bluuebunny/crossref_metadata_2025 huggingface dataset:
Acoustics of Tone in Indian Punjabi
Authors: Evans Jonathan , Yeh Wen‐Chi , Kulkarni Rukmini
Published: September 2018

This study explores the effects of tone on fundamental frequency in Punjabi, one of few Indo‐European languages to have lexical tone. Previous studies present conflicting claims regarding the direction of pitch movement, the location in the word of the tone, and interactions between tone and prosodic structure. For the present study, Punjabi speakers of India were presented with a production task, based on a metrically balanced corpus. Results show that Punjabi tone tends to be most fully realized on stressed syllables, where it occurs as a significant fall in fundamental frequency. On non‐stressed syllables, tone can be realized as falling, high, or may not be realized. In some cases, syllable length plays a role in determining where in the word the pitch falls. There are implications for the diachronic trajectory of tonogenesis, which was concomitant with the loss of murmured stops in Punjabi. First, the intrinsic pitch lowering of murmured voicing has led to a falling tone in prosodically prominent positions. Second, tonogenesis in Punjabi has resulted in a privative tone system, in which syllables are either tonal or toneless, rather than a system in which there are multiple tone values, or in which most syllables are specified for tone.
Mechanising Historical Phonology
Authors: Sims‐Williams Patrick
Published: September 2018

The Neogrammarian approach to historical phonology involves propounding sound‐change laws and explaining exceptions by means such as sub‐laws, rearranging the relative chronology, and appeal to special factors such as analogy, borrowing, and sporadic phenomena like metathesis. Progress is mostly made manually, but in the second half of the twentieth century some linguists looked forward to the ‘triumph of the electronic Neogrammarian’. Although this has not been realized yet, there are opportunities to make important advances. This paper offers a critical survey of the field since the 1950s and suggestions for the future.
Survival and success of family‐owned small businesses after hurricane Katrina: Impact of disaster assistance and adaptive capacity
Authors: Haynes George W. , Danes Sharon M. , Schrank Holly L. , Lee Yoon
Published: September 2018

The study's purpose is to examine the relative importance of direct disaster assistance to family‐owned small firms on their survival and success while considering the components of their adaptive capacity after experiencing Hurricane Katrina. This study employed data from the 2013 and 2015 Small Business Survival and Demise after a Natural Disaster Project (SBSD), a project funded by the National Science Foundation. The logistic regression results show that family businesses with SBA loans (or loan guarantees) were significantly more likely to survive. In addition, family businesses where household and family issues were more frequently in conflict with work demands were more likely to survive. On the other hand, the OLS regression results indicate that family businesses with more stress and more family–business conflict were less likely to succeed.
Predictors of sling revision after mid‐urethral sling procedures: a case–control study
Authors: Clancy AA , Gauthier I , Ramirez FD , Hickling D , Pascali D
Published: September 2018

Objective

To identify patient characteristics and surgical factors predictive of complications requiring mid‐urethral sling (MUS) revision/removal.

Design

Case–control study.

Setting

Tertiary academic centre in Canada.

Population

One hundred and seven women undergoing MUS revision/removal between 2005 and 2016 were matched with 214 controls by date of index MUS procedure (2:1 ratio).

Methods

Data on patient and surgical factors were obtained via manual electronic and paper chart review. Three sets of pre‐specified simple and multivariable logistic regression models were fitted to: (1) examine previously reported risk factors for MUS revision after primary surgical treatment; (2) identify preoperative predictors of MUS complications requiring revision/removal; and (3) identify surgical factors associated with this outcome after adjusting for potential confounding factors.

Main outcome measures

Crude and adjusted odds ratios (ORs) with 95% confidence intervals (95% CIs) for patient and surgical factors.

Results

The median time to MUS revision was 153 days (interquartile range, IQR 49–432 days). Active smoking status (OR 2.29, 95% CI 1.13–4.63, P = 0.03), having had a previous hysterectomy (OR 3.88, 95% CI 2.02–7.46, P < 0.01), and undergoing concomitant pelvic organ prolapse surgery at the time of the index MUS procedure (OR 2.63, 95% CI 1.32–5.52, P < 0.01) were independently associated with the need for MUS revision/removal. Sling type (obturator versus retropubic), method of tensioning (to cough versus over instrument), anaesthetic type, and estimated blood loss were not associated with this outcome in the analysis presented here.

Conclusions

Active smoking status, having had a previous hysterectomy, and undergoing concomitant surgery for pelvic organ prolapse are risk factors for requiring subsequent MUS revision/removal.

Tweetable abstract

Risk factors for sling revision include smoking, previous hysterectomy, and concomitant prolapse surgery.
Pricing Credit Risk for Mortgages: Credit Risk Spreads and Heterogeneity across Housing Markets
Authors: Dunsky Robert M. , Follain James R. , Giertz Seth H.
Published: September 2018

We develop a Monte Carlo procedure to project MSA‐level house‐price paths from 2013 to 2023. These price paths are applied to a fixed portfolio of synthetic mortgages in order to estimate credit risk spreads (CRS) for each MSA. Like the well‐known annual percentage rate (APR)–which converts an array of fees into an all‐encompassing annual measure of costs to borrowers–the CRS is a holistic measure that encompasses both expected losses from default plus the cost of capital (or unexpected credit losses) needed to cover losses in a stress scenario. We find variation in the CRS across MSAs, with the range spanning 37 basis points. This range spans 86 basis points for those carrying first‐loss positions, such as private mortgage insurers. We conclude that, in order to accurately price credit risk, it is necessary to monitor more than borrower characteristics, but also local economic conditions.
Should freestanding emergency departments be considered in Australia?
Authors: de Alwis Waruna
Published: September 2018

