bluuebunny/crossref_metadata_2025 huggingface dataset:
Pedigree reconstruction from SNP data: parentage assignment, sibship clustering and beyond
Authors: Huisman Jisca
Published: March 2017

Data on hundreds or thousands of single nucleotide polymorphisms (SNPs) provide detailed information about the relationships between individuals, but currently few tools can turn this information into a multigenerational pedigree. I present the r package sequoia, which assigns parents, clusters half‐siblings sharing an unsampled parent and assigns grandparents to half‐sibships. Assignments are made after consideration of the likelihoods of all possible first‐, second‐ and third‐degree relationships between the focal individuals, as well as the traditional alternative of being unrelated. This careful exploration of the local likelihood surface is implemented in a fast, heuristic hill‐climbing algorithm. Distinction between the various categories of second‐degree relatives is possible when likelihoods are calculated conditional on at least one parent of each focal individual. Performance was tested on simulated data sets with realistic genotyping error rate and missingness, based on three different large pedigrees (N = 1000–2000). This included a complex pedigree with overlapping generations, occasional close inbreeding and some unknown birth years. Parentage assignment was highly accurate down to about 100 independent SNPs (error rate <0.1%) and fast (<1 min) as most pairs can be excluded from being parent–offspring based on opposite homozygosity. For full pedigree reconstruction, 40% of parents were assumed nongenotyped. Reconstruction resulted in low error rates (<0.3%), high assignment rates (>99%) in limited computation time (typically <1 h) when at least 200 independent SNPs were used. In three empirical data sets, relatedness estimated from the inferred pedigree was strongly correlated to genomic relatedness.
Acupuncture reduces relapse to cocaine‐seeking behavior via activation of GABA neurons in the ventral tegmental area
Authors: Jin Wyju , Kim Min Sun , Jang Eun Young , Lee Jun Yeon , Lee Jin Gyeom , Kim Hong Yu , Yoon Seong Shoon , Lee Bong Hyo , Chang Suchan , Kim Jae Hyo , Choi Kwang H. , Koo Ho , Gwak Young Seob , Steffensen Scott C. , Ryu Yeon‐Hee , Kim Hee Young , Yang Chae Ha
Published: March 2017

There is growing public interest in alternative approaches to addiction treatment and scientific interest in elucidating the neurobiological underpinnings of acupuncture. Our previous studies showed that acupuncture at a specific Shenmen (HT7) points reduced dopamine (DA) release in the nucleus accumbens (NAc) induced by drugs of abuse. The present study was carried out to evaluate the effects of HT7 acupuncture on γ‐aminobutyric acid (GABA) neuronal activity in the ventral tegmental area (VTA) and the reinstatement of cocaine‐seeking behavior. Using microdialysis and in vivo single‐unit electrophysiology, we evaluated the effects of HT7 acupuncture on VTA GABA and NAc DA release and VTA GABA neuronal activity in rats. Using a within‐session reinstatement paradigm in rats self‐administering cocaine, we evaluated the effects of HT7 stimulation on cocaine‐primed reinstatement. Acupuncture at HT7 significantly reduced cocaine suppression of GABA release and GABA neuron firing rates in the VTA. HT7 acupuncture attenuated cocaine‐primed reinstatement, which was blocked by VTA infusions of the selective GABAB receptor antagonist 2‐hydroxysaclofen. HT7 stimulation significantly decreased acute cocaine‐induced DA release in the NAc, which was also blocked by 2‐hydroxysaclofen. HT7 acupuncture also attenuated cocaine‐induced sensitization of extracellular DA levels in the NAc. Moreover, HT7 acupuncture reduced both locomotor activity and neuronal activation in the NAc induced by acute cocaine in a needle‐penetration depth‐dependent fashion. These results suggest that acupuncture may suppress cocaine‐induced DA release in the NAc and cocaine‐seeking behavior through activation of VTA GABA neurons. Acupuncture may be an effective therapy to reduce cocaine relapse by enhancing GABAergic inhibition in the VTA.
The prevalence of diabetes after gestational diabetes – An Australian perspective
Authors: Moses Robert Geoffrey , Goluza Ivana , Borchard Jay Philip , Harman Alexandra , Dunning Alicia , Milosavljevic Marianna
Published: March 2017

Background

Women with gestational diabetes mellitus (GDM) are likely to develop diabetes in later life. International reports and reviews indicate a variable but generally high rate of conversion. However, data from international reports are difficult to apply to an Australian population.

Aim

To investigate in Australia, in a representative population, the prevalence of diabetes developing in women who have been diagnosed with one criteria and who have had uniform standards of clinical care.

Material and methods

This study considered women referred with a diagnosis of GDM according to the Australasian Diabetes in Pregnancy Society criteria and seen by one practitioner over a 20 year period, from 1991 to 2010. The area of referral had an ethnic distribution similar to the overall Australian demography.

Results

Despite, in some cases, being more than 25 years since the pregnancy, more than half the women were contactable and the majority agreed to have their diabetes status declared or determined. The overall prevalence was 10.3%. The prevalence at each 10 year age increment was more than twice the figure reported from the AusDiab study. A higher maternal body mass index and a positive family history of diabetes were the strongest predictive factors. The prevalence of undiagnosed diabetes was 0.9%.

