bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of the distribution and scholarly output from National Institute of Academic Anaesthesia (NIAA) research grants
Authors: El‐Boghdadly K. , Docherty A. B. , Klein A. A.
Published: March 2018

The National Institute of Academic Anaesthesia (NIAA) was founded in 2008 to lead a UK strategy for developing academic anaesthesia. We aimed to assess the distribution of applications and quantify the academic returns of NIAA‐supported research grants, as this has hitherto not been analysed. We sought data on the baseline characteristics of all grant applicants and recipients. Every grant recipient from 2008 to 2015 was contacted to ascertain the status of their supported research projects. We also examined Google Scholar, Scopus® database and InCites Journal Citation Reports for citation, author and journal metrics, respectively. In total, 495 research project applications were made, with 150 grants being awarded. Data on 121 out of 150 (80.7%) grant awards, accounting for £3.5 million, were collected, of which 91 completed studies resulted in 140 publications and 2759 citations. The median (IQR [range]) time to first or only publication was 3 (2–4 [0–9]) years. The overall cost per publication was £14,970 (£7457–£24,998 [£2212–£73,755]) and the cost per citation was £1515 (£323–£3785 [£70–£36,182]), with 1 (0–2 [0–8]) publication and 4 (0–25 [0–265]) citations resulting per grant. The impact factor of journals in which publications arose was 4.7 (2.5–6.2 [0–47.8]), with the highest impact arising from clinical and basic science studies, particularly in the fields of pain and peri‐operative medicine. Grants were most frequently awarded to clinical and basic science categories of study, but in terms of specialty, critical care medicine and peri‐operative medicine received the greatest number of grants. Superficially, there seemed a geographical disparity, with 123 (82%) grants being awarded to researchers in England, London receiving 48 (32%) of these. However, this was in proportion to the number of grant applications received by country or city of application, such that there was no significant difference in overall success rates. There was no significant difference in productivity in terms of publications and citations from grants awarded to each city. The 150 grants were awarded to 107 recipients (identified as the most senior applicant for each grant), 27 of whom received ≥ two grants. Recipients had a median career total of 21 (8–76 [0–254]) publications and 302 (44–1320 [0–8167]) citations, with an h‐index of 8 (3–22 [0–54]). We conclude that a key determinant of grant success is simply applying. This is the first study to report the distribution and scholarly output of individual anaesthesia research grants, particularly from a collaborative body such as the NIAA, and can be used as a benchmark to further develop academic anaesthesia in the UK and beyond.
Rapid review shows that probiotics and fermented infant formulas do not cause d‐lactic acidosis in healthy children
Authors: Łukasik J , Salminen S , Szajewska H
Published: March 2018

Aim

Extensive ongoing research on probiotics and infant formulas raises a number of safety questions. One concern is the potential influence of d‐lactic acid‐containing preparations on the health of infants and children. The aim of this review was to summarise the available knowledge on the ingestion of d‐lactic acid‐producing bacteria, acidified infant formulas and fermented infant formulas as a potential cause of paediatric d‐lactic acidosis.

Methods

A Medline database search was performed in July 2017, with no restrictions on the language, article type or publication date. The 1715 search results were screened for clinical trials, review articles, case series and case reports of relevance to the topic.

Results

We identified five randomised controlled trials from 2005 to 2017 covering 544 healthy infants and some case reports and experimental studies. No clinically relevant adverse effects of d‐lactic acid‐producing probiotics and fermented infant formulas were described in healthy children. However, a harmless, subclinical accumulation of d‐lactate was theoretically possible. The only known cases of paediatric d‐lactic acidosis occurred in patients with short bowel syndrome or, historically, in infants fed with acidified formulas.

Conclusion

Our main finding was that probiotics and fermented formulas did not cause d‐lactic acidosis in healthy children.
Localised prostate cancer in elderly men aged 80–89 years, findings from a population‐based registry
Authors: Vatandoust Sina , Kichenadasse Ganessan , O'Callaghan Michael , Vincent Andrew D. , Kopsaftis Tina , Walsh Scott , Borg Martin , Karapetis Christos S. , Moretti Kim
Published: March 2018

Objectives

To investigate the rate of prostate cancer‐specific mortality (PCSM) and disease characteristics in patients diagnosed with localised prostate cancer at age 80–89 years in comparison with men diagnosed at age 70–79 years.

Patients and Methods

This is a retrospective study of data from the South Australian Prostate Cancer Clinical Outcomes Collaborative (SA‐PCCOC). Included were men diagnosed between 2005 and 2014, aged ≥70 years with no evidence of metastatic disease at presentation. Propensity score matching and competing risk Fine and Grey regression were used to assess the chance of treatment (curative vs non‐curative) and treatment effect on PCSM.

Results

Of the 1 951 eligible patients, 1 428 (76%) were aged 70–79 years and 460 (24%) were aged 80–89 years at diagnosis, with a median (interquartile range) age of 74 (72–76) and 83 (81–85) years, respectively. The 80–89 years group had higher Gleason scores and Prostate Specific Antigen (PSA) values (all P < 0.001) in comparison with the younger group. The 80–89 years group were less likely to be treated with curative treatment (odds ratio 0.12, 95% confidence interval 0.09–0.16; P < 0.001). The proportion of deaths attributable to prostate cancer was similar in both groups: 73 of 263 deaths (28%) in the 80–89 years group vs 97 of 310 deaths (31%) in the 70–79 years group. The risk of PCSM in individuals treated with curative intent was reduced in both groups.

