bluuebunny/crossref_metadata_2025 huggingface dataset:
Minor physical anomalies in schizophrenia and bipolar I disorder and the neurodevelopmental continuum of psychosis
Authors: Akabaliev Valentin Hristov , Sivkov Stefan Todorov , Mantarkov Mladen Yordanov
Published: May 2014

Objectives

Minor physical anomalies (MPAs) have been investigated by numerous studies in patients with schizophrenia in support of the neurodevelopmental hypothesis of the disorder, but have rarely been examined in patients with bipolar disorder or in direct comparisons between the two conditions. The main objective of the present study was to compare the prevalence of MPAs in psychiatrically healthy controls, patients with bipolar I disorder, and patients with schizophrenia.

Methods

A slightly modified version of the Waldrop Physical Anomaly Scale was used to assess MPAs in psychiatrically healthy controls (n = 103), patients with bipolar I disorder (n = 61), and patients with schizophrenia (n = 128).

Results

In five out of six topographic regions (mouth, feet, head, eyes, and ears) there was a pattern of lowest regional MPA scores in controls, intermediate in bipolar I disorder, and highest in schizophrenia. The cephalofacial composite score and the total MPA score showed the same pattern, with all between‐group differences being statistically significant. Seven individual MPAs in the discriminant analysis model contributed independently to the prediction of the triple‐dependent status of ‘psychiatrically healthy control, bipolar I disorder patient, schizophrenia patient’: high/arched palate, fine electric hair, large gap between first and second toes, third toe ≥ second toe, epicanthus, malformed ears, and furrowed tongue.

Conclusions

Our findings support the existence of a continuum of neurodevelopmental adversity within the clinical spectrum of psychosis, with bipolar I disorder occupying an intermediate position between psychiatric health and schizophrenia.
Reactive aggression and peer victimization from pre‐kindergarten to first grade: Accounting for hyperactivity and teacher–child conflict
Authors: Runions Kevin C.
Published: May 2014

Background

The role of reactive aggression in the development of peer victimization remains unclear due in part to a failure to account for confounding problems of behavioural undercontrol (e.g., hyperactivity). As well, the school social context has rarely been examined to see whether these risks are mediated by relationships with teachers.

Aims

This study tests the prospective relations between reactive aggression, hyperactivity, victimization, and teacher–child (T‐C) relationship, to determine whether conflict mediates the relationships between externalizing problems and victimization.

Sample

A sample of 1,114 Australian students were followed from pre‐kindergarten through first grade.

Methods

Cross‐lagged path analyses were conducted, with comparison of gender‐moderating models and autocorrelation models. Full‐information maximum likelihood was deployed to account for missingness.

Results

Best fitting models found that the relationship of early externalizing problems to later victimization was mediated by T‐C conflict. No evidence of victimization increasing externalizing problems nor gender differences were observed. T–C conflict in kindergarten predicted subsequent increases in victimization, reactive aggression, and hyperactivity.

Conclusions

Understanding the processes whereby externalizing problems confer risk of victimization involves understanding the whole social context of classrooms, including relationships with teachers. Finer‐grained research is needed to better understand how peer dynamics may be influenced by observation of T–C relationships. Pre‐service teacher education needs to ensure a focus on the potential social impact of teacher's relationships with students.
Prognostic impact of KMT2E transcript levels on outcome of patients with acute promyelocytic leukaemia treated with all‐trans retinoic acid and anthracycline‐based chemotherapy: an International Consortium on Acute Promyelocytic Leukaemia study
Authors: Lucena‐Araujo Antonio R. , Kim Haesook T. , Jacomo Rafael H. , Melo Raul A. , Bittencourt Rosane , Pasquini Ricardo , Pagnano Katia , Fagundes Evandro M. , de Lourdes Chauffaille Maria , Chiattone Carlos S. , Lima Ana S. , Kwaan Hau C. , Gallagher Robert , Niemeyer Charlotte M. , Schrier Stanley L. , Tallman Martin S. , Grimwade David , Ganser Arnold , Berliner Nancy , Ribeiro Raul C. , Lo‐Coco Francesco , Löwenberg Bob , Sanz Miguel A. , Rego Eduardo M.
Published: May 2014

The KMT2E (MLL5) gene encodes a histone methyltransferase implicated in the positive control of genes related to haematopoiesis. Its close relationship with retinoic acid–induced granulopoiesis suggests that the deregulated expression of KMT2E might lead acute promyelocytic leukaemia (APL) blasts to become less susceptible to the conventional treatment protocols. Here, we assessed the impact of KMT2E expression on the prognosis of 121 APL patients treated with ATRA and anthracycline‐based chemotherapy. Univariate analysis showed that complete remission (P = 0·006), 2‐year overall survival (OS) (P = 0·005) and 2‐year disease‐free survival (DFS) rates (P = 0·037) were significantly lower in patients with low KMT2E expression; additionally, the 2‐year cumulative incidence of relapse was higher in patients with low KMT2E expression (P = 0·04). Multivariate analysis revealed that low KMT2E expression was independently associated with lower remission rate (odds ratio [OR]: 7·18, 95% confidence interval [CI]: 1·71–30·1; P = 0·007) and shorter OS (hazard ratio [HR]: 0·27, 95% CI: 0·08–0·87; P = 0·029). Evaluated as a continuous variable, KMT2E expression retained association with poor remission rate (OR: 10·3, 95% CI: 2·49–43·2; P = 0·001) and shorter survival (HR: 0·17, 95% IC: 0·05–0·53; P = 0·002), while the association with DFS was of marginal significance (HR: 1·01; 95% CI: 0·99–1·02; P = 0·06). In summary, low KMT2E expression may predict poor outcome in APL patients.
Explaining young adults' drinking behaviour within an augmented Theory of Planned Behaviour: Temporal stability of drinker prototypes
Authors: van Lettow Britt , de Vries Hein , Burdorf Alex , Conner Mark , van Empelen Pepijn
Published: May 2014

Objectives

Prototypes (i.e., social images) predict health‐related behaviours and intentions within the context of the Theory of Planned Behaviour (TPB). This study tested the moderating role of temporal stability of drinker prototype perceptions on prototype–intentions and prototype–behaviour relationships, within an augmented TPB. The study examined abstainer, moderate drinker, heavy drinker, tipsy, and drunk prototypes.

