bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of dendritic cells in male reproductive tract
Authors: Wang Peng , Duan Yong‐Gang
Published: June 2016

Dendritic cells (DCs) are the most potent professional antigen‐presenting cells. The central role of various DC subsets as bridges between innate and adaptive immunity has become more and more evident. However, the role of DC subsets in male reproductive tract remains largely unexplored, in particular distinct DC subsets (including myeloid and plasmacytoid DCs), their maturation stage, and tissue distribution, as well as state of health or disease. Furthermore, infection and inflammation of male genital tract are thought to be a primary etiological factor of male infertility. This review sheds some light on this complex and rapidly growing field. It summarized the recent findings and deals with the characterization and role of DCs in male reproductive tract, that is, testis, epididymis, prostate, seminal vesicle, semen, and foreskin, which might help to understand the immunopathological mechanisms of male infertility and design effective vaccines for male reproductive health.
Socio‐economic profile and working conditions of freelancers in co‐working spaces and work collectives: evidence from the design sector in Greece
Authors: Avdikos Vasilis , Kalogeresis Athanasios
Published: June 2016

Third places, such as business incubators, co‐working spaces and work collectives, represent a new ecosystem of collaborative working practices in the creative economy that alters significantly the spatial distribution of work and the notion of ‘workplace’. Collaborative workplaces emerged after the gradual collapse of the stable employment paradigm that was one of the main features of the Keynesian welfare state and as a response to precarious working conditions that were augmented during the recent economic crisis and the subsequent recession. The paper contributes to the critical understanding of these new geographies of workplace and working conditions that third places manifest. Using data from a large survey about the economics and the working conditions of Greek designers and from four interviews with freelancers in work collectives and facilitators of co‐working spaces, the paper sheds light on the socio‐economic profile and the working conditions of Greek freelance designers that use co‐working spaces and work collectives as means of reducing precarious working conditions and personal–professional risks. The results show that designers in third places, in contrast to freelancers who use formal workplaces or work from home, work long hours with poor pay and a large proportion have no safety net with regard to social security. Third places can be enclaves of the shadow economy and of very specific precarious working conditions. On the other hand, third places help freelance designers become more embedded to business networks, both local and foreign, rather than working in isolation. Networking effects between freelancers and self‐employed who choose to work in third places usually result in greater opportunities for outsourcing and subcontracting and in more exports.
Studies of the pharmacokinetic profile, in vivo efficacy and safety of injectable altrenogest for the suppression of oestrus in mares
Authors: McConaghy FF , Green LA , Colgan S , Morris LH
Published: June 2016

Objective

To investigate the efficacy and safety of the long‐acting altrenogest injection (NV Readyserve® injection) for horses.

Design

A single‐dose pharmacokinetic (PK) study was conducted. The in vivo efficacy study was a blinded, repeated measures design evaluating behaviour scores. The safety study was a non‐blinded, controlled, parallel‐group, randomised‐block design as per the VICH protocol.

Methods

In the PK study, serial blood samples were obtained for analysis of plasma altrenogest for 150 h following the injection and a non‐compartmental PK analysis was performed. For the efficacy study, 12 mares in oestrus were treated; they were monitored daily for 10 days for signs of oestrus during teasing and given a behaviour score that was compared with pretreatment scores. A standard safety study was conducted at 1‐, 3‐ and 5‐fold the recommended dosage for 84 days. Physical, haematological and biochemical examinations were performed.

Results

Mean plasma altrenogest concentrations were greater than ≈0.5 ng/mL for 148 h following administration. Oestrous behaviour was suppressed in all mares within 24 h of administration. Two mares returned to oestrus by day 6 and the rest on days 7–10. In the safety study there were no significant differences in the physical and haematological examinations, but minor biochemical changes in muscle enzymes. There was a low incidence of injection site reactions following the 3‐ and 5‐fold dose, predominantly for pectoral injections.

Conclusion

These studies support the efficacy and safety of a single dose of Readyserve® injection for the suppression of the signs of oestrus in mares for 5–7 days.
Biotic homogenization of herb layer composition between two contrasting beech forest communities on limestone over 50 years
Authors: Heinrichs Steffi , Schmidt Wolfgang
Published: June 2016

Questions

How do vegetation changes in a limestone beech forest community on dry and nutrient‐poor slopes differ from changes in a community on moist and nutrient‐rich soils over the past 50 yr? Have temporal changes led to a further differentiation between communities?

Location

Ancient, beech‐dominated forest region on limestone in central Germany.

Methods

We compared vegetation relevés sampled between 1955 and 1960 and resurveyed between 2009 and 2012 on quasi‐permanent plots in the Carici‐Fagetum primuletosum (n = 26) on dry, nutrient‐poor and sun‐exposed slopes, and in the Hordelymo‐Fagetum allietosum (n = 25) on nutrient‐rich plateau sites with mesic soils in spring. We concentrated on changes in species richness, vegetation structure and vegetation composition, identified winner and loser species and calculated pair‐wise dissimilarity indices within and between communities to test for differentiation or homogenization over time.

Results

Our results show a more pronounced change in community composition in the Carici‐Fagetum primuletosum within 50 yr compared to the Hordelymo‐Fagetum allietosum. Despite no significant increase in total canopy cover, shade‐tolerant, mesophilous, nutrient‐demanding species expanded, whereas light‐demanding, drought‐tolerant, oligotrophic, often Red List species decreased. Changes in the Hordelymo‐Fagetum allietosum were more random. Overall, vegetation dynamics led to a homogenization between the two contrasting communities caused by a loss of specialized species from the Carici‐Fagetum community and a gain in generalist species in both communities.

