bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating the impact of buffers to account for scientific uncertainty when setting TACs: application to red king crab in Bristol Bay, Alaska
Authors: Punt André E. , Siddeek M. S. M. , Garber-Yonts Brian , Dalton Michael , Rugolo Louis , Stram Diana , Turnock Benjamin J. , Zheng Jie
Published: March 2012

Punt, A. E., Siddeek, M. S. M., Garber-Yonts, B., Dalton, M., Rugolo, L., Stram, D., Turnock, B. J., and Zheng, J. 2012. Evaluating the impact of buffers to account for scientific uncertainty when setting TACs: application to red king crab in Bristol Bay, Alaska. – ICES Journal of Marine Science, 69: 624–634. Increasingly, scientific uncertainty is being accounted for in fisheries management by implementing an uncertainty buffer, i.e. a difference between the limit catch level given perfect information and the set catch. An approach based on simulation is outlined, which can be used to evaluate the impact of different buffers on short- and long-term catches, discounted revenue, the probability of overfishing (i.e. the catch exceeding the true, but unknown, limit catch), and the stock becoming overfished (i.e. for crab, mature male biomass, MMB, dropping below one-half of the MMB corresponding to maximum sustainable yield). This approach can be applied when only a fraction of the uncertainty related to estimating the limit catch level is quantified through stock assessments. The approach is applied for illustrative purposes to the fishery for red king crab, Paralithodes camtschaticus, in Bristol Bay, AK.
μ-Opioid Receptor Gene A118G Polymorphism Predicts Survival in Patients with Breast Cancer
Authors: Bortsov Andrey V. , Millikan Robert C. , Belfer Inna , Boortz-Marx Richard L. , Arora Harendra , McLean Samuel A.
Published: March 2012

Background

Preclinical studies suggest that opioids may promote tumor growth. Genetic polymorphisms have been shown to affect opioid receptor function and to modify the clinical effects of morphine. In this study we assessed the association between six common polymorphisms in the μ-opioid receptor gene, including the well known A118G polymorphism, and breast cancer survival.

Methods

A total of 2,039 women ages 23-74 yr (38% African-American, 62% European-American, 55% postmenopausal) diagnosed with breast cancer between 1993-2001 were followed through 2006. Genotyping was performed using the TaqMan platform (Applied Biosystems Inc., Foster City, CA). Kaplan-Meier curves, log-rank tests, and Cox proportional hazard models were used to examine the association between each genotype and survival.

Results

After Bonferroni correction for multiple testing, patient genotype at A118G was associated with breast cancer-specific mortality at 10 yr. Women with one or more copies of the G allele had decreased breast cancer-specific mortality (P < 0.001). This association was limited to invasive cases only; effect size appeared to increase with clinical stage. Cox regression model adjusted for age and ethnicity also showed decreased mortality in A/G and G/G genotypes compared with A/A genotype (hazard ratio = 0.57 [0.38, 0.85] and 0.32 [0.22, 0.49], respectively; P = 0.006).

Conclusions

These results suggest that opioid pathways may be involved in tumor growth. Further studies examining the association between genetic variants influencing opioid system function and cancer survival are warranted.
Impaired Gastric Emptying and Small Bowel Transit in Children With Mitochondrial Disorders
Authors: Bhardwaj Jatinder , Wan David Q. , Koenig Mary Kay , Liu Yuying , Hashmi Syed Shahrukh , Rhoads Jon Marc
Published: March 2012

Objectives:

The primary aim of our study was to evaluate gastric emptying (GE) and intestinal transit time (ITT) in children with mitochondrial disorders (MD), and secondarily to evaluate the effect of prokinetics in those with prolonged GE.

Methods:

We enrolled subjects 3 to 18 years with MD and having any of the following gastrointestinal (GI) symptoms: abdominal pain, vomiting, constipation, diarrhea, or gastroesophageal reflux. Abdominal pain was scored by visual analog pain scale (1–10). Age‐appropriate diet was labeled with radioactive technetium‐99 sulfur colloid and its movement tracked along the GI tract. Delayed GE based on our institutional standards was defined as half emptying time >90 minutes for a solid and >60 minutes for a semisolid meal. Prolonged ITT was defined as >4 hours for the tracer to pass from mouth to cecum. A prokinetic was instituted to those with delayed GE, and the study was repeated if possible in 4 to 8 weeks.

Results:

Of the 26 subjects, 18 (69%) had delayed GE (median GE 99 minutes) and 12 (46%) had prolonged ITT. The study was repeated in 9 subjects after administering a prokinetic for >1 month. GE normalized in only 3 subjects (median GE on treatment 128 minutes). Mean abdominal pain score, which was 4.8 (max 10) in the 9 subjects, did not improve (5.6 after prokinetic therapy).