The concept of freestanding EDs is a popular operational model of emergency care in the USA. This model has been described as an emergency physician‐created innovative solution in resolving ongoing overcrowding issues in EDs. A decentralised community‐based emergency care model may be a solution to meet the increasing demand for emergency and unscheduled acute care in Australia. It may also help to reduce the number of acute hospital admissions through EDs. The aim of freestanding EDs should be to manage and discharge a cohort of patients, mainly in Australasian Triage Scale 3 and 4 categories, currently seen in hospital‐based EDs. This article briefly examines the potential merits and issues if this concept is considered in Australia. It also provides an early proposed model for such EDs.
Shifting dynamics of Chinese settlement in Australia: an urban geographic perspective
Authors: Wang Siqin , Sigler Thomas , Liu Yan , Corcoran Jonathan
Published: September 2018

The so‐called Asian Century has brought with it sweeping changes in the profile of migration to Australia. This paper focuses on examining post‐2000 migration from Mainland China, which has rapidly ascended to now become Australia's top non‐Commonwealth country of origin. Significantly, the profile of post‐2000 Mainland China‐born (MC‐born) migrants has changed to mirror broader global shifts towards highly skilled, education‐related, and investment‐focused migration, all of which reflect the mobility of wealthy and/or educated cohorts. Little empirical work has focused on the degree to which this change in the profile of migration has led to the formation of novel settlement patterns. This paper aims to examine the socio‐economic characteristics of MC‐born migrants in Australian cities, to identify sub‐metropolitan areas of concentration, and to visualise spatial change in settlement patterns over time. The data indicate that although Sydney is still home to half of MC‐born migrants at a national scale, the number of migrants has increased at a more rapid rate in medium‐sized capital cities such as Adelaide and Perth. Results reveal an increasingly decentralised and suburbanised concentration of MC‐born migrants at a metropolitan scale that is linked to areas of earlier Chinese settlement, or corresponding to access to educational resources and employment opportunities. The observed patterns support the segmented assimilation theory in that the spatial settlement patterns among MC‐born migrants assume variegated forms based on individuals' socio‐economic characteristics and metropolitan‐scale factors.
Making “space” for women and girls in sport: an agenda for Australian geography
Authors: Pavlidis Adele
Published: September 2018

In this article, I argue that there is need to rethink how sport is inherently spatial and political. I outline the importance of doing research on the spatiality of inequality in sport and consider the ways in which ideas about affective atmospheres and textures can support nuanced understandings of sport, particularly for girls and women. From change rooms to board rooms, sporting fields to dance halls, sport happens somewhere—it is inherently spatial. Australian geographers continue to make scholarly and practical impacts of social and cultural significance by focusing on spatiality, but the geography of sport has yet to be fully developed in that respect, notwithstanding influential work on sport in rural communities and surfing and sporting events. Despite such contributions, there is still considerable work to be done, particularly in the area of women's and girls' team sport. Sport is an arena where geographers can make broader and, importantly, bolder contributions, and a concern with spatiality gives geographers unique and critical insights into sport and its manifestation across scales from the global to the local.
Beyond the post‐political: is public participation in Australian cities at a turning point?
Authors: Legacy Crystal , Rogers Dallas , Cook Nicole , Ruming Kristian
Published: September 2018

This special section builds on Planning the Post‐Political City—Part 1 to examine if and how planning is showing signs of a post‐democratic turn taking place in Australian cities. In Part 1, we presented a collection of papers examining Australia as a post‐political landscape, exploring the new ways in which Australian publics are resisting dominant neoliberal practices and logics of growth and, in doing so, are intervening in decision‐making practices to assert new forms of power and participation. In Part 2, we show how participatory practices continue to evolve. We use this brief editorial to ask a foundational question: have those implicated in the governance and management of Australian cities embarked on a post‐democratic path? As they are presented with new exclusionary and managerial governance systems, the public's participation suggests at the very least that post‐political and post‐democratic conditions are neither immutable nor inevitable. However, more democratic forms of governance rely on a rich array of activist types and approaches requiring greater institutional support in order to challenge Australia's post‐political condition.
Complementary feeding: Attitudes, knowledge and practices of urban families in northern Thailand
Authors: Kittisakmontri Kulnipa , Fewtrell Mary , Roekworachai Koonkoaw , Phanpong Chotiros , Lanigan Julie
Published: September 2018

Aim

Urban families in middle‐income countries are currently facing cultural and lifestyle transition. Changing from an agricultural to an industrial society may affect family roles and child‐care practices. The present study aims to reveal family attitudes, knowledge and practices focusing on complementary feeding (CF).

Methods

A cross‐sectional study was conducted in three Child Health Clinics in Chiang Mai, Thailand. Self‐administered questionnaires were given to families caring for healthy infants and children less than 18 months of age during October to November 2016.

