bluuebunny/crossref_metadata_2025 huggingface dataset:
Sympatric Asian felid phylogeography reveals a major Indochinese–Sundaic divergence
Authors: Luo Shu‐Jin , Zhang Yue , Johnson Warren E. , Miao Lin , Martelli Paolo , Antunes Agostinho , Smith James L. D. , O'Brien Stephen J.
Published: March 2014

The dynamic geological and climatological history of Southeast Asia has spawned a complex array of ecosystems and 12 of the 37 known cat species, making it the most felid‐rich region in the world. To examine the evolutionary histories of these poorly studied fauna, we compared phylogeography of six species (leopard cat Prionailurus bengalensis, fishing cat P. viverrinus, Asiatic golden cat Pardofelis temminckii, marbled cat P. marmorata, tiger Panthera tigris and leopard P. pardus) by sequencing over 5 kb of DNA each from 445 specimens at multiple loci of mtDNA, Y and X chromosomes. All species except the leopard displayed significant phylogenetic partitions between Indochina and Sundaland, with the central Thai–Malay Peninsula serving as the biogeographic boundary. Concordant mtDNA and nuclear DNA genealogies revealed deep Indochinese–Sundaic divergences around 2 MYA in both P. bengalensis and P. marmorata comparable to previously described interspecific distances within Felidae. The divergence coincided with serial sea level rises during the late Pliocene and early Pleistocene, and was probably reinforced by repeated isolation events associated with environmental changes throughout the Pleistocene. Indochinese–Sundaic differentiations within P. tigris and P. temminckii were more recent at 72–108 and 250–1570 kya, respectively. Overall, these results illuminate unexpected, deep vicariance events in Southeast Asian felids and provide compelling evidence of species‐level distinction between the Indochinese and Sundaic populations in the leopard cat and marbled cat. Broader sampling and further molecular and morphometric analyses of these species will be instrumental in defining conservation units and effectively preserving Southeast Asian biodiversity.
Young–age‐onset pancreatoduodenal carcinoma in Shwachman–Diamond syndrome
Authors: Nakaya Takeo , Kurata Atsushi , Hashimoto Hirotsugu , Nishimata Shigeo , Kashiwagi Yasuyo , Fujita Koji , Kawashima Hisashi , Kuroda Masahiko
Published: March 2014

Shwachman–Diamond syndrome, which is characterized by pancreatic fatty degeneration, skeletal growth retardation, and hematological dysfunction, is a congenital disease caused by SBDS gene mutations. Although hematological disorders often accompany this syndrome, carcinomas associated with this syndrome have not been reported except in one breast cancer and one moderately differentiated pancreatic cancer case. We report on an autopsy of a 24‐year‐old case of pancreatoduodenal carcinoma in Shwachman–Diamond syndrome. The histology of the tumor was undifferentiated carcinoma, which seems to have originated from either the pancreatic duct or the duodenal epithelium. The tumor was intermingled with two pathological changes characteristic of Shwachman–Diamond syndrome: fatty degeneration of the pancreas and inflammation of the villous stroma of the duodenum. Considering that SBDS protein regulates mitosis and its suppression causes genomic instability, this case might provide an example of carcinogenesis based on genomic instability, together with degenerative changes and chronic inflammation, at a very young age.
Clinicopathological significance of ‘atypical ductal proliferation’ in core needle biopsy of the breast
Authors: Abe Eriko , Suzuki Koyu , Hayashi Naoki , Yang Yang , Chih‐Ping Li , Uno Mieko , Akiyama Futoshi , Yamauchi Hideko , Nakamura Seigo , Tsugawa Koichiro , Tsunoda Hiroko , Ohde Sachiko , Sasano Hironobu
Published: March 2014

Atypical ductal proliferation or ADP has been used in histopathological diagnosis of core needle biopsy (CNB) but its details have not been well studied. Therefore, we examined the clinicopathological characteristics of the initial CNB cases diagnosed as ‘ADP ’ who subsequently turned out to be malignant, and compared the findings to those that did not. Among 101 cases initially diagnosed as ADP in CNB, the second biopsy revealed no carcinoma (38), ductal carcinoma in situ (DCIS) (45) and invasive carcinoma (18). Significant differences were detected between those which turned out to be carcinoma and those that did not, in the status of myoepithelial cells identified by p63 immunohistochemistry (P = 0.026) and ultrasound (US) categories (P < 0.001). We further compared the histopathological characteristics of those initially diagnosed as ADP and subsequently as DCIS or invasive ductal carcinoma (IDC) with those initially diagnosed as such. DCIS or IDC cases initially diagnosed as ADP had significantly lower Ki67 labeling index (P < 0.01, P < 0.01) and histological grade using Van nuys prognostic index (P < 0.01) or Nottingham histological grades (P < 0.01) respectively than those initially as DCIS or IDC. An assessment of myoepithelial components with US findings might contribute to determine the subsequent clinical algorithm of the patients diagnosed as ADP at initial CNB.
Inflammation of colon adenoma in the setting of type 1 autoimmune pancreatitis
Authors: Uehara Takeshi , Hamano Hideaki , Suga Tomoaki , Kawa Shigeyuki , Yoshizawa Akihiko , Kobayashi Yukihiro , Murata Kazuya , Oki Keiko , Sano Kenji , Onodera Rie , Ota Hiroyoshi
Published: March 2014

