bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytotoxicity effects of three-dimensional graphene in NIH-3T3 fibroblasts
Authors: Zhang Bowei , Ni Hongwei , Chen Rongsheng , Zhang Tongcun , Li Xi , Zhan Weiting , Wang Zhenyu , Xu Yao
Published: April 2016

We present an evaluation of the in vitro cytotoxicity of 3D graphene sheets fabricated by carbonization of polydopamine (PDA) films on a template of aligned nanopore arrays (NPAs) on a stainless steel surface.
Self-assembled fibrillar networks comprised of a naturally-occurring cyclic peptide—LOB3
Authors: Rogers M. A. , Feng Q. , Ladizhansky V. , Good D. B. , Smith A. K. , Corridini M. , Grahame D. A. S. , Bryksa B. C. , Jadhav P. D. , Sammynaiken S. , Lim L.-T. , Guild B. , Shim Y. Y. , Burnett P.-G. , Reaney M. J. T.
Published: April 2016

LOB3, a naturally-occurring orbitide, is capable of self-assembling into 1D nano-fibers and ultimately 3D molecular gel networks in acetonitrile.
Synthesis and electrochemical properties of lithium zinc titanate as an anode material for lithium ion batteries via microwave method
Authors: Li ZhouFu , Cui YanHui , Wu JunWei , Du ChenQiang , Zhang XinHe , Tang ZhiYuan
Published: April 2016

Lithium zinc titanate (Li2ZnTi3O8) anode material has been synthesized via a microwave method for the first time.
ZnO–graphene–polyaniline nanoflowers: solution synthesis, formation mechanism and electrochemical activity
Authors: Bera Susanta , Naskar Atanu , Pal Moumita , Jana Sunirmal
Published: April 2016

Morphology dependent electrochemical activity of conducting ZnO–graphene–polyaniline nanocomposite.
Synthetic cobalt clays for the storage and slow release of therapeutic nitric oxide
Authors: Fernandes Ana C. , Pinto Moisés L. , Antunes Fernando , Pires João
Published: April 2016

Nitric oxide (NO) is one of the smallest endogenous molecules with particularly interesting aspect roles in biological systems, despite its toxicological potential.
Indium chloride catalyzed three-component reaction for the synthesis of 2-((oxoindolin-3-yl)-4,5,6,7-tetrahydro-1H-indol-1-yl)benzamides
Authors: Jiang Yan-Hong , Yan Chao-Guo
Published: April 2016

In the presence of indium chloride as a Lewis acid catalyst, the three-component reaction afforded functionalized 2-((oxoindolin-3-yl)-4,5,6,7-tetrahydro-1H-indol-1-yl)benzamides in satisfactory yields.
Crumpled N-doped carbon nanotubes encapsulated with peapod-like Ge nanoparticles for high-rate and long-life Li-ion battery anodes
Authors: Huo Kaifu , Wang Lei , Peng Changjian , Peng Xiang , Li Yuanyuan , Li Qingwei , Jin Zhenzhen , Chu Paul K.
Published: April 2016

Peapod-like Ge/CNx is designed as a high-performance anode for lithium-ion batteries, which boasts high capacity, excellent cyclability and rate capability.
Post-transcriptional regulation of Wnt co-receptor LRP6 and RNA-binding protein HuR by miR-29b in intestinal epithelial cells
Authors: Li Yanwu , Chen Gang , Wang Jun-Yao , Zou Tongtong , Liu Lan , Xiao Lan , Chung Hee Kyoung , Rao Jaladanki N. , Wang Jian-Ying
Published: April 2016

MicroRNAs (miRNAs) control gene expression by binding to their target mRNAs for degradation and/or translation repression and are implicated in many aspects of cellular physiology. Our previous study shows that miR-29b acts as a biological repressor of intestinal mucosal growth, but its exact downstream targets remain largely unknown. In the present study, we found that mRNAs, encoding Wnt co-receptor LRP6 (low-density lipoprotein-receptor-related protein 6) and RNA-binding protein (RBP) HuR, are novel targets of miR-29b in intestinal epithelial cells (IECs) and that expression of LRP6 and HuR is tightly regulated by miR-29b at the post-transcriptional level. miR-29b interacted with both Lrp6 and HuR mRNAs via their 3′-UTRs and inhibited LRP6 and HuR expression by destabilizing Lrp6 and HuR mRNAs and repressing their translation. Studies using heterologous reporter constructs revealed a greater repressive effect of miR-29b through a single binding site in the Lrp6 or HuR 3′-UTR, whereas deletion mutation of this site prevented miR-29b-induced repression of LRP6 and HuR expression. Repression of HuR by miR-29b in turn also contributed to miR-29b-induced LRP6 inhibition, since ectopic overexpression of HuR in cells overexpressing miR-29b restored LRP6 expression to near normal levels. Taken together, our results suggest that miR-29b inhibits expression of LRP6 and HuR post-transcriptionally, thus playing a role in the regulation of IEC proliferation and intestinal epithelial homoeostasis.
Structural evidence of the species-dependent albumin binding of the modified cyclic phosphatidic acid with cytotoxic properties
Authors: Sekula Bartosz , Ciesielska Anna , Rytczak Przemyslaw , Koziołkiewicz Maria , Bujacz Anna
Published: April 2016