Conclusion

In a representative population, after GDM, the prevalence of diabetes of 10.3% was far lower than that reported internationally but was still about twice the rate for the overall Australian population.
Mobilizing the Public Against the President: Congress and the Political Costs of Unilateral Action
Authors: Christenson Dino P. , Kriner Douglas L.
Published: March 2017

Prior scholarship overlooks the capacity of other actors to raise the political costs of unilateral action by turning public opinion against the president. Through a series of five experiments embedded in nationally representative surveys, we demonstrate Congress's ability to erode support for unilateral actions by raising both constitutional and policy‐based objections to the exercise of unilateral power. Congressional challenges to the unilateral president diminish support for executive action across a range of policy areas in both the foreign and domestic realm and are particularly influential when they explicitly argue that presidents are treading on congressional prerogatives. We also find evidence that constitutional challenges are more effective when levied by members of Congress than by other actors. The results resolve a debate in the literature and suggest a mechanism through which Congress might exercise a constraint on the president, even when it is unable to check him legislatively.
Prevalence of type I sensitization to alpha‐gal in forest service employees and hunters
Authors: Fischer J. , Lupberger E. , Hebsaker J. , Blumenstock G. , Aichinger E. , Yazdi A. S. , Reick D. , Oehme R. , Biedermann T.
Published: March 2017

Background

The production of IgE molecules specific to the carbohydrate galactose‐α‐1,3‐galactose (alpha‐gal) is known to induce delayed anaphylaxis against mammalian meat. Tick bites constitute the primary sensitization source, as ticks transfer alpha‐gal in their saliva to a host during a bite. The reported prevalence of alpha‐gal‐specific IgE (alpha‐gal‐sIgE) positivity varies between different populations from diverse geographic regions.

Objective

To investigate the prevalence of alpha‐gal‐sIgE positivity in a population of forest service employees who are highly exposed to ticks in comparison with a residential population and a historic sample.

Methods

A cross‐sectional study evaluating 300 forest service employees and hunters from southwest Germany was performed. Alpha‐gal‐sIgE levels were assessed by ImmunoCAP assay. The prevalence of alpha‐gal‐sIgE‐positive individuals was compared with a matched cohort composed of a residential population and blood samples from forest service employees collected 15 years ago.

Results

In the study population, the prevalence of alpha‐gal‐sIgE‐positive (≥0.10 kUA/L) individuals was 35.0%, whereas the prevalence of individuals with alpha‐gal‐sIgE levels ≥0.35 kUA/L was 19.3%. Alpha‐gal‐sIgE positivity was associated with total IgE levels and recent tick bites. Mammalian meat‐induced delayed anaphylaxis was found in 8.6% of the participants with alpha‐gal‐sIgE levels ≥0.35 kUA/L. For forest service employees and hunters, the odds ratio for alpha‐gal‐sIgE positivity was 2.48 compared to the residential population. The prevalence of alpha‐gal‐sIgE positivity in the current and historic cohort was comparable.

Conclusion

Forest service employees and hunters compose a population with a high prevalence of alpha‐gal‐sIgE positivity and carry a considerable risk of red meat allergy.
Oxidative stress serves as a key checkpoint for IL‐33 release by airway epithelium
Authors: Uchida M. , Anderson E. L. , Squillace D. L. , Patil N. , Maniak P. J. , Iijima K. , Kita H. , O'Grady S. M.
Published: March 2017

Background

Interleukin (IL)‐33 is implicated in the pathophysiology of asthma and allergic diseases. However, our knowledge is limited regarding how IL‐33 release is controlled. The transcription factor nuclear factor‐erythroid‐2‐related factor 2 (Nrf2) plays a key role in antioxidant response regulation.

Objective

The goal of this project was to investigate the role of cellular oxidative stress in controlling IL‐33 release in airway epithelium.

Methods

Complementary approaches were used that included human bronchial epithelial cells and mouse models of airway type‐2 immunity that were exposed to fungus Alternaria extract. The clinically available Nrf2 activator 2‐cyano‐3,12‐dioxooleana‐1,9‐dien‐28‐oic acid methyl ester (CDDO‐Me) was used to evaluate the role of Nrf2‐induced antioxidant molecules.

Results

Human bronchial epithelial cells produced reactive oxygen species (ROS) when they were exposed to Alternaria extract. ROS scavengers, such as glutathione (GSH) and N‐acetyl cysteine, prevented extracellular secretion of ATP and increases in intracellular calcium concentrations that precede IL‐33 release. Administration of CDDO‐Me to mice enhanced expression of a number of antioxidant molecules in the lungs and elevated lung levels of endogenous GSH. Importantly, CDDO‐Me treatment reduced allergen‐induced ATP secretion and IL‐33 release by airway epithelial cells in vitro and protected mice from IL‐33 release and asthma‐like pathological changes in the lungs.

Conclusions

The balance between oxidative stress and antioxidant responses plays a key role in controlling IL‐33 release in airway epithelium. The therapeutic potential of Nrf2 activators needs to be considered for asthma and allergic airway diseases.
Reduced anterior chamber contamination by frequent surface irrigation with diluted iodine solutions during cataract surgery
Authors: Shimada Hiroyuki , Arai Shinji , Nakashizuka Hiroyuki , Hattori Takayuki , Yuzawa Mitsuko
Published: March 2017

Purpose

To verify that ocular surface irrigation with 0.025% povidone–iodine (PI) or 0.0025% polyvinyl alcohol–iodine (PAI) during cataract surgery minimizes bacterial contamination of the anterior chamber.

