bluuebunny/crossref_metadata_2025 huggingface dataset:
FUNCTIONAL AND ANATOMICAL OUTCOMES OF CHOROIDAL NEOVASCULARIZATION COMPLICATING BEST1-RELATED RETINOPATHY
Authors: Khan Kamron N. , Mahroo Omar A. , Islam Farrah , Webster Andrew R. , Moore Anthony T. , Michaelides Michel
Published: October 2016

Purpose:

To describe the presenting features and functional outcomes in a series of patients with choroidal neovascular membrane complicating BEST1-related retinopathy (Best disease and autosomal recessive bestrophinopathy).

Methods:

Retrospective review of consecutive cases at a tertiary care eye hospital. Patients were identified retrospectively over an 11-year period. Records were reviewed to extract demographic as well as functional and anatomical outcome data.

Results:

Fourteen eyes of 12 patients were identified (11 Best disease and 1 autosomal recessive bestrophinopathy). Median follow-up was 2.8 years (range 0.8–6). The median age at choroidal neovascular membrane discovery was 15.5 years (range 6–72). Choroidal neovascular membranes were active early in the disease course before vitelliruption. Seven eyes were treated with intravitreal bevacizumab, 7 eyes were monitored by observation alone. On average, patients required a single treatment (median = 1, range 1–10). The median gain in visual acuity was greater in the treated versus the observed group—0.46 versus 0.17 decimalized units of Snellen acuity, respectively (P < 0.05 Mann–Whitney U test). Although a significant reduction in central macular thickness was evident in both groups, 150 μm (treated) and 104 μm (observed), active treatment was not associated with greater thinning than observation (P > 0.05 Mann–Whitney U test).

Conclusion:

There is a high rate of spontaneous recovery of BEST1-related choroidal neovascular membrane, and overall the authors observed a gain in visual acuity associated with a reduction in central macular thickness. Active treatment, here with intravitreal bevacizumab, is associated with better functional outcomes than observation alone.
Accounting for Ethnicity-Related Differences in Ocular Surface Integrity as a Step Toward Understanding Contact Lens Discomfort
Authors: Chan Stefanie M. , Svitova Tatyana F. , Lin Meng C.
Published: October 2016

Contact lens discomfort is a common problem that can lead to unsuccessful or limited contact lens wear. Although many factors may contribute to contact lens discomfort, limited research has explored the influence of ethnicity-related differences in the anatomy and physiology of the ocular surface. Therefore, we performed a search of the literature in PubMed using key words related to “ocular surface” paired with the terms “race” and “ethnicity.” The goal of this review was to determine potential areas of research regarding ethnicity differences, particularly between Asian and non-Asian eyes, in ocular surface integrity to advance our understanding of contact lens discomfort.
A regulated environment for micro-organs defines essential conditions for intercellular Ca2+waves
Authors: Narciso Cody E. , Contento Nicholas M. , Storey Thomas J. , Hoelzle David J. , Zartman Jeremiah J.
Published: October 2016

The mechanical stress state of an organ is a critical, but still poorly understood, driver of organogenesis and regeneration. Here we report a chip-based regulated environment for micro-organs (REM-Chip) that enables systematic investigations of the crosstalk between an organ’s mechanical stress environment and biochemical signaling under a multitude of genetic and chemical perturbations. This method has enabled us to identify essential conditions for generating organ-scale intercellular calcium (Ca2+) waves (ICWs) inDrosophilawing imaginal discs that are also observedin vivo. Spontaneous ICWs require the presence of components in fly extract-based growth serum (FEX). Using the REM-Chip, we demonstrate that the release and not the initial application of mechanical compression is sufficient but not necessary to initiate ICWs. Further, the extent of the Ca2+response is heterogeneous between discs and correlates with the degree of spontaneous ICWs activity in the pre-stress state. This system and method enable detailed examinations of the interplay between mechanical stress state, biochemical regulatory networks, and physiology in complex, hierarchically organized organ cultures.
Quantification of in vivo progenitor mutation accrual with ultra-low error rate and minimal input DNA using SIP-HAVA-seq
Authors: Taylor Pete H. , Cinquin Amanda , Cinquin Olivier
Published: October 2016

Assaying in vivo accrual of DNA damage and DNA mutations by stem cells and pinpointing sources of damage and mutations would further our understanding of aging and carcinogenesis. Two main hurdles must be overcome. First, in vivo mutation rates are orders of magnitude lower than raw sequencing error rates. Second, stem cells are vastly outnumbered by differentiated cells, which have a higher mutation rate—quantification of stem cell DNA damage and DNA mutations is thus best performed from small, well-defined cell populations. Here we report a mutation detection technique, based on the “duplex sequencing” principle, with an error rate below ∼10−10 and that can start from as little as 50 pg DNA. We validate this technique, which we call SIP-HAVA-seq, by characterizing Caenorhabditis elegans germline stem cell mutation accrual and asking how mating affects that accrual. We find that a moderate mating-induced increase in cell cycling correlates with a dramatic increase in accrual of mutations. Intriguingly, these mutations consist chiefly of deletions in nonexpressed genes. This contrasts with results derived from mutation accumulation lines and suggests that mutation spectrum and genome distribution change with replicative age, chronological age, cell differentiation state, and/or overall worm physiological state. We also identify single-stranded gaps as plausible deletion precursors, providing a starting point to identify the molecular mechanisms of mutagenesis that are most active. SIP-HAVA-seq provides the first direct, genome-wide measurements of in vivo mutation accrual in stem cells and will enable further characterization of underlying mechanisms and their dependence on age and cell state.
Serving yourself: value self-creation in health care service
Authors: Zainuddin Nadia , Tam Leona , McCosker Angie
Published: October 2016

Purpose

This paper aims to investigate the concept of value self-creation and provides a formal definition for this concept. The paper suggests that it sits within an overall continuum of value creation that includes value delivery and value co-creation.

