bluuebunny/crossref_metadata_2025 huggingface dataset:
Demystifying the Social Impacts of Biofuels at Local Levels: Where is the Evidence?
Authors: Hodbod Jennifer , Tomei Julia
Published: July 2013

Since the turn of the century, biofuels have been promoted not only for their potential to mitigate climate change and address energy security but also for the potential benefits to socio‐ecological systems. However, the purported benefits were almost immediately called into question as evidence began to emerge of the potential negative consequences of biofuel production. Recent debates have highlighted the social impacts, particularly land access and food security, yet much of the academic literature on these social impacts remains in high level. This paper identifies peer‐reviewed literature that documents the social impacts of biofuel expansion at the local (household and community) scale. A systematic review identified just seventeen research papers that presented evidence of the local livelihood impacts of biofuel production and processing. Three issues emerge from the review as especially important at the local level: household economics, food security and ecosystem services. Within the research, there is a bias towards the cultivation of Jatropha curcas in particular geographies (Africa and Asia). The evidence also shows that the costs and benefits are unevenly distributed within and between communities, with consequences for the ways in which social, economic and environmental impacts are experienced. We conclude by arguing that more evidence on the impacts of biofuels at the local level is desperately needed in order to demystify this complex issue and stimulate a more nuanced understanding of the winners and losers of this commodity.
Oral health–related quality of life and associated factors in Southern Brazilian elderly
Authors: Silva Alexandre E.R. , Demarco Flávio F. , Feldens Carlos A.
Published: July 2013

Objective

The aim of the present study was to describe oral health–related quality of life (OHRQoL) and associated factors in elderly individuals treated at Family Health Units in urban areas of the city of Pelotas, Brazil.

Methods

The sample was composed of 438 individuals aged 60 years old or older. Demographic, socio‐economic, general health and behavioural variables were collected using standardised questionnaires. OHRQoL was measured with the oral health impact profile (OHIP‐14). Poisson regression analysis was employed to identify factors associated with OHRQoL.

Results

The mean total OHIP‐14 score was 9.1 (standard deviation: 10.6), and major impacts were related to feeling conscious of psychological discomfort (28.1%) and difficulty eating (24.4%) due to teeth, mouth or dentures. The multivariate analysis revealed higher oral health impact scores among non‐White individuals [Prevalence ratios (PR) = 1.33, 95% CI: 1.07–1.66; p = 0.011], those with depressive symptoms (PR = 1.61, 95% CI: 1.30–1.99; p < 0.001), tobacco users (PR = 1.46, 95% CI: 1.07–1.99; p = 0.016), non‐denture users (PR = 1.42, 95% CI: 1.10–1.85, p = 0.008), those with a perceived need for dental treatment (PR = 1.99, 95% CI: 1.58–2.51; p < 0.001) and those with poor or very poor self‐rated oral health (PR = 2.86, 95% CI: 1.93–4.24; p < 0.001). Lower scores were found among individuals aged 80 years or older (PR = 0.52, 95% CI: 0.33–0.82; p = 0.005) and those with household income of more than 1.5 times the minimum wage (PR = 0.65, 95% CI: 0.46–0.93; p = 0.018).

Conclusions

The findings of the present study underscore the need for public policies aimed at reducing social inequalities and providing adequate dental treatment to improve OHRQoL among elderly individuals.
The Definitional Ambiguities of Kidnapping and Abduction, and its Categorisation: The Case for a More Inclusive Typology
Authors: Noor‐Mohamed Mohd Kassim
Published: July 2013

This article sets out to provide a broad overview of the ways in which kidnapping and abduction can be contextualised and understood. First, it will review kidnapping and abduction by examining the varying definitions used by practitioners, academics, governmental organisations, non‐governmental organisations and private sector interests. Second, a discussion of related offences, including piracy, hostage‐taking, hijacking, tiger kidnap, express kidnap and state‐sponsored rendition, and others is undertaken. Third, there will be an examination and review of the various typologies that have been suggested by researchers in the field, culminating in the suggestion of a revised and comprehensive typology.
Evaluation of parameters affecting modified atmosphere packaging engineering design for pomegranate arils
Authors: Caleb Oluwafemi J. , Mahajan Pramod V. , Manley Marena , Opara Umezuruike Linus
Published: July 2013

This study evaluated the effects of passive modified atmosphere packaging design parameters as a function of the amount of product (g), temperature (°C) and time (days) on two pomegranate cultivars. Arils (75, 100 and 125 g) were packed in trays, heat sealed with polylid film and stored at 5, 10 and 15 °C for 14 days, and analysed for physicochemical parameters viz headspace gas composition, weight loss, total soluble solids, titratable acidity, pH, anthocyanin, aerobic‐mesophilic bacterial and fungal load (log CFU g−1). At the highest temperature and weight, O2 concentration continuously decreased below the critical limit (2%) after 4 days, while at 5 °C, this lower limit was not reached. Shelf life of arils was limited to 10, 7 and 3 days by fungal growth ≥2 log CFU g−1 at 5, 10 and 15 °C, respectively. Using unsteady‐state equation, a good agreement was found between simulated and experimental gas composition data.
Moisture sorption and thermodynamic properties of cassava starch and soy protein concentrate based edible films
Authors: Enyinnaya Chinma Chiemela , Chukwuma Ariahu Charles , Alakali Joseph
Published: July 2013

