bluuebunny/crossref_metadata_2025 huggingface dataset:
Does previous chemotherapy‐induced nausea and vomiting predict postoperative nausea and vomiting?
Authors: da Silva H. B. G. , Sousa A. M. , Guimarães G. M. N. , Slullitel A. , Ashmawi H. A.
Published: June 2015

Background

Postoperative nausea and vomiting (PONV) remains a problem in the postoperative period. Previous PONV in oncology patients has recently been associated with chemotherapy‐induced nausea and vomiting (CINV). We assessed if CINV could improve Apfel's heuristic for predicting PONV.

Methods

We conducted a retrospective study of 1500 consecutive patients undergoing intermediate or major cancer surgery between April and July 2011. PONV was assessed in the first postoperative day during post‐anaesthesia care. The assigned anaesthetist completed an electronic medical record with all of the studied variables. Multiple logistic regression analyses were performed to assess whether any of the variables could add predictive ability to Apfel's tallying heuristic, and receiver operating characteristic (ROC) curves were modelled. The areas under the curve (AUC) were used to compare the model's discriminating ability for predicting patients who vomited from those who did not vomit.

Results

The overall incidence of PONV was 26%. Multiple logistic regressions identified two independent predictors for PONV (odds ratio; 95% CI), Apfel's score (1.78; 1.23–2.63) and previous chemotherapy‐induced vomiting (3.15; 1.71–5.9), Hosmer–Lemeshow's P < 0.0001. Previous CINV was the most significant predictor to be added to Apfel's heuristic in this population.

Conclusions

A history of chemotherapy‐induced nausea vomiting was a strong predictor for PONV and should be investigated as an added risk factor for PONV in the preoperative period of oncology surgery in prospective studies.
Childhood neglect predicts disorganization in schizophrenia through grey matter decrease in dorsolateral prefrontal cortex
Authors: Cancel A. , Comte M. , Truillet R. , Boukezzi S. , Rousseau P.‐F. , Zendjidjian X. Y. , Sage T. , Lazerges P.‐E. , Guedj E. , Khalfa S. , Azorin J.‐M. , Blin O. , Fakra E.
Published: June 2015

Objective

Psychosocial trauma during childhood is associated with schizophrenia vulnerability. The pattern of grey matter decrease is similar to brain alterations seen in schizophrenia. Our objective was to explore the links between childhood trauma, brain morphology and schizophrenia symptoms.

Method

Twenty‐one patients with schizophrenia stabilized with atypical antipsychotic monotherapy and 30 healthy control subjects completed the study. AnatomicalMRIimages were analysed using optimized voxel‐based morphometry (VBM). Childhood trauma was assessed with the Childhood Trauma Questionnaire, and symptoms were rated on the Scale for the Assessment of Negative Symptoms (SANS) and Scale for the Assessment of Positive Symptoms (SAPS) (disorganization, positive and negative symptoms). In the schizophrenia group, we used structural equation modelling in a path analysis.

Results

Total grey matter volume was negatively associated with emotional neglect (EN) in patients with schizophrenia. Whole‐brainVBManalyses of grey matter in the schizophrenia group revealed a specific inversed association between EN and the right dorsolateral prefrontal cortex (DLPFC). Path analyses identified a well‐fitted model in which EN predicted grey matter density in DLPFC, which in turn predicted the disorganization score.

Conclusion

Our findings suggest that EN during childhood could have an impact on psychopathology in schizophrenia, which would be mediated by developmental effects on brain regions such as theDLPFC.
Ahead of its time: 40 years after the advice versus treatment family study
Authors: Orford Jim
Published: June 2015

Griffith Edwards’ proposal for the alcohol ‘treatment versus advice’ study—also known as ‘the family study’—illustrates how ahead of his time he was. The sample consisted of 100 married men who attended with their wives for a comprehensive assessment. Those randomized to ‘advice’ were told that the responsibility for attaining the goal of abstinence lay in the patient's hands, supported by his wife, that no further intervention was indicated, but that the research social worker would ‘keep a watching brief’ by visiting the home every 4 weeks for 12 months. Across multiple outcome measures there was no evidence that ‘treatment’—considerable in amount by modern standards—was better than advice. Conversely, marital variables such as wives’ alcohol‐related hardship were significantly predictive of the outcome of the drinking problem. The study was arguably one of the principal sources of the whole ‘brief treatments’/‘brief interventions’ movement which gathered momentum from then on and which, arguably, has itself become the conventional wisdom. The findings questioned the very nature of the addiction change process, suggesting that non‐specific factors might be the more important, an issue that still remains unresolved. It is less clear that the study has left such a mark in terms of the development of a family and social model of addiction treatment and change. For example, it continues to be a struggle to help treatment organizations to become more family‐inclusive.
Empowerment through education and science: three intersecting strands in the career of Griffith Edwards
Authors: Crome Ilana
Published: June 2015

This paper describes three important strands in the career of Griffith Edwards that define him as a leader and an innovator. Believing that education and science were critical for the development of addiction as a profession and as a field of inquiry, his approach was multi‐faceted: educating all doctors to appreciate the fundamental issues in addiction; training psychiatrists in the complexity of ‘dual diagnosis’ and specific specialist intervention; and teaching that addiction could be a chronic condition which required care management over the life course. These three inter‐related areas are directly related to the need for a range of practitioners to have an understanding of addiction so that patients can be properly managed. The greater our understanding of the nature of addiction behaviour, the more likely the potential to optimize treatment and train practitioners from different professional disciplines.
Conceiving of Telecom: The Politics of Australian Telecommunications Reform 1967–1972
Authors: Doyle John
Published: June 2015

