bluuebunny/crossref_metadata_2025 huggingface dataset:
Karabournaki
Authors: Saripanidi Vivi
Published: June 2016

The coastal site at Karabournaki in Thessalonike is identified with the main settlement of ancient Therme, which was one of the major ports of the northern Aegean. Inhabited probably from the Late Bronze Age until Roman times, the settlement flourished particularly during the Archaic period. Apart from graves, excavations at this site have revealed residential quarters, along with the remains of metallurgical and pottery production activities.
Pyla‐
Kokkinokremos
Authors: Georgiou Artemis
Published: June 2016

Pyla‐
Kokkinokremos
was a short‐lived settlement (ca. 1225–1175
bce
) established on the southeastern coast of Cyprus.
Teichos Dymaion
Authors: Giannopoulos Theodoros G.
Published: June 2016

Teichos Dymaion (“Wall of Dymaeans”) is a multi‐period fortified acropolis in the westernmost part of Achaia, in the northwestern Peloponnese in southern Greece. The name of the site goes back to the Hellenistic period (323–30
bce
), when the citadel was used by the Achaian city of Dyme. However, the main phase of the fortification dates back to the Late Bronze Age or Mycenaean period (1700–1050
bce
), probably to the thirteenth century
bce
.
Shawushka
Authors: Beckman Gary
Published: June 2016

Shawushka is a prominent Hurrian goddess of sexuality, warfare, and magic identified early on with Mesopotamian Ištar. Most information concerning her has been found at the Hittite capital Hattusa, where her cult was introduced in the fifteenth century
bce
from Hurrian‐influenced Kizzuwatna/Cilicia.
Dusares
Authors: Tholbecq Laurent
Published: June 2016

Dusares, mentioned in both Nabataean inscriptions and classical sources, held a dominant position among Nabataean divinities. Apparently associated with the Nabataean dynasty during the independent kingdom, the god was later referred to by various cities of Roman
Provincia Arabia
as an important marker of identity.
Philotimia
Authors: Ferrucci Stefano
Published: June 2016

Philotimia
, literally “love of honor,” was listed, in the fourth century
bce
, among Athenian “civic virtues,” recognized by the
polis
in honorary decrees, and considered a positive model for social and political conduct, mainly in relation to public offices (
archai)
and liturgies. A “system of honors” emerged ca. 350
bce
, and established a pattern of relations between the wealthy and the political community, continued and reinforced in Hellenistic times, when the king (
basileus
) appears as the main benefactor of the
polis
.
Philotimia
was, on the other hand, an ambivalent and controversial concept, owing to the potential risk of excess in striving for honors and in ostentatious spending to obtain them.
Syme, Ronald (1903–1989)
Authors: Pelling Christopher B. R.
Published: June 2016

Sir Ronald Syme was a New Zealand‐born, Oxford‐based scholar, often regarded as the greatest Roman historian of the twentieth century. His two great works, noted for their distinctive style as well as for their historical acumen, are
The Roman Revolution
(1939) and
Tacitus
(1958), but he wrote prolifically on other periods and authors, including late antiquity and the
Historia Augusta
.
Leo I, emperor
Authors: Rizos Efthymios
Published: June 2016

Leo I reigned as East Roman emperor from 457 to 474
ce
. He supported Chalcedonian Orthodoxy and attempted unsuccessfully to reconquer North Africa from the Vandals. He came into conflict with the Gothic patrician Aspar and had him murdered.
Leo
III
, emperor
Authors: Rizos Efthymios
Published: June 2016

Leo III reigned as Byzantine emperor from 717 to 741 and was the founder of the Isaurian dynasty. He is remembered as the emperor who initiated Byzantine iconoclasm.
Breastfeeding
Authors: Totelin Laurence M. V.
Published: June 2016

Evidence for ancient breastfeeding is abundant but difficult to interpret. It relates mostly to the upper classes and to slaves, and more to breastfeeding by wet‐nurses than by mothers. The extent of maternal breastfeeding must be assessed through comparative studies. Breastfeeding was the object of debates in antiquity.
Syncretism
Authors: Pedrucci Giulia
Published: June 2016

Marked by its conflicting etymology and predisposed by its past use in theology as a pejorative and biased term, syncretism has entered the study of religion, including anthropology, for the purpose of describing processes in religion of integration, acculturation, transformation, and innovation in various fields of study. In order to reach an agreement on this heated debate one must consider all the aspects connected with the category, whether we are talking about syncretism as a descriptive, taxonomic, discursive, political, or explanatory term.
Iasos, Bronze Age and Early Iron Age
Authors: Kelder Jorrit M.
Published: June 2016

Iasos is a site on the Anatolian southwest coast occupied from the Late Neolithic until the Middle Ages. Renowned for its excellent harbors in Classical times, Iasos was involved in Aegean trade already from the Early Bronze Age. During the Late Bronze Age, the site was drawn deeper into the Aegean orbit, and was characterized by strong Minoan, and later Mycenaean, cultural influence.
Lex Oppia
Authors: Hopwood Bronwyn
Published: June 2016

The
Lex Oppia
, passed in 215
bce
and repealed in 195
bce
, prohibited women from using more than half an ounce of gold, purple‐dyed clothing, or carriages except during public religious festivals. The law has become a focal point in discussions of Roman luxury and women's rights.
Tell Abu Hawam
Authors: Vacek Alexander
Published: June 2016

Tell Abu Hawam was a harbor town located in the bay of Haifa in Israel. It was occupied from the Middle Bronze Age to the medieval period. During the Late Bronze Age the site was an important harbor, which connected the Mediterranean with Israel and the Jordan valley.
Porada, Edith
Authors: Bahrani Zainab
Published: June 2016

