bluuebunny/crossref_metadata_2025 huggingface dataset:
Victimization and depression among youth with disabilities in the US child welfare system
Authors: Berg K. L. , Shiu C.‐S. , Msall M. E. , Acharya K.
Published: March 2015

Aim

This study aimed to examine the prevalence of victimization among a United States‐wide cohort of youth with disabilities (YWD) investigated for maltreatment in the child welfare system (CWS) and their correlation with mental health.

Methods

Data were drawn from baseline interviews in the second National Survey of Child and Adolescent Well‐Being, a national representative survey of youth involved in the CWS. Interviews took place between 2008 and 2009 and included 675 youth, 11–17 years old and residing with biological families across 83 counties nationwide. The sample consisted of 405 females (60.1%) and 270 males (39.9%), mean age = 13.5 years. We identified YWD if they reported one or more physical or neurodevelopmental health condition (n = 247). Reported victimization experiences and Children's Depression Inventory (CDI) scores were analysed using weighted regression analyses.

Results

One‐quarter of YWD in the CWS reported three or more victimizations during the prior year compared with 19% of youth without disabilities. The odds of YWD reporting a one‐unit increase in level of victimization was 75% higher (P < 0.05) than youth without disabilities. Prevalence of clinical depression was significantly higher among YWD (14 vs. 5.5%; P < 0.05). Unlike youth without disabilities, the odds of clinical depression were 92% higher for every one‐unit increase in victimization among YWD, controlling for covariates (P < 0.05). Of CWS‐involved youth who reported three or more victimizations, 24.4% of YWD and 2.2% of non‐disabled youth had CDI scores in the clinical range.

Conclusion

YWDs in the US CWS are at high risk of experiencing victimization and clinical depression. Our findings suggest that health professionals need to screen CWS‐involved YWD for multiple forms of victimization, and develop and implement trauma‐informed services that target the mental health sequelae that may jeopardize their independence in adulthood.
CD14 expression is increased on monocytes in patients with anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis and correlates with the expression of ANCA autoantigens
Authors: Tarzi R M , Liu J , Schneiter S , Hill N R , Page T H , Cook H T , Pusey C D , Woollard K J
Published: March 2015

Monocyte subsets with differing functional properties have been defined by their expression of CD14 and CD16. We investigated these subsets in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) and determined their surface expression of ANCA autoantigens. Flow cytometry was performed on blood from 14 patients with active AAV, 46 patients with AAV in remission and 21 controls. The proportion of classical (CD14highCD16neg/low), intermediate (CD14highCD16high) and non-classical (CD14lowCD16high) monocytes and surface expression levels of CD14 and CD16 were determined, as well as surface expression of proteinase 3 (PR3) and myeloperoxidase (MPO) on monocyte subsets. There was no change in the proportion of monocytes in each subset in patients with AAV compared with healthy controls. The expression of CD14 on monocytes from patients with active AAV was increased, compared with patients in remission and healthy controls (P < 0·01). Patients with PR3-ANCA disease in remission also had increased monocyte expression of CD14 compared with controls (P < 0·01); however, levels in patients with MPO-ANCA disease in remission were lower than active MPO-ANCA patients, and not significantly different from controls. There was a correlation between CD14 and both PR3 and MPO expression on classical monocytes in AAV patients (r = 0·79, P < 0·0001 and r = 0·42, P < 0·005, respectively). In conclusion, there was an increase in monocyte CD14 expression in active AAV and PR3-ANCA disease in remission. The correlation of CD14 expression with ANCA autoantigen expression in AAV may reflect cell activation, and warrants further investigation into the potential for increased CD14 expression to trigger disease induction or relapse.
Anti-tumour necrosis factor treatment increases circulating T helper type 17 cells similarly in different types of inflammatory arthritis
Authors: Hull D N , Williams R O , Pathan E , Alzabin S , Abraham S , Taylor P C
Published: March 2015

We investigated changes in circulating T helper type 17 (Th17) cells following anti-tumour necrosis factor (TNF) in rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) patients. Peripheral blood mononuclear cells (PBMC) were isolated from 25 RA, 15 AS and eight PsA patients at baseline 4 and 12 weeks after treatment, and Th17 cell frequencies were analysed using interleukin (IL)-17 enzyme-linked immunospot (ELISPOT) and flow cytometry. A significant increase in IL-17-producing cells was observed by ELISPOT in RA and AS patients at 12 weeks. Flow cytometry confirmed significant increases in CD4+IL-17+ cells at 12 weeks in RA and AS and 4 weeks in PsA patients. Anti-TNF treatment increases circulating Th17 cells in three different diseases.
Origin of MLH1, MSH2, MSH6 and PMS2 mutations can help inform long‐term care strategies for patients with colorectal and endometrial cancer
Authors: Hickmott J. W.
Published: March 2015

Colon and Endometrial Cancers with Mismatch Repair Deficiency can arise from somatic, rather than germline, mutations

Haraldsdottir et al. (2014)

Gastroenterology 147:1308–1316
Bright fluorescent dsDNA probes: novel polycationic asymmetric monomethine cyanine dyes based on thiazolopyridine‐quinolinium chromophore
Authors: Vasilev Aleksey , Lesev Nedyalko , Dimitrova Sonya , Nedelcheva‐Veleva Marina , Stoynov Stoyno , Angelova Silvia
Published: March 2015