Conclusion

The drastic changes in the Carici‐Fagetum community indicate the higher susceptibility of marginal sites – that often have a high conservation value – to local environmental changes. In particular, N deposition and the abandonment of former (more traditional) forest management, such as coppice‐with‐standards and wood pasture, are responsible for this development. On the other hand, the increasing temperatures from climate change are not sufficient to secure the survival of the once frequent thermophilous species. Therefore, adequate forest management and conservation measures, such as the removal of competitive or exotic tree species or the re‐establishment of coppice‐with‐standards management, are necessary to counteract the on‐going biotic homogenization of beech forest communities and should focus on marginal sites.
Subjective well‐being amongst migrant children in China: unravelling the roles of social support and identity integration
Authors: Ni S. , Chui C. H.‐K. , Ji X. , Jordan L. , Chan C. L.‐W.
Published: June 2016

Background

Migrant children refer to rural children who accompany one or both parents to urban area. Empirical evidence showed that compared with their urban counterparts, migrant children had poorer developmental, emotional and psychological health.

Method

A sample of 1306 migrant children were recruited to examine the characteristics of migrant children and investigate the effects of identity integration, support and socioeconomic factors (e.g. age, gender, type of school, family socioeconomic status, city type) on their subjective wellbeing.

Results

Children with higher levels of identity integration, social support, family socioeconomic status, who attended public school and who lived in the third‐tiered city of Weihai demonstrated better subjective wellbeing. Social support remained a strong predictor for subjective wellbeing, despite a significant mediating effect of identity integration.

Conclusions

These results highlight the need for policymakers and practitioners alike to address individual factors pertaining to psychological adjustments, as well as social determinants of subjective wellbeing in the context of migration.
Bone Remodeling Around Implants with External Hexagon and Morse‐Taper Connections: A Randomized, Controlled, Split‐Mouth, Clinical Trial
Authors: Pessoa Roberto S. , Sousa Ravel M. , Pereira Leandro M. , Neves Flavio D. , Bezerra Fabio J.B. , Jaecques Siegfried V.N. , Sloten Jos V. , Quirynen Marc , Teughels Wim , Spin‐Neto Rubens
Published: June 2016

Objectives

To evaluate clinical, radiographic, microbiologic, and biomechanical parameters related to bone remodeling around implants with external hexagon (EH) and Morse‐taper (MT) connections.

Materials and Methods

Twelve totally edentulous patients received four custom‐made implants in the interforaminal region of the mandible. Two of those implants had the same macroscopic design, but different prosthetic connections. All patients received an immediate implant‐supported prosthesis. Clinical parameters (periimplant probing pocket depth (PPD), modified gingival index (mGI), and mucosal thickness (MTh)) were evaluated at 12 months follow‐up. The distance between the top of the implant and the first bone‐to‐implant contact (IT‐FBIC) was evaluated on standardized digital peri‐apical radiographs acquired at 1, 3, 6, and 12 months follow‐up. Samples of the subgingival microbiota were collected 1, 3, and 6 months after implant loading and used for the quantification of Tanerella forsythia, Porphyromonas gingivalis, Aggragatibacter actinomycetemcomitans, Prevotella intermedia, and Fusobacterium nucleatum. Further, 36 computerized‐tomography based finite element (FE) models were accomplished, simulating each patient under three loading conditions.

Results

The evaluated clinical parameters were equal for EH and MT implants. Mean IT‐FBIC was significantly different between the tested connections (1.17 ± 0.44 mm for EH, and 0.17 ± 0.54 mm for MT, considering all evaluated time periods). No significant microbiological differences could be observed between tested connections. FE analysis showed a significantly higher peak of equivalent (EQV) strain (p = 0.005) for EH (mean 3,438.65 µε) compared to MT (mean 840.98 µε) connection.

Conclusions

Radiographic periimplant bone loss depends on the implant connection type. MT connections showed less periimplant bone loss, compared to EH connections.
Attitudes to Price Risk and Uncertainty: The Earnest Search for Identification and Policy Relevance
Authors: Bellemare Marc F. , Lee Yu Na
Published: June 2016

After several decades of neglect, the food crises of 2007–08 and 2010–11 have brought food price volatility back on the policy agenda. The study of price volatility, however, is really the study of price risk and uncertainty as they relate to individuals, households, and firms. Because the study of behavior in the face of risk and uncertainty has mostly focused on behavior in the face of income risk and uncertainty, we first review the theoretical and empirical literatures on behavior in the face of price risk and uncertainty. Then, because policy recommendations are only as good as the empirical findings on which they are based, and because market‐level phenomena such as price risk do not lend themselves well to randomization, we discuss the ways in which experimental economics can inform our understanding of price risk. Finally, because expected utility—the workhorse model used to study behavior in the face of risk and uncertainty—fails to account for a number of behaviors, we discuss how insights from behavioral economics could be incorporated into the study of price risk, with the ultimate goal of generating more policy‐relevant findings.