Edith Porada was a leading twentieth‐century art historian and archaeologist of the ancient Near East.
Preliminary Outcomes of a Cross‐Site Cognitive–Behavioral and Neuromuscular Integrative Training Intervention for Juvenile Fibromyalgia
Authors: Tran Susan T. , Guite Jessica W. , Pantaleao Ashley , Pfeiffer Megan , Myer Gregory D. , Sil Soumitri , Thomas Staci M. , Ting Tracy V. , Williams Sara E. , Edelheit Barbara , Ounpuu Sylvia , Rodriguez‐MacClintic Jennifer , Zemel Lawrence , Zempsky William , Kashikar‐Zuck Susmita
Published: June 2016

Objective

Cognitive–behavioral therapy (CBT) is effective in reducing disability among youth with juvenile fibromyalgia (FM); however, engagement in moderate to vigorous physical activity remains poor, even after CBT. The purpose of this study was to evaluate the feasibility and preliminary outcomes of an innovative program combining CBT with specialized neuromuscular exercise: the Fibromyalgia Integrative Training for Teens (FIT Teens) program.

Methods

Adolescents with juvenile FM (n = 22, all female, ages 12–18 years) from 2 urban children's hospitals participated in the 8‐week FIT Teens intervention. Participants completed measures of pain intensity, functional disability, depressive symptoms, pain catastrophizing, fear of movement, and readiness to change at baseline and after the intervention.

Results

The feasibility of the intervention across 2 sites was documented, including high retention rates (80%). Participants showed significant decreases in functional disability (P < 0.05), depression (P < 0.001), fear of movement (P < 0.01), and pain catastrophizing (P < 0.001) from pre‐ to postintervention. Results of the readiness to change measure indicated a significant decrease in precontemplation (P < 0.01) and increase in action/maintenance scores (P < 0.001). All results demonstrated medium to large effect sizes.

Conclusion

Adolescents with juvenile FM reported significant improvements in physical function and reduced fear of movement following the intervention. Improvement in physical function was achieved in a shorter time frame than in a prior trial of CBT without an exercise component. Further work is needed to compare the FIT Teens program with existing approaches and determine whether objective changes in exercise participation are achieved.
Rates of Serious Infections in HIV‐Infected Patients Receiving Tumor Necrosis Factor Inhibitor Therapy for Concomitant Autoimmune Diseases
Authors: Wangsiricharoen Sintawat , Ligon Colin , Gedmintas Lydia , Dehrab Admad , Tungsiripat Marisa , Bingham Clifton , Lozada Carlos , Calabrese Leonard
Published: June 2016

Objective

To estimate the incidence of serious infections in patients with HIV infection and autoimmune disease who were treated with tumor necrosis factor (TNF) inhibitors, and to compare these rates by stratified viral load levels.

Methods

Using a unified search strategy, 4 centers identified HIV‐infected patients exposed to TNF inhibitors. Patient characteristics and infection data were assessed via chart review in all patients who were ≥18 years old and who received TNF inhibitor therapy after HIV diagnosis, between January 1999 and March 2015.

Results

We studied 23 patients with 26 uses of TNF inhibitor therapy (86.7 person‐years of followup). Two (8.7%) experienced at least 1 serious infection episode, for an overall incidence rate of 2.55 per 100 patient‐years (95% confidence interval [95% CI] 0.28–9.23). The incidence rate per 100 patient‐years was 3.28 (95% CI 0.04–18.26) among patients with a viral load >500 copies/ml at therapy initiation and 2.09 (0.03–11.65) among patients with a viral load ≤500 copies/ml.

Conclusion

This study suggests that the rate of serious infections in patients with HIV infection under active care who have received treatment with TNF inhibitors may be comparable to the rates observed in registry databases.
Inflammatory Arthritis Prevalence and Health Services Use in the First Nations and Non–First Nations Populations of Alberta, Canada
Authors: Barnabe Cheryl , Jones C. Allyson , Bernatsky Sasha , Peschken Christine A. , Voaklander Don , Homik Joanne , Crowshoe Lynden F. , Esdaile John M. , El‐Gabalawy Hani , Hemmelgarn Brenda
Published: June 2016

Objective

To estimate prevalence of rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic disease (PsD), and crystal‐related arthritis and health care use for inflammatory arthritis in First Nations and non–First Nations patients in Alberta, Canada.

Methods

Population‐based cohorts of adults with RA, AS, PsD, and crystal‐related arthritis were defined, with First Nations determination by premium payer status, to estimate prevalence rates. Rates of outpatient primary care, specialist visits, and hospitalizations (all‐cause, inflammatory‐arthritis specific) were estimated.

Results

RA affected 3 times as many First Nations residents compared to non–First Nations residents (standardized rate ratio [SRR] 3.2, 95% confidence interval [95% CI] 2.9–3.4). AS and PsD were more prevalent in First Nations (AS 0.6 per 100 residents; SRR 2.7, 95% CI 2.3–3.2 and PsD 0.3 per 100 residents; SRR 1.5, 95% CI 1.3–1.9), whereas crystal‐related arthritis was less prevalent (SRR 0.7, 95% CI 0.6–0.7). First Nations patients were more likely to have primary care visits (SRR 1.7, 95% CI 1.6–1.8) and less likely to have specialist visits (SRR 0.6, 95% CI 0.6–0.7) for RA relative to non–First Nations individuals. In PsD and crystal‐related arthritis, First Nations people had higher rates of cause‐specific hospitalizations.

