bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and safety of canagliflozin monotherapy in subjects with type 2 diabetes mellitus inadequately controlled with diet and exercise
Authors: Stenlöf K. , Cefalu W. T. , Kim K.‐A. , Alba M. , Usiskin K. , Tong C. , Canovatchel W. , Meininger G.
Published: December 2012

Aims

Canagliflozin is a sodium glucose co‐transporter 2 inhibitor in development for type 2 diabetes mellitus (T2DM). The efficacy and safety of canagliflozin were evaluated in subjects with T2DM inadequately controlled with diet and exercise.

Methods

In this 26‐week, randomized, double‐blind, placebo‐controlled, phase 3 trial, subjects (N = 584) received canagliflozin 100 or 300 mg or placebo once daily. Primary endpoint was the change from baseline in haemoglobin A1c (HbA1c) at week 26. Secondary endpoints included the proportion of subjects achieving HbA1c < 7.0%; change from baseline in fasting plasma glucose (FPG), 2‐h postprandial glucose (PPG) and systolic blood pressure (BP); and percent change in body weight, high‐density lipoprotein cholesterol (HDL‐C) and triglycerides. Adverse events (AEs) were recorded throughout the study.

Results

At week 26, HbA1c was significantly reduced from baseline with canagliflozin 100 and 300 mg compared with placebo (−0.77, −1.03 and 0.14%, respectively; p < 0.001 for both). Both canagliflozin doses significantly decreased FPG, 2‐h PPG, body weight and systolic BP (p < 0.001 for all), and increased HDL‐C compared with placebo (p < 0.01 for both). Overall incidences of AEs were modestly higher with canagliflozin versus placebo; rates of serious AEs and AE‐related discontinuations were low and similar across groups. Incidences of genital mycotic infections, urinary tract infections and osmotic diuresis‐related AEs were higher with canagliflozin; these led to few discontinuations. The incidence of hypoglycaemia was low across groups.

Conclusion

Canagliflozin treatment improved glycaemic control, reduced body weight and was generally well tolerated in subjects with T2DM inadequately controlled with diet and exercise.
Comparative study of sitagliptin with pioglitazone in Japanese type 2 diabetic patients: the COMPASS randomized controlled trial
Authors: Takihata M. , Nakamura A. , Tajima K. , Inazumi T. , Komatsu Y. , Tamura H. , Yamazaki S. , Kondo Y. , Yamada M. , Kimura M. , Terauchi Y.
Published: December 2012

Aims

To compare the efficacy and safety of these two agents and the impact on surrogate markers related to diabetic complications in Japanese type 2 diabetic patients.

Methods

In a multicenter, open‐label trial, 130 patients whose diabetes had been inadequately controlled (HbA1c, 6.9–9.5%) with metformin and/or sulphonylurea were randomly assigned to a sitagliptin group (50 mg/day) or a pioglitazone group (15 mg/day) and were followed up for 24 weeks. At 16 weeks, if the patient's HbA1c level was ≥6.5%, the dose of sitagliptin or pioglitazone was increased up to 100 or 30 mg/day, respectively. Main outcome measure was the difference in the mean changes in the HbA1c level from baseline at 24 weeks between these two groups.

Results

Of the 130 patients who were enrolled, 115 subjects (sitagliptin group: 58 patients, pioglitazone group: 57 patients) completed this trial. At 0 weeks, the mean HbA1c level was 7.47 ± 0.66% in the sitagliptin group and 7.40 ± 0.61% in the pioglitazone group. At 24 weeks, the mean changes in the HbA1c level from baseline were −0.86 ± 0.63% versus −0.58 ± 0.68% (p = 0.024). Hypoglycaemia (2 patients, 3.4% vs. 2 patients, 3.5%), gastrointestinal symptoms (3 patients, 5.2% vs. 1 patient, 1.8%) and pretibial oedema (0 patients, 0% vs. 39 patients, 68.4%, p < 0.001) were observed for 24 weeks.

Conclusions

Sitagliptin was not only more tolerable, but also more effective than pioglitazone in Japanese type 2 diabetic patients who had been treated with metformin and/or sulphonylurea.
Higher protein diet for weight management in young overweight women: a 12‐month randomized controlled trial
Authors: Griffin H. J. , Cheng H. L. , O'Connor H. T. , Rooney K. B. , Petocz P. , Steinbeck K. S.
Published: December 2012

Clinical research on weight management in young women is limited. This randomized controlled trial compared the efficacy of two iso‐energetically restricted (5600 kJ) diets [higher protein (HP): 32% protein, 41% carbohydrate, 25% fat or higher carbohydrate (HC): 20, 58, 21%, respectively] in 71 (HP: n = 36; HC: n = 35) young healthy women (18–25 years; body mass index ≥ 27.5 kg/m2) for weight (kg; percent weight loss), body composition, metabolic and iron changes assessed at baseline, 6 and 12 months. Data: mean (95% CI). In HP completers at 6 months, percent weight loss was higher [HP: 9.3 (5.6–13.1); HC: 5.1 (2.3–7.9)%; p = 0.06]; although, this did not reach statistical significance. Absolute weight [HP: 8.9 (5.3–12.5); HC: 4.6 (2.2–7.0) kg; p = 0.034] and fat loss [HP: 8.0 (4.4–11.5); HC: 3.4 (1.3–5.6) kg; p = 0.022] were significantly greater. No significant between‐diet differences were observed at 12 months. Biochemistry remained within normal ranges with HP showing superior preservation of ferritin at 6 months [HP: 53 (40–66); HC: 46 (30–61) µg/l; p = 0.029]. Both diets supported clinically meaningful weight loss with HP tending to be more effective in the medium‐term.
The efficacy and safety of ezetimibe/simvastatin combination compared with intensified lipid‐lowering treatment strategies in diabetic subjects with and without metabolic syndrome
Authors: Jimenez J. G. , Rosen J. B. , Pirags V. , Massaad R. , Hanson M. E. , Brudi P. , Triscari J.
Published: December 2012

Aims

The objective was to assess the consistency of effect of switching to ezetimibe/simvastatin 10/20 mg versus doubling the baseline statin dose (to simvastatin 40 mg or atorvastatin 20 mg) or switching to rosuvastatin 10 mg across subgroups of subjects with (n = 617) and without (n = 191) metabolic syndrome (MetS).