Cyclic phosphatidic acids (cPAs) are naturally occurring, very active signalling molecules, which are involved in several pathological states, such as cancer, diabetes or obesity. As molecules of highly lipidic character found in the circulatory system, cPAs are bound and transported by the main extracellular lipid binding protein–serum albumin. Here, we present the detailed interactions between human serum albumin (HSA) and equine serum albumin (ESA) with a derivative of cPA, 1-O-myristoyl-sn-glycerol-2,3-cyclic phosphorodithioate (Myr-2S-cPA). Initial selection of the ligand used for the structural study was made by the analysis of the therapeutically promising properties of the sulfur containing analogues of cPA in respect to the unmodified lysophospholipids (LPLs). Substitution of one or two non-bridging oxygen atoms in the phosphate group with one or two sulfur atoms increases the cytotoxic effect of cPAs up to 60% on the human prostate cancer (PC) cells. Myr-2S-cPA reduces cancer cell viability in a dose-dependent manner, with IC50 value of 29.0 μM after 24 h incubation, which is almost 30% lower than IC50 of single substituted phosphorothioate cPA. Although, the structural homology between HSA and ESA is big, their crystal complexes with Myr-2S-cPA demonstrate significantly different mode of binding of this LPL analogue. HSA binds three molecules of Myr-2S-cPA, whereas ESA only one. Moreover, none of the identified Myr-2S-cPA binding sites overlap in both albumins.
Survey of recent progress on lightning and lightning protection research
Authors: Zeng Rong , Zhuang Chijie , Zhou Xuan , Chen She , Wang Zezhong , Yu Zhanqing , He Jinliang
Published: April 2016

Lightning and lightning induced effects have significant influence on many aspects affecting the public, which makes the research of lightning and lightning protection very important. However, due to the strong randomness and complex discharge mechanisms of lightning, the understanding of lightning is still far from satisfactory. On the basis of the International Conference on Lightning Protection 2014, this study gives a review of recent progress on lightning and lightning protection research covering the following aspects: lightning locating and observation, lightning physics, lightning electromagnetic transients, and lightning protection for various systems. The goals of this study are to give readers an overall introduction to the recent progress in lightning and lightning protection research, and to motivate them to conduct further studies to address the unsolved problems in lightning‐related research.
Making analytics actionable at AllDrinksSoft: MyResults and AMPlify
Authors: Schultze Ulrike
Published: April 2016

AllDrinksSoft (ADS), a US-based manufacturer and distributor of non-alcoholic beverages, began its journey into Business Analytics (BA) by developing two performance dashboards: one for its branches and one for its sales staff. By recounting the development and implementation of these two applications, and considering how improvements to them might be prioritized, this case explores ADS's journey into BA. In so doing, it highlights questions about the meaning of BA, the various ways in which analytics solutions can be designed and implemented, what the stages of BA maturity look like and how organizations might progress along this maturity trajectory.
Scattering pulse of label free fine structure cells to determine the size scale of scattering structures
Authors: Zhang Lu , Chen Xingyu , Zhang Zhenxi , Chen Wei , Zhao Hong , Zhao Xin , Li Kaixing , Yuan Li
Published: April 2016

Scattering pulse is sensitive to the morphology and components of each single label-free cell. The most direct detection result, label free cell’s scattering pulse is studied in this paper as a novel trait to recognize large malignant cells from small normal cells. A set of intrinsic scattering pulse calculation method is figured out, which combines both hydraulic focusing theory and small particle’s scattering principle. Based on the scattering detection angle ranges of widely used flow cytometry, the scattering pulses formed by cell scattering energy in forward scattering angle 2°–5° and side scattering angle 80°-110° are discussed. Combining the analysis of cell’s illuminating light energy, the peak, area, and full width at half maximum (FWHM) of label free cells’ scattering pulses for fine structure cells with diameter 1–20 μm are studied to extract the interrelations of scattering pulse’s features and cell’s morphology. The theoretical and experimental results show that cell’s diameter and FWHM of its scattering pulse agree with approximate linear distribution; the peak and area of scattering pulse do not always increase with cell’s diameter becoming larger, but when cell’s diameter is less than about 16 μm the monotone increasing relation of scattering pulse peak or area with cell’s diameter can be obtained. This relationship between the features of scattering pulse and cell’s size is potentially a useful but very simple criterion to distinguishing malignant and normal cells by their sizes and morphologies in label free cells clinical examinations.
A phononic crystal strip based on silicon for support tether applications in silicon-based MEMS resonators and effects of temperature and dopant on its band gap characteristics
Authors: Ha Thi Dep , Bao JingFu
Published: April 2016

Phononic crystals (PnCs) and n-type doped silicon technique have been widely employed in silicon-based MEMS resonators to obtain high quality factor (Q) as well as temperature-induced frequency stability. For the PnCs, their band gaps play an important role in the acoustic wave propagation. Also, the temperature and dopant doped into silicon can cause the change in its material properties such as elastic constants, Young’s modulus. Therefore, in order to design the simultaneous high Q and frequency stability silicon-based MEMS resonators by two these techniques, a careful design should study effects of temperature and dopant on the band gap characteristics to examine the acoustic wave propagation in the PnC. Based on these, this paper presents (1) a proposed silicon-based PnC strip structure for support tether applications in low frequency silicon-based MEMS resonators, (2) influences of temperature and dopant on band gap characteristics of the PnC strips. The simulation results show that the largest band gap can achieve up to 33.56 at 57.59 MHz and increase 1280.13 % (also increase 131.89 % for ratio of the widest gaps) compared with the counterpart without hole. The band gap properties of the PnC strips is insignificantly effected by temperature and electron doping concentration. Also, the quality factor of two designed length extensional mode MEMS resonators with proposed PnC strip based support tethers is up to 1084.59% and 43846.36% over the same resonators with PnC strip without hole and circled corners, respectively. This theoretical study uses the finite element analysis in COMSOL Multiphysics and MATLAB softwares as simulation tools. This findings provides a background in combination of PnC and dopant techniques for high performance silicon-based MEMS resonators as well as PnC-based MEMS devices.
Replacing synthetic N with clovers or alfalfa in bermudagrass pastures. 3. Performance of growing steers
Authors: Beck P. , Hess T. , Hubbell D. , Jennings J. , Gadberry M. S. , Sims M.
Published: April 2016

