bluuebunny/crossref_metadata_2025 huggingface dataset:
Closed Primaries and Party Support in Congress
Authors: Haeberle Steven H.
Published: January 2016

Nominating procedures in the American states rely on three types of primary elections: closed, open, and blanket. These systems vary with regard to the extent partisanship is injected into the process. The data show that members of Congress with the highest levels of party support in the House of Representatives are elected in states using closed primaries. However, this relationship between partisanship in office and use of the closed primary appears to result from the common determination of these two variables by regional differences and traditional patterns of interparty competition at the state level. In other words, the state systems that value partisanship the most will likely have closed primaries and elect representatives more likely to support their party.
The Wisconsin Open Primary 1968 to 1984
Authors: Hedlund Ronald D. , Watts Meredith W.
Published: January 2016

Statewide surveys from the five most recent presidential primaries in Wisconsin are used to examine voting trends of independents and party identifiers in Wisconsin presidential primaries. The primary concerns are (1) the extent and direction of crossover voting, (2) election-specific factors that effect crossover voting, and (3) possible inconsistency between crossover voting and future vote choices.
Electoral Competition, 1958-1984: Impact on State Legislative Turnover in the Indiana House
Authors: Crawley Gary L.
Published: January 2016

This article addresses the widespread notion that the decline in membership turnover in American state legislatures during the last two decades was primarily due to a decline in voluntary withdrawals from office and was unrelated to electoral competition. A theory of membership turnover is presented that incorporates electoral competition as a factor in an incumbent's decision to seek reelection and his/her ability to win. Several hypotheses are tested with data on turnover in the Indiana House of Representatives. This article departs from previous efforts in that electoral competition is measured at the district level and incumbents' decisions to run for higher office are distinguished from other forms of voluntary withdrawal.
Norcantharidin Inhibits SK-N-SH Neuroblastoma Cell Growth by Induction of Autophagy and Apoptosis
Authors: Han Zeping , Li Baoxia , Wang Juanjuan , Zhang Xiangqiang , Li Zhenhua , Dai Liting , Cao Mingrong , Jiang Jianwei
Published: January 2016

Norcantharidin, a low-toxic analog of the active anticancer compound cantharidin in Mylabris, can inhibit proliferation and induce apoptosis of multiple types of cancer cells. However, the anticancer activities of norcantharidin with respect to neuroblastoma, and its underlying mechanisms, have not been investigated. Therefore, our study was designed to determine the efficacy of norcantharidin on SK-N-SH neuroblastoma cell death and to elucidate detailed mechanisms of activity. In the present study, norcantharidin suppressed the proliferation and cloning ability of SK-N-SH cells in a dose-dependent manner, apparently by reducing the mitochondrial membrane potential and arresting SK-N-SH cells at the G2/M stage, accompanied by elevated expressions of p21 and decreased expressions of cyclin B1 and cell division control 2. Treatment by norcantharidin induced significant mitophagy and autophagy, as demonstrated by a decrease in Translocase Of Outer Mitochondrial Membrane 20 (TOM20), increased beclin1 and LC3-II protein expression, reduced protein SQSTM1/p62 expression, and accumulation of punctate LC3 in the cytoplasm of SK-N-SH cells. In addition, norcantharidin induced apoptosis through regulating the expression of B-cell lymphoma 2–associated X protein/B-cell lymphoma 2 and B-cell lymphoma 2–associated X protein/myeloid cell leukemia 1 and activating caspase-3 and caspase-9–dependent endogenous mitochondrial pathways. We also observed an increase in phosphor–AMP-activated protein kinase accompanied with a decrease in phosphor-protein kinase B and mammalian target of rapamycin expression after treatment with norcantharidin. Subsequent studies indicated that norcantharidin participates in cellular autophagy and apoptosis via activation of the c-Jun NH2-terminal kinases/c-Jun pathway. In conclusion, our results demonstrate that norcantharidin can reduce the mitochondrial membrane potential, induce mitophagy, and subsequently arouse cellular autophagy and apoptosis; the AMP-activated protein kinase, protein kinase B/mammalian target of rapamycin, and c-Jun NH2-terminal kinases/c-Jun signaling pathways are widely involved in these processes. Thus, the traditional Chinese medicine norcantharidin could be a novel therapeutic strategy for treating neuroblastoma.
Development of the UK Vessel Health and Preservation (VHP) framework: a multi-organisational collaborative
Authors: Hallam Carole , Weston Valya , Denton Andrea , Hill Steve , Bodenham Andrew , Dunn Helen , Jackson Tim
Published: January 2016

Vascular access is an important part of many patient care management plans but has some unwanted risks. Previous work published by Moureau et al. (2012) inspired a working group led by the UK Infection Prevention Society (IPS) to produce a vessel health and preservation (VHP) framework. This was with the intention of producing a resource for frontline staff to be able to assess and select the best vascular access device to meet the individual patient’s needs and to preserve veins for future use.