Moisture sorption isotherms and thermodynamic properties of cassava starch and soy protein concentrate–based edible films were investigated. Equilibrium moisture content was determined at various temperatures (10, 20, 30 and 40 °C) and relative humidities (17–83%) using gravimetric method, and the results were analysed using four sorption isotherm models. The equilibrium moisture of edible films (both adsorption and desorption modes) decreased with soy protein concentrate addition and temperature at constant water activity. The monolayer moisture content values of cassava starch–soy protein concentrate edible films decreased with increase in temperature and soy protein level.GABand Oswin models (%RMS≤10) best described the isotherms of the biofilms with the monolayer moisture contents, isosteric enthalpy and entropy higher for adsorption with significant kinetic compensations. The moisture sorption and thermodynamic properties of cassava starch–soy protein concentrate edible films showed that they are suitable for packaging applications.
The psychology of penile cancer from presentation to rehabilitation
Authors: Bullen Kathryn , Chichlowska Susan Carnes , Rahman Rachel , Tod David
Published: July 2013

Penile cancer is an uncommon, gender‐specific, malignancy that has the potential to profoundly affect physical, social, sexual and psychological functions. For most patients the method of treatment is surgery. The degree of surgical intervention is dependent on the stage of the disease at presentation. To date, relatively little is known about the impact of penile cancer surgery on psychological function and overall quality of life in men. Understanding the outcomes of treatment will influence the development of optimal methods of rehabilitation. This paper provides an outline of the context of two reviews of the existing literature: (i) a systematic review of the quantitative literature and (ii) a meta‐synthesis of the qualitative literature. The implications for clinical practice, and an outline of forthcoming research are also presented.
Epidemiology and outcomes of adults with asthma who were hospitalized or died with 2009 pandemic influenza A (H1N1) – California, 2009
Authors: Mortensen Eva , Louie Janice , Pertowski Carol , Cadwell Betsy L. , Weiss Edward , Acosta Meileen , Matyas Bela T.
Published: July 2013

Background

Asthma was the most common chronic condition among adults hospitalized for 2009 pandemic influenza A (H1N1) (pH1N1).

Objectives

We describe the epidemiology and factors for severe outcomes among adults with asthma who were hospitalized or died from pH1N1 in California.

Methods

We reviewed California Department of Public Health pH1N1 reports from April 23, 2009 through August 11, 2009. Reports were included if the patient had pH1N1 (or non‐subtypeable influenza A) infection by polymerase chain reaction in an adult (age ≥ 18 years) with asthma who was hospitalized or died. Patients were classified as having intermittent or persistent asthma on the basis of regular medications. Risk factors associated with severe outcomes (i.e., intensive care unit admission or death) vs those with less severe outcomes were assessed by chi‐square tests and logistic regression.

Results

Among 744 identified patients, 170 (23%) had asthma (61% intermittent, 39% persistent). 132 of 142 (93%) patients had other chronic medical conditions. Severe outcomes occurred in 54 of 162 (33%), more commonly among those with renal disease (64% versus 31%; P = 0.04) and chest radiograph infiltrates (54% versus 11%; P < 0.01), less commonly among those who received antivirals within 48 hours of symptom onset (22% versus 44%; P = 0.02). In multivariable analysis, chest radiograph infiltrates were associated with severe outcomes (adjusted odds ratio 9·38, 95% confidence interval 3·05–28·90).

Conclusions

One third of adults with asthma who died or were hospitalized with pH1N1 experienced severe outcomes. Early empiric antiviral therapy should be encouraged, especially among asthma patients.
Treatment of chronic diabetic lower leg ulcers with activated protein C: a randomised placebo‐controlled, double‐blind pilot clinical trial
Authors: Whitmont Kaley , McKelvey Kelly J , Fulcher Gregory , Reid Ian , March Lyn , Xue Meilang , Cooper Alan , Jackson Christopher J
Published: July 2013

Lower leg ulcers are a serious and long‐term complication in patients with diabetes and pose a major health concern because of the increasing number of patients diagnosed with diabetes each year. This study sought to evaluate the clinical benefit of topical activated protein C (APC) on chronic lower leg ulcers in patients with diabetes. Twelve patients were randomly assigned to receive either APC (N = 6) or physiological saline (placebo; N = 6) in a randomised, placebo‐controlled, double‐blind pilot clinical trial. Treatment was administered topically, twice weekly for 6 weeks with final follow‐up at 20 weeks. Wound area was significantly reduced to 34·8 ± 16·4% of week 0 levels at 20 weeks in APC‐treated wounds (p = 0·01). At 20 weeks, three APC‐treated wounds had completely healed, compared to one saline‐treated wound. Full‐thickness wound edge skin biopsies showed reduced inflammatory cell infiltration and increased vascular proliferation following APC treatment. Patient stress scores were also significantly reduced following APC treatment (p < 0·05), demonstrating improved patient quality of life as assessed by the Cardiff Wound Impact Questionnaire. This pilot trial suggests that APC is a safe topical agent for healing chronic lower leg ulcers in patients with diabetes and provides supporting evidence for a larger clinical trial.
Mechanical properties of human articular disk and its influence on TMJ loading studied with the finite element method
Authors: TANAKA E. , SASAKI A. , TAHMINA K. , YAMAGUCHI K. , MORI Y. , TANNE K.
Published: July 2013