This article explores the politics of telecommunications reform between 1967 and 1972, during which time Labor developed a new policy approach that included committing to reconstitute the Postmaster‐General's Department as a relatively independent statutory authority. This represented the first serious attempt to reconcile the conflicting objectives of Australian policy: to provide affordable universal services by a government department expected to operate as a “business‐like” enterprise, and ended the political consensus about how national telecommunications should be delivered. The paper contrasts Labor's policy with the Liberal‐Country government's more incremental approach; and highlights a significant public policy shift that has received insufficient attention.
Greater Expectations: A Field Experiment to Improve Accountability in Mali
Authors: Gottlieb Jessica
Published: June 2015

I argue that if citizens systematically underestimate what their government can and should do for them, then they will hold politicians to a lower standard and sanction poor performers less often. A field experiment across 95 localities in Mali in which randomly assigned localities receive a civics course identifies the effect of raising voter expectations of government on their willingness to hold leaders accountable. The course provides information about local government capacity and responsibility as well as how local politicians perform relative to others, effectively raising voter expectations of what local governments can and should do. Survey experiments among individuals in treated and control communities (N = 5,560) suggest that people in treated villages are indeed more likely to sanction poor performers and vote based on performance more often. A behavioral outcome—the likelihood that villagers challenge local leaders at a town hall meeting—adds external validity to survey findings.
Indication for cataract surgery. Do we have evidence of who will benefit from surgery? A systematic review and meta‐analysis
Authors: Kessel Line , Andresen Jens , Erngaard Ditte , Flesner Per , Tendal Britta , Hjortdal Jesper
Published: June 2015

The need for cataract surgery is expected to rise dramatically in the future due to the increasing proportion of elderly citizens and increasing demands for optimum visual function. The aim of this study was to provide an evidence‐based recommendation for the indication of cataract surgery based on which group of patients are most likely to benefit from surgery. A systematic literature search was performed in the MEDLINE, CINAHL, EMBASE and COCHRANE LIBRARY databases. Studies evaluating the outcome after cataract surgery according to preoperative visual acuity and visual complaints were included in a meta‐analysis. We identified eight observational studies comparing outcome after cataract surgery in patients with poor (<20/40) and fair (>20/40) preoperative visual acuity. We could not find any studies that compared outcome after cataract surgery in patients with few or many preoperative visual complaints. A meta‐analysis showed that the outcome of cataract surgery, evaluated as objective and subjective visual improvement, was independent on preoperative visual acuity. There is a lack of scientific evidence to guide the clinician in deciding which patients are most likely to benefit from surgery. To overcome this shortage of evidence, many systems have been developed internationally to prioritize patients on waiting lists for cataract surgery, but the Swedish NIKE (Nationell Indikationsmodell för Katarakt Ekstraktion) is the only system where an association to the preoperative scoring of a patient has been related to outcome of cataract surgery. We advise that clinicians are inspired by the NIKE system when they decide which patients to operate to ensure that surgery is only offered to patients who are expected to benefit from cataract surgery.
Randomised clinical study: Aspergillus niger‐derived enzyme digests gluten in the stomach of healthy volunteers
Authors: Salden B. N. , Monserrat V. , Troost F. J. , Bruins M. J. , Edens L. , Bartholomé R. , Haenen G. R. , Winkens B. , Koning F. , Masclee A. A.
Published: June 2015

Background

Aspergillus niger prolyl endoprotease (AN‐PEP) efficiently degrades gluten molecules into non‐immunogenic peptides in vitro.

Aim

To assess the efficacy of AN‐PEP on gluten degradation in a low and high calorie meal in healthy subjects.

Methods

In this randomised, double‐blind, placebo‐controlled, cross‐over study 12 healthy volunteers attended to four test days. A liquid low or high calorie meal (4 g gluten) with AN‐PEP or placebo was administered into the stomach. Via a triple‐lumen catheter gastric and duodenal aspirates were sampled, and polyethylene glycol (PEG)‐3350 was continuously infused. Acetaminophen in the meals tracked gastric emptying time. Gastric and duodenal samples were used to calculate 240‐min area under the curve (AUC0–240 min) of ?‐gliadin concentrations. Absolute ?‐gliadin AUC0–240 min was calculated using duodenal PEG‐3350 concentrations.

Results

AN‐PEP lowered α‐gliadin concentration AUC0–240 min, compared to placebo, from low and high calorie meals in stomach (low: 35 vs. 389 μg × min/mL; high: 53 vs. 386 μg × min/mL; P < 0.001) and duodenum (low: 7 vs. 168 μg × min/mL; high: 4 vs. 32 μg × min/mL; P < 0.001) and absolute α‐gliadin AUC0–240 min in the duodenum from low (2813 vs. 31 952 μg × min; P < 0.001) and high (2553 vs. 13 095 μg × min; P = 0.013) calorie meals. In the placebo group, the high compared to low calorie meal slowed gastric emptying and lowered the duodenal α‐gliadin concentration AUC0–240 min (32 vs. 168 μg × min/mL; P = 0.001).

