bluuebunny/crossref_metadata_2025 huggingface dataset:
Les corridors maritimes stratégiques dans l'Arctique canadien : un programme adapté au tourisme marin  ?
Authors: Têtu Pierre‐Louis
Published: October 2018

Dans l'Arctique canadien, la réduction de la banquise estivale permet une meilleure accessibilité et donc un développement accru de la navigation touristique. Cet article souligne ainsi un accroissement sensible depuis 1990 des navires de croisière et des embarcations de plaisance dans l'archipel arctique canadien, notamment pour les régions stratégiques du détroit de Lancaster et les régions du sud‐est de l'île de Baffin. Les analyses suggèrent que les navires de croisières comme les embarcations de plaisance tendent à naviguer à l'intérieur des corridors primaires. En ce qui a trait aux corridors secondaires, il y a toujours plus de navires de croisière et d'embarcations de plaisance qui parcourent des distances en dehors de ceux‐ci, et c'est particulièrement notable au niveau du corridor secondaire 4 de l'Arctique de l'Ouest. En somme, l'activité maritime touristique se tient principalement dans des zones situées entre 0 et 15 milles nautiques et au‐delà de la bordure externe d'un corridor, primaire ou secondaire. Le programme des corridors maritimes stratégiques nordiques constitue un outil important pour minimiser les risques liés à la navigation. Il faut donc continuer à encourager sa mise en œuvre à travers une approche multipartite et en tenant compte des représentations des Inuits
Authoritarian elites
Authors: Newson Adlai , Trebbi Francesco
Published: October 2018

We explore the role of ruling elites in autocratic regimes and provide an assessment of tools useful to clarify the structure of opaque political environments. We first showcase the importance of analyzing autocratic regimes as non‐unitary actors by discussing extant work on non‐democracies in sub‐Saharan Africa and China, where the prevailing view of winner‐take‐all contests can be clearly rejected. We show how specific biographical information about powerful cadres helps shed light upon the composition of the inner circles that empower autocrats. We further provide an application of these methods to the Democratic People's Republic of Korea (DPRK), one of the most personalistic, opaque and data‐poor political regimes in the world today. Employing information from DPRK state media on participants at official state events, we are able to trace the evolution and consolidation of Supreme Leader Kim Jong Un around the transition period following the death of his father, Kim Jong Il. The internal factional divisions of the DPRK are explored during and after this transition. Final general considerations for the future study of the political economy of development are presented.
A retro‐prospective long‐term follow‐up of Brånemark single implants in the anterior maxilla in young adults. Part 1: Clinical and radiographic parameters
Authors: Winitsky Nicole , Olgart Kerstin , Jemt Torsten , Smedberg Jan‐Ivan
Published: October 2018

Background

Single implant restorations have become the primary treatment option for young adults with missing anterior teeth. Yet, long‐term studies of single‐implants are limited in the literature.

Purpose

To report long‐term survival, success, and complications in young adults with single‐implants in the anterior maxilla.

Materials and Methods

A group of 42 patients (mean age 20.7 years) received 53 anterior maxillary single‐implants during 1996 and 1997. Data were collected at delivery of the crown, at 1‐year examination, and at 14‐20‐year examination. Descriptive statistics, estimated cumulative survival rates, Pearson correlation test, and t‐test were performed.

Results

After 14‐20 years, 40 out of 42 patients were examined. Two patients were lost to follow‐up, two implants failed and ten original single‐crown restorations were replaced. Estimated cumulative survival rates were 96.1% for implants and 80.4% for implant‐supported crowns. Complications were seen in 21 patients. Mean probing depth was 4.0 ± 1.8 mm and mean marginal bone loss was 0.1 ± 1.1 mm. No correlation was found between marginal bone loss and probing depth, occlusal contact in maximal intercuspal position or usage of nicotine.

Conclusions

Long‐term prognosis of single implant treatments in the anterior maxilla in young adults must be regarded as good, with high survival and success rates.
Reliability and validity of various laboratory methods of body composition assessment in young adults
Authors: Schubert Matthew M. , Seay Rebekah F. , Spain Katie K. , Clarke Holly E. , Taylor James K.
Published: October 2018

Accurate measures of body composition (BC) are essential for performance and health. In addition to accuracy, BC measures should be practical and be minimally invasive to maximize their utility. The purpose of the present study was to compare the day‐to‐day variability and validity of four common laboratory‐based body composition assessments to a criterion four‐compartment model. Dual x‐ray absorptiometry (DXA), air displacement plethysmography (BP), multi‐frequency bioelectrical impedance (MF‐BIA) and underwater weighing (UWW) were performed twice in a sample of 32 young men and women. Participants were assessed in a fasted, euhydrated state 2–7 days apart. All methods were compared to a criterion four‐compartment model using BP‐derived body volume, DXA‐derived bone mineral content and MF‐BIA‐derived total body water (4CBP). Additional four‐compartment models using UWW‐ and DXA‐derived body volume were also examined (4CUWW) and (4CDXA). Validity results were conducted with paired t‐tests and Bland–Altman analysis. Reliability was determined using intraclass correlations (ICC), coefficients of variation (CV) and standard error of the measurement (SEM). Validity analysis revealed that all methods overestimated per cent body fat and fat mass, and underestimated fat‐free mass when compared with 4CBP, but only DXA and BP were significantly different (P<0·008). All measures were highly reliable across days (ICCs > 0·9, CVs < 12%). Results of the present study indicate that typical laboratory‐based methods of body composition are valid and reliable. However, we caution that results should not be translated between methods and assessments should be performed with the same instrument when the goal is to monitor changes in body composition over time.
Ferritin heavy/light chain (FTH1/FTL) expression, serum ferritin levels, and their functional as well as prognostic roles in acute myeloid leukemia
Authors: Bertoli Sarah , Paubelle Etienne , Bérard Emilie , Saland Estelle , Thomas Xavier , Tavitian Suzanne , Larcher Marie‐Virginie , Vergez François , Delabesse Eric , Sarry Audrey , Huguet Françoise , Larrue Clément , Bosc Claudie , Farge Thomas , Sarry Jean Emmanuel , Michallet Mauricette , Récher Christian
Published: October 2018