Design and Methods

An online prospective study with 1‐month follow‐up was conducted among 410 young adults (18–25 years old, Mage = 21.0, SD = 2.14, 21.7% male). Assessed were prototype perceptions (favourability and similarity, T1, T2), stability of prototype perceptions, TPB variables (T1), intentions (T2), and drinking behaviour (T2). Intention analyses were corrected for baseline behaviour; drinking behaviour analyses were corrected for intentions and baseline behaviour.

Results

Hierarchical regressions showed that prototype stability moderated the relationships of drunk and abstainer prototype similarity with intentions. Similarity to the abstainer prototype explained intentions to drink sensibly more strongly among individuals with stable perceptions than among those with unstable perceptions. Conversely, intentions were explained stronger among individuals with stable perceptions of dissimilarity to the drunk prototype than among those with unstable perceptions. No moderation effects were found for stability of favourability or for relationships with behaviour.

Conclusions

Stable prototype similarity perceptions were more predictive of intentions than unstable perceptions. These perceptions were most relevant in enhancing the explanation of young adults' intended drinking behaviour. Specifically, young adults' health intentions seem to be guided by the dissociation from the drunk prototype and association with the abstainer prototype.

Statement of contribution

What is already known on this subject?

Prototypes have augmented the Theory of Planned Behaviour in explaining risk behaviour.

Temporal stability has been shown to successfully extend the TPB in explaining intentions.

Temporal stability of TPB variables can moderate the relationships with behaviour and intentions.

What does this study add?

Stability of prototype perceptions moderates the prototype–intentions relationship.

Stability of abstainer and drunk prototype similarity enhances the explanation of (intentional) drinking.

Stable prototype perceptions are more explanatory than unstable perceptions.
Effects of Educational Interventions Targeting Reading Comprehension and Underlying Components
Authors: Melby‐Lervåg Monica , Lervåg Arne
Published: May 2014

In most school subjects, students' comprehension of what they read is crucial, as is improving that comprehension. In this article, we review studies on the effects of interventions on reading comprehension. A simple view of reading sees reading comprehension as the product of linguistic comprehension and decoding skills, while an augmented view also emphasizes domain general cognitive skills (e.g., working memory, auditory processing). Studies that target skills directly related to reading comprehension through strategy training show moderate to large effects. In studies that target reading comprehension through the underlying components (i.e., decoding, linguistic comprehension, and domain‐general cognitive skills), training decoding has the largest effect on standardized tests of reading comprehension (small to moderate effects). Studies targeting linguistic comprehension have mixed results, highlighting the need for more randomized controlled trials that measure effects on reading comprehension. Finally, domain general interventions show little promise in terms of effects on reading comprehension.
Cognitive and Neural Mechanisms Underlying Socioeconomic Gradients in Language Development: New Answers to Old Questions
Authors: Demir Özlem Ece , Küntay Aylin C.
Published: May 2014

Although researchers have studied disparities in early language development related to socioeconomic status (SES), it is unclear how early and through which mechanisms these differences emerge. As income inequality continues to widen across the world, it is crucial to examine the child‐level mechanisms that mediate the effects of SES on individual differences in language development. A deeper understanding of the nature of the differences will allow development of more effective intervention techniques. In this article, we discuss work on child‐level cognitive and neural mechanisms underlying the relation between SES and early language development. We discuss possible factors behind individual differences in child‐level mechanisms and cascading effects of these differences. We conclude with recommendations for research.
Understanding the U.S. Immigrant Paradox in Childhood and Adolescence
Authors: Marks Amy K. , Ejesi Kida , García Coll Cynthia
Published: May 2014

The immigrant paradox in childhood and adolescence is a population‐level phenomenon wherein U.S.‐born youth (or more highly acculturated immigrants) have less optimal developmental outcomes than newcomer immigrant youth. These patterns, which hold true after accounting for the generally lower income and parent education levels among first‐generation immigrant families, have existed for decades in the United States. In this article, we address this topic in child development research, offering insights into studies to explain why the paradox occurs from the standpoint of both risk and resilience. We also present ideas for research and implications for developing policies and methods for effective practice with immigrant families.
Immigrant Adolescents' Adaptation to a New Context: Ethnic Friendship Homophily and Its Predictors
Authors: Titzmann Peter F.
Published: May 2014

Although interethnic friendships are among the best indicators of social adaptation to a new cultural context, adolescent immigrants form friendships predominantly within their own ethnic community, a phenomenon called friendship homophily. In this article, I focus on the acculturation of immigrant adolescents and on the factors that lead them to form friendships within their group, including acculturation‐related behaviors, mutual attitudes of native and immigrant groups, developmental age‐related considerations, and the context in which these adolescents live. The results present opportunities not only for reducing friendship homophily but also point to the complexity of acculturation research and the need to study side effects of adolescents' adaptation to a new context.
Prognostic markers of sarcoidosis: an analysis of patients from everyday pneumological practice
Authors: Doubková Martina , Pospíšil Zdeněk , Skřičková Jana , Doubek Michael
Published: May 2014

Introduction

Although sarcoidosis is a well‐known disease, sarcoidosis patient outcome and the role of prognostic markers in everyday practice have not yet been well described. Therefore, the goal of the present study was to analyse the fate of sarcoidosis patients and the factors influencing the disease's behaviour in routine practice.

