bluuebunny/crossref_metadata_2025 huggingface dataset:
Accuracy in quantitative phase analysis of mixtures with large amorphous contents. The case of stoneware ceramics and bricks
Authors: Gualtieri Alessandro F. , Riva Vincenzo , Bresciani Andrea , Maretti Stefano , Tamburini Marco , Viani Alberto
Published: April 2014

For the first time, this work inspects the accuracy of quantitative phase analysis of both crystalline and amorphous components of stoneware tiles and bricks. A number of variables were considered: the nature of the internal standard, experimental conditions and counting statistics. The so-calledG-factor method has also been applied. The results of the X-ray powder diffraction analysis have been compared with the results obtained with optical microscopy and image analysis. Only the mixtures spiked with corundum and silicon yielded accurate weight estimates of the amorphous fraction, whereas the use of highly X-ray absorbing internal standards (such as fluorite, rutile and zincite) resulted in gross underestimations. In fact, microabsorption effects are found to drastically reduce the accuracy of the results when standards with linear X-ray absorption coefficients higher than 100 cm−1are employed. It was found that very low counting statistics reduced the calculated amorphous fractions in both bricks and stoneware tiles owing to partial masking of the major peak of the internal standard, namely corundum. The application of theG-factor method to the systems investigated was also evaluated. The results are poorer than those obtained using the internal standard.
Chronic exposure to low‐dose radiation atChernobyl favours adaptation to oxidative stress in birds
Authors: Galván Ismael , Bonisoli‐Alquati Andrea , Jenkinson Shanna , Ghanem Ghanem , Wakamatsu Kazumasa , Mousseau Timothy A. , Møller Anders P.
Published: April 2014

Ionizing radiation produces oxidative stress, but organisms can adapt to their exposure with physiological adaptive responses. However, the role of radioadaptive responses in wild populations remains poorly known.

At Chernobyl, studies of birds and other taxa including humans show that chronic exposure to radiation depletes antioxidants and increases oxidative damage. Here, we present analyses of levels of the most important intracellular antioxidant (i.e. glutathione,GSH), its redox status,DNAdamage and body condition in 16 species of birds exposed to radiation at Chernobyl. We use an approach that allows considering the individual bird as the sampling unit while controlling for phylogenetic effects, thus increasing the statistical power by avoiding the use of species means as done for most previous comparative studies.

As a consequence, we found a pattern radically different from previous studies in wild populations, showing thatGSHlevels and body condition increased, and oxidative stress andDNAdamage decreased, with increasing background radiation. Thus, when several species are considered, the overall pattern indicates that birds are not negatively affected by chronic exposure to radiation and may even obtain beneficial hormetic effects following an adaptive response. Analysis of the phylogenetic signal supports the existence of adaptation in the studied traits, particularly inGSHlevels andDNAdamage.

We also show that, under equal levels of radiation, the birds that produce larger amounts of the pigment pheomelanin and lower amounts of eumelanin pay a cost in terms of decreasedGSHlevels, increased oxidative stress andDNAdamage, and poorer body condition. Radiation, however, diminished another potential cost of pheomelanin, namely its tendency to produce free radicals when exposed to radiation, because it induced a change towards the production of less pro‐oxidant forms of pheomelanin with higher benzothiazole‐to‐benzothiazine ratios, which may have facilitated the acclimation of birds to radiation exposure.

Our findings represent the first evidence of adaptation to ionizing radiation in wild animals, and confirm that pheomelanin synthesis represents an evolutionary constraint under stressful environmental conditions because it requiresGSHconsumption.
Bile‐induced peptidoglycan remodelling in Salmonella enterica
Authors: Hernández Sara B. , Cava Felipe , Pucciarelli M. Graciela , García‐del Portillo Francisco , de Pedro Miguel A. , Casadesús Josep
Published: April 2014

Changes in the peptidoglycan (PG) structure of Salmonella enterica are detected in the presence of a sublethal concentration of sodium deoxycholate (DOC): (i) lower proportions of Braun lipoprotein (Lpp)‐bound muropeptides; (ii) reduced levels of muropeptides cross‐linked by L(meso)‐diaminopimelyl‐D(meso)‐diaminopimelic acid (L‐D) peptide bridges (3‐3 cross‐links). Similar structural changes are found in S. enterica cultures adapted to grow in the presence of a lethal concentration of DOC, suggesting that reduced anchoring of Braun protein to PG and low occurrence of 3‐3 cross‐links may increase S. enterica resistance to bile. This view is further supported by additional observations: (i) A triple mutant lacking L,D‐transpeptidases YbiS, ErfK, and YcfS, which does not contain Lpp anchored to PG, is hyper‐resistant to bile; (ii) enhanced 3‐3 cross‐linking upon overexpression of YnhG transpeptidase causes a decrease in bile resistance. These observations suggest that remodelling of the cell wall may be added to the list of adaptive responses that permit survival of S. enterica in the presence of bile.
Transversing the Vertical Case Study: A Methodological Approach to Studies of Educational Policy as Practice
Authors: Bartlett Lesley , Vavrus Frances
Published: April 2014

How can scholars trace the global production and circulation of educational policies? The vertical case study incorporates three elements: “vertical” attention across micro‐, meso‐, and macro‐levels, or scales; a “horizontal” comparison of how policies unfold in distinct locations; and a “transversal,” processual analysis of the creative appropriation of educational policies across time. The second half of the article draws upon an ethnographic study of learner‐centered pedagogy in Tanzania to exemplify the vertical case study approach.
Immigrant Students and the Ecology of Externalization in a Secondary School in Spain
Authors: Poveda David , Jociles María Isabel , Franzé Adela
Published: April 2014

