bluuebunny/crossref_metadata_2025 huggingface dataset:
Growing into teen fatherhood: a grounded theory study
Authors: Uengwongsapat C. , Kantaruksa K. , Klunklin A. , Sansiriphun N.
Published: November 2017

Background

Becoming an adolescent father is a significant and critical life event. Expectant fathers are faced with a concurrent dual developmental crisis: being an adolescent and becoming a father. This transition has a tremendous impact on these adolescents, their families and society. The impact on these individuals and society does not, at this point, seem to be clearly understood.

Purpose

To explore the process of Thai adolescents becoming first‐time fathers with an unplanned pregnancy during their girlfriend's pregnancy.

Methods

A grounded theory approach was used, drawing upon semi‐structured interviews with 16 expectant fathers in Chiang Mai, Thailand.

Findings

‘Growing into teen fatherhood’ was the basic social process that emerged as the core category. These fathers used this process for developing themselves to fatherhood. This process was further divided into three phases: enduring the conflict of future role, accepting impending fatherhood and developing a sense of being teen expectant father. Throughout this process, the participants encountered many conflicts and challenges. They employed various strategies to manage the emotional, financial and interpersonal challenges they faced during the transition to fatherhood.

Conclusion

This study provides data as well as anecdotal evidence for healthcare professionals to better understand adolescent fathers and their unique challenges during their girlfriend's pregnancy. A better understanding of these rich findings will enable healthcare professionals to assist young men and boys in their struggle to transition to fatherhood.

Implications for nursing policy

Our data may guide policymakers in developing support groups, effective mentoring programs and national follow‐up services as standard services in hospitals’ care for first‐time adolescent fathers in Thailand.
The external phenotype–skeleton link in post‐hatch farmed Chinook salmon (Oncorhynchus tshawytscha)
Authors: De Clercq A , Perrott M R , Davie P S , Preece M A , Huysseune A , Witten P E
Published: November 2017

Skeletal deformities in farmed fish are a recurrent problem. External malformations are easily recognized, but there is little information on how external malformations relate to malformations of the axial skeleton: the external phenotype–skeleton link. Here, this link is studied in post‐hatch to first‐feed life stages of Chinook salmon (Oncorhynchus tshawytscha) raised at 4, 8 and 12°C. Specimens were whole‐mount‐stained for cartilage and bone, and analysed by histology. In all temperature groups, externally normal specimens can have internal malformations, predominantly fused vertebral centra. Conversely, externally malformed fish usually display internal malformations. Externally curled animals typically have malformed haemal and neural arches. External malformations affecting a single region (tail malformation and bent neck) relate to malformed notochords and early fusion of fused vertebral centra. The frequencies of internal malformations in both externally normal and malformed specimens show a U‐shaped response, with lowest frequency in 8°C specimens. The fused vertebral centra that occur in externally normal specimens represent a malformation that can be contained and could be carried through into harvest size animals. This study highlights the relationship between external phenotype and axial skeleton and may help to set the framework for the early identification of skeletal malformations on fish farms.
Low fermentable oligo‐di‐mono‐saccharides and polyols diet versus general dietary advice in patients with diarrhea‐predominant irritable bowel syndrome: A randomized controlled trial
Authors: Zahedi Mohammad Javad , Behrouz Vahideh , Azimi Maryam
Published: November 2017

Background and Aim

Recent evidence indicates that new approach of the diet with low fermentable oligo‐di‐mono‐saccharides and polyols (FODMAPs) may have an effective role in management of the patients with irritable bowel syndrome (IBS). We compared the results of low FODMAP diet with current dietary treatment, general dietary advices (GDA), on the clinical response in patients with diarrhea subtype of IBS (IBS‐D).

Methods

In this randomized, controlled, single‐blind trial, we included 110 patients with IBS‐D in two intervention groups. Participants were randomly assigned to the low FODMAP diet (n = 55) and GDA (n = 55) for 6 weeks after a 10‐day screening period. Gastrointestinal symptoms and bowel habit status were evaluated using a symptom severity scoring system and Bristol stool form scale pre‐intervention and post‐intervention. Patients completed 3‐day food diary before and after the intervention.

Results

Of 110 patients, 101 completed the dietary interventions. At the baseline, the nutrient intake, severity of symptoms, and demographic data were similar between two groups. After 6 weeks, the low FODMAP diet improves significantly overall gastrointestinal symptoms scores, stool frequency, and consistency versus GDA group (P < 0.001, P < 0.001, and P = 0.003, respectively). Compared with the baseline, both intervention groups expressed a significant reduction in overall scores of symptom severity scoring system, abdominal pain, distension, consistency, and frequency, but this reduction is greater in low FODMAP diet group.

Conclusions

Both low FODMAP diet and GDA in patients with IBS‐D led to adequate improvement of gastrointestinal symptoms for 6 weeks. However, the low FODMAP diet has greater benefits in IBS improvement.
Barriers to adopting a Mediterranean diet in Northern European adults at high risk of developing cardiovascular disease
Authors: Moore S. E. , McEvoy C. T. , Prior L. , Lawton J. , Patterson C. C. , Kee F. , Cupples M. , Young I. S. , Appleton K. , McKinley M. C. , Woodside J. V.
Published: November 2017

Background

Strong evidence links the consumption of a Mediterranean diet (MD) with a reduced cardiovascular disease (CVD) risk; however, there is uncertainty as to whether non‐Mediterranean regions will adopt this diet. The present qualitative research aimed to investigate attitudes towards a MD in individuals at high CVD risk in a Northern European population. This information is needed to inform development of MD interventions in non‐Mediterranean high‐risk populations.