Results

One‐hundred and eight respondents completed questionnaires. The study found different attitudes and knowledge gaps between the respondents who were mothers and other family members (‘others’). The ‘others’ were less likely to value CF as a crucial factor promoting child growth and development. Moreover, they had misperceptions about the benefits of animal‐based protein and were less confident in their ability to feed the child properly. Most families reported timely introduction of complementary food, using proper milk products and encouraging age‐appropriate feeding methods. However, there were undesirable practices including delaying introduction of animal‐based protein, inadequate food diversity, the use of seasoning, feeding premasticated food and offering food as a reward.

Conclusions

These findings suggest that nutritional education should be extended to all caregivers involved in CF to improve the adherence to feeding recommendations.
The Dissipative Potential of Gamma Irradiation in Residues of Imidacloprid and Thiamethoxam in the Postharvest of Common Beans
Authors: Armelim José Maurício , Mendes Kassio Ferreira , Pimpinato Rodrigo Floriano , Tornisielo Valdemar Luiz
Published: September 2018

Gamma irradiation (60Co) in postharvest of common beans (Phaseolus vulgaris L.), has already proven beneficial, regarding the prolongation of shelf life and physical, chemical, and organoleptic aspects of grains. However, few prior studies have investigated the effect of gamma irradiation on the dissipation of pesticides in foods, especially insecticides in beans. This study aimed to evaluate the waste dissipation of two insecticides, imidacloprid and thiamethoxam, used in the cultivation of common bean, a variety of Carioca, using gamma irradiation. Ground bean samples were spiked each insecticide in the laboratory at 3, 4, and 5 mg/kg, and were then irradiated at 0, 1, and 2 kGy per irradiator with a 60Co source. Liquid chromatography‐tandem mass spectrometry was used to quantify the insecticides. The irradiation promoted dissipation of thiamethoxam at 1 and 2 kGy doses, with the highest dissipation verified at 2 kGy. In general, at this higher dose of irradiation the reduction dissipation of thiamethoxam was 66% of the mean value found in the treatment without irradiation and ∼44% relative to the 1 kGy dose. Conversely, imidacloprid showed no effect of irradiation on waste dissipation, except in the treatment of 5 mg/kg at 2 kGy dose. From the results, it was concluded that the gamma irradiation might have applicability in dissipating thiamethoxam in real bean samples.

Practical Application

Pesticide residues remaining from bean cultivation, sensitive to optimal doses of gamma irradiation, can be transformed into other less harmful or nonharmful substances, increasing the quality of the beans before the food arrives at the consumer's table. Irradiation of the grains after harvest also eliminates the need for application of other pesticides to preserve the grains during storage, as the technique is capable of eradicating deteriorating agents, such as microorganisms and insects.
BASTA – Taxonomic classification of sequences and sequence bins using last common ancestor estimations
Authors: Kahlke Tim , Ralph Peter J.
Published: September 2018

Identification of the taxonomic origin of a DNA sequence is crucial for many sequencing projects, e.g. metagenomics studies, identification of contaminations in whole genome sequencing projects and filtering of organisms of interest in marker‐gene based community analyses.

Last common ancestor algorithms are powerful approaches to estimate the taxonomy of a given sequence and have been widely used for classification of next‐generation sequencing (NGS) reads, also known as 2nd generation sequencing reads.

Here, we present BASTA (https://github.com/timkahlke/BASTA), a basic sequence taxonomy annotator, which extends last common ancestor estimations from sequencing reads to any kind of nucleotide or amino acid sequence utilizing NCBI taxonomies of user‐defined best hits.

BASTA can be configured to use the output of many common sequence comparison tools, e.g. BLAST and Diamond, in conjunction with either provided or user‐defined target sequence databases.
Outliving Death: Ebola, Zombies, and the Politics of Saving Lives
Authors: Gomez‐Temesio Veronica
Published: September 2018

Treatment units were created all across the country with a mission to save lives when the Ebola outbreak hit Guinea in 2014. These units were exceptional sites of biomedical and biosecurity technology. Nevertheless, the concrete procedures to contain the virus reduced the people quarantined to dangerous bodies. The emergency therefore created zombies, haunting figures trapped between life and death. The figure of the zombie shed light on the failure of the humanitarian engagement: when humanitarianism was driven by an ethical imperative of saving lives at any cost, its concrete procedures failed to preserve political and social existence. Zombies also related to the legacy of the slave trade. Connecting the zombie with the postcolonial context of Guinea, I will argue that humanitarian teams were dealing with already devalued lives. Zombies is then another word for pariah citizens of a global world. But people never live in utter subjection. The zombie is thus not only a metaphor for the commodification of life. It also invokes a slave rebellion. Enduring the politics of saving lives, zombies nevertheless resisted the confinement: to the quarantine but also to our analytical gaze. Zombies are thus the ones who outlive not only death in life but also conceptual death. [life, violence, humanitarian aid, zombie, Ebola]
Plasma progesterone, estradiol, and unconjugated estriol concentrations in twin pregnancies: Relation with cervical length and preterm delivery
Authors: Johnsson Vilma L. , Pedersen Nina G. , Worda Katharina , Krampl‐Bettelheim Elisabeth , Skibsted Lillian , Hinterberger Stefan , Strobl Isolde , Bowman Maria E. , Smith Roger , Tabor Ann , Rode Line
Published: September 2018

Introduction

The aim of this study was to examine the association between plasma hormone concentrations, cervical length, and preterm delivery in twin pregnancies, including the effect of progesterone treatment.