Methods

This was a post hoc analysis of a randomized, double‐blind, 6‐week study of adults 18–79 years with cardiovascular disease and diabetes mellitus with low‐density lipoprotein cholesterol (LDL‐C) ≥70 and ≤160 mg/dl. The percent change in LDL‐C and other lipids was estimated within each subgroup separately. Safety and tolerability were assessed.

Results

In subjects with MetS, percent changes in LDL‐C and other lipids were greater with ezetimibe/simvastatin versus doubling baseline statin or numerically greater versus switching to rosuvastatin, except high‐density lipoprotein cholesterol and apolipoprotein (Apo) AI (mean percent changes in LDL‐C were: −22.49% ezetimibe/simvastatin, −9.64% doubled baseline statin and −19.20% rosuvastatin). In subjects without MetS, percent changes in LDL‐C, total cholesterol and Apo B were greater with ezetimibe/simvastatin versus doubling baseline statin or numerically greater versus switching to rosuvastatin (mean percent changes in LDL‐C were: −25.14% ezetimibe/simvastatin, −4.75% doubled baseline statin and −19.75% rosuvastatin). Safety profiles were generally similar.

Conclusion

These results showed that switching to ezetimibe/simvastatin 10/20 mg was more effective at reducing LDL‐C, total cholesterol and Apo B versus doubling the baseline statin dose to simvastatin 40 mg or atorvastatin 20 mg or switching to rosuvastatin 10 mg regardless of MetS status. These results were generally similar to those of the full cohort.
The “Encounter” as an “Event of Truth” in Education: An Anthropological‐Pedagogical Approach
Authors: Pantazis Vasileios E.
Published: December 2012

In this essay, Vasileios Pantazis examines how two philosophers having different orientations acknowledge and study the phenomenon of the “encounter” (Begegnung) and its fundamental importance to human life and education. On the one hand, Otto Friedrich Bollnow drew on existential philosophy and philosophical anthropology in his analysis of the encounter, while Alain Badiou, on the other hand, used psychoanalysis, mathematics, and Plato in exploring the concept. The approach Pantazis takes in this essay aims at fusing the concept of the encounter as developed by Bollnow with a philosophical view, specifically Badiou's understanding of the encounter in the context of his concept “event of truth.” Through the “fusion of horizons,” as Hans‐Georg Gadamer put it, between these two views, Pantazis seeks to enrich the concept of the encounter and to draw out a renewed meaning for philosophical and educational theory.
Levinas and the Mission of Education
Authors: Zhao Guoping
Published: December 2012

The current educational discourse on Emmanuel Levinas's concept of subjectivity has focused on the pure openness and subjection of the self to the other. Based on such an understanding, some educational theorists hold that Levinas's work has given us new hope for the mission of education, while others deny its relevance. I suggest that this interpretation of Levinas has missed the complete structure of his account of subjectivity, and, as a result, a full appreciation of its potential for education is yet to be realized. Offering a different account of Levinas's subjectivity, I join Gert Biesta and Sharon Todd in seeing Levinas as essentially important in providing new inspiration, a new way out of both the humanist trap of a fixed essence, where education inevitably becomes socialization, and the posthumanist impasse, where education loses its ground and its orientation. Levinas's subjectivity has made it possible for us to forge a pedagogy that is different from socialization and interruption — a pedagogy of becoming — and allows a genuine educational mission of subjectification, albeit toward a new, much different subjectivity.
Epistemic Progress: A Construct for Understanding and Evaluating Inquiry
Authors: Golding Clinton
Published: December 2012

In this essay Clinton Golding introduces a new construct and area of research — epistemic progress — and argues that it can shed new light on educational inquiry. By clearly distinguishing progress through developing better ideas (epistemic progress) from progress through developing better inquiry skills (procedural progress), teachers and students can better understand, participate in, and evaluate inquiry. In addition, epistemic progress complements other epistemic constructs, such as “knowledge,” and could provide new insights about different kinds of inquiry or research, as well as about the diverse disciplines and areas of study.
Higher Education, Academic Communities, and the Intellectual Virtues
Authors: Jones Ward E.
Published: December 2012

Because higher education brings members of academic communities in direct contact with students, the reflective higher education student is in an excellent position for developing two important intellectual virtues: confidence and humility. However, academic communities differ as to whether their members reach consensus, and their teaching practices reflect this difference. In this essay, Ward Jones argues that both consensus‐reaching and non‐consensus‐reaching communities can encourage the development of intellectual confidence and humility in their students, although each will do so in very different ways.
Host feeding experience affects host plant odour preference of the polyphagous leafminer Liriomyza bryoniae
Authors: Radžiutė Sandra , Būda Vincas
Published: December 2012