Methods

Focus groups (n = 12) were held with individuals at high CVD risk from Northern Europe (≥2 CVD risk factors, aged ≥50 years, no established CVD/type 2 diabetes). Attitudes to dietary change towards a MD were explored. Data were analysed using inductive thematic analysis.

Results

Sixty‐seven adults participated (60% female, mean age 64 years). There was some awareness of the term MD but limited knowledge of its composition. Barriers to general dietary change were evident, including perception of expense, concern over availability, expectation of time commitment, limited knowledge, lack of cooking skills, amount and conflicting nature of media information on diets, changing established eating habits and resistance to dietary change. Barriers specific to MD adoption were also identified, including perceived difficulty living in a colder climate, perceived impact on body weight, acceptability of a MD and cultural differences.

Conclusions

Knowledge of a MD was limited in this Northern European sample at high CVD risk. In addition to general barriers to dietary change, barriers specific to a MD were identified. These findings have implications for the development of interventions aiming to promote MD adoption in non‐Mediterranean populations.
Attention‐Deficit Hyperactivity Disorder: Clinical Considerations for Women
Authors: Marraccini Marisa E. , Weyandt Lisa L. , Gudmundsdottir Bergljot Gyda , Oster Danielle R. , McCallum Alison
Published: November 2017

Attention‐deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by hyperactivity, impulsivity, and/or inattention. Women with ADHD represent a particularly vulnerable group, given their increased risk for psychosocial and parenting difficulties. Women's health care clinicians should expect to encounter women with diagnosed and undiagnosed ADHD that may or may not be treated. Pharmacologic intervention, namely, prescription stimulants, is an important consideration for pregnant and breastfeeding women with ADHD, especially because the US Food and Drug Administration has determined that there is not enough information to confirm either harm or lack of harm to the developing fetus following exposure to these drugs. Due to the increase in use of prescription stimulants without a prescription, clinicians are also likely to encounter women misusing stimulants for a variety of reasons. This article provides an overview of ADHD diagnosis, outlines effective treatment options, and offers insight into the importance for clinicians to consider prescription stimulant misuse. Guidance concerning treatment of ADHD during pregnancy and lactation is reviewed.
The evolution of bite force in horned lizards: the influence of dietary specialization
Authors: Meyers Jay J. , Nishikawa Kiisa C. , Herrel Anthony
Published: November 2017

Dietary specialization is an important driver of the morphology and performance of the feeding system in many organisms, yet the evolution of phenotypic specialization has only rarely been examined within a species complex. Horned lizards are considered primarily myrmecophagous (ant eating), but variation in diet among the 17 species of horned lizards (Phrynosoma) makes them an ideal group to examine the relationship between dietary specialization and the resultant morphological and functional changes of the feeding system. In this study, we perform a detailed analysis of the jaw adductor musculature and use a biomechanical model validated with in vivo bite force data to examine the evolution of bite force in Phrynosoma. Our model simulations demonstrate that bite force varies predictably with respect to the gape angle and bite position along the tooth row, with maximal bite forces being attained at lower gape angles and at the posterior tooth positions. Maximal bite forces vary considerably among horned lizards, with highly myrmecophagous species exhibiting very low bite forces. In contrast, members of the short‐horned lizard clade are able to bite considerably harder than even closely related dietary generalists. This group appears to be built for performing crushing bites and may represent a divergent morphology adapted for eating hard prey items. The evolutionary loss of processing morphology (teeth, jaw and muscle reduction) and bite force in ant specialists may be a response to the lack of prey processing rather than a functional adaptation per se.
Smoking cessation leads to changes in survivin expression in oral mucosa
Authors: Lima Celina F. , Crastechini Erica , dos Santos Nathalia C. , Prado Ribeiro Ana Carolina , Brandão Thais B. , Castro Félix C. F. , Issa Jaqueline S. , Almeida Janete D.
Published: November 2017

Background

Survivin is an inhibitor protein of apoptosis and plays a role in oral carcinogenesis mechanism.

Methods

The aim of this study was to evaluate the effect of smoking in survivin expression of oral mucosa of chronic smokers with and without oral squamous cell carcinoma (OSCC). The study was composed of three groups: Group 1—26 patients smoking more than 20 cigarettes/day/10 years without either history of oral malignant neoplasia or visible clinical signs in the examined site; Group 2—26 patients with OSCC; Group 3—22 patients surgically treated for OSCC for at least 1 month. The immunohistochemistry was performed with 1 smear for each group and analyzed by microscopy regarding extension, intensity of positive cells for survivin, and intracellular location.

Results

The survivin expression was observed in 100% of the cases in Group 1, 88.5% in Group 2, and 100% in Group 3. Concerning to Groups 1 and 3, the survivin expression with cytoplasmic location occurred in 100%, while in Group 2 occurred in 87.5%. The cytoplasmic and nuclear expression was observed only in Group 2, with 7.69%. The results were correlated with clinical‐pathological data by Fischer's exact test with significant relation between smoking cessation and intensity (P = .015) for Group 2.