Methods

The study was a retrospective analysis of 306 consecutive patients (181 females and 125 males; median age 45 years) diagnosed with sarcoidosis in the years 2003–2012.

Results

Through the use of uniparametric analysis, it was determined that the stage of the disease, organ involvement, CD4/CD8 ratio in the bronchoalveolar lavage fluid (BALF), serum and urine calcium levels, smoking, and pulmonary functions had a significant influence on spontaneous sarcoidosis resolution. Multiparametric analysis revealed that spontaneous resolution was significantly positively influenced by female gender, a less advanced disease stage, a higher CD4/CD8 ratio in the BALF, lymphocytosis in the BALF and normal pulmonary functions at diagnosis. During follow‐up, only three patients died. The causes of death were respiratory failure with pneumonia (n = 2) and heart attack caused by sarcoidosis heart involvement (n = 1).

Conclusion

The data show sarcoidosis as a disorder with high variability in clinical and laboratory findings but with good general prognosis.
Sclerotherapy of varicose veins in dermatology
Authors: Lorenz Marthe Barbara , Gkogkolou Paraskevi , Goerge Tobias
Published: May 2014

Venous disorders rank among the most frequent diseases in the German population. Early diagnostic investigation and treatment can prevent their progression and may reduce the risk for secondary diseases. The therapeutic spectrum for varicose veins includes conservative as well as interventional and surgical methods. Because it is minimally invasive and well‐tolerated, sclerotherapy represents an important treatment method for venous insufficiency, recurrent varicosis and venous malformations. We review the role of sclerotherapy as a treatment option of chronic venous insufficiency in dermatology.
Sklerotherapie der Varikosis in der Dermatologie
Authors: Lorenz Marthe Barbara , Gkogkolou Paraskevi , Goerge Tobias
Published: May 2014

Venenerkrankungen zählen zu den häufigsten Volkskrankheiten in Deutschland. Durch frühzeitige Diagnostik und Behandlung kann ein Fortschreiten der chronischen venösen Insuffizienz bis ins hohe Alter verhindert und das Auftreten von Folgeerkrankungen reduziert werden. Das therapeutische Spektrum der Varikosis umfasst neben konservativen Maßnahmen auch interventionelle und operative Verfahren. Insbesondere die Sklerotherapie stellt aufgrund ihrer geringen Invasivität und guten Verträglichkeit eine wichtige Behandlungsform von insuffizienten Varizen, Rezidivvarikosen und venösen Malformationen dar. Der folgende Artikel beschreibt die Sklerotherapie als Behandlungsform der chronischen venösen Insuffizienz in der Dermatologie.
Autoantibodies in psoriatic patients treated with anti‐TNF‐α therapy
Authors: Bardazzi Federico , Odorici Giulia , Virdi Annalucia , Antonucci Valentina Angela , Tengattini Vera , Patrizi Annalisa , Balestri Riccardo
Published: May 2014

Background

TNF‐α inhibitors have been associated with induction of autoantibodies and autoimmune diseases. We retrospectively evaluated the incidence of autoantibodies ANA, ENA, anti‐dsDNA, the occurrence of clinical symptoms and possibly related treatment failure.

Patients and methods

The titers of ANA, ENA and anti‐dsDNA were evaluated from blood samples every six months in 128 patients receiving a TNF‐α inhibitor (adalimumab, etanercept, infliximab).

Results

Overall 37% of 128 patients treated with anti‐TNF‐α drug developed autoantibodies, mostly induced by infliximab; 48.48 % of patients who received infliximab presented autoantibodies. One patient developed a drug‐induced lupus erythematosus. Forty‐five patients were switched to one or more additional TNF‐α inhibitors and 25 developed autoantibodies.

Conclusions

An increased autoantibody titer is not predictive of treatment failure; particular attention to all phenomena suggestive for autoimmunity is needed in patients with a positive autoantibody titer. Further studies are needed to clarify the role of autoantibodies during anti‐TNF‐ α therapy.
Autoantikörper bei Patienten mit Psoriasis unter Anti‐TNF‐α‐Therapie
Authors: Bardazzi Federico , Odorici Giulia , Virdi Annalucia , Antonucci Valentina Angela , Tengattini Vera , Patrizi Annalisa , Balestri Riccardo
Published: May 2014

Hintergrund

TNF‐α‐Inhibitoren werden mit einer Induktion von Autoantikörpern und Autoimmunerkrankungen in Verbindung gebracht. Wir evaluierten in einer retrospektiven Untersuchung das Vorkommen der Autoantikörper ANA, ENA und Anti‐dsDNA‐Ak sowie das Auftreten klinischer Symptome und ein möglicherweise damit im Zusammenhang stehendes Therapieversagen.

Patienten und Methoden

In sechsmonatigen Abständen wurden die ANA‐, ENA und Anti‐dsDNA‐Ak‐Titer im Blut von 128 Patienten untersucht, die TNF‐α‐Inhibitoren (Adalimumab, Etanercept, Infliximab) erhielten.

Ergebnisse

37 % der untersuchten 128 Patienten entwickelten unter der Therapie mit TNF‐α‐Inhibitoren Autoantikörper. Zumeist wurden diese durch Infliximab induziert: Bei 48,48 % der mit Infliximab behandelten Patienten traten Autoantikörper auf. Ein Patient entwickelte einen medikamenteninduzierten Lupus erythematodes. Bei 45 Patienten war ein Therapiewechsel zu einem oder mehreren alternativen TNF‐α‐Inhibitoren erforderlich und 25 Patienten entwickelten Autoantikörper.