Seven tri‐ and tetracationic monomeric and homodimeric monomethine cyanine dyes based on thiazolo[4,5‐b]pyridinium and quinolinium end groups were synthesised and characterised. The dyes were tested as fluorescent DNA intercalating probes to apply in DNA gel electrophoresis. The DNA samples stained with all dyes from the series demonstrated bright fluorescent signals. DNA fragments were successfully visualised under orange and green filters as well as under standard UV transillumination. Two of the studied dyes revealed higher sensitivity to DNA when compared with the commercial dimeric cyanine dye TOTO‐1. Their sensitivity reached that of the commercial dimeric cyanine dye YOYO‐1, but the emission was shifted to longer wavelengths. These qualities make the dyes suitable to apply in a wide range of medical and scientific analytical methods.
Non‐thermal plasma degradation of dye using an underwater dielectric barrier discharge created inside a porous hydrophobic ceramic tube
Authors: Jo Jin‐Oh , Moon Soo Hyoung , Mok Young Sun
Published: March 2015

An alternating‐current‐driven, atmospheric‐pressure, non‐thermal plasma reactor was applied to the degradation of dye in water. The plasma reactor, made of a porous hollow ceramic tube, was placed underwater and was able to disperse plasmatic gas containing various reactive species into aqueous dye solution as small bubbles through the micropores of the tube. The hydrophobic coating on the surface of the ceramic tube effectively prevented the water from permeating through it. This wastewater treatment system was able immediately to transfer plasmatic gas to aqueous solution across the porous ceramic tube and provide a large gas–liquid interfacial area, allowing efficient dye treatment. So as to simulate real dyeing wastewater, an aqueous solution comprising two different azo dyes was used. The effect of discharge power, treatment time, and flow rate of oxygen used for the creation of plasma was examined. The results suggest that this system may be useful for the treatment of organic wastewater.
Pneumomediastinum as a complication of critical pertussis
Authors: Monaco Francesco , Barone Mario , Manfredi Valeria G. , Marando Rosario , Nunnari Flavia , David Antonio , Monaco Maurizio , Cascio Antonio
Published: March 2015

Background and Aims

Pertussis is a common and potentially serious disease affecting mainly infants and young children. In its non‐classic presentation, pertussis can be clinically indistinguishable from other respiratory illnesses. Pertussis today often remains underdiagnosed in adults. Our aims was to report a complicated cases of pertussis.

Results

A case of serologically confirmed pertussis occurred in an 18‐year‐old man presenting with pneumomediastinum, subcutaneous emphysema in the neck and chest, and persistent attacks of coughing with apnea that required treatment in the intensive care unit.

Conclusion

Pneumomediastinum and subcutaneous emphysema have never been described in adult patients with pertussis. Physicians should be aware that patients presenting with persistent cough and pneumomediastinum may have pertussis and include this in their differential diagnosis.
DCTN4 as a modifier of chronic Pseudomonas aeruginosa infection in cystic fibrosis
Authors: Viel Marion , Hubert Dominique , Burgel Pierre‐Regis , Génin Emmanuelle , Honoré Isabelle , Martinez Brigitte , Gaitch Natacha , Chapron Jeanne , Kanaan Reem , Dusser Daniel , Girodon Emmanuelle , Bienvenu Thierry
Published: March 2015

Background and Aims

Pseudomonas aeruginosa (Pa) infection in cystic fibrosis (CF) patients is associated with worse long‐term pulmonary disease and shorter survival, and chronic Pa infection (CPA) is associated with reduced lung function, faster rate of lung decline, increased rates of exacerbations and shorter survival. By using exome sequencing and extreme phenotype design, it was recently shown that isoforms of dynactin 4 (DCTN4) may influence Pa infection in CF, leading to worse respiratory disease. The purpose of this study was to investigate the role of DCTN4 missense variants on Pa infection incidence, age at first Pa infection and chronic Pa infection incidence in a cohort of adult CF patients from a single centre.

Methods

Polymerase chain reaction and direct sequencing were used to screen DNA samples for DCTN4 variants.

Results

A total of 121 adult CF patients from the Cochin Hospital CF centre have been included, all of them carrying two CFTR defects: 103 developed at least 1 pulmonary infection with Pa, and 68 patients of them had CPA. DCTN4 variants were identified in 24% (29/121) CF patients with Pa infection and in only 17% (3/18) CF patients with no Pa infection. Of the patients with CPA, 29% (20/68) had DCTN4 missense variants vs 23% (8/35) in patients without CPA. Interestingly, p.Tyr263Cys tend to be more frequently observed in CF patients with CPA than in patients without CPA (4/68 vs 0/35), and DCTN4 missense variants tend to be more frequent in male CF patients with CPA bearing two class II mutations than in male CF patients without CPA bearing two class II mutations (P = 0.06).