Although immunoglobulin G4‐related diseases (IgG4‐RD) have been found to affect many organs, little is known about their effects on the colonic mucosae. Pathological examination of colon adenomas has shown inflammatory cell infiltration into the stroma. We therefore assessed the clinicopathological characteristics of colon adenomas in patients with type 1 autoimmune pancreatitis (AIP‐1), a representative IgG4‐RD. Both colon adenomas from patients with (IgG4 adenomas) and without (Non‐IgG4 adenomas) IgG4‐RD were characterized by moderate to severe lymphoplasmacytic and eosinophilic inflammation without fibrosis or phlebitis. The ratio of IgG4‐positive to IgG‐positive plasma cells (IgG4/IgG ratio) and the numbers of IgG4‐positive plasma cells were significantly higher in IgG4 adenomas than in Non‐IgG4 adenomas. IgG4‐positive plasma cells tended to be distributed diffusely in lower areas of the mucosae in IgG4 adenomas. We were unable to confirm whether IgG4 adenomas constituted an IgG4‐RD. However, IgG4 adenomas in the setting of IgG4‐RD may provide useful pathological information, supplementing a diagnosis of IgG4‐RD outside the colon, or may facilitate examination for IgG4‐RD, especially AIP‐1. IgG4 adenomas warrant further investigation.
Interspecific variation in pollen–ovule ratio is negatively correlated with pollen transfer efficiency in a natural community
Authors: Gong Y.‐B. , Huang S.‐Q.
Published: March 2014

The pollination efficiency hypothesis has long been proposed as an explanation for interspecific variation in pollen–ovule (P:O) ratios. However, no empirical study onP:Oratios has directly and quantitatively measured pollen transfer efficiency (PE). Here, we use aPEindex, defined as the proportion of pollen grains removed from anthers that are subsequently deposited on conspecific stigmas, as a direct and quantitative measure ofPE. We investigatedP:Oratios, pollen removal and pollen deposition in 26 plant species in an alpine meadow, over three consecutive years. Our community survey showed that nearly 5% of removed pollen was successfully deposited on conspecific stigmas. ThePEindex ranged from 0.01% up to 78.56% among species, and correlated negatively with theP:Oratio across years. This correlation was not changed by controlling for phylogenetic relationships among species, suggesting that the interspecific variation inP:Oratios can be attributed to the probability of pollen grains reaching a stigma. The results indicate that the pollination efficiency hypothesis can help to explain interspecific variation inP:Oratios.
Moderators of Candidate Name‐Order Effects in Elections: An Experiment
Authors: Kim Nuri , Krosnick Jon , Casasanto Daniel
Published: March 2014

Past studies of elections have shown that candidates whose names were listed at the beginning of a list on a ballot often received more votes by virtue of their position. This article tests speculations about the cognitive mechanisms that might be responsible for producing the effect. In an experiment embedded in a large national Internet survey, participants read about the issue positions of two hypothetical candidates and voted for one of them in a simulated election in which candidate name order was varied. The expected effect of position appeared and was strongest (1) when participants had less information about the candidates on which to base their choices, (2) when participants felt more ambivalent about their choices, (3) among participants with more limited cognitive skills, and (4) among participants who devoted less effort to the candidate evaluation process. The name‐order effect was greater among left‐handed people when the candidate names were arrayed horizontally, but there was no difference between left‐ and right‐handed people when the names were arrayed vertically. These results reinforce some broad theoretical accounts of the cognitive process that yield name‐order effects in elections.
Effect of Supplementation with a Lipid‐Based Nutrient Supplement on the Micronutrient Status of Children Aged 6–18 Months Living in the Rural Region of Intibucá, Honduras
Authors: Siega‐Riz Anna M. , Estrada Del Campo Yaniré , Kinlaw Alan , Reinhart Gregory A. , Allen Lindsay H. , Shahab‐Ferdows Setareh , Heck Jeff , Suchindran Chirayath M. , Bentley Margaret E.
Published: March 2014

Background

Lipid‐based nutrient supplements (LNS) have been effective in the treatment of acute malnutrition among children. We evaluated the use of LNS supplementation for improving the micronutrient status of young children.

Methods

A 12‐month randomised controlled trial was conducted among children aged 6–18 months living in Intibucá, Honduras. Communities (n = 18) were randomised into clusters matched by poverty indicators (9 intervention, n = 160 and 9 controls, n = 140). Intervention participants received LNS. All children received food vouchers and nutrition education. Primary outcomes included measures of micronutrient status: at baseline, 6 and 12 months' blood were collected for assessment of folate, iron, zinc, riboflavin, and vitamin B12 status; haemoglobin was measured every 3 months; and dietary and anthropometry collected monthly. Longitudinal analyses were based on intent to treat and LNS adherence. Generalised estimating equations were used in the estimation of generalised linear regression models specified for the data.

Results

At 6‐month follow‐up, children in the intervention group had a lower proportion classified as deficient for B12 (43.6%) compared with the control (67.7%; P = 0.03). The intervention group had a higher mean concentration for folate at 6 months (P = 0.06), and improvements continued through 12 months for folate (P = 0.002) and vitamin A deficiency (P = 0.03). This pattern of results, with improved significance, remained in subanalysis based on LNS adherence.

Conclusion

These data demonstrate that LNS improved select micronutrient status in young non‐malnourished Honduran children.
Cystatin C: A potential biomarker for pulmonary arterial hypertension
Authors: Fenster Brett E. , Lasalvia Luis , Schroeder Joyce D. , Smyser Jamey , Silveira Lori J. , Buckner J. Kern , Brown Kevin K.
Published: March 2014

Background and Objective

Cystatin C (CysC), a novel marker of renal function, predicts left heart failure and cardiovascular mortality. The hypothesis that serum CysC levels correlate with right ventricular (RV) morphology, function and pressure in pulmonary arterial hypertension (PAH) was tested.