Schlussfolgerungen

Ein erhöhter Autoantikörpertiter ist nicht als prädiktiv für ein Therapieversagen zu werten. Bei Patienten mit nachgewiesenen Autoantikörpern ist besondere Aufmerksamkeit hinsichtlich der Entwicklung autoimmuner Erkrankungen nötig. Weitere Untersuchungen sind erforderlich, um die Rolle von Autoantikörpern während einer Therapie mit TNF‐α‐Inhibitoren genau zu klären.
The environment‐pathogen‐host axis in communicable and non‐communicable diseases: Recent advances in experimental and clinical research
Authors: Gilles Stefanie , Traidl‐Hoffmann Claudia
Published: May 2014

Allergies and autoimmune diseases are spreading worldwide. Control of infections, on the other hand, remains an issue, even in the post‐antibiotic era. Chronic or poorly controlled infections occur in immune compromised individuals such as HIV patients, hospitalized patients exposed to multi‐resistant bacteria, or patients on immunosuppressive treatment. They may become an even more emerging issue in an ageing population. At the same time, profound environmental changes such as global warming, urbanization, increasing environmental pollution and novel food engineering technologies may alter the abundance or aggressiveness of allergens/allergen carriers in our environment. Likewise, changes in dietary habits – and possibly also use of antibiotics – have an impact on the composition of our natural microbial flora in the gut, airways and skin, which may alter susceptibility for common diseases, among them allergies, asthma and atopic eczema. At the recently founded Institute of Environmental Medicine of the Technische Universität Munich, located in Augsburg at the UNIKA‐T, experimental, clinical and translational research is focused on the complex interactions of environment, pathogen and host in expression or control of communicable and non‐communicable diseases. We present our research concept and recent findings in environment – host interactions.
Die Achse Umwelt‐Erreger‐Wirt bei übertragbaren und nicht übertragbaren Krankheiten: Jüngste Fortschritte in der experimentellen und klinischen Forschung
Authors: Gilles Stefanie , Traidl‐Hoffmann Claudia
Published: May 2014

Allergien und Autoimmunerkrankungen sind weltweit auf dem Vormarsch. Die Kontrolle von Infektionskrankheiten stellt jedoch auch im postantibiotischen Zeitalter eine Herausforderung dar. Chronische und/oder schwer kontrollierbare Infektionen treten bei Menschen mit Immunschwäche auf, wie z. B. bei HIV‐Patienten, hospitalisierten Patienten, die multiresistenten Bakterien ausgesetzt sind, oder bei Patienten unter immunsuppressiver Therapie. In einer alternden Bevˆlkerung drohen solche Erkrankungen an Bedeutung zuzunehmen. Gleichzeitig können Veränderungen der Umwelt, wie globale Erwärmung, Urbanisierung, zunehmende Umweltverschmutzung und neue Entwicklungen in der Lebensmitteltechnologie zu einer Veränderung in der Häufigkeit und Aggressivität von Allergenen führen. Veränderte Ernährungsgewohnheiten und möglicherweise auch der Einsatz von Antibiotika haben zudem einen Einfluss auf die Zusammensetzung der natürlichen mikrobiellen Flora von Darm, Atemwegen und Haut, was die Suszeptibilität für Erkrankungen wie Allergien, Asthma und Neurodermitis verändern könnte. Am kürzlich neu gegründeten Institut für Umweltmedizin der Technischen Universität München mit Sitz am UNIKA‐T in Augsburg liegt der Schwerpunkt der experimentellen, klinischen und translationalen Forschung auf den komplexen Wechselwirkungen zwischen Umwelt, Erreger und Wirt in der Ausprägung oder Kontrolle von übertragbaren und nicht‐übertragbaren Erkrankungen. Wir stellen hier unser Forschungskonzept vor und präsentieren unsere jüngsten Erkenntnisse auf dem Gebiet der Umwelt‐Wirt‐Interaktionen.
Cooperation between the occupational health insurance and physicians practicing occupational dermatology: Optimization potential in quality assurance
Authors: Elsner Peter , Aberer Werner , Bauer Andrea , Diepgen Thomas Ludwig , Drexler Hans , Fartasch Manigé , John Swen Malte , Schuhmacher‐Stock Uta , Wehrmann Wolfgang , Weisshaar Elke
Published: May 2014

Background

Quality assurance is a task of the medical profession, but it is also a duty of the occupational health insurance (OHI). Data on the interaction quality between physicians practicing occupational dermatology and the OHI are limited.

Material and Methods

An online survey was performed in 854 German members of the Working Group on Occupational and Environmental Dermatology in October 2013. Items included demographic data, a judgment on the cooperation between the dermatologists and OHI companies, an economic grading of the current compensation scheme, and prioritization of optimization tasks.

Results

182 members (21.3 % of the invited population) participated in the survey. The cooperation with the OHI companies was judged as “very good” by 10.8 %, as “good” by 56.7  %, as “satisfactory” by 24.2 %, as “sufficient” by 7.0 % and as “inadequate” by 1.3 %. 93.4 % of the interviewed mentioned problems and improvement potentials in the cooperation of their practice or clinic with OHI companies. Main points of criticisms were reimbursement (44.7 %), followed by impairments of the treatment options (36.5 %) and the delay or scope of the treatment in the dermatologist's procedure (29.4 %).