Conclusions:

A high prevalence of delayed GE and prolonged ITT was seen in children with MD having GI symptoms, and these abnormalities were poorly responsive to prokinetic therapy.
The effect of the signalling scheme on the robustness of pattern formation in development
Authors: Kang Hye-Won , Zheng Likun , Othmer Hans G.
Published: March 2012

Pattern formation in development is a complex process which involves spatially distributed signals called morphogens that influence gene expression and thus the phenotypic identity of cells. Usually different cell types are spatially segregated, and the boundary between them may be determined by a threshold value of some state variable. The question arises as to how sensitive the location of such a boundary is to variations in properties, such as parameter values, that characterize the system. Here, we analyse both deterministic and stochastic reaction-diffusion models of pattern formation with a view towards understanding how the signalling scheme used for patterning affects the variability of boundary determination between cell types in a developing tissue.
Unusual combinatorial involvement of poly-A/T tracts in organizing genes and chromatin in Dictyostelium
Authors: Chang Gue Su , Noegel Angelika A. , Mavrich Travis N. , Müller Rolf , Tomsho Lynn , Ward Elissa , Felder Marius , Jiang Cizhong , Eichinger Ludwig , Glöckner Gernot , Schuster Stephan C. , Pugh B. Franklin
Published: March 2012

Dictyosteliumdiscoideum is an amoebozoa that exists in both a free-living unicellular and a multicellular form. It is situated in a deep branch in the evolutionary tree and is particularly noteworthy in having a very A/T-rich genome. Dictyostelium provides an ideal system to examine the extreme to which nucleotide bias may be employed in organizing promoters, genes, and nucleosomes across a genome. We find that Dictyostelium genes are demarcated precisely at their 5′ ends by poly-T tracts and precisely at their 3′ ends by poly-A tracts. These tracts are also associated with nucleosome-free regions and are embedded with precisely positioned TATA boxes. Homo- and heteropolymeric tracts of A and T demarcate nucleosome border regions. Together, these findings reveal the presence of a variety of functionally distinct polymeric A/T elements. Strikingly, Dictyostelium chromatin may be organized in di-nucleosome units but is otherwise organized as in animals. This includes a +1 nucleosome in a position that predicts the presence of a paused RNA polymerase II. Indeed, we find a strong phylogenetic relationship between the presence of the NELF pausing factor and positioning of the +1 nucleosome. Pausing and +1 nucleosome positioning may have coevolved in animals.
MiR‐21 regulates epithelial‐mesenchymal transition phenotype and hypoxia‐inducible factor‐1α expression in third‐sphere forming breast cancer stem cell‐like cells
Authors: Han Mingli , Wang Yimeng , Liu Manran , Bi Xiaokai , Bao Junjie , Zeng Ni , Zhu Zhikun , Mo Zhiqiang , Wu Chengyi , Chen Xin
Published: March 2012

Cancer stem cells (CSCs) are predicted to be critical drivers of tumor progression due to their “stemness”, but the molecular mechanism of CSCs in regulating metastasis remains to be elucidated. Epithelial‐mesenchymal transition (EMT), hypoxia‐inducible factor (HIF)‐1α, and miR‐21, all of which contribute to cell migration for metastasis, are interrelated with CSCs. In the present study, third‐sphere forming (3‐S) CSC‐like cells, which showed elevated CSC surface markers (ALDH1+ and CD44+/CD24−/low) and sphereforming capacity as well as migration and invasion capacities, were cultured and isolated from breast cancer MCF‐7 parental cells, to evaluate the role of miR‐21 in regulating the CSC‐like cell biological features, especially EMT. EMT, which was assessed by overexpression of mesenchymal cell markers (N‐cadherin, Vimentin, alpha‐smooth muscle actin [α‐SMA]) and suppression of epithelial cell marker (E‐cadherin), was induced in 3‐S CSC‐like cells. Moreover, both of HIF‐1α and miR‐21 were upregulated in the CSC‐like cells. Interestingly, antagonism of miR‐21 by antagomir led to reversal of EMT, downexpression of HIF‐1α, as well as suppression of invasion and migration, which indicates a key role of miR‐21 involved in regulate CSC‐associated features. In conclusion, we demonstrated that the formation of CSC‐like cells undergoing process of EMT‐like associated with overexpression of HIF‐1α, both of which are regulated by miR‐21. (Cancer Sci 2012; 103: 1058–1064)
Microencapsulation of small intestinal neuroendocrine neoplasm cells for tumor model studies
Authors: Rokstad Anne M. , Gustafsson Björn I. , Espevik Terje , Bakke Ingunn , Pfragner Roswitha , Svejda Bernhard , Modlin Irvin M. , Kidd Mark
Published: March 2012

Basic cancer research is dependent on reliable in vitro and in vivo tumor models. The serotonin (5‐HT) producing small intestinal neuroendocrine tumor cell line KRJ‐1 has been used in in vitro proliferation and secretion studies, but its use in in vivo models has been hampered by problems related to the xeno‐barrier and tumor formation. This may be overcome by the encapsulation of tumor cells into alginate microspheres, which can function as bioreactors and protect against the host immune system. We used alginate encapsulation of KRJ‐1 cells to achieve long‐term functionality, growth and survival. Different conditions, including capsule size, variations in M/G content, gelling ions (Ca2+/Ba2+) and microcapsule core properties, and variations in KRJ‐1 cell condition (single cells/spheroids) were tested. Viability and cell growth was evaluated with MTT, and confocal laser scanner microscopy combined with LIVE/DEAD viability stains. 5‐HT secretion was measured to determine functionality. Under all conditions, single cell encapsulation proved unfavorable due to gradual cell death, while encapsulation of aggregates/spheroids resulted in surviving, functional bioreactors. The most ideal spheroids for encapsulation were 200–350 μm. Long‐term survival (>30 days) was seen with solid Ca2+/Ba2+ microbeads and hollow microcapsules. Basal 5‐HT secretion was increased (sixfold) after hollow microcapsule encapsulation, while Ca2+/Ba2+ microbeads was associated with normal basal secretion and responsiveness to cAMP/PKA activation. In conclusion, encapsulation of KRJ‐1 cells into hollow microcapsules produces a bioreactor with a high constitutively activate basal 5‐HT secretion, while Ca2+/Ba2+ microbeads provide a more stable bioreactor similar to non‐encapsulated cells. Alginate microspheres technology can thus be used to tailor different functional bioreactors for both in vitro and in vivo studies. (Cancer Sci 2012; 103: 1230–1237)
Systematic review: the role of liver transplantation in the management of hepatocellular carcinoma
Authors: Maggs J. R. L. , Suddle A. R. , Aluvihare V. , Heneghan M. A.
Published: March 2012

Background

Hepatocellular carcinoma (HCC) is a major cause of morbidity and mortality worldwide. Liver transplantation offers a potential cure for this otherwise devastating disease. The selection of the most appropriate candidates is paramount in an era of graft shortage.