Design/methodology/approach

A proposed model of value self-creation was developed and empirically tested in a health care self-service, bowel screening. An online, self-completion survey was administered to Australian men and women aged 50 years and above, as this represents the primary target population for bowel screening.

Findings

The results of the structural equation modelling in AMOS suggest that consumers can self-create value, leading to desired outcomes of satisfaction with the consumption experience and behavioural intentions to engage with the self-service again in the future. The findings provide empirical evidence to suggest that consumers’ behavioural contributions represent the most important consumer contributions in self-service, followed by cognitive contributions.

Originality/value

The study provides an empirically validated model of value self-creation in health care self-service. Much of the existing research on value co-creation has concentrated on traditional service types and is ill-placed to explain the value creation processes in self-services. This study offers originality by addressing this gap and demonstrating to service managers how they can manage consumer contributions towards a self-service and facilitate value-self creation, even though they are not present during the consumption stage of the consumption process.
Ascertaining the factors that influence the acceptance and purposeful use of cloud computing in medical libraries in India
Authors: Yuvaraj Mayank
Published: October 2016

Purpose

This paper aims to identify the factors that influence the acceptance and purposeful use of cloud computing technologies in Indian medical libraries.

Design/methodology/approach

To meet the stated objectives, a three-round Delphi study was carried out; a panel of 32 participants, with expertise and experience of cloud computing in the context of Indian medical libraries, was constituted.

Findings

During the study, the participants identified about 60 different factors, and a consensus was reached on 42 of these, which were considered to have a direct impact on the levels of acceptance and purposeful use of cloud computing technologies in Indian medical libraries. The study points out significant factors that should be addressed to accelerate the acceptance and purposeful use of cloud computing technologies in Indian medical libraries.

Originality/value

The study is the first attempt to study the factors responsible for the adoption of cloud computing in Indian medical libraries through the Delphi technique.
Distinctive services in academic librarianship
Authors: Harris Sasekea
Published: October 2016

Purpose

Collection content is no longer the primary distinctive signifier of excellence in the present libraries. In an information market where technology has increased access to content, thereby providing resources at one’s fingertips, the provision of services is increasingly becoming a distinctive signifier of excellence and quality. In such an open/service-oriented marketplace, what are the services that are signifiers of excellence and consequently distinguish a library? This paper aims to review select literature within the USA to identify the services that are signifiers of excellence and that will consequently distinguish a library in the current era and investigate the extent to which said services identified in the review of the literature are provided by the University of the West Indies (UWI) Mona library, but focus specifically on only those that meet the additional criteria of placing the UWI Mona library as either the first to introduce the service in Jamaica or as the only library in Jamaica with the particular service offering. These two additional criteria provide the added signature or uniqueness essential to being distinguished.

Design/methodology/approach

Through the use of a mixed methods research, this paper highlights library service offerings considered as distinctive signifiers of excellence within the American literature and also within the UWI Mona Library – that will distinguish a library.

Findings

This paper reveals services incorporating technology, the library as a place/space, teaching and research and personal attention to users as distinctive signifiers of excellence. In this regard, within the UWI Mona Library, services offered such as the Virtual Reference Service, Extended Opening Service, Halls of Residence Librarian Service, Information Commons Service, Information Literacy Service and the West Indies and Special Collection Research Service were found to incorporate the aforementioned service themes and placed the UWI Mona library as either the first to introduce the service in Jamaica or as the only library in Jamaica with the particular service offering, consequently distinguishing the UWI Mona Library from other academic libraries in Jamaica.

Originality/value

This paper is of value, as it provides the library and information community with an outline of services that distinguish a library; it offers library managers in Jamaica and the rest of the world the opportunity to compare services in their libraries with that of other libraries as outlined within the literature review as well as within the UWI Mona library; it highlights how the UWI Mona library, an academic library in the Caribbean, compares on the international library scene, with particular reference to the USA; it informs current and potential library users of how the UWI Mona library is trending in service culture and a focus on distinctive services can promote a community of academic library service best practice.
Modelling and optimization of laser polishing of additive laser manufacturing surfaces
Authors: Rosa Benoit , Mognol Pascal , Hascoët Jean-Yves
Published: October 2016

Purpose

Direct metal deposition (DMD) with laser is an additive manufacturing process enabling rapid manufacturing of complex metallic and thin parts. However, the final quality of DMD-manufactured surfaces is a real issue that would require a polishing operation. Polishing processes are usually based on abrasive or chemical techniques. These conventional processes are composed by many drawbacks such as accessibility of complex shapes, environmental impacts, high time consumption and cost, health risks for operators, etc. […] This paper aims to solve these problems and improve surface quality by investigating the laser polishing (LP) process.