Conclusions

The proportion of prostate cancer deaths was similar in both groups. These findings support carefully selected individualised management of elderly patients diagnosed with localised prostate cancer.
Violated Women, Reason, andLo Políticoin the Imaginary of the Guatemalan Nation
Authors: TORRES M. GABRIELA
Published: March 2018

Guatemalan newspapers are dappled with the spectre of women's violence and the bodily evidence of the military response that is typical for a woman's transgression of gender roles. Gendered representations of violence – so often repeated in the media – engender particular forms of political agency. This article explores how political violence is imagined with women's bodies and suggests that such violence is always built on pre‐existing cultural practices. It argues that gender categorization is paramount to constructing a modern Guatemalan nation that all too often works to exclude women as knowing participants in Lo Político.
THE CLEANSING EFFECT OF R&D SUBSIDIES
Authors: Haruyama Tetsugen
Published: March 2018

The paper develops a patent race model with a particular emphasis upon heterogeneity of competing R&D firms. It is demonstrated that R&D subsidies generate the cleansing effect
where relatively lower productivity firms drop out of the race and innovation accelerates due to expanded R&D investment by the remaining firms as well as new entrants with higher productivity than exiting firms.
EXAMINING THE STABILITY OF OKUN'S COEFFICIENT
Authors: Michail Nektarios A.
Published: March 2018

The stability of Okun's law coefficient in the United States from 1949 to 2015 is examined using a regression with GARCH errors in order to capture the volatility of the series. Rolling estimations suggest that taking the volatility of the series into account yields more stable results compared to the simple OLS estimation, irrespective of the specification (gap or growth model), the data frequency (monthly or quarterly), or the length of the rolling window. The results also suggest that the persistence of shocks became much more important in explaining contemporaneous volatility when data from the recent global financial crisis were incorporated. In contrast, the feedthrough of output shocks in next period's output volatility was more important in the past, and especially during the 1970s stagflation period, but has been declining since.
New technologies and the political economy of geomorphology
Authors: Inkpen Rob
Published: March 2018

New technologies enable high‐resolution monitoring techniques and the generation of big data and have been heralded as increasing the depth of our understanding of geomorphic phenomena. These technologies, however, also provide us with a convenient entry point into the increasingly constraining political economy of geomorphology. Building on the work of Stuart Lane and of critical physical geographers, this paper traces and examines the multiple roles that new technologies have played in constraining research questions and directing resources. Using the activity sphere framework outlined by David Harvey, the influence of new technologies can be traced around the spheres and their constraining of existing relations within academia and explanation identified.
Five‐year refractive changes in a rural Chinese adult population and its related factors: the Handan Eye Study
Authors: Li Shi‐Ming , Lin Caixia , Wan Yue , Cao Kai , Hao Jie , Zhang Ye , Hu Ailian , Wu Jian , Friedman David S , Wang Ningli ,   the Handan Eye Study Group
Published: March 2018

Importance

Provision of refractive changes is important to predict eye care needs for aging population.

Background

To provide 5‐year refractive changes in a rural Chinese adult population.

Design

Population‐based longitudinal study.

Participants

At baseline, 6830 subjects aged 30+ years took part in the Handan Eye Study. A total of 5394 of the 6323 survivors (85.3%) participated in the 5‐year follow‐up.

Methods

Ocular examinations including standardized refraction were performed according to the same protocol at both baseline and follow‐up.

Main Outcome Measures

Change in spherical equivalent (SE; sphere + 1/2 cylinder) and astigmatism.

Results

A total of 3970 right eyes were available for refraction analysis. The 5‐year change in SE for all subjects was +0.17 diopters (D), and was −0.21D, +0.14D, +0.40D and +0.08D for subjects aged 30–39, 40–49, 50–59, and 60–69 years, respectively. By binary regression analysis, myopic shift was associated with severe nuclear opacity, longer axil length, diabetes and large change of lens power, while hyperopic shift was associated with older age and ocular hypertension at baseline. There was a mean change of 0.18D in the against‐the‐rule astigmatism.

Conclusions and Relevance

There was a myopic shift for those 30–39 years old and a hyperopic shift from 40 to 69 years old in a rural Chinese adult population. Those with severe nuclear opacity, longer axil length, diabetes and large change of lens power tended to have a myopic shift, while those being older and having ocular hypertension at baseline were prone to have a hyperopic shift. There was also an increase in against‐the‐rule astigmatism in this population.
Cladistics and insular evolution, an unfortunate marriage? Another tangle in the Deinogalerix analysis of Borrani et al. (2017)
Authors: van den Hoek Ostende Lars W.
Published: March 2018