Methods

The study was a prospective, interventional case series. First, the bactericidal effect of PI or PAI against Staphylococcus aureus was evaluated in vitro. Next, in 400 eyes undergoing cataract surgery, the ocular surface was irrigated every 20 seconds during surgery with balanced salt solution (BSS; 200 eyes) or BSS containing 0.025% PI (100 eyes) or 0.0025% PAI (100 eyes). At the completion of surgery, anterior chamber fluid was cultured bacteriologically. Visual acuity (VA) and corneal endothelial cell density were measured before and 7 days after surgery.

Results

A marked bactericidal effect was observed when S. aureus was directly exposed for 15 seconds to 0.01% PI or 0.001% PAI diluted in BSS. When the two solutions were stored at room temperature, bactericidal effect did not attenuate after 60 min. The bacterial detection rate at the completion of surgery was significantly reduced in 0.025% PI (0%, 0/100 eyes) or 0.0025% PAI group (0%, 0/100 eyes) compared to BSS group (5%, 10/200 eyes) (p = 0.0340). No differences in postoperative visual acuity and postoperative corneal endothelial cell density were observed between three groups.

Conclusion

In cataract surgery, irrigation every 20 seconds of the operative field with 0.025% PI or 0.0025% PAI, both of which contain 0.0025% available iodine concentration, achieved a very low bacterial contamination rate in the anterior chamber.
Dissecting microRNA dysregulation in age‐related macular degeneration: new targets for eye gene therapy
Authors: Askou Anne Louise , Alsing Sidsel , Holmgaard Andreas , Bek Toke , Corydon Thomas J.
Published: March 2017

MicroRNAs (miRNAs) are key regulators of gene expression in humans. Overexpression or depletion of individual miRNAs is associated with human disease. Current knowledge suggests that the retina is influenced by miRNAs and that dysregulation of miRNAs as well as alterations in components of the miRNA biogenesis machinery are involved in retinal diseases, including age‐related macular degeneration (AMD). Furthermore, recent studies have indicated that the vitreous has a specific panel of circulating miRNAs and that this panel varies according to the specific pathological stress experienced by the retinal cells. MicroRNA (miRNA) profiling indicates subtype‐specific miRNA profiles for late‐stage AMD highlighting the importance of proper miRNA regulation in AMD. This review will describe the function of important miRNAs involved in inflammation, oxidative stress and pathological neovascularization, the key molecular mechanisms leading to AMD, and focus on dysregulated miRNAs as potential therapeutic targets in AMD.
Statin Use Correlates with Reduced Risk of Pyogenic Liver Abscess: A Population‐Based Case–Control Study
Authors: Liao Kuan‐Fu , Cheng Kao‐Chi , Lin Cheng‐Li , Lai Shih‐Wei
Published: March 2017

Little research is available on the relationship between statin use and pyogenic liver abscess. The objective of the study was to determine whether prior use of statins is associated with pyogenic liver abscess. This case–control study was conducted to analyse the claim data of the Taiwan National Health Insurance Program. There were 1828 participants aged 20–84 years with first episode of pyogenic liver abscess from 2000 to 2013 as the cases and 1828 randomly selected participants without pyogenic liver abscess matched with sex, age and index year as the controls. Statin use was defined as ‘current’, ‘recent’ or ‘past’ if the statin prescription was filled ≤3 months, 3–6 months or >6 months before the date of pyogenic liver abscess diagnosis, respectively. Relative risk of pyogenic liver abscess associated with statin use was estimated by the odds ratio (OR) with 95% confidence interval (CI) using the multivariable logistic regression model. After controlling for potential confounders, the adjusted ORs of pyogenic liver abscess were 0.65 for participants with current use of statins (95% CI 0.50, 0.84), 0.74 for participants with recent use of statins (95% CI 0.49, 1.11), and 1.10 for participants with past use of statins (95% CI 0.90, 1.34), compared with participants with never use of statins. In the further analysis, the adjusted ORs of pyogenic liver abscess were 0.65 for participants with cumulative duration of statin use ≥12 months (95% CI 0.48, 0.88) and 0.68 for participants with cumulative duration of statin use <12 months (95% CI 0.43, 1.07), compared with participants with never use of statins. Our findings provide strong evidence that patients with current use of statins are associated with a 35% reduced odds of pyogenic liver abscess. The protective effect is stronger for longer duration of statin use.
Safety and benefits of antenatal oral iron supplementation in low‐income countries: a review
Authors: Mwangi Martin N. , Prentice Andrew M. , Verhoef Hans
Published: March 2017

The World Health Organization recommends universal iron supplementation of 30–60 mg/day in pregnancy but coverage is low in most countries. Its efficacy is uncertain, however, and there has been a vigorous debate in the last decade about its safety, particularly in areas with a high burden of malaria and other infectious diseases. We reviewed the evidence on the safety and efficacy of antenatal iron supplementation in low‐income countries. We found no evidence that daily supplementation at a dose of 60 mg leads to increased maternal Plasmodium infection risk. On the other hand, recent meta‐analyses found that antenatal iron supplementation provides benefits for maternal health (severe anaemia at postpartum, blood transfusion). For neonates, there was a reduced prematurity risk, and only a small or no effect on birth weight. A recent trial showed, however, that benefits of antenatal iron supplementation on maternal and neonatal health vary by maternal iron status, with substantial benefits in iron‐deficient women. The benefits of universal iron supplementation are likely to vary with the prevalence of iron deficiency. As a consequence, the balance between benefits and risks is probably more favourable in low‐income countries than in high‐income countries despite the higher exposure to infectious pathogens.
Hashimoto's thyroiditis: relative recurrence risk ratio and implications for screening of first‐degree relatives
Authors: Bothra Nikita , Shah Nalini , Goroshi Manjunath , Jadhav Swati , Padalkar Sheetal , Thakkar Hemangini , Toteja Gurudayal Singh , Shivane Vyankatesh , Lila Anurag , Bandgar Tushar
Published: March 2017

Context

The relative recurrence risk ratio (λR) for Hashimoto's thyroiditis (HT) has not been widely studied. The age at which thyroid function evaluation should be initiated for relatives of HT patients remains unclear.