Aim

To review systematically the role of liver transplantation in the management of HCC in current clinical practice.

Methods

An electronic literature search using PUBMED (1980–2010) was performed. Search terms included HCC, hepatoma, liver cancer, and liver transplantation.

Results

Liver transplantation is a highly successful treatment for HCC, in patients within Milan criteria (MC), defined as a solitary tumour ≤50 mm in diameter or ≤3 tumours ≤30 mm in diameter in the absence of extra‐hepatic or vascular spread. Other eligibility criteria for liver transplantation are also used in clinical practice, such as the University of California, San Francisco criteria, with outcomes comparable to MC. Loco‐regional therapies have a role in the bridging treatment of HCC by minimising wait‐list drop‐out secondary to tumour progression. Beyond MC, encouraging results have been demonstrated for patients with down‐staged tumours. Post‐liver transplantation, there is no evidence to support a specific immunosuppressive regimen. In the context of an insufficient cadaveric donor pool to meet demand, the role of adult living donation may be increasingly important.

Conclusions

Liver transplantation offers a curative therapy for selected patients with HCC. The optimisation of eligibility criteria is paramount to ensure that maximum benefit is accrued. Although wait‐list therapies have been incorporated into clinical practice, additional high quality data are required to support this strategy.
Myelodysplasia and acute myeloid leukaemia in cases of aplastic anaemia and congenital neutropenia following G‐CSF administration
Authors: Imashuku Shinsaku , Hibi Shigeyoshi , Kataoka‐Morimoto Yoshiko , Yoshihara Takao , Ikushima Satoshi , Morioka Yoshihito , Todo Shinjiro
Published: March 2012

Summary. Myelodysplasia and acute myeloid leukaemia (MDS/AML) developed in three cases of severe aplastic anaemia (SAA) and one case of congenital neutropenia (CN, Kostmann's disease) who received recombinant human granulocyte colony‐stimulating factor (G‐CSF) are reported. In these four MDS/AML cases, age at diagnosis of SAA/CN was 0–13 years, the cumulative dose of G‐CSF was 98 μg/kg to 10 mg/kg over 1–57 months, and the interval from initiation of G‐CSF to MDS/AML was 25, 23, 31 and 57 months, respectively. These results suggest a link between SAA/CN and MDS/AML in relation to G‐CSF administration; however, large studies are necessary to determine if such a risk is significant in patients with SAA/CN who are treated with G‐CSF.
Amino‐terminal propeptide of C‐type natriuretic peptide (NTproCNP) predicts height velocity in healthy children
Authors: Olney Robert C. , Permuy Joseph W. , Prickett Timothy C. R. , Han Joan C. , Espiner Eric A.
Published: March 2012

Objective

C‐type natriuretic peptide (CNP) is a paracrine regulatory factor of the growth plate and plays a key role in endochondral growth. Its amino‐terminal propeptide (NTproCNP) is an equimolar product of CNP biosynthesis and is easily measured in plasma. Preliminary studies suggest that NTproCNP levels correlate with height velocity in sheep and children. The objectives of the study were to correlate NTproCNP levels with height velocity and to define the reference range for plasma CNP and NTproCNP across childhood.

Design

This was a prospective, cross‐sectional, observational study of healthy children.

Patients

Participants were 258 healthy children between 2 months and 20 years of age.

Measurements

Anthropometrics were obtained and CNP and NTproCNP levels were determined by radioimmunoassay.

Results

For both sexes, CNP and NTproCNP levels were high in infancy, lower in early childhood, rising during puberty, then falling to low adult levels. Levels of NTproCNP peaked at 14·1 years in boys and 11·9 years in girls, coincident with the age of peak height velocity. Levels of NTproCNP varied with pubertal status, peaking at genital Tanner stage IV in boys and III in girls. There was a highly significant correlation between NTproCNP and height velocity.

Conclusions

C‐type natriuretic peptide plays an integral role in endochondral growth. We show here that CNP synthesis (as measured by NTproCNP levels in plasma) is closely related to linear growth in healthy children at all ages. We propose NTproCNP as a biomarker of linear growth.
Range of variability of channel complexity in urban, restored and forested reference streams
Authors: LAUB BRIAN G. , BAKER Daniel W. , BLEDSOE Brian P. , PALMER MARGARET A.
Published: March 2012

Summary 1. Channel complexity is an important ecological property of stream systems and is often targeted for restoration in channelised urban streams. However, channel complexity is rarely defined explicitly, and little research on channel complexity has been conducted in streams in urban catchments that have not been directly channelised by human activities. Therefore, it remains unclear whether restoration of non‐channelised urban streams has improved complexity.

2. We explicitly define channel complexity and use a multimetric approach to provide a comprehensive assessment of complexity in multiple restored, urban and forested streams on the Maryland Coastal Plain and two streams of differing land use in Colorado. We also expand on the Maryland and Colorado results with a literature survey of channel complexity from diverse geographical regions.