Insular taxa, such as the late Miocene giant erinaceid Deinogalerix and the insular hominin Homo floresiensis, display a surprisingly primitive placement in cladistic analyses of their respective groups. This has led to speculations of early dispersal onto islands, not corroborated by biogeographical evidence. Insular evolution is notorious for vast phenotypic changes in at least part of the island fauna. These changes encompass typical apomorphies, but, as they may also include evolutionary reversals, a parsimony‐based tree will inevitably yield a more basic position in cladograms. Therefore, we need to be cautious in drawing hasty conclusions from phylogenetic trees including insular taxa. Scrutiny is required to monitor possible evolutionary reversals and scenarios should be tested against biogeography to test their viability.
School‐based physical therapy services and student functional performance at school
Authors: Mccoy Sarah Westcott , Effgen Susan K , Chiarello Lisa A , Jeffries Lynn M , Villasante Tezanos Alejandro G
Published: March 2018

Aim

We explored relationships of school‐based physical therapy to standardized outcomes of students receiving physical therapy.

Method

Using a practice‐based evidence research design, School Function Assessment (SFA) outcomes of 296 students with disabilities (mean age 7y 4mo [standard deviation 2y]; 166 males, 130 females), served by 109 physical therapists, were explored. After training, therapists completed 10 SFA scales on students at the beginning and end of the school year. Therapists collected detailed weekly data on services (activities, interventions, types, student participation) using the School‐Physical Therapy Interventions for Pediatrics (S‐PTIP) system. Stepwise linear regressions were used to investigate S‐PTIP predictors of SFA outcomes.

Results

Predictors of SFA section outcomes varied in strength, with the coefficient of determination (R2) for each outcome ranging from 0.107 to 0.326. Services that correlated positively with the SFA outcomes included mobility, sensory, motor learning, aerobic/conditioning, functional strengthening, playground access interventions, and higher student participation during therapy (standardized β=0.11–0.26). Services that correlated negatively with the SFA outcomes included providing services within student groups, within school activity, with students not in special education, during recreation activities, and with positioning, hands‐on facilitation, sensory integration, orthoses, and equipment interventions (standardized β=−0.14 to −0.22).

Interpretation

Consideration of outcomes is prudent to focus services. Overall results suggest we should emphasize active mobility practice by using motor learning interventions and engaging students within therapy sessions.

What this paper adds

No specific interventions predicted positively on all School Function Assessment (SFA) outcomes.

Active movement practice seems related to overall better SFA outcomes.

Active mobility practice improved SFA participation, mobility, recreation, and activities of daily living.

Engaging students in therapy activities and interventions improved outcomes.
Chronic pain: a source of disability in its own right?
Authors: McGuire Brian E , Lydon Helena K
Published: March 2018

This commentary is on the original article by de la Vega et al. on pages 596–601 of this issue.
Baseline characteristics and enrichment results from the SONAR trial
Authors: Heerspink Hiddo J.L. , Andress Dennis L. , Bakris George , Brennan John J. , Correa‐Rotter Ricardo , Hou Fan Fan , Kitzman Dalane W. , Kohan Donald , Makino Hirofumi , McMurray John , Perkovic Vlado , Tobe Sheldon , Wigderson Melissa , Yi Tingting , Parving Hans‐Henrik , de Zeeuw Dick
Published: March 2018

Aim

The SONAR trial uses an enrichment design based on the individual response to the selective endothelin receptor antagonist atrasentan on efficacy (the degree of the individual response in the urinary albumin‐to‐creatinine ratio [UACR]) and safety/tolerability (signs of sodium retention and acute increases in serum creatinine) to assess the effects of this agent on major renal outcomes. The patient population and enrichment results are described here.

Methods

Patients with type 2 diabetes with an estimated glomerular filtration rate (eGFR) within 25 to 75 mL/min/1.73 m2 and UACR between 300 and 5000 mg/g were enrolled. After a run‐in period, eligible patients received 0.75 mg/d of atrasentan for 6 weeks. A total of 2648 responder patients in whom UACR decreased by ≥30% compared to baseline were enrolled, as were 1020 non‐responders with a UACR decrease of <30%. Patients who experienced a weight gain of >3 kg and in whom brain natriuretic peptide exceeded ≥300 pg/mL, or who experienced an increase in serum creatinine >20% (0.5 mg/dL), were not randomized.

Results

Baseline characteristics were similar for atrasentan responders and non‐responders. Upon entry to the study, median UACR was 802 mg/g in responders and 920 mg/g in non‐responders. After 6 weeks of treatment with atrasentan, the UACR change in responders was −48.8% (95% CI, −49.8% to −47.9%) and in non‐responders was −1.2% (95% CI, −6.4% to 3.9%). Changes in other renal risk markers were similar between responders and non‐responders except for a marginally greater reduction in systolic blood pressure and eGFR in responders.