Conclusions

AN‐PEP significantly enhanced gluten digestion in the stomach of healthy volunteers. Increasing caloric density prolonged gastric residence time of the meal. Since AN‐PEP already degraded most gluten from low calorie meals, no incremental effect was observed by increasing meal caloric density. ClinicalTrials.gov, Number: NCT01335503; www.trialregister.nl, Number: NTR2780.
Aberrant GSTP1 promoter methylation predicts short‐term prognosis in acute‐on‐chronic hepatitis B liver failure
Authors: Gao S. , Sun F.‐K. , Fan Y.‐C. , Shi C.‐H. , Zhang Z.‐H. , Wang L.‐Y. , Wang K.
Published: June 2015

Background

Glutathione‐S‐transferase P1 (GSTP1) methylation has been demonstrated to be associated with oxidative stress induced liver damage in acute‐on‐chronic hepatitis B liver failure (ACHBLF).

Aim

To evaluate the methylation level of GSTP1 promoter in acute‐on‐chronic hepatitis B liver failure and determine its predictive value for prognosis.

Methods

One hundred and five patients with acute‐on‐chronic hepatitis B liver failure, 86 with chronic hepatitis B (CHB) and 30 healthy controls (HC) were retrospectively enrolled. GSTP1 methylation level in peripheral mononuclear cells (PBMC) was detected by MethyLight. Clinical and laboratory parameters were obtained.

Results

GSTP1 methylation levels were significantly higher in patients with acute‐on‐chronic hepatitis B liver failure (median 16.84%, interquartile range 1.83–59.05%) than those with CHB (median 1.25%, interquartile range 0.48–2.47%; P < 0.01) and HC (median 0.80%, interquartile range 0.67–1.27%; P < 0.01). In acute‐on‐chronic hepatitis B liver failure group, nonsurvivors showed significantly higher GSTP1 methylation levels (P < 0.05) than survivors. GSTP1 methylation level was significantly correlated with total bilirubin (r = 0.29, P < 0.01), prothrombin time activity (r = −0.24, P = 0.01) and model for end‐stage liver disease (MELD) score (r = 0.26, P = 0.01). When used to predict 1‐ or 2‐month mortality of acute‐on‐chronic hepatitis B liver failure, GSTP1 methylation showed significantly better predictive value than MELD score [area under the receiver operating characteristic curve (AUC) 0.89 vs. 0.72, P < 0.01; AUC 0.83 vs. 0.70, P < 0.05 respectively]. Meanwhile, patients with GSTP1 methylation levels above the cut‐off points showed significantly poorer survival than those below (P < 0.05).

Conclusions

Aberrant GSTP1 promoter methylation exists in acute‐on‐chronic hepatitis B liver failure and shows high predictive value for short‐term mortality. It might serve as a potential prognostic marker for acute‐on‐chronic hepatitis B liver failure.
Towards Development of a Dermal Pain Model: In Vitro Activation of Rat and Human Transient Receptor Potential Ankyrin Repeat 1 and Safe Dermal Injection of o‐Chlorobenzylidene Malononitrile to Rat
Authors: Annas Anita , Berg Anna‐Lena , Nyman Eva , Meijer Thomas , Lundgren Viveka , Franzén Bo , Ståhle Lars
Published: June 2015

During clinical development of analgesics, it is important to have access to pharmacologically specific human pain models. o‐Chlorobenzylidene malononitrile (CS) is a selective and potent agonist of the transient receptor potential ankyrin repeat 1 (TRPA1), which is a transducer molecule in nociceptors sensing reactive chemical species. While CS has been subject to extensive toxicological investigations in animals and human beings, its effects on intradermal or subcutaneous injection have not previously been reported. We have investigated the potential of CS to be used as an agonist on TRPA1 in human experimental pain studies. A calcium influx assay was used to confirm the capacity of CS to activate TRPA1 with >100,000 times the selectivity over the transient receptor potential vanilloid receptor 1. CS dose‐dependently (EC50 0.9 μM) released calcitonin gene‐related peptide in rat dorsal root ganglion cultures, supporting involvement in pain signalling. In a local tolerance study, injection of a single intradermal dose of 20 mM CS to rats resulted in superficial, circular crusts at the injection sites after approximately 4 days. The histopathology evaluation revealed a mild, acute inflammatory reaction in the epidermis and dermis at the intradermal CS injection site 1 day after administration. After 14 days, the epidermal epithelium was fully restored. The symptoms were not considered to be adverse, and it is suggested that doses up to 20 μL of 20 mM CS can be safely administered to human beings. In conclusion, our data support development of a CS human dermal pain model.
Finding death in meaninglessness: Evidence that death‐thought accessibility increases in response to meaning threats
Authors: Webber David , Zhang Rui , Schimel Jeff , Blatter Jamin
Published: June 2015

The meaning maintenance model proposes that violations to one's expectations will cause subsequent meaning restoration. In attempts to distinguish meaning maintenance mechanisms from mechanisms of terror management, previous research has failed to find increased death‐thought accessibility (DTA) in response to various meaning threats. The present research suggests that this failure may have resulted from methodological differences in the way researchers measured DTA. Studies 1a and 1b found that by replacing this method with a standard method employed when studying worldview and self‐esteem threats, DTA increased in response to two different meaning violations. Study 2 found increased DTA, but only among individuals high in personal need for structure, when using this standard DTA procedure, but not when using the procedure taken from previous meaning maintenance studies. Interestingly, these studies did not find increased meaning restoration, so an additional study (Study 3) was designed to provide a theoretically informed examination of this null effect. A meaning restoration effect was observed after removing the standard DTA assessment procedure, but only among participants high in personal need for structure. Implications for the threat‐compensation literature are discussed.
Salvinorin A analogues PR‐37 and PR‐38 attenuate compound 48/80‐induced itch responses in mice
Authors: Salaga M , Polepally P R , Zielinska M , Marynowski M , Fabisiak A , Murawska N , Sobczak K , Sacharczuk M , Do Rego J C , Roth B L , Zjawiony J K , Fichna J
Published: June 2015

Background and Purpose

The opioid system plays a crucial role in several physiological processes in the CNS and in the periphery. It has also been shown that selective opioid receptor agonists exert potent inhibitory action on pruritus and pain. In this study we examined whether two analogues of Salvinorin A, PR‐37 and PR‐38, exhibit antipruritic properties in mice.