Conclusions

While most physicians practicing occupational dermatology give a positive judgment of their cooperation with OHI companies, quality optimization potentials exist regarding the reimbursement of dermatological services, especially regarding time‐intensive counselling in the prevention of occupational skin diseases, in the enablement of diagnostic and therapeutic procedures according to current guidelines and in a timely preventive intervention to use the therapeutic window before chronification of skin diseases may occur.
Diverse juvenile life‐history behaviours contribute to the spawning stock of an anadromous fish population
Authors: Walsworth Timothy E. , Schindler Daniel E. , Griffiths Jennifer R. , Zimmerman Christian E.
Published: May 2014

Habitat quality often varies substantially across space and time, producing a shifting mosaic of growth and mortality trade‐offs across watersheds. Traditional studies of juvenile habitat use have emphasised the evolution of single optimal strategies that maximise recruitment to adulthood and eventual fitness. However, linking the distribution of individual behaviours that contribute to recruitment at the population level has been elusive, particularly for highly fecund aquatic organisms. We examined juvenile habitat use within a population of sockeye salmon (Oncorhynchus nerka) that spawn in a watershed consisting of two interconnected lakes and a marine lagoon. Otolith microchemical analysis revealed that the productive headwater lake accounted for about half of juvenile growth for those individuals surviving to spawn in a single river in the upper watershed. However, 47% of adults had achieved more than half of their juvenile growth in the downstream less productive lake, and 3% of individuals migrated to the estuarine environment during their first summer and returned to freshwater to overwinter before migrating back to sea. These results describe a diversity of viable habitat‐use strategies by juvenile sockeye salmon that may buffer the population against poor conditions in any single rearing environment, reduce density‐dependent mortality and have implications for the designation of critical habitat for conservation purposes. A network of accessible alternative habitats providing trade‐offs in growth and survival may be important for long‐term viability of populations.
Predictors of splenic function preservation in children with sickle cell anemia treated with hydroxyurea
Authors: Nottage Kerri A. , Ware Russell E. , Winter Bryan , Smeltzer Matthew , Wang Winfred C. , Hankins Jane S. , Dertinger Stephen D. , Shulkin Barry , Aygun Banu
Published: May 2014

Background

More than 90% of children with sickle cell anemia (SCA) lose splenic function by the age of 2 yrs. Splenic function may improve with hydroxyurea, but previous studies are conflicting. We prospectively evaluated the effect of hydroxyurea on splenic filtrative function.

Methods

Children with SCA enrolled in the Hydroxyurea Study of Long‐Term Effects (HUSTLE‐NCT00305175) underwent clinical evaluations including Tc99m liver–spleen (LS) scans before hydroxyurea initiation and after 3 yrs of treatment to maximum tolerated dose (MTD). LS scans were classified as follows: no uptake, <10% uptake, decreased but ≥10% uptake, and normal.

Results

Mean age (N = 40) was 9.1 yrs, range 2.3–17.0. After 3 yrs of treatment, 13 (33%) had uptake on LS scan. These 13 children were younger (median age 6.0 vs. 10.6 yrs, P = 0.008), had a higher HbF at baseline (mean 10.2% vs. 5.8%, P = 0.004) and after 3 yrs (22.9% vs. 13.9%, P < 0.001), achieved MTD more rapidly (median 288 vs. 358 d, P = 0.021), and were more likely to have baseline splenic uptake (P < 0.001).

Conclusions

Hydroxyurea at MTD is associated with preserved or improved splenic filtrative function, with 33% demonstrating LS scan uptake after 3 yrs. Younger age, higher %HbF, and baseline splenic function are associated with a favorable outcome.
Cord blood CD34+ cells expanded on Wharton's jelly multipotent mesenchymal stromal cells improve the hematopoietic engraftment in NOD/SCID mice
Authors: Milazzo Luisa , Vulcano Francesca , Barca Alessandra , Macioce Giampiero , Paldino Emanuela , Rossi Stefania , Ciccarelli Carmela , Hassan Hamisa J. , Giampaolo Adele
Published: May 2014

Objective

This study aims to investigate the capability of Wharton's jelly multipotent mesenchymal stromal cells (WJ‐MSC) to support the in vitro expansion of hematopoietic stem/progenitor cells (HSPC) derived from cord blood (CB) in the absence of exogenous cytokines, and the effect on engraftment of the expanded cells in a mouse model.

Methods

CB‐CD34+ cells were seeded on WJ‐MSC layer and cultured in HP01 serum‐free medium. Day‐7 and day‐13 expanded cells were transplanted in NOD/SCID mice. After 8 wk, engraftment was evaluated in mouse bone marrow as percentage of human CD45+ cells.

Results

CD34+ population was expanded without increasing the differentiation rate. Co‐culture increased the expansion of the CD34+ cells by 2.0 and 7.3 times after 7 and 13 d, respectively, and maintained the CD34+ cells up to day 20. In particular, earlier CD34+/CD90+ and CD34+/CD33− subtypes were increased. An advantage of the day‐7 co‐cultured HSPC in respect of HSPC at day 0 in the engraftment of NOD/SCID mice was obtained both as percentage of mice engrafted (100% vs. 75%) and as percentage of chimerism.