Methods

As part of a prospective study, 14 PAH subjects and 10 matched controls underwent same‐day echocardiography, cardiac magnetic resonance imaging (CMR), and phlebotomy for CysC, brain natriuretic peptide (BNP), and N‐terminal BNP (NT‐ProBNP). RV ejection fraction (RVEF), end‐diastolic volume, end‐systolic volume and mass were calculated using CMR. RV systolic pressure (RVSP), strain and diastolic function (including tricuspid valve (TV) E velocity, A velocity, e′ velocity, E/A ratio and E/e′ ratio) were assessed using echocardiography.

Results

RVSP was significantly elevated in PAH subjects versus controls (57 ± 17 vs. 28 ± 8 mm Hg, P < 0.0001). CysC was abnormally elevated in the PAH cohort when compared with controls (1.00 ± 0.23 vs 0.78 ± 0.05 mg/L, P = 0.001). CysC positively correlated with RVSP (rho 0.61, P = 0.002), RV end‐diastolic volume (rho 0.50, P = 0.01), RV end‐systolic volume (rho 0.58, P = 0.003), mass index (rho 0.66, P = 0.0004), strain (rho 0.51, P = 0.01) and strain rate (rho 0.51, P = 0.01) and negatively correlated with RVEF (rho −0.58, P = 0.003) and TV e′ (rho −0.75, P < 0.0001). The same correlations with BNP and NT‐ProBNP were comparable with CysC.

Conclusions

In a small cohort, CysC accurately correlates with RV pressure, function and morphology. CysC may represent a novel PAH biomarker.
Labor Union Political Strategy in an Era of Decline and Revitalization
Authors: Albert Kyle
Published: March 2014

U.S. labor unions faced sharp membership losses over the last few decades, and some responded by ushering in a new, revitalized model of organizing. Yet we know little about how these forces may be shaping the political activities of the labor movement. Has crisis prompted unions to take aim at public policies inhibiting union vitality, or have unions turned outward to embrace broader social causes? This paper uses an original dataset of union appearances in congressional hearings to analyze unions’ legislative advocacy activities. Findings suggest substantial differences between those unions that are likely to appear in hearings on core labor‐related topics and those that appear in hearings on broad social issues: AFL‐CIO unions are more likely to participate in hearings on core labor issues, while unions commonly cited as “revitalized” and public sector unions are more likely to appear in hearings on broad social issues.
Pseudo‐hypoproteinemia in a hyperbilirubinemic dog with immune‐mediated hemolytic anemia
Authors: Garner Bridget C. , Priest Heather , Smith Jo
Published: March 2014

A 10‐year‐old spayed female Miniature Poodle was presented to the University of Georgia veterinary teaching hospital for evaluation of lethargy, vomiting and anorexia of 4 days' duration. Physical examination, history and a minimum database led to a diagnosis of immune‐mediated hemolytic anemia accompanied by marked hyperbilirubinemia. Refractometric protein determination was within the reference interval, whereas the biuret method indicated hypoproteinemia. This discrepancy was attributed to interference of bilirubin and biliverdin with the spectrophotometric read‐out of the biuret total protein assay. The albumin concentration, determined by bromcresol green, and refractometric total protein were less affected by this interference.
Effect of Pin Tip Dual Clearance on Flow and Heat Transfer at Low Reynolds Numbers
Authors: Seibert Michael L. , Blackwell Neal E. , Tafti Danesh K.
Published: March 2014

This paper examines the augmentation of heat and mass transfer due to dual clearances on cylindrical pin fins, relative to a channel between parallel plates, in mini/microchannel reactors at low Reynolds numbers. In this work, diffusion limitations to heat and mass transfer in smooth-walled mini/microchannel reactors were minimized by the implementation of microcylinder pin fins with dual clearances that, (1) promote the production of instabilities in the wakes that enhance mixing and (2) reduce the viscosity dominated regions at pin-wall interfaces. A smooth catalyst coating is assumed on all exposed surfaces of the microchannel interior walls and pin fins. Due to the analogy of heat and mass transfer, augmentation of the Nusselt number is equivalent to the augmentation of the Sherwood number. Heat transfer augmentation is investigated in air (Pr = 0.705) at dual clearances ranging from 0 to 0.4 of the channel height and Reynolds numbers from 10 to 600. The pin fins and the clearance augmented the heat transfer coefficient by a factor of 4.0. The combination of the augmentation of the heat transfer coefficient and the increase in the surface area, by the clearances, results in an increase in the conductance over a plane channel, by a factor of 7.1. The results are extendable to overcoming laminar diffusion with laminar periodic wakes of fuel vapors such as methanol vapor in air where Scfuel ∼ Prair. For turbulent wakes impinging upon downstream pins, the results can be extended to fuel vapors with (Scfuel)turb ∼ (Prair)turb. A large eddy simulation (LES) approach was used in this study.
Molecular beam epitaxy using bismuth as a constituent in InAs and a surfactant in InAs/InAsSb superlattices
Authors: Webster Preston T. , Riordan Nathaniel A. , Gogineni Chaturvedi , Liu Shi , Lu Jing , Zhao Xin-Hao , Smith David J. , Zhang Yong-Hang , Johnson Shane R.
Published: March 2014