Experimental Approach

To examine the antiscratch effect of PR‐37 and PR‐38 we used a mouse model of compound 48/80‐induced pruritus. In order to elucidate the mechanism of action of tested compounds, specific antagonists of opioid and cannabinoid receptors were used. The effect of PR‐37 on the CNS was assessed by measuring motor parameters and exploratory behaviours in mice.

Key Results

PR‐37 and PR‐38, jnjected s.c., significantly reduced the number of compound 48/80‐induced scratching behaviours in mice in a dose‐ and time‐dependent manner. PR‐38 was also active when orally administered. The antiscratch activity of PR‐37 was blocked by the selective κ opioid receptor antagonist, nor‐binaltorphimine, and that of PR‐38 by the selective μ opioid receptor antagonist, β‐funaltrexamine.

Conclusion and Implications

In conclusion, a novel framework for the development of new antipruritic drugs derived from salvinorin A has been validated.
Src/STAT3‐dependent heme oxygenase‐1 induction mediates chemoresistance of breast cancer cells to doxorubicin by promoting autophagy
Authors: Tan Qixing , Wang Hongli , Hu Yongliang , Hu Meiru , Li Xiaoguang ,   Aodengqimuge , Ma Yuanfang , Wei Changyuan , Song Lun
Published: June 2015

Chemotherapeutic resistance in breast cancer, whether acquired or intrinsic, remains a major clinical obstacle. Thus, increasing tumor cell sensitivity to chemotherapeutic agents will be helpful in improving the clinical management of breast cancer. In the present study, we found an induction of HO‐1 expression in doxorubicin (DOX)‐treated MDA‐MB‐231 human breast adenocarcinoma cells, which showed insensitivity to DOX treatment. Knockdown HO‐1 expression dramatically upregulated the incidence of MDA‐MB‐231 cell death under DOX treatment, indicating that HO‐1 functions as a critical contributor to drug resistance in MDA‐MB‐231 cells. We further observed that DOX exposure induced a cytoprotective autophagic flux in MDA‐MB‐231 cells, which was dependent on HO‐1 induction. Moreover, upregulation of HO‐1 expression required the activation of both signal transducer and activator of transcription (STAT)3 and its upstream regulator, protein kinase Src. Abrogating Src/STAT3 pathway activation attenuated HO‐1 and autophagy induction, thus increasing the chemosensitivity of MDA‐MB‐231 cells. Therefore, we conclude that Src/STAT3‐dependent HO‐1 induction protects MDA‐MB‐231 breast cancer cells from DOX‐induced death through promoting autophagy. In the following study, we further demonstrated the contribution of Src/STAT3/HO‐1/autophagy pathway activation to DOX resistance in another breast cancer cell line, MDA‐MB‐468, which bears a similar phenotype to MDA‐MB‐231 cells. Therefore, activation of Src/STAT3/HO‐1/autophagy signaling pathway might play a general role in protecting certain subtypes of breast cancer cells from DOX‐induced cytotoxicity. Targeting this signaling event may provide a potential approach for overcoming DOX resistance in breast cancer therapeutics.
Individual Differences in Theory of Mind From Preschool to Adolescence: Achievements and Directions
Authors: Hughes Claire , Devine Rory T.
Published: June 2015

In this article, we provide a state‐of‐the‐science overview of research on normative individual differences in theory of mind. We begin by examining achievements in research on individual differences in theory of mind in the preschool years and more recent work on middle childhood and adolescence. In doing so, we outline several converging lines of evidence for social influences on individual differences in theory of mind, and assess the claim that individual differences in theory of mind matter for children's social lives. We then evaluate two conceptualizations of individual differences in theory of mind: the developmental lag and genuine differences accounts. By placing the study of individual differences in theory of mind center stage, we aim to highlight fruitful avenues for research on normative variation in theory of mind both within and beyond the preschool years.
Evaluation of the Surface Treatment on Bone Healing in a Transmucosal 1‐mm Area of Implant Abutment: An Experimental Study in the Rabbit Tibia
Authors: Gehrke Sergio Alexandre , da Silva Neto Ulisses Tavares
Published: June 2015

Purpose

The objective of the present study was to investigate the effect on bone tissue healing patterns in 1‐mm area treated in the transmucosal surface of the abutment in the tibia of rabbits.

