occupy the cold or wet edge of the species' climatic range; mid‐latitude, high elevation populations occupy the cold margin. Aspect and insolation of P. coulteri populations changed significantly across latitudes and elevations. Unexpectedly, northern, low‐elevation stands occupy north‐facing aspects and receive low insolation, while central, high‐elevation stands grow on more south‐facing aspects that receive higher insolation. Modeled future climate suitability is projected to be highest in the central, high elevation portion of the species range, and in low‐lying coastal regions under some scenarios, with declining suitability in northern areas under most future scenarios. For P. coulteri, the lack of high elevation habitat combined with a major dispersal barrier may limit northward movement in response to a warming climate. Our analyses demonstrate the importance of distinguishing geographically vs. climatically marginal populations, and the importance of quantitative analysis of the realized climate space to understand species range limits.
Host phenology, geographic range size and regional occurrence explain interspecific variation in damselfly–water mite associations
Authors: Mlynarek Julia J. , Knee W. , Forbes Mark R.
Published: November 2014

In this study, we tested which host species’ characteristics explain the nature and level of parasitism for host damselfly (Coenagrionidae)–water mite (Arrenuridae) parasite associations. Prevalence and intensity of mite parasites, and mite species richness were examined in relation to geographic range size, regional occurrence, relative local abundance, phenology and body size of host damselfly species. A total of 7107 damselfly individuals were collected representing 16 species from 13 sites in southeastern Ontario and southwestern Quebec, Canada. Using comparative methods, differences in prevalence and intensity of parasitism could be predicted by a host species’ geographic range and phenology. Barcoding based on Cytochrome Oxidase I revealed 15 operational taxonomic units (OTUs) for mite species. The number of mite OTUs known to infest a given host species was explained by a host species’ regional occurrence. Our findings demonstrate the need to measure factors at several ecological scales in order to understand the breadth of evolutionary interactions with host–parasite associations and the selective ‘milieu’ for particular species of both hosts and parasites.
Projected impacts of climate warming on the functional and phylogenetic components of coastal Mediterranean fish biodiversity
Authors: Albouy Camille , Leprieur Fabien , Le Loc'h François , Mouquet Nicolas , Meynard Christine N. , Douzery Emmanuel J. P. , Mouillot David
Published: November 2014

Climate warming affects biodiversity distribution across all ecosystems. However, beyond changes in species richness, impacts on other biodiversity components are still overlooked, particularly in the marine realm. Here we forecasted the potential effect of climate warming on the phylogenetic and functional components of coastal Mediterranean fish biodiversity. To do so, we used species distribution models to project the potential distribution of 230 coastal fish species by the end of the 21st century based on the IPCC A2 scenario implemented with the Mediterranean climatic model NEMOMED8. From these projections, we assessed the changes in phylogenetic (PD) and functional diversity (FD) of fish assemblages at multiple spatial scales using a dated molecular phylogeny and an extensive functional trait database. At the scale of the entire Mediterranean Sea, the projected extinctions of 40 coastal fish species would lead to a concomitant erosion of PD and FD (13.6 and 3%, respectively). However, a null model revealed that species loss at this scale would not lead to a disproportionate erosion of PD and FD. Similar results were found when considering fish assemblages at the grid cell scale. Indeed, at this scale, the projected changes in species richness would lead to unexpected losses of PD and FD for localized and small areas only. A disproportionate erosion of PD under climate warming was only forecasted when analysing fish assemblages at an intermediate spatial scale, namely the Mediterranean marine ecoregions. Overall, our results emphasize the importance of considering multiple spatial scales when assessing potential impacts of climate warming on the multiple components marine biodiversity.
Influence of temperature on germination ofQuercus ilexinPhytophthora cinnamomi,P. gonapodyides, P. quercinaandP. psychrophilainfested soils
Authors: Martín‐García J. , Solla A. , Corcobado T. , Siasou E. , Woodward S.
Published: November 2014