The working group produced a framework that used available evidence, expert opinion and some small scale testing of the components of the framework. The work so far has received positive feedback but further work is required to formally evaluate the VHP framework in clinical practice to measure both staff knowledge and patient outcomes.
Anti-Inflammatory Polymeric Coatings for Implantable Biomaterials and Devices
Authors: Bridges Amanda W. , García Andrés J.
Published: January 2016

Synthetic polymer coatings are used extensively in modern medical devices and implants because of their material versatility and processability. These coatings are designed for specific applications by controlling composition and physical and chemical properties, and they can be formed into a variety of complex structures and shapes. However, implantation of these materials into the body elicits a strong inflammatory host response that significantly limits the integration and biological performance of devices. Biomaterial-mediated inflammation is a complex reaction involving protein adsorption, leukocyte recruitment and activation, secretion of inflammatory mediators, and fibrous encapsulation of the implant. Significant research efforts have focused on modifying material properties using various anti-inflammatory polymeric surface coatings to generate more biocompatible implants. This minireview provides a brief background on the events of biomaterial-mediated inflammation and highlights various approaches used for modifying material surfaces to modulate inflammatory responses. These include both passive and active strategies, such as nonfouling surface treatments and delivery of anti-inflammatory agents, respectively. Novel approaches will be needed to extend the in vivo lifetime and performance of devices and reduce the need for multiple implantation surgeries.
Full-Contact Practice and Injuries in College Football
Authors: Steiner Mark E. , Berkstresser Brant D. , Richardson Lars , Elia Greg , Wang Frank
Published: January 2016

Background:

Despite recent restrictions being placed on practice in college football, there are little data to correlate such changes with injuries.

Hypothesis:

Football injuries will correlate with a team’s exposure to full-contact practice, total practice, and total games.

Study Design:

Descriptive epidemiological study.

Methods:

All injuries and athlete injury exposures (AE × Min = athletes exposed × activity duration in minutes) were recorded for an intercollegiate football team over 4 consecutive fall seasons. Weekly injuries and injury rates (injuries per athletic injury exposure) were correlated with the weekly exposures to full-contact practices, total practices, formal scrimmages, and games.

Results:

The preseason practice injury rate was over twice the in-season practice injury rate ( P < 0.001). For preseason, injury exposures were higher for full-contact practice ( P = 0.0166), total practices ( P = 0.015), and scrimmages/games ( P = 0.034) compared with in-season. Preseason and in-season practice injuries correlated with exposure to full-contact practice combined with scrimmages for preseason ( P < 0.008) and full-contact practice combined with games for in-season ( P = 0.0325). The game injury rate was over 6 times greater than the practice injury rate ( P < 0.0001). Concussions constituted 14.5% of all injuries, and the incidence of concussions correlated with the incidence of all injuries ( P = 0.0001). Strength training did not correlate with injuries.

Conclusion:

Decreased exposure to full-contact practice may decrease the incidence of practice injuries and practice concussions. However, the game injury rate was over 6 times greater than the practice injury rate and had an inverse correlation with full-contact practice.
Hypothetical Sentencing Decisions Are Associated With Actual Capital Punishment Outcomes
Authors: Wilson John Paul , Rule Nicholas O.
Published: January 2016

Recent research has highlighted a relationship between perceptions of trustworthiness from faces and capital sentencing outcomes. Here, we extended those findings by replicating the relationship between trustworthiness and the death penalty among a new sample of targets convicted of capital murder in Arkansas and by demonstrating that facial trustworthiness guides naive sentencing decisions. First, trustworthiness differentiated convicted murderers sentenced to life from those sentenced to death using a novel stimulus population. Next, we found experimental evidence that people used inferences of trustworthiness from faces when making hypothetical capital sentencing judgments for noncriminal targets presented as murderers. Finally, naive participants viewing photographs of actual convicted criminals without any additional information allocated hypothetical sentences that matched those that were actually received in court. Facial trustworthiness, but not other inferences (i.e., Afrocentricity, attractiveness, and maturity), accounted for this relationship. These data therefore suggest that perceptions of trustworthiness guide individuals’ decisions about legal punishment.
Social Working Memory Training Improves Perspective-Taking Accuracy
Authors: Meyer Meghan L. , Lieberman Matthew D.
Published: January 2016

Despite the importance of perspective taking for navigating the social world, even healthy adults frequently misinterpret what other people think and feel. Yet, to date, no research examines whether perspective-taking accuracy can be improved among healthy adult samples. Building off of work suggesting that social working memory (SWM) capacity (i.e., the ability to maintain and manipulate social cognitive information in mind) predicts perspective-taking skills, we developed a novel SWM training intervention to test the hypothesis that SWM training improves perspective-taking accuracy. Participants were randomly assigned to complete 12 days of either SWM training or nonsocial, “cognitive working memory” (CWM) training (active control condition). Perspective-taking accuracy was assessed pre- and posttraining. SWM training significantly increased perspective-taking accuracy and these improvements significantly surpassed improvements made by participants who underwent CWM training. SWM training therefore may be an efficient route toward improved perspective-taking accuracy.
Imaging features of spinal tanycytic ependymoma
Authors: Tomek Michal , Jayajothi Anandapadmanabhan , Brandner Sebastian , Jaunmuktane Zane , Lee Cheong Hung , Davagnanam Indran
Published: January 2016

Tanycytic ependymoma is an unusual morphological variant of WHO grade II ependymoma, typically arising from the cervical or thoracic spinal cord. Although the literature deals extensively with pathological features of this tumour entity, imaging features have not been well characterised. The purpose of this study was to review magnetic resonance imaging (MRI) features of spinal tanycytic ependymomas reported in the literature to date, exemplified by a case of a patient with tanycytic ependymoma of the conus medullaris presenting to our hospital.