Material and methods

This study included 191 women pregnant with twins from a randomized placebo‐controlled trial. A baseline blood sample was collected at 18‐24 weeks before treatment with vaginal progesterone (n = 95) or placebo pessaries (n = 96), and 167 (87.4%) women had a second sample collected after 4‐8 weeks of treatment. At baseline, 155 (81.2%) women had their cervical length measured. Progesterone, estradiol, and unconjugated estriol concentration was measured, and the association between hormone concentrations, cervical length, and gestational age at delivery was examined. Hormone concentrations were compared in the placebo and progesterone group. Statistical analysis included Spearman's rho, Mann‐Whitney U test, Cuzick's test for trends, and linear regression analyses.

Results

A short cervical length was associated with preterm delivery. Cervical length and hormone concentrations were not associated (Spearman's rho; progesterone −.05, estradiol .04, estriol .08). Decreasing gestational age at delivery was associated with higher progesterone and estradiol concentrations at baseline (P trend; progesterone 0.04, estradiol 0.02) but not in the second sample or in the weekly change between samples. Progesterone treatment did not increase the progesterone concentration.

Conclusions

Plasma concentrations of progesterone, estradiol, and unconjugated estriol at 18‐24 weeks are not associated with cervical length or preterm delivery in twin pregnancies. Vaginal progesterone treatment does not increase the circulating progesterone concentration in twin pregnancies. Cervical length, but not hormone concentration, is predictive of preterm delivery in twin gestations.
Adherence to a Mediterranean diet, lifestyle and age‐related macular degeneration: the Coimbra Eye Study – report 3
Authors: Raimundo Miguel , Mira Filipe , Cachulo Maria da Luz , Barreto Patrícia , Ribeiro Luísa , Farinha Cláudia , Laíns Inês , Nunes Sandrina , Alves Dalila , Figueira João , Merle Bénédicte MJ , Delcourt Cécile , Santos Lèlita , Silva Rufino
Published: September 2018

Purpose

To characterize the lifestyle and nutritional risk profile associated with the Mediterranean diet in a Portuguese population with and without age‐related macular degeneration (AMD).

Methods

Nested case–control study (n = 883) within the Coimbra Eye Study, including 434 subjects with AMD and 449 age‐ and sex‐matched subjects without AMD. All enrolled subjects underwent a full risk assessment, including lifestyle‐related risk factors and a thorough food frequency questionnaire. This allowed us to build an adherence score to the Mediterranean diet (mediSCORE, range 0–9) constructed from individual food intakes. Food intake was also further analysed by conversion to micronutrient consumption.

Results

Our results suggest that physical activity has a protective role in AMD [p = 0.018 after multivariate adjustment, OR: 0.69 (0.51–0.93)]. High (mediSCORE ≥6) was also found to be protective [p = 0.041, OR: 0.62 (95% CI: 0.38–0.97)]. Food group analysis unveiled a specific protective role for increased fruits consumption (p = 0.029). Finally, micronutrient analysis revealed a protective role associated with increased consumption of caffeine, fibres, beta‐carotene, vitamin C and vitamin E (p < 0.05).

Conclusion

High mediSCORE appears to confer protection against the development of AMD in a Mediterranean population. This effect is driven by increased consumption of fruits and some antioxidant micronutrients, which emerged as statistically significant protective factors. Further studies are required to establish dietary recommendations with clinical application.
The rim area of the optic nerve head, assessed with Heidelberg retina tomography, is smaller in prematurely born children than in children born at term
Authors: Åkerblom Hanna , Holmström Gerd , Larsson Eva
Published: September 2018

Purpose

To examine the optic nerve head with Heidelberg tomography (HRT) in prematurely born school‐age children and compare them to children born at term.

Methods

Sixty‐three 5–16‐year‐old children born with a gestational age (GA) of ≤32 weeks were included in the study and compared to 54 children of the same age, born at term. In the preterm group, 29 children had had retinopathy of prematurity (ROP) and nine children had neurological complications. The optic nerve head was assessed with HRT. Three measurements were performed, and the different topographic parameters were noted.

Results

Rim area of the optic nerve was significantly smaller in prematurely born children than in children born at term. The mean difference was 0.146 mm2 (p = 0.02). No difference between the groups was found regarding disc area or cup area. In the preterm group, both disc and rim areas were reduced with increasing GA. No correlations with birthweight, ROP or neurological complications were found.

Conclusion

Reduced rim area of the optic nerve head was found in preterm children of school age. Previous ROP or neurological complication did not influence the result, suggesting the preterm birth per se was the reason for the reduction. Establishing whether this finding was caused by disturbed maturation of the optic nerve or by injury of the axons, or a combination of the two, will require further research.
Unnecessary harm is avoided by reliable paediatric index of mortality2 scores without arterial gas sampling
Authors: Kalzén Håkan , Hannegård Hamrin Tova , Lindberg Lars , Ingemanson Ola , Radell Peter J. , Eksborg Staffan
Published: September 2018

Aim

To investigate whether unnecessary harm could be avoided in children admitted to paediatric intensive care (PICU), we analysed the impact of arterial blood gas on the paediatric index of mortality score2 (PIM2) and the derived predicted death rate (PDR).