Après avoir été négligée pendant plusieurs décennies, la volatilité des prix alimentaires a été remise à l'ordre du jour par les crises alimentaires de 2007‐2008 et 2010‐2011. L'étude de la volatilité des prix est toutefois équivalente à l'étude du risque et de l'incertitude relatifs aux prix et de leurs conséquences en ce qui a trait aux individus, aux ménages, et aux firmes. Comme l'étude du comportement face au risque et à l'incertitude a surtout porté sur le risque et l'incertitude relatifs au revenu, nous offrons tout d'abord une revue de la littérature portant sur le risque et l'incertitude relatifs aux prix. Ensuite, parce que les recommandations de politique économique ne sont aussi bonnes que les résultats empiriques sur lesquelles elles sont fondées, et parce que les phénomènes de marché comme la volatilité des prix sont difficiles à étudier par randomisation, nous expliquons comment les économies expérimentale et comportementale peuvent améliorer notre compréhension du comportement face au risque et à l'incertitude des prix. Finalement, parce que la théorie de l'utilité espérée—le modèle de référence en ce qui a trait à l'étude du risque et de l'incertitude—peine à expliquer plusieurs comportements, nous présentons la façon dont certains résultats en économie comportementale peuvent être incorporés dans l'étude du risque et de l'incertitude relatifs aux prix, dans le but de générer des recommandations de politique économique qui sont plus utiles.
INCOME INSTABILITY AND THE RESPONSE OF THE SAFETY NET
Authors: Hardy Bradley L.
Published: June 2016

This paper examines the response of safety net transfer and tax programs to earnings and income shocks across recessions since the early 1980s. Safety net programs in the United States are designed to dampen economic instability and maintain basic needs for families. Such programs, including TANF, SNAP (food stamps), and the Earned Income Tax Credit (EITC), have been tested during and between recessions of the past 30 years, including the recent 2007–2009 Great Recession. I use matched data in the March Current Population Survey (CPS) from 1980 to 2012 to estimate pre‐ and post‐transfer income instability over the 1980s, 1990s, and 2000s, as well as across recessions. The results are disaggregated by family structure, race, income, and education. Transfer programs are associated with lowered instability levels and flatter trend growth from 1980 to 2012 among socioeconomically disadvantaged subgroups, while the tax system reduces income instability for families in the top 40th percentile of the income distribution. Although the largest instability reductions occur among the poor, since 1980 the safety net appears less responsive to instability for the bottom income quintile, female‐headed families, and black families. (JEL I38, J63)
RISKS TO THE RETURNS TO MEDICAL INNOVATION: THE CASE OF MYRIAD GENETICS
Authors: Clemens Jeffrey , Veuger Stan
Published: June 2016

We describe the broad range of uncertainties faced by the developers of medical technologies. Empirically, we estimate the asset market incidence of two realizations of uncertainties we classify as ex post policy risks. The events we analyze concern the intellectual property of Myriad Genetics, Inc., an American molecular diagnostics firm. In June 2013, the Supreme Court invalidated several of Myriad's intellectual property claims. Subsequently, the Center for Medicare and Medicaid Services (CMS) re‐evaluated the reimbursements it pays for the services at issue in the Supreme Court's ruling. Each of these events moved Myriad's market capitalization by several hundred million dollars, or on the order of 20%. Myriad's exposure to the realization of these events reflected the concentration of its revenue streams among the affected services. We discuss the implications of the risks we analyze for the total volume of medical innovation and for its organization across firms. (JEL I18, O3, D8)
Textile applications of commercial photochromic dyes. Part 6: photochromic polypropylene fibres
Authors: Little Anna F. , Christie Robert M.
Published: June 2016

Two commercial photochromic dyes, a spirooxazine and a napthopyran, were successfully incorporated into polypropylene fibres by melt extrusion to produce fibres that showed intense photochromism. The technical performance of the photochromic dyes was investigated using a methodological approach that has been established and validated for the dyes applied by screen printing onto textiles in previous publications in this series. These parallel investigations allowed a comparison of the properties of the dyes in polypropylene and screen printed on cotton. The photocolorability of both dyes was found to be significantly higher in polypropylene compared with screen prints on cotton when applied at the same dye concentration. Of particular interest was the observation of positive solvatochromism, providing evidence that the photochromism is due to the colorants in solution in both media. The colour development rates during UV exposure of the dyes applied by screen printing cotton and by extrusion into polypropylene were similar. However, differences were observed in the thermal fading rates after removal of the UV source, in that the spirooxazine dye reverted more slowly in polypropylene, while the reverse was true in the case of the naphthopyran. Both dyes showed better photostability in polypropylene than in screen‐printed textiles. A UV absorber and two hindered amine light stabilisers were found significantly to enhance the photostability of the dyes in polypropylene, although the presence of the UV absorber reduced the degree of photocoloration.
Synthesis of quenchers to control the fluorescence of Rhodamine B and improve the contrast ratio of blue filters for LCDs
Authors: Lee Hyun‐Young , Kwon Hye‐Sun , Oh Jin‐kyu , Kim Kyung‐Won , Lee Hye‐Min , Choi Jae‐Hong
Published: June 2016