We examine how counselors, teachers, and other professionals at a secondary school in Madrid (Spain) understand cultural diversity and work with immigrant students' educational circumstances. Our analysis suggests that cultural diversity is largely construed as a problem and the explanation of educational difficulties is organized around an “externalizing logic” in which responsibility for educational outcomes is transferred to process and programs outside “ordinary” teachers' realm of action. We analyze these discourses and institutional practices from an ecological perspective: within the context of the local changing demographics of the school, regional/national policy measures around diversity, and wider conceptualizations of cultural diversity in Spain's education system.
Nonreassuring Fetal Heart Rate Decreases Heart Rate Variability in Newborn Infants
Authors: Sheen Tzong‐Chyi , Lu Ming‐Huei , Lee Mei‐Yu , Chen Su‐Ru
Published: April 2014

Background

Nonreassuring fetal status (NRFS) refers to a compromised fetal condition which implies hypoxia. The influence of intrapartum hypoxia on autonomic nervous system function in early postnatal life is unknown. This study explored the influence of NRFS on the heart rate variability (HRV) of newborn infants.

Methods

Singleton newborn infants delivered through Cesarean delivery (CD) with indications of elective purpose (n = 32), dystocia (n = 29), or NRFS (n = 22), and through vaginal birth (VB) (n = 80) were consecutively collected. HRV parameters including standard deviation of average NN intervals (SDANN), low frequency (LF), high frequency (HF), LF%, HF%, and total power (TP), were obtained for analysis in 3 days postpartum. An independent t‐test or one‐way ANOVA was used to compare differences in numeric data.

Results

SDANN, HF, HF%, and TP of newborn infants in the VB group were significantly higher than those in the CD group. The NRFS group had significantly lower SDANN, HF, and TP than those of the elective group, and significantly lower HF, HF%, and TP than those of the dystocia group.

Conclusions

Newborn infants delivered through Cesarean section had lower HRV, especially those who experienced NRFS during labor. The long‐term effects of changes of HRV in neonates require further evaluation.
Children with Down's syndrome display high rates of hyperuricaemia
Authors: Kashima Ayako , Higashiyama Yukie , Kubota Masaru , Kawaguchi Chiharu , Takahashi Yukihiro , Nishikubo Toshiya
Published: April 2014

Aim

Several studies show that hyperuricaemia, abnormally high levels of uric acid in the blood, frequently occurs in adult Down's syndrome patients, but paediatric research is scarce. We aimed to clarify its prevalence in paediatric Down's syndrome patients and its association with lifestyle‐related laboratory variables and nutritional intake, to consider possible effects in later life.

Methods

We compared 52 Down's syndrome patients, from one to 15 years of age, with age‐matched controls. Hyperuricaemia was defined using reference values established for children, as uric acid z‐scores of more than 2.0. Nutritional intake was estimated using 3‐day dietary records.

Results

Hyperuricaemia occurred in 17 Down's patients (32.7%) and was significantly higher in Down's patients than the controls. The prevalence was also significantly higher in males. There were no significant differences between hyperuricaemia‐positive and hyperuricaemia‐negative patients in terms of age, body mass index standard deviation scores, fasting blood glucose, insulin, homeostasis model assessment‐insulin resistance and triglyceride, and purine body intake was similar. There were differences in high‐density lipoprotein cholesterol.

Conclusion

We found high rates of hyperuricaemia from early childhood in Down's syndrome patients. This suggests careful management of Down's syndrome patients, as hyperuricaemia is an independent risk factor for lifestyle‐related diseases in adulthood.
Subnormal levels of vitamin D are associated with acute wheeze in young children
Authors: Stenberg Hammar Katarina , Hedlin Gunilla , Konradsen Jon R. , Nordlund Björn , Kull Inger , Giske Christian G. , Pedroletti Christophe , Söderhäll Cilla , Melén Erik
Published: April 2014

Aim

This study evaluated risk factors for acute wheeze in preschool children and investigated whether subnormal levels of vitamin D were associated with increased risk for acute wheeze, atopy or viral/bacterial respiratory infections.

Methods

We recruited 130 children with acute wheeze, aged 6 months to 4 years, from paediatric emergency departments in Stockholm, Sweden, and 101 age‐matched controls with no history of wheeze or sensitisation to airborne allergens. Parents answered standardised questionnaires, and blood samples were analysed for specific IgE to airborne and food allergens and levels of 25 hydroxyvitamin D (25(OH)D). Nasopharyngeal virus samples were collected during the emergency department visit in the group of children with wheeze, and a subset were also tested for bacteria.

Results

Vitamin D insufficiency (25(OH)D < 75 nmol/L (30 ng/mL)) was associated with an odds ratio of 2.7 (95% confidence interval 1.1–6.2) for acute wheeze. However, no association was found between vitamin D insufficiency and atopy, presence of virus or bacteria or recurrent infections. Children older than 24 months were particularly at risk of subnormal vitamin D levels, irrespective of wheezing history.