3. Many streams draining urban catchments in Maryland had relatively high values of some complexity metrics compared to forested reference streams in Maryland and compared to the values for pristine streams calculated from the literature. This suggests that streams in urban catchments that are not directly manipulated by human activities (e.g. channelisation or piping) may be able to maintain channel structures beneficial for aquatic organisms even when impervious surfaces are the dominant form of land use in the catchment.

4. Restored streams in Maryland had equal or lower values of many complexity metrics compared to streams draining urban catchments in Maryland. This suggests that restoration of streams draining urban catchments did not improve the overall channel complexity.

5. Our results highlight the need to explicitly define and measure the attributes of channel complexity that are targeted during restoration, to determine whether the streams in urban catchments are truly degraded with respect to channel complexity.

6. Combined with recent synthesis work suggesting that biodiversity may not be improved by increasing the channel complexity, these results indicate that targeting catchment processes may prove a more useful approach to restoration than attempting to move channel complexity in streams draining urban catchments towards conditions in forested reference streams.
Diet‐Induced Obesity Resistance of Kv1.3−/− Mice is Olfactory Bulb Dependent
Authors: Tucker K. , Overton J. M. , Fadool D. A.
Published: March 2012

Gene‐targeted deletion of the voltage‐gated potassium channel, Kv1.3 (Kv1.3−/−), increases olfactory sensitivity and discriminatory ability, and causes resistance to diet‐induced obesity (DIO) in mice. The present study aimed to determine whether the enhanced olfactory ability of the Kv1.3−/− mouse contributes to the resistance to DIO. Kv1.3+/+ and Kv1.3−/− mice were subject to bilateral olfactory bulbectomy (OBX) or sham surgery at 9 weeks of age and placed on either a control chow diet or a 32% moderately high‐fat diet (MHF). Caloric and water intake, locomotor activity and oxygen consumption were monitored after 5 weeks of diet treatment. At the end of 26 weeks of diet treatment, fat pad weight and blood chemistry were evaluated. Kv1.3+/+ mice exhibited a significant increase in weight, adiposity, fasting glucose and fasting leptin in response to the MHF‐diet, with or without OBX. When treated with a MHF‐diet, Kv1.3−/− mice gained significantly less weight than Kv1.3+/+ mice and exhibited a significant increase in light phase metabolism. OBX of Kv1.3−/− mice prevented the resistance to DIO and concomitant up‐regulation of light phase metabolism at the same time as decreasing dark phase metabolism and total energy expenditure. These findings suggest that pathways activated in Kv1.3−/− that increased energy expenditure and led to resistance to DIO are olfactory bulb dependent. Thus, these findings add to a growing body of evidence suggesting that the olfactory system can modulate the pathways involved in the regulation of energy balance.
Risk of asthma and allergic outcomes in the offspring in relation to maternal food consumption during pregnancy: A Finnish birth cohort study
Authors: Erkkola Maijaliisa , Nwaru Bright I. , Kaila Minna , Kronberg‐Kippilä Carina , Ilonen Jorma , Simell Olli , Veijola Riitta , Knip Mikael , Virtanen Suvi M.
Published: March 2012

To cite this article: Erkkola M, Nwaru BI, Kaila M, Kronberg‐Kippilä C, Ilonen J, Simell O, Veijola R, Knip M, Virtanen SM. Risk of asthma and allergic outcomes in the offspring in relation to maternal food consumption during pregnancy: A Finnish birth cohort study. Pediatr Allergy Immunol 2012: 23: 186–194.

Background:  Epidemiological and immunological studies suggest that maternal diet during pregnancy might affect the development of allergic diseases in the offspring. The authors set out to study the effect of maternal food consumption during pregnancy on the emergence of the International Study of Asthma and Allergies in Childhood (ISAAC)‐based allergic outcomes: asthma, allergic rhinitis, and wheeze by the 5 yr of age.

Methods:  Data from 2441 children at 5 yr of age were analyzed within the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Nutrition Study, a population‐based birth cohort study. Maternal diet was assessed with a validated food frequency questionnaire.

Results:  In multiple regression models adjusted for known confounders, low maternal consumption of leafy vegetables (adjusted odds ratio [aOR]: 1.55; 95% CI: 1.21, 1.98), malaceous fruits (aOR: 1.45; 95% CI: 1.15, 1.84), and chocolate (aOR: 1.36; 95% CI: 1.09, 1.70) were positively associated with the risk of wheeze in children. High maternal consumption of fruit and berry juices was positively associated with the risk of allergic rhinitis (aOR: 1.40; 95% CI: 1.03, 1.90) in children. No associations were observed between maternal food consumption and asthma.

Conclusions:  Development of allergic diseases in preschool children may be influenced by intrauterine exposure to maternal diet.
Relations of nutritional intake to age, sex and body mass index in Japanese elderly patients with type 2 diabetes: The Japanese Elderly Diabetes Intervention Trial
Authors: Yoshimura Yukio , Kamada Chiemi , Takahashi Keiko , Kaimoto Tae , Iimuro Satoshi , Ohashi Yasuo , Araki Atsushi , Umegaki Hiroyuki , Sakurai Takashi , Ito Hideki ,   the Japanese Elderly Diabetes Intervention Trial Study Group
Published: March 2012

Aim:  To determine the status of nutritional intake in elderly Japanese patients with type 2 diabetes aged 65 years or older, and to clarify relations of nutritional intake to age, sex and body mass index (BMI).