Conclusions

The extension and intensity of survivin expression in the cytological smears were related to the smoking cessation in the group with OSCC. However, the smoking history (packs/years) did not influence the survivin expression.
Three‐Dimensional Accuracy of Digital Static Interocclusal Registration by Three Intraoral Scanner Systems
Authors: Wong Kuan Yee , Esguerra Roxanna Jean , Chia Vanessa Ai Ping , Tan Ying Han , Tan Keson Beng Choon
Published: November 2017

Purpose

Prior studies have defined the accuracy of intraoral scanner (IOS) systems but the accuracy of the digital static interocclusal registration function of these systems has not been reported. This study compared the three‐dimensional (3D) accuracy of the digital static interocclusal registration of 3 IOS systems using the buccal bite scan function.

Materials and Methods

Three IOS systems compared were 3MTM True Definition Scanner (TDS), TRIOS Color (TRC), and CEREC AC with CEREC Omnicam (CER). Using each scanner, 7 scans (n = 7) of the mounted and articulated SLA master models were obtained. The measurement targets (SiN reference spheres and implant abutment analogs) were in the opposing models at the right (R), central (C), and left (L) regions; abutments #26 and #36, respectively. A coordinate measuring machine with metrology software compared the physical and virtual targets to derive the global 3D linear distortion between the centroids of the respective target reference spheres and abutment analogs (dRR, dRC, dRL, and dRM) and 2D distances between the pierce points of the abutment analogs (dXM, dYM, dZM), with 3 measurement repetitions for each scan.

Results

Mean 3D distortion ranged from –471.9 to 31.7 μm for dRR, –579.0 to –87.0 μm for dRC, –381.5 to 69.4 μm for dRL, and –184.9 to –23.1 μm for dRM. Mean 2D distortion ranged from –225.9 to 0.8 μm for dXM, –130.6 to ‐126.1 μm for dYM, and –34.3 to 26.3 μm for dZM. Significant differences were found for interarch distortions across the three systems. For dRR and dRL, all three test groups were significantly different, whereas for dRC, the TDS was significantly different from the TRC and CER. For 2D distortion, significant differences were found for dXM only.

Conclusions

Interarch and global interocclusal distortions for the three IOS systems were significantly different. TRC performed overall the best and TDS was the worst. The interarch (dRR, dRC, dRL) and interocclusal (dXM) distortions observed will affect the magnitude of occlusal contacts of restorations clinically. The final restoration may be either hyperoccluded or infraoccluded, requiring compensations during the CAD design stage or clinical adjustments at issue.
Crystalline structure of pulverized dental calculus induces cell death in oral epithelial cells
Authors: Ziauddin S. M. , Yoshimura A. , Montenegro Raudales J. L. , Ozaki Y. , Higuchi K. , Ukai T. , Kaneko T. , Miyazaki T. , Latz E. , Hara Y.
Published: November 2017

Background and Objective

Dental calculus is a mineralized deposit attached to the tooth surface. We have shown that cellular uptake of dental calculus triggers nucleotide‐binding oligomerization domain‐like receptor family pyrin domain‐containing 3 (NLRP3) inflammasome activation, leading to the processing of the interleukin‐1β precursor into its mature form in mouse and human phagocytes. The activation of the NLRP3 inflammasome also induced a lytic form of programmed cell death, pyroptosis, in these cells. However, the effects of dental calculus on other cell types in periodontal tissue have not been investigated. The aim of this study was to determine whether dental calculus can induce cell death in oral epithelial cells.

Material and Methods

HSC‐2 human oral squamous carcinoma cells, HOMK107 human primary oral epithelial cells and immortalized mouse macrophages were exposed to dental calculus or 1 of its components, hydroxyapatite crystals. For inhibition assays, the cells were exposed to dental calculus in the presence or absence of cytochalasin D (endocytosis inhibitor), z‐YVAD‐fmk (caspase‐1 inhibitor) or glyburide (NLRP3 inflammasome inhibitor). Cytotoxicity was determined by measuring lactate dehydrogenase (LDH) release and staining with propidium iodide. Tumor necrosis factor‐α production was quantified by enzyme‐linked immunosorbent assay. Oral epithelial barrier function was examined by permeability assay.

Results

Dental calculus induced cell death in HSC‐2 cells, as judged by LDH release and propidium iodide staining. Dental calculus also induced LDH release from HOMK107 cells. Following heat treatment, dental calculus lost its capacity to induce tumor necrosis factor‐α in mouse macrophages, but could induce LDH release in HSC‐2 cells, indicating a major role of inorganic components in cell death. Hydroxyapatite crystals also induced cell death in both HSC‐2 and HOMK107 cells, as judged by LDH release, indicating the capacity of crystal particles to induce cell death. Cell death induced by dental calculus was significantly inhibited by cytochalasin D, z‐YVAD‐fmk and glyburide, indicating NLRP3 inflammasome involvement. In permeability assays, dental calculus attenuated the barrier function of HSC‐2 cell monolayers.