SUMMARY The present study was designed to investigate the elastic modulus of human temporomandibular joint (TMJ) disk under tension and its influences on TMJ loading. Seven human TMJ disks served as specimens. Continuous tensile stress was applied to each specimen, and the elastic moduli of human TMJ disks were calculated at 2% strain. Furthermore, using a three‐dimensional finite element model of the mandible including the TMJ, changes in the TMJ stresses during clenching were evaluated in association of varying elastic moduli of the articular disk determined by the tensile tests. The elastic moduli at 2% strain varied from 27·1 to 65·2 MPa with a mean of 47·1 MPa. A significant correlation was found between the elastic moduli and age (P < 0·01). On the surface of condyle, compressive stress in the anterior area and tensile stress in the posterior area increased when the elastic moduli of the TMJ disk was varied from 25 to 65 MPa. In the TMJ disk, shear stresses in all the areas became larger with greater stiffness. In conclusion, it is shown that the elastic modulus of human TMJ disk is increased with age and that higher stiffness of the disk exerts substantial influences on mechanical loading for the TMJ structures.
Introduction: les marchés du travail européens face à la crise
Authors: TORRES Raymond
Published: July 2013

Il y a 8 millions de chômeurs de plus en Europe depuis que la crise financière a éclaté en 2008. L'auteur examine ici les autres risques d'une récession prolongée: exclusion du marché du travail, coût économique du chômage de longue durée, capacité réduite, pour les entreprises, d'investir et de créer des emplois. L'auteur porte un regard critique sur les réactions politiques européennes, surtout l'austérité budgétaire, avec ses conséquences durables sur les marchés du travail, les économies et les sociétés. Il présente les contributions à ce numéro spécial et s'appuie sur leurs résultats empiriques pour examiner les choix politiques qui permettraient de renverser la tendance.
Les courbes de Beveridge et de Phillips face à la crise dans la zone euro
Authors: SELL Friedrich L. , REINISCH David C.
Published: July 2013

Alors que l'on critique le courant dominant de l'économie politique qui n'a su ni prévoir ni annoncer la crise mondiale, les auteurs renversent la question: que donnent, empiriquement, des concepts traditionnels de l'économie du travail ou de la macroéconomie, comme les courbes de Beveridge et de Phillips, face au «test de résistance« que représente la crise? Fondé sur des données concernant onze pays de la zone euro de 2007 à 2010, l'examen des relations entre les taux d'inflation, de chômage et de vacances de postes confirme les corrélations postulées, ce qui implique un dosage subtil entre politiques de l'offre et de la demande.
Effets permanents et temporaires du chômage sur la mortalité: l'expérience européenne
Authors: BENDER Keith A. , ECONOMOU Athina , THEODOSSIOU Ioannis
Published: July 2013

Les recherches récentes sur la relation entre le chômage et la mortalité sont contradictoires. La présente étude utilise une méthodologie statistique pour décomposer les effets du chômage en effets temporaires et effets permanents, et évalue cette relation à l'aide de données agrégées collectées dans onze pays européens durant la période 1971–2001. Généralement, l'effet temporaire d'une hausse du chômage tend à faire baisser la mortalité, tandis que l'effet permanent tend à la faire augmenter. Il est important de noter que ce dernier est d'ordinaire plus fort que le premier. Ces résultats sont valables pour quasiment tous les indicateurs de la mortalité.
Le chômage partiel: réponse de l'Allemagne face à la grande récession
Authors: BRENKE Karl , RINNE Ulf , ZIMMERMANN Klaus F.
Published: July 2013

Dans le courant de l'année 2009, au plus fort de la crise économique, on dénombrait 1,5 million de salariés au chômage partiel en Allemagne. Sans le recours à ce dispositif, le taux de chômage aurait doublé. Le chômage partiel a sans aucun doute contribuéà atténuer l'impact de la crise sur le marché du travail allemand, mais les auteurs tiennent à rappeler qu'il a été utilisé dans des circonstances particulières, propres à l'Allemagne, et qu'il n'est dès lors pas possible de procéder à des généralisations quant à son efficacité. Par ailleurs, ils soulignent que les récentes modifications du régime du chômage partiel ont ouvert la voie à certains abus, comme en témoigne le nombre important de bénéficiaires du dispositif dans des secteurs d'activité qui n'ont pas été touchés par la crise et la constitution d'un chômage partiel de longue durée.
Characterization of Drought in the South Atlantic, United States
Authors: Patterson Lauren A. , Lutz Brian D. , Doyle Martin W.
Published: July 2013

Drought has been less extensively characterized in the humid South Atlantic compared to the arid western United States. Our objective was to characterize drought in the South Atlantic and to understand whether drought has become more severe in this region over time. Here we used monthly streamflow to characterize hydrological drought. Hydrological drought occurred when streamflow fell below the 20th percentile over three consecutive months and terminated once streamflow remained above the 20th percentile for three consecutive months. We characterized the frequency, duration, magnitude, and severity of events using the above definition. Significant changes in drought characteristics were tested with Mann‐Kendall over three periods: 1930‐2010, 1930‐1969, and 1970‐2010. We show that 71% of drought events were shorter than six months, while 7% were multiyear events. There was little evidence of trends in drought characteristics to support the claim of drought becoming more severe in the South Atlantic over the 20th Century. The one exception was a significant increase in the joint probability of nearby basins being simultaneously in drought conditions in the southern portion of the study area from 1970 to 2010. While drought characteristics have changed little through time, decreasing average streamflow in non drought periods coupled with increasing water demand provide the context within which recent multiyear drought events have produced significant stress on existing water infrastructure.
A System Dynamics Model for Conjunctive Management of Water Resources in the Snake River Basin
Authors: Hoekema David J. , Sridhar Venkataramana
Published: July 2013