The objective of this study was to evaluate the performance of steers (n = 590, 263 ± 30.6 kg) grazing alfalfa (ALF, Medicago sativa L.) or a combination of white (Trifolium repens L.) and red (Trifolium pretense L.) clovers (CLVR) inter-seeded into bermudagrass (Cynodon dactylon L. Pers.) pastures compared with fertilisation with 0 (0N), 56 (56N), or 112 (112N) kg nitrogen (N)/ha (n = 4, 0.8-ha pastures per treatment) in north-east Arkansas (USA) over 4 years. The carryover N benefit of CLVR or ALF was compared with N fertilisation rates during the fifth year on performance of growing steers (n = 120; 235 ± 22.6 kg). Average daily gain increased with N application rate and legume pastures were similar to 56N; but liveweight gain per steer grazing legume pastures tended to be greater than 112N. Steer grazing days per hectare and liveweight gain per hectare were greater for ALF and CLVR than bermudagrass monocultures regardless of N fertilisation rate. Steer average daily gain, grazing days per hectare and liveweight gain per hectare for carryover N from legumes did not differ from 56N. These results indicate that replacing synthetic N by inter-seeding legumes into bermudagrass swards has the potential to improve individual animal performance and production per unit area and carryover benefits of legume N may be equivalent to 56 kg N/ha.
Opioid Overdose Prevention in a Residential Care Setting: Naloxone Education and Distribution
Authors: Pade Patricia , Fehling Patrick , Collins Sophie , Martin Laura
Published: April 2016

Background: Patients with opioid use disorders are at an increased risk for overdose death if they had a previous overdose, have co-occurring medical and psychiatric comorbidity, and are high-dose opioid users transitioning to relative abstinence or abstinence, i.e., those individuals discharging from drug treatment programs. Despite the success of opioid overdose prevention programs utilizing naloxone, residential substance abuse treatment centers often emphasize abstinence-based care for those suffering from addiction and do not adopt harm reduction approaches such as naloxone education and distribution. This performance improvement project reports the implementation of an opioid overdose prevention program provided to patients and their family members in a residential treatment setting. Methods: Opioid-dependent inpatients ( N = 47) along with their family members received overdose prevention training consistent with guidelines established by the Harm Reduction Coalition. Patient family members were queried regarding their awareness of past opioid overdose by the patient. A pre- and post-training questionnaire based on a 5-point Likert scale assessing ability to recognize overdose, fear of overdose, comfort in assisting with overdose, perception of life-threatening nature of addiction, and the value of overdose management was administered. Pre and post scores for each Likert scale were analyzed using paired 2-tailed t tests. Results: Thirty-two percent of patient family members were aware that the patient had a prior overdose. Statistically significant improvements in the ability of patients and families to recognize an opioid overdose as well as in their comfort to assist with an overdose were demonstrated. The pre- and post-education responses were both notably high for perceived value in learning about overdose and prevention. Conclusions: Implementation of opioid overdose prevention programs within residential treatment programs, sober living homes, and therapeutic communities would be well received and is strongly encouraged.
Racial Differences and the Role of Neighborhood in the Sequencing of Marijuana and Tobacco Initiation among Urban Youth
Authors: Green Kerry M. , Johnson Renee M. , Milam Adam J. , Furr-Holden Debra , Ialongo Nicholas S. , Reboussin Beth A.
Published: April 2016

Background: With patterns of initiation of tobacco and marijuana changing, there is increasing evidence that marijuana use may serve as an antecedent to tobacco use among adolescents. However, studies have not fully characterized the prevalence of these patterns among vulnerable youth and have rarely examined the factors that predict the sequencing of onset of tobacco and marijuana use. Methods: Utilizing longitudinal data from a sample of urban youth followed from age 6 to age 18, the authors identify the sequencing of initiation of tobacco and marijuana and test whether race and 5 neighborhood factors (i.e., perceived disorder, drug activity, drug access, exposure to violence, and exposure to violent victimization) predict onset sequencing. Results: Various sequencing patterns were observed, with 12.4% of the sample initiating marijuana use before tobacco use was initiated. In adjusted logistic regression models, black youth were 2.66 times as likely as whites to initiate marijuana before tobacco compared with initiating tobacco before marijuana ( P = .032). Youth with greater exposure to violent victimization were 3.89 times as likely to initiate marijuana first than initiate tobacco first ( P = .002). Other neighborhood factors were not statistically significantly associated with sequencing. Conclusions: Black youth and youth with greater exposure to victimization had an increased risk of initiating marijuana before tobacco, which suggests that this pattern may be rooted in specific risk factors. Substance use prevention efforts should consider taking into account that marijuana use may put certain youth at risk of initiating tobacco. Future research needs to monitor sequencing, as well as risk factors for and consequences of the various patterns, particularly since marijuana use and the mixing of tobacco and marijuana use are gaining acceptability in general populations.
Intoxication and Binge and High-Intensity Drinking among US Young Adults in their Mid-20s
Authors: Terry-McElrath Yvonne M. , Patrick Megan E.
Published: April 2016