Methods

From January 1, 2008 to December 31, 2010, 1793 consecutive admissions, newborn infants to 16 years of age (median 0.71 years) from a single, tertiary PICU in Gothenburg Sweden, were collected. Admission information on arterial oxygen tension (PaO2) and fraction of inspired oxygen (FiO2) was extracted from 990 admissions.

Results

There was close agreement between PIM2 score and PDR regardless of whether the PaO2/FiO2 ratio was omitted or not. In the subgroup of admissions with a respiratory admission diagnosis, the inclusion of the PaO2/FiO2 ratio increased the accuracy of the PIM2 score as well as the PDR. The standard mortality ratio was slightly but not significantly overestimated by excluding the PaO2/FiO2 ratio.

Conclusion

To avoid unnecessary harm to children admitted to PICU, an arterial blood gas analysis should only be performed if clinically indicated or if the child has a respiratory admission diagnosis. Estimation of the PIM2 score and PDR will not be less accurate by this approach.
Proactive Vitality Management, Work Engagement, and Creativity: The Role of Goal Orientation
Authors: Bakker Arnold B. , Petrou Paraskevas , Op den Kamp Emma M. , Tims Maria
Published: September 2018

This study tested the hypothesis that individuals can proactively manage their own energetic, affective, and cognitive resources in order to be creative at work. Building on proactivity and creativity literatures, we propose a theoretical model in which employees who proactively manage their vitality are more engaged in their work and show improved creative performance. We also tested the boundary conditions of this process. Participants were Dutch employees from various occupations who filled out a background questionnaire and five weekly surveys. The results of multilevel modelling analyses offered support for our model. Weekly proactive vitality management was positively related to changes in weekly creativity through changes in weekly work engagement. As predicted, learning goal orientation strengthened and performance goal orientation weakened the links between proactive vitality management and engagement, and between engagement and creativity. We discuss the theoretical contributions, and indicate how these findings can be used in daily working life.
Cystatin C measurement leads to lower metformin dosage in elderly type 2 diabetic patients
Authors: Šálek Tomáš , Adamíková Alena
Published: September 2018

The aim of this study was to provide evidence for the hypothesis that estimated glomerular filtration rate from serum Cystatin C (eGFRcys) is better to be determined for all elderly type 2 diabetes mellitus (T2DM) patients based on eGFRcys upward and downward reclassification rate for hypothetical metformin dose reduction by eGFRcys at the GFR decision point of 45 mL/min/1.73 m2. A total of 265 consecutive T2DM elderly patients (age range 65‐91 years) from outpatient diabetic clinic were included in the study. The Kidney Disease Improving Global Outcomes (KDIGO) guidelines for metformin dosing were strictly followed. Estimated glomerular filtration rate from serum creatinine (eGFRcrea) led to results of metformin eligibility. Each of the results of eGFRcrea‐based eligibility was further compared to eGFRcys‐based eligibility. Creatinine was measured by enzymatic method standardized against international reference material SRM 967. Cystatin C was determined by method traceable to DA ERM 471 international standard. eGFRcrea and eGFRcys were calculated according to Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) equations. A downward reclassification rate was higher than upward reclassification rate (31 vs 3, respectively; P < 0.0001). The median (IQR) eGFRcrea was higher than eGFRcys (73 (58‐85) vs 63 (50‐75) mL/min/1.73 m2, respectively; P < 0.0001). eGFRcys reclassified significant proportion of patients with T2DM from metformin eligible CKD stages to less or non‐eligible stages. The downward reclassification was more frequent in patients older than 80 years (P < 0.01). Cystatin C‐based eGFR selects more complicated patients, where lower doses of metformin are possibly advisable. We recommend calculating both eGFRcrea and eGFRcys for metformin dosing in elderly patients with T2DM.
Quantitation of escitalopram and its metabolites by liquid chromatography‐tandem mass spectrometry in psychiatric patients: New metabolic ratio establishment
Authors: Canbolat Fadime , Tasdemir Erinç Dilek Meltem , Evrensel Alper , Aydın Ahmet , Tarhan Kaşif Nevzat
Published: September 2018

Therapeutic drug monitoring (TDM) is used to determine the concentration of drug in plasma/serum to adjust the dose of the therapeutic drug. Selective and sensitive analytical methods are used to determine drug and metabolite levels for the successful application of TDM. The aim of the study was to develop and validate using LC‐MS/MS to analyse quantitative assay of escitalopram (S‐CT) and metabolites in human plasma samples. In order to provide a convenient and safe treatment dose, it was aimed to determine the levels of S‐CT and its metabolites in the patients’ plasma. A new method with short sample preparation and analysis time was developed and validated using LC‐MS/MS to analyse quantitative assay of S‐CT and its metabolites in plasma. Also, plasma samples of 30 patients using 20 mg S‐CT between the ages of 18 and 65 years were analysed by the validated method. The mean values of S‐CT, demethyl escitalopram and didemethyl escitalopram in plasma of patients were 27.59, 85.52 and 44.30 ng/mL, respectively. At the end of the analysis, the metabolic ratio of S‐CT and metabolites was calculated. It is considered that the method for the quantitative analysis of S‐CT and its metabolites in human plasma samples may contribute to the literature on account of its sensitive and easy application. Additionally, the use of our data by physicians will contribute to the effective drug treatment for their patients who take S‐CT.
Women from racial or ethnic minority and low socioeconomic backgrounds receive more prenatal education: Results from the 2012 to 2014 Pregnancy Risk Assessment Monitoring System
Authors: Nguyen Minh N. , Siahpush Mohammad , Grimm Brandon L. , Singh Gopal K. , Tibbits Melissa K.
Published: September 2018

Background

Racial or ethnic and socioeconomic disparities in adverse birth outcomes are well known, but few studies have examined disparities in the receipt of prenatal health education. The objectives of this study were to examine racial or ethnic and socioeconomic variations in receiving (1) comprehensive prenatal health education and (2) education about human immunodeficiency virus (HIV) testing, breastfeeding, alcohol, and smoking cessation from health care practitioners.