Objectives

We previously reported the prognostic value of serum ferritin in younger patients with intermediate‐risk acute myeloid leukemia (AML). The aims of this study were to confirm this finding in a larger cohort regardless of age and prognostic subgroups, to explore the expression and functional role of ferritin in AML cells as well as the regulation of serum ferritin levels in AML patients.

Patients/Materials/Methods

Serum ferritin levels at diagnosis were collected in a cohort of 525 patients treated by intensive chemotherapy. In silico, in vitro,and in vivo analyses were conducted to assess the pattern of expression and functional role ofFTH1andFTLin AML.

Results

We confirmed the independent prognostic value of serum ferritin. In transcriptomic databases,FTH1andFTLwere overexpressed in AML and leukemic stem cells compared to normal hematopoietic stem cells. The gene signature designed from AML patients overexpressingFTH1revealed a significant enrichment in genes of the immune and inflammatory response including Nf‐KB pathway, oxidative stress, or iron pathways. This gene signature was enriched in cytarabine‐resistant AML cells in a patient‐derived xenograft model. FTH1 protein was also overexpressed in patient's samples and correlated with the in vitro cytotoxic activity of cytarabine. Lastly, we demonstrated that chemotherapy induced an inflammatory response including a significant increase in serum ferritin levels between day 1 and 8 of induction chemotherapy that was blocked by dexamethasone.

Conclusion

Ferritin is deregulated in most AML patients likely through inflammation, associated with chemoresistance, and could represent a new therapeutic target.
Differential effects of D1 and D2 dopamine agonists on memory, motivation, learning and response time in non‐human primates
Authors: Marino Robert A. , Levy Ron
Published: October 2018

Dopamine (DA) plays a critical role in cognition, motivation and information processing. DA action has been shown to both improve and/or impair cognition across different receptor types, species, subjects and tasks. This complex relationship has been described as an inverted U‐shaped function and may be due to the differential effects of DA receptor activation in the striatum and prefrontal cortex. We have investigated the effects of selective DA agonists on cognitive performance in healthy monkeys using a touch screen running tasks from the CAmbridge Neuropsychological Test Automated Battery (CANTAB). One of two DA agonist drugs or placebo was administered prior to each daily CANTAB session: Dihydrexidine hydrochloride (selective D1 agonist, 0.4–0.9 mg/kg), or sumanirole maleate (selective D2 agonist 0.05–0.3 mg/kg). Three CANTAB tasks were tested: (a) “self‐ordered sequential search task” which tested spatial working memory, (b) “reversal learning task,” which tested association learning, cognitive flexibility and attention and (c) “visually guided reaching task,” which tested reaction time and accuracy. At high dosages, the D2 agonist improved spatial working memory performance, while impairing reversal learning and slowing reach response latency. No consistent cognitive effects were observed with the D1 agonist across the dosages tested. A significant decrease in trial completion rate was observed at the higher dosages of both the D1 and D2 agonists which were consistent with decreased motivation. These results are consistent with task‐specific effects of a D2 agonist as well as dose specific insensitivities of a D1 agonist on cognitive and motor behaviors in a healthy monkey.
Intravenous immunoglobulin for treatment of chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy in France: are daily practices in accordance with guidelines?
Authors: Rosier C. , Graveline N. , Lacour A. , Antoine J.‐C. , Camdessanché J.‐P.
Published: October 2018

Background and purpose

Chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN) are rare autoimmune diseases. Guidelines were published in 2010 for their diagnosis and treatment. In France, intravenous immunoglobulins (IVIGs) are mainly used for the first‐line treatment. The burden of healthcare costs is often underlined but rarely studied. The aim of this survey was to compare to guidelines, the daily practice of French neurologists with IVIGs for CIDP and MMN treatment.

Methods

This was a retrospective observational study consisting of an online questionnaire performed between March and May 2014. A total of 49 questionnaires were included, a quarter of which were from neurologists working in neuromuscular reference centers (NRCs).

Results

A total of 182 patient case reports were studied. Patients were referred to an NRC for initial diagnosis in approximately 30% of cases in CIDP and 50% of cases in MMN. The initial management of IVIG (frequency, dose and duration) was not different between NRCs and non‐NRCs. Guidelines were followed and neurologists were relatively at ease in diagnosing and treating patients.