Conclusion

Dental calculus induces pyroptotic cell death in human oral epithelial cells and the crystalline structure plays a major role in this process. Oral epithelial cell death induced by dental calculus might be important for the etiology of periodontitis.
Computing sleep deficiency
Authors: Erren Thomas C. , Groß J. Valerie , Lewis Philip
Published: November 2017

Sleep deficiency is a major public health concern. Since epidemiological studies play an important role in public health evaluations, this theoretical paper pursues answers to the question: ‘How can we compute sleep deficiency as informative measures of exposures or doses in observational research?’ Starting from the social jetlag concept and based on the chronodisruption rationale, we illustrate and discuss five approaches (one established and four untested, each with unique strengths and limitations) to quantify sleep deficiency by focusing on the timing and duration of sleep. Hitherto, social jetlag and chronodisruption rationale were neither explicitly proposed nor developed as assessments of sleep deficiency but, as we suggest, could potentially be utilized to this end. This first foray into computing sleep deficiency in epidemiological studies makes clear that laboratory, field and epidemiological collaboration is pre‐requisite to elucidating potential (co‐)causal roles of sleep deficiency in disease endpoints.
Trends in hepatitis C‐related mortality in Switzerland
Authors: Keiser O. , Giudici F. , Müllhaupt B. , Junker C. , Dufour J. ‐F. , Moradpour D. , Bruggmann P. , Terziroli B. , Semela D. , Brezzi M. , Bertisch B. , Estill J. , Negro F. , Spoerri A. ,   the Swiss Hepatitis C Cohort Study and the Swiss National Cohort
Published: November 2017

In order to accurately assess the burden of hepatitis C (HCV) and develop effective interventions, we must understand the magnitude and trends of mortality related to the disease. In the United States, HCV‐related mortality is continuously increasing. We have no comparable data for Switzerland and other European countries, although a modelling study predicted a similar increase. We analysed time trends (1 January 1995‐31 December 2014) in HCV‐specific mortality rates in the Swiss general population using the death registry of the Swiss Federal Statistical Office (SFSO). We compared HCV‐related mortality to HIV‐related and hepatitis B (HBV)‐related mortality. To determine potential under‐reporting in HCV‐related mortality, we probabilistically linked the SFSO data to persons who died in the Swiss Hepatitis C Cohort Study (SCCS). SFSO data showed that HCV‐related mortality more than doubled between 1995 and 2003, but has since stabilized at ~2.5/100 000 person‐years. Since 2000, HCV‐related mortality has been higher than HIV‐related mortality and was about fivefold higher in 2014. HBV‐related mortality remained low at ~0.5/100 000 person‐years. Of 4556 persons in the SCCS, 421 have died and 86.2% could be linked to the death registry. According to the SCCS, 133 deaths were HCV‐related. HCV was not mentioned on the SFSO death certificate of 45% of these (n = 60/133). In conclusion, HCV‐related mortality remained constant, possibly because quality of care was high, or because of under‐reporting or because mortality has not yet increased. However, HCV‐related mortality is now much higher than HIV‐ and HBV‐related mortality, and under‐reporting was common.
Virtue and the Law: The Good Moral Character Requirement in Occupational Licensing, Bar Regulation, and Immigration Proceedings
Authors: Rhode Deborah L.
Published: November 2017

Character plays a crucial role in US law. This article explores flaws in how moral character requirements determine who can work in licensed occupations, who can practice law, and who can immigrate to the United States or become a citizen. Section I summarizes psychological research on character, which raises questions about a central legal premise that individuals have a settled disposition capable of accurately predicting their behavior independent of situational influences. Section II examines the role of moral character as an employment credential. Almost a third of the workforce is covered by licensing laws that typically require proof of good character and often unjustly penalize the seventy million Americans with criminal records. Section III examines the idiosyncratic and inconsistent application of moral character requirements for lawyers. Section IV focuses on similar flaws in immigration contexts. Section V identifies reform strategies to improve the fairness of character-related decisions in the law.
On the Value of Monitoring Information for the Structural Integrity and Risk Management
Authors: Thöns Sebastian
Published: November 2017

This article introduces an approach and framework for the quantification of the value of structural health monitoring (SHM) in the context of the structural risk and integrity management for systems. The quantification of the value of SHM builds upon the Bayesian decision and utility theory, which facilitates the assessment of the value of information associated with SHM. The principal approach for the quantification of the value of SHM is formulated by modeling the fundamental decision of performing SHM or not in conjunction with their expected utilities. The expected utilities are calculated accounting for the probabilistic performance of a system in conjunction with the associated structural integrity and risk management actions throughout the life cycle, the associated benefits, structural risks, and costs and when performing SHM, the SHM information, their probabilistic outcomes, and costs. The calculation of the expected utilities necessitates a comprehensive and rigorous modeling, which is introduced close to the original formulations and for which analysis characteristics and simplifications are described and derived. The framework provides the basis for the optimization of the structural risk and integrity management based on utility gains including or excluding SHM and inspection information. Studies of fatigue deteriorating structural systems and their characteristics (1) provide decision support for the performance of SHM, (2) explicate the influence of the structural component and system characteristics on the value of SHM, and (3) demonstrate how an integral optimization of SHM and inspection strategies for an efficient structural risk and integrity management can be performed.
Family and Social Context Contributes to the Interplay of Economic Insecurity, Food Insecurity, and Health
Authors: HIGASHI ROBIN T. , LEE SIMON CRADDOCK , PEZZIA CARLA , QUIRK LISA , LEONARD TAMMY , PRUITT SANDI L.
Published: November 2017

In this study, we show how household health, economic instability, and food insecurity are inextricably linked and how disruptions in individual health or income create cumulative and interdependent challenges faced by multiple household members. Drawing upon semistructured focus groups with English‐ and Spanish‐speaking clients of an urban food pantry, we demonstrate: (1) the impact of economic scarcity on health, (2) the impact of one household member's health on the health and food security of all household members, and (3) food‐sharing behaviors among family and social networks, including multigenerational families and nonkin individuals. We identify the gap in the literature between household‐level assessments of food insecurity and individual‐level health reports, which may obscure poor health among other household members. Understanding the social and family context of health and food insecurity may inform future interventions that address the interrelated challenges of diverse and disadvantaged households and communities.
Wearable gait sensors to measure ataxia due to spinocerebellar degeneration
Authors: Terayama Keiichiro , Sakakibara Ryuji , Ogawa Akihiro
Published: November 2017

Background and Aim

Limited attention has been paid to the relationship between wearable gait sensors in cerebellar ataxia.