Conclusions

The enrichment period has successfully identified a population with a profound UACR reduction without clinical signs of sodium retention in whom a large atrasentan effect on clinically important renal outcomes is possible. The SONAR trial aims to establish whether atrasentan confers renal protection.
Institutional design of voluntary sustainability standards systems: Evidence from a new database
Authors: Fiorini Matteo , Hoekman Bernard , Jansen Marion , Schleifer Philip , Solleder Olga , Taimasova Regina , Wozniak Joseph
Published: March 2018

Voluntary sustainability standards (VSS) have become a significant element of the governance of international trade and production. Even though VSS are not mandatory (required by law), in practice they are often necessary for producers to participate in global value chains. Finally, VSS are often considered costly for producers. This article provides an overview of the global VSS landscape, and addresses the following questions: how producer‐friendly are VSS, and how do their practices towards producers vary with relevant features of VSS institutional design? The analysis is empirical, and it is based on a data collection project called Standards Map (SM), launched in 2011 by the International Trade Centre (ITC). The analysis covers a population of up to 180 VSS. This large‐n approach allows for a macro‐perspective which complements the existing literature characterized by micro‐level studies. Our analysis documents a significant heterogeneity in producer‐friendly practices across VSS. We find that participation in meta‐governance organizations (such as ISEAL full membership) is strongly associated with producer‐friendly practices. Moreover, the location of headquarters in Organisation for Economic Co‐operation and Development (OECD) member countries, the engagement of buyers in the board or management of the scheme and the influence of producers in decision‐making are also positively associated with our measures of producer friendliness, although these relationships are found to be less robust. The dimension of VSS we have focused on is just one element of the information contained in the SM database. Other relevant dimensions of standards systems, such as the structure of requirements, their product scope—and other aspects of institutional design, such as verification procedures, stakeholder engagement, harmonization or convergence vs. competition between different schemes—can all be analysed using the database. We hope the descriptive analysis undertaken in this article will help the research community to make better use of this source of information.
Natural history of myocardial deformation in children, adolescents, and young adults exposed to anthracyclines: Systematic review and meta‐analysis
Authors: Tuzovic Mirela , Wu Pei‐Tzu , Kianmahd Samuel , Nguyen Kim‐Lien
Published: March 2018

Objective

Anthracyclines are widely used to treat solid and hematologic malignancies, but are known to cause cardiotoxicity. As more childhood cancer survivors reach adulthood due to improvements in oncologic treatments, they become susceptible to late and progressive anthracycline‐induced cardiotoxicity. Nonetheless, diagnostic criteria for early detection of cardiac dysfunction are not well defined in children, adolescent, and young adults (CAYA, ages 1–40 years). We present a natural history of the changes in myocardial deformation in CAYA patients after anthracycline therapy.

Methods

We performed a literature review search between 2001 and 2016 using PubMed with the following search terms: strain (or deformation), torsion (or twist), children (or adolescent or young adult), cardiotoxicity (or dysfunction), and anthracyclines (or doxorubicin). A total of 23 articles were reviewed. Fourteen articles were incorporated in the meta‐analysis.

Results

Strain abnormalities are observed at both short‐term and long‐term follow‐up. Global longitudinal strain (GLS) abnormalities are common during or early after chemotherapy, whereas changes in global circumferential strain (GCS) are more significant and consistent on long‐term follow‐up. Although global radial strain and torsional parameters are also often abnormal late after chemotherapy, there are few studies evaluating these parameters.

Conclusion

There are significant abnormalities in GLS and GCS following anthracycline therapy acutely and late after treatment. The prognostic value of these strain abnormalities warrants further investigation.
Indirubin and NAD+ prevent mitochondrial ischaemia/reperfusion damage in fatty livers
Authors: Teodoro João Soeiro , Varela Ana Teresa , Duarte Filipe Valente , Gomes Ana Patrícia , Palmeira Carlos Marques , Rolo Anabela Pinto
Published: March 2018

Background

Fatty livers are considerably more susceptible to acute stressors, such as ischaemia/reperfusion (I/R). As the incidence of I/R is high due to surgical events and some pathologies, there is an urgent need to find strategies against I/R injury (I/RI) in fatty livers. We postulate that an acute pretreatment with indirubin‐3′‐oxime (Ind) or NAD+ prevents mitochondrial dysfunction associated with warm I/RI in fatty livers.

Materials and Methods

Zucker fatty rats were subjected to warm ischaemia and 12 hours of reperfusion. Ind or NAD+ was administered in the hepatic artery 30 minutes before ischaemia. Hepatic mitochondrial isolation was performed, and functional assays as well as molecular analysis were performed.

Results

Pretreatment decreased markers of liver injury while preserving mitochondrial cytochrome c content, which is related to the prevention of calcium‐induced mitochondrial permeability transition (mPT), the decline in mitochondrial respiratory state 3 and ATP content. The generation of reactive oxygen species (ROS) was also diminished. Inhibition of GSK‐3ß by Ind resulted in the prevention of cyclophilin‐D (CypD) phosphorylation, unabling it to bind to the adenine nucleotide translocator (ANT), thus, preventing mPT induction. Furthermore, deacetylation of CypD at Lys residue by sirtuin 3 (SIRT3) caused its dissociation from ANT, contributing to an increase in mPT threshold in NAD+‐pretreated animals.