Alloying bismuth with InAs provides a ternary material system near the 6.1 Å lattice constant, which covers the technologically important mid- and long-wavelength infrared region. One challenge for this material system is that it is not straightforward to incorporate bismuth into the bulk InAs lattice, since bismuth has a tendency to surface-segregate and form droplets during growth. In this work, the conditions for InAsBi growth using molecular beam epitaxy are explored. A growth window is identified (temperatures ⪞ 270 °C, V/III flux ratios 0.98 ⪝ As/In ⪝ 1.02, and Bi/In ≅ 0.065) for droplet-free, high-quality crystalline material, where InAsBi layers with compositions of up to 5.8% bismuth (nearly lattice-matched to GaSb) are attained. The structural quality of InAsBi bulk and quantum well samples is evaluated using x-ray diffraction and transmission electron microscopy. The optical quality is assessed using photoluminescence, which is observed from quantum well structures up to room temperature and from thick, low Bi-content bulk layers at low temperatures. Bismuth is also used as a surfactant during the growth of InAs/InAsSb superlattices at 430 °C where it is observed that a small bismuth flux changes the surface reconstruction of InAs from (2×1) to (1×3), reduces the sticking coefficient of antimony, results in a slight increase in photoluminescence intensity, does not significantly incorporate, and does not alter the surface morphology.
Depression and anxiety in prostate cancer: a systematic review and meta-analysis of prevalence rates
Authors: Watts Sam , Leydon Geraldine , Birch Brian , Prescott Philip , Lai Lily , Eardley Susan , Lewith George
Published: March 2014

Objectives

To systematically review the literature pertaining to the prevalence of depression and anxiety in patients with prostate cancer as a function of treatment stage.

Design

Systematic review and meta-analysis.

Participants

4494 patients with prostate cancer from primary research investigations.

Primary outcome measure

The prevalence of clinical depression and anxiety in patients with prostate cancer as a function of treatment stage.

Results

We identified 27 full journal articles that met the inclusion criteria for entry into the meta-analysis resulting in a pooled sample size of 4494 patients. The meta-analysis of prevalence rates identified pretreatment, on-treatment and post-treatment depression prevalences of 17.27% (95% CI 15.06% to 19.72%), 14.70% (95% CI 11.92% to 17.99%) and 18.44% (95% CI 15.18% to 22.22%), respectively. Pretreatment, on-treatment and post-treatment anxiety prevalences were 27.04% (95% CI 24.26% to 30.01%), 15.09% (95% CI 12.15% to 18.60%) and 18.49% (95% CI 13.81% to 24.31%), respectively.

Conclusions

Our findings suggest that the prevalence of depression and anxiety in men with prostate cancer, across the treatment spectrum, is relatively high. In light of the growing emphasis placed on cancer survivorship, we consider that further research within this area is warranted to ensure that psychological distress in patients with prostate cancer is not underdiagnosed and undertreated.
Interaction of sleep quality and sleep duration on impaired fasting glucose: a population-based cross-sectional survey in China
Authors: Lou Peian , Chen Peipei , Zhang Lei , Zhang Pan , Chang Guiqiu , Zhang Ning , Li Ting , Qiao Cheng
Published: March 2014

Objectives

To explore the interactions of sleep quality and sleep duration and their effects on impaired fasting glucose (IFG) in Chinese adults.

Design

Cross-sectional survey.

Setting

Community-based investigation in Xuzhou, China.

Participants

15 145 Chinese men and women aged 18–75 years old who fulfilled the inclusion criteria.

Primary and secondary outcome measures

The Pittsburgh Sleep Quality Index was used to produce sleep quality categories of good, common and poor. Fasting blood glucose levels were assessed for IFG. Sleep duration was measured by average hours of sleep per night, with categories of <6, 6–8 and >8 h. The products of sleep and family history of diabetes, obesity and age were added to the logistic regression model to evaluate the addictive interaction and relative excess risk of interaction (RERI) on IFG. The attributable proportion (AP) of the interaction and the synergy index (S) were applied to evaluate the additive interaction of two factors. Bootstrap measures were used to calculate 95% CI of RERI, AP and S.

Results

The prevalence of IFG was greatest in those with poor sleep quality and short sleep duration (OR 6.37, 95% CI 4.66 to 8.67; p<0.001) compared with those who had good sleep quality and 6–8 h sleep duration, after adjusting for confounders. After adjusting for potential confounders RERI, AP and S values (and their 95% CI) were 1.69 (0.31 to 3.76), 0.42 (0.15 to 0.61) and 2.85 (2.14 to 3.92), respectively, for the interaction between poor sleep quality and short sleep duration, and 0.78 (0.12 to 1.43), 0.61 (0.26 to 0.87) and −65 (−0.94 to −0.27) for the interaction between good sleep quality and long sleep duration.

Conclusions

The results suggest that there are additive interactions between poor sleep quality and short sleep duration.
Effects of alternative forest management on biomass and species diversity in the face of climate change in the northern Great Lakes region (USA)
Authors: Duveneck Matthew J. , Scheller Robert M. , White Mark A.
Published: March 2014