Design:  Clinical parameters and nutritional intake were investigated and compared in 912 (417 men, 495 women) elderly Japanese patients with type 2 diabetes registered to the Japanese Elderly Diabetes Intervention Trial.

Results:  The mean daily energy intake of patients was 1802 kcal in men and 1661 kcal in women, respectively. The energy intakes per kilogram of standard bodyweight in both sexes and the energy intakes per kilogram of present bodyweight in men increased significantly with age. The protein : fat : carbohydrate (PFC) energy ratio (%E) was 15.2:25.4:59.5 in men, and 15.7:25.8:58.6 in women, respectively. Grain, oil, alcohol and soft drink intakes were higher in men than in women. Potato, fruit and green vegetable intakes were higher in women than in men. Fruit intake showed a significant age‐related increase in men. In women, there was an age‐related significant decrease of meat intake. An increase of BMI correlated with a significant increase in bodyweight, waist circumference, hip circumference, waist‐to‐hip ratio, triglycerides and diastolic blood pressure. The mean energy intake of three BMI groups, lean (BMI < 18.5 kg/m2), normal (18.5 kg/m2 ≦ BMI < 25 kg/m2) and obese (25 kg/m2 ≦ BMI), were 1625, 1796 and 1839 kcal in men, and 1655, 1647 and 1685 kcal in women, respectively. However, BMI‐related increase of energy intake did not reach statistically significant levels in both sexes. Energyintake per kilogram of present bodyweight decreased as BMI increased in both sexes. Energy intake per kilogram of standard bodyweight increased significantly as BMI increased in men only, but not in women. There were no differences in PFC energy ratios among the three BMI groups. In contrast, intake of soft drinks in men increased significantly as BMI increased. In women, intakes of alcohol and soft drink increased significantly as BMI increased.

Conclusion:  An increased energy intake per kilogram of standard bodyweight correlated with increase of BMI in men, but not in women. Intakes of soft drinks in both sexes and alcohol in women correlated with increase of BMI. These results suggest there are sex differences in the pathogenesis of obesity in elderly type 2 diabetic patients from an aspect of nutritional intake. Geriatr Gerontol Int 2012; 12 (Suppl. 1): 29–40.
Lower physical activity is a strong predictor of cardiovascular events in elderly patients with type 2 diabetes mellitus beyond traditional risk factors: The Japanese elderly diabetes intervention trial
Authors: Iijima Katsuya , Iimuro Satoshi , Shinozaki Tomohiro , Ohashi Yasuo , Sakurai Takashi , Umegaki Hiroyuki , Araki Atsushi , Ouchi Yasuyoshi , Ito Hideki ,   the Japanese Elderly Diabetes Intervention Trial Investigator Group
Published: March 2012

Aim:  It is well known that a decline in physical activity is associated with lifestyle‐related diseases including cardiovascular (CV) events. However, little is known about the association between physical activity and CV events in elderly patients, because recent accumulating reports have mainly dealt with middle‐aged populations. In this study, we investigated the correlation between physical activity and CV events in Japanese elderly patients with type 2 diabetes mellitus (T2DM).

Methods:  A total of 938 Japanese elderly patients with T2DM (447 men and 491 women, mean age 71.9 years) enrolled (2000–2002) in the Japanese Elderly Diabetes Intervention Trial (J‐EDIT) were used in this study. Physical activity consisting of three components, work, sports and leisure‐time, of their lifestyle was evaluated using the Baecke questionnaire at baseline. Total activity score (TAS) as a sum of each activity score was divided into four quartiles (Q1 to Q4).

Results:  During a follow‐up period of 65.2 months, 165 events and 71 deaths in total occurred. Higher TAS grade was associated with reduced risk of all events (hazard ratios: 0.82, 0.77 and 0.54 in Q2, Q3 and Q4, respectively) with statistical significance. Even after multivariate adjustment for covariates, higher TAS grade was a strong predictor of all events, and the prediction by TAS of cerebrovascular events was more effective than that of cardiac events. In contrast, all‐cause mortality gradually decreased according to TAS grade; however, no statistical significance was found. Among the four grades of TAS, no significant change in several parameters, such as profiles of lipid and glucose metabolism, blood pressure, physical measurements, cognitive function and depression scale, was found throughout the follow‐up period, suggesting that the higher level of physical activity itself was associated with the risk reduction of primary events.

Conclusion:  Lower physical activity is a strong and independent predictor of all CV events in the elderly with T2DM beyond traditional risk factors. In addition to strict management of each atherosclerotic risk factor, engagement with patients to augment and maintain the level of physical activity in their lifestyle is also essential in clinical practice. Geriatr Gerontol Int 2012; 12 (Suppl. 1): 77–87.
Risk factors associated with cognitive decline in the elderly with type 2 diabetes: Pooled logistic analysis of a 6‐year observation in the Japanese elderly diabetes intervention trial
Authors: Umegaki Hiroyuki , Iimuro Satoshi , Shinozaki Tomohiro , Araki Atsushi , Sakurai Takashi , Iijima Katsuya , Ohashi Yasuo , Ito Hideki ,   the Japanese Elderly Diabetes Intervention Trial Study Group
Published: March 2012

Aim:  Considerable attention has been paid to the association between type 2 diabetes mellitus (T2DM) and cognitive dysfunction in the elderly. T2DM is often comorbid with several other metabolic disturbances, including hypertension and dyslipidemia. These comorbid diseases might be associated with cognitive impairment. Many clinical indices should be included as variables for the association with cognitive decline. In the current study, we tried to identify the associated factors with cognitive decline during a 6‐year period in elderly T2DM considering the changes in the clinical indices during the follow‐up period.

