bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nonparametric Methods for Analyzing Recurrent Gap Time Data with Application to Infections After Hematopoietic Cell Transplant
Authors: Lee Chi Hyun , Luo Xianghua , Huang Chiung-Yu , DeFor Todd E. , Brunstein Claudio G. , Weisdorf Daniel J. 
Published: November 2015

Summary
Infection is one of the most common complications after hematopoietic cell transplantation. Many patients experience infectious complications repeatedly after transplant. Existing statistical methods for recurrent gap time data typically assume that patients are enrolled due to the occurrence of an event of interest, and subsequently experience recurrent events of the same type; moreover, for one-sample estimation, the gap times between consecutive events are usually assumed to be identically distributed. Applying these methods to analyze the post-transplant infection data will inevitably lead to incorrect inferential results because the time from transplant to the first infection has a different biological meaning than the gap times between consecutive recurrent infections. Some unbiased yet inefficient methods include univariate survival analysis methods based on data from the first infection or bivariate serial event data methods based on the first and second infections. In this article, we propose a nonparametric estimator of the joint distribution of time from transplant to the first infection and the gap times between consecutive infections. The proposed estimator takes into account the potentially different distributions of the two types of gap times and better uses the recurrent infection data. Asymptotic properties of the proposed estimators are established.
A Rank-Sum Test for Clustered Data When the Number of Subjects in a Group within a Cluster is Informative
Authors: Dutta Sandipan , Datta Somnath 
Published: November 2015

Summary
The Wilcoxon rank-sum test is a popular nonparametric test for comparing two independent populations (groups). In recent years, there have been renewed attempts in extending the Wilcoxon rank sum test for clustered data, one of which (Datta and Satten, 2005, Journal of the American Statistical Association 100, 908–915) addresses the issue of informative cluster size, i.e., when the outcomes and the cluster size are correlated. We are faced with a situation where the group specific marginal distribution in a cluster depends on the number of observations in that group (i.e., the intra-cluster group size). We develop a novel extension of the rank-sum test for handling this situation. We compare the performance of our test with the Datta–Satten test, as well as the naive Wilcoxon rank sum test. Using a naturally occurring simulation model of informative intra-cluster group size, we show that only our test maintains the correct size. We also compare our test with a classical signed rank test based on averages of the outcome values in each group paired by the cluster membership. While this test maintains the size, it has lower power than our test. Extensions to multiple group comparisons and the case of clusters not having samples from all groups are also discussed. We apply our test to determine whether there are differences in the attachment loss between the upper and lower teeth and between mesial and buccal sites of periodontal patients.
N‐terminally and C‐terminally truncated forms of glucose‐dependent insulinotropic polypeptide are high‐affinity competitive antagonists of the human GIP receptor
Authors: Hansen L S , Sparre‐Ulrich A H , Christensen M , Knop F K , Hartmann B , Holst J J , Rosenkilde M M 
Published: November 2015

Background and PurposeGlucose‐dependent insulinotropic polypeptide (GIP) affects lipid, bone and glucose homeostasis. High‐affinity ligands for the GIP receptor are needed to elucidate the physiological functions and pharmacological potential of GIP in vivo. GIP(1–30)NH2 is a naturally occurring truncation of GIP(1–42). Here, we have characterized eight N‐terminal truncations of human GIP(1–30)NH2.Experimental ApproachCOS‐7 cells were transiently transfected with human GIP receptors and assessed for cAMP accumulation upon ligand stimulation or competition binding with 125I‐labelled GIP(1–42), GIP(1–30)NH2, GIP(2–30)NH2 or GIP(3–30)NH2.Key ResultsGIP(1–30)NH2 displaced 125I‐GIP(1–42) as effectively as GIP(1–42) (Ki 0.75 nM), whereas the eight truncations displayed lower affinities (Ki 2.3–347 nM) with highest affinities for GIP(3–30)NH2 and GIP(5–30)NH2 (5–30)NH2. Only GIP(1–30)NH2 (Emax 100% of GIP(1–42)) and GIP(2–30)NH2 (Emax 20%) were agonists. GIP(2‐ to 9–30)NH2 displayed antagonism (IC50 12–450 nM) and Schild plot analyses identified GIP(3–30)NH2 and GIP(5–30)NH2 as competitive antagonists (Ki 15 nM). GIP(3–30) NH2 was a 26‐fold more potent antagonist than GIP(3–42). Binding studies with agonist (125I‐GIP(1–30)NH2), partial agonist (125I‐GIP(2–30)NH2) and competitive antagonist (125I‐GIP(3–30)NH2) revealed distinct receptor conformations for these three ligand classes.Conclusions and ImplicationsThe N‐terminus is crucial for GIP agonist activity. Removal of the C‐terminus of the endogenous GIP(3–42) creates another naturally occurring, more potent, antagonist GIP(3–30)NH2, which like GIP(5–30)NH2, was a high‐affinity competitive antagonist. These peptides may be suitable tools for basic GIP research and future pharmacological interventions.
Did Canadian welfare reform work? The effects of new reform strategies on social assistance participation
Authors: Berg Nathan , Gabel Todd 
Published: November 2015