In this study, seven quenchers (derived from either anthraquinone, phthalimidylazo, or dipyrromethene chromophores) were prepared as candidates for additives to suppress fluorescence in blue colour filters and thus improve their contrast ratio. To reduce fluorescence effectively, quenchers must have typical properties such as spectral compatibility by which the absorbance spectrum of the quencher overlaps the fluorescence emission spectrum, exhibit high molar extinction coefficients, and exert little influence on the colour of the blue filter. The seven quenchers possessed absorption maxima of approximately 570–620 nm and reduced fluorescence (by more than 24%). Those quenchers tested in filter coatings increased their contrast ratios by about 50%. They thus effectively quenched fluorescence of the blue filter but without greatly affecting the chromaticity coordinates of the filters.
Estimating high‐risk cannabis and opiate use in Ankara, Istanbul and Izmir
Authors: Kraus Ludwig , Hay Gordon , Richardson Clive , Yargic Ilhan , Ilhan Mustafa Necmi , Ay Pinar , Karasahin Füsun , Pinarci Mustafa , Tuncoglu Tolga , Piontek Daniela , Schulte Bernd
Published: June 2016

Introduction and Aims

Information on high‐risk drug use in Turkey, particularly at the regional level, is lacking. The present analysis aims at estimating high‐risk cannabis use (HRCU) and high‐risk opiate use (HROU) in the cities of Ankara, Istanbul and Izmir.

Design and Methods

Capture–recapture and multiplier methods were applied based on treatment and police data stratified by age and gender in the years 2009 and 2010. Case definitions refer to ICD‐10 cannabis (F.12) and opiate (F.11) disorder diagnoses from outpatient and inpatient treatment records and illegal possession of these drugs as recorded by the police.

Results

High‐risk cannabis use was estimated at 28 500 (8.5 per 1000; 95% confidence interval 7.3–10.3) and 33 400 (11.9 per 1000; 95% confidence interval 10.7–13.5) in Ankara and Izmir, respectively. Using multipliers based on capture–recapture estimates for Izmir, HRCU in Istanbul was estimated up to 166 000 (18.0 per 1000; range: 2.8–18.0). Capture–recapture estimates of HROU resulted in 4800 (1.4 per 1000; 95% confidence interval 0.9–1.9) in Ankara and multipliers based on these gave estimates up to 20 000 (2.2 per 1000; range: 0.9‐2.2) in Istanbul. HROU in Izmir was not estimated due to the low absolute numbers of opiate users.

Discussion and Conclusions

While HRCU prevalence in both Ankara and Izmir was considerably lower in comparison to an estimate for Berlin, the rate for Istanbul was only slightly lower. Compared with the majority of European cities, HROU in these three Turkish cities may be considered rather low. [Kraus L, Hay G, Richardson C, Yargic I, Ilhan N M, Ay P, Karasahin F, Pinarci M, Tuncoglu T, Piontek D, Schulte B Estimating high‐risk cannabis and opiate use in Ankara, Istanbul and Izmir Drug Alcohol Rev 2016;00:000‐000]
Use of Swedish smokeless tobacco (snus) and the risk of Type 2 diabetes and latent autoimmune diabetes of adulthood (LADA)
Authors: Rasouli B. , Andersson T. , Carlsson P.‐O. , Grill V. , Groop L. , Martinell M. , Midthjell K. , Storm P. , Tuomi T. , Carlsson S.
Published: June 2016

Aims

It has been suggested that moist snuff (snus), a smokeless tobacco product that is high in nicotine and widespread in Scandinavia, increases the risk of Type 2 diabetes. Previous studies are however few, contradictory and, with regard to autoimmune diabetes, lacking. Our aim was to study the association between snus use and the risk of Type 2 diabetes and latent autoimmune diabetes of adulthood (LADA).

Method

Analyses were based on incident cases (Type 2 diabetes, n = 724; LADA, n = 200) and population‐based controls (n = 699) from a Swedish case–control study. Additional analyses were performed on cross‐sectional data from the Norwegian HUNT study (n = 21 473) with 829 prevalent cases of Type 2 diabetes. Odds ratios (OR) were estimated adjusted for age, BMI family history of diabetes and smoking. Only men were included.

Results

No association between snus use and Type 2 diabetes or LADA was seen in the Swedish data. For Type 2 diabetes, the OR for > 10 box‐years was 1.00 [95% confidence interval (CI), 0.47 to 2.11] and for LADA 1.01 (95% CI, 0.45 to 2.29). Similarly, in HUNT, the OR for Type 2 diabetes in ever‐users was estimated at 0.91 (95% CI, 0.75 to 1.10) and in heavy users at 0.92 (95% CI, 0.46 to 1.83).

Conclusion

The risk of Type 2 diabetes and LADA is unrelated to the use of snus, despite its high nicotine content. This opens the possibility of the increased risk of Type 2 diabetes seen in smokers may not be attributed to nicotine, but to other substances in tobacco smoke.
Analysis of cell‐free fetal DNA for non‐invasive prenatal diagnosis in a family with neonatal diabetes
Authors: De Franco E. , Caswell R. , Houghton J. A. L. , Iotova V. , Hattersley A. T. , Ellard S.
Published: June 2016

Aims

An early genetic diagnosis of neonatal diabetes guides clinical management and results in improved treatment in ~ 40% of patients. In the offspring of individuals with neonatal diabetes, a prenatal diagnosis allows accurate estimation of the risk of developing diabetes and, eventually, the most appropriate treatment for the baby. In this study, we performed non‐invasive prenatal genetic testing for a fetus at risk of inheriting a paternal KCNJ11 p.R201C mutation causing permanent neonatal diabetes.