Northern Great Lakes forests represent an ecotone in the boreal–temperate transition zone and are expected to change dramatically with climate change. Managers are increasingly seeking adaptation strategies to manage these forests. We explored the efficacy of two alternative management scenarios compared with business-as-usual (BAU) management: expanding forest reserves meant to preserve forest identity and increase resistance, and modified silviculture meant to preserve forest function and increase adaptive capacity. Our study landscapes encompassed northeastern Minnesota and northern Lower Michigan, which are predicted to experience significant changes in a future climate and represent a gradient of latitude, forest type, and management. We used the LANDIS-II forest simulation model to simulate forest change under current climate, low emissions climate, and high emissions climate futures. Our results suggest that under a low emissions climate scenario, expanded reserves and modified silviculture strategies can be effective at increasing resistance by preserving forest composition, including legacy species (e.g., balsam fir (Abies balsamea (L.) Mill.)), and increasing adaptive capacity by maintaining or increasing aboveground biomass compared with BAU management. Under a high emissions climate scenario, the expanded reserve strategy was not effective at preserving legacy species; however, the modified silviculture strategy was effective at increasing aboveground biomass compared with BAU management. These results highlight alternative management options and limitations in the face of climate change.
The unbiasedness of a generalized mirage boundary correction method for Monte Carlo integration estimators of volume
Authors: Lynch Thomas B. , Gove Jeffrey H.
Published: March 2014

The typical “double counting” application of the mirage method of boundary correction cannot be applied to sampling systems such as critical height sampling (CHS) that are based on a Monte Carlo sample of a tree (or debris) attribute because the critical height (or other random attribute) sampled from a mirage point is generally not equal to the critical height measured from the original sample point. A generalization of the mirage method is proposed for CHS and related techniques in which new samples of critical heights or other dimensions are obtained from mirage points outside the tract boundary. This is necessary because, in the case of CHS, the critical height actually depends on the distance between the tree and a randomly located sample point. Other spatially referenced individual tree attribute or coarse woody debris (CWD) estimators that use Monte Carlo integration with importance sampling have been developed in which the tree or CWD attribute estimate also depends on the distance between the tree and the sample point. The proposed modified mirage method is shown to be design unbiased. The proof includes general application to Monte Carlo integration estimators for objects such as CWD sampled from points.
Vector meson fragmentation using a model with broken SU(3) at the next-to-leading order
Authors: Saveetha H. , Indumathi D. , Mitra Subhadip
Published: March 2014

A detailed study of fragmentation of vector mesons at the next-to-leading order (NLO) in QCD is given for e+e- scattering. A model with broken SU(3) symmetry using three input fragmentation functions α(x, Q2), β(x, Q2) and γ(x, Q2) and a strangeness suppression parameter λ describes all the light quark fragmentation functions for the entire vector meson octet. At a starting low energy scale of [Formula: see text] for three light quarks (u, d, s) along with initial parametrization, the fragmentation functions are evolved through DGLAP evolution equations at NLO and the cross-section is calculated. The heavy quarks contribution are added in appropriate thresholds during evolution. The results obtained are fitted at the momentum scale of [Formula: see text] for LEP and SLD data. Good-quality fits are obtained for ρ, K*, ω and ϕ mesons, implying the consistency and efficiency of this model. Strangeness suppression in this model is understood both in terms of ratios of quark fragmentation functions alone as well as in terms of observables; the latter yield a suppression through the K*/ρ multiplicity ratio of about 0.23 while the x dependence of this suppression is also parametrized through the cross-section ratios.
GENETIC MUTATIONS ARE CHARACTERIZED BY INCREASE IN ENTROPY AT THE TRANSCRIPTIONAL LEVEL
Authors: GOV ESRA , ARGA KAZIM YALCIN
Published: March 2014

Predicting the genomic and phenotypic re-programming in organisms undergoing genetic perturbations is a challenging task in modern biology. It is hypothesized that genomic alterations perturb the dynamics of biological information flow. In the present study, a statistical data analysis framework was designed and the network entropy concept was employed to quantify the level of disorder at the transcriptional level as a result of the genomic re-programming of S. cerevisiae cells under genetic perturbations. The customized re-programming in transcription levels to different genetic modifications was observed and genetic mutations were characterized by enhanced network entropies, which revealed higher degree of randomness in mRNA expression levels. To our knowledge, this study constitutes the first numerical demonstration on the conservative energetic state of the microorganisms against genetic perturbations.
DIAGNOSTIC AND THERAPEUTIC TREATMENTS OF PLAQUES IN THE CAROTID BIFURCATION — STUDIES IN MODELS WITH STENTS AND FILTERS
Authors: LIEPSCH D. , BALASSO A. , ZIMMER C. , BERGER H. , BURKHART R. , ECKSTEIN H.-H.
Published: March 2014

Fluid dynamics, especially forces and velocity distribution, influence the development of plaques. Flow parameters: pulsatility, the non-Newtonian flow behavior of blood and wall elasticity are considered. Flow visualization techniques (dyes and birefringent solution with a photo-elasticity apparatus) and LDA measurements demonstrate the importance of the flow. Accurate in vivo velocity measurements are necessary to calculate shear stresses. Different bifurcation angles and flow rate ratios were tested in true to life artery models. The most important fluid dynamic factors at bifurcations are the flow rate ratio and the geometry which create flow separation regions which are responsible for platelet aggregation and intima damage. It is necessary to measure all three velocity components to calculate the velocity vector. The highest shear stresses in a healthy carotid artery are 16 Pa and are found just at the apex. In artery models with 90% stenosis, shear stresses up to 250 Pa were found. Distally, vortices were created where particles remained over several pulse cycles. Measurements show that stents must be selected carefully and placed precisely. Filters must be closed during the systolic phase before removal, so that no trapped particles can escape.
INTIMAL HYPERPLASIA AND WALL SHEAR IN ARTERIAL BYPASS Y-GRAFTING AND CONSEQUENCE GRAFTING: A NUMERICAL STUDY
Authors: DO HUNG , OWIDA AMAL A. , MORSI YOSRY S.
Published: March 2014