AbstractThis paper measures the extent to which declines in social assistance (SA) participation were associated with novel and aggressive reforms referred to as new reform strategies: work requirements, diversion, earning exemptions and time limits. Controlling for province‐specific benefit levels, eligibility requirements, GDP growth, labour market conditions and demographics, SA participation rates were more than one percentage point lower (equivalent to a 13% decline) in provinces with new reforms. Work requirements with strong sanctions had the sharpest negative associations. New reform strategies explain at least 10% of observed declines in SA participation, twice that of benefit levels and eligibility requirements.
Estimating future dental services' demand and supply: a model for Northern Germany
Authors: Jäger Ralf , van den Berg Neeltje , Hoffmann Wolfgang , Jordan Rainer A. , Schwendicke Falk 
Published: November 2015

AbstractObjectivesTo plan dental services, a spatial estimation of future demands and supply is required. We aimed at estimating demand and supply in 2030 in Northern Germany based on the expected local socio‐demography and oral‐health‐related morbidity, and the predicted number of dentists and their working time.MethodsAll analyses were performed on zip‐code level. Register data were used to determine the number of retiring dentists and to construct regression models for estimating the number of dentists moving into each zip‐code area until 2030. Demand was modelled using projected demography and morbidities. Demand‐supply ratios were evaluated and spatial analyses applied. Sensitivity analyses were employed to assess robustness of our findings.ResultsCompared with 2011, the population decreased (−7% to −11%) and aged (from mean 46 to 51 years) until 2030. Oral‐health‐related morbidity changed, leading to more periodontal and fewer prosthetic treatments needs, with the overall demand decreasing in all scenarios (−25% to −33%). In contrast, the overall number of dentists did only limitedly change, resulting in moderate decrease in the supplied service quantities (max. −22%). Thus, the demand–supply ratio increased in all but the worst case scenario, but was unequally distributed between spatial units, with several areas being over‐ and some being under‐ or none‐serviced in 2030.ConclusionsWithin the limitations of the underlying data and the required assumptions, this study expects an increasingly polarized ratio of dental services demand and supply in Northern Germany. Our estimation allows to assess the impact of different influence factors on demand or supply and to specifically identify potential challenges for workforce planning and regulation in different spatial units.
Variability in penetrance of multiple endocrine neoplasia 2A with amino acid substitutions in RET codon 634
Authors: Machens Andreas , Dralle Henning 
Published: November 2015