A Medline search of the English literature for all previously published cases of spinal tanycytic ependymoma was carried out and the reported MRI features reviewed. The tumours were found to be typically well-demarcated masses, predominantly showing isointensity on T1-weighted signal, and T2-weighted hyperintensity, with variable patterns of contrast enhancement. A cystic component was seen in half of the cases, and in a minority a mural nodule was present within the cyst wall. Associated syrinx formation was observed in one-third of the cases and haemorrhage was rare, which may be helpful pointers in differentiating the lesion from other ependymoma subtypes.

In conclusion, MRI characteristics of spinal tanycytic ependymoma are variable and non-specific, and radiological diagnosis thus remains challenging, although certain predominant features are identified in this report. Knowledge of these is important in the diagnostic differentiation from other intramedullary and extramedullary spinal tumours in order to guide appropriate surgical management.
Click here to consent forever: Expiry dates for informed consent
Authors: Custers Bart
Published: January 2016

The legal basis for processing personal data and some other types of Big Data is often the informed consent of the data subject involved. Many data controllers, such as social network sites, offer terms and conditions, privacy policies or similar documents to which a user can consent when registering as a user. There are many issues with such informed consent: people get too many consent requests to read everything, policy documents are often very long and difficult to understand and users feel they do not have a real choice anyway. Furthermore, in the context of Big Data refusing consent may not prevent predicting missing data. Finally, consent is usually asked for when registering, but rarely is consent renewed. As a result, consenting once often implies consent forever. At the same time, given the rapid changes in Big Data and data analysis, consent may easily get outdated (when earlier consent no longer reflects a user’s preferences). This paper suggests expiry dates for consent, not to settle questions, but to put them on the table as a start for further discussion on this topic. Although such expiry dates may not solve all the issues of informed consent, they may be a useful tool in some situations.
Identities in Conflict
Authors: Ahuja Kanika , Dhillon Megha Dev , Akalamkam Kalyani , Papneja Deepika
Published: January 2016

Kashmir has witnessed violent conflict for many years, and India has been one of the main players in this conflict. This study used the method of drawings to assess how this ongoing conflict has shaped the identities of young Muslims in Kashmir. The identities they expressed were compared with those expressed by young Muslims in Delhi. At each location, one group of participants was asked to draw on the theme “Me and my country” while the other group was asked to draw whatever they desired. When allowed to draw what they wished, adolescents in Kashmir drew symbols of regional identity more often and symbols of India less often than adolescents in Delhi. “I dominant” identities were depicted only by the Delhi-based sample. Drawings from Kashmir did not represent high levels of violence or a fractured relationship with the Indian state. Possible reasons have been discussed.
Factors Significant to Thermal Comfort Within Residential Neighborhoods of Ibadan Metropolis and Preferences in Adult Residents’ Use of Spaces
Authors: Adunola Adewale Oluseyi , Ajibola Kolawole
Published: January 2016

The study examined the significance of five sets of variables classified under personal characteristics, adaptive actions, climatic factors, building spatial characteristics, and neighborhood location characteristics in the determination of indoor thermal comfort and the impact of spatial comfort on residents’ preferences in space use. A thermal comfort survey was conducted among residents of 528 buildings in 12 selected residential neighborhoods of Ibadan metropolis in Nigeria. The impact of the urban microclimate on the building spaces was found significant. Indoor comfort assessment varied according to the different building design typology. The location and building characteristics were found to influence the indoor comfort of respondents. It was found that there were differences in air temperature measured within the spaces in the buildings. The thermal assessment of respondents for different spaces in their respective buildings also varied. There was very strong correlation between the most comfortable spaces, the most used spaces, and the first choice spaces voted by respondents at different periods of the day. Residents utilized adaptive actions and exhibited thermal consideration in the use of spaces. Adaptive movement from space to space due to variation in spatial comfort was confirmed in the study.
Engaging the Student Role
Authors: McLuhan Arthur
Published: January 2016

Working within the symbolic interactionist tradition, this article presents an ethnographic research agenda for studying the ways that “people engage roles as students.” Using an ethnographic study of two Protestant Christian seminaries as an illustrative case, I consider the ways the student role may be conceptualized and studied as ethnographic instances of “education in the making.” This includes the matters of people (a) entering into the student role, (b) attending to instruction, (c) being assessed, (d) sustaining efforts, (e) attending to one’s peers, (f) encountering difficulties, (g) experiencing failure and termination, and (h) pursuing subsequent studies. I concentrate on establishing the fundamental elements of theory and methods that can focus research and comparative analyses on the activities that constitute the student role.
Probing the Unique Contributions of Self-Concept, Task Values, and Their Interactions Using Multiple Value Facets and Multiple Academic Outcomes
Authors: Guo Jiesi , Nagengast Benjamin , Marsh Herbert W. , Kelava Augustin , Gaspard Hanna , Brandt Holger , Cambria Jenna , Flunger Barbara , Dicke Anna-Lena , Häfner Isabelle , Brisson Brigitte , Trautwein Ulrich
Published: January 2016