Design/methodology/approach

Based on melting material by laser, the LP process enables the smoothing of initial topography. However, the DMD process and the LP processes are based on laser technology. In this context, the laser DMD process is used directly on the same machine for the polishing operation. Currently, few studies focus on LP of additive laser manufacturing surfaces, and it tends to limit the industrial use of additive manufacturing technology. The proposed study describes an experimental analysis of LP surfaces obtained by DMD process.

Findings

The investigation results in the improvement of a complete final surface quality, according to LP parameters. For mastering LP processes, operating parameters are modelled.

Originality/value

This experimental study introduces the LP of thin and complex DMD parts, to develop LP applications. The final objective is to create a LP methodology for optimizing the final topography and productivity time according to parts’ characteristics.
Lipoxygenases: From Isolation to Application
Authors: Hayward Stefan , Cilliers Tertius , Swart Pieter
Published: October 2016

The positive effect of lipoxygenase, added as an enzyme‐active soy flour, during the production of white bread is well established. In addition to increasing the mixing tolerance and overall dough rheology, lipoxygenase is also an effective bleaching agent. It is known that these effects are mediated by enzyme‐coupled cooxidation of gluten proteins and carotenoids. However, the mechanism whereby these effects are achieved is not yet fully understood. In order to gain a better understanding into the reactions governing the beneficial effects of lipoxygenases in bread dough, an in‐depth knowledge of the lipoxygenase catalytic mechanism is required. Until now no single review combining the molecular enzymology of lipoxygenase enzymes and their application in the baking industry has been presented. This review, therefore, focuses on the extraction and molecular characterization of lipoxygenases in addition to the work done on the application of lipoxygenases in the baking industry.
Testing genotyping strategies for ultra‐deep sequencing of a co‐amplifying gene family: MHC class I in a passerine bird
Authors: Biedrzycka Aleksandra , Sebastian Alvaro , Migalska Magdalena , Westerdahl Helena , Radwan Jacek
Published: October 2016

Characterization of highly duplicated genes, such as genes of the major histocompatibility complex (MHC), where multiple loci often co‐amplify, has until recently been hindered by insufficient read depths per amplicon. Here, we used ultra‐deep Illumina sequencing to resolve genotypes at exon 3 of MHC class I genes in the sedge warbler (Acrocephalus schoenobaenus). We sequenced 24 individuals in two replicates and used this data, as well as a simulated data set, to test the effect of amplicon coverage (range: 500–20 000 reads per amplicon) on the repeatability of genotyping using four different genotyping approaches. A third replicate employed unique barcoding to assess the extent of tag jumping, that is swapping of individual tag identifiers, which may confound genotyping. The reliability of MHC genotyping increased with coverage and approached or exceeded 90% within‐method repeatability of allele calling at coverages of >5000 reads per amplicon. We found generally high agreement between genotyping methods, especially at high coverages. High reliability of the tested genotyping approaches was further supported by our analysis of the simulated data set, although the genotyping approach relying primarily on replication of variants in independent amplicons proved sensitive to repeatable errors. According to the most repeatable genotyping method, the number of co‐amplifying variants per individual ranged from 19 to 42. Tag jumping was detectable, but at such low frequencies that it did not affect the reliability of genotyping. We thus demonstrate that gene families with many co‐amplifying genes can be reliably genotyped using HTS, provided that there is sufficient per amplicon coverage.
Substance use disorders and referral to treatment in substantiated cases of child maltreatment
Authors: Steenrod Shelley , Mirick Rebecca
Published: October 2016

Parents with substance use disorders (SUD) require treatment and support in order to provide children with appropriate care and protection. Using the 2012 National Child Abuse and Neglect Data System (NCANDS), this paper analysed 464 313 substantiated child maltreatment reports to determine (i) the proportion and characteristics of reports involving substance abuse; and (ii) the child and caregiver/perpetrator (C/P) characteristics that predicted referral to treatment as recorded in service plans. Findings indicate that 12% (N = 53 234) of maltreatment reports involved C/P SUD. Yet, of those reports, only (19%) (N = 10 088) were referred to substance abuse treatment as part of their service plan, indicating a large gap between those who need treatment and those who receive it. This finding is important given that parental SUD is consistently linked to poorer child outcomes. Amongst other variables, reports indicate that C/P with co‐occurring emotional disturbance were three times more likely to be referred to treatment for SUD as part of service plans. Additional research is needed regarding the characteristics that distinguish C/P who receive referrals for SUD treatment in substantiated cases of child maltreatment.
Reexamining the Prohibition of Gestational Surrogacy in Sunni Islam
Authors: Muaygil Ruaim A.
Published: October 2016