Methods

Data were drawn from the 2012 to 2014 Pregnancy Risk Assessment Monitoring System (PRAMS). Twenty‐seven states were included with an analysis sample size of 68 025 participants. Receiving counseling on all listed health topics during prenatal care visits was denoted as comprehensive prenatal health education. Logistic regression was used to examine the association of racial or ethnic and socioeconomic variables with receiving comprehensive prenatal health education, and HIV testing, breastfeeding, alcohol, and smoking cessation advice separately.

Results

Multivariable results showed that racial or ethnic minorities and women with a high school degree or less; receiving Women, Infant, and Children (WIC) assistance; and on Medicaid during pregnancy have higher odds of receiving comprehensive prenatal health education (all P  ≤0 .001). Results were similar for receiving HIV testing, breastfeeding, alcohol, and smoking counseling. Low household income was associated with receiving counseling on HIV testing, alcohol, and smoking (all P ≤ 0.001).

Conclusion

Despite reporting higher levels of prenatal health education on a variety of health‐related topics, disadvantaged women continue to experience disparities in adverse birth outcomes suggesting that education is insufficient in promoting positive behaviors and birth outcomes.
Long‐term testosterone therapy in type 2 diabetes is associated with reduced mortality without improvement in conventional cardiovascular risk factors
Authors: Hackett Geoffrey , Cole Nigel , Mulay Akhilesh , Strange Richard C. , Ramachandran Sudarshan
Published: September 2018

Objectives

To further characterize the beneficial impact of testosterone replacement therapy (TRT) on the association between mortality and hypogonadism (HG) in men with type 2 diabetes (T2DM), by determining, firstly, if changes in cardiovascular disease (CVD) risk factors after TRT play a role, secondly, whether the reduction in mortality is lost when TRT is discontinued and, finally, the presence of subgroups where benefit may be greater.

Materials and Methods

We studied 857 men with T2DM, screened for the BLAST randomized controlled trial, over 3.8 years of follow‐up. The men were stratified first by testosterone levels: group 1: total testosterone (TT) >12 nmol/L and free testosterone (FT) >0.25 nmol/L; Group 2: TT ≤12 nmol/L or FT ≤0.25 nmol/L. Group 2 was further stratified into those not on TRT (Group 2a) and those on TRT (Group 2b). Group 2b was further stratified by whether TRT was discontinued (Group 2b1) or not (Group 2b2). The principal outcome, mortality, was studied using Cox regression.

Results

We found that TRT was not associated with improvements in CVD risk factors. CVD risk factors (baseline and changes during follow‐up) were not associated with mortality. Men in Group 1 and Group 2b were found to have lower mortality (reference: Group 2a), even with CVD risk factors included in the regression models. Mortality was lower in men in Group 2b1 (6.2%) and Group 2b2 (0%) compared with those in Group 2a (16.9%). The lower mortality associated with Group 1 and Group 2b was observed primarily in older (>64.6 years) and less overweight (≤93.8 kg) men.

Conclusions

The benefits associated with normal testosterone levels and TRT (even after discontinuation) do not appear to be related to improvements in the CVD risk factors studied. In view of TRT having greater impact in men of lower weight, better outcomes may be achieved with concurrent TRT and weight reduction programmes.
Holocene vegetation change in northernmost Fennoscandia and the impact on prehistoric foragers 12 000–2000 cal. aBP– A review
Authors: Sjögren Per , Damm Charlotte
Published: September 2018

While single pollen records are widely used in reconstructing the environment for nearby prehistoric settlements, they are less helpful when addressing large‐scale issues of variation in human settlement patterns. In order to assess the impact of vegetation change on regional prehistoric settlement and subsistence patterns in an ecotone sensitive area, we inferred the general change in main vegetation types based on palaeobotanical investigations from across northernmost Fennoscandia. Tundra vegetation was predominant during the Lateglacial and earliest parts of the Holocene. Maritime birch forests rich in ferns started to expandc. 11 000 cal. aBPand became dominant from 10 000 cal. aBP. Pine expanded from theNEof the investigation area and pine‐birch forest dominated in the inland around 8000 cal. aBP. A gradual degeneration of forest towards more open birch woodland startedc. 6000 cal. aBPwith the most marked change around 3500 cal. aBP. Along the northern outer coast, this eventually led to open heathland. Comparison with the archaeological setting suggests a general correlation between low forest cover and extensive mobility patterns, while widespread and varied forest cover appear to have led to a more sedentary way of life. The background for this is arguably that the forested landscapes hosted a larger diversity of resources within a shorter foraging distance, while areas and periods with low forest cover required longer travels to obtain the desired prey and materials.
Adenosine A2A receptors facilitate synaptic NMDA currents in CA1 pyramidal neurons
Authors: Mouro Francisco M , Rombo Diogo M , Dias Raquel B , Ribeiro Joaquim A , Sebastião Ana M
Published: September 2018

Background and Purpose

NMDA receptors play a key role in both synaptic plasticity and neurodegeneration. Adenosine is an endogenous neuromodulator and through membrane receptors of the A2A subtype can influence both synaptic plasticity and neuronal death. The present work was designed to evaluate the influence of adenosine A2A receptors upon NMDA receptor activity in CA1 hippocampal neurons. We discriminated between modulation of synaptic versus extrasynaptic receptors, since extrasynaptic NMDA receptors are mostly associated with neurodegeneration while synaptic NMDA receptors are linked to plasticity phenomena.