Conclusions

Our observations reinforce that DCTN4 missense variants, especially p.Tyr263Cys, may be involved in the pathogenesis of CPA in male CF.
Trichoblastoma, syringocystadenoma papilliferum, desmoplastic trichilemmoma and tumor of the follicular infundibulum with signet‐ring cells, all arising in nevus sebaceus
Authors: Dore Emilie , Noe Megan H. , Swick Brian L.
Published: March 2015

Herein, we describe a 63‐year‐old male with multiple tumors arising within a nevus sebaceus on the posterior scalp. On histopathologic examination, four distinct tumors were identified: trichoblastoma, syringocystadenoma papilliferum, desmoplastic trichilemmoma and tumor of the follicular infundibulum (TFI). Within the TFI component of the nevus sebaceus, there was intracytoplasmic accumulation of eosinophilic keratin, as shown on pancytokeratin‐stained sections, imparting a signet‐ring appearance to the cells. To our knowledge, this is the first report of signet‐ring cells arising within a TFI occurring in a nevus sebaceus. We discuss this case as well as review the literature on multiple tumors arising within nevus sebaceus and signet‐ring cell changes in primary cutaneous tumors.
Efficacy and tolerability of saxagliptin compared with glimepiride in elderly patients with type 2 diabetes: a randomized, controlled study (GENERATION)
Authors: Schernthaner G. , Durán‐Garcia S. , Hanefeld M. , Langslet G. , Niskanen L. , Östgren C. J. , Malvolti E. , Hardy E.
Published: March 2015

Aims

To assess the efficacy and safety of adjunctive saxagliptin vs glimepiride in elderly patients with type 2 diabetes (T2D) and inadequate glycaemic control.

Methods

In this multinational, randomized, double‐blind, phase IIIb/IV study (GENERATION; NCT01006603), patients aged ≥65 years were randomized (1 : 1) to receive saxagliptin 5 mg/day or glimepiride ≤6 mg/day, added to metformin, during a 52‐week treatment period. The primary endpoint was achievement of glycated haemoglobin (HbA1c) <7.0% at week 52 without confirmed/severe hypoglycaemia. The key secondary endpoint was incidence of confirmed/severe hypoglycaemia. Safety and tolerability were also assessed.

Results

Of 720 patients randomized (360 in each treatment group; mean age 72.6 years; mean T2D duration 7.6 years), 574 (79.8%) completed the study (saxagliptin 80.3%; glimepiride 79.2%). Similar proportions of patients achieved the primary endpoint with saxagliptin and glimepiride (37.9 vs 38.2%; odds ratio 0.99, 95% confidence interval 0.73, 1.34; p = 0.9415); however, a significant treatment‐by‐age interaction effect was detected (p = 0.0389): saxagliptin was numerically (but not significantly) superior to glimepiride for patients aged <75 years (39.2 vs 33.3%) and numerically inferior for patients aged ≥75 years (35.9 vs 45.5%). The incidence of confirmed/severe hypoglycaemia was lower with saxagliptin vs glimepiride (1.1 vs 15.3%; nominal p < 0.0001). Saxagliptin was generally well tolerated, with similar incidences of adverse events compared with glimepiride.

Conclusion

As avoiding hypoglycaemia is a key clinical objective in elderly patients, saxagliptin is a suitable alternative to glimepiride in patients with T2D aged ≥65 years.
Deferasirox chelation therapy in patients with transfusion‐dependent MDS: a ‘real‐world’ report from two regional Italian registries: Gruppo Romano Mielodisplasie and Registro Basilicata
Authors: Maurillo Luca , Breccia Massimo , Buccisano Francesco , Voso Maria Teresa , Niscola Pasquale , Trapè Giulio , Tatarelli Caterina , D'Addosio Ada , Latagliata Roberto , Fenu Susanna , Piccioni Anna Lina , Fragasso Alberto , Aloe Spiriti Maria A. , Refrigeri Marco , Criscuolo Marianna , Musto Pellegrino , Venditti Adriano
Published: March 2015

Deferasirox (DFX) is an orally administered iron chelator approved for use in patients with transfusion‐dependent iron overload due to myelodysplastic syndromes (MDS). The safety and efficacy of DFX has been explored in clinical trial settings, but there is little data on unselected patients with MDS. The aim of this study was to retrospectively evaluate the safety, compliance, efficacy and effect on haematopoiesis of DFX in a large ‘real‐world’ MDS population. One hundred and eighteen patients with transfusion‐dependent MDS were treated with DFX across 11 centres in Italy. Serum ferritin levels, haematological response, dosing, adverse events and transfusion dependence were recorded at baseline, 3, 6, 12 and 24 months following initiation of treatment. DFX reduced mean serum ferritin levels from 1790 to 1140 ng/mL (P < 0.001), with 7.1% of patients achieving transfusion independence. Significant haematological improvement was seen in erythroid (17.6%), platelet (5.9%) and neutrophil counts (7.1%). Adverse events were reported in 47.5% of patients, including gastrointestinal and renal toxicity. Regression analysis showed that higher starting doses of DFX are associated with transfusion independence at 24 months. DFX is a safe, effective treatment for transfusion‐dependent MDS that can lead to transfusion independence and haematological improvement in a subset of patients.
The First Member State Rebellion? The European Court of Justice and the Negotiations of the ‘Luxembourg Protocol’ of 1971
Authors: Fritz Vera
Published: March 2015

This article delves into the history of the negotiations of the ‘Luxembourg protocol’ of 1971, which conferred jurisdiction upon the European Court of Justice (ECJ) for the interpretation of the 1968 Brussels convention. The protocol provided a preliminary ruling procedure that had undergone restrictive modifications in comparison with the European Economic Community (EEC) treaty's original (Article 177). Some have, therefore, interpreted the outcome of the negotiations as a sign that the mechanism was being criticised in national administrations. This article will, for the first time, bring to the surface archival evidence to explain why the protocol contained an altered version of Article 177 EEC. Furthermore, it will reveal that the governments' experts' intention to limit the procedure in the protocol caused serious concern inside the ECJ, of which some members consequently repeatedly urged national decision‐makers to opt for formulas identical with Article 177 EEC.
A promising surgical approach to equine glaucoma
Authors: Lassaline M.
Published: March 2015