The progression of intimal hyperplasia is considered to be the main cause of bypass failure and is directly related to the individual blood rheology, local arterial geometry and placement of the junctions, graft diameter and graft surface characteristics as well as the degree of compliance. In this paper we use commercial computational fluid dynamics (CFD) ANSYS to examine under the correct physiological flow conditions the hemodynamic forces of composite bypass with internal mammary artery in Y-grafting and consequence grafting which is known to achieve high patency rate and highly recommended by clinicians. Particular emphasis is given here on the parameters that could initiate the development of intimal hyperplasia within these bypass configurations. The hemodynamic flow patterns between the consequence grafting and the composite Y-grafting are observed here to be different. Moreover, on both end-to-side and side-to-side configurations, the circulating flows are detected in the vicinity of the junction area, while the Dean flow vortexes are only observed on the end-to-side configuration. Likewise, the hemodynamic flow on the end-to-side configuration on the LCX of both 45° and 90° Y-grafting is found to be smoother than that of the junction on the LCA, regardless of the changing of anastomosis angles. The high WSS gradients are observed at the vicinity of the toe and on the bed of the junction, while the low WSS are presented at the distal of the stenosis and at the stagnation point. The clinical relevance of the results are presented and discussed with particular focus on the factors and the flow patterns that trigger the development of intimal hyperplasia.
Similarities and Differences in the Oncology Drug Approval Process between FDA and European Union with Emphasis on In Vitro Companion Diagnostics
Authors: Senderowicz Adrian M. , Pfaff Otmar
Published: March 2014

Drug approval [U.S. Food and Drug Administration (FDA), or market authorization for the European Union's European Medicines Agency (EMA)] is the most significant regulatory milestone for any drug, as drugs can only be marketed after marketing approval by a health authority. This article focuses on the main regulatory aspects of the drug approval process in the European Union (EU) and the United States. Although the procedures, requirements, and timelines for drug approvals are different between the EU and the United States, several global harmonization efforts have been developed during the past few years to have more consistent regulatory procedures/outcomes in different parts of the world. One of the most different procedures/requirements among these regions is co-development, also known as in vitro companion diagnostic. In the United States, it is expected that for a drug that requires an in vitro diagnostic test to select the population to be treated, the companion diagnostic should be already/concomitantly approved by the FDA. In the EU, these requirements are not as stringent as in the United States. However, it is anticipated that in the very near future, legislation changes in the EU will lead to similar requirements for the companion diagnostics for EMA. In summary, although the principles, procedures, and requirements for drug approvals may differ between the United States and EMA, novel efforts to harmonize them are being considered and implemented, thereby leading to simpler global drug development. It is of outmost importance that drug developers understand and appreciate differences in regional regulations. Otherwise, lack of understanding may lead to rejection or delays in drug approvals for useful anticancer agents.

See all articles in this CCR Focus section, “The Precision Medicine Conundrum: Approaches to Companion Diagnostic Co-development.”

Clin Cancer Res; 20(6); 1445–52. ©2014 AACR.
Disruption of Polycomb Repressor Complex-Mediated Gene Silencing Reactivates HIV-1 Provirus in Latently Infected Cells
Authors: Yoon Cheol-Hee , Jang Dai-Ho , Kim Kyung-Chang , Park Soon Young , Kim Hye-young , Kim Sung Soon , Chi Sung-Gil , Choi Byeong-Sun
Published: March 2014

Objectives: Persistent HIV-1 infections are characterized by a long silent infection period in resting CD4+ T cells, which allows them to escape the host immune response. Several HIV-1 latency mechanisms have been reported, but the molecular mechanism underlying polycomb repressor complex (PRC)-mediated HIV-1 latency remains poorly understood. Methods: Expression of PRC proteins in latent cells was measured by Western blot. Knockdowns of PRC genes were conducted by the specific siRNA and methylations at H3K27 on the proviral LTR were investigated by ChIP assay. Results: PRC proteins (EED, BMI-1, and RNF2) were dramatically downregulated in latent cells after PMA treatment. The downregulation of PRC proteins was followed by a decrease in the methylation of H3K27 and ubiquitination of H2AK119 in the PMA-treated latent cells. siRNA knockdowns of EED and BMI-1 also enhanced HIV-1 reactivation significantly in latently infected cells. By contrast, proteasomal inhibitor MG132 successfully abrogated the PMA-induced downregulation of PRCs. In particular, di-/tri-methylations of histone-3 in the proviral LTR was absent from latent cells after PMA treatment. Conclusions: This study shows that PRC is strongly related to the control of HIV-1 latency and that PRC-breaking agents may be helpful for purging HIV-1 from latent reservoirs.
Gender‐Specific Risk Factors for Peripheral Artery Disease in a Voluntary Screening Population
Authors: Hiramoto Jade S. , Katz Ronit , Weisman Steven , Conte Michael
Published: March 2014

Background

Women have high rates of peripheral artery disease (
PAD
) despite fewer cardiovascular disease (
CVD
) risk factors, compared to men. We sought to determine the gender‐specific prevalence of low ankle brachial index (
ABI
) and the relationship to C‐reactive protein (
CRP
) levels and
CVD
risk factors in the Life Line Screening population.

