bluuebunny/crossref_metadata_2025 huggingface dataset:
Death in the clinic: women's perceptions and experiences of discarding supernumerary IVF embryos
Authors: de Lacey Sheryl
Published: October 2016

Perspectives on the status of human embryos and whether they should be discarded differ globally. Some countries protect embryos in law while in other countries embryos ‘die’ or ‘succumb’ in assisted reproductive technology clinics on a daily basis. This study analyses interview data drawn from a larger qualitative study conducted in South Australia from 2004–2007. 21 women and 12 of 21 partners were interviewed about the decision they made to discard their embryos. The analysis reported here sought to examine the ways in which women constructed and experienced the decision to discard embryos. The article highlights the ways in which embryo discard is a contested discursive space. Embryo death is sequestered through their confinement in the laboratory and their invisibility to the naked eye. The clinic treated embryo discard as disposal of biological waste and failed to acknowledge the meaning of the event. By contrast women experienced emotional bereavement described as similar to early pregnancy loss, and described experiences of attachment and grief. For sensitive and compassionate care these differences in perceptions of embryo discard need to be addressed.
Advanced maternal age increases the risk of very preterm birth, irrespective of parity: a population‐based register study
Authors: Waldenström U , Cnattingius S , Vixner L , Norman M
Published: October 2016

Objective

To investigate whether advanced maternal age is associated with preterm birth, irrespective of parity.

Design

Population‐based registry study.

Setting

Swedish Medical Birth Register.

Population

First, second, and third live singleton births to women aged 20 years or older in Sweden, from 1990 to 2011 (n = 2 009 068).

Methods

Logistic regression analysis was used in each parity group to estimate risks of very and moderately preterm births to women at 20–24, 25–29, 30–34, 35–39, and 40 years or older, using 25–29 years as the reference group. Odds ratios (ORs) were adjusted for year of birth, education, country of birth, smoking, body mass index, and history of preterm birth. Age‐related risks of spontaneous and medically indicated preterm births were also investigated.

Main outcome measures

Very preterm (22–31 weeks of gestation) and moderately preterm (32–36 weeks) births.

Results

Risks of very preterm birth increased with maternal age, irrespective of parity: adjusted ORs in first, second, and third births ranged from 1.18 to 1.28 at 30–34 years, from 1.59 to 1.70 at 35–39 years, and from 1.97 to 2.40 at ≥40 years. In moderately preterm births, age‐related associations were weaker, but were statistically significant from 35–39 years in all parity groups. Advanced maternal age increased the risks of both spontaneous and medically indicated preterm births.

Conclusions

Advanced maternal age is associated with an increased risk of preterm birth, irrespective of parity, especially very preterm birth. Women aged 35 years and older, expecting their first, second, or third births, should be regarded as a risk group for very preterm birth.

Tweetable abstract

Women aged 35 years and older should be regarded as a risk group for very preterm birth, irrespective of parity.
Serious maternal complications in relation to severe pre‐eclampsia: a retrospective cohort study of the impact of hospital volume
Authors: Ananth CV , Lavery JA , Friedman AM , Wapner RJ , Wright JD
Published: October 2016

Objective

We examined rates of serious maternal complications in relation to severe pre‐eclampsia based on the delivering hospital's annualised volume.

Design

Retrospective cohort study.

Population and setting

Singleton deliveries (n = 25 782 235) in 439 hospitals in the USA.

Methods

Annualised hospital volume was categorised as 25–500, 501–1000, 1001–2000 and >2000.

Main outcome measures

Rates of in‐hospital maternal death and serious maternal complications, including puerperal cerebrovascular disorders, pulmonary oedema, disseminated intravascular coagulation, acute renal, heart and liver failure, sepsis, haemorrhage and intubation in relation to severe pre‐eclampsia. We derived adjusted risk ratio (RR) and 95% confidence interval (CI), from hierarchical Poisson regression models.

Results

Severe pre‐eclampsia was associated with an 8.7‐fold (95% CI 7.6, 10.1) risk of composite maternal complications, with similar RRs across levels of hospital volumes. However, compared with hospitals with low annual volume (<2000), maternal mortality rates in relation to severe pre‐eclampsia were lower in high volume hospitals. The rates of serious maternal complications were 410.7 per 10 000 to women who delivered in hospitals with a high rate of severe pre‐eclampsia (≥2.12%) and 584.8 per 10 000 to women who delivered in hospitals with low severe pre‐eclampsia rates (≤0.41; RR 1.75, 95% CI 1.24, 2.45).

Conclusions

While the risks of serious maternal complications in relation to severe pre‐eclampsia was similar across hospital delivery volume categories, deaths showed lower rates in large delivery volume hospitals than in smaller volume hospitals. The risk of complications was increased in hospitals with low compared with high severe pre‐eclampsia rates.