Conclusion

Our findings support the hypothesis that subnormal levels of vitamin D are associated with acute wheeze in young children.
Population Pharmacokinetic Meta‐Analysis of Vortioxetine in Healthy Individuals
Authors: Areberg Johan , Petersen Kamilla B. , Chen Grace , Naik Himanshu
Published: April 2014

The objective was to describe the pharmacokinetics of vortioxetine and evaluate the effect of intrinsic and extrinsic factors in the healthy population. Data from 26 clinical pharmacology studies were pooled. A total of 21,758 vortioxetine quantifiable plasma concentrations were collected from 887 subjects with corresponding demography. The doses ranged from 2.5 to 75 mg (single dose) and 2.5–60 mg (multiple QD doses). The pharmacokinetics of vortioxetine was best characterised by a two‐compartment model with first‐order absorption, lag‐time and linear elimination, with interindividual error terms for absorption rate constant, oral clearance and central volume of distribution. The population mean was 32.7 L/hr for oral clearance and 1.97∙103 L for the central volume of distribution. The average elimination half‐life was 65.8 hr. CYP2D6 inferred metabolic status (ultra, extensive, intermediate or poor metabolisers) and age on oral clearance and height on central volume of distribution were identified as statistically significant covariate–parameter relationships. For CYP2D6 poor metabolisers, CL/F was approximately 50% to that seen in CYP2D6 extensive metabolisers. The impact of height on V2/F and age on CL/F was low and not considered to be clinically relevant. The final model was found to be reliable, stable and predictive. A reliable, stable and predictive pharmacokinetic model was developed to characterise pharmacokinetics of vortioxetine in the healthy population.
The effect of labour on ownership decisions in two cultures: Developmental evidence from Japan and the United Kingdom
Authors: Kanngiesser Patricia , Itakura Shoji , Hood Bruce M.
Published: April 2014

Creative labour has an effect on children's and adults' ownership decisions in Western cultures. We investigated whether preschoolers and adults from an Eastern culture (Japan) would show a similar bias. In a first‐party task (Experiment 1), in which participants created their own objects, Japanese preschoolers but not adults assigned ownership to creators. When participants watched videos of third‐party conflicts between owners of materials and creators (Experiment 2), Japanese adults, but not preschoolers, transferred ownership to creators. In a British comparison group, both preschoolers and adults showed an effect of creative labour in the third‐party task. A bias to attribute ownership on the basis of creative labour is thus not specific to Western culture.
‘Double‐Hit’ cytogenetic status may not be predicted by baseline clinicopathological characteristics and is highly associated with overall survival in B cell lymphoma patients
Authors: Landsburg Daniel J. , Nasta Sunita D. , Svoboda Jakub , Morrissette Jennifer J. D. , Schuster Stephen J.
Published: April 2014

‘Double‐Hit’ (DH) B cell non‐Hodgkin lymphomas are characterized by the presence of a MYC rearrangement and additional rearrangement(s) most commonly involving BCL2 and/or BCL6. Patients with DH lymphomas are unlikely to achieve long‐term survival when treated with standard immunochemotherapy alone. DH gene rearrangements can be identified through metaphase karyotyping or more sensitive fluorescence in situ hybridization (FISH), although the latter is not routinely performed. We report 53 cases of B cell lymphoma that underwent diagnostic metaphase karyotying or FISH for MYC rearrangements. DH lymphoma was detected in 17 cases. No baseline factor, including age, serum lactate dehydrogenase, stage, International Prognostic Index or histology predicted for DH status. The median overall survival was significantly shorter for DH compared to non‐DH lymphoma patients (8·2 vs. 56·8 months, P < 0·001). DH status retained the most statistically significant association with overall survival on multivariate Cox regression analysis. DH status could not be inferred by baseline disease‐ or patient‐related characteristics and was most predictive of overall survival in this cohort of B cell lymphoma patients. These findings support the practice of routine performance of FISH for DH gene rearrangements on B cell lymphoma specimens in order to effectively identify DH patients who may benefit from risk‐adapted therapy.
Epidemiology of systemic mastocytosis in Denmark
Authors: Cohen Sarah S. , Skovbo Stine , Vestergaard Hanne , Kristensen Thomas , Møller Michael , Bindslev‐Jensen Carsten , Fryzek Jon P. , Broesby‐Olsen Sigurd
Published: April 2014

Mastocytosis is a heterogeneous group of diseases characterized by abnormal proliferation of mast cells. Systemic mastocytosis (SM), in which abnormal mast cells are present in tissues beyond the skin, is divided into seven subcategories with varying degrees of severity and prognosis. Very little is known about the epidemiology of SM and its subcategories. This retrospective cohort study of 548 adults with SM diagnosed 1997–2010 was constructed using linked Danish national health registries. The most common subtype of mastocytosis was indolent SM (including urticaria pigmentosa) (n = 450; 82%), followed by SM with subtype unknown (n = 61; 11%), SM with associated clonal haematological non‐mast cell lineage disease (n = 24; 4%), aggressive SM (n = 8; 2%), and mast cell leukaemia (n = 5; 1%). The incidence rate for SM (all subtypes including urticaria pigmentosa) was 0·89 per 100 000 per year. Cumulative incidence was 12·46 per 100 000, and the 14‐year limited‐duration prevalence as of 1 January, 2011 was 9·59 per 100 000. This nationwide cohort from Denmark is the first population‐based epidemiological study of mastocytosis. In this cohort of patients aged 15 years and older, SM was found to be overall relatively rare with notable variation by subtype for patient characteristics, survival and epidemiological measures.
Specific molecular signatures of non‐tumor liver tissue may predict a risk of hepatocarcinogenesis
Authors: Utsunomiya Tohru , Shimada Mitsuo , Morine Yuji , Tajima Atsushi , Imoto Issei
Published: April 2014