Conclusions

Pretreatment with Ind or NAD+ protects fatty livers by maintaining mitochondrial calcium homoeostasis, thus, preserving mitochondrial function and energetic balance. As such, CypD might be a new protective target against I/RI in fatty livers.
The start of a new wave: Developments in proteasome inhibition in multiple myeloma
Authors: Yong Kwee , Gonzalez‐McQuire Sebastian , Szabo Zsolt , Schoen Paul , Hajek Roman
Published: March 2018

Multiple myeloma (MM) accounts for 10% of hematological cancers. Stem cell transplantation remains the cornerstone of first‐line treatment for eligible patients, but historically, pharmaceutical treatment options for MM have been limited. The proteasome was identified as a target for MM therapy in the early 2000s and, in 2004, the boronic acid proteasome inhibitor bortezomib gained European approval. Bortezomib now plays a major role in MM treatment, but the duration of its use can be limited by toxicities such as peripheral neuropathy and the development of resistance. A new generation of proteasome inhibitors has since entered the treatment landscape: carfilzomib, an epoxyketone‐based agent with a distinct mode of action, high clinical efficacy, and lower levels of peripheral neuropathy compared with bortezomib, received approval in 2015 for use in patients with relapsed and/or refractory MM (RRMM). Ixazomib, a second‐generation, orally administered, boronic acid proteasome inhibitor, has also been approved for use in patients with RRMM. In just over a decade, proteasome inhibitor‐based regimens have become an integral component of MM treatment; with more proteasome inhibitors in development, this remains a vibrant research area with potential to improve the lives of patients with MM in the years to come.
How ecology shapes exploitation: a framework to predict the behavioural response of human and animal foragers along exploration–exploitation trade‐offs
Authors: Monk Christopher T. , Barbier Matthieu , Romanczuk Pawel , Watson James R. , Alós Josep , Nakayama Shinnosuke , Rubenstein Daniel I. , Levin Simon A. , Arlinghaus Robert
Published: April 2018

Understanding how humans and other animals behave in response to changes in their environments is vital for predicting population dynamics and the trajectory of coupled social‐ecological systems. Here, we present a novel framework for identifying emergent social behaviours in foragers (including humans engaged in fishing or hunting) in predator–prey contexts based on the exploration difficulty and exploitation potential of a renewable natural resource. A qualitative framework is introduced that predicts when foragers should behave territorially, search collectively, act independently or switch among these states. To validate it, we derived quantitative predictions from two models of different structure: a generic mathematical model, and a lattice‐based evolutionary model emphasising exploitation and exclusion costs. These models independently identified that the exploration difficulty and exploitation potential of the natural resource controls the social behaviour of resource exploiters. Our theoretical predictions were finally compared to a diverse set of empirical cases focusing on fisheries and aquatic organisms across a range of taxa, substantiating the framework's predictions. Understanding social behaviour for given social‐ecological characteristics has important implications, particularly for the design of governance structures and regulations to move exploited systems, such as fisheries, towards sustainability. Our framework provides concrete steps in this direction.
Demand for neurological services in Central Eastern Europe: a 10‐year national survey in Hungary
Authors: Oberfrank F. , Ajtay A. , Bereczki D.
Published: March 2018

Background and purpose

In order to plan neurological capacities at a national level for the next decade, the current use of neurological services should be evaluated. We analyzed the utilization of neurological services in Hungary, a country with a single‐payer health insurance system covering the whole population.

Methods

We created a database from medical reports submitted to the National Health Insurance Fund from all hospitals and outpatient services between 2004 and 2013. The number of subjects presenting to the neurological healthcare system and their major diagnoses by 10th International Classification of Diseases categories were analyzed. The overall healthcare service utilization of these patients was also estimated.

Results

Of the 10 million inhabitants, 2.9 million people used an inpatient or outpatient neurological service at least once over the 10‐year period. Annually, 1% of the population was admitted to neurological inpatient wards and 6% of the population used some neurological outpatient service. Major reasons for using neurological services were: cerebrovascular diseases (I60–I69; 1.2 million patients), episodic and paroxysmal disorders (G40–G47; 1.3 million patients) and general symptoms and signs (R50–R56; 1.3 million patients). The 2.9 million people had 12.7 million hospital admissions to any ward and 365.7 million outpatient visits to any specialist during the 10 years.

Conclusions

The demand for neurological services is high in Hungary; close to 30% of the population used an inpatient or outpatient neurological service at least once during this 10‐year period. Results from this project provide data for international comparisons and help to ensure better informed and more focused resource allocation.
Dose optimization of tacrolimus with therapeutic drug monitoring and CYP3A5 polymorphism in patients with myasthenia gravis
Authors: Chen D. , Hou S. , Zhao M. , Sun X. , Zhang H. , Yang L.
Published: April 2018

Background and purpose

Tacrolimus is beneficial for treatment of myasthenia gravis (MG) and has a narrow therapeutic range. Therefore, therapeutic drug monitoring is essential for tacrolimus to optimize dosage and prevent adverse reactions. However, no studies have explored the factors influencing tacrolimus blood concentration in patients with MG. Thus, we aimed to analyze these factors and discuss how to optimize tacrolimus dosage for MG treatment.

Methods

Data regarding clinical characteristics, therapeutic drugs and adverse reactions of patients with MG who received tacrolimus were collected from 2013 to 2015 at Beijing Hospital. Tacrolimus whole‐blood concentrations were measured by chemiluminescent microparticle immunoassay and CYP3A5*3 gene polymorphism was detected by digital fluorescence molecule hybridization fluorescence. Regression analysis was applied to analyze the factors influencing blood concentrations and adverse reactions.