Methods:  The subjects in the present study were 63 Japanese Elderly Interventional Trial participants who were administered the Mini‐Mental State Examination at baseline, at the third year, and at the end of the 6‐year follow‐up period. We applied the pooled logistic analysis method to consider the changes in clinical indices during the observation period and tried to identify the factors associated with cognitive decline during the 6 years in elderly type 2 diabetics using repeated measured data for glycated hemoglobin A1c, blood pressure and serum lipids.

Results:  In the current study, low high‐density lipoprotein‐cholesterol and higher diastolic blood pressure were significantly associated with cognitive decline by pooled logistic analysis in the 6‐year observation of older diabetic subjects. Higher glycated hemoglobin A1c had a tendency toward association with cognitive decline.

Conclusion:  The results suggest that comprehensive management of diabetes, including dyslipidemia and hypertension, might contribute to the prevention of declines in cognitive function in older diabetic patients. Geriatr Gerontol Int 2012; 12 (Suppl. 1): 110–116.
A prospective, randomized comparative study of patient perceptions and preferences of two types of indwelling voice prostheses
Authors: Hancock Kelli , Ward Elizabeth , Lawson Nadine , As‐Brooks Corina J. van
Published: March 2012

Background: Technical and device life issues are frequently the focus of post‐laryngectomy rehabilitation studies examining indwelling voice prostheses. Patient perceptions and preferences are considered less often.

Aims: To determine patient perceptions of two indwelling voice prostheses across parameters relating to device use and maintenance and to determine what factors contribute to patient preferences.

Methods & Procedures: In a randomized, cross‐over study, 31 laryngectomy patients completed a 3‐week trial of both the new indwelling Provox Vega and a comparator device, the Blom–Singer Classic Indwelling. Patient perceptions of the insertion process, cleaning and care, and voicing were explored after each trial. At the end, overall preference and factors influencing device preference were examined.

Outcome & Results: At the conclusion of the crossover trial, a significantly higher proportion of patients felt voice effort, overall voicing, bloating, and ease and effectiveness of cleaning were superior for the Provox Vega. No preference was noted for insertion processes. Overall device preference was influenced by improved voicing followed by cleaning and care.

Conclusions & Implications: Patients do not perceive all indwelling devices as equal and should have the opportunity to trial different devices to find the best device for their needs.
Community‐based early intervention for language delay: a preliminary investigation
Authors: Ciccone Natalie , Hennessey Neville , Stokes Stephanie F.
Published: March 2012

Background: A trial parent‐focused early intervention (PFEI) programme for children with delayed language development is reported in which current research evidence was translated and applied within the constraints of available of clinical resources. The programme, based at a primary school, was run by a speech–language pathologist with speech–language pathology students.

Aim: To investigate the changes in child language development and parent and child interactions following attendance at the PFEI.

Methods & Procedures: Eighteen parents and their children attended six, weekly group sessions in which parents were provided with strategies to maximize language learning in everyday contexts. Pre‐ and post‐programme assessments of vocabulary size and measures of parent–child interaction were collected.

Outcome & Results: Parents and children significantly increased their communicative interactions from pre‐ to post‐treatment. Children's expressive vocabulary size and language skills increased significantly. Large‐effect sizes were observed.

Conclusions & Implications: The positive outcomes of the intervention programme contribute to the evidence base of intervention strategies and forms of service delivery for children at risk of language delay.
A Matching Prior for the Shape Parameter of the Skew‐Normal Distribution
Authors: CABRAS STEFANO , RACUGNO WALTER , CASTELLANOS MARÍA EUGENIA , VENTURA LAURA
Published: March 2012

Abstract. This paper deals with the issue of performing a default Bayesian analysis on the shape parameter of the skew‐normal distribution. Our approach is based on a suitable pseudo‐likelihood function and a matching prior distribution for this parameter, when location (or regression) and scale parameters are unknown. This approach is important for both theoretical and practical reasons. From a theoretical perspective, it is shown that the proposed matching prior is proper thus inducing a proper posterior distribution for the shape parameter, also when the likelihood is monotone. From the practical perspective, the proposed approach has the advantages of avoiding the elicitation on the nuisance parameters and the computation of multidimensional integrals.
Clopidogrel Increases Bleeding Complications in Patients Undergoing Heart Rhythm Device Procedures
Authors: BOULÉ STÉPHANE , MARQUIÉ CHRISTELLE , VANESSON‐BRICOUT CLAIRE , KOUAKAM CLAUDE , BRIGADEAU FRANÇOIS , GUÉDON‐MOREAU LAURENCE , ACHERÉ CHARLES , GOÉMINNE‐BOULÉ CÉLINE , LACROIX DOMINIQUE , KLUG DIDIER , KACET SALEM
Published: March 2012

Background:

Management of antiplatelet therapy at the time of device implantation remains controversial. This study aimed to assess the risk of bleeding complications in patients receiving clopidogrel at the time of cardiac device surgery.

Methods:

We performed a retrospective case‐control study. Between 2004 and 2010, 101 consecutive patients receiving clopidogrel underwent cardiac device surgery (pacemaker or implantable cardioverter–defibrillator implantation, and generator replacement) in our institution. Controls were 1:1 matched on age, sex, device, type of procedure, number of leads implanted, and venous approach (cephalic or subclavian). A significant bleeding complication was defined as pocket hematoma requiring surgical evacuation or prolonged hospitalization, hemothorax, pericardial effusion, or tamponade.