Tweetable abstract

Hospital volume had little impact on the association between severe pre‐eclampsia and maternal complications.
State of the Science: Tools and Measurement for Shared Decision Making
Authors: Sepucha Karen R. , Breslin Maggie , Graffeo Charles , Carpenter Christopher R. , Hess Erik P.
Published: October 2016

Shared decision making (SDM) has been advocated as an approach to selecting medical tests and treatments for many situations. The goal of SDM is to ensure that patients are well informed, are meaningfully involved in decisions, and receive treatments that meet their goals and preferences. There is considerable evidence about the tools used to promote SDM, called patient decision aids, and many different measures have been developed to assess the impact of SDM. However, fairly little is known about the applicability of the tools and measures in the emergency department (ED) setting. This article builds on insights from two keynote lectures presented at the 2016 Academic Emergency Medicine Consensus Conference discussing the state of the science for measurement of SDM and the design of patient decision aids to promote SDM conversations and highlights some key areas for further research to advance SDM in the ED.
Quality of life, anxiety and depression symptoms in early and late pregnancy in women with pregestational diabetes
Authors: Do Nicoline C. , Secher Anna L. , Cramon Per , Ringholm Lene , Watt Torquil , Damm Peter , Mathiesen Elisabeth R.
Published: October 2016

Introduction

The aim of this study was to explore changes in health‐related quality of life, anxiety and depression symptoms during pregnancy in women with pregestational diabetes.

Material and methods

An observational cohort study including 137 pregnant women with pregestational diabetes (110 with type 1 and 27 with type 2). To evaluate changes from early to late pregnancy, the internationally validated questionnaires 36‐Item Short‐Form Health Survey (SF‐36) and Hospital Anxiety and Depression Scale (HADS) were completed at 8 and 33 gestational weeks.

Results

From early to late pregnancy, the SF‐36 scales Physical Function, Role Physical, Bodily Pain and Physical Component Summary worsened (p < 0.0001 for all scales). Physical Component Summary score deteriorated from mean 52.3 (SD 6.5) to 40.0 (9.7) (p < 0.0001) and the deterioration was negatively associated with gestational weight gain in multiple linear regression (β = −0.34/kg, p = 0.03). The SF‐36 scale Mental Health improved (p = 0.0009) and the Mental Component Summary score increased moderately from 47.6 (10.6) to 53.5 (8.6) (p < 0.0001). Greater improvement in Mental Component Summary score was seen with lower HbA1c in late pregnancy. The HADS anxiety score improved slightly from 5.0 (3.3) to 4.5 (3.4) (p = 0.04) whereas the HADS depression score remained unchanged. The prevalence of women with HADS anxiety or depression score ≥8 did not change.

Conclusions

Physical quality of life deteriorated whereas mental quality of life improved slightly during pregnancy in women with pregestational diabetes. A minor reduction in anxiety and stable depression symptoms was observed. The results on mental health are reassuring, considering the great demands that pregnancy places on women with pregestational diabetes.
Acute physical exercise and long‐term individual shear rate therapy increase telomerase activity in human peripheral blood mononuclear cells
Authors: Zietzer A. , Buschmann E. E. , Janke D. , Li L. , Brix M. , Meyborg H. , Stawowy P. , Jungk C. , Buschmann I. , Hillmeister P.
Published: October 2016

Aim

Physical activity is a potent way to impede vascular ageing. However, patients who suffer from peripheral artery disease (PAD) are often unable to exercise adequately. For those patients, we have developed individual shear rate therapy (ISRT), which is an adaptation of external counterpulsation and enhances endovascular fluid shear stress to increase collateral growth (arteriogenesis). To evaluate the effects of physical exercise and ISRT on the telomere biology of peripheral blood mononuclear cells (PBMCs), we conducted two clinical trials.

Methods

In the ISRT‐1 study, we assessed PBMC telomerase activity in 26 young healthy volunteers upon a single (short‐term) ISRT session and a single treadmill running session. In the ISRT‐2 study, we investigated PBMC telomere biology of 14 elderly patients with PAD, who underwent 30 h of (long‐term) ISRT within a 5‐week period.

Results

We demonstrate that telomerase activity significantly increased from 39.84 Total Product Generated (TPG) Units ± 6.15 to 58.10 TPG ± 10.46 upon a single treadmill running session in healthy volunteers. In the ISRT‐2 trial, PBMC telomerase activity and the mRNA expression of the telomere‐protective factor TRF2 increased from 40.87 TPG ± 4.45 to 60.98 TPG ± 6.83 and 2.10‐fold ± 0.40, respectively, upon long‐term ISRT in elderly patients with PAD.

Conclusion

In summary, we show that acute exercise and long‐term ISRT positively affect PBMC telomerase activity, which is indicative for an improved regenerative potential of immune cells and vascular tissues. Long‐term ISRT also enhances the gene expression of the telomere‐protective factor TRF2.
3,5‐diiodothyronine (3,5‐T2) reduces blood glucose independently of insulin sensitization in obese mice
Authors: da Silva Teixeira S. , Filgueira C. , Sieglaff D. H. , Benod C. , Villagomez R. , Minze L. J. , Zhang A. , Webb P. , Nunes M. T.
Published: October 2016

Aim

Thyroid hormones regulate metabolic response. While triiodothyronine (T3) is usually considered to be the active form of thyroid hormone, one form of diiodothyronine (3,5‐T2) exerts T3‐like effects on energy consumption and lipid metabolism. 3,5‐T2 also improves glucose tolerance in rats and 3,5‐T2 levels correlate with fasting glucose in humans. Presently, however, little is known about mechanisms of 3,5‐T2 effects on glucose metabolism. Here, we set out to compare effects of T3, 3,5‐T2 and another form of T2 (3,3‐T2) in a mouse model of diet‐induced obesity and determined effects of T3 and 3,5‐T2 on markers of classical insulin sensitization to understand how diiodothyronines influence blood glucose.