Background: Alcohol use is a key risk factor for young adult mortality and disease, but limited research has focused on high-risk alcohol use among individuals moving from early young adulthood into building and maintaining an initial structure of adult life. This study estimated the prevalence of a range of alcohol use behaviors among US young adults aged 25/26, examined evidence for historical change in prevalence rates, and estimated associations between alcohol use and key demographic, substance use, and adult social role characteristics. Methods: Data were obtained from 3542 individuals selected for follow-up from the nationally representative 12th-grade student Monitoring the Future study. Respondents self-reported alcohol use behaviors at age 25/26 during calendar years 2005–2014. Results: Two fifths (39.9%) of young adults aged 25/26 reported being intoxicated at least once in the past 30 days; 25.6% reported usually experiencing a sustained high of 3 or more hours when drinking alcohol. Past-2-week binge drinking (5+ drinks in a row) was reported by 36.3% of respondents. Past-2-week high-intensity drinking (10+ drinks in a row) was reported by 12.4%. These age 25/26 alcohol use prevalence rates remained stable over the 10 years of data examined, in contrast to significant declines over historical time in alcohol prevalence rates among these same individuals at age 18. High-risk drinking was particularly associated with being male, white, unmarried, employed, a nonparent, and an alcohol user before finishing high school. Conclusions: Among US young adults in their mid-20s, alcohol use was highly normative and frequently included participation in high-risk drinking behaviors. High-risk alcohol use prevention approaches developed specifically to reach young adults in their mid-20s are needed, as well as efforts to increase proactive clinician screening to identify young adults participating in high-risk alcohol use.
Co-Prescription of Naloxone as a Universal Precautions Model for Patients on Chronic Opioid Therapy—Observational Study
Authors: Takeda Mikiko Y. , Katzman Joanna G. , Dole Ernest , Bennett Melissa Heinz , Alchbli Amal , Duhigg Daniel , Yonas Howard
Published: April 2016

Background: The epidemic of lethal prescription opioid overdose is one of the most pressing public health problems in the United States. In an ambulatory clinic setting, current practice guidelines suggest that health care providers should screen patient's aberrant drug-related behaviors. Given the difficulty of predicting which patients on chronic opioid therapy (COT) will experience opioid overdose, a new paradigm of harm reduction is called for. In previous studies, naloxone, an opioid antagonist, was given only to high-risk patients. However, if naloxone is co-prescribed in a Universal Precautions manner for all patients receiving COT, this may have a significant impact on intentional and unintentional opioid overdose deaths. Methods: Adult patients treated with COT for chronic noncancer pain are eligible study participants at the University of New Mexico Pain Center. The primary goal of this 1-year study was to develop an efficient Universal Precautions model for co-prescribing of naloxone with COT in the ambulatory clinic setting. Outcome measures included demographic data, detailed medical and substance use history, current morphine equivalent dose (MED), other “high-risk” medications used, and opioid misuse risk. Results: One hundred and sixty-four patients were enrolled in this study. All subjects were educated about the risks of opioid overdose and provided naloxone rescue kits. No overdoses occurred in the study population. Follow-up data illustrated that approximately 57% of the cohort had depressive disorder, the median MED was 90 mg/day, and the median Current Opioid Misuse Measure score (COMM) was 5.0. Conclusions: The ambulatory co-prescribing of naloxone in a Universal Precautions model for all patients prescribed COT can be adopted as a useful public health intervention. This study illustrates a model that can be used to educate patients, caregivers, and an interdisciplinary team of health care professionals in an academic medical center.
Digital resource developments for mathematics education involving homework across formal, non‐formal and informal settings
Authors: Radović Slaviša , Passey Don
Published: April 2016

The aim of this paper is to explore further an under‐developed area – how drivers of curriculum, pedagogy and assessment conceptions and practices shape the creation and uses of technologically based resources to support mathematics learning across informal, non‐formal and formal learning environments. The paper considers: the importance of mathematics learning in informal and non‐formal as well as formal settings; how curriculum focuses on pedagogy supporting these needs, contrasting this focus in England and Serbia; and in these contexts, the roles of homework, the potential of technologies and the roles of the teacher. Technological developments to support mathematics learning for 11‐ to 14‐year‐old pupils in the two countries are explored and contrasted, and ways that recent developments inform our understandings of formal, informal and non‐formal learning through learning activities, learning support and settings are modelled. The conception of ‘extended pedagogies’ is introduced; implications are outlined.
Chronic Thromboembolic Pulmonary Hypertension, Pregnancy, and a Pulmonary Endarterectomy: A Rare Challenge
Authors: Rosenzweig Erika B. , Biscotti Mauer , Cleary Kirsten , Smiley Richard , Bacchetta Matthew D.
Published: April 2016