Herbivorous insects use highly specific volatiles or blends of volatiles characteristic to particular plant species to locate their host plants. Thus, data on olfactory preferences can be valuable in developing integrated pest management tools that deal with manipulation of pest insect behaviour. We examined host plant odour preferences of the tomato leafminer, Liriomyza bryoniae (Kaltenbach) (Diptera: Agromyzidae), which is an economically important agricultural pest widespread throughout Europe. The odour preferences of leafminers were tested in dependence of feeding experiences. We ranked host plant odours by their appeal to L. bryoniae based on two‐choice tests using a Y‐tube olfactometer with five host plants: tomato, Solanum lycopersicum Mill.; bittersweet, Solanum dulcamara L.; downy ground‐cherry, Physalis pubescens L. (all Solanaceae); white goosefoot, Chenopodium album L. (Chenopodiaceae); and dead nettle, Lamium album L. (Lamiaceae). The results imply that ranking of host plant odours by their attractiveness to L. bryoniae is complicated due to the influence of larval and adult feeding experiences. Without any feeding experience as an adult, L. bryoniae males showed a preference for the airflow with host plant odour vs. pure air, whereas females did not display a preference. Further tests revealed that adult feeding experience can alter the odour choice of L. bryoniae females. After feeding experience, females showed a preference for host plant odour vs. pure air. Feeding experience in the larval stage influenced the choice by adults of both sexes: for males as well as females reared on bittersweet the odour of that plant was the most attractive. Thus, host feeding experience both in larval and/or adult stage of polyphagous tomato leafminer L. bryoniae influences host plant odour preference by adults.
A spectrophotometric technique for measuring particle ingestion by black fly larvae
Authors: Iburg Joseph P. , Gray Elmer W. , Wyatt Roger D. , Noblet Raymond
Published: December 2012

A spectrophotometric technique was developed to provide insight into the feeding behavior of Simulium vittatum Zetterstedt (Diptera: Simuliidae) larvae. Larvae were exposed to water insoluble Neon Red particles (NRP) (DayGlo®) in a controlled current. The insoluble particles were available for capture by the cephalic fans of the larvae and subsequent ingestion. The length of gut occupied by the particles after a given exposure time was determined by visual inspection and measured with the aid of a dissecting microscope. Larvae were then homogenized in acetone to solubilize the particles. After filtration, the quantity of pigmented particles in the alimentary tract of the larvae was determined using spectrophotometric analysis. The quantity of particles per unit length of the alimentary tract was calculated. Experiments were conducted to determine the ideal concentration of NRP for obtaining an accurate measure of ingestion without interfering with normal larval feeding behavior. Larval mortality following ingestion of insecticidal proteins produced by Bacillus thuringiensis ssp. israelensis was used as an indirect measure of feeding behavior for these experiments. A concentration of 15 p.p.m. of NRP in the larval medium was the highest concentration used that did not interfere with larval mortality following exposure to the insecticidal proteins. Additional experiments demonstrated that components of the experimental matrix did not interfere with NRP absorbance. The final experiment revealed that the consumption of NRP and insecticidal proteins by larvae was influenced by clay and cellulose in the larval medium.
Herbivore community promotes trait evolution in a leaf beetle via induced plant response
Authors: Utsumi Shunsuke , Ando Yoshino , Roininen Heikki , Takahashi Jun‐ichi , Ohgushi Takayuki
Published: December 2012

Several recent studies have emphasised that community composition alters species trait evolution. Here, we demonstrate that differences in composition of local herbivore communities lead to divergent trait evolution of the leaf beetle Plagiodera versicolora through plant‐mediated indirect interactions. Our field surveys, genetic analyses and community‐manipulation experiments show that herbivore community composition determines the degree of herbivore‐induced regrowth of willows (Salicaceae), which in turn, promotes the divergent evolution of feeding preference in the leaf beetle from exclusive preference for new leaves to a lack of preference among leaf‐age types. Regrowth intensity depends both on the differential response of willows to different herbivore species and the integration of those herbivore species in the community. Because herbivore‐induced regrowth involves phenological changes in new leaf production, leaf beetle populations develop divergent feeding preferences according to local regrowth intensity. Therefore, herbivore community composition shapes the selection regime for leaf beetle evolution through trait‐mediated indirect interactions.
The effect of early prednisolone treatment on the generalization rate in ocular myasthenia gravis
Authors: Zach H. , Cetin H. , Hilger E. , Paul A. , Wuschitz B. , Jung R. , Auff E. , Zimprich F.
Published: December 2012

Background and purpose

Several small retrospective studies have observed that patients with a purely ocular manifestation of myasthenia gravis (MG) are significantly less likely to convert to a generalized disease when treated early on with corticosteroids. However, given the limited number of reported patients in the literature these findings still remain controversial.

Methods

In order to increase the number of published cases, we performed a retrospective analysis on 44 patients with newly diagnosed ocular MG who were subsequently either treated with corticosteroids or received no immunosuppressive therapy at all. The generalization rate was assessed at the end of a 2‐year follow‐up period.

Results

Whereas none of 17 treated patients generalized, 11 of 27 (41%) untreated patients developed generalized symptoms. The difference between the groups was significant (P = 0.003).

Conclusions

Our results agree well with previous studies on this issue. Taken together, published data indicate risk ratios for generalization of below 0.32 under corticosteroid treatment in comparison to untreated patients.
Long‐term MRI findings in neuromyelitis optica: seropositive versus seronegative patients
Authors: Kıyat‐Atamer A. , Ekizoğlu E. , Tüzün E. , Kürtüncü M. , Shugaiv E. , Akman‐Demir G. , Eraksoy M.
Published: December 2012

Background and purpose

Neuromyelitis optica (NMO) is a severe demyelinating inflammatory disorder associated with serum antibodies against aquaporin 4 (AQP4‐Ab). A significant number of patients with NMO remain seronegative over time. Long‐term observational magnetic resonance imaging (MRI) studies of the CNS in patients with NMO are rare or of limited duration. The objective of this study is to determine long‐term MRI characteristics of seropositive and seronegative patients, and assess possible overlap with multiple sclerosis (MS).