Conclusions

This was the first national study to describe the implementation of the European Federation of Neurological Sciences/Peripheral Nerve Society guidelines in the daily management of IVIGs in patients with MMN and CIDP in France. Efforts are needed to improve long‐term tailored treatment and home treatment to reduce economic costs.
Consensus on diagnosis and management of psychogenic non‐epileptic seizures: a wide view of a challenging condition
Authors: Brigo F. , Lattanzi S.
Published: October 2018

Click here to view the accompanying paper in this volume.
Abnormal temporal lobe morphology in asymptomatic relatives of patients with hippocampal sclerosis: A replication study
Authors: Yaakub Siti Nurbaya , Barker Gareth J. , Carr Sarah J. , Abela Eugenio , Koutroumanidis Michalis , Elwes Robert D. C. , Richardson Mark P.
Published: October 2018

We investigated gray and white matter morphology in patients with mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE+HS) and first‐degree asymptomatic relatives of patients with mTLE+HS. Using T1‐weighted magnetic resonance imaging (MRI), we sought to replicate previously reported findings of structural surface abnormalities of the anterior temporal lobe in asymptomatic relatives of patients with mTLE+HS in an independent cohort. We performed whole‐brain MRI in 19 patients with mTLE+HS, 14 first‐degree asymptomatic relatives of mTLE+HS patients, and 32 healthy control participants. Structural alterations in patients and relatives compared to controls were assessed using automated hippocampal volumetry and cortical surface–based morphometry. We replicated previously reported cortical surface area contractions in the ipsilateral anterior temporal lobe in both patients and relatives compared to healthy controls, with asymptomatic relatives showing similar but less extensive changes than patients. These findings suggest morphologic abnormality in asymptomatic relatives of mTLE+HS patients, suggesting an inherited brain structure endophenotype.
Hybridization rate and hybrid fitness for Camelina microcarpa Andrz. ex DC (♀) and Camelina sativa (L.) Crantz(Brassicaceae) (♂)
Authors: Martin Sara L. , Lujan‐Toro Beatriz E. , Sauder Connie A. , James Tracey , Ohadi Sara , Hall Linda M.
Published: October 2018

Hybridization between crops and their wild relatives has the potential to introduce novel variation into wild populations. Camelina (Camelina sativa) is a promising oilseed and cultivars with modified seed characteristics and herbicide resistance are in development, prompting a need to evaluate the potential for novel trait introgression into weedy relatives. Little‐podded false flax (littlepod; Camelina microcarpa) is a naturalized weed in Canada and the USA. Here we evaluated the hybridization rate between the three cytotypes of littlepod (♀) and camelina (♂), assessed characteristics of hybrids, and evaluated the fitness of hexaploid littlepod and camelina hybrids in the glasshouse and field. In total we conducted, 1,005 manual crosses with diploid littlepod, 1, 172 crosses with tetraploid littlepod, and 896 crosses with hexaploid littlepod. Hybrids were not produced by the diploids, but were produced by the tetraploids and hexaploids at rates of one hybrid for 2,000 ovules pollinated and 24 hybrids for 25 ovules pollinated, respectively. Hybrids between tetraploid littlepod and camelina showed low pollen fertility and produced a small number of seeds. In the glasshouse, hybrids between hexaploid littlepod and camelina also showed significantly lower pollen fertility and seed production than parental lines, but their seeds showed high viability. A similar pattern was observed in field trials, with hybrids showing earlier flowering, reduced biomass, seed production and seed weight. However, seed produced by the hybrids showed greater viability than that produced by hexaploid littlepod and is potentially the result of a shortened lifecycle. The introgression of lifecycle traits into littlepod populations may facilitate range expansion and contribute to crop gene persistence. Consequently, future work should evaluate the hybridization rate in the field, the fitness of advanced generation backcrosses, and the role of time to maturity in limiting hexaploid littlepod's distribution.
Enhancing Groundwater Remediation in Air Sparging by Changing the Pulse Duration
Authors: Neriah Asaf B. , Paster Amir
Published: October 2018

An important operation parameter in the design of a pulsed air sparging (PAS) system is the pulse duration (PD). To study the effect of the PD on the remediation process, a series of laboratory experiments and numerical simulations were performed. The experimental apparatus was a cylindrical tank, packed with fine sand and partially filled by water contaminated with toluene. Toluene concentrations in water and in effluent air were measured over time during the application of PAS, which was applied with three different PD. Next, the T2VOC model, an extension of the TOUGH2 simulation program, was used to simulate the two‐phase flow and transport processes for these cases. The simulation model was calibrated to the experimental results, and then run with a range of PD values. Results showed that there exists an optimal PD which yields the highest remediation efficiency. Next, it was shown that this PD may be obtained by performing a PAS pilot test and measuring the groundwater pressure response in a monitoring well. The characteristic time which describes the exponential decay of the pressure response was shown to provide an adequate estimate for the optimal PD. The estimation improved by taking a number of injection cycles.
Helicobacter pylori VacA, a distinct toxin exerts diverse functionalities in numerous cells: An overview
Authors: Chauhan Nidhi , Tay Alfred Chin Yen , Marshall Barry J. , Jain Utkarsh
Published: October 2018

Background

Helicobacter pylori, gastric cancer‐causing bacteria, survive in their gastric environment of more than 50% of the world population. The presence of H. pylori in the gastric vicinity promotes the development of various diseases including peptic ulcer and gastric carcinoma. H. pylori produce and secret Vacuolating cytotoxin A (VacA), a major toxin facilitating the bacteria against the host defense system. The toxin causes multiple effects in epithelial cells and immune cells, especially T cells, B cells, and Macrophages.