The preceding case report by Wilsonet al. (2015) describes the surgical placement of aBaerveldt glaucoma shunt in a glaucomatous equine eye that had been refractory to aggressive medical and repeated surgical therapies yet maintained functional vision. Shunt placement surgery successfully maintained vision and intraocular pressure in the normal range in the affected eye. This is the first report of long‐term successful glaucoma filtration surgery in a horse. Glaucoma shunt placement shows promise for maintaining vision and comfort in equine eyes affected with glaucoma. There is much to be learned in terms of the most appropriate implant type for the equine eye, the risk of complications such as ocular hypotony or tube fibrosis, and the utility of combination therapy with transcleral cyclophotocoagulation and implant placement, but with the report of one case in which gonioimplant placement has been associated with intraocular pressure control for over one year, further investigations appear warranted. This case provides a glimmer of hope for long‐term treatment of a painful, blinding disease that has traditionally carried a poor prognosis in horses.
Surrogate assisted‐hybrid differential evolution algorithm using diversity control
Authors: S. Miruna Joe Amali , S. Baskar
Published: March 2015

Evolutionary algorithms (EAs) being a major optimization framework, typically require a considerable number of function evaluations to locate an optimal solution for computationally intensive real‐world optimization problems. In order to solve complex multimodal problems within a limited computational budget, surrogate models are integrated with EA. The overall performance of such algorithms not only depends on the construction and integration procedure of the model, but also on the efficiency of the underlying EA in overcoming premature convergence. This can be achieved through diversity control and parameter adaptation methodology in EAs. In this paper, an improved algorithm, namely Diversity Controlled Parameter adapted Differential Evolution with Local Search (DCPaDE‐LS) is integrated into two dynamic surrogate models and two variants, namely Surrogate Assisted Parameter adapted Differential Evolution with Artificial Neural Networks and Response Surface Methodology (SAPDE‐ANN and SAPDE‐RSM) are proposed. They reduce the exact function evaluations for complex, multimodal problems. The performance of the proposed variants are compared on a set of 26 bound‐constrained benchmark functions scalable with 10 and 30 dimensions, with respect to average number of function evaluations (NFE), success rate (SR) and % reduction in NFE in 30 independent trials. The SAPDE variants are compared with Self‐adaptive Differential Evolution, DCPaDE‐LS, Increasing Population Size Covariance Matrix Adaptation Evolution Strategy and Comprehensive Learning Particle Swarm Optimization. The SAPDE variants are able to reduce the NFE without loss in SR for all the functions. The algorithms are also validated using 12 solvable functions from CEC 2005. Of the two variants, SAPDE‐ANN reports reduced NFE in more functions compared with SAPDE‐RSM. Results reveal that the proposed SAPDE algorithm can be applied to real‐world optimization problems.
GxxxG motifs hold the TIM23 complex together
Authors: Demishtein‐Zohary Keren , Marom Milit , Neupert Walter , Mokranjac Dejana , Azem Abdussalam
Published: March 2015

Approximately 99% of the mitochondrial proteome is nucleus‐encoded, synthesized in the cytosol, and subsequently imported into and sorted to the correct compartment in the organelle. The translocase of the inner mitochondrial membrane 23 (TIM23) complex is the major protein translocase of the inner membrane, and is responsible for translocation of proteins across the inner membrane and their insertion into the inner membrane. Tim23 is the central component of the complex that forms the import channel. A high‐resolution structure of the import channel is still missing, and structural elements important for its function are unknown. In the present study, we analyzed the importance of the highly abundant GxxxG motifs in the transmembrane segments of Tim23 for the structural integrity of the TIM23 complex. Of 10 glycines present in the GxxxG motifs in the first, second and third transmembrane segments of Tim23, mutations of three of them in transmembrane segments 1 and 2 resulted in a lethal phenotype, and mutations of three others in a temperature‐sensitive phenotype. The remaining four caused no obvious growth phenotype. Importantly, none of the mutations impaired the import and membrane integration of Tim23 precursor into mitochondria. However, the severity of growth impairment correlated with the destabilization of the TIM23 complex. We conclude that the GxxxG motifs found in the first and second transmembrane segments of Tim23 are necessary for the structural integrity of the TIM23 complex.
The Knowledge–Innovation Nexus. Its Spatially Differentiated Returns to Innovation
Authors: Capello Roberta , Lenzi Camilla
Published: March 2015

Innovative activities have been long considered as a predominant urban phenomenon suggesting that the innovative capacity of a region highly depends on its urbanization level. This paper tests empirically this statement by studying the impact of knowledge on innovation in 262 regions of theEuropeanUnion, ranked according to their degree of urbanization. Based on an original database encompassing several knowledge and innovation indicators, and a regional typology and ranking of city regions, the paper shows that when the source of innovation is formal knowledge (i.e.,R&D), the benefits accruing from innovation are spatially rather selective and concentrated in first‐rank city regions. On the contrary, when the source of innovation is qualified human capital, the innovation advantages are more diffused and penetrate also in second‐ and third‐rank city regions. Moreover, innovative activities aimed at introducing new products require a more balanced mix ofR&Dand human capital inputs whereas innovative activities aimed at introducing new processes tend to be relatively more human capital intensive.
Consumer vulnerability: are older people more vulnerable as consumers than others?
Authors: Berg Lisbet
Published: March 2015