Methods and Results

Between April 2005 and August 2011, 133 750 women and 71 996 men had
ABI
and
CRP
measured at a Life Line Screening Center. Women were slightly older than men, whereas men were more likely to be current smokers, have diabetes mellitus (
DM
), and coronary artery disease (
CAD
) (
P
<0.001 for each). Women were more likely to have
ABI
≤1.0, compared to men (26.6% versus 14.4%, respectively;
P
<0.001), as well as
ABI
≤0.9 (4.1% women versus 2.6% men;
P
<0.001). Women had higher median
CRP
levels (1.94 mg/L; interquartile range [
IQR],
0.89, 4.44 mg/L), compared to men (1.35 mg/L;
IQR,
0.73, 2.80 mg/L;
P
<0.001). Men and women shared similar risk factors for
ABI
≤0.9, including older age, black race, smoking,
DM
, hypertension, hypercholesterolemia,
CAD
, and elevated
CRP
levels. In an adjusted model, there were significant interactions between gender and age (
P
<0.001),
CRP
(
P
<0.001),
CAD
(
P
=0.03), and
DM
(
P
=0.06) with
ABI
as the outcome. The associations between age,
CRP
,
CAD
, and
DM
with
ABI
≤0.9 were stronger in men than in women.

Conclusions

Women participating in the Life Line Screening had higher
CRP
levels and a higher prevalence of
PAD,
compared to men. Neither higher
CRP
levels nor conventional
CVD
risk factors explained the excess prevalence of
PAD
in women.
Stroke Thrombolysis
Authors: Meretoja Atte , Keshtkaran Mahsa , Saver Jeffrey L. , Tatlisumak Turgut , Parsons Mark W. , Kaste Markku , Davis Stephen M. , Donnan Geoffrey A. , Churilov Leonid
Published: March 2014

Background and Purpose—

Stroke thrombolysis is highly time-critical, but data on long-term effects of small reductions in treatment delays have not been available. Our objective was to quantify patient lifetime benefits gained from faster treatment.

Methods—

Observational prospective data of consecutive stroke patients treated with intravenous thrombolysis in Australian and Finnish centers (1998–2011; n=2258) provided distributions of age, sex, stroke severity, onset-to-treatment times, and 3-month modified Rankin Scale in daily clinical practice. Treatment effects derived from a pooled analysis of thrombolysis trials were used to model the shift in 3-month modified Rankin Scale distributions with reducing treatment delays, from which we derived the expected lifetime and level of long-term disability with faster treatment.

Results—

Each minute of onset-to-treatment time saved granted on average 1.8 days of extra healthy life (95% prediction interval, 0.9–2.7). Benefit was observed in all groups: each minute provided 0.6 day in old severe (age, 80 years; National Institutes of Health Stroke Scale [NIHSS] score, 20) patients, 0.9 day in old mild (age, 80 years; NIHSS score, 4) patients, 2.7 days in young mild (age, 50 years; NIHSS score, 4) patients, and 3.5 days in young severe (age, 50 years; NIHSS score, 20) patients. Women gained slightly more than men over their longer lifetimes. In the whole cohort, each 15 minute decrease in treatment delay provided an average equivalent of 1 month of additional disability-free life.

Conclusions—

Realistically achievable small reductions in stroke thrombolysis delays would result in significant and robust average health benefits over patients’ lifetimes. The awareness of concrete importance of speed could promote practice change.
Use of EEG Workload Indices for Diagnostic Monitoring of Vigilance Decrement
Authors: Kamzanova Altyngul T. , Kustubayeva Almira M. , Matthews Gerald
Published: March 2014

Objective:

A study was run to test which of five electroencephalographic (EEG) indices was most diagnostic of loss of vigilance at two levels of workload.

Background:

EEG indices of alertness include conventional spectral power measures as well as indices combining measures from multiple frequency bands, such as the Task Load Index (TLI) and the Engagement Index (EI). However, it is unclear which indices are optimal for early detection of loss of vigilance.

Method:

Ninety-two participants were assigned to one of two experimental conditions, cued (lower workload) and uncued (higher workload), and then performed a 40-min visual vigilance task. Performance on this task is believed to be limited by attentional resource availability. EEG was recorded continuously. Performance, subjective state, and workload were also assessed.

Results:

The task showed a vigilance decrement in performance; cuing improved performance and reduced subjective workload. Lower-frequency alpha (8 to 10.9 Hz) and TLI were most sensitive to the task parameters. The magnitude of temporal change was larger for lower-frequency alpha. Surprisingly, higher TLI was associated with superior performance. Frontal theta and EI were influenced by task workload only in the final period of work. Correlational data also suggested that the indices are distinct from one another.

Conclusions:

Lower-frequency alpha appears to be the optimal index for monitoring vigilance on the task used here, but further work is needed to test how diagnosticity of EEG indices varies with task demands.

Application:

Lower-frequency alpha may be used to diagnose loss of operator alertness on tasks requiring vigilance.
Theoretical and experimental compressive strength of a glass fiber – vinyl ester pultruded composite
Authors: Thompson Ronald H , Joseph Paul , Delfino Antonio
Published: March 2014

A simple method of compressive strength measurement of a continuously pultruded unidirectional glass-vinyl ester rod is developed. Measured compressive strength was quite high. Compared to a unidirectional composite laminate of the same composition, compressive strength values were doubled. The study shows that glass fiber composites have the potential for high compressive strength. This potential is reached with excellent fiber alignment and suitable matrix characteristics. Results of both laminate and pultruded composites are shown to be consistent with model predictions, with the primary delineating factor being fiber alignment.
More Diverse Yet Less Tolerant? How the Increasingly Diverse Racial Landscape Affects White Americans’ Racial Attitudes
Authors: Craig Maureen A. , Richeson Jennifer A.
Published: March 2014