Objective

We aimed to correlate a bed‐side ataxia measure with wearable gait sensor parameters in patients with spinocerebellar degeneration (SCD).

Methods

We recruited 14 SCD patients capable of walking independently: six men and eight women, mean age 59.4 years, disease duration 5.3 years, pure cerebellar type 10, cerebellar‐plus type 4, but with few symptoms other than cerebellar ataxia. All patients were assessed by the Scale for the Assessment and Rating of Ataxia (SARA) and the Gait‐Kun system, a wearable gait sensor with triple‐axial accelerometers. Statistical analysis was performed by Spearman's rank correlation coefficient test and multiple regression analysis test. Significance was estimated as P < 0.05.

Results

We found that (i) the Gait‐Kun system can be used easily in cerebellar ataxia patients; (ii) Spearman's rank correlation coefficient test showed a close relationship between SARA gait subcategory and (a) converted number of steps (indicating shorter stride) (P < 0.01) and (b) step‐width variation (indicating staggering) (P < 0.01); and (iii) multiple regression analysis showed a close relationship between SARA gait and converted number of steps (indicating shorter stride) (P = 0.001).

Conclusion

Using the Gait‐Kun system (wearable sensors), there was a close relationship between SARA gait subcategory and both converted number of steps and step‐width variation, indicating that not only step‐width variability but also shorter stride is a feature of ataxic gait abnormalities.
Fusarium graminearum: pathogen or endophyte of North American grasses?
Authors: Lofgren Lotus A. , LeBlanc Nicholas R. , Certano Amanda K. , Nachtigall Jonny , LaBine Kathryn M. , Riddle Jakob , Broz Karen , Dong Yanhong , Bethan Bianca , Kafer Christopher W. , Kistler H. Corby
Published: November 2017

Mycotoxin‐producing Fusarium graminearum and related species cause Fusarium head blight on cultivated grasses, such as wheat and barley. However, these Fusarium species may have had a longer evolutionary history with North American grasses than with cultivated crops and may interact with the ancestral hosts in ways which are biochemically distinct.

We assayed 25 species of asymptomatic native grasses for the presence of Fusarium species and confirmed infected grasses as hosts using re‐inoculation tests. We examined seed from native grasses for the presence of mycotoxin‐producing Fusarium species and evaluated the ability of these fungi to produce mycotoxins in both native grass and wheat hosts using biochemical analysis.

Mycotoxin‐producing Fusarium species were shown to be prevalent in phylogenetically diverse native grasses, colonizing multiple tissue types, including seeds, leaves and inflorescence structures. Artificially inoculated grasses accumulated trichothecenes to a much lesser extent than wheat, and naturally infected grasses showed little to no accumulation.

Native North American grasses are commonly inhabited by Fusarium species, but appear to accommodate these toxigenic fungi differently from cultivated crops. This finding highlights how host identity and evolutionary history may influence the outcome of plant–fungal interactions and may inform future efforts in crop improvement.
Clinical and histopathologic features of antibody‐mediated rejection among pediatric renal transplant recipients with preformed vs de novo donor‐specific antibodies
Authors: Steggerda Justin A. , Kim Irene K. , Haas Mark , Zhang Xiaohai , Kang Alexis , Pizzo Helen , Kamil Elaine , Jordan Stanley , Puliyanda Dechu
Published: November 2017

Preformed and de novo donor specific antibodies (pDSA and dnDSA) are risk factors for ABMR. This study compares the effects of pDSA vs dnDSA in pediatric kidney transplant recipients. Sixteen pediatric patients with biopsy‐proven ABMR were evaluated. Strong DSA (MFI >10 000) was recorded at transplant, rejection, and follow‐up. DSAs with the highest MFI were termed iDSAs. Allograft biopsies were scored according to Banff 2013 criteria. Seven of 16 (44%) patients had pDSA at transplant; 9 (56%) developed dnDSA. Patients with pDSA developed ABMR earlier (median = 63 vs 1344 days, P = .017), while patients with dnDSA were more likely to have strong Class II iDSA (100% vs 28%, P = .009). Viral infection or non‐adherence was more common in patients developing dnDSA (88.8% vs 28.6%, P < .01). Pathology in those with pDSAs demonstrated worse transplant glomerulitis (g score 1.57 ± 0.98 vs 0.56 ± 0.73, P = .031); however, those with dnDSAs exhibited higher C4d+ ABMR (P = .013). Patients developing dnDSAs showed ABMR later post‐transplant with predominance of HLA‐Class II iDSAs. Inadequate immunosuppression likely contributes to dnDSA formation. Patients with no DSA who have unprotocolized decreases in immunosuppression should be screened for dnDSA as it could lead to early intervention and potentially better outcomes.
Ageing impairs parasite‐specific antibody responses in cystic echinococcosis
Authors: Mourglia‐Ettlin G. , Miles S. , Hernández A. , Dematteis S.
Published: November 2017