Experimental Approach

Whole‐cell patch‐clamp recordings were obtained to evaluate NMDA receptor actions on CA1 pyramidal neurons of young adult (5–10 weeks) male Wistar rat hippocampus.

Key Results

Activation of A2A receptors with CGS 21680 (30 nM) consistently facilitated chemically‐evoked NMDA receptor‐currents (NMDA‐PSCs) and afferent‐evoked NMDA‐currents (NMDA‐EPSCs), an action prevented by an A2A receptor antagonist (SCH58261, 100 nM) and a PKA inhibitor, H‐89 (1 μM). These actions did not reflect facilitation in glutamate release since there was no change in NMDA‐EPSCs paired pulse ratio. A2A receptor actions were lost in the presence of an open‐channel NMDA receptor blocker, MK‐801 (10 μM), but persisted in the presence of memantine, at a concentration (10 μM) known to preferentially block extrasynaptic NMDA receptors.

Conclusion and Implications

These results show that A2A receptors exert a positive postsynaptic modulatory effect over synaptic, but not extrasynaptic, NMDA receptors in CA1 neurons and, therefore, under non‐pathological conditions may contribute to shift the dual role of NMDA receptors towards enhancement of synaptic plasticity.
Prolonged inhibition of hepatocellular carcinoma cell proliferation by combinatorial expression of defined transcription factors
Authors: Takashima Yasuo , Horisawa Kenichi , Udono Miyako , Ohkawa Yasuyuki , Suzuki Atsushi
Published: September 2018

Hepatocellular carcinoma (HCC) accounts for a large proportion of liver cancer cases and has an extremely poor prognosis. Therefore, novel innovative therapies for HCC are strongly desired. As gene therapy tools for HCC, 2 hepatic transcription factors (TF), HNF4A and HNF1A, have been used to suppress proliferation and to extinguish cancer‐specific characteristics of target cells. However, our present data demonstrated that single transduction of HNF4A or HNF1A had only a limited effect on suppression of HCC cell proliferation. Thus, in this study, we examined whether combinations of TF could show more effective antitumor activity, and found that combinatorial transduction of 3 hepatic TF, HNF4A, HNF1A and FOXA3, suppressed HCC cell proliferation more stably than single transduction of these TF. The combinatorial transduction also suppressed cancer‐specific phenotypes, such as anchorage‐independent growth in culture and tumorigenicity after transplantation into mice. HCC cell lines transduced with the 3 TF did not recover their proliferative property after withdrawal of anticancer drugs, indicating that combinatorial expression of the 3 TF suppressed the growth of all cell subtypes within the HCC cell lines, including cancer stem‐like cells. Transcriptome analyses revealed that the expression levels of a specific gene set involved in cell proliferation were only decreased in HCC cells overexpressing all 3 TF. Moreover, combined transduction of the 3 TF could facilitate hepatic differentiation of HCC cell lines. Our strategy for inducing stable inhibition and functional differentiation of tumor cells using a defined set of TF will become an effective therapeutic strategy for various types of cancers.
Non‐atopic rhinitis at age 6 is associated with subsequent development of asthma
Authors: Carr Tara F. , Stern Debra A. , Halonen Marilyn , Wright Anne L. , Martinez Fernando D.
Published: September 2018

Background

It has been postulated that the association between allergic rhinitis and asthma is attributable to the progressive clinical expression of respiratory inflammation during childhood. The role of non‐allergic rhinitis in early life in relation to subsequent asthma has not been extensively explored.

Objective

We sought to determine whether rhinitis in early life was associated with risk of asthma development into adulthood, and whether this relationship is independent of allergic sensitization.

Methods

Participants were identified from the Tucson Children's Respiratory Study, a non‐selected birth cohort. Allergy skin prick testing was performed at age 6 years using house dust mix, Bermuda, mesquite, olive, mulberry, careless weed, andAlternariaaeroallergens. Atopy was defined as ≥1 positive tests. Physician‐diagnosed active asthma from age 6 to 32 and physician‐diagnosed rhinitis at age 6 were determined by questionnaire. Participants with asthma or active wheezing at age 6 were excluded from analyses. Risk estimates were obtained with Cox regression.

Results

There were 521 participants who met inclusion criteria. The hazard ratio for subsequently acquiring a diagnosis of asthma between the ages of 8 and 32 for those with non‐atopic rhinitis was 2.1 (95%CI: 1.2, 3.4,P = 0.005), compared with the non‐atopic no rhinitis group, after adjusting for sex, ethnicity, maternal asthma, maternal education and smoking, and history of 4+ colds per year at age 6. Among the atopic participants, both the active and no rhinitis groups were more likely to develop and have asthma through age 32. The relation between non‐atopic rhinitis and asthma was independent of total serum IgE levels at age 6.