Advances in reproductive medicine have provided new, and much needed, hope for millions of people struggling with infertility. Gestational surrogacy is one such development that has been gaining popularity with infertile couples, especially those unable to benefit from other reproductive procedures such as In Vitro Fertilization. For many Muslim couples, however, surrogacy remains a nonviable option. Islamic scholars have deemed the procedure incompatible with Islam and have prohibited its use. This paper examines the arguments presented for proscribing surrogacy arrangements in Sunni Islam in particular. These include preservation of lineage, exclusion of third parties in reproduction, upholding the rights of the child, and protection from the negative effects of surrogacy arrangements. The rationales for banning surrogacy are subsequently refuted utilizing Islamic law “Sharia”, bioethics, and medical evidence. The paper also presents reasons for why surrogacy is not only consistent with Sunni Islamic teachings, but is also both ethically justified and medically necessary. Lastly, Islamic scholars are urged to take into account the arguments presented in this paper and reconsider their rulings on the permissibility of surrogacy.
Profile of diabetes in men aged 79–97 years: the Western Australian Health in Men Study
Authors: Henze M. , Alfonso H. , Flicker L. , George J. , Chubb S. A. P. , Hankey G. J. , Almeida O. P. , Golledge J. , Norman P. E. , Yeap B. B.
Published: October 2016

Aims

To investigate behavioural, physical and biochemical characteristics associated with diabetes in the oldest age group of elderly men.

Methods

We conducted a cross‐sectional analysis of community‐dwelling men aged 79–97 years from Perth, Western Australia. Lifestyle behaviours, self‐rated health, physical function, and fasting glucose and HbA1c levels were assessed.

Results

Of 1426 men, 315 had diabetes (22%). Men with diabetes were of similar age to men without (84.9 vs 84.5 years; P = 0.14). Only 26.5% of men with diabetes self‐rated their health as excellent or very good, compared with 40.6% of men without diabetes (P < 0.001). Diabetes was associated with less involvement with recreational walking (32.7 vs 41.0%; P < 0.01) and leisure activities (19.0 vs 26.5%; P < 0.01). Men with diabetes had poorer physical function on multiple measures, including longer times for the Timed Up‐and‐Go test (15.0 ± 6.9 s vs 13.4 ± 5.3 s; P < 0.001) and weaker knee extension (20.2 vs 21.9 kg; P < 0.001). In multivariate analyses, diabetes was associated with an increased prevalence of myocardial infarction (odds ratio 1.80, 95% CI 1.25–2.60; P < 0.001) and falls resulting in injury (odds ratio 1.55, 95% CI 1.06–2.26; P = 0.02). Average HbA1c was 49 ± 8 mmol/mol (6.6 ± 0.8%) in men with diabetes, with 90.6% of these men on diet or oral hypoglycaemic therapy.

Conclusions

In older men, diabetes is associated with poorer self‐perceived health, reduced healthy lifestyle behaviours and physical function, heart disease and injurious falls. The majority of these men with diabetes had good glycaemic control. Encouraging healthy lifestyle behaviours and improving physical function should be evaluated as interventions to improve quality‐of‐life and health outcomes.
Effects of renal impairment on the pharmacokinetics and pharmacodynamics of a novel dipeptidyl peptidase‐4 inhibitor, evogliptin (DA‐1229)
Authors: Oh Jaeseong , Kim Andrew HyoungJin , Lee SeungHwan , Cho Hyunjeong , Kim Yon Su , Bahng Mi Young , Yoon Seo Hyun , Cho Joo‐Youn , Jang In‐Jin , Yu Kyung‐Sang
Published: October 2016

Evogliptin is a novel potent and selective dipeptidyl peptidase‐4 (DPP‐4) inhibitor. The aim of the present study was to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of evogliptin in participants with renal impairment (RI). An open‐label, parallel‐group clinical study was conducted in participants with mild, moderate and severe RI and in matched participants with normal renal function (NRF). A single oral 5‐mg dose of evogliptin was administered and serial blood and urine samples were obtained to assess the PK and PD characteristics of evogliptin. Baseline urine samples were collected to evaluate endogenous CYP3A metabolic markers. The plasma exposure to evogliptin and degree of DPP‐4 activity inhibition increased with decreasing renal function. The mean areas under the concentration–time curves from 0 to 120 hours were increased 1.2‐, 1.8‐ and 1.98‐fold in the mild, moderate and severe RI groups, respectively, compared with the NRF group. The levels of CYP3A metabolic markers were lower in the RI group than in the NRF group. The increase in the plasma concentration of evogliptin is unlikely to result in changes in its efficacy or safety, considering the results of previous clinical studies.
Early life diets with prebiotics and bioactive milk fractions attenuate the impact of stress on learned helplessness behaviours and alter gene expression within neural circuits important for stress resistance
Authors: Mika Agnieszka , Day Heidi E. W. , Martinez Alexander , Rumian Nicole L. , Greenwood Benjamin N. , Chichlowski Maciej , Berg Brian M. , Fleshner Monika
Published: October 2016

Manipulating gut microbes may improve mental health. Prebiotics are indigestible compounds that increase the growth and activity of health‐promoting microorganisms, yet few studies have examined how prebiotics affect CNS function. Using an acute inescapable stressor known to produce learned helplessness behaviours such as failure to escape and exaggerated fear, we tested whether early life supplementation of a blend of two prebiotics, galactooligosaccharide (GOS) and polydextrose (PDX), and the glycoprotein lactoferrin (LAC) would attenuate behavioural and biological responses to stress later in life. Juvenile, male F344 rats were fed diets containing either GOS and PDX alone, LAC alone, or GOS, PDX and LAC. All diets altered gut bacteria, while diets containing GOS and PDX increased Lactobacillus spp. After 4 weeks, rats were exposed to inescapable stress, and either immediately killed for blood and tissues, or assessed for learned helplessness 24 h later. Diets did not attenuate stress effects on spleen weight, corticosterone and blood glucose; however, all diets differentially attenuated stress‐induced learned helplessness. Notably, in situ hybridization revealed that all diets reduced stress‐evoked cfos mRNA in the dorsal raphe nucleus (DRN), a structure important for learned helplessness behaviours. In addition, GOS, PDX and LAC diet attenuated stress‐evoked decreases in mRNA for the 5‐HT1A autoreceptor in the DRN and increased basal BDNF mRNA within the prefrontal cortex. These data suggest early life diets containing prebiotics and/or LAC promote behavioural stress resistance and uniquely modulate gene expression in corresponding circuits.
Are fingernails a key to unlocking the puzzle of mammalian limb regeneration?
Authors: Lehoczky Jessica A.
Published: October 2016