Humoral immunity wanes during healthy ageing, increasing susceptibility to infections in the elderly. In this sense, information about parasite infections and human immunosenescence is scarce. Cystic echinococcosis (CE) is an infectious disease caused by the larval stage of the cestode parasite Echinococcus granulosus, whose prevalence in humans shows an increase with host age. Susceptibility to human CE has been associated with humoral immunity to some extent, and, therefore, we have here analysed the influence of host age on the serological profile of young, middle‐aged and aged patients. Our results highlighted the detrimental influence of ageing on the intensity and quality of the antiparasite antibody response. Remarkable differences in serological profiles between young and aged individuals were observed. In this sense, through Principal Components Analysis, we identified aged patients as those exhibiting overall less intense antibody responses, mainly in isotypes/subclasses supposed to exert efficient antiparasite activities (eg IgE and IgG1). Thus, these humoral defects could at least partially explain the reported increase in CE prevalence among older individuals, as a weaker immune response in the elderly might facilitate the establishment and maintenance of the parasite infection. Finally, a possible association between age‐dependent susceptibility to CE and host immunosenescence is discussed.
Saddlebags: A software interface for submitting full‐length HLA allele sequences to the EMBL‐ENA nucleotide database
Authors: Matern B. M. , Groeneweg M. , Voorter C. E. M. , Tilanus M. G. J.
Published: November 2017

Submission of full‐length HLA allele sequences presents a unique challenge, both for high‐throughput sequencing laboratories and smaller diagnostic laboratories. HLA's extensive polymorphism means that accurate representation and annotation of allele sequence is of critical importance, and curators of nucleotide databases must establish submission formats to ensure high‐quality data and prevent ambiguities. The IPD‐IMGT/HLA database is established as the standard repository for HLA sequences, and it is a major goal of the 17th International HLA and Immunogenetics Workshop to fill the IPD‐IMGT/HLA database with full‐length HLA sequences. The process of preparing sequence annotation and metadata is cumbersome and error prone, and it is desirable to create a straightforward and concise method of preparing sequence submissions. We introduce Saddlebags, a software tool for rapid generation of HLA (novel) full‐length allele sequence submissions. HLA allele sequences are submitted first to EMBL European Nucleotide Archive (EMBL‐ENA), and metadata is gathered for subsequent preparation of an IPD‐IMGT/HLA formatted submission. Combining these steps into a pipeline reduces effort and minimizes errors for submitting laboratories. This software has been used by Maastricht University Medical Center Transplantation Immunology Laboratory to submit 79 novel alleles to EMBL‐ENA, and the tool is freely available for the HLA community.
Investigation of Forming Cylindrical Parts in a Modified Hydrodynamic Deep Drawing Assisted by Radial Pressure With Inward Flowing Liquid
Authors: Yazdi Milad Sadegh , Bakhshi-Jooybari Mohammad , Gorji Hamid , Shakeri Mohsen , Khademi Maziar
Published: November 2017

Among the sheet hydroforming processes, hydrodynamic deep drawing (HDD) process has been used to form complex shapes and can produce parts with high drawing ratio. Studies showed that radial pressure created on the edge of the sheet can decrease the drawing force and increase drawing ratio. Thus, increasing of radial pressure to an amount greater than chamber pressure, and independent control of these pressures, is the basic idea in this study. In this research, the effect of radial and chamber pressures on formability of St13 and pure copper sheets in the process of hydrodynamic deep drawing assisted by radial pressure (HDDRP) with inward flowing liquid is investigated. Giving that a significant portion of the maximum thinning of the formed part occurs in the beginning of the process, the pressure supply system used in the experimental tests was designed in a way, which provides simultaneous control of the radial and chamber pressures throughout the process. Thickness distribution, forming force, and tensile stresses are the parameters that were evaluated in this study. Results indicated that using a higher radial pressure than the chamber pressure and controlling their values in the initial stages of the process enhances the thickness distribution of the formed part in all regions. A comparison between the thickness distribution and maximum forming force of the formed parts by the HDDRP and HDDRP with inward flowing liquid methods showed that by applying the later method, parts with more uniform thickness distribution and less maximum thinning and forming force can be achieved.
Experimental Evaluation of Novel Hybrid Microwave/Ultrasonic Technique to Locate and Characterize Pipe Wall Thinning
Authors: Alobaidi Wissam M. , Kintner Clifford E. , Alkuam Entidhar A. , Sasaki Kota , Yusa Noritaka , Hashizume Hidetoshi , Sandgren Eric
Published: November 2017