The influence of temperature on germination ofQuercus ilexacorns inPhytophthorainfested soils was quantified for the first time. Radicle damage and mortality ofQ. ilexseeds germinating at 17, 20, 23 and 26°C inPhytophthora cinnamomi,P. gonapodyides, P. quercinaandP. psychrophilainfested soils were assessed and related toin vitromycelium growth of the same isolates of the pathogens. The optimum growth temperatures of isolates ofP. cinnamomi,P. gonapodyides,P. quercinaandP. psychrophilawere 20–23, 23–26, 20–23 and 20°C, respectively. At 17 and 20°C, all fourPhytophthoraspecies caused 100% acorn mortality, whereas at 26°C, acorn mortality was 100, 10, 25 and 0% inP. cinnamomi,P. gonapodyides, P. quercinaandP. psychrophilainfested soils, respectively. At 23°C,P. cinnamomiandP. gonapodyidesreduced acorn radicle length more thanP. quercinaandP. psychrophila, whereas at 26°C, onlyP. cinnamomicaused further reduction in radicle length. The higher susceptibility of germinating acorns in comparison to seedlings reported in the literature indicates age‐related susceptibility ofQ. ilextoPhytophthora. The seedling/pathogen growth ratio was inversely related to the reduction in radicle length at different temperatures ( = 0.84, p < 0.0001), suggesting that rapid germination may allow seedlings to escape from infection. Increasing temperatures had different effects on damage to acorns depending on the pathogen present in the soil, indicating thatPhytophthoraspecies × temperature interactions determinedQ. ilexgermination. The effects of temperature on the impacts ofPhytophthoraspecies based on climate change predictions for Mediterranean countries are discussed.
Increased expression of TRPV1 in the trigeminal ganglion is involved in orofacial pain during experimental tooth movement in rats
Authors: Qiao Hu , Gao YuNan , Zhang Caidi , Zhou Hong
Published: November 2014

To investigate whether transient receptor potential vanilloid type 1 (TRPV1) is involved in pain induced by experimental tooth movement, experiments were performed in male Sprague‐Dawley rats weighing 200–250 g. Directed face‐grooming behavior was used to evaluate nocifensive behavior in rats during experimental tooth movement. The distribution of TRPV1 in the trigeminal ganglion (TG) was evaluated by immunohistochemistry, and its expression was detected by western blotting at several time points following the application of various magnitudes of force during tooth movement. Immunohistochemical analysis revealed that TRPV1 was expressed in TG, and its expression was increased after experimental tooth movement. Western blot results also showed that experimental tooth movement led to a statistically significant increase in expression of TRPV1 protein in TG. Meanwhile, the time spent on directed face‐grooming peaked on day 1 and thereafter showed a gradual decrease. In addition, both the change in TRPV1 expression in the TG and directed face‐grooming behavior were modulated in a force‐dependent manner and in concert with initial orthodontic pain responses. Our results reveal that TRPV1 expression is modulated by experimental tooth movement and is involved in tooth‐movement pain.
Peptide sequences converting polyglutamine into a prion in yeast
Authors: Odani Wataru , Urata Kazuhiro , Okuda Momoko , Okuma Shunsuke , Koyama Hiroko , Pack Chan‐Gi , Fujiwara Kei , Nojima Tatsuya , Kinjo Masataka , Kawai‐Noma Shigeko , Taguchi Hideki
Published: November 2014

Amyloids are ordered protein aggregates composed of cross‐β sheet structures. Amyloids include prions, defined as infectious proteins, which are responsible for mammalian transmissible spongiform encephalopathies, and fungal prions. Although the conventional view is that typical amyloids are associated with nontransmissible mammalian neurodegenerative diseases such as Alzheimer's disease, increasing evidence suggests that the boundary between transmissible and nontransmissible amyloids is ambiguous. To clarify the mechanism underlying the difference in transmissibility, we investigated the dynamics and the properties of polyglutamine (polyQ) amyloids in yeast cells, in which the polyQ aggregates are not transmissible but can be converted into transmissible amyloids. We found that polyQ had an increased tendency to form aggregates compared to the yeast prion Sup35. In addition, we screened dozens of peptides that converted the nontransmissible polyQ to transmissible aggregates when they flanked the polyQ stretch, and also investigated their cellular dynamics aiming to understand the mechanism of transmission.
Quantifying drylands' drought resistance and recovery: the importance of drought intensity, dominant life history and grazing regime
Authors: Ruppert Jan C. , Harmoney Keith , Henkin Zalmen , Snyman Hennie A. , Sternberg Marcelo , Willms Walter , Linstädter Anja
Published: November 2014