Methods

Clinical and radiological characteristics of 28 patients with NMO at onset and of 17 patients after an average follow‐up time of 9 years were recorded. Fifty percent of patients were seropositive for AQP4‐Ab. Onset and final brain/spinal MRI scans were retrospectively analysed and compared.

Results

Significantly more patients in the seronegative group had brain lesions at onset. Spinal lesions of seropositive patients were longer and showed increased cord swelling at onset MRI scans. After the follow‐up time the differences between both groups disappeared. Patients in the seropositive group tended to develop brain lesions over time. No patient fulfilled Barkhof's or McDonald's radiological criteria for MS at onset or over time.

Conclusion

Brain MRI features show differences between seropositive and seronegative patients at time of onset in NMO, but differences between groups vanish over time. None of the AQP4‐negative patients fulfill radiological MS criteria on a long‐term basis, suggesting that seronegative NMO constitutes an independent entity.
Dental fear and sense of coherence among 18‐yr‐old adolescents in Finland
Authors: Jaakkola Sirkka , Rautava Päivi , Saarinen Maiju , Lahti Satu , Mattila Marja‐Leena , Suominen Sakari , Räihä Hannele , Aromaa Minna , Honkinen Päivi‐Leena , Sillanpää Matti
Published: December 2012

The aim was to investigate whether dental fear was associated with the sense of coherence (SOC) among 18‐yr‐old adolescents (n = 777). Cross‐sectional data from a prospective cohort of a random sample of families from Finland and their first‐born children were used. Dental fear was measured using the Modified Dental Anxiety Scale and categorized as high dental fear for scores of 19–25 and as no to moderate dental fear for scores of 5–18. Sense of coherence was measured using a 13‐item version of Antonovsky's Sense of Coherence Questionnaire, dichotomized as scores 13–63 for weak SOC and as scores of 64–91 for strong SOC. Gender and education were included as background factors in the logistic regression analyses. The prevalence of high dental fear was 8%. Those reporting high dental fear reported more often a weaker SOC than did those with no to moderate dental fear (69% vs. 31%, OR = 2.5, 95% CI = 1.4–4.4), also when adjusted for gender and education (OR = 2.2, 95% CI = 1.2–3.9). According to the theory of salutogenesis, as proposed by Antonovsky, SOC is a resource instrument especially in situations of tension or strain and hence a strong SOC might protect against high dental fear.
Risk factors for large colon volvulus in theUK
Authors: Suthers J. M. , Pinchbeck G. L. , Proudman C. J. , Archer D. C.
Published: December 2012

Reasons for performing study

Risk factors for large colon volvulus (LCV) in the horse have not been previously reported. Knowledge of these risk factors may allow the introduction of measures that could be taken to minimise the incidence ofLCV.

Objectives

To investigate risk factors forLCVin the horse.

Methods

A prospective, multicentre, unmatched case‐control study was conducted over a 24 month period in theUK. Data on 69 cases and 204 control horses, from 4 veterinary hospitals, were obtained via telephone questionnaires. Multivariable logistic regression was used to identify associations between horse and management‐level variables and the likelihood ofLCV.

Results

Increasing height, multiple colic episodes in the previous 12 months and mares, with a greater odds ratio in mares that had previously foaled, were associated with increased risk ofLCV. Receiving medication (excluding anthelmintic treatment) in the previous 7 days and quidding behaviour were also associated with increased risk. Management‐level variables associated with greater risk ofLCVwere an increase in the hours of stabling in the previous 14 days, an increasing number of horses on the premises, and 3 or more people involved in the horse's care. Variables related to nutrition associated with increased risk ofLCVwere being fed hay, being fed sugar‐beet, a change in pasture in the previous 28 days, and an alteration in the amount of forage fed in the last 7 days.

Conclusions

This study has identified factors that may assist in the recognition of horses with increased risk ofLCVand factors that might be altered to minimise the incidence ofLCV.

Potential relevance

Clinicians can use this information to identify horses at risk ofLCVand to provide evidence‐based advice to owners of these horses.

See also correspondence by Durham
There is more than one ‘killer shrimp’: trophic positions and predatory abilities of invasive amphipods of Ponto‐Caspian origin
Authors: BACELA‐SPYCHALSKA KAROLINA , VAN DER VELDE GERARD
Published: December 2012

1. Biological invasions are regarded as one of the greatest threats to biological diversity. One of the macroinvertebrate groups with the largest number of invasive species in fresh water are gammarid amphipods. Their omnivorous (including predatory) feeding behaviour may facilitate their spread and establishment in new areas.

2. Dikerogammarus villosus, the ‘killer shrimp’, is a well‐known example of a Ponto‐Caspian gammarid that is a very effective predator and successful coloniser in Europe. There are, however, other invasive Ponto‐Caspian amphipods, which have spread successfully in Northern, Central and Western Europe. Our aim here was to test whether two of such invaders (Pontogammarus robustoides and Dikerogammarus haemobaphes) are also more predacious than a native species (Gammarus fossarum).