Objective

To study λR and age‐related prevalence of HT in first‐degree relatives of HT patients.

Methods

First‐degree relatives (n = 861) of 264 HT patients were evaluated for goitre, thyroid function tests, thyroid antibodies (TAb) and urinary iodide concentration (UIC). HT was defined as TAb positivity and hypothyroidism (subclinical/overt). λR was calculated as {number of index patients whose relatives (of particular subtype) had HT/number of index patients having relatives of same subtype}÷ population prevalence of HT (5·1%). The age‐related prevalence of HT was studied using Kaplan–Meier method.

Results

A total of 861 relatives (205 parents, 336 siblings and 320 offspring) participated in the study. About 38·3% were TAb positive. The prevalence of HT was 16·7% (22·9% in parents, 19·6% in siblings and 9·6% in offspring). TAb positivity (48·3% vs 33·1%) and HT (23·5% vs 13·6%) were significantly more common in the goitrous group (n = 267) vs nongoitrous group. The median UIC for the study population was 182·5 μg/l. Computed λR was 9·1 for any one relative being affected, 5·9 for parents, 6·3 for siblings and 3·1 for offspring. The prevalence of HT increased with age and exceeded the adult population prevalence of 5·1% at 20 years in females and 27 years in males.

Conclusions

Relatives of HT patients have a ninefold increased risk for developing HT as compared to the general population. The risk of developing HT exceeds that of the general population at 20 years in females and 27 years in males.
Threats to intact tropical peatlands and opportunities for their conservation
Authors: Roucoux K.H. , Lawson I.T. , Baker T.R. , Del Castillo Torres D. , Draper F.C. , Lähteenoja O. , Gilmore M.P. , Honorio Coronado E.N. , Kelly T.J. , Mitchard E.T.A. , Vriesendorp C.F.
Published: March 2017

Large, intact areas of tropical peatland are highly threatened at a global scale by the expansion of commercial agriculture and other forms of economic development. Conserving peatlands on a landscape scale, with their hydrology intact, is of international conservation importance to preserve their distinctive biodiversity and ecosystem services and maintain their resilience to future environmental change. We explored threats to and opportunities for conserving remaining intact tropical peatlands; thus, we excluded peatlands of Indonesia and Malaysia, where extensive deforestation, drainage, and conversion to plantations means conservation in this region can protect only small fragments of the original ecosystem. We focused on a case study, the Pastaza‐Marañón Foreland Basin (PMFB) in Peru, which is among the largest known intact tropical peatland landscapes in the world and is representative of peatland vulnerability. Maintenance of the hydrological conditions critical for carbon storage and ecosystem function of peatlands is, in the PMFB, primarily threatened by expansion of commercial agriculture linked to new transport infrastructure that is facilitating access to remote areas. There remain opportunities in the PMFB and elsewhere to develop alternative, more sustainable land‐use practices. Although some of the peatlands in the PMFB fall within existing legally protected areas, this protection does not include the most carbon‐dense (domed pole forest) areas. New carbon‐based conservation instruments (e.g., REDD+, Green Climate Fund), developing markets for sustainable peatland products, transferring land title to local communities, and expanding protected areas offer pathways to increased protection for intact tropical peatlands in Amazonia and elsewhere, such as those in New Guinea and Central Africa which remain, for the moment, broadly beyond the frontier of commercial development.
Comparing reliabilities of strip and conventional patch testing
Authors: Dickel Heinrich , Geier Johannes , Kreft Burkhard , Pfützner Wolfgang , Kuss Oliver
Published: March 2017

Background

The standardized protocol for performing the strip patch test has proven to be valid, but evidence on its reliability is still missing.

Objective

To estimate the parallel‐test reliability of the strip patch test as compared with the conventional patch test.

Methods

In this multicentre, prospective, randomized, investigator‐blinded reliability study, 132 subjects were enrolled. Simultaneous duplicate strip and conventional patch tests were performed with the Finn Chambers® on Scanpor® tape test system and the patch test preparations nickel sulfate 5% pet., potassium dichromate 0.5% pet., and lanolin alcohol 30% pet. Reliability was estimated by the use of Cohen's kappa coefficient.

Results

Parallel‐test reliability values of the three standard patch test preparations turned out to be acceptable, with slight advantages for the strip patch test. The differences in reliability were 9% (95%CI: −8% to 26%) for nickel sulfate and 23% (95%CI: −16% to 63%) for potassium dichromate, both favouring the strip patch test.