Some mammalian digit tips, including those of mice and human children, can regenerate following amputation, whereas mammalian limb regeneration does not occur. One major difference between the digit tip and the rest of the limb is the presence of the nail, which is necessary for this type of regeneration. This couples well with the finding that canonical Wnt signalling and Lgr6, an agonist of Wnt signalling that marks nail stem cells, are necessary for digit tip regeneration. This viewpoint essay discusses the role of the nail in digit tip regeneration and explores whether nail stem cells and their presumptive niche can be solely accountable for why regeneration is possible in the digit tip, but not the rest of the limb.
A new brain dopamine‐deficient Drosophila and its pharmacological and genetic rescue
Authors: Cichewicz K. , Garren E. J. , Adiele C. , Aso Y. , Wang Z. , Wu M. , Birman S. , Rubin G. M. , Hirsh J.
Published: October 2016

Dopamine (DA) is a neurotransmitter with conserved behavioral roles between invertebrate and vertebrate animals. In addition to its neural functions, in insects DA is a critical substrate for cuticle pigmentation and hardening. Drosophila tyrosine hydroxylase (DTH) is the rate limiting enzyme for DA biosynthesis. Viable brain DA‐deficient flies were previously generated using tissue‐selective GAL4‐UAS binary expression rescue of a DTH null mutation and these flies show specific behavioral impairments. To circumvent the limitations of rescue via binary expression, here we achieve rescue utilizing genomically integrated mutant DTH. As expected, our DA‐deficient flies have no detectable DTH or DA in the brain, and show reduced locomotor activity. This deficit can be rescued by l‐DOPA/carbidopa feeding, similar to human Parkinson's disease treatment. Genetic rescue via GAL4/UAS‐DTH was also successful, although this required the generation of a new UAS‐DTH1 transgene devoid of most untranslated regions, as existing UAS‐DTH transgenes express in the brain without a Gal4 driver via endogenous regulatory elements. A surprising finding of our newly constructed UAS‐DTH1m is that it expresses DTH at an undetectable level when regulated by dopaminergic GAL4 drivers even when fully rescuing DA, indicating that DTH immunostaining is not necessarily a valid marker for DA expression. This finding necessitated optimizing DA immunohistochemistry, showing details of DA innervation to the mushroom body and the central complex. When DA rescue is limited to specific DA neurons, DA does not diffuse beyond the DTH‐expressing terminals, such that DA signaling can be limited to very specific brain regions.
Inhibition of DNA methyltransferases regulates cocaine self‐administration by rats: a genome‐wide DNA methylation study
Authors: Fonteneau M. , Filliol D. , Anglard P. , Befort K. , Romieu P. , Zwiller J.
Published: October 2016

DNA methylation is a major epigenetic process which regulates the accessibility of genes to the transcriptional machinery. In the present study, we investigated whether modifying the global DNA methylation pattern in the brain would alter cocaine intake by rats, using the cocaine self‐administration test. The data indicate that treatment of rats with the DNA methyltransferase inhibitors 5‐aza‐2′‐deoxycytidine (dAZA) and zebularine enhanced the reinforcing properties of cocaine. To obtain some insights about the underlying neurobiological mechanisms, a genome‐wide methylation analysis was undertaken in the prefrontal cortex of rats self‐administering cocaine and treated with or without dAZA. The study identified nearly 189 000 differentially methylated regions (DMRs), about half of them were located inside gene bodies, while only 9% of DMRs were found in the promoter regions of genes. About 99% of methylation changes occurred outside CpG islands. Gene expression studies confirmed the inverse correlation usually observed between increased methylation and transcriptional activation when methylation occurs in the gene promoter. This inverse correlation was not observed when methylation took place inside gene bodies. Using the literature‐based Ingenuity Pathway Analysis, we explored how the differentially methylated genes were related. The analysis showed that increase in cocaine intake by rats in response to DNA methyltransferase inhibitors underlies plasticity mechanisms which mainly concern axonal growth and synaptogenesis as well as spine remodeling. Together with the Akt/PI3K pathway, the Rho‐GTPase family was found to be involved in the plasticity underlying the effect of dAZA on the observed behavioral changes.
Expression and release of platelet protein disulphide isomerase in patients with haemophilia A
Authors: Voigtlaender M. , Holstein K. , Spath B. , Bokemeyer C. , Langer F.
Published: October 2016

Introduction

Despite similar residual factor VIII activity, patients with haemophilia A (HA) show significant interindividual variability with regard to bleeding frequency and severity, suggesting that additional factors modulate thrombin generation and fibrin deposition. Protein disulphide isomerase (PDI) is an abundant oxidoreductase that exerts pleiotropic effects in primary and secondary haemostasis and contributes to thrombosis and vascular inflammation.