Methods

This review describes the diverse functionalities of protein toxin VacA. The specific objective of this review is to address the overall structure, mechanism, and functions of VacA in various cell types. The recent advancements are summarized and discussed and thus conclusion is drawn based on the overall reported evidences.

Results

The searched articles on H. pylori VacA were evaluated and limited up to 66 articles for this review. The articles were divided into four major categories including articles on vacA gene, VacA toxin, distinct effects of VacA toxin, and their effects on various cells. Based on these studies, the review article was prepared.

Conclusions

This review describes an overview of how VacA is secreted by H. pylori and contributes to colonization and virulence in multiple ways by affecting epithelial cells, T cells, Dendritic cells, B cells, and Macrophages. The reported evidence suggests that the comprehensive outlook need to be developed for understanding distinctive functionalities of VacA.
Data set for the reporting of carcinoma of renal tubular origin: recommendations from the International Collaboration on Cancer Reporting (ICCR)
Authors: Delahunt Brett , Srigley John R , Judge Meagan J , Amin Mahul B , Billis Athanase , Camparo Philippe , Evans Andrew J , Fleming Stewart , Griffiths David F , Lopez‐Beltran Antonio , Martignoni Guido , Moch Holger , Nacey John N , Zhou Ming
Published: October 2018

Aims

The International Collaboration on Cancer Reporting (ICCR) has provided detailed data sets based upon the published reporting protocols of the Royal College of Pathologists, the Royal College of Pathologists of Australasia and the College of American Pathologists.

Methods and results

The data set for carcinomas of renal tubular origin treated by nephrectomy was developed to provide a minimum structured reporting template suitable for international use, and incorporated recommendations from the 2012 Vancouver Consensus Conference of the International Society of Urological Pathology (ISUP) and the fourth edition of the World Health Organisation Bluebook on tumours of the urinary and male genital systems published in 2016. Reporting elements were divided into those, which are required and recommended components of the report. Required elements are: specimen laterality, operative procedure, attached structures, tumour focality, tumour dimension, tumour type, WHO/ISUP grade, sarcomatoid/rhabdoid morphology, tumour necrosis, extent of invasion, lymph node status, surgical margin status, AJCC TNM staging and co‐existing pathology. Recommended reporting elements are: pre‐operative treatment, details of tissue removed for experimental purposes prior to submission, site of tumour(s) block identification key, extent of sarcomatoid and/or rhabdoid component, extent of necrosis, presence of tumour in renal vein wall, lymphovascular invasion and lymph node status (size of largest focus and extranodal extension).

Conclusions

It is anticipated that the implementation of this data set in routine clinical practice will inform patient treatment as well as provide standardised information relating to outcome prediction. The harmonisation of data reporting should also facilitate international research collaborations.
Tumor growth velocity: A modified tumor growth rate defining tumor progression during sorafenib treatment in patients with metastatic renal cell carcinoma
Authors: Wang Hong‐Kai , Xu Wen‐Hao , Ma Chun‐Guang , Zhou Liang‐Ping , Shi Guo‐Hai , Zhang Hai‐Liang , Ye Ding‐Wei
Published: October 2018

Objectives

To investigate the role of tumor growth velocity in defining tumor progression in metastatic renal cell carcinoma patients treated with the vascular endothelial growth factor tyrosine kinase inhibitor, sorafenib.

Methods

A modified calculation for tumor growth velocity was introduced to evaluate the tumor growth velocity, before and after sorafenib withdrawal. Known prognostic factors together with tumor growth velocity before drug withdrawal and tumor growth velocity after drug withdrawal were compared using a χ2‐test from a contingency table, and partial likelihood test from a Cox regression model for overall survival.

Results

A total of 114 patients who reached progressive disease and withdrew from sorafenib were enrolled after a median follow‐up period of 107.8 months. Tumor growth velocity before drug withdrawal was 7.347 ± 4.040, and tumor growth velocity after drug withdrawal was 11.647 ± 5.937 (P < 0.001). Higher tumor growth velocity before drug withdrawal was correlated with a higher risk Memorial Sloan Kettering Cancer Center score (P = 0.022), Karnofsky Performance Status <80 (P = 0.028), non‐clear cell carcinoma (P = 0.037), higher tumor nucleus grade (P < 0.001) and best treatment response (P < 0.001). Patients with tumor growth velocity before drug withdrawal >5.0 had shorter overall survival (P < 0.001). On multivariate analysis, factors associated with overall survival were high/intermediate Memorial Sloan Kettering Cancer Center risk score (hazard ratio 2.119, P = 0.006), non‐clear histological subtype (hazard ratio 1.900, P = 0.031), tumor growth velocity before drug withdrawal ≥5.0 (hazard ratio 2.758, P < 0.001) and progressive disease as best response (hazard ratio 2.069, P = 0.001).

Conclusions

Significantly faster tumor growth can be observed if sorafenib is discontinued in the case of disease progression. Thus, we suggest not to withdraw targeted agents until tumor growth velocity is >5.0.
Medical complications of homelessness: a neglected side of men’s health
Authors: Brown Mark A. , Gellatley Wendy , Hoffman Anna , Dowdell Lisa , Camac Anne , Francois Rachel , Boston Belinda , Zekry Amany
Published: October 2018

Background

Homelessness is an increasing societal and health issue associated with high rates of substance abuse and mental health disorders. Homeless people die more often and at a younger age than others.