Hepatocellular carcinoma (HCC) is one of the most common human cancers and a major cause of cancer‐related death worldwide. The bleak outcomes of HCC patients even after curative treatment have been, at least partially, attributed to its multicentric origin. Therefore, it is necessary to examine not only tumor tissue but also non‐tumor liver tissue to investigate the molecular mechanisms operating during hepatocarcinogenesis based on the concept of “field cancerization”. Several studies previously investigated the association of molecular alterations in non‐tumor liver tissue with clinical features and prognosis in HCC patients on a genome‐wide scale. In particular, specific alterations of DNA methylation profiles have been confirmed in non‐tumor liver tissue. This review focuses on the possible clinical value of array‐based comprehensive analyses of molecular alterations, especially aberrant DNA methylation, in non‐tumor liver tissue to clarify the risk of hepatocarcinogenesis. Carcinogenetic risk estimation based on specific methylation signatures may be advantageous for close follow‐up of patients who are at high risk of HCC development. Furthermore, epigenetic therapies for patients with chronic liver diseases may be helpful to reduce the risk of HCC development because epigenetic alterations are potentially reversible, and thus provide promising molecular targets for therapeutic intervention.
Clinicopathological and prognostic impact of imaging of breast cancer angiogenesis and hypoxia using diffuse optical spectroscopy
Authors: Nakamiya Noriko , Ueda Shigeto , Shigekawa Takashi , Takeuchi Hideki , Sano Hiroshi , Hirokawa Eiko , Shimada Hiroko , Suzuki Hiroaki , Oda Motoki , Osaki Akihiko , Saeki Toshiaki
Published: April 2014

Near‐infrared diffuse optical spectroscopy (DOS) imaging can non‐invasively measure tumor hemoglobin concentration using high contrast to normal tissue, thus providing vascularity and oxygenation status. We assessed the clinical usefulness of DOS imaging in primary breast cancer. In all, 118 women with a histologically confirmed diagnosis of primary malignant tumor were enrolled. All participants underwent testing using time‐resolved DOS before treatment initiation. Visual assessment of DOS imaging for detecting tumors was carried out by two readers blinded to the clinical data. Relative total hemoglobin (rtHb) and oxygen saturation (stO2) of the tumors was compared with clinicopathological variables and 10‐year prognosis was calculated. Sensitivity for detecting a tumor based on the rtHb breast map was 62.7% (74/118). The sensitivity depended on T stage: 100% (7/7) for T3, 78.9% (45/57) for T2, 44.7% (17/38) for T1, and 31.3% (5/16) for Tis. Tumors showed unique features of higher rtHb with a wider range of stO2 than normal breast tissue, depending on histological type. There was a significant correlation of rtHb with tumor size, lymphatic vascular invasion, and histological grade, and of stO2 with age and tumor size. Neither rtHb nor stO2 correlated with intrinsic biomarkers such as estrogen receptor, progesterone receptor, or human epidermal growth factor receptor 2; rtHb inversely correlated with 10‐year relapse‐free survival and overall survival, with statistical significance. Diffuse optical spectroscopy imaging has limited utility for the early detection of breast cancer; nonetheless, the findings suggest that the degree of tumor angiogenesis and hypoxia may be associated with tumor aggressiveness and poor prognosis.
Aporphinoid Antagonists of 5‐HT2A Receptors: Further Evaluation of Ring A Substituents and the Size of Ring C
Authors: Ponnala Shashikanth , Kapadia Nirav , Navarro Hernán A. , Harding Wayne W.
Published: April 2014

A series of ring A‐modified analogs of nantenine as well as structural variants in ring C were synthesized and evaluated for antagonist activity at 5‐HT2A and α1A receptors. Halogenation improves 5‐HT2A antagonist potency in molecules containing a C1 methoxyl/C2 methoxyl or C1 methoxyl/C2 hydroxyl moiety. Bromination or iodination (but not chlorination) with the latter moiety also significantly increased α1A antagonist potency. Homologation or contraction of ring C adversely affected antagonist activity at both receptors, implying that a six‐membered ring C motif is beneficial for high antagonist potency at both receptors. Molecular docking studies suggest that the improved antagonist activity (by virtue of improved affinity) of C3‐halogenated aporphines in this study is attributable to favorable interactions with the C3 halogen and F339 and/or F340.
Combined 1H‐NMR and Molecular Dynamics Studies on Conformational Behavior of a Model Heptapeptide, GRGDSPC
Authors: Kulkarni Ashok K. , Ojha Rajendra P.
Published: April 2014

Among various strategies, the de novo design and in silico approaches are being used to develop the short peptides, models of modified peptides, and mimetics as clinically useful drugs with improved stability and bioavailability. The resulting models will help to isolate the factors behind the folded structure formation and contribute useful information about de novo peptide design. The combined 1H‐NMR spectroscopic and molecular dynamics methods were used to investigate the conformational behavior of an Arg‐Gly‐Asp (RGD)‐containing peptide, GRGDSPC, the cell‐binding heptapeptide of extracellular matrix protein, fibronectin. The formation of two fused weak β‐turns of type II (HB, 4→1) and type II’ (HB, 7→4) from simulation studies has been consistent with NMR data. The sustainable ‘S’‐shaped molecular structure (which remained unchanged during the entire simulation) and the conformational transitions due to interconversions between multiple turns initiated at Asp4, Ser5, and Cys7 imply that the peptide is flexible in nature. Thus, the model of ‘S’‐shaped structure with flexible multiple turns for GRGDSPC peptide may provide the structural rationale for antagonistic properties of this heptapeptide toward the treatment of integrin‐mediated cellular abnormal behaviors such as thrombosis and metastasis.
Antibody Against N‐terminal Domain of Phospholipid Scramblase 1 Induces Apoptosis in Colorectal Cancer Cells Through the Intrinsic Apoptotic Pathway
Authors: Chen Chun‐Yu , Chen Jinn‐Shiun , Chou Yeh‐Pin , Kuo Yung‐Bin , Fan Chung‐Wei , Chan Err‐Cheng
Published: April 2014