Results:

Bleeding complications occurred more frequently in patients receiving clopidogrel at the time of device procedure: 11.9% versus 4.0% (P = 0.037; odds radio [OR] 3.27 [1.02–10.5]). Significant bleeding complications were noted in 12 patients (11.9%) receiving clopidogrel, including two patients with pericardial effusion and one patient with hemothorax. Four controls (4.0%) had bleeding complications (three pocket hematomas and one pericardial effusion). The single factor associated with increased bleeding complications in patients receiving clopidogrel was subclavian puncture (P = 0.008). In the entire cohort (n = 202), multivariate analysis identified two independent predictors of significant bleeding complications: clopidogrel treatment at the time of surgery (P = 0.03; OR 3.7 [1.1–12.6]) and subclavian venous puncture (P = 0.03; OR 3.44 [1.1–10.4]).

Conclusions:

Clopidogrel treatment at the time of heart rhythm device procedures is associated with an increased risk of significant bleeding complications. Subclavian puncture seems to strongly increase hemorrhagic complications in this setting. (PACE 2012; 1–7)
Live/Real Time Three‐Dimensional Transthoracic Echocardiographic Assessment of the Involvement of Cardiac Valves and Chambers in Carcinoid Disease
Authors: Dumaswala Bhavin , Bicer Elif Ijlal , Dumaswala Komal , Donmez Cevdet , Bhagatwala Kunal D. , Karia Nidhi , McKay Joshua , Joshi Deepak , Sadat Kamel , Nanda Navin C.
Published: March 2012

We present an adult with metastatic carcinoid disease affecting the heart, in whom live/real time three‐dimensional transthoracic echocardiography (3DTTE) provided incremental value over two‐dimensional transthoracic echocardiography (2DTTE). Initial 2DTTE was able to demonstrate severe pulmonic and tricuspid regurgitation, but was unable to visualize the posterior leaflet of the tricuspid valve or the right (right anterior) leaflet of the pulmonic valve. Further analysis with 3DTTE demonstrated thickening, restricted mobility, and noncoaptation of all three leaflets of both the tricuspid and the pulmonary valves. En face viewing of tricuspid and pulmonary regurgitation vena contractas permitted more reliable quantification of regurgitation severity. In addition, localized, linear, echogenic areas consistent with carcinoid deposits were noted along the inner walls of the right atrium, atrial septum, and inferior vena cava. To the best of our knowledge, endocardial carcinoid deposits have never been reported by 2D or 3D echocardiography. En face viewing of these deposits by 3DTTE enabled measurement of their dimensions and areas. Subcostal examination also identified large circumscribed hepatic lesions consistent with metastatic disease. Neither the carcinoid deposits nor the metastatic lesions were detected by 2DTTE. This case demonstrates the usefulness of 3DTTE as a supplement to 2DTTE in more comprehensively assessing carcinoid involvement of the heart. (Echocardiography 2012;29:E72‐E77)
Attentional Factors in Conceptual Congruency
Authors: Santiago Julio , Ouellet Marc , Román Antonio , Valenzuela Javier
Published: March 2012

Conceptual congruency effects are biases induced by an irrelevant conceptual dimension of a task (e.g., location in vertical space) on the processing of another, relevant dimension (e.g., judging words’ emotional evaluation). Such effects are a central empirical pillar for recent views about how the mind/brain represents concepts. In the present paper, we show how attentional cueing (both exogenous and endogenous) to each conceptual dimension succeeds in modifying both the manifestation and the symmetry of the effect. The theoretical implications of this finding are discussed.
Tissue engineering and regenerative medicine –where do we stand?
Authors: Horch Raymund E. , Kneser Ulrich , Polykandriotis Elias , Schmidt Volker J. , Sun Jiaming , Arkudas Andreas
Published: March 2012

Introduction

Intrinsic and extrinsic vascularization of TE constructs – the AV‐loop model

Gene Transfer Techniques

Combining mesenchymal stem cells with the AV‐loop model of intrinsic vascularization

TE and RM in the context of Cancer Research

Newly discovered cells of potential benefit for RM

Summary

Tissue Engineering (TE) in the context of Regenerative Medicine (RM) has been hailed for many years as one of the most important topics in medicine in the twenty‐first century. While the first clinically relevantTEefforts were mainly concerned with the generation of bioengineered skin substitutes, subsequentlyTEapplications have been continuously extended to a wide variety of tissues and organs. The advent of either embryonic or mesenchymal adult stem‐cell technology has fostered many of the efforts to combine this promising tool withTEapproaches and has merged the field into the term Regenerative Medicine. As a typical example in translational medicine, the discovery of a new type of cells called Telocytes that have been described in many organs and have been detected by electron microscopy opens another gate toRM. Besides cell‐therapy strategies, the application of gene therapy combined withTEhas been investigated to generate tissues and organs. The vascularization of constructs plays a crucial role besides the matrix and cell substitutes. Therefore, novelin vivomodels of vascularization have evolved allowing axial vascularization with subsequent transplantation of constructs. This article is intended to give an overview over some of the most recent developments and possible applications inRMthrough the perspective ofTEachievements and cellular research. The synthesis ofTEwith innovative methods of molecular biology and stem‐cell technology appears to be very promising.
Deletion of angiotensin II type 1 receptor gene or scavenge of superoxide prevents chronic alcohol‐induced aortic damage and remodelling
Authors: Bai Yang , Tan Yi , Wang Bo , Miao Xiao , Chen Qiang , Zheng Yang , Cai Lu
Published: March 2012