Materials and Methods

Forty‐six abutments were divided into two groups: control group (CG) with 14 abutments with smooth surface and experimental group (EG) with 32 abutments presenting a 1‐mm area of the transmucosal surface treated through sandblasting with microparticles of titanium oxide followed by acid etching. Five samples of each group were analyzed using an optical laser profilometer for surface roughness characterization. Thirty‐six Morse taper implants (3.5 mm in diameter and 7 mm in length) were inserted 1.5 mm subcrestal into the tibiae of nine rabbits. The implants were removed after 8, 10, and 12 weeks for histological analysis. The histological slides were prepared and analyzed qualitatively in relation to the new bone at the interface bone‐abutment and quantitatively, in relation to bone height from the base of the implant. These data were computed and statistically compared inside the groups using analysis of variance and the U‐test between groups for same time.

Results

Both groups exhibited bone growth in the direction and over the surface of the abutments, with good healing. However, the EG group showed an increased height of bone formation in the crestal direction, and highly significant differences were observed (p < .001) between these measured values.

Conclusions

Under the limitations of the present study, histological follow‐up at 8, 10, and 12 weeks showed that transmucosal 1‐mm area of implant abutment with treatment of the surface facilitated the maintenance of bone height around the abutment compared with the same abutment with the totally smooth surface.
A quantification of regenerated bone tissue in human sinus biopsies: influences of anatomical region, age and sex
Authors: Reich Karoline Maria , Huber Christian Domitian , Heimel Patrick , Ulm Christian , Redl Heinz , Tangl Stefan
Published: June 2015

Objectives

Sinus augmentation is a standard procedure to increase vertical bone supply for dental implants in the atrophic posterior maxilla. Despite the longstanding application of this method, information about some basic factors that could potentially influence bone regeneration after sinus augmentation is rare. The objective of this study was therefore to quantify the impact of the maxillary region (premolar/molar) and patients' age and sex on bone regeneration after sinus grafting.

Material and methods

Sinus augmentation procedures were performed in 107 patients (66 female: 52.8 ± 11.0 years, 41 male: 50.6 ± 11.3 years). After 6 ± 1 months, 201 sinus biopsies were harvested and histomorphometrically analysed. Height (oldHt) and bone volume fraction of pristine bone (oldBV/TV), as well as the amount of new bone (newBV/TV) and bone‐to‐bone substitute contact (BBSC) in the augmentation area, were assessed.

Results

In women, newBV/TV in the augmented sinus decreased significantly by 0.22 ± 0.08% per year. In men, no similar trend was observed. There were strong influences of the maxillary region and the dimensions of the host bone. In the premolar region, newBV/TV was 23.1 ± 7.9% and 25.1 ± 10.1%; in the molar region, newBV/TV averaged 20.4 ± 9.4% and 17.8 ± 8.8% for women and men, respectively. The greater the thickness of the wall of the sinus floor (mainly in the former premolar region), the greater was the amount of new bone tissue formed in the spaces in‐between bone substitute particles.

Conclusions

These empirical results derived from a large human sample, link factors that influence the quality of biomaterial integration to the known clinical risks for the success of dental implants.
A meta‐analysis of functional group responses to forest recovery outside of the tropics
Authors: Spake Rebecca , Ezard Thomas H. G. , Martin Philip A. , Newton Adrian C. , Doncaster C. Patrick
Published: June 2015

Both active and passive forest restoration schemes are used in degraded landscapes across the world to enhance biodiversity and ecosystem service provision. Restoration is increasingly also being implemented in biodiversity offset schemes as compensation for loss of natural habitat to anthropogenic development. This has raised concerns about the value of replacing old‐growth forest with plantations, motivating research on biodiversity recovery as forest stands age. Functional diversity is now advocated as a key metric for restoration success, yet it has received little analytical attention to date. We conducted a meta‐analysis of 90 studies that measured differences in species richness for functional groups of fungi, lichens, and beetles between old‐growth control and planted or secondary treatment forests in temperate, boreal, and Mediterranean regions. We identified functional‐group–specific relationships in the response of species richness to stand age after forest disturbance. Ectomycorrhizal fungi averaged 90 years for recovery to old‐growth values (between 45 years and unrecoverable at 95% prediction limits), and epiphytic lichens took 180 years to reach 90% of old‐growth values (between 140 years and never for recovery to old‐growth values at 95% prediction limits). Non‐saproxylic beetle richness, in contrast, decreased as stand age of broadleaved forests increased. The slow recovery by some functional groups essential to ecosystem functioning makes old‐growth forest an effectively irreplaceable biodiversity resource that should be exempt from biodiversity offsetting initiatives.
Attributes of God: Conceptual Foundations of a Foundational Belief
Authors: Shtulman Andrew , Lindeman Marjaana
Published: June 2015

Anthropomorphism, or the attribution of human properties to nonhuman entities, is often posited as an explanation for the origin and nature of God concepts, but it remains unclear which human properties we tend to attribute to God and under what conditions. In three studies, participants decided whether two types of human properties—psychological (mind‐dependent) properties and physiological (body‐dependent) properties—could or could not be attributed to God. In Study 1 (n = 1,525), participants made significantly more psychological attributions than physiological attributions, and the frequency of those attributions was correlated both with participants’ religiosity and with their attribution of abstract, theological properties. In Study 2 (n = 99) and Study 3 (n = 138), participants not only showed the same preference for psychological properties but were also significantly faster, more consistent, and more confident when attributing psychological properties to God than when attributing physiological properties. And when denying properties to God, they showed the reverse pattern—that is, they were slower, less consistent, and less confident when denying psychological properties than when denying physiological properties. These patterns were observed both in a predominantly Christian population (Study 2) and a predominantly Hindu population (Study 3). Overall, we argue that God is conceptualized not as a person in general but as an agent in particular, attributed a mind by default but attributed a body only upon further consideration.
Immunology of metal allergies
Authors: Schmidt Marc , Goebeler Matthias
Published: June 2015

Allergic contact hypersensitivity to metal allergens is a common health concern worldwide, greatly impacting affected individuals with regard to both quality of life and their ability to work. With an estimated 15–20 % of the Western population hypersensitive to at least one metal allergen, sensitization rates for metallic haptens by far outnumber those reported for other common triggers of allergic contact dermatitis such as fragrances and rubber. Unfortunately, the prevalence of metal‐induced hypersensitivity remains high despite extensive legislative efforts to ban/reduce the content of allergy‐causing metals in recreational and occupational products.