Drawing on expectancy-value theory, the present study examined the unique contributions of the four major value beliefs and self-concept on achievement, self-reported effort, and teacher-rated behavioral engagement in mathematics. In particular, we examined the multiplicative effects of self-concept and task values on educational outcomes using the latent moderated structural equation approach. Participants were 1,868 German ninth-grade students. The data analyses relied on a higher-order structure of value beliefs, which is suited to parsing the differential patterns of predictive relations for different value beliefs. The findings revealed that (a) self-concept was more predictive of achievement, whereas value beliefs were more predictive of self-rated effort; (b) self-concept and value beliefs emerged as equally important predictors of teacher-reported engagement; (c) among the four value beliefs, achievement was more associated with low cost, whereas effort was more associated with attainment value; and (d) latent interactions between self-concept and value beliefs predicted the three outcomes synergistically.
Research and Policy Considerations for English Learner Equity
Authors: Robinson-Cimpian Joseph P. , Thompson Karen D. , Umansky Ilana M.
Published: January 2016

English learners (ELs), students from a home where a language other than English is spoken and who are in the process of developing English proficiency themselves, represent more than 10% of the U.S. student population. Oftentimes, education policies and practices create barriers for ELs to achieve access and outcomes that are equitable to those of their non-EL peers. Recent education research—often using experimental and quasi-experimental designs—provides new insights on how to evaluate EL policies, as well as how best to alter current policies to yield more equitable outcomes for ELs. Topics discussed include (a) EL classification and services, (b) language of instruction, (c) access to core content, and (d) assessments.
Self-Regulated Strategy Development in Writing
Authors: Harris Karen R. , Graham Steve
Published: January 2016

U.S. students are not performing well in writing, both typically achieving students and students with learning disabilities (LD). Factors that impact learning to write include the complexity of writing and learning to write, challenges in developing effective writing instruction, teacher preparation for teaching writing, and instructional models in use in today’s schools. These factors have influenced the development of Self-Regulated Strategy Development (SRSD) for writing, and its scientific evidence base. Potential policy implications follow from SRSD research in the areas of evidence-based practices, teacher development, curriculum development and reform, and research. For evidence-based practices such as SRSD to transform education, as they have medicine, effective partnerships between policymakers and education stakeholders, our students, and our schools are critical.
Research and Policy on Disability
Authors: Farmer Thomas W. , Gatzke-Kopp Lisa M. , Lee David L. , Dawes Molly , Talbott Elizabeth
Published: January 2016

Bridging special education (SE) and developmental science recognizes their shared focus on individual adaptation, growth, and outcomes. Adaptation continuously aligns the proclivities of students and the opportunities of their contexts. Considerations for the adaptation of students with disabilities include developmental malleability, problem behavior, intervention supports, and SE services. Policy implications center on the need to focus on the individual in context in both research and intervention, merge data from the implementation of intensive interventions and person-oriented analysis to establish comprehensive frameworks that include a focus on neurophysiological processes, and train the next generation of SE leaders in intensive interventions and applied developmental science.
Effect of a Clinical Pharmacist–Managed Service on Blood Pressure in an Underserved Population With Resistant Hypertension
Authors: Wooley Andrea C. , Brooks Amie D. , Stacy Zachary A.
Published: January 2016

Background. Evidence indicates pharmacist-managed hypertension clinics are beneficial in reducing blood pressure (BP). There is currently no evidence evaluating the effect of pharmacist-managed resistant hypertension clinics in a medically underserved patient population. Objective. To determine the impact of a pharmacist-managed resistant hypertension service on BP in a medically underserved population. Methods. This was a prospective cohort study evaluating 12 medically underserved patients enrolled in a pharmacist-managed resistant hypertension service at the St Louis County Department of Health. BP was measured in clinic and at home. Follow-up occurred biweekly by phone and in clinic at least monthly while uncontrolled. This study was approved by the St Louis College of Pharmacy Institutional Review Board and St Louis County Department of Health director for clinical and research services. Primary outcome of change in home systolic BP and secondary outcomes of change in home diastolic BP and clinic systolic and diastolic BP were evaluated. Results. Twelve patients were included in the analysis (2 patients did not receive home BP monitors). Home systolic BP was reduced from the first encounter, 140 (12) mm Hg, to last contact, 130 (15) mm Hg ( P = .01). Clinic systolic BP also decreased significantly from the first encounter, 152 (10) mm Hg, to last contact, 136 (17) mm Hg ( P = .004). Clinic BP goal and home BP goal was attained by 30% and 40% of participants, respectively. Conclusions. A pharmacist-managed resistant hypertension service is effective in significantly reducing BP in medically underserved patients.
MS3ALIGN: an efficient molecular surface aligner using the topology of surface curvature
Authors: Shivashankar Nithin , Patil Sonali , Bhosle Amrisha , Chandra Nagasuma , Natarajan Vijay
Published: January 2016

Background

Aligning similar molecular structures is an important step in the process of bio-molecular structure and function analysis. Molecular surfaces are simple representations of molecular structure that are easily constructed from various forms of molecular data such as 3D atomic coordinates (PDB) and Electron Microscopy (EM) data.