Methods

A droplet digital polymerase chain reaction assay was used to detect the presence of the mutation in cell‐free circulating DNA (cfDNA) extracted from maternal plasma at 12 and 16 weeks’ gestation.

Results

The mutation was not detected in the cfDNA samples, suggesting that the fetus had not inherited the KCNJ11 mutation. The fetal DNA fraction was estimated at 6.2% and 10.7%, which is above the detection limit of the assay. The result was confirmed by Sanger sequencing after the baby's birth, confirming that the baby's risk of developing neonatal diabetes was reduced to that of the general population.

Conclusions

We report the first case of non‐invasive prenatal testing in a family with neonatal diabetes. A prenatal diagnosis in families at high risk of monogenic diabetes informs both prenatal and postnatal management. Although the clinical impact of this novel technology still needs to be assessed, its implementation in clinical practice (including cases at risk of inheriting mutations from the mother) will likely have a positive impact upon the clinical management of families affected by monogenic diabetes.
Left atrial remodeling in patients undergoing percutaneous mitral valve repair with the MitraClip system: an advanced echocardiography study
Authors: Toprak Cuneyt , Kahveci Gokhan , Kilicgedik Alev , Pala Selcuk , Kirma Cevat , Tabakci Mehmet Mustafa , Inanir Mehmet , Esen Ali Metin
Published: June 2016

Background

The goal of this study was to determine changes in left atrial (LA) function with two‐dimensional speckle tracking echocardiography (2DSTE) and real‐time full‐volume three‐dimensional echocardiography (RT3DE) after percutaneous mitral valve repair with the MitraClip system. Furthermore, we investigated whether baseline and/or changes in LA function after MitraClip repair had any impact on prognosis.

Methods

A total of 25 consecutive patients (age: 57±12 years, 76% male) with moderate‐to‐severe or severe mitral regurgitation (MR) were included. Patients underwent 2DSTE and RT3DE before the clip implantation and after the 12‐month follow‐up. Prognostic data were also recorded via the use of telephone calls and follow‐up visits for 12 months after the procedure.

Results

Compared with the baseline, the LA reservoir strain (LA‐Res) (7.66±4.3% vs 11.15±7.5%, P<.001) and LA contraction strain (LA‐Pump) (4.64±4.3% vs 7.63±5.8%, P=.001) improved significantly after MitraClip repair; significant improvements were also seen in three‐dimensional (3D) minimum LA volume index (LAV min) and maximum LA volume index (LAV max). On the other hand, conventional LA indices did not change. In total, eleven major adverse cardiac events (MACE) were observed at the 1‐year follow‐up. In univariate analyses, the preprocedural echocardiographic parameters that were associated with the MACE within 1 year after MitraClip repair were 3D‐LAV min and LA‐Res. Furthermore, these indices significantly correlated with improved functional parameters and MR reduction.

Conclusion

In conclusion, a successful MitraClip procedure can reverse the process of LA remodeling within 12 months, and this can be detected by 2DSTE and RT3DE. Also, patients with preprocedural lower LA‐Res and higher 3D‐LAV min had the worst prognoses at the 1‐year follow‐up.
Correlates of health‐related quality of life in children with drug resistant epilepsy
Authors: Conway Lauryn , Smith Mary Lou , Ferro Mark A. , Speechley Kathy N. , Connoly Mary B. , Snead O. Carter , Widjaja Elysa ,   the PEPSQOL Study Team
Published: June 2016

Objective

Health‐related quality of life (HRQL) is compromised in children with epilepsy. The current study aimed to identify correlates of HRQL in children with drug resistant epilepsy.

Methods

Data came from 115 children enrolled in the Impact of Pediatric Epilepsy Surgery on Health‐Related Quality of Life Study (PEPSQOL), a multicenter prospective cohort study. Individual, clinical, and family factors were evaluated. HRQL was measured using the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE), a parent‐rated epilepsy‐specific instrument, with composite scores ranging from 0 to 100. A series of univariable linear regression analyses were conducted to identify significant associations with HRQL, followed by a multivariable regression analysis.

Results

Children had a mean age of 11.85 ± 3.81 years and 65 (56.5%) were male. The mean composite QOLCE score was 60.18 ± 16.69. Child age, sex, age at seizure onset, duration of epilepsy, caregiver age, caregiver education, and income were not significantly associated with HRQL. Univariable regression analyses revealed that a higher number of anti‐seizure medications (p = 0.020), lower IQ (p = 0.002), greater seizure frequency (p = 0.048), caregiver unemployment (p = 0.010), higher caregiver depressive and anxiety symptoms (p < 0.001 for both), poorer family adaptation, fewer family resources, and a greater number of family demands (p < 0.001 for all) were associated with lower HRQL. Multivariable regression analysis showed that lower child IQ (β = 0.20, p = 0.004), fewer family resources (β = 0.43, p = 0.012), and caregiver unemployment (β = 6.53, p = 0.018) were associated with diminished HRQL in children.

Significance

The results emphasize the importance of child cognition and family variables in the HRQL of children with drug‐resistant epilepsy. The findings speak to the importance of offering comprehensive care to children and their families to address the nonmedical features that impact on HRQL.
Development and validation of the NDDI‐E‐Y: a screening tool for depressive symptoms in pediatric epilepsy
Authors: Wagner Janelle L. , Kellermann Tanja , Mueller Martina , Smith Gigi , Brooks Byron , Arnett Alex , Modi Avani C.
Published: June 2016

Objectives

To validate the revised 12‐item revised Neurological Disorders Depression Inventory‐Epilepsy for Youth (NDDI‐E‐Y), a self‐report screening tool for depressive symptoms tailored to youth ages 12–17 with epilepsy.