3. Stable isotope analysis (δ15N and δ13C) of Ponto‐Caspian amphipods coexisting in a reservoir demonstrated that the trophic positions of P. robustoides and D. haemobaphes were similar to that of D. villosus. Echinogammarus ischnus and Chelicorophium curvispinum occupied the lowest position in the food web, while the native Gammarus fossarum (collected from another waterbody) had an intermediate trophic position.

4. Stomach content analysis of P. robustoides, D. haemobaphes and G. fossarum collected in the field, as well as laboratory feeding experiments, was used to compare diet and feeding preferences among the two invasive and one native species. All three species were omnivorous and predacious. However, the two invasive species (P. robustoides and D. haemobaphes) were more effective predators than G. fossarum and showed a clear preference for animal prey and tissue.

5. Pontogammarus robustoides and D. haemobaphes may, like D. villosus, also be called ‘killer shrimps’ and could have a similar impact as invaders of European freshwater and brackish waterbodies.
Crypsis in a heterogeneous environment: relationships between changeable polymorphic colour patterns and behaviour in a galaxiid fish
Authors: MAGELLAN KIT , SWARTZ ERNST R.
Published: December 2012

1. The ability to achieve optimal camouflage varies between microhabitats in heterogeneous environments, potentially restricting individuals to a single habitat or imposing a compromise on crypsis to match several habitats. However, animals may exhibit morphological and behavioural attributes that enhance crypsis in different habitats.

2. We used an undescribed fish species, Galaxias‘nebula’, to investigate two objectives. First, we examined two potential methods of enhancing crypsis: change in colour pattern and selection of a suitable background. Second, we characterised the colour pattern of this unstudied fish and assessed its capacity for crypsis.

3. No background selection was apparent but the area of dark pigment expressed varied between backgrounds, which may negate the requirement to be choosy about habitats. The capacity to change colour and selection of a background that maximises crypsis are most likely separate, non‐mutually exclusive strategies.

4. Galaxias‘nebula’ exhibits polymorphic, non‐interchangeable colour patterns that have elements of both background pattern matching and disruptive colouration. This, coupled with habitat characteristics, suggests a combination of generalist and specialist strategies of habitat use. The fish’s camouflage strategy and air‐breathing ability may be key to survival under increasing pressure from habitat degradation and invasive predators.
Methane emissions from wetlands: biogeochemical, microbial, and modeling perspectives from local to global scales
Authors: Bridgham Scott D. , Cadillo‐Quiroz Hinsby , Keller Jason K. , Zhuang Qianlai
Published: December 2012

Understanding the dynamics of methane (CH4) emissions is of paramount importance because CH4 has 25 times the global warming potential of carbon dioxide (CO2) and is currently the second most important anthropogenic greenhouse gas. Wetlands are the single largest natural CH4 source with median emissions from published studies of 164 Tg yr−1, which is about a third of total global emissions. We provide a perspective on important new frontiers in obtaining a better understanding of CH4 dynamics in natural systems, with a focus on wetlands. One of the most exciting recent developments in this field is the attempt to integrate the different methodologies and spatial scales of biogeochemistry, molecular microbiology, and modeling, and thus this is a major focus of this review. Our specific objectives are to provide an up‐to‐date synthesis of estimates of global CH4 emissions from wetlands and other freshwater aquatic ecosystems, briefly summarize major biogeophysical controls over CH4 emissions from wetlands, suggest new frontiers in CH4 biogeochemistry, examine relationships between methanogen community structure and CH4 dynamics in situ, and to review the current generation of CH4 models. We highlight throughout some of the most pressing issues concerning global change and feedbacks on CH4 emissions from natural ecosystems. Major uncertainties in estimating current and future CH4 emissions from natural ecosystems include the following: (i) A number of important controls over CH4 production, consumption, and transport have not been, or are inadequately, incorporated into existing CH4 biogeochemistry models. (ii) Significant errors in regional and global emission estimates are derived from large spatial‐scale extrapolations from highly heterogeneous and often poorly mapped wetland complexes. (iii) The limited number of observations of CH4 fluxes and their associated environmental variables loosely constrains the parameterization of process‐based biogeochemistry models.
Response to ocean acidification in larvae of a large tropical marine fish, Rachycentron canadum
Authors: Bignami Sean , Sponaugle Su , Cowen Robert K.
Published: December 2012

Currently, ocean acidification is occurring at a faster rate than at any time in the last 300 million years, posing an ecological challenge to marine organisms globally. There is a critical need to understand the effects of acidification on the vulnerable larval stages of marine fishes, as there is potential for large ecological and economic impacts on fish populations and the human economies that rely on them. We expand upon the narrow taxonomic scope found in the literature today, which overlooks many life history characteristics of harvested species, by reporting on the larvae of Rachycentron canadum (cobia), a large, highly mobile, pelagic‐spawning, widely distributed species with a life history and fishery value contrasting other species studied to date. We raised larval cobia through the first 3 weeks of ontogeny under conditions of predicted future ocean acidification to determine effects on somatic growth, development, otolith formation, swimming ability, and swimming activity. Cobia exhibited resistance to treatment effects on growth, development, swimming ability, and swimming activity at 800 and 2100 μatm pCO2. However, these scenarios resulted in a significant increase in otolith size (up to 25% larger area) at the lowest pCO2 levels reported to date, as well as the first report of significantly wider daily otolith growth increments. When raised under more extreme scenarios of 3500 and 5400 μatm pCO2, cobia exhibited significantly reduced size‐at‐age (up to 25% smaller) and a 2–3 days developmental delay. The robust nature of cobia may be due to the naturally variable environmental conditions this species currently encounters throughout ontogeny in coastal environments, which may lead to an increased acclimatization ability even during long‐term exposure to stressors.
Angiotensin I‐Converting Enzyme Gene (I/D) Polymorphism in Patients With Migraine
Authors: Horasanlı Bahriye , Ataç F. Belgin , Çöven İlker , Karakurum Goksel Basak , Benli Sibel
Published: December 2012