Recent Census Bureau projections indicate that racial/ethnic minorities will comprise over 50% of the U.S. population by 2042, effectively creating a so-called “majority–minority” nation. Across four experiments, we explore how presenting information about these changing racial demographics influences White Americans’ racial attitudes. Results reveal that exposure to the changing demographics evokes the expression of greater explicit and implicit racial bias. Specifically, Whites exposed to the racial demographic shift information preferred interactions/settings with their own ethnic group over minority ethnic groups; expressed more negative attitudes toward Latinos, Blacks, and Asian Americans; and expressed more automatic pro-White/anti-minority bias. Perceived threat to Whites’ societal status mediated the effects of the racial shift information on explicit racial attitudes. These results suggest that rather than ushering in a more tolerant future, the increasing diversity of the nation may instead yield intergroup hostility. Implications for intergroup relations and media framing of the racial shift are discussed.
Biomechanical Consequences of Coracoclavicular Reconstruction Techniques on Clavicle Strength
Authors: Spiegl Ulrich J. , Smith Sean D. , Euler Simon A. , Dornan Grant J. , Millett Peter J. , Wijdicks Coen A.
Published: March 2014

Background:

Lateral clavicle fractures have been reported after coracoclavicular (CC) ligament reconstructions with bone tunnels through the clavicle.

Purpose:

To biomechanically compare clavicle strength following 2 common CC reconstruction techniques with different bone tunnel diameters.

Study Design:

Controlled laboratory study.

Methods:

Testing was performed on 2 groups of matched-pair cadaveric clavicles. Clavicles were prepared with either 2.4-mm tunnels and cortical fixation button (CFB) devices or 6.0-mm tunnels with hamstring tendon grafts (TGs) and tenodesis screws; contralateral clavicles were left intact. A 3-point bending load was applied to the distal clavicles at a rate of 15 mm/min until failure. Ultimate failure load and anterior-posterior width of the clavicles 45 mm medial from the lateral border were recorded. Strength reduction was determined as the percentage reduction in ultimate failure load between paired intact and surgically prepared clavicles. Relative tunnel size was determined as the quotient of tunnel diameter and clavicle width, reported as a percentage.

Results:

The TG technique significantly reduced clavicle strength relative to intact ( P = .011) and caused significantly more strength reduction (mean, −30.7%; range, 8.1% to −62.5%) than the CFB technique (mean, −3.8%; range, 34.2% to −28.1%; P = .031). The CFB technique was not significantly different from intact ( P = .314). There was a significant correlation between clavicle width and strength reduction (τ = −0.36, P = .04) and between relative tunnel size and strength reduction (τ = 0.51, P = .005).

Conclusion:

The TG reconstruction technique with 6.0-mm tunnels, grafts, and tenodesis screws caused significantly more reduction of clavicle strength compared with the CFB technique with 2.4-mm tunnels and CFB device. Additionally, relative tunnel width correlated highly with the strength reduction.

Clinical Relevance:

This information can influence intraoperative decision making based on the individual clavicle width and might influence postoperative treatment protocols. Large bone tunnels may predispose patients to clavicle fractures after anatomic CC reconstructions.
Significant Publications About the Medication Use Process in 2012
Authors: Moore Sarah J. , Jenkins Alexander T. , Poppe Lindsey B. , Rowe Erinn C. , Eckel Stephen F.
Published: March 2014

Purpose:

This article identifies, prioritizes, and summarizes the published literature on the medication use process (MUP) from calendar year 2012 that can impact health-system pharmacists’ daily practice.

The MUP is the foundational system that provides the framework for safe patient care within the health care environment. The MUP is defined in this article as having the following components: prescribing/transcribing, dispensing, administration, and monitoring. A PubMed search was conducted in January 2013 for calendar year 2012 using targeted Medical Subject Headings (MeSH) keywords, providing a total of 944 articles. A thorough review identified 46 potentially significant articles: 14 for prescribing/transcribing, 12 for dispensing, 10 for administration, and 10 for monitoring. Peer review led to the selection of key articles from each category. These articles are briefly summarized, with a mention of why this article is important within health-system pharmacy. The other articles are listed for further review and evaluation.

Conclusion:

It is important to routinely review the published literature and to incorporate significant findings into daily practice. Health-system pharmacists have an active role in improving the MUP in their institution and awareness of the significant published studies can assist in changing practice at the institutional level.
The Impact of DSM-5 A-Criteria Changes on Parent Ratings of ADHD in Adolescents
Authors: Sibley Margaret H. , Yeguez Carlos E.
Published: March 2014

Objective: Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) A-criteria for ADHD were expanded to include new descriptors referencing adolescent and adult symptom manifestations. This study examines the effect of these changes on symptom endorsement in a sample of adolescents with ADHD (N = 259; age range = 10.72-16.70). Method: Parent ratings were collected and Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; DSM-IV-TR) and DSM-5 endorsement of ADHD symptoms were compared. Results: Under the DSM-5, there were significant increases in reported inattention, but not hyperactivity/impulsivity (H/I) symptoms, with specific elevations for certain symptoms. The average adolescent met criteria for less than one additional symptom under the DSM-5, but the correlation between ADHD symptoms and impairment was attenuated when using the DSM-5 items. Impulsivity items appeared to represent adolescent deficits better than hyperactivity items. Results were not moderated by demographic factors. Conclusion: In a sample of adolescents with well-diagnosed DSM-IV-TR ADHD, developmental symptom descriptors led parents to endorse slightly more symptoms of inattention, but this elevation is unlikely to be clinically meaningful.