Conclusion

The estimated prevalence of RA, AS, and PsD was higher in the First Nations population, while crystal‐related arthritis was less prevalent compared to the non–First Nations population. First Nations people were more likely to see primary care physicians and were less likely to see specialists for inflammatory arthritis care.
Efficacy of a Rheumatoid Arthritis–Specific Smoking Cessation Program: A Randomized Controlled Pilot Trial
Authors: Aimer Pip , Treharne Gareth J. , Stebbings Simon , Frampton Chris , Cameron Vicky , Kirby Sandra , Stamp Lisa K.
Published: June 2016

Objective

Smoking adversely influences comorbidities in rheumatoid arthritis (RA). The aim of this pilot study was to investigate whether smoking cessation is increased following a 3‐month smoking cessation intervention tailored for people with RA.

Methods

Thirty‐nine current smokers with RA were recruited. Participants were randomized into the control group to receive the current local standard of care for smoking cessation (i.e., ABC = brief advice and subsidized nicotine replacement therapy [NRT], or into the intervention group to receive ABC plus additional smoking cessation advice for 3 months (ABC+), including face‐to‐face, telephone, and e‐mail contact. Advice was tailored to the participants' specific needs from a range of intervention tools focused on education about smoking and RA, pain control, exercise, coping, and support. The primary outcome was smoking cessation at 6 months. The secondary outcome was sustained reduction in smoking at 6 months. Disease and psychosocial characteristics of quitters and nonquitters were examined.

Results

The overall smoking cessation rate was 24%. There was no significant difference in smoking cessation rates between the ABC and ABC+ groups (21% versus 26%; P = 0.70). The mean number of cigarettes smoked daily was reduced by 44% (P < 0.001) but did not differ between ABC and ABC+ groups (mean reduction 47% versus 41%; P = 0.72). Successful quitters had more years in education and had smoked less across their lifetime, but these differences were not statistically significant.

Conclusion

Smoking cessation in RA may lead to a reduced comorbid burden. The lack of added benefit of the tailored intervention suggests that brief advice and NRT are currently the best practice for supporting people with RA who wish to quit smoking.
Turning the tables of sex distinction in craniofacial identification: Why females possess thicker facial soft tissues than males, not vice versa
Authors: Stephan Carl N. , Preisler Rory , Bulut Ozgur , Bennett Mike
Published: June 2016

Males are universally reported to possess larger facial soft‐tissue thickness (FSTT) than females, however, this observation oversimplifies the raw data yielding an underpowered assessment of FSTT sex‐patterning where: differences are small (η2 < 5%) and inconsistent (females are routinely larger than males at the cheeks). Here we investigate body‐size normalized data to assess whether more general and improved understanding of FSTT sex‐variation in humans is possible. FSTTs were measured in 52 healthy living Australians aged 18 to 30 years using B‐mode ultrasound. Participants' stature and body mass were also measured. Sex differences were calculated before and after normalization by the aforementioned body‐composition variables. Methods were repeated in three other independent samples to evaluate reproducibility: 100 American Whites and 60 American Blacks measured by B‐mode ultrasound; and 50 Turkish residents measured by regular supine CT. Compared to raw mean differences (F < M, by −6%), females displayed much thicker FSTTs than males when normalized for body mass (F > M, by +16%). Consequently, while the sexes share similar raw values, females possess much larger FSTTs for their relatively lighter bodies. The relative FSTT difference was 2.7× larger than the raw mean difference. Sex differences in FSTT are of larger magnitude and reversed direction in mass normalized data. Contrary to popular thought, females possess much larger FSTTs than males owing to their generically lighter bodies (−18 kg). These data patterns help explain why the pooling of sex‐categorized FSTT does not jeopardize the sex‐difference—it is encoded more strongly in terms relative to body mass.
Basis for the gain and subsequent dilution of epidermal pigmentation during human evolution: The barrier and metabolic conservation hypotheses revisited
Authors: Elias Peter M. , Williams Mary L.
Published: June 2016

The evolution of human skin pigmentation must address both the initial evolution of intense epidermal pigmentation in hominins, and its subsequent dilution in modern humans. While many authorities believe that epidermal pigmentation evolved to protect against either ultraviolet B (UV‐B) irradiation‐induced mutagenesis or folic acid photolysis, we hypothesize that pigmentation augmented the epidermal barriers by shifting the UV‐B dose–response curve from toxic to beneficial. WhereaserythemogenicUV‐B doses produce apoptosis and cell death,suberythemogenicdoses benefit permeability and antimicrobial function. Heavily melanized melanocytes acidify the outer epidermis and emit paracrine signals that augment barrier competence. Modern humans, residing in the cooler, wetter climes of south‐central Europe and Asia, initially retained substantial pigmentation. While their outdoor lifestyles still permitted sufficient cutaneous vitamin D3 (VD3) synthesis, their marginal nutritional status, coupled with cold‐induced caloric needs, selected for moderate pigment reductions that diverted limited nutritional resources towards more urgent priorities (=metabolic conservation). The further pigment‐dilution that evolved as humans reached north‐central Europe (i.e., northern France, Germany), likely facilitated cutaneous VD3 synthesis, while also supporting ongoing, nutritional requirements. But at still higher European latitudes where little UV‐B breaches the atmosphere (i.e., present‐day UK, Scandinavia, Baltic States), pigment dilution alone could not suffice. There, other nonpigment‐related mutations evolved to facilitate VD3 production; for example, in the epidermal protein, filaggrin, resulting in reduced levels of its distal metabolite,trans‐urocanic acid, a potent UV‐B chromophore. Thus, changes in human pigmentation reflect a complex interplay between latitude, climate, diet, lifestyle, and shifting metabolic priorities.
Constructing cranial ontogenetic trajectories: A comparison of growth, development, and chronological age proxies using a known‐age sample of Macaca mulatta
Authors: Simons Evan A. , Frost Stephen R.
Published: June 2016