The aging population is an important consumer policy concern. And one relevant question to ask is: are there reasons to worry about consumer vulnerability among older people? The aim of the project was twofold: First, to gain insight into what makes people vulnerable as consumers, more precisely to reveal significant vulnerability drivers. Second, if possible, to distinguish particularly vulnerable consumer groups and their needs for targeted consumer policy measures. The project builds on a qualitative pilot study among older people, followed by a large nationally representative survey among people living in Norway, between 18 and 95 years old. Based on the analysis of 2100 telephone interviews, this paper rejects our a priori assumption, that older people constitutes a vulnerable consumer group. Although older people have several reduced capabilities that could act as vulnerability drivers, older people appeared to be less likely than other age groups to make unfortunate decisions in the markets. Older people also show a much more environmentally friendly consumption pattern than younger generations. The main individual vulnerability drivers appeared to be; poor economic awareness and lack of time. The results also indicate that people who lack calculating skills, as well as people living in households with scarce financial resources, are more likely than others to make economically unfortunate consumer choices.
Elevated serum adenosine deaminase levels in secondary hemophagocytic lymphohistiocytosis
Authors: Chen W. , Zhang S. , Zhang W. , Yang X. , Xu J. , Qiu H. , Zhang X. , Li J.
Published: March 2015

Introduction

Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory condition caused by activated T cells and macrophages. Adenosine deaminase (ADA) plays an important role in immune regulation, especially in the proliferation, maturation, and differentiation of lymphocytes. Its role has been studied in inflammation and malignancy. Here, we present for the first time the alteration of ADA in secondary HLH (sHLH).

Methods

Serum ADA levels were measured in 20 cases with lymphoma‐associated hemophagocytic syndrome (LAHS), 15 with infection‐associated hemophagocytic syndrome (IAHS), six with macrophage activation syndrome (MAS) as experimental group. Additionally, we enrolled 20 cases with lymphoma, 15 with infection, six with autoimmunity who were all not associated with HLH as conditional control group and 20 healthy subjects as blank group. We also demonstrated the ADA levels in 20 LAHS cases and 21 benign disease‐associated HLH cases (IAHS and MAS).

Results

Serum ADA levels were significantly higher in patients with LAHS, IAHS, and MAS compared to the healthy subjects (P < 0.001) and conditional control group (P < 0.05). Serum ADA levels of patients with LAHS were significantly higher than benign disease‐associated HLH cases (P < 0.05). The optimum ADA cutoff point for LAHS was 89.25 U/L, with a sensitivity and specificity of 85.0% and 76.2%, respectively.

Conclusion

Serum ADA levels were increased in sHLH suggesting a partial role of activated T‐cell response in the disease pathophysiology. Serum ADA levels were particularly higher in LAHS and probably be a potential indicator of underlying lymphoma in sHLH patients.
An updated survey for the 2007–2013 period of randomized controlled trials for psoriasis: treatment modalities, study designs, comparators, outcome measures and sponsorship
Authors: Manalo I.F. , Gilbert K.E. , Wu J.J.
Published: March 2015

Background

Two reports from the European Dermato‐Epidemiology Network psoriasis project have analysed randomized controlled trials for psoriasis published during the periods of 1977–2000 and 2001–2006.

Objective

We sought to update the analysis of randomized controlled trials for the 2007–2013 period from 10 high‐impact dermatology and medical journals.

Methods

This survey was conducted by electronic search on the PubMed database for eligible papers. We assessed and compared results to the two aforementioned published reports.

Results

In total, 84 studies were evaluated. Over half of the total trials studied novel therapeutics: 40 (47.6%) trials examined biologics and five (6.0%) examined novel oral agents. Proportion of trials studying more than one treatment modality increased from 7.1% in 2001–2006 to 25.0% in 2007–2013, with a decreased proportion of placebo‐controlled studies from 69.3% to 47.1%.

Conclusion

The proportion of trials on novel therapies, including novel oral and biologic agents, has increased. The quality of trials has improved in the aspects of increased active treatment comparisons, including between biologics and conventional agents, and increased study size. Further insight into the influence of pharmaceutical companies can be studied by extending analysis to extension studies and subanalyses.
Life Cycle Assessment Software: Selection Can Impact Results
Authors: Speck Ricky , Selke Susan , Auras Rafael , Fitzsimmons James
Published: March 2015

When software is used to facilitate life cycle assessments (LCAs), the implicit assumption is that the results obtained are not a function of the choice of software used. LCAs were done in both SimaPro and GaBi for simplified systems of creation and disposal of 1 kilogram each of four basic materials (aluminum, corrugated board, glass, and polyethylene terephthalate) to determine whether there were significant differences in the results. Data files and impact assessment methodologies (Impact 2002, ReCiPe, and TRACI 2) were ostensibly identical (although there were minor variations in the available ReCiPe version between the programs that were investigated). Differences in reported impacts of greater than 20% for at least one of the four materials were found for 9 of the 15 categories in Impact 2002+, 7 of the 18 categories in ReCiPe, and four of the nine categories in TRACI. In some cases, these differences resulted in changes in the relative rankings of the four materials. The causes of the differences for 14 combinations of materials and impact categories were examined by tracing the results back to the life cycle inventory data and the characterization factors in the life cycle impact assessment (LCIA) methods. In all cases examined, a difference in the characterization factors used by the two programs was the cause of the differing results. As a result, when these software programs are used to inform choices, the result can be different conclusions about relative environmental preference that are functions purely of the software implementation of LCIA methods, rather than of the underlying data.
Foundations of Financial Well‐Being: Insights into the Role of Executive Function, Financial Socialization, and Experience‐Based Learning in Childhood and Youth
Authors: DREVER ANITA I. , ODDERS‐WHITE ELIZABETH , KALISH CHARLES W. , ELSE‐QUEST NICOLE M. , HOAGLAND EMILY M. , NELMS EMORY N.
Published: March 2015