Results

It was shown that there was a correlation between concentration and dosage. Furthermore, co‐administration of proton pump inhibitor and clarithromycin and CYP3A5*3 gene polymorphism could significantly increase the tacrolimus whole‐blood levels. Adverse reactions were related to blood concentration, CYP3A5 genetic polymorphisms and combined medication though logistic regression analysis.

Conclusions

The concentration of tacrolimus is affected by many factors. Therapeutic drug monitoring and detection of CYP3A5 gene polymorphism was essential for dosage optimization in patients with MG.
Common data elements for epilepsy mobile health systems
Authors: Goldenholz Daniel M. , Moss Robert , Jost David A. , Crone Nathan E. , Krauss Gregory , Picard Rosalind , Caborni Chiara , Cavazos Jose E. , Hixson John , Loddenkemper Tobias , Salazar Tracy Dixon , Lubbers Laura , Harte‐Hargrove Lauren C. , Whittemore Vicky , Duun‐Henriksen Jonas , Dolan Eric , Kasturia Nitish , Oberemk Mark , Cook Mark J. , Lehmkuhle Mark , Sperling Michael R. , Shafer Patricia O.
Published: March 2018

Objective

Common data elements (CDEs) are currently unavailable for mobile health (mHealth) in epilepsy devices and related applications. As a result, despite expansive growth of new digital services for people with epilepsy, information collected is often not interoperable or directly comparable. We aim to correct this problem through development of industry‐wide standards for mHealth epilepsy data.

Methods

Using a group of stakeholders from industry, academia, and patient advocacy organizations, we offer a consensus statement for the elements that may facilitate communication among different systems.

Results

A consensus statement is presented for epilepsy mHealth CDEs.

Significance

Although it is not exclusive, we believe that the use of a minimal common information denominator, specifically these CDEs, will promote innovation, accelerate scientific discovery, and enhance clinical usage across applications and devices in the epilepsy mHealth space. As a consequence, people with epilepsy will have greater flexibility and ultimately more powerful tools to improve their lives.
Nouveau signalement de Hypocryphalus scabricollis (Eichhoff, 1878) en Tunisie, un ravageur émergent sur figuier (Ficus carica L.)
Authors: Gaaliche B. , Ben Abdelaali N. , Mouttet R. , Ben Halima‐Kamel M. , Hajlaoui M. R.
Published: March 2018

Hypocryphalus scabricollis (Eichhoff) (Coleoptera, Curculionidae, Scolytinae) est un nouveau ravageur observé sur le figuier (Ficus carica L.). Les dégâts néfastes observés sur cette plante hôte en Tunisie sont décrits et illustrés. Cet article décrit l'identification morphologique de l'espèce et donne des informations sur la biologie du ravageur et les recommandations initiales pour son contrôle. Ceci est un nouveau signalement pour la Tunisie.
A guide to studying human dermal adipocytes in situ
Authors: Nicu Carina , Pople Jennifer , Bonsell Laura , Bhogal Ranjit , Ansell David M. , Paus Ralf
Published: March 2018

Dermal white adipose tissue (DWAT) is a main component of human skin, composed of individual lipid‐laden mesenchymal cells known as dermal adipocytes (DAs). Besides their well‐known role in lipid storage and release, DAs also promote skin immunity, wound healing and hair follicle cycling and are important players in cutaneous neuroendocrinology. The ever‐growing insights into DWAT functions, albeit mostly in mice, have invited speculation that it may be involved in multiple skin diseases ranging from fibrosis to alopecia and psoriasis, thus designating human DWAT a clinically relevant, but as yet insufficiently investigated skin compartment. Therefore, this practical, user‐friendly guide aims to introduce the techniques available to study human DWAT in situ and ex vivo, including immunohistochemistry, immunofluorescence microscopy and analysis via quantitative immunohistomorphometry. Here, we provide information on a collection of stains comprising pre‐adipocyte (Pref1) and mature adipocyte markers (Perilipin1, Caveolin1), as well as various lipid (OilRedO, BODIPY) and histochemical stains (H&E, trichrome) available for use on human DWAT. We offer the reader guidelines on fixing, processing and staining human DAs and highlight caveats and solutions to common problems that one may encounter when studying this fascinating skin compartment. We also suggest standard methods for conducting quantitative immunohistomorphometry on human DWAT and its individual adipocytes to quantify cell size, number, lipid content and fluorescence intensity of adipose‐specific markers. Finally, we briefly introduce in situ hybridization, transmission electron microscopy and essentials of magnetic resonance imaging imaging as additional tools for instructively interrogating this largest, but still least‐known compartment of human skin.
The Nem1/Spo7–Pah1/lipin axis is required for autophagy induction after TORC1 inactivation
Authors: Rahman Muhammad Arifur , Mostofa Md. Golam , Ushimaru Takashi
Published: March 2018