Conclusions

Although the increase in hematopoietic progenitors is not dramatic as in the presence of added cytokines, this study demonstrates the effectiveness of the WJ‐MSC not only to preserve the CD34+ population but also to improve the repopulating efficacy of the amplified HSPC, also in the absence of added cytokines and growth factors.
A single institution experience on 314 newly diagnosed advanced Hodgkin lymphoma patients: the role of ABVD in daily practice
Authors: Andjelic Bosko , Antic Darko , Jakovic Ljubomir , Todorovic Milena , Bogdanovic Andrija , Djurasinovic Vladislava , Bila Jelena , Mihaljevic Biljana
Published: May 2014

Based on the results of clinical trials, there is no global consensus on the optimal first‐line therapy for patients with advanced Hodgkin lymphoma (HL) with both ABVD and BEACOPP currently being used. However, the results of clinical trials are usually better than those in daily practice. We thus describe here our experience on 314 advanced classical HL patients treated with ABVD at the Clinical Center of Serbia and associated centers between 1997 and 2008. The median follow‐up for all patients was 91 months; the estimated 5‐yr event‐free survival was 62% and the 5‐yr overall survival (OS) 76%. Multivariate Cox regression analysis revealed that patients with IPS ≥ 3 and extranodal disease involving more than one site have a poorer outcome. The data presented here show on overall improvement in outcome as compared to more previous data and illustrate the problems of treating advanced stage HL outside the setting of a clinical trial.
Necrotizing fasciitis in two patients with myelodysplastic syndrome treated with azacitidine
Authors: Lai Shiue‐Wei , Huang Tzu‐Chuan , Ye Ren‐Hua , Wu Yi‐Ying
Published: May 2014

Azacitidine is a novel agent for treating myelodysplastic syndromes (MDS). It has a relatively safe toxicity profile with very few reported skin toxicities. Patients with MDS were prone to get severe infections, especially via respiratory tract, urinary system, and bloodstream. However, necrotizing fasciitis (NF) is a relatively rare event in patients with MDS, and it is hard to diagnose early. Here, we report two MDS cases that developed NF in lower extremities while receiving azacitidine treatment. One of them survives after emergent fasciotomy along with the administration of broad‐spectrum antibiotics and intravenous immunoglobulin.
Turoctocog alfa (NovoEight®) – from design to clinical proof of concept
Authors: Ezban Mirella , Vad Knud , Kjalke Marianne
Published: May 2014

Turoctocog alfa (NovoEight®) is a recombinant factor VIII (rFVIII) with a truncated B‐domain made from the sequence coding for 10 amino acids from the N‐terminus and 11 amino acids from the C‐terminus of the naturally occurring B‐domain. Turoctocog alfa is produced in Chinese hamster ovary (CHO) cells without addition of any human‐ or animal‐derived materials. During secretion, some rFVIII molecules are cleaved at the C‐terminal of the heavy chain (HC) at amino acid 720, and a monoclonal antibody binding C‐terminal to this position is used in the purification process allowing isolation of the intact rFVIII. Viral inactivation is ensured by a detergent inactivation step as well as a 20‐nm nano‐filtration step. Characterisation of the purified protein demonstrated that turoctocog alfa was fully sulphated at Tyr346 and Tyr1664, which is required for optimal proteolytic activation by thrombin. Kinetic assessments confirmed that turoctocog alfa was activated by thrombin at a similar rate as seen for other rFVIII products fully sulphated at these positions. Tyr1680 was also fully sulphated in turoctocog alfa resulting in strong affinity (low nm Kd) for binding to von Willebrand factor (VWF). Half‐lives of 7.2 ± 0.9 h in F8‐KO mice and 8.9 ± 1.8 h haemophilia A dogs supported that turoctocog alfa bound to VWF after infusion. Functional studies including thromboelastography analysis of human haemophilia A whole blood with added turoctocog alfa and effect studies in mice bleeding models demonstrated a dose‐dependent effect of turoctocog alfa. The non‐clinical data thus confirm the haemostatic effect of turoctocog alfa and, together with the comprehensive clinical evaluation, support the use as FVIII replacement therapy in patients with haemophilia A.
Rapid onset of peripheral artery disease in a chronic myeloid leukemia patient without prior arterial disorder: direct relationship with nilotinib exposure and clinical outcome
Authors: Mirault Tristan , Rea Delphine , Azarine Arshid , Messas Emmanuel
Published: May 2014

The second‐generation tyrosine kinase inhibitor (TKI) of the BCR‐ABL1 oncoprotein nilotinib used in patients with chronic myeloid leukemia is suspected to increase the risk of arterial occlusion, especially in patients with pre‐existing cardiovascular risk factors or established cardiovascular diseases. Here, we describe a case of unexpected and rapid onset of symptomatic peripheral artery disease (PAD) associated with silent stenosis of digestive and renal arteries in a nilotinib‐treated patient devoid of significant cardiovascular diseases (CVD) risk factor, prior atherosclerotic disease, or other cause of arterial damage. This is the first report to establish a direct relationship between nilotinib exposure and PAD and to reveal that arterial damage is irreversible despite rapid drug withdrawal. However, functional outcome was favorable upon rapid TKI replacement, specific cardiovascular disease management, and development of collateral arterial network.
Methods and preliminary findings of a cost‐effectiveness study of glass‐ionomer‐based and composite resin sealant materials after 2 yr
Authors: Goldman Ann S. , Chen Xi , Fan Mingwen , Frencken Jo E.
Published: May 2014