Conclusions

The standardized strip patch test method for the detection of allergic contact sensitization in patients with suspected allergic contact dermatitis is reliable. Its application in routine clinical practice can be recommended, especially if the conventional patch test result is presumably false negative.
C‐reactive protein as a predictor of anastomotic leak in the first week after anterior resection for rectal cancer
Authors: Reynolds I. S. , Boland M. R. , Reilly F. , Deasy A. , Majeed M. H. , Deasy J. , Burke J. P. , McNamara D. A.
Published: March 2017

Aim

Anastomotic leak (AL) after anterior resection results in increased morbidity, mortality and local recurrence. The aim of this study was to assess the ability of C‐reactive protein (CRP) to predict AL in the first week after anterior resection for rectal cancer.

Method

A retrospective review of a prospectively maintained database that included all patients undergoing anterior resection between January 2008 and December 2013 was performed. The ability of CRP to predict AL was assessed using area under the receiver–operating characteristics (AUC) curves. The severity of AL was defined using the International Study Group of Rectal Cancer (ISREC) grading system.

Results

Two‐hundred and eleven patients were included in the study. Statistically significant differences in mean CRP values were found between those with and without an AL on postoperative days 5, 6 and 7. A CRP value of 132 mg/l on postoperative day 5 had an AUC of 0.75, corresponding to a sensitivity of 70%, a specificity of 76.6%, a positive predictive value of 16.3% and a negative predictive value of 97.5%. Multivariable analysis found that a CRP of > 132 mg/l on postoperative day 5 was the only statistically significant patient factor that was linked to an increased risk of AL (HR = 8.023, 95% CI: 1.936–33.238, P = 0.004).

Conclusion

Early detection of AL may minimize postoperative complications. CRP is a useful negative predictive test for the development of AL following anterior resection.
Regional Bans on Wild‐Bird Trade Modify Invasion Risks at a Global Scale
Authors: Cardador Laura , Lattuada Matteo , Strubbe Diederik , Tella José L. , Reino Luís , Figueira Rui , Carrete Martina
Published: March 2017

Wildlife trade is currently the most important and increasing source of vertebrate invasive species. However, exhaustive analyses of potential side effects of trade regulations on this pathway of introduction are lacking. We addressed this by combining environmental niche models and global trade data on parrots (Psittaciformes), one of the most widely traded and worldwide invasive taxa. We used the wild bird trade bans of United States (1992) and Europe (2005) as case‐studies. Results showed that regional bans can generate geographic redirections in trade, with important consequences on worldwide invasion risk. While the amount of parrots traded internationally remained largely constant, changes in trade destination occurred. Consequently, the world surface predicted at risk of parrot invasions increased with successive bans. Of concern, a redirection of trade toward developing countries was observed. Attention should be paid on the mismatch between the global requirements of invasion management and the regional scales governing trade regulations.
ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology
Authors: Scheffer Ingrid E. , Berkovic Samuel , Capovilla Giuseppe , Connolly Mary B. , French Jacqueline , Guilhoto Laura , Hirsch Edouard , Jain Satish , Mathern Gary W. , Moshé Solomon L. , Nordli Douglas R. , Perucca Emilio , Tomson Torbjörn , Wiebe Samuel , Zhang Yue‐Hua , Zuberi Sameer M.
Published: March 2017

The International League Against Epilepsy (ILAE) Classification of the Epilepsies has been updated to reflect our gain in understanding of the epilepsies and their underlying mechanisms following the major scientific advances that have taken place since the last ratified classification in 1989. As a critical tool for the practicing clinician, epilepsy classification must be relevant and dynamic to changes in thinking, yet robust and translatable to all areas of the globe. Its primary purpose is for diagnosis of patients, but it is also critical for epilepsy research, development of antiepileptic therapies, and communication around the world. The new classification originates from a draft document submitted for public comments in 2013, which was revised to incorporate extensive feedback from the international epilepsy community over several rounds of consultation. It presents three levels, starting with seizure type, where it assumes that the patient is having epileptic seizures as defined by the new 2017 ILAE Seizure Classification. After diagnosis of the seizure type, the next step is diagnosis of epilepsy type, including focal epilepsy, generalized epilepsy, combined generalized, and focal epilepsy, and also an unknown epilepsy group. The third level is that of epilepsy syndrome, where a specific syndromic diagnosis can be made. The new classification incorporates etiology along each stage, emphasizing the need to consider etiology at each step of diagnosis, as it often carries significant treatment implications. Etiology is broken into six subgroups, selected because of their potential therapeutic consequences. New terminology is introduced such as developmental and epileptic encephalopathy. The term benign is replaced by the terms self‐limited and pharmacoresponsive, to be used where appropriate. It is hoped that this new framework will assist in improving epilepsy care and research in the 21st century.
Parental Perceived Control and Social Support: Linkages to Change in Parenting Behaviors During Early Adolescence
Authors: Lippold Melissa A. , Glatz Terese , Fosco Gregory M. , Feinberg Mark E.
Published: March 2017