Methods

Cell‐ and protein‐based assays of thyroid hormone action. Assays of metabolic parameters in mice. Analysis of transcript and protein levels in different tissues by qRT‐PCR and Western blot.

Results

T3 and 3,5‐T2 both reduce body weight, adiposity and body temperature despite increased food intake. 3,3′‐T2 lacks these effects. T3 and 3,5‐T2 reduce blood glucose levels, whereas 3,3′‐T2 worsens glucose tolerance. Neither T3 nor 3,5‐T2 affects markers of insulin sensitization in skeletal muscle or white adipose tissue (WAT), but both reduce hepatic GLUT2 glucose transporter levels and glucose output. T3 and 3,5‐T2 also induce expression of mitochondrial uncoupling proteins (UCPs) 3 and 1 in skeletal muscle and WAT respectively.

Conclusions

3,5‐T2 influences glucose metabolism in a manner that is distinct from insulin sensitization and involves reductions in hepatic glucose output and changes in energy utilization.
The long‐term effects of forcible assimilation policy: The case of Indian boarding schools
Authors: Feir Donna L.
Published: October 2016

For decades in North America and Australia, Indigenous children were forcibly removed from their homes and placed in boarding schools. These schools had the stated goal of cultural assimilation and are perceived as educational failures. I offer the first causal evidence on the long‐run effects of these schools. I identify these effects using the interaction of changes in Canadian national policy and regional variation in the power of the Catholic Church. I find that the average boarding school had substantial effects on both cultural and economic assimilation. However, I find suggestive evidence this is not true for highly abusive schools.
Crime, apprehension and clearance rates: Panel data evidence from Canadian provinces
Authors: Curry Philip A. , Sen Anindya , Orlov George
Published: October 2016

The Becker model of crime establishes the importance of the probability of apprehension as a key factor in a rational individual's decision to commit a crime. In this respect, most empirical studies based on US data have relied on variation in the number of police officers to estimate the impact of the probability of apprehension or capture. We measure the probability of apprehension by clearance rates and study their effects on crime rates, employing a panel of Canadian provinces from 1986 to 2005. OLS, GMM, GLS and IV estimates yield statistically significant elasticities of clearance rates, ranging from −0.2 to −0.4 for violent crimes and from −0.5 to −0.6 for property crimes. These findings reflect the importance of police force crime‐solving productivity.
Hidden costs of supply management in a small market
Authors: Carter Colin A. , Mérel Pierre
Published: October 2016

Canada regulates its dairy and poultry industries through supply management. The supply‐management programs use target prices, production quotas and import tariff‐rate quotas to raise domestic prices. Canadian supply‐managed producers cannot export their output to world markets as exports would be considered subsidized under World Trade Organization rules. In this paper, we show that once foregone export opportunities are accounted for, supply management may no longer be beneficial to domestic producers of the supply‐managed commodities. The extent to which foregone profits from exports dominate domestic rents depends on Canada's comparative advantage, domestic market elasticities and the extent of supply management distortion in the domestic market.
On Lionel McKenzie's 1957 intrusion into 20th‐century demand theory
Authors: Khan M. Ali , Schlee Edward E.
Published: October 2016

In this essay, we read McKenzie's 17 paragraphs of 1957 on “Demand Theory Without a Utility Index” as an opening to the narrative of 20th‐century demand theory and as a lever for the understanding of what has now reached culmination as the neoclassical theory of demand. In tracking the influence of these paragraphs on both theoretical and applied work, we also use them as a foothold for reflection on the process of theorizing to argue for the view that one cannot neglect the (changing) problematic that the theory is adduced to address, that the historical narrative behind a particular theorem is indispensable in understanding the theorem itself. This implicit theorizing of the process of theorizing then forces us to consider Stigler's distinction between textual and scientific exegesis and confront it to a second‐order level of theorizing, and thereby bring out the continuity, possibly not quite seamless, between a theorem and its history.
Who invests more in advanced abatement technology? Theory and evidence
Authors: Cao Jing , Qiu Larry D. , Zhou Mohan
Published: October 2016

We study firm investment in abatement technology under a heterogeneous‐firm framework. We find that more‐productive firms make more (less) investment in abatement technology if investment and productivity are complements (substitutes). Under linear demand, firms’ abatement investments exhibit an inverted U‐shape with respect to productivity level. This finding is in contrast to results in existing studies. We also find that in response to tightened environmental regulations, more‐productive firms raise their respective investments in abatement technology, whereas less‐productive firms do the opposite. More‐productive firms have lower pollution emission intensity. The key theoretical predictions are confirmed by empirical tests using Chinese data.
Manufacturers and retailers in the global economy
Authors: Raff Horst , Schmitt Nicolas
Published: October 2016

We develop a model with multi‐product retailers acting as intermediaries between manufacturers and consumers. We show that the rise in retailer product assortment, the rise of up‐front payments in many retail markets and the observed shift in employment from manufacturing to retailing may be the consequence of the global integration of product markets. We also identify a novel benefit from market integration consisting of efficiency gains in the vertical distribution chain.
Demographic change, human capital accumulation and R&D‐based growth
Authors: Hashimoto Ken‐ichi , Tabata Ken
Published: October 2016