Autophagy is a process that requires intense membrane remodeling and consumption. The nutrient‐responsive TORC1 (target of rapamycin complex 1) kinase regulates autophagy. However, how TORC1 controls autophagy via lipid/membrane biogenesis is unknown. TORC1 regulates the function of yeast phosphatidate phosphatase lipin Pah1 via the Nem1/Spo7 phosphatase complex. Here, we show that the Nem1/Spo7–Pah1 axis is required for autophagy induction after TORC1 inactivation and survival during starvation. Furthermore, this axis was critical for nucleophagy (both micronucleophagy and macronucleophagy) and was required for proper localization of micronucleophagy factor Nvj1 and macronucleophagy receptor Atg39. This study indicated that the Nem1/Spo7–Pah1 axis controlled by TORC1 is a critical branch for autophagy induction in nutrient starvation conditions.
Cysteine dioxygenase is essential for mouse sperm osmoadaptation and male fertility
Authors: Asano Atsushi , Roman Heather B. , Hirschberger Lawrence L. , Ushiyama Ai , Nelson Jacquelyn L. , Hinchman Meleana M. , Stipanuk Martha H. , Travis Alexander J.
Published: March 2018

Sperm entering the epididymis are immotile and cannot respond to stimuli that will enable them to fertilize. The epididymis is a highly complex organ, with multiple histological zones and cell types that together change the composition and functional abilities of sperm through poorly understood mechanisms. Sperm take up taurine during epididymal transit, which may play antioxidant or osmoregulatory roles. Cysteine dioxygenase (CDO) is a critical enzyme for taurine synthesis. A previous study reported that male CDO−/− mice exhibit idiopathic infertility, prompting us to investigate the functions of CDO in male fertility. Immunoblotting and quantitative reverse transcription‐polymerase chain reaction analysis of epididymal segments showed that androgen‐dependent CDO expression was highest in the caput epididymidis. CDO−/− mouse sperm demonstrated a severe lack of in vitro fertilization ability. Acrosome exocytosis and tyrosine phosphorylation profiles in response to stimuli were normal, suggesting normal functioning of pathways associated with capacitation. CDO−/− sperm had a slight increase in head abnormalities. Taurine and hypotaurine concentrations in CDO−/− sperm decreased in the epididymal intraluminal fluid and sperm cytosol. We found no evidence of antioxidant protection against lipid peroxidation. However, CDO−/− sperm exhibited severe defects in volume regulation, swelling in response to the relatively hypo‐osmotic conditions found in the female reproductive tract. Our findings suggest that epididymal CDO plays a key role in post‐testicular sperm maturation, enabling sperm to osmoregulate as they transition from the male to the female reproductive tract, and provide new understanding of the compartmentalized functions of the epididymis.
A spidroin‐derived solubility tag enables controlled aggregation of a designed amyloid protein
Authors: Sarr Médoune , Kronqvist Nina , Chen Gefei , Aleksis Rihards , Purhonen Pasi , Hebert Hans , Jaudzems Kristaps , Rising Anna , Johansson Jan
Published: March 2018

Amyloidogenesis is associated with more than 30 diseases, but the molecular mechanisms involved in cell toxicity and fibril formation remain largely unknown. The inherent tendency of amyloid‐forming proteins to aggregate renders expression, purification, and experimental studies challenging. NT* is a solubility tag derived from a spider silk protein that was recently introduced for the production of several aggregation‐prone peptides and proteins at high yields. Herein, we investigate whether fusion to NT* can prevent amyloid fibril formation and enable controlled aggregation for experimental studies. As an example of an amyloidogenic protein, we chose the de novo‐designed polypeptide β17. The fusion protein NT*‐β17 was recombinantly expressed in Escherichia coli to produce high amounts of soluble and mostly monomeric protein. Structural analysis showed that β17 is kept in a largely unstructured conformation in fusion with NT*. After proteolytic release, β17 adopts a β‐sheet conformation in a pH‐ and salt‐dependent manner and assembles into amyloid‐like fibrils. The ability of NT* to prevent premature aggregation and to enable structural studies of prefibrillar states may facilitate investigation of proteins involved in amyloid diseases.
Community activities predict disability and mortality in community‐dwelling older adults
Authors: Okura Mika , Ogita Mihoko , Yamamoto Miki , Nakai Toshimi , Numata Tomoko , Arai Hidenori
Published: March 2018

Aim

With aging, it is important to maintain older community dwellers’ regular engagement with familiar community activities (CA) engaged in close to home to protect them from frailty. Thus, the present study aimed to examine whether CA items or CA score were associated with mortality or the need for care under the new long‐term care insurance service requirements over 3 years among community‐dwelling older Japanese adults.

Methods

We analyzed cohort data for older adults from a prospective cohort study in Kami town, Japan. The response rate to the self‐reported questionnaire was 94.3% (n = 5094), and we followed these participants for 3 years. Our final sample comprised 5076 older adults. Missing data were filled in using multiple imputation. We used seven items to assess CA: (i) volunteer activity; (ii) regional activity related to the neighborhood; (iii) visiting friends; (iv) hobbies or favorite lessons; (v) earning an income; (vi) farm work and growing vegetables; and (vii) shopping daily by oneself. The Kihon Checklist and new long‐term care insurance service certifications were used as the frailty screening and disability indices, respectively.

Results

During the follow‐up survey, 705 participants obtained new long‐term care insurance service certifications and 262 died. Using the receiver operating characteristic curve, the desirable cut‐off of the CA score to predict disability and mortality was at least two items for all elderly age groups in rural areas.