The Pacific Northwest is expected to witness changes in temperature and precipitation due to climate change. In this study, we enhance the Snake River Planning Model (SRPM) by modeling the feedback loop between incidental recharge and surface water supply resulting from surface water and groundwater extraction for irrigation and provide a case study involving climate change impacts and management scenarios. The new System Dynamics‐Snake River Planning Model (SD‐SRPM) is calibrated to flow at Box Canyon Springs located along a major outlet of the East Snake Plain Aquifer. A calibration of the model to flow at Box Canyon Springs, based on historic diversions (1950‐1995) resulted in an r2 value of 0.74 and a validation (1996‐2005) r2 value of 0.60. After adding irrigation entities to the model an r2 value of 0.91, 0.88, and 0.87 were maintained for modeled vs. observed (1991‐2005) end‐of‐month reservoir content in Jackson Lake, Palisades, and American Falls, the three largest irrigation reservoirs in the system. The scenarios that compared the impacts of climate change were based on ensemble mean precipitation change scenarios and estimated changes to crop evapotranspiration (ET). Increased ET, despite increased precipitation, generally increased surface water shortages and discharge of springs. This study highlights the need to develop and implement models that integrate the human‐natural system to understand the impacts of climate change.
Cognitive and behavioral indicators of ADHD symptoms prior to school age
Authors: Arnett Anne Bernard , MacDonald Beatriz , Pennington Bruce F.
Published: July 2013

Background

Previous research on the etiology of ADHD symptoms suggests that neuropsychological differences may be present as early as birth; however, the diagnosis is typically not given until school age. This study aimed to (a) identify early behavioral and cognitive markers of later significant parent and/or teacher ratings of ADHD symptomology, (b) examine sex differences in these predictors, and (c) describe the developmental trajectories of comorbid symptoms in school‐aged children.

Methods

1,106 children and at least one parent enrolled in the NICHD Study of Early Child Care and Youth Development were followed from 1 month of age through 6th grade. Effect size calculations, discriminant function analysis, and growth curve analyses were conducted to address the three aims.

Results

Children with high‐ versus low‐ADHD symptomology at 3rd grade could be distinguished using cognitive and behavioral measures as early as 15 months (females) and 24 months (males). Sensitivity and specificity were modest at 15, 24, and 26 months. Growth curves revealed significant differences between high‐ and low‐ADHD groups in comorbid symptoms at kindergarten and significantly different slopes for externalizing, social skills, and academic skills ratings across elementary school. There were few gender differences on cognitive and behavioral variables within the high‐ADHD group.

Conclusions

Cognitive and behavioral markers of ADHD symptoms are present in children prior to entry into formal schooling, but current behavioral screeners are not developmentally sensitive to these differences in infancy and toddlerhood.
Preschool predictors of childhood anxiety disorders: a prospective community study
Authors: Wichstrøm Lars , Belsky Jay , Berg‐Nielsen Turid Suzanne
Published: July 2013

Background

Anxiety disorders are often present at preschool age. Research on older children and studies contrasting preschoolers with high versus low behavioral inhibition (BI) highlight several risk factors, but these have not been investigated in community samples of young children. Child, parent, and peer factors at age 4 were therefore examined as potential predictors of anxiety disorders at age 6.

Methods

Two birth cohorts of 4‐year olds living in the city of Trondheim, Norway, were screened for emotional and behavioral problems. A subsample oversampled for emotional and behavioral problems were drawn to take part in the study; 82.1% consented. Parents of 1000 children were interviewed with the Preschool Age Psychiatric Assessment and provided ratings of children's BI, victimization by peers and their own anxiety symptoms. Assessments of attachment and parent–child interaction were based on observation. Preschool teachers rated children's social competence. Children were reassessed after 2 years (N = 797).

Results

High scores on BI, attention‐deficient/hyperactivity disorder, parental anxiety, and peer victimization, along with low scores on social skills at age 4 collectively predicted anxiety disorders at age 6 after controlling for initial anxiety and other disorders. The effect of parental anxiety did only apply to children with high levels of BI. No effects of age‐4 anxiety, gender, parenting, parental SES, divorce, peer acceptance, or attachment emerged.