Employing an overlapping generations model of R&D‐based growth with endogenous fertility and education decisions, we examine how demographic changes induced by an increase in life expectancy influence the long‐run growth rate of the economy. We demonstrate that life expectancy, when relatively low (high), positively (negatively) affects economic growth. This paper also compares the growth implications of child education subsidy policies (i.e., policies for enhancing basic education) and child rearing subsidy policies (i.e., pro‐natal policies) and demonstrate that while the child education subsidies consistently foster economic growth, child rearing subsidies may negatively affect economic growth.
Is Canada an optimal currency area? An inflation targeting perspective
Authors: Chaban Maxym , Voss Graham M.
Published: October 2016

We propose a method, based on the currency union model of Galí and Monacelli, to determine whether a region within an existing currency area belongs in the currency union. The method involves assessing the predictability of regional inflation rates at medium term horizons. We apply the method to the Canadian provinces and find that for all but Alberta there is little evidence of costs in terms of inflation arising from national monetary policy. For Alberta, the evidence suggests that they are not as well served by the inflation targeting framework and that a more flexible policy environment might improve inflation outcomes.
Rockets and feathers meet markup margins: Applications to the oil and gasoline industry
Authors: Mann Janelle
Published: October 2016

This article investigates the existence of asymmetric price transmission between crude oil, rack (wholesale) and retail gasoline prices. A threshold cointegration technique is used, with regime switches being triggered by the size of the markup margin. There is consistent evidence of band‐TAR in which the crude, rack and retail prices are free to diverge until the markup margin is squeezed or stretched beyond a lower or upper critical threshold. This finding indicates that abnormally high markup margins cannot be sustained, which provides evidence against market power exertion. The threshold error correction models indicate that there is no systematic relationship between the speed of adjustment back to the long‐run relationship and the markup margin, which rules out the existence of “rockets and feathers.”
Measuring the contribution of durable goods to the welfare cost of inflation
Authors: Mansoorian Arman , Michelis Leo
Published: October 2016

In this paper, we measure the contribution of durable goods to the welfare cost of inflation, in the context of an endogenous growth model with durable and nondurable goods, where purchases of the latter require only a partial cash payment compared with the former. Unlike existing measures, our proposed welfare measure is computationally efficient and relatively easy to implement.We find that durability adds a significant component to the welfare costs of inflation.
Public–private mix of health expenditure: A political economy and quantitative analysis
Authors: Li Shuyun May , Moslehi Solmaz , Yew Siew Ling
Published: October 2016

This paper constructs a simple model to examine decisions on public and private health spending under majority voting. In the model, agents with heterogeneous incomes choose how much to consume and spend on health care and vote for public health expenditure. The health status of an agent is determined by a CES composite of public and private health expenditure. The existence and uniqueness of the voting equilibrium are established. A quantitative exercise reveals the importance of the relative effectiveness of public and private health expenditure and their substitutability in determining the public‐private mix of health expenditure and in accounting for the observed differences across a sample of 22 advanced democratic countries.
IgE and allergen‐specific immunotherapy‐induced IgG4 recognize similar epitopes of Bet v 1, the major allergen of birch pollen
Authors: Groh N. , von Loetzen C. S. , Subbarayal B. , Möbs C. , Vogel L. , Hoffmann A. , Fötisch K. , Koutsouridou A. , Randow S. , Völker E. , Seutter von Loetzen A. , Rösch P. , Vieths S. , Pfützner W. , Bohle B. , Schiller D.
Published: October 2016

Background

Allergen‐specific immunotherapy (AIT) with birch pollen generates Bet v 1‐specific immunoglobulin (Ig)G4 which blocks IgE‐mediated hypersensitivity mechanisms. Whether IgG4 specific for Bet v 1a competes with IgE for identical epitopes or whether novel epitope specificities of IgG4 antibodies are developed is under debate.

Objective

We sought to analyze the epitope specificities of IgE and IgG4 antibodies from sera of patients who received AIT.

Methods

15 sera of patients (13/15 received AIT) with Bet v 1a‐specific IgE and IgG4 were analyzed. The structural arrangements of recombinant (r)Bet v 1a and rBet v 1a_11x, modified in five potential epitopes, were analyzed by circular dichroism and nuclear magnetic resonance spectroscopy. IgE binding to Bet v 1 was assessed by ELISA and mediator release assays. Competitive binding of monoclonal antibodies specific for Bet v 1a and serum IgE/IgG4 to rBet v 1a and serum antibody binding to a non‐allergenic Bet v 1‐type model protein presenting an individual epitope for IgE was analyzed in ELISA and western blot.

Results

rBet v 1a_11x had a Bet v 1a – similar secondary and tertiary structure. Monomeric dispersion of rBet v 1a_11x was concentration and buffer‐dependent. Up to 1500‐fold increase in the EC50 for IgE‐mediated mediator release induced by rBet v 1a_11x was determined. The reduction of IgE and IgG4 binding to rBet v 1a_11x was comparable in 67% (10/15) of sera. Bet v 1a‐specific monoclonal antibodies inhibited binding of serum IgE and IgG4 to 66.1% and 64.9%, respectively. Serum IgE and IgG4 bound specifically to an individual epitope presented by our model protein in 33% (5/15) of sera.

Conclusion and Clinical Relevance

Patients receiving AIT develop Bet v 1a‐specific IgG4 which competes with IgE for partly identical or largely overlapping epitopes. The similarities of epitopes for IgE and IgG4 might stimulate the development of epitope‐specific diagnostics and therapeutics.
Associations between postpartum depressive symptoms and childhood asthma diminish with child age
Authors: Kozyrskyj A.L. , Letourneau N.L. , Kang L. J. , Salmani M.
Published: October 2016

Background

Affecting 19% of women, postpartum depression is a major concern to the immediate health of mothers and infants. In the long‐term, it has been linked to the development of early‐onset asthma at school entry, but only if the depression persists beyond the postnatal period. No studies have tested whether associations with postpartum depressive symptoms and early‐onset asthma phenotypes persist into later school age.