Projected global change will increase the level of land‐use and environmental stressors such as drought and grazing, particularly in drylands. Still, combined effects of drought and grazing on plant production are poorly understood, thus hampering adequate projections and development of mitigation strategies. We used a large, cross‐continental database consisting of 174 long‐term datasets from >30 dryland regions to quantify ecosystem responses to drought and grazing with the ultimate goal to increase functional understanding in these responses. Two key aspects of ecosystem stability, resistance to and recovery after a drought, were evaluated based on standardized and normalized aboveground net primary production (ANPP) data. Drought intensity was quantified using the standardized precipitation index. We tested effects of drought intensity, grazing regime (grazed, ungrazed), biome (grassland, shrubland, savanna) or dominant life history (annual, perennial) of the herbaceous layer to assess the relative importance of these factors for ecosystem stability, and to identify predictable relationships between drought intensity and ecosystem resistance and recovery. We found that both components of ecosystem stability were better explained by dominant herbaceous life history than by biome. Increasing drought intensity (quasi‐) linearly reduced ecosystem resistance. Even though annual and perennial systems showed the same response rate to increasing drought intensity, they differed in their general magnitude of resistance, with annual systems being ca. 27% less resistant. In contrast, systems with an herbaceous layer dominated by annuals had substantially higher postdrought recovery, particularly when grazed. Combined effects of drought and grazing were not merely additive but modulated by dominant life history of the herbaceous layer. To the best of our knowledge, our study established the first predictive, cross‐continental model between drought intensity and drought‐related relative losses in ANPP, and suggests that systems with an herbaceous layer dominated by annuals are more prone to ecosystem degradation under future global change regimes.
Association between level of brachial‐ankle pulse wave velocity and onset of activities of daily living impairment in community‐dwelling older individuals
Authors: Kuroiwa Yumi , Miyano Ichiro , Nishinaga Masanori , Takata Jun , Shimizu Yuji , Okumiya Kiyohito , Matsubayashi Kozo , Ozawa Toshio , Kitaoka Hiroaki , Doi Yoshinori , Yasuda Nobufumi
Published: November 2014

Aim

The purpose of the present study was to clarify the longitudinal association between brachial‐ankle pulse wave velocity (baPWV) and the onset of impairment in activities of daily living (ADL) among community‐dwelling individuals.

Methods

Deaths and the onsets of ADL impairment during 3 years were followed for 450 individuals without ADL impairment at entry who were aged 65 years or older (men : women 181:269; mean age 77 years). They were dichotomized on the median baPWV value at entry.

Results

Within 3 years, 28 died and 60 had an onset of ADL impairment. The high baPWV group had a higher incidence of deaths (high baPWV group vs low baPWV group, 9.3% vs 3.1%) and ADL impairment (high baPWV group vs low baPWV group, 20.7% vs 9.3%). After adjustment for age, sex and systolic blood pressure, as compared with the low baPWV group, the high baPWV group had increased risk for mortality (adjusted odds ratio 3.22; 95% confidence interval 1.26–8.22) and the onset of ADL impairment (adjusted odds ratio 1.94; 95% confidence interval 1.03–3.63). When the onset of ADL impairment was grouped according to medical conditions that preceded/accompanied the onset of ADL impairment, elevated baPWV was associated with increased risk for the onset of ADL impairment after/accompanying fall/fracture.

Conclusions

The assessment of arterial stiffness by baPWV contributes to identifying functionally independent community‐dwelling older individuals at risk for ADL impairment, in particular ADL impairment associated with fall/fracture, as well as for mortality. Geriatr Gerontol Int 2015; 15: 840–847.