Phospholipid scramblase 1 involve in biological processes including phospholipid movement, proliferation, and apoptosis. Treatment with an antiphospholipid scramblase 1 antibody (NP1) has been demonstrated to inhibit cell proliferation in colorectal cancer. This study aimed to explore the role of NP1 treatment in the apoptosis of colorectal cancer cells. Results showed that NP1 treatment significantly increases the apoptosis of colorectal cancer cells via the activation of caspase 8, caspase 9, and caspase 3. Moreover, pretreatment with a caspase 8 inhibitor did not fully prevent the apoptotic effects of NP1. Taken together, these data indicate NP1 induces cell apoptosis primary through the intrinsic apoptotic pathway. NP1 may serve as a potential therapeutic agent.
Frequency, severity and causes of unexpected allergic reactions to food: a systematic literature review
Authors: Versluis A. , Knulst A. C. , Kruizinga A. G. , Michelsen A. , Houben G. F. , Baumert J. L. , van Os‐Medendorp H.
Published: April 2014

Food allergic patients have to deal with an avoidance diet. Confusing labelling terms or precautionary labels can result in misinterpretation and risk‐taking behaviour. Even those patients that strictly adhere to their diet experience (sometimes severe) unexpected allergic reactions to food. The frequency, severity and causes of such reactions are unknown. The objective of this review was to describe the frequency, severity and causes of unexpected allergic reactions to food in food allergic patients aged > 12 years, in order to develop improved strategies to deal with their allergy. A systematic review was carried out by two researchers, in six electronic databases (CINAHL, Cochrane, EMBASE, Medline, Psychinfo and Scopus). The search was performed with keywords relating to the frequency, severity and causes of unexpected allergic reactions to food. This resulted in 24 studies which met the inclusion criteria; 18 observational and six qualitative studies. This review shows that knowledge about the frequency of unexpected reactions is limited. Peanut, nuts, egg, fruit/vegetables and milk are the main causal foods. Severe reactions and even fatalities occur. Most reactions take place at home, but a significant number also take place when eating at friends' houses or in restaurants. Labelling issues, but also attitude and risky behaviour of patients can attribute to unexpected reactions. We conclude that prospective studies are needed to get more insight in the frequency, severity, quantity of unintended allergen ingested and causes of unexpected allergic reactions to food, to be able to optimize strategies to support patients in dealing with their food allergy. Although the exact frequency is not known, unexpected reactions to food occur in a significant number of patients and can be severe. For clinical practice, this means that patient education and dietary instructions are necessary.
Protein truncating variants of SLC30A8 reduce type 2 diabetes mellitus risk in humans
Authors: Yakala G.K.
Published: April 2014

Loss‐of‐function mutations in SLC30A8 protect against type 2 diabetes

Flannick et al. (2014)

Nat Genet. doi: 10.1038/ng.2915.
Spondyloepimetaphyseal dysplasia with joint laxity (Beighton type); mutation analysis in eight affected South African families
Authors: Vorster A.A. , Beighton P. , Ramesar R.S.
Published: April 2014

Spondyloepimetaphyseal dysplasia with joint laxity (SEMD‐JL), type 1 is an autosomal recessive disorder which has been identified in more than 30 affected children in the Afrikaans‐speaking community of South Africa. Sequencing of B3GALT6 revealed a specific mutation, c.235A > G, in homozygous form in four families, while three others were compound heterozygotes for this mutation in combination with the c.200C > T mutation. In addition, a proband from one family carried the c.16C > T mutation combined with c.200C > T. In a series of five Iranian persons, mutations in B3GALT6 have been implicated in a syndrome characterised by skeletal abnormalities with intellectual disability, bone and connective tissue fragility. Other mutations in B3GALT6 resulted in the classical SEMD‐JL phenotype in seven Japanese families and in a syndrome which has been likened to a progeroid form of Ehlers–Danlos syndrome (EDS). It is evident that there is considerable intragenic heterogeneity in B3GALT6. One of the mutations, c.200C > T, in the affected South Africans was also present in one of the Japanese persons and the respective phenotypes were identical. The multiplicity of allelic mutations and the phenotypic differences in the affected persons supports the concept that a spectrum of connective tissue disorders is programmed by mutations in B3GALT6.
Coupled exposure to ingredients of cosmetic products: III. Ultraviolet filters
Authors: Uter Wolfgang , Gonçalo Margarida , Yazar Kerem , Kratz Eva‐Maria , Mildau Gerd , Lidén Carola
Published: April 2014

Background

The use of cosmetics exposes consumers to mixtures of ingredients, many of which are potential allergens. Ultraviolet (UV) filters are used not just in sunscreens, but also in other products. Many UV filters are known contact allergens and photoallergens.

Objective

To examine the pattern of co‐exposure to UV filters in cosmetics.

Methods

A survey of products marketed in Germany, conducted in 2006–2009 by the Chemical and Veterinary Investigation Office in Karlsruhe, identified 4447 products (of all 5667 cosmetic products examined) (i) that were categorizable according to Annex I to the Cosmetics Directive, and (ii) with information on the presence of UV filters or zinc oxide. The occurrence and co‐occurrence of UV filters were analysed and presented in tabular and graphical format.