The cost‐effectiveness of glass‐carbomer, conventional high‐viscosity glass‐ionomer cement (HVGIC) [without or with heat (light‐emitting diode (LED) thermocuring) application], and composite resin sealants were compared after 2 yr in function. Estimated net costs per sealant were obtained from data on personnel time (measured with activity sampling), transportation, materials, instruments and equipment, and restoration costs for replacing failed sealants from a community trial involving 7‐ to 9‐yr‐old Chinese children. Cost data were standardized to reflect the placement of 1,000 sealants per group. Outcomes were the differences in the number of dentine caries lesions that developed between groups. The average sealant application time ranged from 5.40 min (for composite resin) to 8.09 min (for LED thermocured HVGIC), and the average cost per sealant for 1,000 performed per group (simulation sample) ranged from $US3.73 (for composite resin) to $US7.50 (for glass‐carbomer). The incremental cost‐effectiveness of LED thermocured HVGIC to prevent one additional caries lesion per 1,000 sealants performed was $US1,106 compared with composite resin. Sensitivity analyses showed that differences in the cost of materials across groups had minimal impact on the overall cost. Cost and effectiveness data enhance policymakers’ ability to address issues of availability, access, and compliance associated with poor oral‐health outcomes, particularly when large numbers of children are excluded from care, in economies where oral health services are still developing.
Malocclusion and quality of life in Brazilian preschoolers
Authors: Sousa Raulison V. , Clementino Marayza A. , Gomes Monalisa C. , Martins Carolina C. , Granville‐Garcia Ana F. , Paiva Saul M.
Published: May 2014

The aim of the present study was to assess the impact of malocclusion on oral health‐related quality of life (OHRQoL) among preschool children and their families. This study involved 732 preschoolers. Parents/caregivers filled out the Brazilian version of the Early Childhood Oral Health Impact Scale (B‐ECOHIS) and a questionnaire addressing sociodemographic data. Overbite, overjet, and crossbite were recorded during the clinical examination. Bivariate and multiple Poisson regression analyses were performed and prevalence ratio (PR) were calculated (α = 5%). The prevalence of negative impact from malocclusion on OHRQoL was 27.6% among the children and 22.3% among the families. Mother's schooling (PR = 1.37; 95% CI: 1.10–1.70), parent's/caregiver's assessment of child's oral health (PR = 2.07; 95% CI: 1.60–2.58), history of toothache (PR = 3.84; 95% CI: 2.34–6.30), and visits to the dentist (PR = 0.59; 95% CI: 0.37–0.94) remained significantly associated with OHRQoL in the final model for the children, whereas parent's/caregiver's assessment of child's oral health (PR = 2.32; 95% CI: 1.71–3.14) and history of toothache (PR = 2.28; 95% CI: 1.69–3.09) remained significantly associated with OHRQoL for the families. Malocclusion was not associated with a negative impact on OHRQoL. In contrast, parents’/caregivers’ perceptions regarding the oral health of their children and a history of toothache were predictors of a negative impact on the OHRQoL.
Expression ofCD163, interleukin‐10, and interferon‐gamma in oral squamous cell carcinoma: mutual relationships and prognostic implications
Authors: Wang Shan , Sun Miao , Gu Chuanwen , Wang Xiaolong , Chen Dong , Zhao Eryang , Jiao Xiaohui , Zheng Jinhua
Published: May 2014

Tumor‐associated macrophages (TAMs) and their associated inflammatory cytokines represent the major inflammatory component of the stroma of many tumors and can affect prognosis in the case of neoplasms. The objective of this study was to determine the prognostic significance ofCD163+cells, interleukin‐10 (IL‐10), and interferon‐gamma (IFN‐γ) in oral lesions associated with oral squamous cell carcinoma (OSCC). The levels ofCD163,IFN‐γ, andIL‐10 in the tissue samples of 240 patients withOSCCand 58 patients with other oral lesions were assessed by immunohistochemistry. Individuals with lowIFN‐γlevels, highIL‐10 levels, and lowCD163 levels were of special concern with respect toOSCCprogression. We found that high levels ofCD163, or a combination of lowIFN‐γlevels, highIL‐10 levels, and lowCD163 levels, were associated with poorer overall survival (OS).CD163+cells provide better predictive power forOSin comparison with traditional markers, such as clinical stage and lymph node metastasis. Therefore,CD163+cells may be effective prognostic predictors ofOSCC.IL‐10 may also indicate poor outcomes whenIFN‐γsecretion is low and the cells areCD163−.
Thermal burn of palate in an elderly diabetic patient
Authors: Kannan Sathya , Chandrasekaran Balamanikandasrinivasan , Muthusamy Senthilkumar , Sidhu Preena , Suresh Nanditha
Published: May 2014

Background

Burns of the oral mucosa may be caused by thermal, mechanical, chemical, electrical or radiation injury. Clinically, these burns can produce localised or diffuse areas of tissue damage depending on the severity and extent of the insult. Most oral thermal burns produce erosions or ulcers on the palate or tongue.

Materials and methods

A case of palatal burn in a 66‐year‐old diabetic patient caused by drinking hot cereal is presented. The role of diabetes in causing oral mucosal dysesthesia that predisposed the occurrence of this burn is also discussed.

Conclusion

Insensate palatal burn as a rare complication of diabetes mellitus is reported here. With the disease being more widespread now, its potential oral complications will be seen with increasing frequency.
The Decline of International Migration as an Economic Force in Rural Areas: A Mexican Case Study
Authors: Jones Richard C.
Published: May 2014

Since 2000, and especially since 2007, there has been a reduction in the importance of international migration and remittances in major global sending regions as a result of recession in receiving countries, anti-immigrant policies, and improvement in economic opportunities in origin countries. A household survey in five rural communities in Zacatecas, Mexico, in 1995 and again in 2009 exemplifies these trends. Among youthful adults likely to have first migrated in the decade prior to each of these years, there was a significant drop in the proportion of active migrants. Among the active migrants, stays abroad became longer and more permanent, and their households exhibited fewer remittances, less family business ownership, and fewer local purchases, in 2009 compared to 1995. Finally, non-migrant households greatly improved their economic status in relation to migrant households over the period, reaching approximate parity with their migrant counterparts.