Prior studies have found that parents’ perceptions of control over their lives and their social support may both be important for parenting behaviors. Yet, few studies have examined their unique and interacting influence on parenting behaviors during early adolescence. This longitudinal study of rural parents in two‐parent families (N = 636) investigated (a) whether perceived control and social support when their youth were in sixth grade were independently or interactively associated with changes in parenting behaviors (discipline, standard setting) and parent–child warmth and hostility 6 months later and (b) if these linkages differed by parent gender. We also investigated the interactive links between perceived control, social support, and parenting. Specifically, we tested if parents’ perceived control moderated the linkages between social support and parenting and if these linkages differed by parent gender. Greater perceived control predicted more increases in parents’ consistent discipline and standard setting, whereas greater social support predicted increases in parent–child warmth and decreases in parent–child hostility. Parental perceived control moderated the effect of social support on parental warmth: For mothers only, social support was significantly linked to parent–child warmth only when mothers had low (but not high) perceived self‐control. The discussion focuses on reasons why perceived control and social support may have associations with different aspects of parenting and why these might differ for mothers and fathers.
Surfing parameter hyperspaces under climate change scenarios to design future rice ideotypes
Authors: Paleari Livia , Movedi Ermes , Cappelli Giovanni , Wilson Lloyd T. , Confalonieri Roberto
Published: March 2017

Growing food crops to meet global demand and the search for more sustainable cropping systems are increasing the need for new cultivars in key production areas. This study presents the identification of rice traits putatively producing the largest yield benefits in five areas that markedly differ in terms of environmental conditions in the Philippines, India, China, Japan and Italy. The ecophysiological model WARM and sensitivity analysis techniques were used to evaluate phenotypic traits involved with light interception, photosynthetic efficiency, tolerance to abiotic stressors, resistance to fungal pathogens and grain quality. The analysis involved only model parameters that have a close relationship with phenotypic traits breeders are working on, to increase the in vivo feasibility of selected ideotypes. Current climate and future projections were considered, in the light of the resources required by breeding programs and of the role of weather variables in the identification of promising traits. Results suggest that breeding for traits involved with disease resistance, and tolerance to cold‐ and heat‐induced spikelet sterility could provide benefits similar to those obtained from the improvement of traits involved with canopy structure and photosynthetic efficiency. In contrast, potential benefits deriving from improved grain quality traits are restricted by weather variability and markedly affected by G × E interactions. For this reason, district‐specific ideotypes were identified using a new index accounting for both their productivity and feasibility.
Mending the hole in multilevel implementation: Administrative cooperation related to worker mobility
Authors: Hartlapp Miriam , Heidbreder Eva G.
Published: March 2017

European economic integration creates unintended consequences for national public administrations. This article offers a conceptual and empirical analysis of how these challenges are met. First, three challenges are identified: a reduced capacity to offer services to citizens who move freely, increasing administrative burdens, and negative externalities for all parts from a single states’ administrative failure. Second, a conceptual framework is developed that links each challenge to a most likely response in form of modes of administrative cooperation. Third, the framework is illustrated by an empirical analysis of the coordination of social security systems, labor inspectorates, and posted workers. The case studies show that horizontal administrative cooperation is developed stepwise over time and in line with the theoretical framework. In sum, we can sustain that horizontal administrative cooperation is a relevant additional integration dynamic that buffers unintended effects of market integration on formally independent but increasingly interdependent member state executive bodies.
Sex differences in vascular dysfunction and cardiovascular outcomes: The cardiac, endothelial function, and arterial stiffness in ESRD (CERES) study
Authors: Guajardo Isabella , Ayer Amrita , Johnson Alexander D. , Ganz Peter , Mills Claire , Donovan Catherine , Scherzer Rebecca , Shah Sanjiv J. , Peralta Carmen A. , Dubin Ruth F.
Published: March 2017

Introduction: Recent studies suggest that women with end‐stage renal disease (ESRD) may have higher rates of mortality than men, but it is unknown whether sex differences in vascular function explain this disparity. The cardiac, endothelial function, and arterial stiffness in ESRD (CERES) study is an ongoing, prospective observational study designed to investigate vascular function, myocardial injury, and cardiovascular outcomes in ESRD.

Methods: Among 200 CERES participants (34% women), we evaluated arterial wave reflections as augmentation index normalized to a heart rate of 75 (AIx75), arterial stiffness as pulse wave velocity, and macro‐ and microvascular endothelial dysfunction as flow‐mediated dilation and velocity time integral (VTI). Over a median of 14 months, participants were followed for the composite outcome of cardiovascular hospitalization or all‐cause death.

Findings: Women had higher arterial wave reflection (Mean, SD AIx75 30% ± 9% for women vs. 21% ± 10% for men; P < 0.001) and worse microvascular function (VTI 55 ± 30 cm for women vs. 70 ± 27 cm for men; P = 0.007). After multivariable adjustment, female sex remained associated with a 0.5‐SD higher AIx75 (95% CI [0.01, 0.9]) and 0.3‐SD lower VTI (95%CI [0.1, 0.7]). Women experienced higher adjusted rates of the composite outcome (HR 2.5; 95%CI [1.1, 5.6]; P = 0.03), and further adjustment for arterial wave reflection attenuated this risk.