Recently, much progress has been made regarding the perception mechanisms underlying the inflammatory responses to this unique group of contact allergens. This review summarizes recent advances in our understanding of this enigmatic disease. Particular emphasis is put on the mechanisms of innate immune activation and T cell activation by common metal allergens such as nickel, cobalt, palladium, and chromate.
Optimal Pricing of Two Successive‐Generation Products with Trade‐in Options under Uncertainty
Authors: Yin Rui , Li Hongmin , Tang Christopher S.
Published: June 2015

To entice consumers to purchase both current and next generation products, many manufacturers and retailers offer trade‐in programs that allow buyers of the first generation product to trade‐in the product and purchase the new generation product at a lower price. By considering the interactions between “forward‐looking” consumers and a firm when a trade‐in program is offered, we analyze a two‐period dynamic game to determine the optimal prices of two successive‐generation products in equilibrium, and examine the conditions under which trade‐in programs are beneficial to the firm. Our model incorporates market heterogeneity (valuation of the first generation product varies among the consumer population), product uncertainty (the incremental value of the new product is uncertain before its introduction), and consumers' forward‐looking behavior (consumers take future product valuation and prices into consideration when making purchasing decisions). With the trade‐in option, we show that consumers are willing to pay a price that is higher than their valuations of the current product. Furthermore, trade‐in programs are more beneficial to the firm when: (i) the durability of the current product is high; (ii) the market heterogeneity is low; or (iii) the uncertainty level (or the expected incremental value) of the new product is high. Finally, when the incremental value of the new product is more uncertain, consumers are more willing to purchase the current product because of the “option” value of the trade‐in programs and thus trade‐in programs can be more beneficial to the firm in this case.
Socio‐economic disparities and functional limitations of children with cerebral palsy
Authors: Durkin Maureen S
Published: June 2015

This commentary is on the original article by Oskoui et al. on pages 160–166 of this issue.
GCK monogenic diabetes and gestational diabetes: possible diagnosis on clinical grounds
Authors: Flack J. R. , Ross G. P. , Cheung N. W.
Published: June 2015

Aim

To determine if the previously published clinical criteria for identifying glucokinase monogenic diabetes [GCK gene mutation in maturity‐onset diabetes of the young (GCK‐MODY)], an elevated antenatal fasting blood glucose of 5.5–8.0 mmol/l, an increment of < 4.6 mmol/l at 2 h in an oral glucose tolerance test and slim are applicable in a large multi‐ethnic cohort of women with gestational diabetes.

Methods

We analysed de‐identified data from all women with gestational diabetes, diagnosed using the Australasian Diabetes in Pregnancy Society (1998) Australian criteria at our institution between 1993 and 2013, making comparisons among those with complete antenatal data including: diagnostic oral glucose tolerance test results meeting the above criteria; pregestational BMI; birth outcomes; and postpartum oral glucose tolerance test data. We categorized these women into two groups: Group A1 had a BMI ≤ 21 kg/m2 and Group A2 had a BMI > 21 kg/m2 and < 25 kg/m2.

Results

Of the 302 women meeting the study entry criteria, we had complete data including a postpartum oral glucose tolerance test result for 171 women: 54 in Group A1 and 117 in Group A2. Ethnicity was significantly different between the groups. The oral glucose tolerance test and postpartum HbA1c results identified few women ( < 14%) in Group A1 and Group A2 who still had ‘possible GCK‐MODY’.

Conclusions

Our findings indicate that previously recommended clinical criteria for the identification of women likely to have GCK‐MODY lack specificity in a cohort of women with multi‐ethnic backgrounds. Using these criteria to select women for testing for GCK‐MODY in pregnancy would therefore be costly and is likely to yield few women positive for this condition.
Plasma insulin profiles after subcutaneous injection: how close can we get to physiology in people with diabetes?
Authors: Home P. D.
Published: June 2015