Aim

To identify health needs and improve healthcare for homeless men.

Methods

A physician‐led clinic was established on‐site at the Mission Australia Centre in Sydney, incorporating: (i) liver screening, including portable fibroscan testing, and on‐site treatment of hepatitis C; (ii) a mental health clinic, staffed by a psychiatrist; and (iii) a nurse‐led clinic to follow up medical issues and deliver vaccinations. Patient data were recorded prospectively to determine what medical problems were encountered so as to drive future healthcare planning.

Results

A total of 257 men was assessed between November 2011 and December 2017. In that time, 561 men resided at the Centre. Of these 257 men who attended the clinic, 61% were <45 years old; 69% were current and 8% former smokers; 62% had a history of chronic alcoholic abuse and 66% other substance abuse; 64% had one or more of depression, anxiety, psychosis or another mental health disorder and 44% had metabolic syndrome features, 38% cardiovascular disease, 29% hepatitis C and 21% a respiratory disorder.

Conclusion

The main health needs of homeless men fall into the categories of mental health; cardiovascular, respiratory and metabolic disorders and addictions and hepatitis C. Establishing on‐site clinics at homeless shelters with expertise to address these issues will likely improve the well‐being of these men, reduce hospital admissions and prolong their lives.
Behaviour change techniques to optimise participation in physical activity or exercise in adolescents and young adults with chronic cardiorespiratory conditions: a systematic review
Authors: Sawyer Abbey , Lewthwaite Hayley , Gucciardi Daniel F. , Hill Kylie , Jenkins Sue , Cavalheri Vinicius
Published: October 2018

Participation in regular physical activity decreases the risk of developing cardiometabolic disease. However, the proportion of people who participate in the recommended amount of physical activity is low, with common barriers including competing interests and inclement weather. In people with chronic cardiorespiratory conditions, participation in physical activity is reduced further by disease‐specific barriers, time burden of treatment and unpleasant symptoms during physical activity. Addressing these barriers during adolescence and early adulthood may promote greater physical activity participation into older age. The aim of this review was to classify interventions aimed at optimising participation in physical activity as ‘promising’ or ‘not promising’ in people aged 15–45 years with chronic cardiorespiratory conditions and categorise the behaviour change techniques (BCT) within these interventions. Nine databases and registries were searched (October 2017) for studies that reported objective measures of physical activity before and after an intervention period. Interventions were classified as ‘promising’ if a between‐group difference in physical activity was demonstrated. Michie et al.’s (2013) v1 Taxonomy was used to unpack the BCT within interventions. Across the six included studies (n = 396 participants), 19 (20%) of 93 BCT were described. The interventions of three studies were classified as ‘promising’. The most commonly used BCT comprised goal setting, action planning and social support. Five BCT were solely used in ‘promising’ interventions. Our review demonstrated that only 20% of BCT have been utilised, and those BCT that were used only in ‘promising’ physical activity interventions in adolescents and adults with chronic cardiorespiratory conditions were isolated.
Tunable trap depth for persistent luminescence by cationic substitution in Pr3+:K1−xNaxNbO3 perovskites
Authors: Li Liyi , Castaing Victor , Rytz Daniel , Sontakke Atul D. , Katayama Yumiko , Tanabe Setsuhisa , Peng Mingying , Viana Bruno
Published: October 2018

The development of efficient red‐emitting persistent phosphor is still an ongoing challenge. In the search of persistent materials in red range, Pr3+ is a good candidate owing to its transitions between 1D2 and 3H4 state at about 612 nm. In this paper, we investigated the red persistent properties of Pr3+‐doped perovskite oxide ABO3, (A: K, Na and B: Nb), which can be elaborated as large single crystal. KNbO3:Pr3+ appears to have weak photoluminescence and no persistent luminescence. However, the cationic substituted compounds K1−xNaxNbO3:Pr3+ (x = 0, 0.4, 0.5, 0.7 0.9, 1) exhibit intense persistent luminescence, which increases steadily with increase in Na content. We correlated persistence behavior with the position of Metal‐to‐Metal Charge Transfer (MMCT) band, which plays crucial role in tuning of the trap depth. The MMCT band position decreases with the addition of Na contents and the thermoluminescence peak shifts toward higher temperature indicating the formation of deeper traps. This is in good agreement with the enhancement of the persistent luminescence suggesting that a proper tailoring of MMCT is needed to design efficient Pr3+‐persistent phosphors with better performance. A detailed analysis on the trap depth, bandgap energy, and persistent luminescence properties is reported tuning the composition in the K1−xNaxNbO3:Pr powder.
Long non‐coding RNA MALAT1 mediates hypoxia‐induced pro‐survival autophagy of endometrial stromal cells in endometriosis
Authors: Liu Hengwei , Zhang Zhibing , Xiong Wenqian , Zhang Ling , Du Yu , Liu Yi , Xiong Xingao
Published: October 2018