Recent morphometric research has generated opposing conclusions regarding the ontogenetic trajectories of catarrhine crania, possibly due to the ontogenetic proxies used to calculate them. Therefore, we used three surrogates: size, molar eruption, and chronological age to generate trajectories in a known‐age sample to produce ontogenetic trajectories and determine the similarities and differences between them. Forty‐three landmarks from an ontogenetic series of 160 Macaca mulatta crania, with associated ages at death, were used to produce ontogenetic trajectories of cranial shape change. These were computed by sex through multivariate regression of Procrustes aligned coordinates against three surrogates for ontogeny: natural log of centroid size (growth), molar eruption stage (development), and chronological age. These trajectories were compared by calculating the angles between them. Each trajectory was also used to produce simulated adults from juveniles, which were then compared with each other and actual adults. The different trajectories are nearly parallel as each of the surrogates track similar aspects of ontogenetic cranial shape change, but chronological age was the most divergent. Simulated adults produced using the developmental stage trajectories were most similar to actual adults. When simulated adults were produced from opposite sex trajectories, they resembled the sex from which the trajectory was produced, not the sex of the juvenile specimen. We discuss properties of the trajectories produced from each of the surrogates, the possible reasons for previously opposing conclusions, how these properties can inform future investigations, and how our investigation bears on analyses of heterochrony.
Morphological and mechanical behavior of chemically treated jute‐PHBV bio‐nanocomposites reinforced with silane grafted halloysite nanotubes
Authors: Zainuddin Shaik , Fahim Abdullah , Shoieb Shaik , Syed Farooq , Hosur Mahesh V. , Li Dawen , Hicks Chelsea , Jeelani Shaik
Published: June 2016

In this study, at first, thin films of poly(3‐hydroxybutyrate‐co−3‐hydroxyvalerate) (PHBV) nanocomposites were prepared by adding 1–3 wt % grafted halloysite nanotubes (G‐HNTs). Jute‐PHBV bio‐nanocomposites were then fabricated using these films and chemically treated jute fibers in a compression mold machine. The effect of treatment and modification on jute fiber and halloysite nanotubes (HNTs), and the change in their morphology was investigated using Fourier transform infrared (FTIR) spectroscopy, X‐ray diffraction (XRD), scanning and transmission electron microscopy (SEM, TEM). Flexural and thermomechanical properties were determined using a three‐point bend test and dynamic mechanical analysis (DMA). The results showed separation of fiber bundles with rough fiber surfaces, and grafting of silane coupling agents on fibers and HNTs after the chemical treatment. As a result, a strong bonding was established between the PHBV, G‐HNTs and jute fibers that lead to significant improvements in flexural and thermomechanical properties of jute‐PHBV bio‐nanocomposites. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43994.
The dominant factor for mechanical property of polyimide films containing heterocyclic moieties: In‐plane orientation, crystallization, or hydrogen bonding
Authors: Luo Longbo , Zhang Jing , Huang Jieyang , Feng Yan , Peng Chaorong , Wang Xu , Liu Xiangyang
Published: June 2016

Crystallization, in‐plane orientation, and hydrogen bonding interactions are three vital factors for enhancing mechanical properties of polyimide (PI) films. However, which is the dominant factor? In this study, three PI films containing heterocyclic moiety, poly(benzoxazole‐imide), poly(benzimidazole‐imide), and poly(pyrimidine‐imide) were chosen to comparative study. The crystallinity of poly(benzoxazole‐imide), poly(benzimidazole‐imide), and poly(pyrimidine‐imide) PI films are 36, 24, and 15%, respectively. The results of small angle X‐ray scattering indicate poly(benzoxazole‐imide) and poly(benzimidazole‐imide) films show periodical lamellar structures, while poly(pyrimidine‐imide) shows no long period due to low crystallinity. In‐plane orientation (P200) is calculated from polarized attenuated total reflection (ATR)‐Fourier transform infrared and refractive indices. The order of in‐plane orientation is poly(benzimidazole‐imide) < poly(benzoxazole‐imide) < poly(pyrimidine‐imide). Hydrogen bonding interactions, which restrict chain motion and hinder spontaneous in‐plane orientation, are only formed in poly(benzimidazole‐imide). The relationship between mechanical properties and three influence factors are discussed, and the order of influence extent for mechanical properties of PI films is hydrogen bonding interactions < degree of crystallization < in‐plane orientation. Two structure models for PI films are proposed in order to further confirm the dominant effect of in‐plane orientation on the mechanical properties. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 44000.
Myeloperoxidase–Antineutrophil Cytoplasmic Antibody (ANCA)–Positive Granulomatosis With Polyangiitis (Wegener's) Is a Clinically Distinct Subset of ANCA‐Associated Vasculitis: A Retrospective Analysis of 315 Patients From a German Vasculitis Referral Center
Authors: Schirmer Jan H. , Wright Marvin N. , Herrmann Kristine , Laudien Martin , Nölle Bernhard , Reinhold‐Keller Eva , Bremer Jan P. , Moosig Frank , Holle Julia U.
Published: June 2016

Objective

To compare the phenotype, clinical course, and outcome of myeloperoxidase (MPO)–antineutrophil cytoplasmic antibody (ANCA)–positive granulomatosis with polyangiitis (Wegener's) (GPA) to proteinase 3 (PR3)–ANCA–positive GPA and to MPO‐ANCA–positive microscopic polyangiitis (MPA).