Results

UV filters or zinc oxide were present in 22.5% of all 4447 products, ranging from almost 100% in sunscreens to a few per cent in, for example, some hair products; they were absent in two product categories. Frequently, several different UV filters were included in one product, for example in sunscreens (median 4) and in perfumes (median 3). The overall most frequent UV filters were butyl methoxydibenzoylmethane and titanium dioxide, combined mostly with octocrylene in sunscreens and with ethylhexyl methoxycinnamate in creams.

Conclusions

The frequent co‐occurrence of UV filters in cosmetic products possibly facilitates sensitization, and may explain why patients often react to chemically unrelated UV filters.
782. EMMENOPTERYS HENRYI
Authors: Upson Tim
Published: April 2014

The Chinese tree Emmenopterys henryi is described and illustrated based on the rare blooming of a specimen at Cambridge University Botanic Garden in summer 2012. Other known flowerings in cultivation are reviewed with particular reference to Britain. The origin of the Cambridge tree, propagated from an original introduction at the Royal Botanic Gardens, Kew and distributed in the early 1980s is discussed. Based on original herbarium collections and archive material the discovery and introduction of this species into cultivation is reviewed.
776. VIOLA TRICOLOR SUBSP. CURTISII
Authors: Rix Martyn
Published: April 2014

The dwarf perennial seaside or sandhill pansy, Viola tricolor L. subsp. curtisii (Forst.) Syme is illustrated and described. The history of its discovery by William Curtis, founder of this magazine, is given, and its relationships and nomenclature are considered.
777. PASSIFLORA TRANSVERSA
Authors: Vanderplank John , Edwards Sara
Published: April 2014

Passiflora transversa Masters, considered by Killip to be a synonym of P. biflora Lam., is reinstated at species rank. It is here illustrated in colour and with black and white line drawings. Its history, distribution, similarities to related species and cultivation are discussed.
778. PASSIFLORA PITTIERI
Authors: Vanderplank John , Edwards Sara , Hilgenhof Rebecca , Rodriguez Carlos M.
Published: April 2014

Passiflora pittieri Mast., a woody liana from Central and South America, is described and illustrated. Its natural history and cultivation are discussed.
779. PASSIFLORA EDULIS f. ALBIDA
Authors: Vanderplank John , Edwards Sara
Published: April 2014

Passiflora edulis f. albida Vanderplank & S. L. Edwards, a new form with white flowers, yellow fruit and black petiole glands is described, and illustrated with a colour painting and black and white line drawings: Its history, taxonomy, distribution, ecology and cultivation are discussed.
Systemic Negligence: Why It Is Morally Important for Developing World Bioethics
Authors: Chakraborti Chhanda
Published: April 2014

In the context of clinical and non‐clinical biomedical practices,negligenceis usually understood as a lapse of a specific professional duty by a healthcare worker or by a medical facility. This paper tries to delineatesystemic negligenceasanother kindof negligence in the context of health systems, particularly in developing countries, that needs to be recognized and addressed.Systemic negligenceis not just a mere collection of stray incidences of medical errors and system failures in a health system, but is proposed in this paper as a more pervasive kind of neglect. Several non‐medical factors, such as lack of social and political will, also contribute to it and hence is more difficult to address in a health system. This paper argues that recognizingsystemic negligenceand including it research agenda have special moral importance for researchers in developing world bioethics, public health ethics and for health activists in the developing world. For, it can be a potent health system barrier, and can seriously impair efforts to ensure patient safety, particularly in the weaker health systems. As it erodes accountability in a health system, addressing it is also important for the twin goals of ensuring patient safety and improving health system performance. Above all, it needs to be addressed because the tolerance of its persistence in a health system seems to undervalue health as a social good.
Motor development in 3‐month‐old healthy term‐born infants is associated with cognitive and behavioural outcomes at early school age
Authors: Hitzert Marrit M , Roze Elise , Van Braeckel Koenraad N J A , Bos Arend F
Published: April 2014

Aim

To determine whether motor development at 3 months of age is associated with cognitive, motor, and behavioural outcomes in healthy children at early school age.

Method

In this cohort study, we included 74 term‐born, healthy children (44 males, 30 females; median gestational age 40.1wks, range 38.0–42.6wks). From video recordings (median 12.9wks, range 9.3–18.6wks), we assessed the quality of fidgety movements, and calculated a motor optimality score. At school age (median 5y 11mo, range 5y 8mo–7y 6mo), we performed detailed cognitive, motor, and behavioural assessments. We examined whether aspects of motor development were associated with functional outcomes.

Results

An age‐adequate motor repertoire, in particular the presence of antigravity, midline leg, and manipulation movements, was related to poorer cognition, whereas variable finger postures was related to better cognition. Children with a monotonous concurrent motor repertoire had better ball skills but experienced more behavioural problems. The presence of antigravity movements tended to be associated with abnormal recognition (odds ratio [OR] 4.4, 95% confidence interval [CI], 0.9–21; R2=0.17; p=0.070), where the absence of variable finger postures was associated with borderline and abnormal visual‐spatial perception (OR 20, 95% CI, 1.7–238; R2=0.39; p=0.018).