Endometriosis is a common gynecological disease characterized by diminished apoptosis, sustained ectopic survival of dysfunctional endometrial cells. Hypoxia has been implicated as a crucial microenvironmental factor that contributes to endometriosis. It has been reported that long non‐coding RNA MALAT1 (lncRNA‐MALAT1) highly expressed in endometriosis and up‐regulated by hypoxia. Hypoxia may also induce autophagy, which might act as cell protective mechanism. However, the relationship between lncRNA‐MALAT1 and autophagy under hypoxia conditions in endometriosis remains unknown. In the present study, we found that both lncRNA‐MALAT1 and autophagy level were up‐regulated in ectopic endometrium from patients with endometriosis, and its expression level correlates positively with that of hypoxia‐inducible factor‐1α (HIF‐1α). In cultured human endometrial stromal cells, both lncRNA‐MALAT1 and autophagy were induced by hypoxia in a time‐dependent manner and lncRNA‐MALAT1 up‐regulation was dependent on HIF‐1α signalling. Our analyses also show that knockdown of lncRNA‐MALAT1 suppressed hypoxia induced autophagy. Furthermore, inhibiting autophagy with specific inhibitor 3‐Methyladenine (3‐MA) and Beclin1 siRNA enhanced apoptosis of human endometrial stromal cells under hypoxia condition. Collectively, our findings identify that lncRNA‐MALAT1 mediates hypoxia‐induced pro‐survival autophagy of endometrial stromal cells in endometriosis.
Retrospective analysis of medical costs and resource utilization for severe hypoglycemic events in patients with type 2 diabetes in Japan
Authors: Ikeda Yuika , Kubo Takekazu , Oda Eisei , Abe Machiko , Tokita Shigeru
Published: October 2018

Aims/Introduction

The present study aimed to describe hospital utilization and examine actual medical costs for severe hypoglycemic events in patients with type 2 diabetes mellitus in Japan.

Materials and Methods

Medical resource utilization associated with severe hypoglycemia was evaluated using a receipt database of acute‐care hospitals in Japan. Patients with type 2 diabetes treated with antihyperglycemic agents were included. Severe hypoglycemic events were identified and divided into two groups: with or without hospitalization. Total and attributable medical costs per event were calculated based on the actual medical treatment after severe hypoglycemic events. Attributable costs were estimated from the receipt codes directly associated with the treatment of severe hypoglycemia.

Results

In the hospitalized patients, the median length of hospital stay was 11 days, and the median total and attributable medical costs were ¥402,081 and ¥302,341, respectively. The majority of the hospitalized patients underwent a radiographic examination and general blood tests. Apart from the hospitalization costs, the costs associated with diagnosis accounted for 29.6% of the total medical costs. In the outpatients, 60.6% visited hospitals only once for the severe hypoglycemic event, whereas 11.4% visited hospitals daily for a week after the severe hypoglycemic event. The mean number of hospital visits of the outpatient after a severe hypoglycemic event was 2.7 ± 2.6 days. The median total and attributable medical costs were ¥265,432 and ¥4,628, respectively.

Conclusions

Significant medical resources are used for the treatment of severe hypoglycemic events of patients with type 2 diabetes in Japan.
Long‐term efficacy and safety results from an open‐label phase III study (UNCOVER‐J) in Japanese plaque psoriasis patients: impact of treatment withdrawal and retreatment of ixekizumab
Authors: Umezawa Y. , Torisu‐Itakura H. , Morisaki Y. , ElMaraghy H. , Nakajo K. , Akashi N. , Saeki H. ,   the Japanese Ixekizumab Study Group
Published: October 2018

Background

Long‐term management of moderate‐to‐severe psoriasis is usually discussed in terms of continuous administration; however, there are many situations in clinical practice where treatment may be withdrawn with subsequent retreatment.

Objective

To assess the clinical course after ixekizumab treatment withdrawal and retreatment, as well as the effectiveness of ixekizumab retreatment, in Japanese patients with plaque psoriasis.

Methods

This single‐arm, open‐label study (UNCOVER‐J; NCT01624233) comprised 78 patients with plaque psoriasis. After ixekizumab treatment (160‐mg loading dose, 80 mg every 2 weeks for the first 12 weeks, and then 80 mg every 4 weeks (IXE Q4W) until Week 52), 70 patients achieved a Psoriasis Area Severity Index (PASI)75 response at Week 52. These 70 patients withdrew from ixekizumab treatment from Weeks 52 to 100. Patients who relapsed (PASI ≤50) during the Treatment Withdrawal Period were retreated with IXE Q4W for 192 weeks.

Results

At Weeks 52, 76 and 100, PASI75 response rates were 100%, 26% and 7%; PASI90 response rates were 87%, 11% and 3%; and PASI100 response rates were 53%, 0% and 0%. After treatment withdrawal, 87% of patients relapsed; median time to relapse was 143 days. After 12 weeks of retreatment with IXE Q4W, 83% of relapsed patients achieved PASI75, 68% achieved PASI90 and 25% achieved PASI100; improvements were maintained up to 120 weeks of retreatment. Treatment‐emergent adverse events and serious adverse events were reported in 56% and 4% of patients during the Treatment Withdrawal Period, and in 88% and 14% of patients during the Retreatment Period.

Conclusion

In patients withdrawn from ixekizumab after achieving PASI75, approximately half relapsed within 5 months of withdrawal; however, most patients recaptured response within 12 weeks, and response was maintained for up to 120 weeks of retreatment.
Physical Activity and Association Between Frailty and All‐Cause and Cardiovascular Mortality in Older Adults: Population‐Based Prospective Cohort Study
Authors: Higueras‐Fresnillo Sara , Cabanas‐Sánchez Verónica , Lopez‐Garcia Esther , Esteban‐Cornejo Irene , Banegas José R. , Sadarangani Kabir P. , Rodríguez‐Artalejo Fernando , Martinez‐Gomez David
Published: October 2018

Objectives

To examine the separate and joint association between physical activity and frailty and long‐term all‐cause and cardiovascular disease (CVD) mortality in older adults.