Methods

We present a Multi-Scale Morse-Smale Molecular-Surface Alignment tool, MS3ALIGN, which aligns molecular surfaces based on significant protrusions on the molecular surface. The input is a pair of molecular surfaces represented as triangle meshes. A key advantage of MS3ALIGN is computational efficiency that is achieved because it processes only a few carefully chosen protrusions on the molecular surface. Furthermore, the alignments are partial in nature and therefore allows for inexact surfaces to be aligned.

Results

The method is evaluated in four settings. First, we establish performance using known alignments with varying overlap and noise values. Second, we compare the method with SurfComp, an existing surface alignment method. We show that we are able to determine alignments reported by SurfComp, as well as report relevant alignments not found by SurfComp. Third, we validate the ability of MS3ALIGN to determine alignments in the case of structurally dissimilar binding sites. Fourth, we demonstrate the ability of MS3ALIGN to align iso-surfaces derived from cryo-electron microscopy scans.

Conclusions

We have presented an algorithm that aligns Molecular Surfaces based on the topology of surface curvature. A webserver and standalone software implementation of the algorithm available at http://vgl.serc.iisc.ernet.in/ms3align.
Molecular dynamics simulation and bioinformatics study on chloroplast stromal ridge complex from rice (Oryza sativa L.)
Authors: Zhang Yubo , Ding Yi
Published: January 2016

Background

Rice (Oryza sativa L.) is one of the most important cereal crops in the world and its yield is closely related to the photosynthesis efficiency. The chloroplast stromal ridge complex consisting of PsaC-PsaD-PsaE plays an important role in plant photosynthesis, which has been a subject of many studies. Till now, the recognition mechanism between PsaC and PsaD in rice is still not fully understood.

Results

Here, we present the interaction features of OsPsaC and OsPsaD by molecular dynamics simulations and bioinformatics. Firstly, we identified interacting residues in the OsPsaC-OsPsaD complex during simulations. Significantly, important hydrogen bonds were observed in residue pairs R19-E103, D47-K62, R53-E63, Y81-R20, Y81-R61 and L26-V105. Free energy calculations suggested two salt bridges R19-E103 and D47-K62 were essential to maintain the OsPsaC-OsPsaD interaction. Supportively, electrostatic potentials surfaces of OsPsaD exhibited electrostatic attraction helped to stabilize the residue pairs R19-E103 and D47-K62. In particular, the importance of R19 was further verified by two 500 ns CG-MD simulations. Secondly, this study compared the stromal ridge complex in rice with that in other organisms. Notably, alignments of amino acids showed these two salt bridges R19-E103 and D47-K62 also existed in other organisms. Electrostatic potentials surfaces and X-ray structural analysis strongly suggested the stromal ridge complex in other organisms adopted a similar and general recognition mechanism.

Conclusions

These results together provided structure basis and dynamics behavior to understand recognition and assembly of the stromal ridge complex in rice.
GBS-SNP-CROP: a reference-optional pipeline for SNP discovery and plant germplasm characterization using variable length, paired-end genotyping-by-sequencing data
Authors: Melo Arthur T. O. , Bartaula Radhika , Hale Iago
Published: January 2016

Background

With its simple library preparation and robust approach to genome reduction, genotyping-by-sequencing (GBS) is a flexible and cost-effective strategy for SNP discovery and genotyping, provided an appropriate reference genome is available. For resource-limited curation, research, and breeding programs of underutilized plant genetic resources, however, even low-depth references may not be within reach, despite declining sequencing costs. Such programs would find value in an open-source bioinformatics pipeline that can maximize GBS data usage and perform high-density SNP genotyping in the absence of a reference.

Results

The GBS SNP-Calling Reference Optional Pipeline (GBS-SNP-CROP) developed and presented here adopts a clustering strategy to build a population-tailored “Mock Reference” from the same GBS data used for downstream SNP calling and genotyping. Designed for libraries of paired-end (PE) reads, GBS-SNP-CROP maximizes data usage by eliminating unnecessary data culling due to imposed read-length uniformity requirements. Using 150 bp PE reads from a GBS library of 48 accessions of tetraploid kiwiberry (Actinidia arguta), GBS-SNP-CROP yielded on average three times as many SNPs as TASSEL-GBS analyses (32 and 64 bp tag lengths) and over 18 times as many as TASSEL-UNEAK, with fewer genotyping errors in all cases, as evidenced by comparing the genotypic characterizations of biological replicates. Using the published reference genome of a related diploid species (A. chinensis), the reference-based version of GBS-SNP-CROP behaved similarly to TASSEL-GBS in terms of the number of SNPs called but had an improved read depth distribution and fewer genotyping errors. Our results also indicate that the sets of SNPs detected by the different pipelines above are largely orthogonal to one another; thus GBS-SNP-CROP may be used to augment the results of alternative analyses, whether or not a reference is available.

Conclusions

By achieving high-density SNP genotyping in populations for which no reference genome is available, GBS-SNP-CROP is worth consideration by curators, researchers, and breeders of under-researched plant genetic resources. In cases where a reference is available, especially if from a related species or when the target population is particularly diverse, GBS-SNP-CROP may complement other reference-based pipelines by extracting more information per sequencing dollar spent. The current version of GBS-SNP-CROP is available at https://github.com/halelab/GBS-SNP-CROP.git
Long-term recovery from acute cold shock in Caenorhabditis elegans
Authors: Robinson Joseph D. , Powell Jennifer R.
Published: January 2016

Background

Animals are exposed to a wide range of environmental stresses that can cause potentially fatal cellular damage. The ability to survive the period of stress as well as to repair any damage incurred is essential for fitness. Exposure to 2 °C for 24 h or longer is rapidly fatal to the nematode Caenorhabditis elegans, but the process of recovery from a shorter, initially non-lethal, cold shock is poorly understood.