Conclusions

Behavioral inhibition, parental anxiety, and peer victimization function as risk factors whereas high social competence may protect against anxiety disorders in young children.
Measuring food intake with digital photography
Authors: Martin C. K. , Nicklas T. , Gunturk B. , Correa J. B. , Allen H. R. , Champagne C.
Published: July 2013

The Digital Photography of Foods Method accurately estimates the food intake of adults and children in cafeterias. When using this method, images of food selection and leftovers are quickly captured in the cafeteria. These images are later compared with images of ‘standard’ portions of food using computer software. The amount of food selected and discarded is estimated based upon this comparison, and the application automatically calculates energy and nutrient intake. In the present review, we describe this method, as well as a related method called the Remote Food Photography Method (RFPM), which relies on smartphones to estimate food intake in near real‐time in free‐living conditions. When using the RFPM, participants capture images of food selection and leftovers using a smartphone and these images are wirelessly transmitted in near real‐time to a server for analysis. Because data are transferred and analysed in near real‐time, the RFPM provides a platform for participants to quickly receive feedback about their food intake behaviour and to receive dietary recommendations for achieving weight loss and health promotion goals. The reliability and validity of measuring food intake with the RFPM in adults and children is also reviewed. In sum, the body of research reviewed demonstrates that digital imaging accurately estimates food intake in many environments and it has many advantages over other methods, including reduced participant burden, elimination of the need for participants to estimate portion size, and the incorporation of computer automation to improve the accuracy, efficiency and cost‐effectiveness of the method.
Spatial organization of fibroblast nuclear chromocenters: component tree analysis
Authors: Snapp Robert R. , Goveia Elyse , Peet Lindsay , Bouffard Nicole A. , Badger Gary J. , Langevin Helene M.
Published: July 2013

The nuclei of mouse connective tissue fibroblasts contain chromocenters which are well‐defined zones of heterochromatin that can be used as positional landmarks to examine nuclear remodeling in response to a mechanical perturbation. This study used component tree analysis, an image segmentation algorithm that detects high intensity voxels that are topologically connected, to quantify the spatial organization of chromocenters in fibroblasts within whole mouse connective tissue fixed and stained with 4',6‐diamidino‐2‐phenylindole (DAPI). The component tree analysis method was applied to confocal microscopy images of whole mouse areolar connective tissue incubated for 30 min ex vivo with or without static stretch. In stretched tissue, the mean distance between chromocenters within fibroblast nuclei was significantly greater (vs. non‐stretched, P < 0.001), corresponding to an average of a 500‐nm increase in chromocenter separation (~10% strain). There was no significant difference in chromocenter number or average size between stretch and no stretch. Average chromocenter distance was positively correlated with nuclear cross‐sectional area (r = 0.78, P < 0.0001), and nuclear volume (r = 0.42, P < 0.0001), and negatively correlated with nuclear aspect ratio (r = −0.65, P < 0.0001) and nuclear concavity index (r = −0.44, P < 0.0001). These results demonstrate that component trees can be successfully applied to the morphometric analysis of nuclear chromocenters in fibroblasts within whole connective tissue. Static stretching of mouse areolar connective tissue for 30 min resulted in substantially increased separation of nuclear chromocenters in connective tissue fibroblasts. This interior remodeling of the nucleus induced by tissue stretch may impact transcriptionally active euchromatin within the inter‐chromocenter space.
Processes Linking Father Absence to Educational Attainment Among African American Females
Authors: Gillette Meghan T. , Gudmunson Clinton G.
Published: July 2013

Previous researchers have assessed how father absence influences both socioeconomic and reproductive development, but have not analyzed these relationships jointly or used theoretical support for explaining why father absence affects socioeconomic and reproductive development, especially for African American girls. Guided by the family economic stress model and psychosocial acceleration theory, this study investigates how and why these relationships exist for 532 African American females. Structural equation modeling revealed that longer duration of father absence predicted lowered educational attainment in early adulthood via lower income, increased economic pressure, accelerated reproductive development, and lowered educational expectations. We include recommendations for the use of these perspectives to better understand the interplay between family socioeconomic processes and reproductive maturation in African American females.
Targeting High‐Risk, Socially Influential Middle School Students to Reduce Aggression: Universal Versus Selective Preventive Intervention Effects
Authors:   Multisite Violence Prevention Project
Published: July 2013

Early adolescence may be an opportune time for violence prevention, particularly if shifts in risk patterns and the importance of peer influence are considered. An important question is whether to target high‐risk students or the entire population. Thirty‐seven schools were randomized to four conditions: universal classroom intervention; selective family intervention; combined interventions; or control to test effects on a high‐risk sample (N = 1,805) of sixth graders targeted due to elevated aggression and social influence. Intent‐to‐treat and dosage‐weighted growth comparisons through two years of postintervention revealed selective intervention benefits for physical aggression, aggressive strategies, and targeted family characteristics. Universal and combined interventions affected valuing academic achievement. Implications for middle school prevention, particularly selective targeting of socially influential high‐risk youth, are discussed.
Phase 2b, randomized, double‐blind 12‐week studies of TZP‐102, a ghrelin receptor agonist for diabetic gastroparesis
Authors: McCallum R. W. , Lembo A. , Esfandyari T. , Bhandari B. R. , Ejskjaer N. , Cosentino C. , Helton N. , Mondou E. , Quinn J. , Rousseau F. ,   The TZP‐102 Phase 2b Study Group
Published: July 2013

Background

TZP‐102, a potent, oral, ghrelin receptor agonist, improved diabetic gastroparesis symptoms in Phase 2a.