Aim

We conducted a pilot study to explore a potential role of platelet PDI in patients with HA.

Methods

Expression and release of platelet PDI were studied by flow cytometry and enzyme‐linked immunosorbent assay, respectively.

Results

Compared to healthy male controls (n = 12), patients with HA (n = 24) showed significantly increased expression of PDI antigen on ADP‐ or TRAP‐6‐, but not on buffer‐treated platelets, a finding that could not be explained by enhanced platelet activation, as indicated by expression of the α‐granule protein, CD62P (P‐selectin). While platelet agonists did not affect PDI secretion in healthy male controls, increased levels of PDI antigen were found in supernatants of TRAP‐6‐treated platelets from patients with HA. Importantly, in two patients with exceedingly high TRAP‐6‐induced PDI release over baseline, findings were consistent when platelets were isolated and stimulated on a separate occasion. No obvious association was found between platelet PDI and bleeding phenotype in this patient cohort.

Conclusion

Agonist‐induced expression and release of platelet PDI were increased in patients with HA. Larger studies are needed to clarify if variations in this platelet response contribute to the diversity in bleeding frequency and severity among patients with congenital factor VIII deficiency.
European retrospective study of real‐life haemophilia treatment
Authors: Berntorp E. , Dolan G. , Hay C. , Linari S. , Santagostino E. , Tosetto A. , Castaman G. , Álvarez‐Román MT. , Parra Lopez R. , Oldenburg J. , Albert T. , Scholz U. , Holmström M. , Schved J.‐F. , Trossaërt M. , Hermans C. , Boban A. , Ludlam C. , Lethagen S.
Published: October 2016

Introduction

Haemophilia treatment varies significantly between individuals, countries and regions and details of bleed rates, factor consumption and injection frequency are often not available.

Aim

To provide an overview of the FVIII/FIX treatment practice and outcome for patients with haemophilia A (HA) or haemophilia B (HB) across Europe.

Methods

Non‐interventional, 12‐month retrospective study where anonymized data were retrieved from haemophilia centres/registers in Belgium, France, Germany, Italy, Spain, Sweden and the United Kingdom. Male patients (all ages) receiving coagulation factor treatment 24 months prior to the study, with basal FVIII/FIX levels ≤5 IU dL−1, without inhibitors, were included. Data were summarized descriptively.

Results

In total, 1346 patients with HA and 312 with HB were included in the analysis; 75% and 57% had severe disease (FVIII/FIX < 1 IU dL−1) respectively. Prophylaxis was most common for severe haemophilia, especially for children, whereas on‐demand treatment was more common for moderate haemophilia in most countries. The mean (SD) prescribed prophylactic treatment ranged from 67.9 (30.4) to 108.4 (78.1) (HA) and 32.3 (10.2) to 97.7 (32.1) (HB) IU kg−1 per week, across countries. Most patients on prophylaxis were treated ≥3 times/week (HA) or two times/week (HB). The median annual bleeding rate (ABR) for patients on prophylaxis ranged from 1.0 to 4.0 for severe HA, and from 1.0 to 6.0 for severe HB, while those with moderate haemophilia generally had slightly higher ABRs. Median ABRs for on‐demand‐treated severe HA ranged from 4.5 to 18.0, and for HB, 1.5 to 14.0.

Conclusion

Treatment practice varied greatly between centres and countries and patients treated on‐demand and prophylactically both experienced bleeds, emphasizing the need for further optimization of care.
Clinical efficacy of desensitizing mouthwashes for the control of dentin hypersensitivity and root sensitivity: a systematic review and meta‐analysis
Authors: Molina A , García‐Gargallo M , Montero E , Tobías A , Sanz M , Martín C
Published: October 2016

Objective

This systematic review aimed to evaluate the scientific evidence on the efficacy of desensitizing mouthwashes for the treatment of dentin hypersensitivity (DH) and root sensitivity (RS).

Material and methods

A thorough search in MEDLINE, PubMed and Cochrane Plus Library was conducted up to February 2015. Randomized clinical trials, parallel, double‐blinded and placebo‐controlled, with a follow‐up of at least 6 weeks, reporting changes on response to tactile stimuli, thermal/evaporative stimuli or patients’ subjective assessment of the pain experienced during their daily life after the home use of desensitizing mouthwashes were considered for inclusion.

Results

The screening of titles and abstracts resulted in seven publications meeting the eligibility criteria. The desensitizing agents evaluated were potassium nitrate (n = 5), aluminium lactate (n = 1) and sodium fluoride (n = 1). A meta‐analysis for each of the hypersensitivity stimuli was performed. Results demonstrated statistically significant reduction in sensitivity scores favouring test group when DH was assessed by means of patients’ self‐reported pain experience (SMD at 8 weeks = 0.77; 95% CI [0.23; 1.31]; P = 0.005). No significant effects were detected in response to tactile or thermal/evaporative stimuli. Meta‐regression analysis demonstrated a tendency towards an increased effect favouring test group for the patients’ subjective perception, whereas tactile and thermal/evaporative stimuli showed a slight tendency towards a reduction in the efficacy of the test mouthwash.