Design

Population‐based prospective cohort study.

Setting

Cohort representative of the noninstitutionalized Spanish population.

Participants

Individuals aged 60 and older (N=3,896) in 2000–01.

Measurements

Participants reported their physical activity using a validated instrument, and frailty was ascertained using the Fatigue, low Resistance, limitation in Ambulation, Illness and weight Loss (FRAIL) scale. Those with 0 frailty criteria were considered to be robust, with 1 or 2 criteria to be prefrail, and with 3 of more criteria to be frail. Participants were followed until 2014 to identify all‐cause and CVD deaths. Associations were summarized using hazard ratios (HRs) and Cox regression after adjustment for main covariates.

Results

During a median 14 years of follow‐up, 1,801 total deaths occurred, 672 from CVD. Compared with being robust, the multivariate hazard ratio (95% confidence interval) for all‐cause mortality was 1.29 (1.14–1.45) in prefrail individuals, and 2.16 (1.82–2.58) in frail individuals (p‐trend <.001). Compared with being physically inactive, being physically active was associated with a statistically significant 18% (1–32%), 28% (16–39%) and 39% (17–55%) lower all‐cause mortality among robust, prefrail, and frail individuals, respectively (all p <.001). Compared with participants who were robust and physically active, those who were frail and inactive showed the highest all‐cause mortality 2.45 (95%CI: 1.95–3.06); however, the hazard ratio (95% confidence interval) for all‐cause mortality in frail individuals who were physically active was comparable to that in pre‐frail and inactive participants: 1.70 (1.32–2.19) and 1.56 (1.34–1.82), respectively. Mortality of prefrail active participants was similar to that of robust inactive participants. Results were similar for CVD mortality.

Conclusion

Physical activity might partly compensate for the greater mortality risk associated with frailty in old age. J Am Geriatr Soc 66:2097–2103, 2018.
SPRINT: Running in the Wrong Direction?
Authors: Clarfield A. Mark
Published: October 2018

See the Reply by Rich et al.
Reply to “SPRINT: Running in the Wrong Direction?”
Authors: Rich Michael W. , Ouslander Joseph G.
Published: October 2018

This letter comments on the letter by Mark A. Clarfield.
Likelihood of Sustaining an Injury in the Setting of Multiple Falls
Authors: Gill Thomas M. , Williams Christianna S.
Published: October 2018

Objectives

To evaluate the relationship between number of falls and risk of injury after a specific fall.

Design

Prospective cohort study.

Setting

Greater New Haven, Connecticut.

Participants

Probability sample of 1,103 community‐living persons aged 72 and older.

Measurements

Falls and fall‐related injuries were ascertained monthly for 3 years using a fall calendar and follow‐up telephone interviews.

Results

Of 606 participants with a fall, 164 (27.0%) had at least 1 fall with a serious injury, and 455 (75.1%) had at least 1 fall with any injury; mean number of falls was 2.6±2.3 (range 1–18), of falls with serious injury was 0.3±0.6 (range 0–4), and of falls with any injury was 1.4±1.4 (range 0–9). On a per‐participant basis, risk of serious injury and any injury increased progressively as the number of falls increased (P < .001). On a per‐fall basis, risk of serious injury and any injury increased from 1 to 2 falls but then decreased from 2 to 3 or 4 falls and from 3 or 4 to 5 or more falls, although these differences were not statistically significant. The results were consistent for women and men and for analyses that evaluated the proportion of falls with injuries.

Conclusion

In community‐living older persons, risk of injury from a specific fall did not differ as the number of falls increased. Falls appear to operate independently in terms of conferring risk of injury in the setting of multiple falls. J Am Geriatr Soc 67:119–123, 2019.
Black–White Marriages: The Moderating Role of Openness on Experience of Couple Discrimination and Marital Satisfaction
Authors: Baptist Joyce , Craig Brianna , Nicholson Bornell
Published: October 2018

This study examined how open communication between spouses may buffer against discrimination experienced by Black–White couples. Results from 178 couples analyzed using a combination of common‐fate and actor–partner interdependence models, indicated that for Black partners, marital satisfaction was not contingent on the level of openness when experiences of couple discrimination were low. When experiences of couple discrimination were high, levels of marital satisfaction were maintained among partners who reported high openness and reduced among partners who reported low openness. Moderation effects were not found for White partners. The results suggest that because Black partners are more aware of and sensitized to discrimination, White partners’ abilities to attune to their partners’ needs for support could help enhance their relationships.
Hardness of the habitual diet and its relationship with cognitive function among 70‐year‐old Japanese elderly: Findings from the SONIC Study
Authors: Okubo Hitomi , Murakami Kentaro , Inagaki Hiroki , Gondo Yasuyuki , Ikebe Kazunori , Kamide Kei , Masui Yukie , Arai Yasumichi , Ishizaki Tatsuro , Sasaki Satoshi , Nakagawa Takeshi , Kabayama Mai , Sugimoto Ken , Rakugi Hiromi , Maeda Yoshinobu ,   SONIC Study Group
Published: October 2018

Background

There is increasing evidence of causal links between poor mastication and cognitive impairment, but possible effects of dietary hardness, which clearly affects mastication, on cognitive function are unknown.