During childhood and youth we build the foundations for financial well‐being later in life, acquiring the knowledge, skills, attitudes, and personality traits that enable us to manage our finances as adults. This article reviews literature from consumer science, developmental psychology, and allied fields to gain insight into moments during youthful development when interventions are likely to have greatest impact. We find promising avenues for influence during each developmental life stage. Many present truly novel approaches to financial education—such as focusing on improving executive function in young children (critical despite lacking apparent “financial content”), emphasizing financial attitude development through dual‐generation financial modeling for elementary and middle school students and their parents, or intentionally teaching financial heuristics and other practical skills to later adolescents and young adults. Overall, this article proposes a range of innovative strategies to improve financial education, from early childhood through young adulthood.
Does feeding frequency, independent of total energy consumption, affect lizard digestive efficiency or growth?
Authors: Moeller K. T. , Elms R. , Sampson S. , Jackson M. L. , Seward M. , DeNardo D. F.
Published: March 2015

Down‐regulation of the digestive system between large meals is thought to afford energetic benefits to animals that feed infrequently. However, this idea has not been thoroughly tested. Thus, we assessed the realized benefits of infrequent feeding by examining how the timing of meal consumption influenced digestive efficiency and whole‐body growth of juvenile Gila monsters, a binge‐feeding lizard. All animals in our study received the same total energy intake for each feeding cycle, but meals were distributed differently over time among groups. One group had a 10–14‐day period of down‐regulation between meal sets while the other group had a constantly activated digestive system. The groups did not show differences in growth; however, differences in digestive efficiency for a specific meal indicate that feeding regime may have caused digestive adjustments (e.g. more efficient digestion) in one treatment group. Overall, our findings show that the energetic benefits of down‐regulation may depend more on species, extent of digestive regulation, or duration of fasting than previously supposed.
Landscape of chromosomal copy number aberrations in gangliogliomas and dysembryoplastic neuroepithelial tumours
Authors: Prabowo Avanita S. , van Thuijl Hinke Foka , Scheinin Ilari , Sie Daoud , van Essen Hendrik F. , Iyer Anand M. , Spliet Wim G.M. , Ferrier Cyrille H. , van Rijen Peter C. , Veersema Tim J. , Thom Maria , Schouten‐van Meeteren Annetteke Y.N. , Reijneveld Jaap C. , Ylstra Bauke , Wesseling Pieter , Aronica Eleonora
Published: March 2015

Aim

Gangliogliomas (GGs) and dysembryoplastic neuroepithelial tumours (DNTs) represent the most common histological entities within the spectrum of glioneuronal tumours (GNTs). The wide variability of morphological features complicates histological classification, including discrimination from prognostically distinct diffuse low‐grade astrocytomas (AIIs). This study was performed to increase our understanding of these tumours.

Methods

We studied chromosomal copy number aberrations (CNAs) by genome‐wide sequencing in a large cohort ofGNTs and linked these to comprehensive histological analysis and clinical characteristics. One hundred fourteenGNTs were studied: 50GGs and 64DNTs. Also, a data set ofCNAsfrom 38 diffuseAIIs was included.

Results

The most frequentCNAsin bothGGs andDNTs were gains at chromosomes 5 and 7, often concurrent, and gain at chromosome 6. None of theCNAswas linked to histological subtype, immunohistochemical features or to clinical characteristics. Comparison ofAIIs and diffuseGNTs revealed that gain at whole chromosome 5 is only observed inGNTs.CNApatterns indicative of chromothripsis were detected in threeGNTs.

Conclusion

We conclude thatGNTswith diverse morphologies share molecular features, and our findings support the need to improve classification and differential diagnosis of tumour entities within the spectrum ofGNTs, as well as their distinction from other gliomas.
Modern disposable hydrogel contact lens removal has a minimal effect on intraocular pressure
Authors: Hamilton‐Maxwell Kirsten , King Nicole
Published: March 2015

Purpose

To determine whether the removal of modern disposable hydrogel contact lenses may influence intraocular pressure (IOP) measurement, and if so, how long the effect may last.

Methods

Twenty‐five healthy experienced contact lens wearers aged 19–25 inserted their lenses at least 30 min prior to the study. Each participant was asked to remove a contact lens from one eye (control eye, selected at random) upon commencement of the study, and then to remove the lens in the other eye (lens‐wearing eye) after a 30 min washout period. IOP was measured immediately in both eyes using non‐contact tonometry, then repeated every 3 min for 12 min. To determine the change in IOP due to lens removal, the IOP in the lens‐wearing eye was compared to the control eye using paired t‐tests at each time point.

Results

The IOP was significantly higher in the lens‐wearing eye immediately following lens removal (0.7 ± 1.0 mmHg, t(24) = 3.46, p < 0.01), but was within baseline values at 3 min (0.2 ± 1.0 mmHg, t(24) = 0.84, p = 0.41), 6 min (0.3 ± 1.1 mmHg, t(24) = 1.39, p = 0.18), 9 min (0.3 ± 1.2 mmHg, t(24) = 1.14, p = 0.27) and 12 min (−0.1 ± 0.9 mmHg, t(24) = −0.49, p = 0.63, paired t‐test).