Conclusions

There exists a tendency towards a decrease in DH or RS scores with time in both treatment groups, with significant differences in favour of test group when sensitivity is evaluated in terms of patients’ self‐reported sensitivity symptoms.
Use of New Imaging CARTO® Segmentation Module Software to Facilitate Ablation of Ventricular Arrhythmias
Authors: TOVIA‐BRODIE OHOLI , BELHASSEN BERNARD , GLICK AHARON , SHMILOVICH HAIM , AVIRAM GALIT , ROSSO RAPHAEL , MICHOWITZ YOAV
Published: October 2016

A New CARTO Software for Ablating Ventricular Arrhythmias

Introduction

A new imaging software (CARTO® Segmentation Module, Biosense Webster) allows preprocedural 3‐D reconstruction of all heart chambers based on cardiac CT. We describe our initial experience with the new module during ablation of ventricular arrhythmias.

Methods and Results

Eighteen consecutive patients with idiopathic ventricular arrhythmias or ischemic ventricular tachycardia (VT) were studied. In the latter group, a combined endocardial and epicardial ablation was performed. Of the 14 patients with idiopathic arrhythmias, 12 were ablated in the outflow tract (OT), 1 in the midseptal left ventricle, and 1 at the left posterior fascicular area; acute successful ablation was achieved in 11 (78.6%) patients. The procedure was discontinued due to close proximity of the arrhythmia origin to the coronary arteries (CA) in 2 patients. Acute successful uncomplicated ablation was achieved in all 4 patients with ischemic VT. During ablation in the coronary cusps commissures, the CARTO® Segmentation Module accurately defined the cusps anatomy. The precise anatomic location provided by the module assisted in successfully ablating when information from activation mapping was not optimal, by ablating at the opposite side of the cusps. In addition, by demonstrating the precise location of the CA, it allowed safe ablation of arrhythmias that originated in close proximity to the CA both in the OT area and the epicardium, eliminating the need for repeat angiography.

Conclusions

The CARTO® Segmentation Module is useful for accurate definition of the exact anatomic location of ventricular arrhythmias and for safely ablating them especially in close proximity to the CA.
The latent structure of Acute Stress Disorder symptoms in trauma‐exposed children and adolescents
Authors: McKinnon Anna , Meiser‐Stedman Richard , Watson Peter , Dixon Clare , Kassam‐Adams Nancy , Ehlers Anke , Winston Flaura , Smith Patrick , Yule William , Dalgleish Tim
Published: October 2016

Background

The revision of Acute Stress Disorder (ASD) in the DSM‐5 (DSM‐5, 2013) proposes a cluster‐free model of ASD symptoms in both adults and youth. Published evaluations of competing models of ASD clustering in youth have rarely been examined.

Methods

We used Confirmatory Factor Analysis (combined with multigroup invariance tests) to explore the latent structure of ASD symptoms in a trauma‐exposed sample of children and young people (N = 594). The DSM‐5 structure was compared with the previous DSM‐IV conceptualization (4‐factor), and two alternative models proposed in the literature (3‐factor; 5‐factor). Model fit was examined using goodness‐of‐fit indices. We also established DSM‐5 ASD prevalence rates relative to DSM‐IV ASD, and the ability of these models to classify children impaired by their symptoms.

Results

Based on both the Bayesian Information Criterion, the interfactor correlations and invariance testing, the 3‐factor model best accounted for the profile of ASD symptoms. DSM‐5 ASD led to slightly higher prevalence rates than DSM‐IV ASD and performed similarly to DSM‐IV with respect to categorising children impaired by their symptoms. Modifying the DSM‐5 ASD algorithm to a 3+ or 4+ symptom requirement was the strongest predictor of impairment.

Conclusions

These findings suggest that a uni‐factorial general‐distress model is not the optimal model of capturing the latent structure of ASD symptom profiles in youth and that modifying the current DSM‐5 9+ symptom algorithm could potentially lead to a more developmentally sensitive conceptualization.
Editorial: Isolating the essential difference – The importance of choosing the right type and sufficient numbers of controls in research on neurodevelopmental disorders and mental health conditions
Authors: Fombonne Eric
Published: October 2016

The question of what constitutes the most appropriate control group in child psychopathology research remains a vexed question as well as one of the most common issues raised in the referees’ reports I read as an editor of JCPP. Yet its importance is often overlooked by authors as they reflect on potential sources of bias in their studies. There is an abundant literature on this question (Rothman, Greenland, & Lash, 2008) that highlights the key issues and pitfalls for research in our field.
Normogram of umbilical artery Doppler indices in singleton pregnancies in south‐western Nigerian women
Authors: Ayoola Oluwagbemiga Oluwole , Bulus Peter , Loto Olabisi Morebisi , Idowu Bukunmi Michael
Published: October 2016

Aim

To determine the Doppler indices of the umbilical arteries in normal singleton pregnancy with a view to generating local reference ranges.

Methods

In this prospective, cross‐sectional study, 400 pregnant women at 15–39 weeks’ gestational age, with estimated fetal weight within the 10th and 90th percentile, no fetal malformation(s), and without any history of maternal medical disease, were recruited. Umbilical arteries were assessed on ultrasound, with the subjects in the supine position. Resistivity index (RI), pulsatility index (PI) and systolic/diastolic (S/D) ratio were recorded and analyzed.