SummaryObjectiveControversy surrounds the importance of the different amino acids substituting for cysteine in REarranged during Transfection (RET) codon 634 for multiple endocrine neoplasia 2A (MEN 2A). This study aimed to clarify the relevance of these amino acid substitutions for the development of MEN 2A.DesignCross‐sectional study at surgical referral centres in Germany.PatientsIncluded were 184 carriers of RET mutations in codon 634.MeasurementsArginine (79 carriers) and tyrosine (50 carriers) substitutions in codon 634 were compared with each other and, for the first time, gauged against a common reference standard comprising all other amino acid substitutions (phenylalanine, 35 carriers; serine, 12 carriers; glycine, 7 carriers; tryptophan, 1 carrier).ResultsArginine substitutions in codon 634 were associated with higher penetrance of medullary thyroid cancer (MTC; 82% vs 62%; P = 0·010), any phaeochromocytoma (44% vs 15%, P < 0·001), bilateral phaeochromocytoma (32% vs 5%; P < 0·001) and primary hyperparathyroidism (18% vs 5%; P = 0·039) relative to the reference standard. The penetrance rates of any phaeochromocytoma (44% vs 26%; P = 0·041) and bilateral phaeochromocytoma (32% vs 14%; P = 0·035) were also higher with arginine than with tyrosine substitutions. Corrected for multiple testing, the associations of arginine with any phaeochromocytoma and bilateral phaeochromocytoma remained statistically significant. Progression of MTC, evidenced by largest primary tumour diameter, nodal status, distant metastasis and biochemical cure, did not differ by amino acid substitution.ConclusionsIn codon 634, arginine substitutions for cysteine may cause slightly higher penetrance rates of MEN 2A which, overall, are too small to treat carriers differently. The mode of action by which arginine exerts these subtle effects warrants further research.
Ibopamine challenge testing becomes negative following successful trabeculectomy surgery
Authors: Landers John , Ullrich Katja , E Craig Jamie 
Published: November 2015

AbstractBackgroundThe ibopamine challenge test correlates well with a patient's peak diurnal intraocular pressure (IOP) measurement. We aimed to investigate the effect that a functioning trabeculectomy has on the ibopamine challenge test.DesignNon‐randomized prospective clinical trial evaluating a diagnostic test.ParticipantsThirteen patients were recruited through glaucoma clinics at the Flinders Medical Centre. Of these, seven required surgical management with trabeculectomy surgery, whilst the remainder were managed medically.MethodsPatients underwent IOP measurement, and then two drops of Ibopamine 2% solution were instilled into the study eye of each patient. After 45 min, IOP was reassesed. A positive challenge test was considered to be a rise in IOP of greater than 3 mmHg. Changes from baseline were determined and compared between groups. Twelve months later, this test was then repeated in all patients.Main Outcome MeasureChange in IOP after ibopamine challenge.ResultsFollowing the ibopamine challenge, IOP increased by 9.2 mmHg (SD 2.8) (100% positive) for medically managed patients and 7.2 mmHg (SD 2.0) (100% positive) for surgically managed patients (P = 0.18). The surgically managed group then underwent trabeculectomy surgery. Twelve months later, the ibopamine challenge was repeated. Following the repeat ibopamine challenge, IOP increased by 7.2 mmHg (SD 2.3) for medically managed patients and 0.3 mmHg (SD 1.3) for surgically managed patients (P < 0.0001). The medically managed group remained 100% positive, whilst the surgically manage group became 0% positive (Fisher Exact P = 0.044).ConclusionsA glaucoma patient with a positive ibopamine challenge will show a negative challenge result when re‐tested following trabeculectomy surgery.
Accrual Index: A Real‐Time Measure of the Timeliness of Clinical Study Enrollment
Authors: Corregano Lauren , Bastert Katelyn , Correa da Rosa Joel , Kost Rhonda G. 
Published: November 2015

AbstractBackgroundAchieving timely accrual into clinical research studies remains a challenge for clinical translational research. We developed an evaluation measure, the Accrual Index (AI), normalized for sample size and study duration, using data from the protocol and study management databases. We applied the AI retrospectively and prospectively to assess its utility.MethodsAccrual Target, Projected Time to Accrual Completion (PTAC), Evaluable Subjects, Dates of Recruitment Initiation, Analysis, and Completion were defined. AI is (% Accrual Target accrued/% PTAC elapsed). Changes to recruitment practices were described, and data extracted from study management databases.ResultsDecember 2014 (or final) AI was analyzed for 101 studies initiating recruitment from 2007 to 2014. Median AI was ≥1 for protocols initiating recruitment in 2011, 2013, and 2014. The AI varied widely for studies pre‐2013. Studies with AI > 4 utilized convenience samples for recruitment. Data‐justified PTAC was refined in 2013–2014 after which the AI range narrowed. Protocol characteristics were not associated with study AI.ConclusionProtocol AI reflects the relative agreement between accrual feasibility assessment (PTAC), and accrual performance, and is affected by recruitment practices. The AI may be useful in managing accountability, modeling accrual, allocating recruitment resources, and testing innovations in recruitment practices.
Beyond naïve cue combination: salience and social cues in early word learning
Authors: Yurovsky Daniel , Frank Michael C. 
Published: November 2015