Methods

Youth at two sites completed the NDDI‐E‐Y during a routine epilepsy visit. Youth at one site also completed the Children's Depression Inventory‐2 (CDI‐2). Seizure and demographic data were abstracted from the electronic medical record. Exploratory factor analyses were conducted. Internal consistency, area under the curve (AUC), and construct validity were assessed.

Results

NDDI‐E‐Y questionnaires were analyzed for 143 youth. The coefficient for internal consistency for the NDDI‐E‐Y was 0.92. Factor analyses suggested a one‐factor solution with all 12 items loading on the factor. The NDDI‐E‐Y was positively correlated with the CDI‐2 (N = 99). Sensitivity and specificity of the NDDI‐E‐Y were high.

Significance

Reliability and construct validity were established for the revised 12‐item NDDI‐E‐Y. The NDDI‐E‐Y is a brief, free measure of depressive symptoms that can be administered during a routine epilepsy visit.
Revised version of quality guidelines for presurgical epilepsy evaluation and surgical epilepsy therapy issued by the Austrian, German, and Swiss working group on presurgical epilepsy diagnosis and operative epilepsy treatment
Authors: Rosenow Felix , Bast Thomas , Czech Thomas , Feucht Martha , Hans Volkmar H. , Helmstaedter Christoph , Huppertz Hans‐Jürgen , Noachtar Soheyl , Oltmanns Frank , Polster Tilman , Seeck Margitta , Trinka Eugen , Wagner Kathrin , Strzelczyk Adam
Published: June 2016

The definition of minimal standards remains pivotal as a basis for a high standard of care and as a basis for staff allocation or reimbursement. Only limited publications are available regarding the required staffing or methodologic expertise in epilepsy centers. The executive board of the working group (WG) on presurgical epilepsy diagnosis and operative epilepsy treatment published the first guidelines in 2000 for Austria, Germany, and Switzerland. In 2014, revised guidelines were published and the WG decided to publish an unaltered English translation in this report. Because epilepsy surgery is an elective procedure, quality standards are particularly high. As detailed in the first edition of these guidelines, quality control relates to seven different domains: (1) establishing centers with a sufficient number of sufficiently and specifically trained personnel, (2) minimum technical standards and equipment, (3) continuous medical education of employees, (4) surveillance by trained personnel during video electroencephalography (EEG) monitoring (VEM), (5) systematic acquisition of clinical and outcome data, (6) the minimum number of preoperative evaluations and epilepsy surgery procedures, and (7) the cooperation of epilepsy centers. These standards required the certification of the different professions involved and minimum numbers of procedures. In the subsequent decade, quite a number of colleagues were certified by the trinational WG; therefore, the executive board of the WG decided in 2013 to make these standards obligatory. This revised version is particularly relevant given that the German procedure classification explicitly refers to the guidelines of the WG with regard to noninvasive/invasive preoperative video‐EEG monitoring and invasive intraoperative diagnostics in epilepsy.
Energy density zone model and fatigue life prediction considering microscopic effects
Authors: Zhang J R , Fan L , Tang X S
Published: June 2016

An energy density zone (EDZ) model is developed for the prediction of fatigue life. The microscopic effects can be involved in the EDZ model. Three scale transitional functions in the model are utilized to describe the trans‐scale behaviours of fatigue failure from micro‐scale to macro‐scale. Fatigue failure behaviours of a low‐alloy and ultra‐high‐strength steel material (i.e. 40CrNi2Si2MoVA steel) is investigated. Two fatigue parameters in the model are determined from the experimental S–N curves for the smooth cylinder specimens (the stress concentration factor, SCF, Kt = 1). Then, fatigue lives of notched specimens with SCFs Kt = 2 and Kt = 3 are predicted respectively by the proposed model. The predicted S–N curves are satisfactory in comparison with the experimental results. Scatter of the fatigue test data can be depicted when the microscopic effects are considered. Influences of microscopic effects on the fatigue behaviours are explored by means of numerical simulations.
Population pharmacokinetic modelling of factor IX activity after administration of recombinant factor IX in patients with haemophilia B
Authors: Suzuki A. , Tomono Y. , Korth‐Bradley J. M.
Published: June 2016

Purpose

The aim is to develop a pharmacokinetic model for factor IX activity (FIX) after BeneFIX (nonacog alfa, rFIX) administration and assess potential covariates using all available clinical data collected during development.

Methods

The data set for model development combined observations from eight studies. Postdose FIX observations were adjusted by subtracting predose FIX if these were above the lower limit of quantification (BLQ) and all BLQ observations were removed. A population pharmacokinetic model was then developed with 4936 observations from 201 patients. Two additional studies (385 observations from 72 patients) became available and were used to evaluate the model.

Results

A two‐compartment model, parameterized for clearance (CL), volume of distribution of the central (V1) and peripheral (V2) compartments, and intercompartmental clearance (Q), with an effect of weight on all parameters was the final model. Weight was incorporated as a power function with exponent estimates close to conventional allometric scaling. Including interoccasion variability (IOV) on CL and V1 showed decreases in the objective function. Investigations of a full block omega matrix lead to the retention of a correlation between V2 and Q. Age was not a significant covariate with weight already included in the model. Observations in the studies used for evaluation were found to be higher than simulated values immediately after dosing, as well as a week after dosing. The differences may be due perhaps to differences in the patients enrolled in the evaluation studies (all were adults) as well as the sample collection time after dosing (longer after dosing in the evaluation studies).