Conclusions

There was a slight statistically significant increase in IOP following contact lens removal, with a maximum duration of 3 min. Given the small magnitude of the change in IOP, and its transient nature, there appears to be no clinical reason to delay IOP measurements following the removal of modern disposable hydrogel contact lenses.
Infection of the brown alga Ectocarpus siliculosus by the oomycete Eurychasma dicksonii induces oxidative stress and halogen metabolism
Authors: Strittmatter Martina , Grenville‐Briggs Laura J. , Breithut Lisa , Van West Pieter , Gachon Claire M. M. , Küpper Frithjof C.
Published: March 2015

Pathogens are increasingly being recognized as key evolutionary and ecological drivers in marine ecosystems. Defence mechanisms of seaweeds, however, have mostly been investigated by mimicking infection using elicitors. We have established an experimental pathosystem between the genome brown model seaweed Ectocarpus siliculosus and the oomycete Eurychasma dicksonii as a powerful new tool to investigate algal responses to infection. Using proteomics, we identified 21 algal proteins differentially accumulated in response to Eu. dicksonii infection. These include classical algal stress response proteins such as a manganese superoxide dismutase, heat shock proteins 70 and a vanadium bromoperoxidase. Transcriptional profiling by qPCR confirmed the induction of the latter during infection. The accumulation of hydrogen peroxide was observed at different infection stages via histochemical staining. Inhibitor studies confirmed that the main source of hydrogen peroxide is superoxide converted by superoxide dismutase. Our data give an unprecedented global overview of brown algal responses to pathogen infection, and highlight the importance of oxidative stress and halogen metabolism in these interactions. This suggests overlapping defence pathways with herbivores and abiotic stresses. We also identify previously unreported actors, in particular a Rad23 and a plastid–lipid‐associated protein, providing novel insights into the infection and defence processes in brown algae.
Expression of Caenorhabditis elegans PCS in the AtPCS1‐deficient Arabidopsis thaliana cad1‐3 mutant separates the metal tolerance and non‐host resistance functions of phytochelatin synthases
Authors: Kühnlenz Tanja , Westphal Lore , Schmidt Holger , Scheel Dierk , Clemens Stephan
Published: March 2015

Phytochelatin synthases (PCS) play key roles in plant metal tolerance. They synthesize small metal‐binding peptides, phytochelatins, under conditions of metal excess. Respective mutants are strongly cadmium and arsenic hypersensitive. However, their ubiquitous presence and constitutive expression had long suggested a more general function of PCS besides metal detoxification. Indeed, phytochelatin synthase1 from Arabidopsis thaliana (AtPCS1) was later implicated in non‐host resistance. The two different physiological functions may be attributable to the two distinct catalytic activities demonstrated for AtPCS1, that is the dipeptidyl transfer onto an acceptor molecule in phytochelatin synthesis, and the proteolytic deglycylation of glutathione conjugates. In order to test this hypothesis and to possibly separate the two biological roles, we expressed a phylogenetically distant PCS from Caenorhabditis elegans in an AtPCS1 mutant. We confirmed the involvement of AtPCS1 in non‐host resistance by showing that plants lacking the functional gene develop a strong cell death phenotype when inoculated with the potato pathogen Phytophthora infestans. Furthermore, we found that the C. elegans gene rescues phytochelatin synthesis and cadmium tolerance, but not the defect in non‐host resistance. This strongly suggests that the second enzymatic function of AtPCS1, which remains to be defined in detail, is underlying the plant immunity function.
Effects of PAR and UV Radiation on the Structural and Functional Integrity of Phycocyanin, Phycoerythrin and Allophycocyanin Isolated from the Marine Cyanobacterium Lyngbya sp. A09DM
Authors: Rastogi Rajesh Prasad , Sonani Ravi Raghav , Madamwar Datta
Published: March 2015

An in vitro analysis of the effects of photosynthetically active and ultraviolet radiations was executed to assess the photostability of biologically relevant pigments phycocyanin (PC), phycoerythrin (PE) and allophycocyanin (APC) isolated from Lyngbya sp. A09DM. Ultraviolet (UV) irradiances significantly affected the integrity of PC, PE and APC; however, PAR showed least effect. UV radiation affected the bilin chromophores covalently attached to phycobiliproteins (PBPs). Almost complete elimination of the chromophore bands associated with α‐ and β‐subunit of PE and APC occurred after 4 h of UV‐B exposure. After 5 h of UV‐B exposure, the content of PC, PE and APC decreased by 51.65%, 96.8% and 96.53%, respectively. Contrary to PAR and UV‐A radiation, a severe decrease in fluorescence of all PBPs was observed under UV‐B irradiation. The fluorescence activity of extracted PBP was gradually inhibited immediately after 15–30 min of UV‐B exposure. In comparison to the PC, the fluorescence properties of PE and APC were severely lost under UV‐B radiation. Moreover, the present study indicates that UV‐B radiation can damage the structural and functional integrity of phycobiliproteins leading to the loss of their ecological and biological functions.
Photodegradation of Hydrophobic Pyridineketoximes in Toluene and Heptane
Authors: Wieszczycka Karolina , Zembrzuska Joanna
Published: March 2015