Results

All the umbilical arteries were paired; no single umbilical artery was seen. Mean RI, PI, and S/D ratio declined with gestational age, and decreased from 1.265 to 0.829, from 0.760 to 0.585 and from 4.068 to 2.365, respectively, from 15 to 39 weeks of gestation. With regard to correlation between gestational age and Doppler indices, r = – 0.598 for PI (P < 0.05), − 0.437 for RI (P < 0.05), and – 0.538 for S/D ratio (P < 0.05). Decline in the Doppler indices was progressive with gestational age.

Conclusion

A normogram of umbilical artery Doppler indices was constructed, which showed that the indices decreased with gestational age. These normative data could serve as reference ranges for evaluation of the umbilical artery circulation in this locality.
Ultrasound sclerotherapy pretreatment could obtain a similar effect to surgical intervention on improving the outcomes of in vitro fertilization for patients with hydrosalpinx
Authors: Song Xiao‐min , Jiang Hong , Zhang Wen‐xiang , Zhou Yun , Ni Feng , Wang Xue‐mei
Published: October 2016

Aim

The aim of this study was to compare the clinical outcomes of in vitro fertilization (IVF) for patients with hydrosalpinx between ultrasound sclerotherapy and surgical intervention.

Methods

The data of 482 IVF/intracytoplasmic sperm injection (ICSI) cycles were divided into three groups according to different intervention protocols before IVF/ICSI. Group A included 265 cycles in which ultrasound sclerotherapy pretreatment was carried out before controlled ovarian hyperstimulation. Group B included 109 cycles in which hydrosalpinx aspiration was carried out under ultrasound guidance on the day of oocyte retrieval. Croup C included 108 cycles in which bilateral salpingectomy was carried out before IVF/ICSI.

Results

The rates of embryo implantation, biochemical pregnancy, clinical pregnancy, multiple pregnancy, and early abortion showed no significant differences between groups A and C (P > 0.05); whereas the rates of embryo implantation, biochemical pregnancy, and clinical pregnancy in group B were significantly lower than those in groups A and C (P < 0.05), and that of early abortion in group B was significantly higher than that in groups A and C (P < 0.05).

Conclusion

Ultrasound sclerotherapy on patients with hydrosalpinx before IVF‐embryo transfer could obtain a similar clinical outcome to surgical intervention.
Medical emergency team may reduce obstetric intensive care unit admissions
Authors: Baek Moon Seong , Son Jeongsuk , Huh Jin Won , Lim Chae‐Man , Koh Younsuck , Won Hye‐Sung , Shim Jae‐Yoon , Hong Sang‐Bum
Published: October 2016

Aim

Some recent studies have reported that early intervention by a medical emergency team (MET) for clinical deterioration before intensive care unit (ICU) admission was associated with a survival benefit in critically ill cancer patients. We hypothesized that early MET intervention for an obstetric crisis in the general wards would be related to favorable outcomes in critically ill obstetric patients.

Methods

Data of obstetric patients who were managed by a MET were collected retrospectively from 1 March 2008 to 30 April 2015. A total of 69 obstetric patients were enrolled. Among them, 48 (69.6%) were treated successfully in the general wards and 21 (30.4%) were transferred to the ICU.

Results

Major causes of MET activation were pulmonary edema (n = 23, 33.3%), hypovolemic shock (n = 19, 27.5%), and septic shock (n = 8, 11.6%). Compared with the patients treated in the general ward, the patients transferred to the ICU had significantly higher severity of illness score. Sequential Organ Failure Assessment score was the most useful for prediction of ICU admission of obstetric patients (AUC, 0.810, P < 0.001), and the ideal cut‐off was 4 (sensitivity, 81%; specificity, 60%). During the study period, in‐hospital mortality of the obstetric patients was 2.9% (2/69).

Conclusion

After MET activation many obstetric patients could be successfully treated in the general wards without mortality. Therefore, MET may reduce ICU admissions in critically ill obstetric patients.
Reconsidering the ‘Symmetry’ Between Institutionalization and Professionalization: The Case of Corporate Social Responsibility Managers
Authors: Risi David , Wickert Christopher
Published: October 2016

The assumption of a mutually supportive, ‘symmetric’ relationship between institutionalization and professionalization is central to the institutionalist perspective on professional work. Our inductive qualitative study of corporate social responsibility (CSR) managers in multinational corporations (MNCs) prompts to rethink the validity of this assumption. We show that as the institutionalization of CSR advances and consolidates, CSR managers are pushed to the organizational periphery. This indicates that the relationship between professionalization and institutionalization can be ‘asymmetric’ under certain conditions. To advance the study of this asymmetry, we develop a conceptual framework and a set of corresponding propositions that explain why some groups are able to advance their professionalization projects, while others cannot. Our study makes three main contributions to the literature: First, we explicate under which conditions the relationship between institutionalization and professionalization is more likely asymmetric than symmetric. Second, our explanation of the shifting organizational positions of different professional groups allows for further delineating occupational from organizational professionals. Third, we contribute to the CSR literature by examining the dynamic yet ambiguous role of CSR managers as driving forces behind the implementation of CSR.