Methods

Patients with type 1 or 2 diabetes, delayed gastric half‐emptying (T1/2), and ≥3 months gastroparesis symptoms randomized 1 : 1 : 1 to double‐blind placebo, 10‐mg, or 20‐mg TZP‐102 once daily for 12 weeks (Study TZP‐102‐CL‐G003). Study TZP‐102‐CL‐G004 patients randomized 1 : 1 to 10‐mg TZP‐102:placebo three‐times‐daily. Primary endpoint was change‐from‐baseline through Weeks 11–12 in Daily Diary of Gastroparesis Symptoms Questionnaire (GSDD) via electronic Patient Recorded Outcome device: worst severity of nausea, early satiety, bloating, and upper abdominal pain in 24 h (0 = none‐to‐5 = very severe). GSDD Composite Score for eligibility was ≥2.5 (Day‐14‐to‐baseline). Patient Overall Treatment Evaluation (OTE) provided an anchor‐based minimal clinically important difference (MCID) for GSDD Composite Score.

Key Results

Study TZP‐102‐CL‐G003 enrolled 201 outpatients: females 72%; Caucasians 87%; type 2 diabetes 61%; insulin‐dependent 65%; age mean ± SD 53 ± 11.3 years; HbA1c 7.8 ± 1.5%; GCSI 3.4 ± 0.7; GSDD Composite 3.6 ± 0.6; gastric T1/2 131 ± 32 min; n = 69 (10‐mg), n = 66 (20‐mg), n = 66 (placebo). Primary endpoint (GSDD): significant improvement in all arms, although not for TZP‐102 vs placebo: mean change‐from‐baseline −1.7, −1.4, −1.5 (10‐mg, 20‐mg, placebo); Gastroparesis Cardinal Symptom Index −1.8, −1.6, −1.5, respectively. The OTE (all patients) at Week‐12 was: Patient 3.7 ± 3.2 and Physician 3.6 ± 3.0 with median score for both of 5.0 = important on scale of improvement; individual MCID was 1.61 and 0.94 for group analyses, greater than expected. Study TZP‐102‐CL‐G004 with similar demographic/disease characteristics was prematurely terminated for efficacy futility (n = 64 with Week‐4 assessments).

Conclusions & Inferences

Efficacy of TZP‐102 was not demonstrated compared with placebo in diabetic gastroparesis; however, there was substantial symptom improvement in all arms (ClinicalTrials.gov NCT01452815/NCT01664637).
Osteogenic effects of resveratrol in vitro: potential for the prevention and treatment of osteoporosis
Authors: Mobasheri Ali , Shakibaei Mehdi
Published: July 2013

There are a number of pharmacological agents for the treatment of bone mineral loss and osteoporosis. Hormone replacement therapy (HRT) with estrogen is an established treatment, but it has several adverse side effects and can increase the risk of cancer, heart disease, and stroke. There is increasing interest in nutritional factors and naturally occurring phytochemical compounds with the potential for preventing age‐related and postmenopausal bone loss. Resveratrol (3,5,4′‐trihydroxy‐trans‐stilbene) is a polyphenolic phytoestrogen with osteogenic and osteoinductive properties. It can modify the metabolism of bone cells and has the capacity to modulate bone turnover. This paper provides an overview of current research on resveratrol and its effects on bone cells in vitro, highlighting the challenges and opportunities facing this area of research, especially in the context of providing nutritional support for postmenopausal women who may not benefit from HRT and older patients with various forms of arthritis, metabolic bone disease, and osteoporosis.
Resveratrol, from experimental data to nutritional evidence: the emergence of a new food ingredient
Authors: Raederstorff Daniel , Kunz Iris , Schwager Joseph
Published: July 2013

The polyphenol resveratrol is found notably in grapes and in a variety of medicinal plants. Recently, resveratrol has been suggested to have cardioprotective effects and to improve metabolic health by mimicking the effects of calorie restriction. Numerous animal and in vitro studies suggest that resveratrol could improve cardiovascular and metabolic health in humans. In view of this compelling preclinical evidence, several human studies investigating the effects of resveratrol on vascular and metabolic health have been initiated. Collectively, the animal, human epidemiological, and first human intervention studies support a role of resveratrol in vascular and metabolic health. This has led to the introduction of the first supplement and food products containing resveratrol and its emergence as a promising new health ingredient. Thus, supplementation with resveratrol may be included in nutritional and lifestyle programs aiming to reduce the risk of vascular and obesity‐related problems.
Importance of lipid microdomains, rafts, in absorption, delivery, and biological effects of resveratrol
Authors: Delmas Dominique , Aires Virginie , Colin Didier J. , Limagne Emeric , Scagliarini Alessandra , Cotte Alexia K. , Ghiringhelli François
Published: July 2013

The preventive effects of the phytoalexin trans‐resveratrol toward cancer have been largely described at the cellular and molecular levels in both in vivo and in vitro models; however, its primary targets are still poorly identified. In this review, we show the crucial role of cell membrane microdomains, that is, lipid rafts, not solely in the initiation of the early biochemical events triggered by resveratrol leading to cancer cell death, but also in resveratrol absorption and distribution. Resveratrol accumulates in lipid rafts and is then taken up by cells through raft‐dependent endocytosis. These events allow early activation of kinase pathways and redistribution of cell death receptors within lipid microdomains, events ultimately leading to apoptotic cell death.
Global climate change and the evolutionary ecology of ecosystem functioning
Authors: Schmitz Oswald J.
Published: July 2013