Results

We report that cold shock of less than 12-hour duration does not initially kill C. elegans, but these worms experience a progression of devastating phenotypes over the next 96 h that correlate with their eventual fate: successful recovery from the cold shock and survival, or failure to recover and death. Cold-shocked worms experience a marked loss of pigmentation, decrease in the size of their intestine and gonads, and disruption to the vulva. Those worms who will successfully recover from the cold shock regain their pigmentation and much of the integrity of their intestine and gonads. Those who will die do so with a distinct phenotype from worms dying during or immediately following cold shock, suggesting independent mechanisms. Worms lacking the G-protein coupled receptor FSHR-1 are resistant to acute death from longer cold shocks, and are more successful in their recovery from shorter sub-lethal cold shocks.

Conclusions

We have defined two distinct phases of death associated with cold shock and described a progression of phenotypes that accompanies the course of recovery from that cold shock. The G-protein coupled receptor FSHR-1 antagonizes these novel processes of damage and recovery.
TREM-like transcript 2 is stored in human neutrophil primary granules and is up-regulated in response to inflammatory mediators
Authors: Thomas Kimberly A , King R Glenn , Sestero Christine M , Justement Louis B
Published: January 2016

The triggering receptor expressed on myeloid cell locus encodes a family of receptors that is emerging as an important class of molecules involved in modulating the innate immune response and inflammation. Of the 4 conserved members, including triggering receptor expressed on myeloid cells 1 and 2 and triggering receptor expressed on myeloid cell-like transcripts 1 and 2, relatively little is known about triggering receptor expressed on myeloid cell-like transcript 2 expression and function, particularly in humans. In this study, experiments were performed to determine if triggering receptor expressed on myeloid cell-like transcript 2 expression is conserved between mouse and human, demonstrating that human triggering receptor expressed on myeloid cell-like transcript 2 is expressed on cells of the lymphoid, as well as myeloid/granuloid lineages, similar to murine triggering receptor expressed on myeloid cell-like transcript 2. Consistent with studies in the mouse, triggering receptor expressed on myeloid cell-like transcript 2 expression is up-regulated in response to inflammatory mediators on human neutrophils. Importantly, it was shown that triggering receptor expressed on myeloid cell-like transcript 2, in resting human neutrophils, is predominantly localized to intracellular vesicles, including secretory vesicles and primary granules; with the majority of triggering receptor expressed on myeloid cell-like transcript 2 stored in primary granules. In contrast to other primary granule proteins, triggering receptor expressed on myeloid cell-like transcript 2 is not expelled on neutrophil extracellular traps but is retained in the plasma membrane following primary granule exocytosis. In summary, these findings establish that triggering receptor expressed on myeloid cell-like transcript 2 expression is conserved between species and is likely to be important in regulating neutrophil antimicrobial function following primary granule exocytosis.
Volasertib Versus Chemotherapy in Platinum-Resistant or -Refractory Ovarian Cancer: A Randomized Phase II Groupe des Investigateurs Nationaux pour l'Etude des Cancers de l'Ovaire Study
Authors: Pujade-Lauraine Eric , Selle Frédéric , Weber Béatrice , Ray-Coquard Isabelle-Laure , Vergote Ignace , Sufliarsky Jozef , Del Campo Josep Maria , Lortholary Alain , Lesoin Anne , Follana Philippe , Freyer Gilles , Pardo Beatriz , Vidal Laura , Tholander Bengt , Gladieff Laurence , Sassi Mouna , Garin-Chesa Pilar , Nazabadioko Serge , Marzin Kristell , Pilz Korinna , Joly Florence
Published: January 2016

Purpose

Volasertib is a potent and selective cell-cycle kinase inhibitor that induces mitotic arrest and apoptosis by targeting Polo-like kinase. This phase II trial evaluated volasertib or single-agent chemotherapy in patients with platinum-resistant or -refractory ovarian cancer who experienced failure after treatment with two or three therapy lines.

Patients and Methods

Patients were randomly assigned to receive either volasertib 300 mg by intravenous infusion every 3 weeks or an investigator’s choice of single-agent, nonplatinum, cytotoxic chemotherapy. The primary end point was 24-week disease control rate. Secondary end points included best overall response, progression-free survival (PFS), safety, quality of life, and exploratory biomarker analyses.