Discussion: Vascular dysfunction may partly explain the association of female sex with higher cardiovascular risk and mortality in patients with ESRD. Further studies are needed to explore whether sex differences in vascular function predict long‐term outcomes, and whether hormonal or inflammatory factors explain these associations.
Iatrogenic hypernatremia in hemodialysis patients: A result of erroneous online conductivity monitor and conductivity meter reading
Authors: Obialo Chamberlain I. , John Smitha , Bashir Khalid
Published: March 2017

Hyponatremia is common in chronic kidney disease and in end stage kidney disease (ESKD) but hypernatremia is infrequent in ESKD. The incidence of hypernatremia is higher in ambulatory peritoneal dialysis (PD) than in hemodialysis (HD) patients. In PD patients it is often a result of excessive ultrafiltration but in HD it is often a result of dialysate composition errors. Dialysate composition errors can inadvertently cause either hyponatremia or hypernatremia. We present two cases of symptomatic hypernatremia which manifested as increased thirst, excessive weight gain and worsening hypertension in HD patients. The hypernatremia was caused by a combination of errors in online conductivity reading and a faulty hand held conductivity meter. Symptoms were relieved in both patients after replacement of the dialysis machine.
Population genetic structure of Helicobacter pylori strains from Portuguese‐speaking countries
Authors: Oleastro Mónica , Rocha Raquel , Vale Filipa F.
Published: March 2017

Background

The human gastric colonizer Helicobacter pylori is useful to track human migrations given the agreement between the bacterium phylogeographic distribution and human migrations. As Portugal was an African and Brazilian colonizer for over 400 years, we hypothesized that Portuguese isolates were likely genetically closer with those from countries colonized by Portuguese in the past. We aimed to characterize the population structure of several Portuguese‐speaking countries, including Portugal, Brazil, Angola, and Cape Verde.

Materials and Methods

We included strains isolated in Portugal from Portuguese and from former Portuguese colonies. These strains were typed by multilocus sequence typing (MLST) for seven housekeeping genes. We also retrieved from Multi Locus Sequence Typing Web site additional housekeeping gene sequences, namely from Angola and Brazil.

Results

We provided evidence that strains from Portuguese belong to hpEurope and that the introgression of hpEurope in non‐European countries that speak Portuguese is low, except for Brazil and Cape Verde, where hpEurope accounted for one quarter and one half of the population, respectively. We found genetic similarity for all strains from Portuguese‐speaking countries that belong to hpEurope population. Moreover, these strains showed a predominance of ancestral Europe 2 (AE2) over ancestral Europe 1 (AE1), followed by ancestral Africa 1.

Conclusions

H. pylori is a useful marker even for relative recent human migration events and may become rapidly differentiated from founder populations. H. pylori from Portuguese‐speaking countries assigned to hpEurope appears to be a hybrid population resulting from the admixture of AE1, AE2 and ancestral hpAfrica1.
Comparison of visual bird migration counts with radar estimates
Authors: Schmidt Matthias , Aschwanden Janine , Liechti Felix , Wichmann Gábor , Nemeth Erwin
Published: March 2017

In the context of an extensive study on bird migration in the Austrian Alps, we compared data from a fixed‐beam radar with data collected by visual observation to estimate the intensity of migrating birds up to a height of 150 m above the ground. Migration traffic rates calculated from visual bird counts and radar measurements were strongly correlated. Using resampling techniques, we calculated a minimum observation effort for counting birds during a 5‐week period of peak migration. We chose ±20% of the real mean as the criterion for a reliable estimation. Our results showed that at least 19 observation days are necessary to assess the mean number of migrants passing within this low altitudinal range.
Non-modifiable determinants of pharmacy residency match rates
Authors: Caballero Joshua , Benavides Sandra , Clauson Kevin A , Hardigan Patrick C , Martinez Brandon K , Llerena Valerie
Published: March 2017

Objective

The purpose of this study was to examine non-modifiable pharmacy program characteristics on residency match rates.

Methods

American Society of Health-System Pharmacists match and non-match lists were de-identified and evaluated for students graduating in 2015. Variables analysed included length of program, type of institution and didactic grading scheme.

Key Findings

Students from 4-year programs, attending a public institution, or using a grade point average had greater odds of matching. Logistic regression model indicated a good model fit (χ2(2) of 4.44, P = 0.108).

Conclusions

Students considering residency training may benefit from awareness of such factors when choosing a pharmacy program.
Cryptotanshinone inhibition of mammalian target of rapamycin pathway is dependent on oestrogen receptor alpha in breast cancer
Authors: Pan Yanhong , Shi Junfeng , Ni Wenting , Liu Yuping , Wang Siliang , Wang Xu , Wei Zhonghong , Wang Aiyun , Chen Wenxing , Lu Yin
Published: March 2017

Cryptotanshinone (CPT) has been demonstrated to inhibit proliferation and mammalian target of rapamycin (mTOR) pathway in MCF‐7 breast cancer cells. However, the same results are unable to be repeated in MDA‐MB‐231 cells. Given the main difference of oestrogen receptor α (ERα) between two types of breast cancer cells, It is possibly suggested that CPT inhibits mTOR pathway dependent on ERα in breast cancer. CPT could significantly inhibit cell proliferation of ERα‐positive cancer cells, whereas ERα‐negative cancer cells are insensitive to CPT. The molecular docking results indicated that CPT has a high affinity with ERα, and the oestrogen receptor element luciferase reporter verified CPT distinct anti‐oestrogen effect. Furthermore, CPT inhibits mTOR signalling in MCF‐7 cells, but not in MDA‐MB‐231 cells, which is independent on binding to the FKBP12 and disrupting the mTOR complex. Meanwhile, increased expression of phosphorylation AKT and insulin receptor substrate (IRS1) induced by insulin‐like growth factor 1 (IGF‐1) was antagonized by CPT, but other molecules of IGF‐1/AKT/mTOR signalling pathway such as phosphatase and tensin homolog (PTEN) and phosphatidylinositol‐4,5‐bisphosphate 3‐kinase (PI3K) were negatively affected. Finally, the MCF‐7 cells transfected with shERα for silencing ERα show resistant to CPT, and p‐AKT, phosphorylation of p70 S6 kinase 1 (p‐S6K1) and eukaryotic initiation factor 4E binding protein 1 (4E‐BP1) were partially recovered, suggesting ERα is required for CPT inhibition of mTOR signalling. Overall, CPT inhibition of mTOR is dependent on ERα in breast cancer and should be a potential anti‐oestrogen agent and a natural adjuvant for application in endocrine resistance therapy.
Comparative RNA‐Seq transcriptome analyses reveal distinct metabolic pathways in diabetic nerve and kidney disease
Authors: Hinder Lucy M. , Park Meeyoung , Rumora Amy E. , Hur Junguk , Eichinger Felix , Pennathur Subramaniam , Kretzler Matthias , Brosius Frank C. , Feldman Eva L.
Published: March 2017