In addition to the wide expression in many tissues including vascular endothelial cells, production of angiotensin II and degradation of bradykinin may indicate that angiotensin‐converting enzyme could be involved in vascular tension and blood pressure. It has been reported that the deletion allele of the angiotensin‐converting enzyme gene is associated with increased serum angiotensin‐converting enzyme levels and linked to cerebrovascular diseases. In this study, the possible association of migraine with aura with the angiotensin‐converting enzyme deletion–deletion (DD) and the angiotensin–converting enzyme insertion–deletion (ID) genotype was investigated in Turkish patients. To investigate the role of the angiotensin‐converting enzyme I/D polymorphism in Turkish patients with migraine with aura, we analyzed the I/D genotype of 53 patients with that disorder. Twenty‐two control subjects, who are volunteer Turkish patients without migraine, were included in the study. The frequency of the angiotensin‐converting enzyme D/D genotype was statistically significant more frequent in patients with migraine with aura (81.1%) than in controls (59.1%) (P < .05). No differences were found regarding the I/I genotype and the I/D genotype between the 2 groups (P > .05). The results of our study revealed that the angiotensin‐converting enzyme D/D genotype was more frequent in patients with migraine with aura than in controls. This might suggest that the angiotensin‐converting enzyme D/D genotype may be a genetic risk factor for migraine with aura in Turkish patients.
Quantitative MRI Studies of Chronic Brain White Matter Hyperintensities in Migraine Patients
Authors: Aradi Mihály , Schwarcz Attila , Perlaki Gábor , Orsi Gergely , Kovács Norbert , Trauninger Anita , Kamson David Olayinka , Erdélyi‐Bótor Szilvia , Nagy Ferenc , Nagy Szilvia Anett , Dóczi Tamás , Komoly Sámuel , Pfund Zoltán
Published: December 2012

Objective

The aim of this study was to examine chronic brain white matter hyperintensities in migraine and to gain data on the characteristics of the lesions.

Background

Migraine associates with a higher incidence of magnetic resonance imaging (MRI)‐visible white matter signal abnormalities. Several attack‐related pathomechanisms have been proposed in the lesion development, including the effect of repeated intracerebral hemodynamic changes.

Methods

Supratentorial white matter hyperintensities of 17 migraine patients were investigated interictally with quantitative MRI, including quantitative single voxel spectroscopy, diffusion, and perfusion MRI at 3.0‐Tesla. The findings were compared with data measured in the contralateral, normal‐appearing white matter of migraineurs and in the white matter of 17 healthy subjects.

Results

Significantly higher apparent diffusion coefficient values, prolonged T2 relaxation times, and decreased N‐acetyl‐aspartate and creatine/phosphocreatine concentrations were found in the white matter hyperintensities. The cerebral blood flow and blood volume values were mildly decreased inside the hyperintensities. Differences were not present between the migraine patients' normal‐appearing white matter and the white matter of healthy subjects.

Conclusions

The MRI measurements denote tissue damage with axonal loss, low glial cell density, and an enlarged extracellular space with an increased extracellular water fraction. These radiological features might be the consequences of microvascular ischemic changes during migraine attacks.
Evaluation of Sumatriptan‐Naproxen in the Treatment of Acute Migraine: A Placebo‐Controlled, Double‐Blind, Cross‐Over Study Assessing Cognitive Function
Authors: Edwards Keith R. , Rosenthal Barbara L. , Farmer Kathleen U. , Cady Roger K. , Browning Rebecca
Published: December 2012

Objective

To assess the cognitive effects of acute migraine and the subsequent impact of acute treatment in a controlled setting.

Background

Cognitive dysfunction may be an associated symptom in patients with migraine with or without aura. The loss of cognitive efficiency in migraine may be disabling and is often under recognized.

Methods

Thirty migraine patients were prospectively studied for cognitive function before and then at the beginning of a migraine using a computerized cognitive battery (Mental Efficacy Workload Test). Each patient then was treated for 2 headaches in a cross‐over manner with sumatriptan‐naproxen (Treximet®) or placebo in a double‐blind, placebo‐controlled fashion with cognitive testing repeated at 1 and 2 hours post‐dose.

Results

Twenty‐five of the 30 screened migraine subjects completed study‐specific procedures and were included in the data analyses. There were no significant side effects from Treximet or placebo and no serious adverse events. At the onset of headache, there was a statistically significant decline in overall cognitive efficiency compared with the baseline cognitive testing (migraine‐free) for all subjects (P = .001 paired samples t‐test). For subjects taking Treximet compared with taking placebo, there was a statistically significant return to cognitive efficiency by measures of immediate and sustained attention, visual‐spatial awareness, mental flexibility, and reaction time between 1 hour and 2 hours (P = .05). There was no statistical significance between patients taking Treximet or placebo in measures of complex reasoning or fine motor coordination. Subanalysis showed a correlation between headache severity and Performance Index in the Treximet group but not in the placebo group (∼Fig. ).