It is well described that patients with group 1 forms of pulmonary arterial hypertension have a high risk of mortality during pregnancy and in the early postpartum period. However, to the authors' knowledge, the diagnosis and management of group 4 pulmonary hypertension due to chronic thromboembolic pulmonary hypertension (CTEPH) during pregnancy with early postpartum pulmonary endarterectomy (PEA) has not been previously reported. We report the case of a 28‐year‐old woman who received a diagnosis of CTEPH during her pregnancy, was managed as an inpatient by a multidisciplinary team throughout the pregnancy and early postpartum period, and underwent PEA 6 weeks after delivery. While the management of acute pulmonary embolus in pregnancy is well described, this unique case of CTEPH diagnosed during pregnancy illustrates several challenging management issues.
Genomic architecture of phenotypic divergence between two hybridizing plant species along an elevational gradient
Authors: Brennan Adrian C. , Hiscock Simon J. , Abbott Richard J.
Published: April 2016

Knowledge of the genetic basis of phenotypic divergence between species and how such divergence is caused and maintained is crucial to an understanding of speciation and the generation of biodiversity. The hybrid zone between Senecio aethnensis and S. chrysanthemifolius on Mount Etna, Sicily, provides a well-studied example of species divergence in response to conditions at different elevations, despite hybridization and gene flow. Here, we investigate the genetic architecture of divergence between these two species using a combination of quantitative trait locus (QTL) mapping and genetic differentiation measures based on genetic marker analysis. A QTL architecture characterized by physical QTL clustering, epistatic interactions between QTLs, and pleiotropy was identified, and is consistent with the presence of divergent QTL complexes resistant to gene flow. A role for divergent selection between species was indicated by significant negative associations between levels of interspecific genetic differentiation at mapped marker gene loci and map distance from QTLs and hybrid incompatibility loci. Within-species selection contributing to interspecific differentiation was evidenced by negative associations between interspecific genetic differentiation and genetic diversity within species. These results show that the two Senecio species, while subject to gene flow, maintain divergent genomic regions consistent with local selection within species and selection against hybrids between species which, in turn, contribute to the maintenance of their distinct phenotypic differences.
Accounting for correlated observations in an age-based state-space stock assessment model
Authors: Berg Casper W. , Nielsen Anders
Published: April 2016

Fish stock assessment models often rely on size- or age-specific observations that are assumed to be statistically independent of each other. In reality, these observations are not raw observations, but rather they are estimates from a catch-standardization model or similar summary statistics based on observations from many fishing hauls and subsamples of the size and age composition of the data. Although aggregation mitigates the strong intra-haul correlation between sizes/ages that is usually found in haul-by-haul data, violations of the independence assumption can have a large impact on the results and specifically on reported confidence bounds. A state-space assessment model that allows for correlations between age groups within years in the observation model for catches and surveys is presented and applied to data on several North Sea fish stocks using various correlation structures. In all cases the independence assumption is rejected. Less fluctuating estimates of the fishing mortality is obtained due to a reduced process error. The improved model does not suffer from correlated residuals unlike the independent model, and the variance of forecasts is decreased.
Tetratricopeptide repeat factor XAB2 mediates the end resection step of homologous recombination
Authors: Onyango David O , Howard Sean M , Neherin Kashfia , Yanez Diana A , Stark Jeremy M
Published: April 2016

We examined the influence of the tetratricopeptide repeat factor XAB2 on chromosomal break repair, and found that XAB2 promotes end resection that generates the 3′ ssDNA intermediate for homologous recombination (HR). Namely, XAB2 is important for chromosomal double-strand break (DSB) repair via two pathways of HR that require end resection as an intermediate step, end resection of camptothecin (Cpt)-induced DNA damage, and RAD51 recruitment to ionizing radiation induced foci (IRIF), which requires end resection. Furthermore, XAB2 mediates specific aspects of the DNA damage response associated with end resection proficiency: CtIP hyperphosphorylation induced by Cpt and BRCA1 IRIF. XAB2 also promotes histone acetylation events linked to HR proficiency. From truncation mutation analysis, the capacity for XAB2 to promote HR correlates with its ability to form a complex with ISY1 and PRP19, which show a similar influence as XAB2 on HR. This XAB2 complex localizes to punctate structures consistent with interchromatin granules that show a striking adjacent-localization to the DSB marker γH2AX. In summary, we suggest that the XAB2 complex mediates DNA damage response events important for the end resection step of HR, and speculate that its adjacent-localization relative to DSBs marked by γH2AX is important for this function.
Characteristics and Distribution of Graduate Medical Education Training Sites: Are We Missing Opportunities to Meet U.S. Health Workforce Needs?
Authors: Blanchard Janice , Petterson Stephen , Bazemore Andrew , Watkins Kayla , Mullan Fitzhugh
Published: April 2016

Purpose

Shortages of generalist physicians in primary care and surgery have been projected. Residency programs that expose trainees to community-based health clinics and rural settings have a greater likelihood of producing physicians who later practice in these environments. The objective of this study was to characterize the distribution of residency training sites in different settings for three high-need specialties—family medicine, internal medicine, and general surgery.

Method

The authors merged 2012 data from the Accreditation Council for Graduate Medical Education Accreditation Data System and 2010 data from the Centers for Medicare and Medicaid Services hospital cost report to match training sites with descriptive data about those locations. They used chi-square tests to compare the characteristics and distribution of residency programs and training sites in family medicine, internal medicine, and general surgery.