Interpretation

Detailed aspects of motor development at 3 months of age are associated with cognition and behaviour, but not with motor outcome, in healthy children at early school age. Our findings suggest that early motor development may be the basis for later cognitive and behavioural performance. Since the associations were only moderate, possible environmental influences should be acknowledged.
Prevalence and risk factors of diabetes and impaired fasting glucose among university applicants in Eastern China: findings from a population‐based study
Authors: Hao C. , Zhang C. , Chen W. , Shi Z.
Published: April 2014

Aims

To investigate the prevalence and risk factors of diabetes and impaired fasting glucose among urban university applicants in Eastern China.

Method

The study uses data from the annual health examination among all students finishing high school who applied for university entrance in Changzhou City in 2012. In total, 6716 students aged 17–19 years had fasting blood glucose, alanine transaminase, height, weight and blood pressure measured. Impaired fasting glucose and diabetes were defined as fasting blood glucose ≥ 5.6 mmol/l (but < 7 mmol/l) and ≥ 7 mmol/l, respectively.

Results

The overall prevalence of impaired fasting glucose and diabetes was 2.40% and 0.13%, respectively (3.67% and 0.09% in boys; 1.09% and 0.18% in girls). In total, 20.9% of boys and 10.6% of girls were overweight/obese. High socio‐economic status was associated with an increased risk of diabetes/impaired fasting glucose, but the association was significant only among boys (adjusted odds ratio 1.94, 95% CI 1.26–2.98). Alanine transaminase levels were significantly and positively related to diabetes/impaired fasting glucose risk. Overweight/obesity was significantly associated with increased risk of impaired fasting glucose/diabetes in girls, but not in boys. Moreover, the number of the above‐mentioned risk factors (i.e. overweight/obesity, elevated alanine transaminase, pre‐hypertension) was significantly and positively related to diabetes/impaired fasting glucose among both boys and girls.

Conclusions

Impaired fasting glucose was prevalent among urban university applicants, in particular boys and those of high socio‐economic status in eastern China. Elevated levels of liver function enzyme appear to be the strongest risk factor for diabetes/impaired fasting glucose.
Combination therapy with metformin plus sulphonylureas versus metformin plus DPP‐4 inhibitors: association with major adverse cardiovascular events and all‐cause mortality
Authors: Morgan C. Ll. , Mukherjee J. , Jenkins‐Jones S. , Holden S. E. , Currie C. J.
Published: April 2014

Aims

To compare the risk of major adverse cardiovascular events (MACE) and mortality for combination therapies with metformin and either sulphonylurea (SU) or dipeptidyl peptidase‐4 inhibitor (DPP‐4i).

Methods

Data were from the UK Clinical Practice Research Datalink (CPRD). Patients with type 2 diabetes were selected if initiated with combination therapies comprising metformin plus SU or DPP‐4i 2007–2012. The co‐primary endpoints were all‐cause mortality and MACE (myocardial infarction or stroke). Times to endpoints were compared using Cox proportional hazards models. Additional analyses were performed on subsets matched directly on key characteristics and by propensity score.

Results

A total of 33 983 patients were prescribed SU and 7864 DPP‐4i, and 5447 patients in each cohort could be matched directly and 6901 by propensity score. In the main analysis, there were 716 MACE events and 1217 deaths. Crude event rates for MACE were 11.3 events per 1000 person‐years (pkpy) for SU, versus 5.3 pkpy for DPP‐4i. For all‐cause mortality, rates were 16.9 versus 7.3 pkpy, respectively. Following adjustment, there was a significant increase in the adjusted hazard ratio (aHR) for all‐cause mortality in those exposed to SU across all analytical models: aHR = 1.357 (95% CI 1.076–1.710) for all subjects, 1.850 (1.245–2.749) directly matched and 1.497 (1.092–2.052) propensity‐matched. For MACE, aHR was 1.710 (1.280–2.285) for all subjects, 1.323 (0.832–2.105) directly matched and 1.547 (1.076–2.225) propensity‐matched.

Conclusions

There was a reduction in all‐cause mortality for patients treated with metformin combined with DPP‐4i versus metformin plus SU, and a similar trend for MACE.
Efficacy and safety of empagliflozin for type 2 diabetes: a systematic review and meta‐analysis
Authors: Liakos A. , Karagiannis T. , Athanasiadou E. , Sarigianni M. , Mainou M. , Papatheodorou K. , Bekiari E. , Tsapas A.
Published: April 2014

Aim

To assess the efficacy and safety of the novel sodium‐glucose cotransporter 2 (SGLT2) inhibitor empagliflozin compared with placebo or other antidiabetic agents in patients with type 2 diabetes.

Methods

We conducted a systematic review and meta‐analysis of randomized controlled trials. We searched Medline, Embase and the Cochrane Library through December 2013 and grey literature. Two reviewers working independently extracted relevant data and carried out risk‐of‐bias assessments. We synthesized results using random‐effects models and computed weighted mean differences (WMDs) and odds ratios (ORs).

Results

We included 10 studies with 6203 participants. Compared with placebo, mean changes in haemoglobin A1c were −0.62% [95% confidence interval (CI) −0.68 to −0.57%] for empagliflozin 10 mg and −0.66% (−0.76 to −0.57%) for empagliflozin 25 mg. Empagliflozin 25 mg daily had glycaemic efficacy similar to metformin or sitagliptin (WMD −0.11%; 95% CI −0.25 to 0.03%), without increasing risk for hypoglycaemia. It was also associated with body weight loss (WMD −1.84; 95% CI −2.30 to −1.38 kg vs. placebo) and had a favourable effect on blood pressure. Incidence of hypoglycaemia with empagliflozin was similar to placebo (OR 1.10; 95% CI 0.87 to 1.39); nevertheless we noted an increased risk for genital tract infections (OR 3.31; 95% CI 1.55 to 7.09). Findings were similar for the 10‐mg dosing regimen.