Conclusion and Clinical Relevance

Childhood rhinitis, even in the absence of atopy, confers significant risk for asthma development through adulthood. These findings underscore the importance of non‐allergic mechanisms in the development of asthma.
Identification of circular RNAs hsa_circ_0044235 in peripheral blood as novel biomarkers for rheumatoid arthritis
Authors: Luo Q , Zhang L , Li X , Fu B , Deng Z , Qing C , Su R , Xu J , Guo Y , Huang Z , Li J
Published: September 2018

Circular RNAs (circRNAs) are a new class of RNAs that can be used as biomarkers in clinical blood samples. However, little is known about circRNAs' diagnostic values for rheumatoid arthritis (RA). In this study, the hsa_circ_0054189, hsa_circ_0008675, hsa_circ_0082689, hsa_circ_0082688, hsa_circ_0010932, hsa_circ_0002473 and hsa_circ_0044235 in peripheral blood were determined by quantitative reverse transcription–polymerase chain reaction (qRT–PCR). For hsa_circ_0044235, only one abnormal expression circRNAs in peripheral blood was selected as a targeted circRNA to explore the diagnostic value for RA. Our work demonstrated that the hsa_circ_0044235 in peripheral blood was decreased significantly in RA patients. The hsa_circ_0044235 in peripheral blood from RA patients did not correlate with C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA) or disease activity score 28 (DAS28). Receiver operating characteristic (ROC) curve analysis suggested that the hsa_circ_0044235 in peripheral blood has significant value in the diagnosis of RA. The risk score based on hsa_circ_0044235 in peripheral blood also distinguished significantly the patients with RA from systemic lupus erythematosus (SLE). This study suggests that the hsa_circ_0044235 in peripheral blood may be a potential biomarker of patients with RA.
Clinical and laboratory features of seventy-eight UK patients with Good’s syndrome (thymoma and hypogammaglobulinaemia)
Authors: Zaman M , Huissoon A , Buckland M , Patel S , Alachkar H , Edgar J D , Thomas M , Arumugakani G , Baxendale H , Burns S , Williams A P , Jolles S , Herriot R , Sargur R B , Arkwright P D
Published: September 2018

Good’s syndrome (thymoma and hypogammaglobulinaemia) is a rare secondary immunodeficiency disease, previously reported in the published literature as mainly individual cases or small case series. We use the national UK-Primary Immune Deficiency (UKPID) registry to identify a large cohort of patients in the UK with this PID to review its clinical course, natural history and prognosis. Clinical information, laboratory data, treatment and outcome were collated and analysed. Seventy-eight patients with a median age of 64 years, 59% of whom were female, were reviewed. Median age of presentation was 54 years. Absolute B cell numbers and serum immunoglobulins were very low in all patients and all received immunoglobulin replacement therapy. All patients had undergone thymectomy and nine (12%) had thymic carcinoma (four locally invasive and five had disseminated disease) requiring adjuvant radiotherapy and/or chemotherapy. CD4 T cells were significantly lower in these patients with malignant thymoma. Seventy-four (95%) presented with infections, 35 (45%) had bronchiectasis, seven (9%) chronic sinusitis, but only eight (10%) had serious invasive fungal or viral infections. Patients with AB-type thymomas were more likely to have bronchiectasis. Twenty (26%) suffered from autoimmune diseases (pure red cell aplasia, hypothyroidism, arthritis, myasthenia gravis, systemic lupus erythematosus, Sjögren’s syndrome). There was no association between thymoma type and autoimmunity. Seven (9%) patients had died. Good’s syndrome is associated with significant morbidity relating to infectious and autoimmune complications. Prospective studies are required to understand why some patients with thymoma develop persistent hypogammaglobulinaemia.
Statins influence epithelial expression of the anti-microbial peptide LL-37/hCAP-18 independently of the mevalonate pathway
Authors: Lüthje P , Walker S , Kamolvit W , Mohanty S , Pütsep K , Brauner A
Published: September 2018

Anti-microbial resistance increases among bacterial pathogens and new therapeutic avenues needs to be explored. Boosting innate immune mechanisms could be one attractive alternative in the defence against infectious diseases. The cholesterol-lowering drugs, statins, have been demonstrated to also affect the immune system. Here we investigate the effect of statins on the expression of the human cathelicidin anti-microbial peptide (CAMP) LL-37/hCAP-18 [encoded by the CAMP gene] and explore the underlying mechanisms in four epithelial cell lines of different origin. Simvastatin induced CAMP expression in bladder epithelial cells telomerase-immortalized uroepithelial cells (TERT-NHUCs), intestinal cells HT-29 and keratinocytes HEKa, but not in airway epithelial cells A549. Gene induction in HEKa cells was reversible by mevalonate, while this effect was independent of the cholesterol biosynthesis pathway in TERT-NHUCs. Instead, inhibition of histone deacetylases by simvastatin seems to be involved. For HT-29 cells, both mechanisms may contribute. In addition, simvastatin increased transcription of the vitamin D-activating enzyme CYP27B1 which, in turn, may activate LL-37/hCAP-18 production. Taken together, simvastatin is able to promote the expression of LL-37/hCAP-18, but cell line-specific differences in efficacy and the involved signalling pathways exist.