Results

The authors identified 1,095 residency programs and 3,373 training sites. The majority of training occurred in private, not-for-profit hospitals. Only 48 (of 1,390; 4%) family medicine training sites and 43 (of 936; 5%) internal medicine training sites were community-based health clinics. Seventy-eight (6%) family medicine sites, 8 (1%) internal medicine sites, and 16 (2%) general surgery sites were located in rural settings. One hundred thirty (14%) internal medicine sites were Department of Veterans Affairs medical facilities compared with 78 (6%) family medicine sites and 94 (9%) general surgery sites (P < .001).

Conclusions

Relatively little training occurs in rural or community-based settings. Expanding training opportunities in these low-access areas could improve physician supply there.
The Prevalence of Congenital Hand and Upper Extremity Anomalies Based Upon the New York Congenital Malformations Registry
Authors: Goldfarb Charles A. , Shaw Neil , Steffen Jennifer A. , Wall Lindley B.
Published: April 2016

Background:

There have been few publications regarding the prevalence of congenital upper extremity anomalies and no recent reports from the United States. The purpose of this investigation was to examine the prevalence of congenital upper extremity anomalies in the total birth population of New York State over a 19-year period utilizing the New York Congenital Malformations Registry (NYCMR) database.

Methods:

The NYCMR includes children with at least 1 birth anomaly diagnosed by 2 years of age and listed by diagnosis code. We scrutinized these codes for specific upper extremity anomalies, including polydactyly, syndactyly, reduction defects, clubhand malformations, and syndromes with upper limb anomalies. We included children born between 1992 and 2010.

Results:

There were a total of 4,883,072 live births in New York State during the study period. The overall prevalence of congenital upper extremity anomalies was 27.2 cases per 10,000 live births. Polydactyly was most common with 12,418 cases and a prevalence rate of 23.4 per 10,000 live births. The next most common anomalies included syndactyly with 627 cases affecting the hands (1498 total) and reduction defects (1111 cases). Specific syndromes were quite rare and were noted in a total of 215 live births. The prevalence of anomalies was higher in New York City compared with New York State populations at 33.0 and 21.9 per 10,000 live births, respectively.

Conclusions:

The NYCMR data demonstrate that congenital upper extremity anomalies are more common than previously reported. This is in large part due to the high prevalence of polydactyly. Although registries are imperfect, such data are helpful in monitoring prevalence rates over time, identifying potential causes or associations, and guiding health care planning and future research.

Level of Evidence:

Level I—diagnostic.
Comparison Between Doppler-Echocardiography and Uncalibrated Pulse Contour Method for Cardiac Output Measurement: A Multicenter Observational Study*
Authors: Scolletta Sabino , Franchi Federico , Romagnoli Stefano , Carlà Rossella , Donati Abele , Fabbri Lea P. , Forfori Francesco , Alonso-Iñigo José M. , Laviola Silvia , Mangani Valerio , Maj Giulia , Martinelli Giampaolo , Mirabella Lucia , Morelli Andrea , Persona Paolo , Payen Didier
Published: April 2016

Objectives:

Echocardiography and pulse contour methods allow, respectively, noninvasive and less invasive cardiac output estimation. The aim of the present study was to compare Doppler echocardiography with the pulse contour method MostCare for cardiac output estimation in a large and nonselected critically ill population.

Design:

A prospective multicenter observational comparison study.

Setting:

The study was conducted in 15 European medicosurgical ICUs.

Patients:

We assessed cardiac output in 400 patients in whom an echocardiographic evaluation was performed as a routine need or for cardiocirculatory assessment.

Interventions:

None.

Measurements and Main Results:

One echocardiographic cardiac output measurement was compared with the corresponding MostCare cardiac output value per patient, considering different ICU admission categories and clinical conditions. For statistical analysis, we used Bland-Altman and linear regression analyses. To assess heterogeneity in results of individual centers, Cochran Q, and the I
2 statistics were applied. A total of 400 paired echocardiographic cardiac output and MostCare cardiac output measures were compared. MostCare cardiac output values ranged from 1.95 to 9.90 L/min, and echocardiographic cardiac output ranged from 1.82 to 9.75 L/min. A significant correlation was found between echocardiographic cardiac output and MostCare cardiac output (r = 0.85; p < 0.0001). Among the different ICUs, the mean bias between echocardiographic cardiac output and MostCare cardiac output ranged from –0.40 to 0.45 L/min, and the percentage error ranged from 13.2% to 47.2%. Overall, the mean bias was –0.03 L/min, with 95% limits of agreement of –1.54 to 1.47 L/min and a relative percentage error of 30.1%. The percentage error was 24% in the sepsis category, 26% in the trauma category, 30% in the surgical category, and 33% in the medical admission category. The final overall percentage error was 27.3% with a 95% CI of 22.2–32.4%.

Conclusions:

Our results suggest that MostCare could be an alternative to echocardiography to assess cardiac output in ICU patients with a large spectrum of clinical conditions.
Development of Novel Criteria of the “Lethal Triad” as an Indicator of Decision Making in Current Trauma Care: A Retrospective Multicenter Observational Study in Japan
Authors: Endo Akira , Shiraishi Atsushi , Otomo Yasuhiro , Kushimoto Shigeki , Saitoh Daizoh , Hayakawa Mineji , Ogura Hiroshi , Murata Kiyoshi , Hagiwara Akiyoshi , Sasaki Junichi , Matsuoka Tetsuya , Uejima Toshifumi , Morimura Naoto , Ishikura Hiroyasu , Takeda Munekazu , Kaneko Naoyuki , Kato Hiroshi , Kudo Daisuke , Kanemura Takashi , Shibusawa Takayuki , Hagiwara Yasushi , Furugori Shintaro , Nakamura Yoshihiko , Maekawa Kunihiko , Mayama Gou , Yaguchi Arino , Kim Shiei , Takasu Osamu , Nishiyama Kazutaka
Published: April 2016

Objectives:

To evaluate the utility of the conventional lethal triad in current trauma care practice and to develop novel criteria as indicators of treatment strategy.