Methods

We characterized all MPO–ANCA–positive patients classified as having GPA by the European Medicines Agency algorithm who attended our center, in a retrospective chart review. A second cohort of patients with PR3‐ANCA–positive GPA matched for age and sex was characterized. Patients with MPO‐ANCA–positive MPA from a recently published cohort were also included in the analysis. All patients were diagnosed and treated according to a standardized interdisciplinary approach at a vasculitis referral center.

Results

Comprehensive data were available for 59 patients with MPO‐ANCA–positive GPA, and they were compared to 118 patients with PR3‐ANCA–positive GPA and 138 patients with MPO‐ANCA–positive MPA. We observed a distinct phenotype in MPO‐ANCA–positive GPA as compared to the other 2 cohorts. Patients with MPO‐ANCA–positive GPA frequently had limited disease without severe organ involvement, had a high prevalence of subglottic stenosis, and had less need for aggressive immunosuppressive therapy (cyclophosphamide/rituximab). The patients with MPO‐ANCA–positive GPA were also younger than the MPA patients and were predominantly female (significantly different than the MPA cohort). While GPA patients had higher survival rates compared to MPA patients (due to a high prevalence of pulmonary fibrosis in MPA), patients with MPO‐ANCA had significantly lower relapse rates than those with PR3‐ANCA.

Conclusion

Patients with MPO‐ANCA−positive GPA show significantly different clinical courses compared to those with PR3‐ANCA−positive GPA or MPO‐ANCA−positive MPA, which should be considered in their clinical management. Classification according to ANCA specificity may improve the evaluation of relapse risk.
Relapsing Polychondritis Can Be Characterized by Three Different Clinical Phenotypes: Analysis of a Recent Series of 142 Patients
Authors: Dion Jérémie , Costedoat‐Chalumeau Nathalie , Sène Damien , Cohen‐Bittan Judith , Leroux Gaëlle , Dion Charlotte , Francès Camille , Piette Jean‐Charles
Published: June 2016

Objective

Relapsing polychondritis (RP) is a rare condition characterized by recurrent inflammation of cartilaginous tissue and systemic manifestations. Data on this disease remain scarce. This study was undertaken to describe patient characteristics and disease evolution, identify prognostic factors, and define different clinical phenotypes of RP.

Methods

We performed a retrospective study of 142 patients with RP who were seen between 2000 and 2012 in a single center.

Results

Of the 142 patients, 86 (61%) were women. The mean ± SD age at first symptoms was 43.5 ± 15 years. Patients had the following chondritis types: auricular (89%; n = 127), nasal (63%; n = 89), laryngeal (43%; n = 61), tracheobronchial (22%; n = 32), and/orcostochondritis (40%; n = 57). The main other manifestations were articular (69%; n = 98), ophthalmologic (56%; n = 80), audiovestibular (34%; n = 48), cardiac (27%; n = 38), and cutaneous (28%; n = 40). At a mean ± SD followup of 13 ± 9 years, the 5‐ and 10‐year survival rates were 95 ± 2% and 91 ± 3%, respectively. Factors associated with death on multivariable analysis were male sex (P = 0.01), cardiac abnormalities (P = 0.03), and concomitant myelodysplastic syndrome (MDS) (P = 0.004) or another hematologic malignancy (P = 0.01). Cluster analysis revealed that separating patients into 3 groups was clinically relevant, thereby separating patients with associated MDS, those with tracheobronchial involvement, and those without the 2 features in terms of clinical characteristics, therapeutic management, and prognosis.

Conclusion

This large series of patients with definite RP revealed an improvement in survival as compared with previous studies. Factors associated with death were male sex, cardiac involvement, and concomitant hematologic malignancy. We identified 3 distinct phenotypes.
Outcome and Trends in Treatment of Systemic Juvenile Idiopathic Arthritis in the German National Pediatric Rheumatologic Database, 2000–2013
Authors: Klotsche Jens , Raab Anna , Niewerth Martina , Sengler Claudia , Ganser Gerd , Kallinich Tilmann , Niehues Tim , Hufnagel Markus , Thon Angelika , Hospach Toni , Horneff Gerd , Minden Kirsten
Published: June 2016

Objective

To investigate the clinical presentation and medical treatment of patients with systemic juvenile idiopathic arthritis (JIA) during the first year of illness. Our study focused on 3‐year outcomes in a subsample of patients who were followed up longitudinally.

Methods

From 2000 to 2013, 597 patients with systemic JIA and a disease duration of ≤12 months were recorded in the National Pediatric Rheumatologic Database. Among those patients, 3‐year outcome data were available for 133. These data included the clinical Juvenile Arthritis Disease Activity Score in 10 joints (JADAS‐10) and the physician's global assessment score (on a numerical rating scale), as well as assessment of joint involvement, growth retardation, and patient‐reported outcomes.

Results

The median clinical JADAS‐10 declined significantly, from 7 in 2000 to 2 in 2013, while the proportion of patients with inactive disease increased from 19% in 2000 to 41% in 2013. The rate of treatment with systemic glucocorticoids and disease‐modifying antirheumatic drugs (DMARDs) remained stable from 2000 to 2013. By 2013, the proportion of patients with systemic JIA who were treated with biologic DMARDs had increased to 20%. At 3‐year follow‐up, 72% of patients with systemic JIA had inactive disease, and 77% had no functional limitations. Growth retardation was associated with persistently high disease activity and continuing treatment with systemic glucocorticoids. At the 3‐year follow‐up, one‐third of patients were still being treated with systemic glucocorticoids.