Environmental warming due to global climate change is an important stressor that stands to alter organismal physiology and, ultimately, carbon cycling in ecosystems. Yet the theoretical framework for predicting warming effects on whole‐ecosystem carbon balance by way of changes in organismal physiology remains rudimentary. This is because ecosystem science has yet to embrace principles of evolutionary ecology that offer the means to explain how environmental stress on organisms mediates ecosystem carbon dynamics. Here, using selected case studies and a theoretical model, I sketch out one framework that shows how increases in animal metabolic rates in response to thermal stress lead to phenotypically plastic shifts in animal elemental demand, from nitrogen‐rich proteins that support production to carbon‐rich soluble carbohydrates that support elevated energy demands. I further show how such a switch in resource selection alters the fate of carbon between atmospheric versus animal, plant, and soil pools. The framework shows that animals, despite having relatively low biomass representation in ecosystems, can nonetheless have disproportionately larger effects on carbon cycling in ecosystems whose effects are exacerbated by environmental stressors like climate warming.
Therapeutic potential of resveratrol in obesity and type 2 diabetes: new avenues for health benefits?
Authors: Timmers Silvie , Hesselink Matthijs K.C. , Schrauwen Patrick
Published: July 2013

The number of people suffering from metabolic disorders is dramatically increasing worldwide. The need for new therapeutic strategies to combat this growing epidemic of metabolic diseases is therefore also increasing. In 2003, resveratrol was discovered to be a small molecule activator of sirtuin 1 (SIRT1), an important molecular target regulating cellular energy metabolism and mitochondrial homeostasis. Rodent studies have clearly demonstrated the potential of resveratrol to improve various metabolic health parameters. To date, however, only limited clinical data are available that have systematically examined the health benefits of resveratrol in metabolically challenged humans. This short review will give an overview of the currently available clinical studies examining the effects of resveratrol on obesity and type 2 diabetes from a human perspective.
The development of mental scenario building and episodic foresight
Authors: Suddendorf Thomas , Redshaw Jonathan
Published: July 2013

Episodic foresight is the future‐directed counterpart of episodic memory. It is a sophisticated, potentially uniquely human capacity, with tremendous adaptive consequences. Here we review what is currently known about its development through early childhood. We tackle this from two distinct perspectives. First, we present the first systematic evaluation of the development of purported components of mental scenario building as highlighted by a theater metaphor: the stage, the playwright, the set, the actors, the director, the executive producer, and the broadcaster. We find that, although there are diverse developmental trajectories, by 4 years of age children have acquired the basic cognitive components required to mentally construct specific future events. Second, we examine recent attempts to test children's episodic foresight more directly and find that results are in line with those examining the development of required components. This is not to say that children younger than four have no inkling of upcoming events or that older children have nothing left to learn about constructing the future. Episodic foresight, and its neurocognitive foundations, continues to develop throughout childhood.
Resveratrol analogs: promising chemopreventive agents
Authors: Ogas Talysa , Kondratyuk Tamara P. , Pezzuto John M.
Published: July 2013

Although resveratrol can modulate multiple stages of carcinogenesis, by most common standards it is not a good drug candidate. Resveratrol lacks potency, high efficacy, and target specificity; it is rapidly metabolized and serum concentrations are low. Using resveratrol as a scaffold, we produced over 100 derivatives, some of which have target specificity in the nanomolar range. Aromatase inhibition was enhanced over 6000‐fold by using 1,3‐thiazole as the central ring of resveratrol. Optimizing the substitution pattern of the two phenyl rings and the central heterocyclic linker led to selective QR1 induction with a CD value of 87 nM. Several derivatives have been selected for evaluation of synergistic effects. Preliminary results with pairs of compounds are promising and further experiments, in a constant multidrug manner, will allow us to create polygonograms for larger combinations of derivatives. The objective is to develop a highly efficacious cocktail of derivatives based on the structure of resveratrol.
An adipocentric perspective of resveratrol as a calorie restriction mimetic
Authors: Barger Jamie L.
Published: July 2013

Adipose tissue is an active endocrine organ that responds to changes in energy balance and influences whole‐body physiology. Adipose tissue dysfunction with obesity is associated with metabolic disease, neurodegeneration, inflammation, and cancer, whereas calorie restriction (CR) decreases both adiposity and disease risk. Although resveratrol does not affect obesity, it mimics long‐term CR by increasing both life span in model organisms and health span in rodents. Because resveratrol's benefits in experimental animals are reminiscent of improved adipose tissue function under CR, this review synthesizes existing data to assess if resveratrol's effects may be mediated by mimicking CR in adipose tissue. In metabolically unhealthy humans, resveratrol consumption recapitulates the health benefits of CR, whereas short‐term resveratrol in otherwise healthy humans mimics CR at the transcriptional, but not physiological, level. This latter observation (neutral effect of short‐term resveratrol) may be protective against future disease risk; however, long‐term studies in healthy humans will be needed to support this hypothesis.
Pleurotomaria DeFrance, 1826 (Gastropoda, Mollusca) from the Lower Bajocian (Middle Jurassic) sediments of Luxembourg, with considerations on its systematics, evolution and palaeobiogeographical history
Authors: MONARI STEFANO , GATTO ROBERTO
Published: July 2013