Conclusions

FIX is appropriately modelled as a two‐compartment model after rFIX administration. When weight is included, no additional effect of age is observed. Longer times of observation after dosing may be helpful in refining the model.
A world‐wide survey and field study in clinical haemostasis laboratories to evaluate FVIII:C activity assay variability of ADYNOVATE and OBIZUR in comparison with ADVATE
Authors: Turecek P. L. , Romeder‐Finger S. , Apostol C. , Bauer A. , Crocker‐Buqué A. , Burger D. A. , Schall R. , Gritsch H.
Published: June 2016

Introduction

Discrepancies have been previously reported for one‐stage clotting and chromogenic assays for FVIII activity analysis. Inter‐laboratory variations in instruments, method of clot detection, assay set‐up, reference standard calibration, reagent source and reagent composition all contribute to assay variability.

Aim

To characterise multilaboratory assay variability in measuring ADYNOVATE, OBIZUR and ADVATE FVIII activity in human plasma and survey multinational FVIII activity assay preferences.

Methods

As samples from patients treated with either of the FVIII products are not available in the quantities required for a systematic collaborative study, haemophilia A plasma was spiked in vitro with either ADYNOVATE (PEGylated rFVIII), OBIZUR [Porcine Sequence Antihaemophilic Factor (Recombinant)] or ADVATE at high (0.80 IU or U mL−1), medium (0.20 IU or U mL−1) and low (0.05 IU or U mL−1) FVIII concentrations, based on labelled potencies. Clinical laboratories used their routine FVIII activity assay to determine FVIII activity of each product. Thirty‐five data sets using one‐stage clotting assay and 11 sets using chromogenic assay were obtained.

Results

A vast majority of laboratories (98%) prefer and rely on the one‐stage clotting assay. Mean recoveries across all concentrations were 113%, 120% and 127% for ADYNOVATE, OBIZUR and ADVATE respectively. Assay variation was comparable between ADVATE, ADYNOVATE and OBIZUR with inter‐laboratory percent coefficients of variation (%CV) ranging from 11 to 22%. Mean chromogenic assay results were 116%, 51% and 113% for ADYNOVATE, OBIZUR and ADVATE respectively. Inter‐laboratory CV's were similar for ADYNOVATE, OBIZUR and ADVATE.

Conclusions

One‐stage clotting assays can and will be used with sufficient accuracy and precision for the measurement of ADYNOVATE, OBIZUR and ADVATE in plasma samples from subjects with haemophilia A. Chromogenic assay underestimates OBIZUR potency, particularly at lower concentrations.
Case report of diet‐related improvements of non‐alcoholic steatohepatitis evaluated by four consecutive liver biopsies
Authors: Kawanaka Miwa , Nouso Kazuhiro , Yano Syoichiro , Nakamura Jun , Nishino Ken , Suehiro Mitsuhiko , Kawamoto Hirofumi
Published: June 2016

We report the case of a 46‐year‐old man who achieved remarkable improvement of characteristic non‐alcoholic steatohepatitis by dieting. Initially, his body mass index was 40.7 kg/m2. He proactively commenced a low calorie diet and his body mass index decreased to 28 kg/m2 after 4 years. During the same period, we carried out liver biopsy four times. Liver fibrosis as well as inflammation, steatosis and ballooning improved, and the non‐alcoholic fatty liver disease activity score decreased from 4 to 0. The fat deposits of liver tissue changed from macrovesicular droplets to microvesicular, and finally disappeared. Along with improved histology, alanine aminotransferase, homeostasis model assessment‐insulin resistance, ferritin, leptin, high‐sensitivity C‐reactive protein and cytokeratin 18 decreased, and adiponectin increased linearly. However, no clear changes were observed in markers for Wisteria floribunda agglutinin‐positive Mac‐2 binding protein (WFA+M2BP), type IV collagen 7S, procollage III peptide and fibrosis‐4 index along with dieting. This is the first study to report gradual improvement of liver histology during four liver biopsies and fibrosis markers in a patient with non‐alcoholic steatohepatitis who achieved complete recovery solely by dieting.
Immunochemical and molecular assessment of urothelial neoplasms and aspects of the 2016 World Health Organization classification
Authors: Compérat Eva , Varinot Justine
Published: June 2016

The new World Health Organization classification of tumours of the urinary system and male genital organs (4th edn) has several changes from previous versions, and was published in January 2016. New pathways have been discovered in the development of bladder cancer, and were included in this new classification. Guidance from the International Collaboration on Cancer Reporting (ICCR) helped to clarify open questions, in conjunction with the new classification. The histological groups of urothelial carcinoma evolved. Grading remained the same, despite controversy among European urologists. Substaging of pT1 tumours is recommended for the first time, and the ICCR has made recommendations on how to report this. Furthermore, worldwide advice has been published on the use of immunohistochemistry, and recommendations have been made to try to standardize the handling of bladder cancer from a histopathological point of view. At a molecular level, bladder cancer groups have been stratified, and an upcoming molecular classification permits a novel view of this malignancy. This review will try to summarize the most important changes.
HIV drug resistance levels in adults failing first‐line antiretroviral therapy in an urban and a rural setting in South Africa
Authors: Rossouw TM , Nieuwoudt M , Manasa J , Malherbe G , Lessells RJ , Pillay S , Danaviah S , Mahasha P , van Dyk G , de Oliveira T
Published: June 2016

Objectives

Urban and rural HIV treatment programmes face different challenges in the long‐term management of patients. There are few studies comparing drug resistance profiles in patients accessing treatment through these programmes. The aim of this study was to perform such a comparison.