The goal of the research was to study the reactivity of the hydrophobic 2‐ and 3‐pyridineketoximes under exposure to UV‐VIS light. The photodegradation was conducted in both toluene and heptane for 10 h under atmosphere of argon. Ten‐hour irradiation experiments demonstrated that the pyridineketoximes underwent the facile E‐Z photoisomerization, photo‐Beckmann rearrangement, and to a lesser extent, the photosubstitution to the pyridine ring. From LC‐MS and NMR analysis of the irradiated solutions, it was found that the photosubstitution proceeded to give the corresponding 6‐substituted 2‐ or 3‐pyridylketoxime via the replacement of the ring hydrogen by the benzyl or heptyl group. The photo‐Beckmann rearrangement led to the formation of the corresponding amides, but also other products formed in the photo‐decomposition reaction.
Disability Benefits in an Age of Austerity
Authors: Beatty Christina , Fothergill Steve
Published: March 2015

This article takes a long‐view of the huge rise in disability claimant numbers in the UK since the early 1980s and looks ahead to the trends that can now be expected to emerge in an era of fiscal austerity and welfare reform. The article's central thesis is that disability numbers are best understood as part of a triangular relationship between levels of employment, unemployment and sickness. In particular, the big decline of industrial employment in many places has often resulted in large‐scale ‘hidden unemployment’ on disability benefits, especially among low‐skilled workers. Looking ahead, the UK's welfare reforms are set to reduce disability claimant numbers but principally by restricting access to Employment and Support Allowance, the new disability benefit. The main effect will be to divert substantial numbers of men and women with ill health or disability onto unemployment benefits instead or, more often, out of the benefits system altogether.
Effect of Grain Size on the Spall Fracture Behaviour of Pure Copper under Plate‐Impact Loading
Authors: Chen T. , Jiang Z. X. , Peng H. , He H. L. , Wang L. L. , Wang Y. G.
Published: March 2015

The effects of grain size on the spall response were investigated for high purity copper materials by plate‐impact experiments including real‐time measurements of the free surface velocity profiles as well as post‐impact fractography studies on the soft‐recovered samples. High purity copper plates were cold rolled and heat treated to produce recrystallized samples with average grain sizes of 78, 273 and 400 μm, respectively. The spall strength estimated from the free surface velocity profile is nearly constant with no significant effect on the grain size. However, differences are observed in the acceleration rate of velocity rebound beyond the minima. This may be attributed to the effect of grain size on the growth rate of damage. Metallographic analyses of the fracture surface show that the characteristic feature of the fracture surface clearly depends on the grain size. In the 78‐ and 273‐μm samples, the fracture surfaces are decorated with large, high‐density ductile dimples suggesting that the preferential failure mode is ductile intergranular fracture. In the 400‐μm samples, the fracture surfaces have a rock candy appearance with small, high density brittle dimples as well as large ductile dimples suggesting that the fracture mode is a mix of both brittle intergranular fracture and ductile transgranular fracture.
Hardy, Littlewood and probability
Authors: Bingham N. H.
Published: March 2015

In this survey, we trace the interplay between the Hardy–Littlewood school of analysis, prominent in the UK in the first half of the last century, and probability theory, barely known in the UK at that time.
In vivo human cardiac shortening and lengthening velocity is region dependent and not coupled with heart rate: ‘longitudinal’ strain rate markedly underestimates apical contribution
Authors: Stöhr Eric J. , Stembridge Mike , Esformes Joseph I.
Published: March 2015

New Findings

What is the central question of this study?

Regulation of cardiac function is typically achieved by changes in heart rate (HR) and cardiac shortening velocity (strain rate; SR), but their interdependence in vivo remains poorly understood.

What is the main finding and its importance?

Using resistance exercise to increase heart rate and arterial resistance physiologically in humans and measuring regional cardiac SR (at the base and apex), we found that HR and SR were not strictly coupled because SR at the base and apex responded differently, despite the same HR. Importantly, our data show that the region‐averaged ‘longitudinal’ SR, which is currently popular in the clinical setting, markedly underestimates the contribution of the apex.

The fundamental importance of cardiac shortening and lengthening velocity (i.e. strain rate; SR) has been demonstrated in vitro. Currently, the interdependence between in vivo SR and HR is poorly understood because studies have typically assessed region‐averaged ‘longitudinal’ strain rate, which is likely to underestimate the apical contribution, and have used non‐physiological interventions that may also have been influenced by multicollinearity caused by concomitant reductions in arterial resistance. Resistance exercise acutely raises HR, blood pressure and arterial resistance and transiently disassociates these cardiovascular factors following exercise. Therefore, we measured SR, HR, blood pressure and arterial resistance in nine healthy men (aged 20 ± 1 years) immediately before, during and after double‐leg‐press exercise at 30 and 60% of maximal strength. Resistance exercise caused a disproportionate SR response at the left ventricular base and apex (interaction effect, P < 0.05). Consequently, associations between HR and regional peak SR were inconsistent and mostly very weak (r2 = 0.0004–0.24). Likewise, the areas under the curve for systolic and diastolic SR and their relationship with systolic and diastolic duration were variable and weak. Importantly, region‐averaged ‘longitudinal’ SR was identical to basal SR, thus, markedly underestimating the apical contribution. In conclusion, in vivo HR and SR are not strictly coupled in healthy humans, which is explained by the region‐specific responses of SR that are not captured by ‘longitudinal SR’. This novel observation emphasizes the independent role of in vivo SR in overall cardiac function during stress and may cause a ‘revival’ of SR as a marker of regional left ventricular (dys)function.