Abstract:  Pleurotomaria species from lower Bajocian (Middle Jurassic) sediments of south‐western Luxembourg housed in the National Natural History Museum of Luxembourg are described. Seven species are recognized, one of which is new, Pleurotomaria faberi sp. nov. A more detailed definition of the diagnostic characters of the genus is proposed and the morphological continuity between Talantodiscus and Pleurotomaria is demonstrated, suggesting that the former cannot be considered as a distinct taxon. The palaeoecology, evolution and palaeobiogeographical history of Pleurotomaria are outlined. Pleurotomaria presumably first appeared in late Middle Triassic of New Zealand where it underwent a relative diversification up to the Hettangian (Early Jurassic). From early Hettangian, most of its evolutionary history took place in Europe and western Tethys. In the European epicontinental seas, Pleurotomaria experienced two important radiations. The first occurred in the Early Jurassic, with a peak in the late Pliensbachian, and was marked by an expansion of the distribution to the central part of western Tethys. After a collapse in species diversity, probably related to the early Toarcian anoxic event, a second radiation occurred. This culminated in the early Bajocian and was mainly confined in a region encompassing southern England, Paris Basin and southern Germany. Low‐spired species, formerly attributed to Talantodiscus, probably originated independently and iteratively during the history of Pleurotomaria. The facies and associated benthic faunas suggest that Pleurotomaria probably lived on shallow soft bottoms composed of mixed calcareous–siliciclastic sediments. The two main Early Jurassic and early Middle Jurassic radiations of the genus took place in these environments. Records of the genus in Jurassic carbonate platform deposits are very few and concern mainly post‐Bajocian species.
Is the number of species on earth increasing or decreasing? Time, chaos and the origin of species
Authors: Bennett K. D.
Published: July 2013

Darwin'sOn theOrigin ofSpecieshas led to a theory of evolution with a mass of empirical detail on population genetics below species level, together with heated debate on the details of macroevolutionary patterns above species level. Most of the main principles are clear and generally accepted, notably that life originated once and has evolved over time by descent with modification. Here,Ireview the fossil and molecular phylogenetic records of the response of life onEarth toQuaternary climatic changes.Isuggest that the record can be best understood in terms of the nonlinear dynamics of the relationship between genotype and phenotype, and between climate and environments. ‘The origin of species’ is essentially unpredictable, but is nevertheless an inevitable consequence of the way that organisms reproduce through time. The process is ‘chaotic’, but not ‘random’.Isuggest that biodiversity is best considered as continuously branching systems of lineages, where ‘species’ are the branch tips. TheEarth's biodiversity should thus (1) be in a state of continuous increase and (2) show continuous discrepancies between genetic and morphological data in time and space.
Drought impact on water use efficiency and intra‐annual density fluctuations in Erica arborea on Elba (Italy)
Authors: BATTIPAGLIA GIOVANNA , DE MICCO VERONICA , BRAND WILLI A. , SAURER MATTHIAS , ARONNE GIOVANNA , LINKE PETRA , CHERUBINI PAOLO
Published: July 2013

Erica arborea (L) is a widespread Mediterranean species, able to cope with water stress and colonize semiarid environments. The eco‐physiological plasticity of this species was evaluated by studying plants growing at two sites with different soil moistures on the island of Elba (Italy), through dendrochronological, wood‐anatomical analyses and stable isotopes measurements. Intra‐annual density fluctuations (IADFs) were abundant in tree rings, and were identified as the key parameter to understand site‐specific plant responses to water stress. Our findings showed that the formation of IADFs is mainly related to the high temperature, precipitation patterns and probably to soil water availability, which differs at the selected study sites. The recorded increase in the 13C‐derived intrinsic water use efficiency at the IADFs level was linked to reduced water loss rather than to increasing C assimilation. The variation in vessel size and the different absolute values of δ18O among trees growing at the two study sites underlined possible differences in stomatal control of water loss and possible differences in sources of water uptake. This approach not only helped monitor seasonal environmental differences through tree‐ring width, but also added valuable information on E. arborea responses to drought and their ecological implications for Mediterranean vegetation dynamics.
Singlet oxygen scavenging activity of tocopherol and plastochromanol in Arabidopsis thaliana: relevance to photooxidative stress
Authors: RASTOGI ANSHU , YADAV DEEPAK KUMAR , SZYMAŃSKA RENATA , KRUK JERZY , SEDLÁŘOVÁ MICHAELA , POSPÍŠIL PAVEL
Published: July 2013

In the present study, singlet oxygen (1O2) scavenging activity of tocopherol and plastochromanol was examined in tocopherol cyclase‐deficient mutant (vte1) of Arabidopsis thaliana lacking both tocopherol and plastochromanol. It is demonstrated here that suppression of tocopherol and plastochromanol synthesis in chloroplasts isolated from vte1 Arabidopsis plants enhanced 1O2 formation under high light illumination as monitored by electron paramagnetic resonance spin‐trapping spectroscopy. The exposure of vte1 Arabidopsis plants to high light resulted in the formation of secondary lipid peroxidation product malondialdehyde as determined by high‐pressure liquid chromatography. Furthermore, it is shown here that the imaging of ultra‐weak photon emission known to reflect oxidation of lipids was unambiguously higher in vte1 Arabidopsis plants. Our results indicate that tocopherol and plastochromanol act as efficient 1O2 scavengers and protect effectively lipids against photooxidative damage in Arabidopsis plants.