To investigate whether chronic alcohol consumption induces vascular injury via angiotensin II (Ang II) type 1 (AT1) receptor‐dependent superoxide generation, male transgenic mice with knockout of AT1 gene (AT1‐KO) and age‐matched wild‐type (WT) C57BL/6 mice were pair‐fed a modified Lieber‐DeCarli alcohol or isocaloric maltose dextrin control liquid diet for 2 months. Ethanol content (%, W/V) in the diet was 4.8 (34% of total calories) at initiation, and gradually increased up to 5.4 (38% of total calories). For some WT mice with and without alcohol treatment, superoxide dismutase mimetic (MnTMPyP) was given simultaneously by intraperitoneal injection at 5 mg/kg body weight daily for 2 months. At the end of studies, aortas were harvested for histopathological and immunohistochemical examination. Significant increases in the wall thickness and structural disarrangement of aorta were found in alcohol group, along with significant increases in aortic oxidative and/or nitrosative damage, expressions of NADPH oxidases (NOXs), inflammatory response, cell death and proliferation, and remodelling (fibrosis). However, these pathological changes were completely attenuated in alcohol‐treated AT1‐KO mice or in alcohol‐treated WT mice that were also simultaneously treated with MnTMPyP for 2 months. These results suggest that chronic alcohol consumption may activate NOX via Ang II/AT1 receptor, to generate superoxide and associated peroxynitrite that in turn causes aortic nitrosative damage, inflammation, cell death and proliferation, and remodelling. Therefore, blocking Ang II/AT1 system or scavenging superoxide may become a potential preventive and/therapeutic approach to alcoholic vascular damage.
Utility of toluidine blue as a diagnostic adjunct in the detection of potentially malignant disorders of the oral cavity – a clinical and histological assessment
Authors: Awan KH , Yang YH , Morgan PR , Warnakulasuriya S
Published: March 2012

Oral Diseases (2012) 18, 728–733

Background:  The value of chairside adjunctive tests in the detection of oral potentially malignant disorders (OPMDs) remains uncertain.

Objectives:  To determine the effectiveness of toluidine blue in detecting leukoplakia and erythroplakia and its accuracy in identifying cases with oral epithelial dysplasia.

Materials and Methods:  Ninety‐two patients attending two oral medicine clinics in London, presenting with white and red patches of the oral mucosa, were investigated by the application of toluidine blue. Eighty‐two patients were clinically diagnosed as OPMDs and 10 were frictional keratoses. A surgical biopsy was performed to assess epithelial dysplasia.

Results:  Of 64 oral leukoplakias, 34 (53.1%) were positive for toluidine blue and among nine erythroplakias seven stained positive. Of 41 oral dysplasia cases, a little more than half of the lesions (n = 23) were stain positive, an estimated sensitivity of 56.1%. TBlue test had a higher sensitivity for detecting higher‐grade dysplastic lesions (5/8 moderate dysplasia, sensitivity 62.5%; 5/7 severe dysplasia; sensitivity 71.4%) compared with lower grades of dysplasia, but the differences were not significant (P = 0.60).

Conclusions:  We report here the utility of TBlue for the detection of oral leukoplakia and erythroplakia. The test has the potential to detect OPMDs and yielded a sensitivity of 56.1% and specificity of 56.9% to detect oral epithelial dysplasia.
Bioenergy from Mountain Pine Beetle Timber and Forest Residuals: A Cost Analysis
Authors: Niquidet Kurt , Stennes Brad , van Kooten G. C.
Published: March 2012

In light of the large volumes of pine killed in the interior forests of British Columbia (BC) by the mountain pine beetle, many forest sector participants are keen to employ forest biomass as an energy source. To assess the feasibility of a wood biomass‐fired power plant in the BC interior, it is necessary to know both how much physical biomass might be available over the life of a plant and its location as transportation cost is likely to be a major operating cost for any facility. To address these issues, we construct a mathematical programming model of fiber flows in the Quesnel Timber Supply Area of BC over a 25‐year time horizon. The focus of the model is on minimizing the cost of supplying feedstock through space and time. Results indicate that over the life of the project, feedstock costs will more than double, increasing from $54.60/bone‐dry tonnes (BDt) ($0.039/kWh) to $116.14/BDt ($0.083/kWh).

En raison de l’important volume de pins dévastés par le dendroctone du pin ponderosa dans les forêts de l’intérieur de la Colombie‐Britannique (BC), de nombreux participants du secteur forestier sont désireux d’utiliser la biomasse forestière comme source d’énergie. Pour évaluer la faisabilité d’une centrale alimentée à la biomasse ligneuse à l’intérieur de la Colombie‐Britannique, il faut connaître la quantité de biomasse disponible pendant la durée de vie de la centrale ainsi que l’emplacement de cette biomasse étant donné que les coûts de transport risquent de représenter des coûts d’exploitation importants pour n’importe quelle installation. Afin d’examiner ces aspects, nous avons élaboré un modèle de programmation mathématique de l’approvisionnement en matière ligneuse dans la zone d’approvisionnement forestier de Quesnel en Colombie‐Britannique, sur un horizon de 25 ans. Le modèle visait principalement à réduire le coût liéà l’approvisionnement en matière première à travers l’espace et le temps. D’après nos résultats, les coûts de la matière première feront plus que doubler au cours de la durée du projet, passant de 54,60 $/tonne anhydre (t.a.) (0,039 $/kWh) à 116,14 $/t.a. (0,083 $/kWh).