Results

Of the 109 patients receiving treatment, 54 received volasertib and 55 received chemotherapy; demographics were well balanced. The 24-week disease control rates for volasertib and chemotherapy were 30.6% (95% CI, 18.0% to 43.2%) and 43.1% (95% CI, 29.6% to 56.7%), respectively, with partial responses in seven (13.0%) and eight (14.5%) patients, respectively. Median PFS was 13.1 weeks and 20.6 weeks for volasertib and chemotherapy (hazard ratio, 1.01; 95% CI, 0.66 to 1.53). Six patients (11%) receiving volasertib achieved PFS fore more than 1 year, whereas no patient receiving chemotherapy achieved PFS greater than 1 year. No relationship between the expression of the biomarkers tested and their response was determined. Patients treated with volasertib experienced more grade 3 and 4 drug-related hematologic adverse events (AEs) and fewer nonhematologic AEs than did patients receiving chemotherapy. Discontinuation resulting from AEs occurred in seven (13.0%) and 15 (27.3%) patients in the volasertib and chemotherapy arms, respectively. Both arms showed similar effects on quality of life.

Conclusion

Single-agent volasertib showed antitumor activity in patients with ovarian cancer. AEs in patients receiving volasertib were mainly hematologic and manageable.
Effect of Pretreatment Renal Function on Treatment and Clinical Outcomes in the Adjuvant Treatment of Older Women With Breast Cancer: Alliance A171201, an Ancillary Study of CALGB/CTSU 49907
Authors: Lichtman Stuart M. , Cirrincione Constance T. , Hurria Arti , Jatoi Aminah , Theodoulou Maria , Wolff Antonio C. , Gralow Julie , Morganstern Daniel E. , Magrinat Gustav , Cohen Harvey Jay , Muss Hyman B.
Published: January 2016

Purpose

CALGB 49907 showed the superiority of standard therapy, which included either cyclophosphamide/doxorubicin (AC) or cyclophosphamide/methotrexate/fluorouracil over single-agent capecitabine in the treatment of patients age ≥ 65 with early-stage breast cancer. The treatment allowed dosing adjustments of methotrexate and capecitabine for pretreatment renal function. The purpose of the current analysis was to assess the relationship between pretreatment renal function and five end points: toxicity, dose modification, therapy completion, relapse-free survival, and overall survival.

Methods

Pretreatment renal function was defined as creatinine clearance (CrCl) using the Cockcroft-Gault equation. Multivariable logistic and proportional hazards regression were used to model separately for each regimen the relationship between CrCl and the first three binary end points and the last two time-to-event end points, respectively, after adjusting for variables of prognostic importance.

Results

Six hundred nineteen assessable patients were analyzed. The incidence of stage III (moderate) or stage IV (severe) renal dysfunction was 72%, 64%, and 75% for treatment with cyclophosphamide/methotrexate/fluorouracil, AC, and capecitabine, respectively. There was no relationship for any regimen between pretreatment renal function and the five end points. For AC, as CrCl increased, the odds of nonhematologic toxicity decreased (P = .008), whereas for capecitabine, as CrCl increased, the odds of experiencing toxicity of any type also increased (P = .035). Patients with renal insufficiency who received dose modifications were not at increased risk for complications compared with those who did not have renal insufficiency and received a full dose.

Conclusion

Excluding from clinical trials patients with renal insufficiency but good performance status on the basis of concern of excessive hematologic toxicity or poor outcomes may not be justified with appropriate dosing modifications. Results should be considered in the design of clinical trials for older patients.
Does Increased Spending on Pharmaceutical Marketing Inhibit Pioneering Innovation?
Authors: Arnold Denis G. , Troyer Jennifer L.
Published: January 2016

The pharmaceutical industry has been criticized for developing and aggressively marketing drugs that do not provide significant health benefits relative to existing drugs but retain the benefits of patent protection. Critics argue that drug marketing increases health care expenditures and provides a disincentive for pioneering drug innovation. However, evidence that marketing expenditures have any relationship to new drug approvals has been anecdotal. We hypothesized that, at publicly traded pharmaceutical firms, increased marketing expenditures will result in a reduced volume of pioneering new drugs in comparison to less innovative new drugs. We also hypothesized that additional research and development spending will result in an increased volume of pioneering new drugs in comparison to less innovative drugs. Results confirm our hypotheses. Specific policy recommendations for altering firms' incentives for the development of pioneering drugs are provided.
Iowa Wavering on Medicaid: From Expansion to Modernization
Authors: Wright Brad , Potter Andrew J. , Nattinger Matthew C.
Published: January 2016

Iowa is one of six states to expand Medicaid through section 1115 waivers. Iowa's alternative approach to Medicaid expansion, known as the Iowa Health and Wellness Plan, was the result of a bipartisan compromise, motivated by the pending expiration of a preexisting section 1115 waiver that served sixty-five thousand Iowans. The Iowa Health and Wellness Plan emphasizes personal responsibility and private involvement. Key features include beneficiary premiums, incentives for healthy behaviors, and premium assistance for some beneficiaries to purchase insurance in the health insurance marketplace. However, Iowa has struggled to implement its expansion as initially envisioned, due largely to the lack of private insurers willing and able to insure new Medicaid enrollees in the marketplace. In 2016 Iowa will dramatically increase the role of managed care in Medicaid, with the vast majority of beneficiaries receiving almost all Medicaid services through a capitated managed care organization. This article highlights the local factors driving expansion, the interplay of the state and federal political landscape, the challenges of providing consumer choice within Iowa's marketplace, and the future of Iowa's Medicaid program under managed care.
Chondrocytic EphrinB2 promotes cartilage destruction by osteoclasts in endochondral ossification
Authors: Tonna Stephen , Poulton Ingrid J. , Taykar Farzin , Ho Patricia W. M. , Tonkin Brett , Crimeen-Irwin Blessing , Tatarczuch Liliana , McGregor Narelle E. , Mackie Eleanor J. , Martin T. John , Sims Natalie A.
Published: January 2016