Many people with diabetes rely on insulin therapy to achieve optimal blood glucose control. A fundamental aim of such therapy is to mimic the pattern of ‘normal’ physiological insulin secretion, thereby controlling basal and meal‐time plasma glucose and fatty acid turnover. In people without diabetes, insulin release is modulated on a time base of 3–10 min, something that is impossible to replicate without intravascular glucose sensing and insulin delivery. Overnight physiological insulin delivery by islet β cells is unchanging, in contrast to requirements once any degree of hyperglycaemia occurs, when diurnal influences are evident. Subcutaneous pumped insulin or injected insulin analogues can approach the physiological profile, but there remains the challenge of responding to day‐to‐day changes in insulin sensitivity. Physiologically, meal‐time insulin release begins rapidly in response to reflex activity and incretins, continuing with the rise in glucose and amino acid concentrations. This rapid response reflects the need to fill the insulin space with maximum concentration as early as 30 min after starting the meal. Current meal‐time insulins, by contrast, are associated with a delay after injection before absorption begins, and a delay to peak because of tissue diffusion. While decay from peak for monomeric analogues is not dissimilar to average physiological needs, changes in meal type and, again, in day‐to‐day insulin sensitivity, are difficult to match. Recent and current developments in insulin depot technology are moving towards establishing flatter basal and closer‐to‐average physiological meal‐time plasma insulin profiles. The present article discusses the ideal physiological insulin profile, how this can be met by available and future insulin therapies and devices, and the challenges faced by healthcare professionals and people with diabetes in trying to achieve an optimum plasma insulin profile.
Impact of empagliflozin added on to basal insulin in type 2 diabetes inadequately controlled on basal insulin: a 78‐week randomized, double‐blind, placebo‐controlled trial
Authors: Rosenstock J. , Jelaska A. , Zeller C. , Kim G. , Broedl U. C. , Woerle H. J. ,   on behalf of the EMPA‐REG BASAL trial investigators
Published: June 2015

Aims

To investigate the efficacy and tolerability of empagliflozin added to basal insulin‐treated type 2 diabetes.

Methods

Patients inadequately controlled [glycated haemoglobin (HbA1c) >7 to ≤10% (>53 to ≤86 mmol/mol)] on basal insulin (glargine, detemir, NPH) were randomized to empagliflozin 10 mg (n = 169), empagliflozin 25 mg (n = 155) or placebo (n = 170) for 78 weeks. The baseline characteristics were balanced among the groups [mean HbA1c 8.2% (67 mmol/mol), BMI 32.2 kg/m2]. The basal insulin dose was to remain constant for 18 weeks, then could be adjusted at investigator's discretion. The primary endpoint was change from baseline in HbA1c at week 18. Key secondary endpoints were changes from baseline in HbA1c and insulin dose at week 78.

Results

At week 18, the adjusted mean ± standard error changes from baseline in HbA1c were 0.0 ± 0.1% (−0.1 ± 0.8 mmol/mol) for placebo, compared with −0.6 ± 0.1% (−6.2 ± 0.8 mmol/mol) and −0.7 ± 0.1% (−7.8 ± 0.8 mmol/mol) for empagliflozin 10 and 25 mg, respectively (both p < 0.001). At week 78, empagliflozin 10 and 25 mg significantly reduced HbA1c, insulin dose and weight vs placebo (all p < 0.01), and empagliflozin 10 mg significantly reduced systolic blood pressure vs placebo (p = 0.004). Similar percentages of patients had confirmed hypoglycaemia in all groups (35–36%). Events consistent with urinary tract infection were reported in 9, 15 and 12% of patients on placebo, empagliflozin 10 and 25 mg, and events consistent with genital infection were reported in 2, 8 and 5%, respectively.

Conclusions

Empagliflozin for 78 weeks added to basal insulin improved glycaemic control and reduced weight with a similar risk of hypoglycaemia to placebo.
Fixed ratio dosing of pramlintide with regular insulin before a standard meal in patients with type 1 diabetes
Authors: Riddle M. C. , Yuen K. C. J. , de Bruin T. W. , Herrmann K. , Xu J. , Öhman P. , Kolterman O. G.
Published: June 2015

Amylin is co‐secreted with insulin and is therefore lacking in patients with type 1 diabetes. Replacement with fixed ratio co‐administration of insulin and the amylin analogue pramlintide may be superior to separate dosing. This concept was evaluated in a ratio‐finding study. Patients with type 1 diabetes were enrolled in a randomized, single‐masked, standard breakfast crossover study using regular human insulin injected simultaneously with pramlintide 6, 9 or 12 mcg/unit insulin or placebo. Insulin dosage was reduced by 30% from patients' usual estimates. Plasma glucose, glucagon and pramlintide and adverse events were assessed. All ratios reduced 0–3‐h glucose and glucagon increments by >50%. No hypoglycaemia occurred. Adverse events were infrequent and generally mild. All pramlintide/insulin ratios markedly and safely reduced glycaemic excursions and suppressed glucagon secretion in the immediate postprandial state. Further study using one of these ratios to explore the efficacy and safety of longer‐term meal‐time and basal hormone replacement is warranted.
Impact of renin‐angiotensin system blockade on clinical outcome in glioblastoma
Authors: Januel E. , Ursu R. , Alkhafaji A. , Marantidou A. , Doridam J. , Belin C. , Levy‐Piedbois C. , Carpentier A. F.
Published: June 2015

Background and purpose

Despite surgery, radiotherapy (RT) and temozolomide (TMZ), the prognosis of glioblastoma (GBM) patients remains dismal. Normally prescribed with the aim to lower blood pressure, angiotensin‐II (Ang‐II) inhibitors were reported to reduce angiogenesis and tumour growth in several tumour models including one glioma. Thus whether treatment with Ang‐II inhibitors could be associated with a better clinical outcome in GBM patients was investigated.

Methods

A series of 81 consecutive patients, homogeneously treated with RT and TMZ for a newly diagnosed, supratentorial GBM, were analysed. The objective of this retrospective study was to assess the impact of angiotensin‐converting enzyme inhibitors (ACEIs) and Ang‐II receptor 1 blockers (ARBs) on functional independence, progression‐free survival (PFS) and overall survival (OS).