Conclusion

The proportion of patients with inactive disease has increased over the past decade. Possible explanations may include improved access to specialized care, additional treatment options, and earlier or faster step‐up treatment. However, challenges in the management of systemic JIA remain, as ∼30% of patients continue to present with ongoing active disease.
Temperature‐controlled down‐conversion luminescence behavior of Eu3+‐doped transparent MF2 (M = Ba, Ca, Sr) glass ceramics
Authors: Zhou B. , E C. Q. , Bu Y. Y. , Meng L. , Yan X. H. , Wang X. F.
Published: June 2016

Eu3+‐doped transparent glass ceramics containing MF2 (M = Ba, Ca, Sr) nanocrystals were fabricated using a melt–quenching method, and the resulting structures were studied using X‐ray diffraction. Levels 5D1 and 5D0 of Eu3+ ions were verified as thermally coupled levels using the fluorescence intensity ratio method. The fluorescence intensity ratios, optical temperature sensitivity and thermal quenching ratios of the transparent glass ceramics were studied as a function of temperature. With an increase in temperature, the relative sensitivity (SR) decreased sharply at first, then slowly increased, before finally decreasing. The minimum SR values of GCBaF2 (GCB), GCCaF2 (GCC) and GCSrF2 (GCS) were 2.8 × 10−4, 0.8 × 10−4 and 1.9 × 10−4 K−1 at 360, 269 and 319 K, respectively. Glass ceramics with an intense emission intensity can be used to convert the measured spectrum into temperature and may have an important role in temperature detectors.
Drugs Against Rare Diseases: Are The Regulatory Standards Higher?
Authors: Gobburu J , Pastoor D
Published: June 2016

The US Food and Drug Administration (FDA) recently issued a draft Guidance for Industry for Rare Diseases: Common Issues in Drug Development (referred to as “Rare Diseases Guidance”). In our opinion, the FDA should consider: (a) explicitly acknowledging the standards are higher for rare diseases for the reasons presented in this article; and (b) illustrating innovative development pathways that may be acceptable for rare diseases, including case studies.
Teaching about Global Complexity: Experiential Conflict Resolution Pedagogy in Higher Education Classrooms
Authors: Romano Arthur , Hirsch Susan F. , Paczynska Agnieszka
Published: June 2016

This article examines the utility of experiential learning activities (ELAs) for teaching about global complexity and conflict resolution in higher education classrooms. It focuses on two key concepts: the nexus between global and local and the precarity experienced within global processes. Research on two ELAs, a multisession simulation and a single‐session image analysis, each designed for use in conflict resolution courses, produced extensive data on student learning. The analysis presented demonstrates that for many students, the ELAs resulted in greater engagement with course materials, more nuanced understandings of global complexity, and increased ability to link theory to practice.
Postsynaptic Y654 dephosphorylation of β‐catenin modulates presynaptic vesicle turnover through increased n‐cadherin‐mediated transsynaptic signaling
Authors: Chen Chin‐Yi , Chen Yi‐Ting , Wang Jen‐Yeu , Huang Yi‐Shuian , Tai Chin‐Yin
Published: June 2016

Synaptic adhesion molecules, which coordinately control structural and functional changes at both sides of synapses, are important for synaptogenesis and synaptic plasticity. Because they physically form homophilic or heterophilic adhesions across synaptic junctions, these molecules can initiate transsynaptic communication in both anterograde and retrograde directions. Using optical imaging approaches, we investigated whether an increase in postsynaptic N‐cadherin could correspondingly alter the function of connected presynaptic terminals. Postsynaptic expression of β‐catenin Y654F, a phosphorylation‐defective form with enhanced binding to N‐cadherin, is sufficient to increase postsynaptic surface levels of N‐cadherin and consequently promote presynaptic reorganizations. Such reorganizations include increases in the densities of the synaptic vesicle protein, Synaptotagmin 1 and the active zone scaffold protein, Bassoon, the number of active boutons and the size of the total recycling vesicle pool. In contrast, synaptic vesicle turnover is significantly impaired, preventing the exchange of synaptic vesicles with adjacent boutons. Together, N‐cadherin‐mediated retrograde signaling, governed by phosphoregulation of postsynaptic β‐catenin Y654, coordinately modulates presynaptic vesicle dynamics to enhance synaptic communication in mature neurons. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 61–74, 2017
Going to political extremes in response to boredom
Authors: Van Tilburg Wijnand A. P. , Igou Eric R.
Published: June 2016

Boredom makes people attempt to re‐establish a sense of meaningfulness. Political ideologies, and in particular the adherence to left‐ versus right‐wing beliefs, can serve as a source of meaning. Accordingly, we tested the hypothesis that boredom is associated with a stronger adherence to left‐ versus right‐wing beliefs, resulting in more extreme political orientations. Study 1 demonstrates that experimentally induced boredom leads to more extreme political orientations. Study 2 indicates that people who become easily bored with their environment adhere to more extreme ends of a political spectrum compared with their less easily bored counterparts. Finally, Study 3 reveals that the relatively extreme political orientations among those who are easily bored can be attributed to their enhanced search for meaning. Overall, our research suggests that extreme political orientations are, in part, a function of boredom's existential qualities.
A 3D‐printed modular reactor setup including temperature and pH control for the compartmentalized implementation of enzyme cascades
Authors: Kazenwadel Franziska , Biegert Ellen , Wohlgemuth Jonas , Wagner Henrike , Franzreb Matthias
Published: June 2016