Remittances channeled into some of the most backward regions and countries of the third World are … likely to play a continuing role locally. [They] are safety nets for poor regions left behind by the agglomerative behavior of international capital, by the preoccupations of the international community with other matters, and by the indifference of their own governments (Jones, 1998).
Recent Immigration to Canada and the United States: A Mixed Tale of Relative Selection
Authors: Kaushal Neeraj , Lu Yao
Published: May 2014

Using large-scale census data and adjusting for sending-country fixed effect to account for changing composition of immigrants, we study relative immigrant selection to Canada and the U.S. during 1990–2006, a period characterized by diverging immigration policies in the two countries. Results show a gradual change in selection patterns in educational attainment and host-country language proficiency in favor of Canada as its post-1990 immigration policy allocated more points to the human capital of new entrants. Specifically, in 1990, new immigrants in Canada were less likely to have a B.A. degree than those in the U.S.; they were also less likely to have a highschool or lower education. By 2006, Canada surpassed the U.S. in drawing highly educated immigrants, while continuing to attract fewer low-educated immigrants. Canada also improved its edge over the U.S. in terms of host-country language proficiency of new immigrants. Entry-level earnings, however, do not reflect the same trend: Recent immigrants to Canada have experienced a wage disadvantage compared to recent immigrants to the U.S., as well as Canadian natives. One plausible explanation is that while the Canadian points system has successfully attracted more educated immigrants, it may not be effective in capturing productivity-related traits that are not easily measurable.
Joined up Justice: Understanding the Links Between Employment, Benefits and Offending
Authors: Wingfield Melissa , Trenell Paul
Published: May 2014

The cycle of prison, unemployment and re-offending dominates many lives. Strangely, data about this all-too-familiar scenario has been lacking: historically the information was split between three different government departments, unshared and in incompatible forms. Melissa Wingfield and Paul Trenell show how data-sharing across government has now yielded insights into the connections between employment, benefits and offending.
The Erebus, the Terror and the North-West Passage: Did Lead Really Poison Franklin's Lost Expedition?
Authors: Millar Keith , Bowman Adrian , Battersby William
Published: May 2014

The Franklin expedition of 1845 tried to find the North-West Passage between the Atlantic and the Pacific oceans. It disappeared into the ice. A classic example of historical detective work seemed to explain its fate – but is it plausible? Keith Millar, Adrian Bowman and William Battersby reanalyse variation in the evidence and evidence for variation.
Data and the Law: Beyond the Sweat of the Brow: Who Owns Published Data? And What is Data?
Authors: van Belle Gerald , Ruiter Leslie
Published: May 2014

You gather data for research, you publish – and who then owns your data? That begs the philosophical question: what is data? The US Supreme Court has ruled that “data” are facts and cannot be copyrighted. So can everyone use your data? And why do authors find themselves paying to use data that others have gathered? In the new age of supposedly open access to digital and big data, Gerald van Belle and Leslie Ruiter discuss the background, current status and future challenges to who legally owns data.
Health Freaks on Trial: Duct Tape, Bull Semen and the Call of Television
Authors: Bland Martin
Published: May 2014

Bull semen cures baldness? Tree bark treats Crohn's disease? Use toothpaste for love-bites and make love to cure a migraine? Prop yourself upside down to avert hair loss, and stick duct tape on verrucas? Martin Bland heard the call of TV to statistically test outlandish home remedies and found 10 minutes of fame and an astonishing clinical result.
Alphonse Bertillon and the Measure of Man: More Expert than Sherlock Holmes
Authors: Farebrother Richard , Champkin Julian
Published: May 2014

“Every measurement slowly reveals the workings of the criminal. Careful observation and patience will reveal the truth.” Thus wrote the French criminologist Alphonse Bertillon, who died 100 years ago in the spring of 1914. Almost forgotten today, he was the most famous criminologist of his time, a household name for his ingenious method of identifying criminals by carefully measuring 11 key dimensions of their bodies. He did more. He established the standardised procedures used in police forces to this day. Richard Farebrother and Julian Champkin look at a flawed near-genius.
Justice is a Full Cooked Breakfast with Trimmings
Authors: Champkin Julian
Published: May 2014

An army marches on its stomach, said Napoleon. Julian Champkin finds that judges sit on theirs.
Effects of Nighttime Single‐Dose Administration of Vasodilating vs Sympatholytic Antihypertensive Agents on Sleep Blood Pressure in Hypertensive Patients With Sleep Apnea Syndrome
Authors: Kario Kazuomi , Kuwabara Mitsuo , Hoshide Satoshi , Nagai Michiaki , Shimpo Masahisa
Published: May 2014

Obstructive sleep apneas syndrome (OSAS) is associated with nocturnal hypertension with higher sleep blood pressure (BP) and its variability, both of which increase cardiovascular risk. In this crossover design study, the effect of nighttime single‐dose administration of vasodilating (nifedipine 40 mg) vs sympatholytic (carvedilol 20 mg) antihypertensive agents on sleep BP in 11 hypertensive OSAS patients was evaluated. The authors recently developed a trigger sleep BP monitor with an oxygen‐triggered function that initiates BP measurement when oxygen desaturation falls. The BP‐lowering effects of nifedipine on the mean (P<.05) and minimum sleep systolic BPs (SBPs) (P<.01) were stronger than those of carvedilol. Sleep SBP surge (difference between the hypoxia‐peak SBP measured by oxygen‐triggered function and SBPs within 30 minutes before and after the peak SBP) was only significantly reduced by carvedilol (P<.05). The nighttime dosing of both vasodilating and sympatholytic antihypertensive drugs is effective to reduce sleep BP but with different BP‐lowering profiles.