Conclusions

CA items and CA score could predict disability and mortality in community‐dwelling older adults in Japanese rural areas. Therefore, it is recommended that older adults from all age groups participate in CA. Geriatr Gerontol Int 2018; 18: 1114–1124.
Employment Growth by Firm Size During the Recent Crisis in Italy: A Multifactor Partitioning Analysis
Authors: Bianchi Annamaria , Biffignandi Silvia
Published: March 2018

The effects on employment growth in firms, grouped by size class, of the economic crisis that began in 2008 are analysed using multifactor partitioning (MFP). Italy's employment growth is decomposed into four explanatory factors: the stage in the business cycle; the effect of firm size; industry composition; and regional distribution; together with the interactions among these four effects. The interpretation of these effects is facilitated by the introduction within the MFP framework of a new decomposition of several key elements. The results show that the adopted approach and the suggested decompositions are useful to study the effect of size on employment change. This effect is found to be negative only for micro units (with less than 10 employees). For the other classes, it is positive. The observed negative changes in these classes are mainly due to the business cycle and an unfavourable industrial composition.
A Method to Create a Horizontal Resistance Layer by Injection of a Viscous Fluid: PLAID
Authors: de Lange W.J. , Vink J.P.M.
Published: March 2018

We present a method to create a horizontal resistance layer at desired depth below soil surface to decrease seepage over a relatively large area. The layer is produced in a continuous process by means of numerous temporary screens of wells. Between each pair of screens groundwater flow is forced in horizontal direction. In the center of such flow, along virtual parallel flow lines, a chemical, viscous and dense fluid is injected that produces a clogging substance within several hours. The impact of density is overcome by the forced flow between screens. The impact of viscosity on the flow distribution is handled by adaptation of the fluxes and heads at the filters in the screens. The resulting procedure includes multistep injection and is supported by model simulations. Though a small‐scale proof of concept has been successful, the composition of the optimal chemical mixture needs further research.
Complex influence of climate on the distribution and body size of an Alpine species
Authors: Baroni Daniele , Masoero Giulia
Published: March 2018

Alpine species with a limited distribution can act as sentinels of climate change, but first we have to identify their climate‐sensitive traits. Here, we adopted a multi‐level approach to define the influence of climate on the geographical distribution and body size of a steno‐endemic Alpine grasshopper, theStenobothrus ursulaeNadig, 1986.

We built a species distribution model (SDM) with the following climatic predictors: precipitation seasonality, precipitation of the wettest month, mean temperature of the driest quarter and isothermality. The model provides a satisfactory representation of the species geographical range, but it also identifies areas suitable in terms of climate in which the species was not found. Therefore, we suggest that climatic and geographic barriers combined with a poor dispersal ability might have limited its distribution.

We measured 309 individuals collected across the whole geographical range. Our results show that increasing elevation was linked both to a decline inS. ursulaebody length (converse Bergmann's rule) and to a decline in sexual size dimorphism (converse Rensch's rule). We demonstrate also that the same climatic predictors that describe the species distribution affect its morphological variation.

Our results suggest that climate affects this species distribution and body size with opposite effects: suitable climatic conditions are found at high elevations, and the fitness‐related trait (i.e. body size) declines with elevations. In the future, distribution and/or morphology of the species might change in order to successfully cope with the changing climate, but its very limited dispersal ability constitutes an issue of concern.
Clinical and dermoscopic response predictors in psoriatic patients undergoing narrowband ultraviolet B phototherapy: results from a prospective study
Authors: Errichetti Enzo , Stinco Giuseppe
Published: March 2018

Background

Although disease severity, gender, body weight, and previous treatments have all been reported to affect clinical response of psoriasis vulgaris to narrowband ultraviolet B (NB‐UVB) therapy, little information about possible local (lesional) influencing factors is available.

Objective

To assess correlations between clinical/dermoscopic findings of psoriatic plaques and therapeutic response to NB‐UVB phototherapy in order to find positive and/or negative response predictor factors to such a treatment.

Methods

For each target lesion, we calculated local psoriasis severity index and assessed dermoscopic findings at the baseline. After 8 weeks of treatment, we evaluated clinical improvement of each lesion, correlating the therapeutic outcome with initial clinical and dermoscopic features.

Results

Ninety‐eight target lesions from 27 patients were included in the study. After 8 weeks of therapy, 31 lesions experienced no/limited improvement, while partial response was observed in 40 plaques and optimal response in 27 lesions. Regarding clinical variables, we found an association between poor therapeutic outcomes and both legs localization and more marked lesion scaling/infiltration. Similarly, globular vessels on dermoscopy were more commonly associated with no/limited response as well as lesions localized on the legs, particularly those showing treatment resistance. Conversely, the presence of dotted vessels carried a higher probability for getting improvement.

Conclusion

Therapeutic response of psoriasis vulgaris to NB‐UVB treatment may be negatively affected by local clinical factors, that is, significant scaling/infiltration and legs localization, and dermoscopy may be useful in highlighting possible response predictors, with globular and dotted vessels associated with bad and good outcomes, respectively.