The majority of the skeleton arises by a process termed endochondral ossification, where cartilaginous templates expand and are resorbed by osteoclasts then replaced by osteoblastic bone formation. EphrinB2 is a receptor tyrosine kinase expressed by osteoblasts and growth plate chondrocytes that promotes osteoblast differentiation and inhibits osteoclast formation. We investigated the role of ephrinB2 in endochondral ossification using osterix-Cre (Osx1Cre) targeted gene deletion. Neonatal Osx1Cre.EfnB2Δ/Δ mice exhibited a transient osteopetrosis. This was demonstrated by increased trabecular bone volume with a high content of growth plate cartilage remnants and increased cortical thickness, but normal osteoclast numbers within the primary spongiosa. On closer examination, osteoclasts at the growth plate of Osx1Cre.EfnB2Δ/Δ mice had abnormal morphology and expressed low levels of tartrate-resistant acid phosphatase; this was not observed in more mature bone. Transmission electron microscopy revealed a lack of sealing zones and poor attachment of Osx1Cre.EfnB2Δ/Δ osteoclasts to growth plate cartilage. Osteoblasts at the growth plate were also poorly attached and impaired in their ability to deposit osteoid. By 6 months of age, trabecular bone mass, osteoclast morphology and osteoid deposition by osteoblasts in Osx1Cre.EfnB2Δ/Δ mice was normal compared to controls. Cultured chondrocytes from Osx1Cre.EfnB2Δ/Δ neonatal mice showed impaired support of osteoclastogenesis but no significant change in RANKL 9 (Tnsf11) levels; instead Adamts4 levels were significantly lowered. Immunohistochemical staining of control neonates showed a population of early hypertrophic chondrocytes positive for ADAMTS4, these cells were not positively stained in Osx1Cre.EfnB2Δ/Δ mice. This suggests that Osx1Cre-expressing cells, including hypertrophic chondrocytes, are dependent on EphrinB2 for their production of cartilage degrading enzymes, including Adamts4 and this may be required for attachment of osteoclasts and osteoblasts to the cartilage surface during endochondral ossification.
Differences in the spatiotemporal expression and epistatic gene regulation of the mesodiencephalic dopaminergic precursor markerPITX3during chicken and mouse development
Authors: Klafke Ruth , Prem Anand A. Alwin , Wurst Wolfgang , Prakash Nilima , Wizenmann Andrea
Published: January 2016

Mesodiencephalic dopaminergic (mdDA) neurons are located in the ventral mesencephalon and caudal diencephalon of all tetrapod species studied so far. They are the most prominent DA neuronal population and are implicated in control and modulation of motor, cognitive and rewarding/affective behaviors. Their degeneration or dysfunction is intimately linked to several neurological and neuropsychiatric human diseases. To gain further insights into their generation, we studied spatiotemporal expression patterns and epistatic interactions in chick embryos of selected marker genes and signaling pathways associated with mdDA neuron development in mouse. We detected striking differences in the expression patterns of the chick orthologs of the mouse mdDA marker genes Pitx3 and Aldh1a1, which suggests important differences between the species in the generation/generating of these cells. We also discovered that the Sonic hedgehog signaling pathway is both, necessary and sufficient for the induction of ectopic PITX3 expression in chick mesencephalon downstream of WNT9A induced LMX1a transcription. These aspects of early chicken development resemble the ontogeny of zebrafish diencephalic DA neuronal populations, and suggest a divergence between birds and mammals during evolution.
RNA-Seq identifies SPGs as a ventral skeletal patterning cue in sea urchins
Authors: Piacentino Michael L. , Zuch Daniel T. , Fishman Julie , Rose Sviatlana , Speranza Emily E. , Li Christy , Yu Jia , Chung Oliver , Ramachandran Janani , Ferrell Patrick , Patel Vijeta , Reyna Arlene , Hameeduddin Hajerah , Chaves James , Hewitt Finnegan B. , Bardot Evan , Lee David , Core Amanda B. , Hogan John D. , Keenan Jessica L. , Luo Lingqi , Coulombe-Huntington Jasmin , Blute Todd A. , Oleinik Ekaterina , Ibn-Salem Jonas , Poustka Albert J. , Bradham Cynthia A.
Published: January 2016

The sea urchin larval skeleton offers a simple model for developmental pattern formation. The calcium carbonate skeleton is secreted by primary mesenchyme cells (PMCs) in response to largely unknown patterning cues expressed by the ectoderm. To discover novel ectodermal cues, we performed an unbiased RNA-seq-based screen and functionally tested candidates; we thereby identified several novel skeletal patterning cues. Among these, we show that SLC26a2/7 is a ventrally expressed sulfate transporter which promotes a ventral accumulation of sulfated proteoglycans that is required for ventral PMC positioning and skeletal patterning. We show that the effects of SLC perturbation are mimicked by manipulation of either external sulfate levels or proteoglycan sulfation. These results identify novel skeletal patterning genes and demonstrate that ventral proteoglycan sulfation serves as a positional cue for the sea urchin skeletal patterning.