Treating insulin resistance with pioglitazone normalizes renal function and improves small nerve fibre function and architecture; however, it does not affect large myelinated nerve fibre function in mouse models of type 2 diabetes (T2DM), indicating that pioglitazone affects the body in a tissue‐specific manner. To identify distinct molecular pathways regulating diabetic peripheral neuropathy (DPN) and nephropathy (DN), as well those affected by pioglitazone, we assessed DPN and DN gene transcript expression in control and diabetic mice with or without pioglitazone treatment. Differential expression analysis and self‐organizing maps were then used in parallel to analyse transcriptome data. Differential expression analysis showed that gene expression promoting cell death and the inflammatory response was reversed in the kidney glomeruli but unchanged or exacerbated in sciatic nerve by pioglitazone. Self‐organizing map analysis revealed that mitochondrial dysfunction was normalized in kidney and nerve by treatment; however, conserved pathways were opposite in their directionality of regulation. Collectively, our data suggest inflammation may drive large fibre dysfunction, while mitochondrial dysfunction may drive small fibre dysfunction in T2DM. Moreover, targeting both of these pathways is likely to improve DN. This study supports growing evidence that systemic metabolic changes in T2DM are associated with distinct tissue‐specific metabolic reprogramming in kidney and nerve and that these changes play a critical role in DN and small fibre DPN pathogenesis. These data also highlight the potential dangers of a ‘one size fits all’ approach to T2DM therapeutics, as the same drug may simultaneously alleviate one complication while exacerbating another.
Establishment and characterization of a cell line from the head kidney of golden pompano Trachinotus ovatus and its application in toxicology and virus susceptibility
Authors: Li P. , Zhou L. , Wei S. , Yang M. , Ni S. , Yu Y. , Cai J. , Qin Q.
Published: March 2017

A cell line derived from the head kidney of golden pompano Trachinotus ovatus (TOHK) was established and characterized in this study. The TOHK cells grew most rapidly at 28° C and the optimum foetal bovine serum concentration in L‐15 medium was 10%. The TOHK cells have a diploid chromosome number of 2N = 54. The transfection efficiency of TOHK cells was 7·5% at the 15th passage and 72% at the 40th passage. The transfection efficiency in TOHK cells was high, so these cells are suitable for foreign gene expression. The cytotoxic effects of heavy metals and extracellular products from Vibrio anguillarum and Vibrio alginolyticus were demonstrated in TOHK cells, so this TOHK cell line could also be applied in environmental monitoring of heavy metals and pathogenic bacteria. TOHK cell line showed high virus susceptibility, such as grouper nervous necrosis virus (GNNV) and Singapore grouper iridovirus (SGIV). Then, TOHK cell line could be used for the study of viral pathogenesis and the development of antiviral strategies.
Acute kidney injury predicts mortality in cirrhotic patients with gastric variceal bleeding
Authors: Hsieh Yun‐Cheng , Lee Kuei‐Chuan , Chen Ping‐Hsien , Su Chien‐Wei , Hou Ming‐Chih , Lin Han‐Chieh
Published: March 2017

Background and Aim

The International Club of Ascites (ICA) recently proposed a new definition of acute kidney injury (AKI) in cirrhotic patients. The study evaluated the ICA‐AKI criteria and their association with the prognosis of cirrhotic patients with gastric variceal bleeding (GVB).

Methods

A retrospective cohort study using prospective database of cirrhotic patients hospitalized with the first presentation of acute GVB at Taipei Veterans General Hospital from April 2007 to December 2010 was performed to evaluate the development of AKI. The study used Cox proportional hazards model to examine the association of ICA‐AKI criteria and mortality.

Results

Of 113 patients, 46 (41%) fulfilled the ICA‐AKI criteria and most (70%) initially had stage 1 AKI. Child‐Pugh score, systemic blood pressure at admission, and number of blood units transfused before endoscopy were independent predictors of AKI. Among patients with AKI, 30% progressed to higher stages with more advanced liver disease, lower serum sodium, more units of blood transfusion, higher frequency of infection, and higher serum creatinine levels at diagnosis of AKI. The 6‐week mortality rate was significantly higher in patients with AKI than in patients without AKI (37% vs 3%, P < 0.001), and AKI stages were independent predictors of 3‐month survival (93% in patients without AKI, 73% in stage 1, and 30% in stages 2 and 3, P = 0.005).

Conclusions

The occurrence of AKI as defined by the ICA criteria is common in cirrhotic patients with acute GVB. The presence of AKI was associated with much higher 6‐week mortality, and the stages of AKI further predicted 3‐month survival.