Conclusions

There is a significant decline in global cognitive efficiency at the onset of an attack of migraine. The use of Treximet allows a significantly faster recovery time in some measures of cognitive efficiency compared with placebo. Decline of cognitive efficiency may be independent of headache severity.
Warming effect on miriplatin–lipiodol suspension for potential use as a chemotherapeutic agent for transarterial chemoembolization of hepatocellular carcinoma: In vitro study
Authors: Kora Shin‐ichi , Urakawa Hiroshi , Mitsufuji Toshimichi , Osame Akinobu , Higashihara Hideyuki , Ohki Toshihiro , Yoshimitsu Kengo
Published: December 2012

Aim

To elucidate whether warming may reduce the viscosity of miriplatin–lipiodol suspension (MPT/LPD) and also the injection pressure through microcatheters, for potential use as a chemotherapeutic agent of transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC).

Methods

Viscosity of MPT/LPD prepared at on‐label dose was measured in vitro at 25°C, 30°C, 40°C, 50°C and 60°C using capillary tube method. Reproducibility of viscosity change was also tested. Injection pressure through two different commercially available microcatheters was measured using a rheometer. Data sampling was performed at least twice for each measurement.

Results

Viscosity of MPT/LPD was significantly reduced as the temperature was elevated (R2 = 0.9586, P < 0.0001, Pearson's correlation); at 40°C, it was almost half of that at room temperature (25°C). Repeated warming and cooling down of MPT/LPD revealed good reproducibility of viscosity change. Injection pressure through either microcatheter showed significant reduction when MPT/LPD was warmed (P < 0.05, Spearman's rank correlation coefficient).

Conclusion

The viscosity and injection pressure through microcatheters of MPT/LPD was confirmed to reduce significantly as the temperature is elevated. MPT/LPD warmed to 40°C has half viscosity as that at room temperature and is considered suitable for clinical use. Warming MPT/LPD may have potential to facilitate the procedure of TACE for HCC.
Detection of highly prevalent hepatitis B virus co‐infection with HIV in Indonesia
Authors: Utsumi Takako , Yano Yoshihiko , Lusida Maria I. , Nasronudin  , Amin Mochamad , Juniastuti  , Soetjipto  , Hotta Hak , Hayashi Yoshitake
Published: December 2012

Aim

The prevalence of hepatitis B virus (HBV) co‐infection with HIV is increasing worldwide because of shared transmission routes. This study aimed to assess the prevalence of HBV and HIV co‐infection in Indonesia, and its molecular and clinical characteristics.

Methods

A total of 118 serum samples from HIV‐infected patients (age 33.3 ± 8.9 years, 99 male, 19 female) collected in 2009 were serologically examined. HBV DNA was assessed by polymerase chain reaction (PCR) analysis targeting the S region.

Results

Overall, 15.3% (18/118) of the patients were hepatitis B surface antigen (HBsAg) positive, whereas 27.1% (32/118) were HBsAg negative but HBV DNA positive, and were considered to have occult HBV infection. HBsAg antibodies and/or HBV core antibodies were detected in 45.6% (31/68) of HBV DNA negative patients.

Conclusion

HBV co‐infection, including occult HBV infection, was common in Indonesian HIV patients. Hepatic damage by the interaction of host immunity and HBV is still a remaining issue in these immunosuppressive patients, and further study will be needed.
Evaluation of the effect of sorafenib using serum NX‐des‐γ‐carboxyprothrombin in patients with hepatocellular carcinoma
Authors: Miyahara Koji , Nouso Kazuhiro , Morimoto Yuki , Tomoda Takeshi , Kobayashi Sayo , Takeuchi Yasuto , Hagihara Hiroaki , Kuwaki Kenji , Ohnishi Hideki , Ikeda Fusao , Miyake Yasuhiro , Nakamura Shinichiro , Shiraha Hidenori , Takaki Akinobu , Yamamoto Kazuhide ,   Okayama Liver Cancer Group
Published: December 2012

Aim

Des‐γ‐carboxyprothrombin (DCP) is known to be increased by the use of sorafenib for the treatment of hepatocellular carcinoma (HCC), despite its therapeutic efficacy. In addition to the tumor progression, hypoxia that impairs vitamin K uptake is known to induce DCP and this mechanism may explain DCP elevation by sorafenib. In this study, we tried to evaluate the effect of sorafenib treatment using a new marker, NX‐DCP, which is specific to vitamin K absence.

Methods

Serum DCP and NX‐DCP were measured in 50 consecutive HCC patients before and 1 week after starting sorafenib, and compared with the treatment effect using the modified Response Evaluation Criteria in Solid Tumors guidelines.

Results

DCP and NX‐DCP increased 1.58‐ (median, range 0.21–28.7) and 1.20‐fold (median, range 0.41–14.2) after the administration of sorafenib, respectively. The increases of both markers were less than twofold in approximately half of the patients (low‐elevation group). However, 12 patients showed over twofold increase of both DCP and NX‐DCP (double‐elevation group), and eight patients showed over twofold increase of DCP alone (DCP‐elevation group). The disease control rate (DCR) of the DCP‐elevation group (12.5%) was significantly lower than those of the double‐elevation group (75.0%, P = 0.020) and the low‐elevation group (60.0%, P = 0.042). Progression‐free survival (PFS) was significantly shorter in the DCP‐elevation group than in the double‐elevation group (P = 0.006) and the low‐elevation group (P = 0.001).

Conclusion

NX‐DCP in combination with DCP could be a useful biomarker of sorafenib treatment for advanced HCC.
Survey of non‐B, non‐C liver cirrhosis in Japan
Authors: Suzuki Yasuaki , Ohtake Takaaki , Nishiguchi Shuhei , Hashimoto Etsuko , Aoyagi Yutaka , Onji Morikazu , Kohgo Yutaka ,   The Japan Non‐B, Non‐C Liver Cirrhosis Study Group
Published: December 2012

Aim

The aim of this survey was to reveal clinical features for each etiology of non‐B, non‐C liver cirrhosis (NBNC LC) in Japan.