Research using microwaves (MWs) to detect pipe wall thinning (PWT) distinguishes the presence of wall thinning, but does not accurately locate the discontinuities. Ultrasonic testing (UT) is capable of accurately locating the PWT defect, but cannot do so without time-consuming linear scanning. This novel work combines the MW technique as a way to predict the location of a series of PWT specimens, and the UT technique as a way to characterize the PWT specimens in terms of location, depth, and profile shape. The UT probe is guided to the predicted location derived from the Phase One MW results, generating the Phase Two results to determine accurate location, depth measurement, and profile shape detection. The work uses the previously successful experimental setup for testing of an aluminum pipe with 154.051 mm inner diameter (ID) and 1 m length. A vector network analyzer (VNA) generates a MW sweeping frequency range of 1.4–2.3 GHz. This signal is propagated within reference pipes with both open end and short-circuit configurations for calibration of the system. The calibrated system is used to detect the presence and location of six PWT specimens, with two profile shapes, at three depths of thinning and three locations along the pipe. The predicted locations from Phase One are then used to guide a calibrated, manually guided straight beam UT probe to the predicted position. From that point, the UT probe is used in order to accurately localize and determine the depth and shape profile of the specimens.
A Cyclic-Plasticity-Based Mechanistic Approach for Fatigue Evaluation of 316 Stainless Steel Under Arbitrary Loading
Authors: Barua Bipul , Mohanty Subhasish , Listwan Joseph T. , Majumdar Saurindranath , Natesan Krishnamurti
Published: November 2017

In this paper, a cyclic-plasticity-based fully mechanistic fatigue modeling approach is presented. This is based on time-dependent stress–strain evolution of the material over the entire fatigue life rather than just based on the end of live information typically used for empirical S∼N curve-based fatigue evaluation approaches. Previously, we presented constant amplitude fatigue test based related material models for 316 stainless steel (SS) base, 508 low alloy steel base, and 316 SS-316 SS weld which are used in nuclear reactor components such as pressure vessels, nozzles, and surge line pipes. However, we found that constant amplitude fatigue data-based models have limitation in capturing the stress–strain evolution under arbitrary fatigue loading. To address the aforementioned limitation, in this paper, we present a more advanced approach that can be used for modeling the cyclic stress–strain evolution and fatigue life not only under constant amplitude but also under any arbitrary (random/variable) fatigue loading. The related material model and analytical model results are presented for 316 SS base metal. Two methodologies (either based on time/cycle or based on accumulated plastic strain energy (APSE)) to track the material parameters at a given time/cycle are discussed and associated analytical model results are presented. From the material model and analytical cyclic plasticity model results, it is found that the proposed cyclic plasticity model can predict all the important stages of material behavior during the entire fatigue life of the specimens with more than 90% accuracy.
Isofocal dose based proximity effect correction tolerance to the effective process blur
Authors: Lopez Gerald G. , Azadi Mohsen , Metzler Meredith G. , Belic Nikola , Hofmann Ulrich
Published: November 2017

The isofocal dose in electron beam lithography (EBL) is defined as the dose that results in the same feature size independent of the effective blur (blureff), which is the result of a combination of resist processing, spot size, beam focus, forward scattering, etc., that contributes to the final resist image. In other words, as blureff changes the same feature size is still obtained while using the same dose. This phenomenon is clearly demonstrated in EBL simulation when varying the blureff. In this work, the authors identify the isofocal dose for a given resist process consisting of 200 nm of ZEP520A from ZEON Chemicals atop a Si substrate using 300 nm line-space tower patterns with pattern densities ranging from 0% to 100% on an Elionix ELS-7500EX 50 keV EBL tool with a fixed 20 MHz clock at 200 pA with a 30 μm final aperture and a 20 nm beam step size. In this experiment, the dominant component of the blureff is the electron beam focus. By comparing line width measurements from tower patterns exposed with a focused beam with those from a defocused beam, the resulting blureff manifest themselves in the exposure latitude as a change in slope for each pattern density. Superimposing the exposure latitudes from each blureff at their specific pattern density, the intersection of said curves indicates the pattern density dependent isofocal dose of the resist process. Despite the difference in the blureff, the response to the correction remains invariant when the density dependent isofocal doses are aligned properly using a tunable proximity effect correction (PEC) algorithm. This means if a PEC yields the appropriate pattern density dependent isofocal doses, the same feature sizes will be consistently attainable across all pattern densities regardless of the beam focus accuracy. The text that follows demonstrates the technique used to empirically identify the pattern density isofocal doses for a given resist processes and its application using a commercially available PEC algorithm.
Extended gamma-ray sources around pulsars constrain the origin of the positron flux at Earth
Authors: Abeysekara A. U. , Albert A. , Alfaro R. , Alvarez C. , Álvarez J. D. , Arceo R. , Arteaga-Velázquez J. C. , Avila Rojas D. , Ayala Solares H. A. , Barber A. S. , Bautista-Elivar N. , Becerril A. , Belmont-Moreno E. , BenZvi S. Y. , Berley D. , Bernal A. , Braun J. , Brisbois C. , Caballero-Mora K. S. , Capistrán T. , Carramiñana A. , Casanova S. , Castillo M. , Cotti U. , Cotzomi J. , Coutiño de León S. , De León C. , De la Fuente E. , Dingus B. L. , DuVernois M. A. , Díaz-Vélez J. C. , Ellsworth R. W. , Engel K. , Enríquez-Rivera O. , Fiorino D. W. , Fraija N. , García-González J. A. , Garfias F. , Gerhardt M. , González Muñoz A. , González M. M. , Goodman J. A. , Hampel-Arias Z. , Harding J. P. , Hernández S. , Hernández-Almada A. , Hinton J. , Hona B. , Hui C. M. , Hüntemeyer P. , Iriarte A. , Jardin-Blicq A. , Joshi V. , Kaufmann S. , Kieda D. , Lara A. , Lauer R. J. , Lee W. H. , Lennarz D. , Vargas H. León , Linnemann J. T. , Longinotti A. L. , Luis Raya G. , Luna-García R. , López-Coto R. , Malone K. , Marinelli S. S. , Martinez O. , Martinez-Castellanos I. , Martínez-Castro J. , Martínez-Huerta H. , Matthews J. A. , Miranda-Romagnoli P. , Moreno E. , Mostafá M. , Nellen L. , Newbold M. , Nisa M. U. , Noriega-Papaqui R. , Pelayo R. , Pretz J. , Pérez-Pérez E. G. , Ren Z. , Rho C. D. , Rivière C. , Rosa-González D. , Rosenberg M. , Ruiz-Velasco E. , Salazar H. , Salesa Greus F. , Sandoval A. , Schneider M. , Schoorlemmer H. , Sinnis G. , Smith A. J. , Springer R. W. , Surajbali P. , Taboada I. , Tibolla O. , Tollefson K. , Torres I. , Ukwatta T. N. , Vianello G. , Weisgarber T. , Westerhoff S. , Wisher I. G. , Wood J. , Yapici T. , Yodh G. , Younk P. W. , Zepeda A. , Zhou H. , Guo F. , Hahn J. , Li H. , Zhang H.
Published: November 2017