AbstractChildren learn their earliest words through social interaction, but it is unknown how much they rely on social information. Some theories argue that word learning is fundamentally social from its outset, with even the youngest infants understanding intentions and using them to infer a social partner's target of reference. In contrast, other theories argue that early word learning is largely a perceptual process in which young children map words onto salient objects. One way of unifying these accounts is to model word learning as weighted cue combination, in which children attend to many potential cues to reference, but only gradually learn the correct weight to assign each cue. We tested four predictions of this kind of naïve cue combination account, using an eye‐tracking paradigm that combines social word teaching and two‐alternative forced‐choice testing. None of the predictions were supported. We thus propose an alternative unifying account: children are sensitive to social information early, but their ability to gather and deploy this information is constrained by domain‐general cognitive processes. Developmental changes in children's use of social cues emerge not from learning the predictive power of social cues, but from the gradual development of attention, memory, and speed of information processing.
Role of neutrophils in atherogenesis: an update
Authors: Pende Aldo , Artom Nathan , Bertolotto Maria , Montecucco Fabrizio , Dallegri Franco 
Published: November 2015

AbstractBackgroundThe role of neutrophils in the beginning and the progression of the atherosclerotic process did not receive much attention until the last years. On the contrary, recent data, in both the experimental animals and humans, suggest important effects of these cells with possible clinical consequences.Materials and methodsThis narrative review was based on the papers found on PubMed and MEDLINE up to July 2015. The search terms used were ‘neutrophil, atherosclerosis’ in combination with ‘recruitment, chemokine, plaque destabilization and pathophysiology’.ResultsDifferent models demonstrate the presence and the actions of neutrophils in the early steps of the atherogenesis confirming the fundamental role of these cells in the response of the innate immune system to different pathogens (in this context the modified lipoproteins). However, also the late phases of the atherosclerotic process, in particular the destabilization of a mature plaque, seem to be modulated by the neutrophils, possibly through the interaction with recently discovered biological systems such as the endocannabinoids.ConclusionsThe understanding of the mechanisms involved in the modulation exerted by neutrophils in atherosclerosis is pivotal in terms of the complete definition of the overall picture. This approach will certainly give us new targets and new pharmacological opportunities for the anti‐inflammatory strategy of the cardiovascular prevention.
Restructuring China's research institutes
Authors: Jiang Renai , Tortorice Daniel L. , Jefferson Gary H. 
Published: November 2015

AbstractOver the past two decades, China's R&D intensity has surged. The institutional arrangements underlying this surge remain unclear. We study the notable restructuring of the country's 5,000 research institutes, begun in 1999. This study first reviews the evolution of China's research institute sector over the period 1995–2010. Then applying OLS, fixed effects, event study and propensity score analysis to institute level data, we find the restructuring programme has accomplished some of its goals. The converted Science and Technology enterprises shifted towards a more commercial mission, the institutes converted to non‐profit research institutes have focused on a more research‐oriented mission.
MALT1 cleaves the E3 ubiquitin ligase HOIL‐1 in activated T cells, generating a dominant negative inhibitor of LUBAC‐induced NF‐κB signaling
Authors: Elton Lynn , Carpentier Isabelle , Staal Jens , Driege Yasmine , Haegman Mira , Beyaert Rudi 
Published: November 2015