Methods

In a nationwide survey of NBNC LC in Japan at the 15th General Meeting of the Japan Society of Hepatology, 6999 NBNC LC patients were registered at 48 medical institutions. Epidemiological and clinical factors were investigated.

Results

The percentage of NBNC LC among LC patients was 26%. NBNC LC patients were categorized into 11 types according to etiological agents: non‐alcoholic steatohepatitis (NASH), 14.5%; alcoholic liver disease (ALD), 55.1%; fatty liver disease (FLD), except NASH, ALD, and other known etiology, 2.5%; primary biliary cirrhosis, 8.0%; other biliary cirrhosis, 0.8%; autoimmune hepatitis, 6.8%; metabolic disease, 0.6%; congestive disease, 0.8%; parasitic disease, 0.2%; other known etiology, 0.2%; and unknown etiology, 10.5%. Compared with previous surveys, the percentage of ALD remained unchanged, whereas that of NASH increased. The mean age and percentage of females were significantly higher in NASH patients than in ALD and FLD patients. Prevalence of diabetes mellitus was significantly higher in NASH and FLD patients than in ALD ones. Prevalence of hepatocellular carcinoma (HCC) in NBNC LC patients was 35.9%. Among NASH, ALD and FLD patients, 50.9%, 34.3% and 54.5% had HCC, respectively. Positivity of hepatitis B core antibody was significantly higher in HCC patients than in those without HCC (41.1% vs 24.8%).

Conclusion

This survey determined the etiology of NBNC LC in Japan. These results should contribute new ideas toward understanding NBNC LC and NBNC HCC.
Comprehensive evaluation of twoHLA‐B17 monoclonal antibodies for flow cytometry‐basedHLA‐B57/B58 screening prior to abacavir prescription
Authors: Stevens R. , Coates E. , Street J. , Cook E. , Darke C.
Published: December 2012

Hypersensitivity reactions to the drug abacavir, used to treatHIV/AIDSpatients, is associated with possession ofHLA‐B*57:01. We have carefully assessed two commercially availableHLA‐B57/B58 murine monoclonal antibodies [0196HAandBIH0243 (OneLambdaInc.)] in a simple flow cytometry‐based assay. The evaluation involved tests on 228 reference and random samples covering 91% of allWHOrecognizedHLA‐A,BandCspecificities. These involved donors with six differentHLA‐B*57 alleles and included 19 examples ofB*57:01. Both antibodies unambiguously detectedB57, but there were small difference in their reactivity againstB57‐positive non‐B*57:01 samples. Importantly, there was no reactivity againstB57/B58‐negative samples. The possible amino acid motifs involved in the reactivity of these antibodies withB57/B58 were delineated. Thus,HLA‐B57/B58, normally present in <10% of patients, can be easily recognized using these two antibodies and further tested by aDNA‐based typing method to identifyB*57:01.
16th IHIW: Global analysis of registry HLA haplotypes from 20 Million individuals: Report from the IHIW Registry Diversity Group
Authors: Maiers M. , Gragert L. , Madbouly A. , Steiner D. , Marsh S. G. E. , Gourraud P.‐A. , Oudshoorn M. , van der Zanden H. , Schmidt A. H. , Pingel J. , Hofmann J. , Müller C. , Eberhard H.‐P.
Published: December 2012

This project has the goal to validate bioinformatics methods and tools for HLA haplotype frequency analysis specifically addressing unique issues of haematopoietic stem cell registry data sets. In addition to generating new methods and tools for the analysis of registry data sets, the intent is to produce a comprehensive analysis of HLA data from 20 million donors from the Bone Marrow Donors Worldwide (BMDW) database. This report summarizes the activity on this project as of the 16IHIW meeting in Liverpool.
Chemokine programming dendritic cell antigen response: part I – select chemokine programming of antigen uptake even after maturation
Authors: Park Jaehyung , Wu Cindy T. , Bryers James D.
Published: December 2012

Here, we report on the successful programming of dendritic cells (DCs) using selectively applied mixtures of chemokines as a novel protocol for engineering vaccine efficiency. Antigen internalization by DCs is a pivotal step in antigen uptake/presentation for bridging innate and adaptive immunity and in exogenous gene delivery used in vaccine strategies. Contrary to most approaches to improve vaccine efficiency, active enhancement of antigen internalization by DCs as a vaccine strategy has been less studied because DCs naturally down‐regulate antigen internalization upon maturation. Whereas chemokines are mainly known as signal proteins that induce leucocyte chemotaxis, very little research has been carried out to identify any additional effects of chemokines on DCs following maturation. Here, immature DCs are pre‐treated with select chemokines before intentional maturation using lipopolysaccharide (LPS). When pre‐treated with a mixture of CCL3 and CCL19 in a 7 : 3 ratio, then matured with LPS, chemokine pre‐treated DCs exhibited 36% higher antigen uptake capacity than immature DCs and 27% higher antigen‐processing capacity than immature DCs treated only with LPS. Further, CCL3 : CCL19 (7 : 3) pre‐treatment of DCs modulated MHC molecule expression and secretion of various cytokines of DCs. Collectively, DC programming was feasible using a specific chemokine combination and these results provide a novel strategy for enhancing DC‐based vaccine efficiency. In Part II, we report on the phenotype changes and antigen presentation capacity of chemokine pre‐treated murine bone marrow‐derived DCs examined in long‐term co‐culture with antigen‐specific CD4+ T cells.