Objective

We investigated the hypothesis that hardness of the habitual diet would be associated with cognitive function among older Japanese adults.

Methods

The subjects of this cross‐sectional study were 635 Japanese community‐dwelling people aged 69‐71 years. The masticatory muscle activity required for the habitual diet was used to determine dietary hardness. Consumption of 38 foods was assessed by a validated, brief‐type, self‐administered diet history questionnaire. A published database was then used to estimate the masticatory muscle activity involved in the ingestion of these foods. The Japanese version of the Montreal Cognitive Assessment (MoCA‐J) was used for the measurement of cognitive function.

Results

The principal contributors to dietary hardness were cooked rice (28.0%), green leafy vegetables (5.1%), dried fish (4.9%), and pork and beef (4.6%). There was a positive association between dietary hardness and MoCA‐J score that was robust to adjustment for potential confounders (MoCA‐J score per 100‐unit increase in dietary hardness: β = 0.83 [95% CI: 0.08, 1.59], P = 0.03). These results did not change materially even after exclusion of subjects who reported substantial changes in their diet for any reason (β = 0.94 [95% CI: 0.02, 1.86], P = 0.04).

Conclusion

This preliminary cross‐sectional study suggests that dietary hardness might have a beneficial effect on cognitive function in older Japanese people. Further prospective studies with more accurate measurements are needed to confirm this finding.
Reduced folate carrier-mediated methotrexate transport in human distal lung epithelial NCl-H441 cells
Authors: Kawami Masashi , Honda Natsuko , Miyamoto Mioka , Yumoto Ryoko , Takano Mikihisa
Published: October 2018

Objectives

We had previously found that reduced folate carrier (RFC; SLC19A1) is mainly involved in an influx of transport of methotrexate (MTX), a folate analogue, using alveolar epithelial A549 cells. Therefore, we examined MTX uptake in NCl-H441 (H441) cells, another in vitro alveolar epithelial model, focusing on the localization of RFC in the present study.

Methods

Transport function of RFC in H441 cells was studied using [3H]MTX.

Key findings

The uptake of MTX was increased remarkably after pretreatment of the cell monolayer with ethylenediaminetetraacetic acid (EDTA) in H441 cells but not in A549 cells, indicating the contribution of the basolaterally located transporter. In addition, folic acid and thiamine monophosphate, RFC inhibitors, inhibited the uptake of MTX from the basolateral side of the H441 cells. In order to compare the function of RFC on the apical and basolateral sides of the cells, the uptake of MTX from each side was examined using a Transwell chamber. Intracellular MTX amounts from the basolateral side were found to be significantly higher than those from the apical side.

Conclusions

These findings suggest that the distribution of MTX in the lung alveolar epithelial cells may be mediated by basolaterally located RFC in alveolar epithelial cells.
Flavonoid composition, cellular antioxidant activity and (myelo)peroxidase inhibition of a Bryonia alba L. (Cucurbitaceae) leaves extract
Authors: Ielciu Irina , Mouithys-Mickalad Ange , Franck Thierry , Angenot Luc , Ledoux Allison , Păltinean Ramona , Cieckiewicz Ewa , Etienne Delphine , Tits Monique , Crişan Gianina , Frédérich Michel
Published: October 2018

Objectives

The aim of the present study consisted in the isolation of flavonoids from the leaves of Bryonia alba L. and evaluation of their antioxidant activity and inhibition on peroxidase-catalysed reactions.

Methods

Flavonoids were isolated by preparative HPLC-DAD and their structures were elucidated by MS and NMR. Inhibitory effect was tested by the horseradish peroxidase and the myeloperoxidase assays. Cellular antioxidant assays consisted in testing the inhibitory activity on the reactive oxygen species released upon activation of neutrophils freshly isolated ex vivo from equine blood and of human monocytes-derived macrophages in vitro. Whole organism toxicity was assessed on zebrafish larvae.

Key findings

Four flavonoids (lutonarin, saponarin, isoorientin and isovitexin) were isolated. The performed assays showed significant antioxidant activity and inhibition for the peroxidase-catalysed reactions. Absence of cellular and zebrafish toxicity was confirmed.

Conclusions

Bryonia alba L. leaves are particularly interesting for their flavonoids content and showed significant inhibitory effect on peroxidase-catalysed oxidation of substrates (Amplex Red and L012), as well as antioxidant/antiradical activity, proving that this species has a medicinal potential. Moreover, the present study highlights the absence of the toxicity of these leaves and offers though a novel perspective on the species, previously known as being toxic.
On Estimation and Inference in Heterogeneous Panel Regressions with Interactive Effects
Authors: Westerlund Joakim
Published: October 2018

Among the existing estimators of interactive effects (IEs) regressions, the common correlated effects (CCE) approach is probably the most popular. A major reason for this popularity is the generality of the approach. In fact, CCE is remarkably general in that it allows ample parameter heterogeneity without placing any restrictions on the true number of common factors. In the present paper, we show that this generality is not unique to CCE but that it is shared by a whole class of estimators. We characterize this class and show that it does not rely on the correct specification of the IEs. In spite of this, the estimators within the class are consistent and asymptotically normal under general conditions. This means that there is not just CCE but, in fact, many estimators to choose from, such as the fixed effects estimator.