Conclusions

Empagliflozin effectively lowers blood glucose and provides additional clinical benefits including body weight and blood pressure reduction. Ongoing trials will elucidate the long‐term safety and effect of empagliflozin on cardiovascular outcomes.
Unhappiness and Job Finding
Authors: Gielen Anne C. , van Ours Jan C.
Published: April 2014

It is puzzling that people feel unhappy when they become unemployed, while simultaneously active labour market policies are needed to bring them back to work. We investigate this using GSOEP data. We find that nearly half of the unemployed do not experience a drop in happiness, which might explain why activation is sometimes needed. Furthermore, even though unhappy unemployed search more actively for a job, it does not speed up their job finding. Apparently, there is no link between unhappiness and job finding rate. Hence there is no contradiction between the unemployed being unhappy and the need for activation policies.
International Competition in Vertically Differentiated Markets with Innovation and Imitation: Trade Policy Versus Free Trade
Authors: Kováč Eugen , Žigić Krešimir
Published: April 2014

The competition between firms from developed (DC) and less developed countries (LDC) is typically in vertically differentiated products. We consider a model of price competition between DC and LDC firms with quality choice and imitation, and study the effects of ex post tariffs. The government faces a choice between commitment to free trade and imposing a tariff. Tariffs can lead to change in the rank of qualities compared to free trade. We identify conditions under which this quality reversal takes place, and show that quality reversal is necessary for trade policy to be superior to free trade in welfare terms.
Increased atmospheric carbon dioxide concentration: effects on eucalypt rust (Puccinia psidii), C:N ratio and essential oils in eucalypt clonal plantlets
Authors: Ghini R. , Leod R. E. de O. Mac , Torre Neto A. , Cardoso D. C. , Bettiol W. , de Morais L. A. S. , Vique B.
Published: April 2014

Evaluation of impacts of high CO2 atmospheric concentration is strategically important for the development of adaptation measures and sustainable crop management. The objective of this study was to evaluate the effects of increased atmospheric CO2 concentration on eucalypt rust (Puccinia psidii), C:N ratio, yield and chemical composition of essential oils and growth of eucalypt clonal plantlets. Two clones with different levels of rust resistance were studied: a Eucalyptus urophylla × E. camaldulensis hybrid (VM 01) and an E. urophylla (clone MN 463). The experiments were performed in open‐top chambers (OTCs) with CO2 mean concentrations (μmol mol−1) of 399 (unenclosed control), 412 (OTCs with ambient CO2 concentration) and 508 (OTCs with high CO2 concentration) and in closed chambers (CCs) with CO2 mean concentrations of 390, 405, 520 and 700. Increased atmospheric CO2 concentrations resulted in a decrease in rust pustules per leaf, uredinia per leaf area, spores per uredinia and area under the disease progress curve in VM 01 (hybrid) clonal plantlets. The disease did not occur in MN 463 clonal plantlets, which demonstrated that high CO2 concentrations did not change the level of rust resistance. Plant growth of the two clones was stimulated by up to 23% in height and 26% in stem diameter in OTCs and by 18% for both clones in CCs. An increased C:N ratio in leaves, stems and roots was observed only for the VM 01 clonal plantlets. Essential oils produced by VM 01 (2.8 g 100 g−1) and MN 463 (1.4 g 100 g−1), as well as the major essential oil compounds (80% 1.8‐cineole for VM 01; 50% 1.8‐cineole and 32% α‐pinene for MN 463), were not altered. In this study, increased concentrations of atmospheric CO2 favourably impacted eucalypt growth and reduced rust severity, while not influencing the production of essential oils.
Aspirin inhibits proliferation and induces apoptosis of multiple myeloma cells through regulation of Bcl‐2 and Bax and suppression of VEGF
Authors: Ding Jiang‐hua , Yuan Li‐ya , Huang Rui‐Bin , Chen Guo‐an
Published: April 2014

Objectives

Aspirin (ASA) has been frequently used for thromboprophylaxis in patients with multiple myeloma (MM) when treated with thalidomide or lenalidomide. Despite the well‐recognized chemopreventive role of ASA in some solid tumors particularly for colon cancer, whether ASA displays the antimyeloma activity remains unclear.

Methods

MM1.S and RPMI‐8226 cell lines harboring K‐Ras and N‐Ras mutation, respectively, were treated with various concentrations of ASA for different hours. The cell proliferation and apoptosis were performed to explore the effects of ASA on myeloma. Then, the exact mechanisms governing ASA's antimyeloma were explored by qRT‐PCR and Western blot. Also, the effect of ASA on tumor growth was observed in NOD/SCID mice bearing myeloma xenografts.

Results

ASA of 0–10 mm concentration inhibits proliferation MM1.S and RPMI‐8226 cells in time‐ and dose‐dependent manner. The myeloma cells exposed to ASA treatment displayed concentration‐dependent apoptosis, which was closely associated with activation of caspases, upregulation of Bax, and downregulation of Bcl‐2 and VEGF. Study in vivo revealed that ASA administration retarded the tumor growth accompanying the survival time of mice bearing myeloma xenografts.

Conclusions

ASA exerted antiproliferative and pro‐apoptotic action in myeloma cells in vitro and delayed the growth of human myeloma cells in vivo. The underlying mechanisms were ascribed to regulation of Bcl‐2 and Bax and suppression of VEGF.