Objective

To determine associations between maternal postpartum depressive symptoms and childhood asthma between the ages of 5–10 by using a nested longitudinal design.

Methods

Data were drawn from the 1994–2004 administrations of the Canadian National Longitudinal Survey of Children and Youth, which tracks the health of a nationally representative sample of children in Canada. Child asthma was diagnosed by a health professional, and maternal depressive symptoms were assessed by the Centre for Epidemiological Studies Depression scale. Analyses were conducted by using a multilevel modelling approach, in which longitudinal assessments of asthma in 1696 children were nested within the exposure of postpartum depression.

Results

Postpartum depressive symptoms had a 1.5‐fold significant association with childhood asthma between the ages 6–8. This was independent of male sex, maternal asthma, non‐immigrant status, low household socioeconomic status, being firstborn, low birthweight, low family functioning and urban–rural residence, of which the first 4 covariates elevated the risk of asthma. Statistical significance was lost at age 8 when maternal prenatal smoking replaced urban–rural residence as a covariate. At ages 9–10, an association was no longer evident.

Conclusions and Clinical Relevance

Women affected by postpartum depressive symptoms are concerned about long‐term health effects of their illness on their infants. Although postpartum depressive symptoms were associated with school‐age asthma at ages 6 and 7, this association diminished later. Both home and school life stress should be considered in future studies on asthma development later in childhood.
Pre‐ and probiotics for allergy prevention: time to revisit recommendations?
Authors: Forsberg A. , West C. E. , Prescott S. L. , Jenmalm M. C.
Published: October 2016

Reduced intensity and diversity of microbial exposure is considered a major factor driving abnormal postnatal immune maturation and increasing allergy prevalence, particularly in more affluent regions. Quantitatively, the largest important source of early immune‐microbial interaction, the gut microbiota, is of particular interest in this context, with variations in composition and diversity in the first months of life associated with subsequent allergy development. Attempting to restore the health consequences of the ‘dysbiotic drift’ in modern society, interventions modulating gut microbiota for allergy prevention have been evaluated in several randomized placebo‐controlled trials. In this review, we provide an overview of these trials and discuss recommendations from international expert bodies regarding prebiotic, probiotic and synbiotic interventions. Recent guidelines from the World Allergy Organization recommend the use of probiotics for the primary prevention of eczema in pregnant and breastfeeding mothers of infants at high risk for developing allergy and in high‐risk infants. It is however stressed that these recommendations are conditional, based on very low‐quality evidence and great heterogeneity between studies, which also impedes specific and practical advice to consumers on the most effective regimens. We discuss how the choice of probiotic strains, timing and duration of administration can critically influence the outcome due to different effects on immune modulation and gut microbiota composition. Furthermore, we propose strategies to potentially improve allergy‐preventive effects and enable future evidence‐based implementation.
Gene mutation analysis of 175 Chinese patients with early‐onset epileptic encephalopathy
Authors: Zhang Q. , Li J. , Zhao Y. , Bao X. , Wei L. , Wang J.
Published: October 2016

The aim of the study is to investigate the genetic characteristics and clinical features of a cohort of Chinese patients with early‐onset epileptic encephalopathies (EOEEs). Targeted next‐generation sequencing (NGS), focusing on 17 genes, was performed on 175 Chinese patients with EOEEs to screen gene mutations. The mutation rate was 32% (56/175). All mutations were de novo and heterozygous, including 41 novel and 15 reported mutations. Patients with cyclin‐dependent kinase‐like 5 (CDKL5) gene mutation accounted for the largest proportion, 13.1% (23/175). All patients with CDKL5 mutation presented severe psychomotor developmental delay and refractory seizures. The female patients presented obvious Rett‐like features, which were not observed in male patients. Potassium channel, voltage‐gated KQT‐like subfamily Q, member 2(KCNQ2) gene mutations were detected in 13 patients. Patients with this mutation presented with early seizure onset within the first week after birth. Valproate (VPA), levetiracetam (LEV) and topiramate (TPM) were effective in most patients. Patients with specific gene mutations presented some unique clinical features, but not always. Many genes are involved in EOEEs. Targeted NGS showed a high diagnostic yield in patients with EOEEs. These findings provide useful insights for recommending treatment of gene‐associated EOEEs using antiepileptic drugs.
Medial Ganglionic Eminence Cells Freshly Obtained or Expanded as Neurospheres Show Distinct Cellular and Molecular Properties in Reducing Epileptic Seizures
Authors: Romariz Simone A. A. , Paiva Daisyléa S. , Galindo Layla T. , Barnabé Gabriela F. , Guedes Vivian A. , Borlongan Cesario V. , Longo Beatriz M.
Published: October 2016

Aims

Medial ganglionic eminence (MGE) progenitors give rise to inhibitory interneurons and may serve as an alternative cell source for large‐scale cell transplantation for epilepsy after in vitro expansion. We investigated whether modifications in the culture medium of MGE neurospheres affect neuronal differentiation and expression of MGE‐specific genes. In vivo, we compared anticonvulsant effects and cell differentiation pattern among neurospheres grown in different culture media and compared them with freshly harvested MGE cells.