Results

Amongst the 81 GBM patients analysed, 26 were already treated for high blood pressure (seven with ACEIs and 19 with ARBs). The number of patients who remained functionally independent at 6 months after RT was higher in the group of patients treated with Ang‐II inhibitors compared to the other patients (85% vs. 56%, P = 0.01). In patients treated with Ang‐II inhibitors, PFS was 8.7 months (vs. 7.2 months in the other patients) and OS was 16.7 months (vs. 12.9 months). The use of Ang‐II inhibitors was a significant prognostic factor for both PFS (P = 0.04) and OS (P = 0.04) in multivariate analysis.

Conclusion

Treatment with Ang‐II inhibitors in combination with RT and TMZ might improve clinical outcome in GBMs. Prospective trials are needed to test this hypothesis.
Anti‐absence activity of mGlu1 and mGlu5 receptor enhancers and their interaction with a GABA reuptake inhibitor: Effect of local infusions in the somatosensory cortex and thalamus
Authors: D'Amore Valerio , von Randow Constanze , Nicoletti Ferdinando , Ngomba Richard Teke , van Luijtelaar Gilles
Published: June 2015

Objective

Glutamate and γ‐aminobutyric acid (GABA) are the key neurotransmitter systems in the cortical‐thalamocortical network, involved in normal and pathologic oscillations such as spike‐wave discharges (SWDs), which characterize different forms of absence epilepsy. Metabotropic glutamate (mGlu) and GABA receptors are widely expressed within this network. Herein, we examined the effects of two selective positive allosteric modulators (PAMs) of mGlu1 and mGlu5 receptors, the GABA reuptake inhibitor, tiagabine, and their interaction in the somatosensory cortex and thalamus on SWDs in WAG/Rij rats.

Methods

Male WAG/Rij rats were equipped with bilateral cannulas in the somatosensory cortex (S1po) or the ventrobasal (VB) thalamic nuclei, and with cortical electroencephalography (EEG) electrodes. Rats received a single dose of the mGlu1 receptor PAM, RO0711401, or the mGlu5 receptor PAM, VU0360172, various doses of tiagabine, or VU0360172 combined with tiagabine.

Results

Both PAMs suppressed SWDs regardless of the site of injection. Tiagabine enhanced SWDs when injected into the thalamus, but, unexpectedly, suppressed SWDs in a dose‐dependent manner when injected into the cortex. Intracortical co‐injection of VU0360172 and tiagabine produced slightly larger effects as compared to either VU0360172 or tiagabine alone. Intrathalamic co‐injections of VU0360172 and subthreshold doses of tiagabine caused an antiabsence effect similar to that exhibited by VU0360172 alone in the first 10 min. At 30 min, however, the antiabsence effect of VU0360172 was prevented by subthreshold doses of tiagabine, and the combination produced a paradoxical proabsence effect at 40 and 50 min.

Significance

These data (1) show that mGlu1 and mGlu5 receptor PAMs reduce absence seizures acting at both thalamic and cortical levels; (2) demonstrate for the first time that tiagabine, despite its established absence‐enhancing effect, reduces SWDs when injected into the somatosensory cortex; and (3) indicate that the efficacy of VU0360172 in the thalamus may be critically affected by the availability of (extra)synaptic GABA.
Mediterranean blue tits as a case study of local adaptation
Authors: Charmantier Anne , Doutrelant Claire , Dubuc‐Messier Gabrielle , Fargevieille Amélie , Szulkin Marta
Published: June 2015

While the study of the origins of biological diversity across species has provided numerous examples of adaptive divergence, the realization that it can occur at microgeographic scales despite gene flow is recent, and scarcely illustrated. We review here evidence suggesting that the striking phenotypic differentiation in ecologically relevant traits exhibited by blue titsCyanistes caeruleusin their southern range‐edge putatively reflects adaptation to the heterogeneity of the Mediterranean habitats. We first summarize the phenotypic divergence for a series of life history, morphological, behavioural, acoustic and colour ornament traits in blue tit populations of evergreen and deciduous forests. For each divergent trait, we review the evidence obtained from common garden experiments regarding a possible genetic origin of the observed phenotypic differentiation as well as evidence for heterogeneous selection. Second, we argue that most phenotypically differentiated traits display heritable variation, a fundamental requirement for evolution to occur. Third, we discuss nonrandom dispersal, selective barriers and assortative mating as processes that could reinforce local adaptation. Finally, we show how population genomics supports isolation – by – environment across landscapes. Overall, the combination of approaches converges to the conclusion that the strong phenotypic differentiation observed in Mediterranean blue tits is a fascinating case of local adaptation.
A new data envelopment analysis method for ranking decision making units: an application in industrial parks
Authors: Izadikhah Mohammad , Farzipoor Saen Reza
Published: June 2015

Relative efficiency of decision‐making units (DMUs) is assessed by classical data envelopment analysis (DEA) models. DEA is a popular technique for efficiency evaluation. There might be a couple of efficient DMUs. Classical DEA models cannot fully rank efficient DMUs. In this paper, a novel technique for fully ranking all DMUs based on changing reference set using a single virtual inefficient DMU is proposed. To this end, the first concept of virtual DMU is defined as average of all inefficient DMUs. Virtual DMU is a proxy of all inefficient DMUs. This new method proposes a new ranking method that takes into account impact of efficient DMUs on virtual DMU and impact of efficient DMUs on influences of other efficient DMUs. A case study is given to show applicability of the proposed approach.