Design:

Retrospective observational study.

Settings:

Fifteen acute critical care medical centers in Japan.

Patients:

In total, 796 consecutive trauma patients who were admitted to emergency departments with an injury severity score of greater than or equal to 16 from January 2012 to December 2012.

Interventions:

None.

Measurements and Main Results:

All data were retrospectively collected, including laboratory data on arrival. Sensitivities to predict trauma death within 28 days of prothrombin time international normalized ratio greater than 1.50, pH less than 7.2, and body temperature less than 35°C were 15.7%, 17.5%, and 15.9%, respectively, and corresponding specificities of these were 96.4%, 96.6%, and 93.6%, respectively. The best predictors associated with hemostatic disorder and acidosis were fibrin/fibrinogen degradation product and base excess (the cutoff values were 88.8 µg/mL and –3.05 mmol/L). The optimal cutoff value of hypothermia was 36.0°C. The impact of the fibrin/fibrinogen degradation product and base excess abnormality on the outcome were approximately three- and two-folds compared with those of hypothermia. Using these variables, if the patient had a hemostatic disorder alone or a combined disorder with acidosis and hypothermia, the sensitivity and specificity were 80.7% and 66.8%.

Conclusions:

Because of the low sensitivity and high specificity, conventional criteria were unsuitable as prognostic indicators. Our revised criteria are assumed to be useful for predicting trauma death and have the potential to be the objective indicators for activating the damage control strategy in early trauma care.
Usability Testing the “Personal Patient Profile–Prostate” in a Sample of African American and Hispanic Men
Authors: Wolpin Seth , Halpenny Barbara , Sorrentino Erica , Stewart Mark , McReynolds Justin , Cvitkovic Ivan , Chang Peter , Berry Donna
Published: April 2016

Shared treatment decision making in a cancer setting requires a patient's understanding of the potential benefits and risks of each treatment option. Graphical display of risk information is one approach to improving understanding. Little is known about how patients engage with infographics in the context of health education materials and whether interactions vary with health literacy levels. We conducted an observational study, using an eye tracker device, of how men with newly diagnosed localized prostate cancer visually engaged with an on-screen infographic depicting risk information in the Personal Patient Profile–Prostate. Health literacy was measured with the Short Assessment of Health Literacy–English. Gaze patterns on an exemplar screens containing infographics about survival were analyzed and explored with respect to sociodemographic and health literacy data. Acceptability of Personal Patient Profile–Prostate was measured with the Acceptability E-scale. Twenty-six English-speaking men participated, and eye tracking data were collected for 12 men on the exemplar page of risk information that we analyzed. We found preliminary evidence of visual scanning and of participants with lower literacy focusing sooner on infographics versus text. Acceptability for Personal Patient Profile–Prostate was high. These findings suggest that infographics may be of higher relative value to participants with low health literacy. Eye trackers may provide valuable information on how people visually engage with infographics and may inform development of health education materials, although care must be taken to minimize data loss.
Prognostic and predictive value of YKL-40 in stage IIB-III melanoma
Authors: Krogh Merete , Christensen Ib , Bouwhuis Marna , Johansen Julia S. , Nørgaard Peter , Schmidt Henrik , Hansson Johan , Suciu Stefan , Eggermont Alexander M.M. , Bastholt Lars
Published: April 2016

This study investigates the prognostic and predictive value of YKL-40 in stage IIB–III melanoma patients who were randomized to adjuvant interferon α-2b (IFN) or observation. Serum YKL-40 was determined postoperatively in patients from the Nordic IFN Trial (n=602), EORTC 18952 (n=246), and EORTC 18991 (n=386) (EORTC, European Organisation for Research and Treatment of Cancer). YKL-40 protein expression was determined in 300 tissue sections of primary melanoma or lymph node metastases from 204 Danish patients from the Nordic IFN Trial. Multivariate Cox analysis (including sex, age, stage, ulceration, YKL-40) showed that elevated baseline YKL-40 level was associated with shorter overall survival (OS) in observation groups from the Nordic IFN Trial and EORTC 18952 [hazard ratio (HR)=1.33; 95% confidence interval (CI) 1.01–1.74; P=0.04], but not in the interferon groups (1-year IFN: HR=0.97; 95% CI 0.76–1.25; P=0.83; 2-years IFN: HR=1.06; 95% CI 0.83–1.34; P=0.64). During follow-up, increases in YKL-40 were significantly associated with shorter OS, but not with recurrence-free survival in univariate analysis. YKL-40 expression was stronger in tumor-associated macrophages than melanoma cells in primary melanoma. High YKL-40 expression in macrophages in lymph node metastases was associated with shorter OS in the observation group (HR=2.76; 95% CI: 1.13–6.76, P=0.02), but not in the interferon-treated groups. YKL-40 was an independent prognostic biomarker of OS in melanoma patients stage IIB–III. High serum YKL-40 in poor-prognosis patients may originate from macrophages in the tumor microenvironment and the melanoma cells. Furthermore, we hypothesize that elevated serum YKL-40 after surgery may predict the efficacy of adjuvant IFN treatment.
Combined Neprilysin and RAS Inhibition in Cardiovascular Diseases: A Review of Clinical Studies
Authors: Tummala Ramyashree , Bhadra Rajarshi , Gupta Anjan , Ghosh Raktim K.
Published: April 2016