Exotic origin for cosmic positrons

Several cosmic-ray detectors have found more positrons arriving at Earth than expected. Some researchers interpret this as a signature of exotic physics, such as the annihilation of dark matter particles. Others prefer a more mundane explanation that involves positron generation at pulsars followed by diffusion to Earth. Abeysekara
et al.
detected extended emission of gamma rays around two nearby pulsars, generated by high-energy electrons and positrons. The size of the extended emission was used to calculate how far positrons generated by the pulsars diffuse through space—which turns out to be insufficient to reach Earth. The excess positrons detected on Earth must therefore have a more exotic origin than nearby pulsars.

Science
, this issue p.
911
Failures to further developing orphan medicinal products after designation granted in Europe: an analysis of marketing authorisation failures and abandoned drugs
Authors: Giannuzzi Viviana , Landi Annalisa , Bosone Enrico , Giannuzzi Floriana , Nicotri Stefano , Torrent-Farnell Josep , Bonifazi Fedele , Felisi Mariagrazia , Bonifazi Donato , Ceci Adriana
Published: November 2017

Objectives

The research and development process in the field of rare diseases is characterised by many well-known difficulties, and a large percentage of orphan medicinal products do not reach the marketing approval.

This work aims at identifying orphan medicinal products that failed the developmental process and investigating reasons for and possible factors influencing failures.

Design

Drugs designated in Europe under Regulation (European Commission) 141/2000 in the period 2000–2012 were investigated in terms of the following failures: (1) marketing authorisation failures (refused or withdrawn) and (2) drugs abandoned by sponsors during development.

Possible risk factors for failure were analysed using statistically validated methods.

Results

This study points out that 437 out of 788 designations are still under development, while 219 failed the developmental process. Among the latter, 34 failed the marketing authorisation process and 185 were abandoned during the developmental process. In the first group of drugs (marketing authorisation failures), 50% reached phase II, 47% reached phase III and 3% reached phase I, while in the second group (abandoned drugs), the majority of orphan medicinal products apparently never started the development process, since no data on 48.1% of them were published and the 3.2% did not progress beyond the non-clinical stage.

The reasons for failures of marketing authorisation were: efficacy/safety issues (26), insufficient data (12), quality issues (7), regulatory issues on trials (4) and commercial reasons (1). The main causes for abandoned drugs were efficacy/safety issues (reported in 54 cases), inactive companies (25.4%), change of company strategy (8.1%) and drug competition (10.8%). No information concerning reasons for failure was available for 23.2% of the analysed products.

Conclusions

This analysis shows that failures occurred in 27.8% of all designations granted in Europe, the main reasons being safety and efficacy issues. Moreover, the stage of development reached by drugs represents a specific risk factor for failures.
Particle and astroparticle physics in China
Authors: Wang Yifang
Published: November 2017

Particle and astroparticle physics activities in China can be classified into four major categories: accelerator-based experiments, underground experiments, cosmic-ray physics at high altitude, and space experiments. An overview of these experiments and their future perspectives are presented.
Extensive Numerical Study and Circuitry Implementation of the Watt Governor Model
Authors: Marcondes D. W. C. , Comassetto G. F. , Pedro B. G. , Vieira J. C. C. , Hoff A. , Prebianca F. , Manchein C. , Albuquerque H. A.
Published: November 2017

In this work we carry out extensive numerical study of a Watt centrifugal governor system model, and we also implement an electronic circuit by analog computation to experimentally solve the model. Our numerical results show the existence of self-organized stable periodic structures (SPSs) on parameter-space of the largest Lyapunov exponent and isospikes of time series of the Watt governor system model. A peculiar hierarchical organization and period-adding bifurcation cascade of the SPSs are observed, and this self-organized cascade accumulates on a periodic boundary. It is also shown that the periods of these structures organize themselves obeying the solutions of Diophantine equations. In addition, an experimental setup is implemented by a circuitry analogy of mechanical systems using analog computing technique to characterize the robustness of our numerical results. After applying an active control of chaos in the experiment, the effect of intrinsic experimental noise was minimized such that, the experimental results are astonishingly well in agreement with our numerical findings. We can also mention as another remarkable result, the application of analog computing technique to perform an experimental circuitry analysis in real mechanical problems.