Methods

We used four variations of cell culture: standard, containing growth factors (EGF/FGF‐2) (GF); addition of retinoic acid (GF‐RA); withdrawal of EGF/FGF‐2 (WD); and addition of retinoic acid and withdrawal of EGF/FGF‐2 (WD‐RA). Based on in vitro results neurosphere‐grown (WD‐RA or GF conditions) or fresh MGE cells were transplanted into the hippocampus.

Results

In vitro WD‐RA showed increased neuronal population and higher expression of Dlx1, Nkx2.1, and Lhx6 genes in comparison with GF culture condition. After transplantation, fresh MGE cells and neurospheres (GF) showed anticonvulsant effects. However, fresh MGE cells differentiated preferentially into inhibitory neurons, while GF gave rise to glial cells.

Conclusion

We conclude that freshly isolated and neurosphere‐grown MGE cells reduced seizures by different mechanisms (inhibitory interneurons vs. astrocytes). Fresh MGE cells appear more appropriate for cell therapies targeting inhibitory interneurons for conferring anticonvulsant outcomes.
Feasibility and preliminary effects of a screening, brief intervention and referral to treatment model to address gender‐based violence among women who use drugs in Kyrgyzstan: Project WINGS (Women Initiating New Goals of Safety)
Authors: Gilbert Louisa , Jiwatram‐Negron Tina , Nikitin Danil , Rychkova Olga , McCrimmon Tara , Ermolaeva Irena , Sharonova Nadejda , Mukambetov Aibek , Hunt Timothy
Published: October 2016

Introduction and aims

Intimate partner violence (IPV) and other forms of gender‐based violence (GBV) are serious public health threats among women who use drugs or engage in binge drinking in Kyrgyzstan. This study aimed to evaluate the feasibility and preliminary effects of a two‐session IPV and GBV screening, brief intervention and referral to treatment model (WINGS) with HIV counselling and testing for women who use drugs or engage in binge drinking in Kyrgyzstan, using a pre/post‐design.

Design and methods

We screened 109 women from harm reduction non‐government organisations in Kyrgyzstan, of whom 78 were eligible, 73 participated in the intervention study, and 66 completed a 3‐month post‐intervention follow‐up. To assess the effects of the intervention, we used random‐effect Poisson and Logistic regression analyses for continuous and dichotomous outcomes respectively.

Results

At baseline, 73% reported any physical or sexual IPV victimisation, and 60% reported any physical or sexual GBV victimisation in the past year. At the 3‐month follow‐up, participants reported experiencing 59% fewer physical IPV incidents in the prior 90 days than at baseline (P < 0.001) and 27% fewer physical GBV incidents than at baseline (P < 0.01). From baseline to the 3‐month follow‐up, participants also reported a 65% reduction in the odds of using any illicit drugs (P < 0.05) and were more likely to report receiving GBV‐related services (P < 0.001).

Discussion and conclusion

The high rates of participation, attendance and retention and significant reductions in IPV and GBV victimisation and drug use from baseline to the 3‐month follow‐up suggest the feasibility and promising effects of this brief intervention. [Gilbert L, Jiwatram‐Negron T, Nikitin D, Rychkova O, McCrimmon T, Ermolaeva I, Sharonova N, Mukambetov A, Hunt T. Feasibility and preliminary effects of a screening, brief intervention and referral to treatment model to address gender‐based violence among women who use drugs in Kyrgyzstan: Project WINGS (Women Initiating New Goals of Safety). Drug Alcohol Rev 2017;36:125–133]
RD Lawrence Lecture 2015 Old habits are hard to break: lessons from the study of hypoglycaemia
Authors: McCrimmon R. J.
Published: October 2016

Despite the introduction of newer technologies and improved insulin formulations, recurrent hypoglycaemia continues to affect the lives of many people with Type 1 and Type 2 diabetes. Developing strategies or therapies designed to prevent or minimize hypoglycaemia risk is of utmost importance to help individuals safely achieve glycaemic targets. Novel, educational or behavioural approaches need to be based on a clear understanding of the mechanisms underpinning both the detection of hypoglycaemia and why repeated exposure to hypoglycaemia leads to the development of a clinical syndrome referred to as impaired awareness of hypoglycaemia. In the present review, I propose that impaired awareness of hypoglycaemia may represent a form of learning called habituation, a response that, at a cellular level, represents a biological adaptation designed to protect the organism from future exposure to that stressor. In diabetes, this survival response to low glucose is, however, overwhelmed by high systemic insulin levels resulting from exogenous insulin therapy, leading to progressively more severe hypoglycaemia. A recognition of the underlying mechanism means that the development of impaired awareness of hypoglycaemia can perhaps be better understood and explained to individuals with diabetes, and novel therapeutic approaches such as dishabituation or cognitive behavioural therapies can be considered.
Circulating adiponectin concentration is inversely associated with glucose tolerance and insulin secretion in people with newly diagnosed diabetes
Authors: Weber K. S. , Strassburger K. , Pacini G. , Nowotny B. , Müssig K. , Szendroedi J. , Herder C. , Roden M. ,   the German Diabetes Study group
Published: October 2016

Aims

To examine the hypothesis that changes in serum adiponectin concentration inversely relate to changes in glucose tolerance and β‐cell function already during the early stage of disease progression in recently diagnosed Type 1 and Type 2 diabetes mellitus.