Human paracaspase 1 (PCASP1), better known as mucosa associated lymphoid tissue lymphoma translocation 1 (MALT1), plays a key role in immunity and inflammation by regulating gene expression in lymphocytes and other immune cell types. Deregulated MALT1 activity has been implicated in autoimmunity, immunodeficiency and certain types of lymphoma. As a scaffold MALT1 assembles downstream signaling proteins for nuclear factor‐κB (NF‐κB) activation, while its proteolytic activity further enhances NF‐κB activation by cleaving NF‐κB inhibitory proteins. MALT1 also processes and inactivates a number of mRNA destabilizing proteins, which further fine‐tunes gene expression. MALT1 protease inhibitors are currently developed for therapeutic targeting. Here we show that T cell activation, as well as overexpression of the oncogenic fusion protein API2–MALT1, induces the MALT1‐mediated cleavage of haem‐oxidized IRP2 ubiquitin ligase 1 (HOIL‐1). In addition, to acting as a K48‐polyubiquitin specific E3 ubiquitin ligase for different substrates, HOIL‐1 co‐operates in a catalytic‐independent manner with the E3 ubiquitin ligase HOIL‐1L interacting protein (HOIP) as part of the linear ubiquitin chain assembly complex (LUBAC). Intriguingly, cleavage of HOIL‐1 does not directly abolish its ability to support HOIP‐induced NF‐κB signaling, which is still mediated by the N‐terminal cleavage fragment, but generates a C‐terminal fragment with LUBAC inhibitory properties. We propose that MALT1‐mediated HOIL‐1 cleavage provides a gain‐of‐function mechanism that is involved in the negative feedback regulation of NF‐κB signaling.
Knowledge, attitudes and beliefs regarding colorectal cancer screening among ethnic minority groups in the Netherlands – a qualitative study
Authors: Woudstra Anke J. , Dekker Evelien , Essink‐Bot Marie‐Louise , Suurmond Jeanine 
Published: November 2015

AbstractBackgroundResearch has shown that ethnic minority groups are less likely to participate in colorectal cancer (CRC) screening than the majority population and hence less likely to be diagnosed at an early stage when treatment is potentially more successful.ObjectiveTo explore knowledge, attitudes and beliefs regarding CRC and CRC screening among ethnic minority groups in the Netherlands.DesignWe conducted qualitative interviews with 30 first‐generation immigrants born in Turkey, Morocco and Surinam. We based the topic guide on the health belief model. Framework analysis was used to analyse our data.ResultsAlthough knowledge of CRC and CRC screening was limited, all respondents felt susceptible to CRC. CRC screening was perceived to mainly benefit those individuals with poor health and symptoms. Although most respondents had a positive attitude towards CRC screening, knowledge about its potential harms was limited and self‐efficacy to participate was low. Adult children acted as important mediators in providing access to information. The language barrier and low literacy formed serious barriers to informed participation in CRC screening.ConclusionTo ensure that all eligible individuals, including ethnic minority groups, have equal opportunities to informed participation in screening, targeted communication strategies should be developed, such as oral and visual channels, and face‐to‐face communication in the mother tongue. This will help ethnic minority groups to make an informed decision about participation in CRC screening.
Preserving fibre health: reducing oxidative stress throughout the life of the hair fibre
Authors: Marsh J. M. , Davis M. G. , Lucas R. L. , Reilman R. , Styczynski P. B. , Li C. , Mamak M. , McComb D. W. , Williams R. E. A. , Godfrey S. , Navqi K. R. , Chechik V. 
Published: November 2015

AbstractHair health is an important attribute to women globally – specifically attributes such as shine, healthy tips, frizz‐free and strength. However, many women will claim to have at least moderate hair damage caused by habits and practices such as washing, combing and brushing, use of heated implements and regular use of chemical treatments. The objective of this work was to investigate two mechanisms of damage – hair colouring and UV exposure – where oxidative processes are involved. The role of copper in these oxidative processes was then investigated: its presence in hair and its consequent impact on hair damage via free radical formation. Finally, the role of chelants N,N’‐ethylene diamine disuccinic acid (EDDS) and histidine in preventing free radical formation was investigated and shown to improve hair health.