In recent years, 3D printers developed rapidly from an expensive niche product used mainly by architects and designers into a versatile tool for engineers helping them to quickly realize and test new ideas. While most of the reported examples still focus on the use of 3D‐printed parts as mechanical but chemically inert tools, we developed a 3D‐printed modular reactor system which allows the fast implementation and testing of enzyme cascades. 3D printing offers several advantages in this context, as complex fluidic structures that cannot be fabricated by other methods can be generated, and the printed reactors are easily scalable in order to adjust their size to specific reaction parameters. Using a so‐called PolyJet technique, highly porous monolithic enzyme carriers were printed and directly UV‐cured from acrylate monomers, allowing simple immobilization of enzymes in a subsequent step. The enzyme immobilisates were fixed in a 3D‐printed housing with integrated fluid distributors forming a compact module to conduct a biotransformation step. Several of such modules can be connected in series to a pumping and analyzing system. A model cascade connecting two enzyme transformation modules, the first containing Glucose Oxidase and the second containing Horseradish Peroxidase, was operated using a commercial FPLC system for flow control and UV–Vis detection of the generated product. In order to adjust the temperature, a Peltier‐based tempering jacket for the enzyme transformation modules was designed. In addition, a flow‐through pH regulation module was developed, based on an electrochemical principle which allows unidirectional pH changes without the need for membranes or discharge of partial fluid streams. Except for the electrodes, also the pH regulation module was fabricated by 3D printing.
Association between polymorphisms in arsenic metabolism genes and urinary arsenic methylation profiles in girls and boys chronically exposed to arsenic
Authors: Recio‐Vega Rogelio , González‐Cortes Tania , Olivas‐Calderón Edgar , Clark Lantz R. , Jay Gandolfi A. , Michel‐Ramirez Gladis
Published: June 2016

Disease manifestations or susceptibilities often differ among individuals exposed to the same concentrations of arsenic (As). These differences have been associated with several factors including As metabolism, sex, age, genetic variants, nutritional status, smoking, and others. This study evaluated the associations between four As metabolism‐related gene polymorphisms/null genotypes with urinary As methylation profiles in girls and boys chronically exposed to As. In a total of 332 children aged 6–12 years, the frequency of AS3MT, GSTO1, GSTT1, and GSTM1 polymorphisms/null genotypes and As urinary metabolites were measured. The results revealed that total As and monomethyl metabolites of As (MMA) levels were higher in boys than in girls. No differences in the frequency of the evaluated polymorphisms were found between girls and boys. In AS3MT‐Met287Thr carriers, %MMA levels were higher and second methylation levels (defined as dimethylarsinic acid divided by MMA) were lower. In children with the GSTM1 null genotype, second methylation levels were higher. In boys, a positive association between the AS3MT‐Met287Thr polymorphism with %MMA and between the GSTO1‐Glu155del and Asv was found; whereas, a negative relationship was identified between AS3MT‐Met287Thr and second methylation profiles. In girls, a positive association was found between the GSTO1‐Ala140Asp polymorphism with second methylation levels. In conclusion, our data indicate that gender, high As exposure levels, and polymorphisms in the evaluated genes negatively influenced As metabolism. Environ. Mol. Mutagen. 57:516–525, 2016. © 2016 Wiley Periodicals, Inc.
Fourier-transform infrared spectroscopy as a novel approach to providing effect-based endpoints in duckweed toxicity testing
Authors: Hu Li-Xin , Ying Guang-Guo , Chen Xiao-Wen , Huang Guo-Yong , Liu You-Sheng , Jiang Yu-Xia , Pan Chang-Gui , Tian Fei , Martin Francis L.
Published: June 2016

Traditional duckweed toxicity tests only measure plant growth inhibition as an endpoint, with limited effects-based data. The present study aimed to investigate whether Fourier-transform infrared (FTIR) spectroscopy could enhance the duckweed (Lemna minor L.) toxicity test. Four chemicals (Cu, Cd, atrazine, and acetochlor) and 4 metal-containing industrial wastewater samples were tested. After exposure of duckweed to the chemicals, standard toxicity endpoints (frond number and chlorophyll content) were determined; the fronds were also interrogated using FTIR spectroscopy under optimized test conditions. Biochemical alterations associated with each treatment were assessed and further analyzed by multivariate analysis. The results showed that comparable x% of effective concentration (ECx) values could be achieved based on FTIR spectroscopy in comparison with those based on traditional toxicity endpoints. Biochemical alterations associated with different doses of toxicant were mainly attributed to lipid, protein, nucleic acid, and carbohydrate structural changes, which helped to explain toxic mechanisms. With the help of multivariate analysis, separation of clusters related to different exposure doses could be achieved. The present study is the first to show successful application of FTIR spectroscopy in standard duckweed toxicity tests with biochemical alterations as new endpoints. Environ Toxicol Chem 2017;36:346–353. © 2016 SETAC
Comparative chronic toxicity of imidacloprid, clothianidin, and thiamethoxam to Chironomus dilutus and estimation of toxic equivalency factors
Authors: Cavallaro Michael C. , Morrissey Christy A. , Headley John V. , Peru Kerry M. , Liber Karsten
Published: June 2016