Methods

Participants in the prospective observational German Diabetes Study (Type 2 diabetes, n = 94; Type 1 diabetes, n = 42) underwent i.v. glucose tolerance and glucagon stimulation testing to assess pre‐hepatic β‐cell function, glucose tolerance index and C‐peptide secretion within the first year of diabetes diagnosis and 2 years later. Associations of changes in serum concentrations of total adiponectin, high‐molecular‐weight adiponectin and their ratio with changes in the aforementioned metabolic variables were calculated using linear regression.

Results

Among people with Type 2 diabetes, 2‐year increases in high‐molecular‐weight adiponectin and in high‐molecular‐weight/total adiponectin ratio were associated with decreases in glucose tolerance index of 0.1%/min (P = 0.020) and 0.8%/min (P = 0.013), respectively. Increases in high‐molecular‐weight/total adiponectin ratio were related to decreases in acute C‐peptide secretion of 54.6% (P = 0.020). Among people with Type 1 diabetes, 2‐year increases in total adiponectin were associated with 2‐year decreases in acute C‐peptide secretion of 56.2% (P = 0.035).

Conclusions

Increases in adiponectin concentrations in the first 2 years after diagnosis were related to a worsening of acute insulin secretion and glucose tolerance index in Type 1 and Type 2 diabetes. (Clinical Trials Registry no.: NCT01055093)
Higher skin autofluorescence in young people with Type 1 diabetes and microvascular complications
Authors: Cho Y. H. , Craig M. E. , Januszewski A. S. , Benitez‐Aguirre P. , Hing S. , Jenkins A. J. , Donaghue K. C.
Published: October 2016

Aim

To test the hypothesis that non‐invasive skin autofluorescence, a measure of advanced glycation end products, would provide a surrogate measure of long‐term glycaemia and be associated with early markers of microvascular complications in adolescents with Type 1 diabetes.

Methods

Forearm skin autofluorescence (arbitrary units) was measured in a cross‐sectional study of 135 adolescents with Type 1 diabetes [mean ± sd age 15.6 ± 2.1 years, diabetes duration 8.7 ± 3.5 years, HbA1c 72 ± 16 mmol/mol (8.7 ± 1.5%)]. Retinopathy, assessed using seven‐field stereoscopic fundal photography, was defined as ≥1 microaneurysm or haemorrhage. Cardiac autonomic function was measured by standard deviation of consecutive RR intervals on a 10‐min continuous electrocardiogram recording, as a measure of heart rate variability.

Results

Skin autofluorescence was significantly associated with age (R2 = 0.15; P < 0.001). Age‐ and gender‐adjusted skin autofluorescence was associated with concurrent HbA1c (R2 = 0.32; P < 0.001) and HbA1c over the previous 2.5–10 years (R2 = 0.34–0.43; P < 0.002). Age‐ and gender‐adjusted mean skin autofluorescence was higher in adolescents with retinopathy vs those without retinopathy [mean 1.38 (95% CI 1.29, 1.48) vs 1.22 (95% CI 1.17, 1.26) arbitrary units; P = 0.002]. In multivariable analysis, retinopathy was significantly associated with skin autofluorescence, adjusted for duration (R2 = 0.19; P = 0.03). Cardiac autonomic dysfunction was also independently associated with skin autofluorescence (R2 = 0.11; P = 0.006).

Conclusions

Higher skin autofluorescence is associated with retinopathy and cardiac autonomic dysfunction in adolescents with Type 1 diabetes. The relationship between skin autofluorescence and previous glycaemia may provide insight into metabolic memory. Longitudinal studies will determine the utility of skin autofluorescence as a non‐invasive screening tool to predict future microvascular complications.
Economic evaluation of chronic disease self‐management for people with diabetes: a systematic review
Authors: Teljeur C. , Moran P. S. , Walshe S. , Smith S. M. , Cianci F. , Murphy L. , Harrington P. , Ryan M.
Published: October 2016

Aims

To systematically review the evidence on the costs and cost‐effectiveness of self‐management support interventions for people with diabetes.

Background

Self‐management support is the provision of education and supportive interventions to increase patients’ skills and confidence in managing their health problems, potentially leading to improvements in HbA1c levels in people with diabetes.

Methods

Randomized controlled trials, observational studies or economic modelling studies were eligible for inclusion in the review. The target population was adults with diabetes. Interventions had to have a substantial component of self‐management support and be compared with routine care. Study quality was evaluated using the Consensus on Health Economic Criteria and International Society of Pharmacoeconomic Outcomes Research questionnaires. A narrative review approach was used.

Results

A total of 16 costing and 21 cost‐effectiveness studies of a range of self‐management support interventions were identified. There was reasonably consistent evidence across 22 studies evaluating education self‐management support programmes suggesting these interventions are cost‐effective or superior to usual care. Telemedicine‐type interventions were more expensive than usual care and potentially not cost‐effective. There was insufficient evidence regarding the other types of self‐management interventions, including pharmacist‐led and behavioural interventions. The identified studies were predominantly of poor quality, with outcomes based on short‐term follow‐up data and study designs at high risk of bias.