Methods

HIV drug resistance data and associated treatment and monitoring information for adult patients failing first‐line therapy in an urban and a rural programme were collected. Data were curated and managed in SATuRN RegaDB before statistical analysis using Microsoft Excel 2013 and stata Ver14, in which clinical parameters, resistance profiles and predicted treatment responses were compared.

Results

Data for 595 patients were analysed: 492 patients from a rural setting and 103 patients from an urban setting. The urban group had lower CD4 counts at treatment initiation than the rural group (98 vs. 126 cells/μL, respectively; P = 0.05), had more viral load measurements performed per year (median 3 vs. 1.4, respectively; P < 0.01) and were more likely to have no drug resistance mutations detected (35.9% vs. 11.2%, respectively; P < 0.01). Patients in the rural group were more likely to have been on first‐line treatment for a longer period, to have failed for longer, and to have thymidine analogue mutations. Notwithstanding these differences, the two groups had comparable predicted responses to the standard second‐line regimen, based on the genotypic susceptibility score. Mutations accumulated in a sigmoidal fashion over failure duration.

Conclusions

The frequency and patterns of drug resistance, as well the intensity of virological monitoring, in adults with first‐line therapy failure differed between the urban and rural sites. Despite these differences, based on the genotypic susceptibility scores, the majority of patients across the two sites would be expected to respond well to the standard second‐line regimen.
Predictors of health‐promoting behaviors in patients with coronary artery disease in the Iranian population
Authors: Hajizadeh‐Sharafabad Fatemeh , Alizadeh Mohammad
Published: June 2016

This study was carried out to determine the predictors of health‐promoting behaviors (HPBs) in patients with coronary artery diseases (CAD) in the Iranian population. In this cross‐sectional descriptive study, 250 eligible patients ages 42–80 years with a body mass index (BMI) between 18 and 45.7 kg/m2 with CAD who were admitted to a cardiac hospital in Urmia, Iran participated. Valid questionnaires used the Health Promoting Lifestyle Profile‐II (HPLP‐II), Cardiac Self‐Efficacy (CSE) and General Self‐Efficacy (GSE) scales to assess HPBs, CSE and GSE, respectively. Fifty five percent of participants were men and mean (SD) age was 59 (12.1) years. Hierarchical multiple regression analysis indicated that CSE, GSE, education and BMI were the best predictors of HPBs, respectively. This model predicted 31% of HPB change (adjusted R2 = 0.31).Responsibility for health and spiritual growth motivates patients to apply HPBs. However, physical activity and stress management are least applied.
Multiple gut–liver axis abnormalities in children with obesity with and without hepatic involvement
Authors: Guercio Nuzio S. , Di Stasi M. , Pierri L. , Troisi J. , Poeta M. , Bisogno A. , Belmonte F. , Tripodi M. , Di Salvio D. , Massa G. , Savastano R. , Cavallo P. , Boffardi M. , Ziegenhardt D. , Bergheim I. , Mandato C. , Vajro P.
Published: June 2016

Background

Gut–liver axis (GLA) dysfunction appears to play a role in obesity and obesity‐related hepatic complications.

Objectives

This study sought to concurrently explore several GLA components in a paediatric obese population with/without liver disease.

Methods

Thirty‐two children (mean age 11.2 years) were enrolled: nine controls with normal weight and 23 patients with obesity (OB+). Of the 23 patients OB(+), 12 had not steatosis (ST−), and 11 had steatosis (ST+) (associated [n = 8] or not [n = 3] with hypertransaminasaemia [ALT +/−]). Subjects were characterized by using auxologic, ultrasonographic and laboratory parameters. A glucose hydrogen breath test was performed to test for small intestinal bacterial overgrowth, a urinary lactulose/mannitol ratio (LMR) was obtained to assess intestinal permeability, and tests for transaminases, blood endogenous ethanol, endotoxin and faecal calprotectin were also conducted.

Results

Eleven out of 23 patients OB(+) (p < 0.05) exhibited pathological (>90th percentile of the control group values) LMR, with values paralleling the grade of liver involvement (normal weight < OB[+] < OB[+]ST[+]ALT[−] < OB[+)]ST[+]ALT[+] [p < 0.05]). LMR significantly correlated with ethanolaemia (r = 0.38, p = 0.05) and endotoxaemia (r = 0.48, p = 0.015) concentrations. Increased permeability was a risk factor for the development of steatosis (p < 0.002). SIBO was present only in patients with obesity. Faecal calprotectin concentrations were within normal limits in all subjects.

Conclusions

Increased permeability, endogenous ethanol and systemic endotoxin concentrations reflect some GLA dysfunction in obesity and its hepatic complications. Pending further results to establish their potential causative roles, the modulation of the GLA appears to represent a possible target for the prevention and treatment of these conditions.