Nontarget aquatic insects are susceptible to chronic neonicotinoid insecticide exposure during the early stages of development from repeated runoff events and prolonged persistence of these chemicals. Investigations on the chronic toxicity of neonicotinoids to aquatic invertebrates have been limited to a few species and under different laboratory conditions that often preclude direct comparisons of the relative toxicity of different compounds. In the present study, full life-cycle toxicity tests using Chironomus dilutus were performed to compare the toxicity of 3 commonly used neonicotinoids: imidacloprid, clothianidin, and thiamethoxam. Test conditions followed a static-renewal exposure protocol in which lethal and sublethal endpoints were assessed on days 14 and 40. Reduced emergence success, advanced emergence timing, and male-biased sex ratios were sensitive responses to low-level neonicotinoid exposure. The 14-d median lethal concentrations for imidacloprid, clothianidin, and thiamethoxam were 1.52 μg/L, 2.41 μg/L, and 23.60 μg/L, respectively. The 40-d median effect concentrations (emergence) for imidacloprid, clothianidin, and thiamethoxam were 0.39 μg/L, 0.28 μg/L, and 4.13 μg/L, respectively. Toxic equivalence relative to imidacloprid was estimated through a 3-point response average of equivalencies calculated at 20%, 50%, and 90% lethal and effect concentrations. Relative to imidacloprid (toxic equivalency factor [TEF] = 1.0), chronic (lethality) 14-d TEFs for clothianidin and thiamethoxam were 1.05 and 0.14, respectively, and chronic (emergence inhibition) 40-d TEFs were 1.62 and 0.11, respectively. These population-relevant endpoints and TEFs suggest that imidacloprid and clothianidin exert comparable chronic toxicity to C. dilutus, whereas thiamethoxam induced comparable effects only at concentrations an order of magnitude higher. However, the authors caution that under field conditions, thiamethoxam readily degrades to clothianidin, thereby likely enhancing toxicity. Environ Toxicol Chem 2017;36:372–382. © 2016 SETAC
Physiological differences in the crab Ucides cordatus from two populations inhabiting mangroves with different levels of cadmium contamination
Authors: Ortega Priscila , Vitorino Hector A. , Moreira Renata G. , Pinheiro Marcelo A.A. , Almeida Alaor A. , Custódio Márcio R. , Zanotto Flávia P.
Published: June 2016

Crustaceans found in metal-contaminated regions are able to survive, and the authors investigated the physiological mechanisms involved by comparing populations from contaminated and noncontaminated areas. The objective of the present study was to measure the cellular transport of a nonessential metal (cadmium [Cd]) in gills and hepatopancreas of Ucides cordatus, together with cell membrane fluidity, metallothionein levels, and lipid peroxidation. The 2 populations compared were from a polluted and a nonpolluted mangrove area of São Paulo State, Brazil. The authors found, for the first time, larger Cd transport in gills and hepatopancreatic cells from crabs living in polluted mangrove areas. The cells also had lower plasma membrane fluidity, increased lipid peroxidation and less metallothionein compared to those from nonpolluted regions. The authors also found larger amounts of Cd in intracellular organelles of gills, but not in the hepatopancreas, from crabs in polluted regions. Therefore, in polluted areas, these animals showed higher Cd transport and lower plasma membrane fluidity and storage of Cd intracellularly in gill cells, whereas hepatopancreatic cells used metallothionein as their main line of defense. The findings suggest that crabs from polluted areas can accumulate Cd more easily than crabs from nonpolluted areas, probably because of an impairment of the regulatory mechanisms of cell membrane transport. Environ Toxicol Chem 2017;36:361–371. © 2016 SETAC
Exploring the Complementarities Within High‐Performance Work Systems: A Set‐Theoretic Analysis of UK Firms
Authors: Meuer Johannes
Published: June 2016

High‐performance work systems (HPWS) are important conceptual instruments in the human resource management literature. Yet our current understanding of the complementarities within HPWS remains limited for two reasons: First, the dominant theoretical perspectives on HPWS provide a landscape of theoretical possibilities rather than an understanding of different possibilities through which HPWS generate positive effects on performance; and second, the literature on HPWS merely proposes several seemingly equally important HR practices. This article explores the internal nature of HPWS by integrating a configurational perspective of core, peripheral, and nonessential HR practices with a typology of complementarities. Analyzing 530 UK‐based firms using fuzzy set qualitative comparative analysis (fsQCA), I identify four frequently implemented HPWS consistently associated with high labor productivity. The complementarities within all HPWS combine pairs of core HR practices with sets of peripheral HR practices. Moreover, the complementarities within three of the four HPWS rely on firms’ avoidance of implementing certain HR practices. The results suggest that the synergies of HPWS arise from efficient complementarities and virtuous overlaps, and reveal the significance of achieving high performance by not implementing HR practices. This article thus advances a new perspective on HPWSs, highlighting the challenges involved in successfully designing HPWS. © 2016 Wiley Periodicals, Inc.
Advanced imaging of tau pathology in Alzheimer Disease: New perspectives from super resolution microscopy and label‐free nanoscopy
Authors: Schierle Gabriele S. Kaminski , Michel Claire H. , Gasparini Laura
Published: June 2016

Alzheimer's disease (AD) is the main cause of dementia in the elderly population. Over 30 million people worldwide are living with dementia and AD prevalence is projected to increase dramatically in the next two decades. In terms of neuropathology, AD is characterized by two major cerebral hallmarks: extracellular β‐amyloid (Aβ) plaques and intracellular Tau inclusions, which start accumulating in the brain 15‐20 years before the onset of symptoms. Within this context, the scientific community worldwide is undertaking a wide research effort to detect AD pathology at its earliest, before symptoms appear. Neuroimaging of Aβ by positron emission tomography (PET) is clinically available and is a promising modality for early detection of Aβ pathology and AD diagnosis. Substantive efforts are ongoing to develop advanced imaging techniques for early detection of Tau pathology. Here, we will briefly describe the key features of Tau pathology and its heterogeneity across various neurodegenerative diseases bearing cerebral Tau inclusions (i.e., tauopathies). We will outline the current status of research on Tau‐specific PET tracers and their clinical development. Finally, we will discuss the potential application of novel super‐resolution and label‐free techniques for investigating Tau pathology at the experimental level and their potential application for AD diagnosis. Microsc. Res. Tech. 79:677–683, 2016. © 2016 Wiley Periodicals, Inc.