Conclusions

Self‐management support education programmes may be cost‐effective. There was limited evidence regarding other formats of self‐management support interventions. The poor quality of many of the studies undermines the evidence base regarding the economic efficiency of self‐management support interventions for people with diabetes.
Threshold loss of discontinuous permafrost and landscape evolution
Authors: Chasmer Laura , Hopkinson Chris
Published: October 2016

This study demonstrates linkages between the 1997/1998 El Niño/Southern Oscillation index and a threshold shift to increased permafrost loss within a southern Taiga Plains watershed, Northwest Territories, Canada. Three‐dimensional contraction of permafrost plateaus and changes in vegetation structural characteristics are determined from multitemporal airborne Light Detection And Ranging (LiDAR) surveys in 2008, 2011 and 2015. Morphological changes in permafrost cover are compared with optical image analogues from 1970, 1977, 2000 and 2008 and time‐series hydro‐climate data. Results demonstrate that significant changes in air temperature, precipitation, runoff and a shortening of the snow‐covered season by 35 days (1998–2014) and 50 days (1998 only) occurred after 1997. The albedo reduction associated with 35 and 50 days less snow cover leads to increases in shortwave energy receipt during the active thaw period of ~12% (3% annually) and ~16% (5% annually), respectively. From 2000 to 2015, sporadic permafrost loss accelerated from 0.19% (of total basin area) per year between 1970 and 2000 to 0.58% per year from 2000 to 2015, with a projected total loss of permafrost by ~2044. From ~1997 to 2011, we observe a corresponding shift to increased runoff ratio. However, observed increases in the proportion of snow precipitation and the volumetric contribution of permafrost loss to runoff post‐1997 (0.6–6.4% per year) cannot fully explain this shift. This suggests increases in drainage efficiency and possible losses from long‐term groundwater storage as a result of subtle terrain morphological and soil zone hydraulic conductivity changes. These hydrological changes appear coincident with high vegetation mortality at plateau margins combined with succession‐related canopy growth in some bog and fen areas, which are presumed to be drying. Similar changes in runoff response were observed at adjacent Birch, Trout and Jean Marie River watersheds indicating that observations are representative of northern Boreal sporadic permafrost/wetland watersheds in the Taiga Plains.
Integrated population modeling reveals the impact of climate on the survival of juvenile emperor penguins
Authors: Abadi Fitsum , Barbraud Christophe , Gimenez Olivier
Published: October 2016

Early‐life demographic traits are poorly known, impeding our understanding of population processes and sensitivity to climate change. Survival of immature individuals is a critical component of population dynamics and recruitment in particular. However, obtaining reliable estimates of juvenile survival (i.e., from independence to first year) remains challenging, as immatures are often difficult to observe and to monitor individually in the field. This is particularly acute for seabirds, in which juveniles stay at sea and remain undetectable for several years. In this work, we developed a Bayesian integrated population model to estimate the juvenile survival of emperor penguins (Aptenodytes forsteri), and other demographic parameters including adult survival and fecundity of the species. Using this statistical method, we simultaneously analyzed capture–recapture data of adults, the annual number of breeding females, and the number of fledglings of emperor penguins collected at Dumont d'Urville, Antarctica, for the period 1971–1998. We also assessed how climate covariates known to affect the species foraging habitats and prey [southern annular mode (SAM), sea ice concentration (SIC)] affect juvenile survival. Our analyses revealed that there was a strong evidence for the positive effect of SAM during the rearing period (SAMR) on juvenile survival. Our findings suggest that this large‐scale climate index affects juvenile emperor penguins body condition and survival through its influence on wind patterns, fast ice extent, and distance to open water. Estimating the influence of environmental covariates on juvenile survival is of major importance to understand the impacts of climate variability and change on the population dynamics of emperor penguins and seabirds in general and to make robust predictions on the impact of climate change on marine predators.
The competitive status of trees determines their responsiveness to increasing atmospheric humidity – a climate trend predicted for northern latitudes
Authors: Tullus Arvo , Kupper Priit , Kaasik Ants , Tullus Hardi , Lõhmus Krista , Sõber Anu , Sellin Arne
Published: October 2016

The interactive effects of climate variables and tree–tree competition are still insufficiently understood drivers of forest response to global climate change. Precipitation and air humidity are predicted to rise concurrently at high latitudes of the Northern Hemisphere. We investigated whether the growth response of deciduous trees to elevated air humidity varies with their competitive status. The study was conducted in seed‐originated silver birch and monoclonal hybrid aspen stands grown at the free air humidity manipulation (FAHM) experimental site in Estonia, in which manipulated stands (n = 3 for both species) are exposed to artificially elevated relative air humidity (6–7% over the ambient level). The study period included three growing seasons during which the stands had reached the competitive stage (trees were 7 years old in the final year). A significant ‘treatment×competitive status’ interactive effect on growth was detected in all years in birch (P < 0.01) and in one year in aspen stands (P = 0.015). Competitively advantaged trees were always more strongly affected by elevated humidity. Initially the growth of advantaged and neutral trees of both species remained significantly suppressed in humidified stands. In the following years, dominance and elevated humidity had a synergistic positive effect on the growth of birches. Aspens with different competitive status recovered more uniformly, attaining similar relative growth rates in manipulated and control stands, but preserved a significantly lower total growth yield due to severe initial growth stress. Disadvantaged trees of both species were never significantly affected by elevated humidity. Our results suggest that air humidity affects trees indirectly depending on their social status. Therefore, the response of northern temperate and boreal forests to a more humid climate in future will likely be modified by competitive relationships among trees, which may potentially affect species composition and cause a need to change forestry practices.