The aim of this comprehensive review article is to emphasize on the possible exploration of a new therapeutic approach in the management of heart failure (HF) and other cardiovascular diseases: the renin–angiotensin–aldosterone system–neprilysin combination inhibitors, also called angiotensin receptor neprilysin inhibitor, valsartan/sacubitril (LCZ696). Sacubitril is an inhibitor of neutral endopeptidase (NEP) which degrades vasoactive peptides such as atrial natriuretic peptide and brain natriuretic peptide. Valsartan is an angiotensin receptor blocker which is usually used in hypertension. Although HF has been a global health burden, for decades there has been lack of novel therapeutic options as many trials failed due to potential side effects. With the published results of the landmark trial Prospective comparison of ARNI with ACEI to Determine the Impact on Global Mortality and morbidity in HF (PARADIGM-HF), a new direction in the treatment of HF is anticipated. This trial showed that LCZ696 was able to reduce the primary composite end point of cardiovascular death or HF hospitalization, and similar reduction was observed for cardiovascular death. This review article also highlights the results of 4 published trials of LCZ696 in both HTN and HF. After the results of PARADIGM-HF trial, the major challenge will be outcome in regular clinical practice, as subjects in the trial were mostly stable New York Heart Association class II patients with no comorbidities. In addition, many trials are simultaneously in progress regarding the use of LCZ696 in patients with diabetes, renal failure, and hepatic impairment. To conclude, sacubitril/valsartan significantly improved morbidity and mortality in patients with chronic HF, but it will need meticulous attention when used in real outpatient practice.
A Liquid Chromatography-Tandem Mass Spectrometry Method for Quantifying Amisulpride in Human Plasma and Breast Milk, Applied to Measuring Drug Transfer to a Fully Breast-Fed Neonate
Authors: O'Halloran Sean J. , Wong Antonia , Joyce David A.
Published: April 2016

Background:

Amisulpride is a second generation atypical antipsychotic drug. The management of psychosis exacerbation in late pregnancy or during lactation is often hampered by inadequate knowledge of risk to the baby from placental transfer or breast milk transfer of drugs. There is no specific information on adverse effects from amisulpride. To gather guiding information from one mother–baby pair, we conducted a drug concentration study on the fourth post-natal day and developed a novel liquid chromatography-tandem mass spectrometry method with application to the very small plasma volumes obtainable from a neonate, requiring 15 μL of plasma, and with application to human breast milk.

Methods:

Plasma and breast milk extracts, spiked with deuterated internal standard (amisulpride-d5) were separated isocratically with a buffered water–methanol–acetonitrile mobile phase. A tandem mass spectrometer in positive electrospray ionisation mode with multiple reaction monitoring was used for detection.

Results:

Method linearity, sensitivity, imprecision, matrix effects, recovery, and overall process efficiency were satisfactory for milk and plasma. No interferences were found from a broad range of psychotropic and general drugs. The breast milk area under the concentration–time curve for the interval 0–12 hours was 10,726 mcg·h·L−1, corresponding to a mean breast milk concentration of 894 mcg/L. Breast milk amisulpride was 12-fold higher than the simultaneous plasma concentration. The baby's plasma amisulpride concentration was 10.5% of the maternal plasma concentration.

Conclusions:

An assay was developed that is suitable for therapeutic drug monitoring of amisulpride. Its application to breast milk and neonate plasma showed that amisulpride partitioned strongly into breast milk and that the neonate reached plasma levels that were more than desirable for a psychotropic drug.
Primary ovarian insufficiency associated with autosomal abnormalities: from chromosome to genome-wide and beyond
Authors: Vichinsartvichai Patsama
Published: April 2016

Objective:

The pathophysiology of primary ovarian insufficiency (POI) is not well elucidated. Many candidate genetic aberrations are on the X-chromosome; on the contrary, many genetic perturbations are also on the autosomes. The aim of this review is to summarize the knowledge of genetic aberrations on autosomes from chromosomal rearrangement, gene abnormality, genome-wide association studies and epigenetics.

Methods:

Searches of electronic databases were performed. Articles and abstracts relevant to POI and genetic studies associated with autosomes were summarized in this interpretive literature review.

Results:

Various genetic aberrations located on the autosomes were found. These abnormalities are from chromosomal rearrangement, which might disrupt the critical region on chromosome loci or disturbance of the meiosis process. Specific gene aberrations are also identified. The genes that have functions in ovarian development, folliculogenesis, and steroidogenesis on autosomes are proposed to be involved from gene association studies. Gene-to-gene interaction or epistasis also might play a role in POI occurrence. Recently, genetic techniques to study the whole genome have emerged. Although no specific conclusion has been made, the studies using genome-wide association to find the specific aberration throughout the genome in POI have been published. Epigenetic mechanisms might also take part in the pathogenesis of POI.

Conclusions:

The considerably complex process of POI is still not well understood. Further research is needed for gene functional validation studies to confirm the contribution of genes in POI, or additional genome-wide association studies using novel clustered regularly interspaced short palindromic repeat/Cas9 technique might make these mechanisms more comprehensible.