bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of downscaled current and future projections of diurnal rainfall patterns for the Himalaya
Authors: Bhatt B. C. , Sobolowski Stefan , King Martin P.
Published: October 2014

In this study we investigate the diurnal precipitation cycle in high‐resolution regional climate simulations for present (2000–2010) and future time periods (2030–2040 and 2040–2050) over subregions of the Himalayas. The future periods are simulated under a high‐emission scenario, Representative Concentration Pathway 8.5 (RCP8.5) in order to maximize any projected externally driven precipitation signal. For present climate, 4‐hourly simulated precipitation is first evaluated against observations to establish model credibility. The diurnal cycle, which is typically characterized by a bimodal structure with primary (secondary) maxima in nighttime (afternoon), is reasonably well represented in the present, giving us confidence when assessing potential future changes. The timing of the precipitation maxima and minima is found to match the observed timings well in the diurnal cycle. In general, the Weather Research and Forecasting model captures the principal shape of the diurnal cycle observed over all the subregions. Under projected future conditions, no significant changes in the diurnal cycle occur. The results suggest modest changes in diurnal precipitation under RCP8.5 emission scenario, as evidenced by an increase in afternoon precipitation around the Himalayas. Although the projected future changes of precipitation presented in this article are within of the expected range of precipitation changes caution must be exercised when interpreting single‐model experiments.
Angiogenic, neurotrophic, and inflammatory system SNPs moderate the association between birth weight and ADHD symptom severity
Authors: Smith Taylor F. , Anastopoulos Arthur D. , Garrett﻿ Melanie E. , Arias‐Vasquez Alejandro , Franke Barbara , Oades Robert D. , Sonuga‐Barke Edmund , Asherson Philip , Gill Michael , Buitelaar Jan K. , Sergeant Joseph A. , Kollins Scott H. , Faraone Stephen V. , Ashley‐Koch Allison ,   the IMAGE Consortium
Published: October 2014

Low birth weight is associated with increased risk for Attention‐Deficit/Hyperactivity Disorder (ADHD); however, the etiological underpinnings of this relationship remain unclear. This study investigated if genetic variants in angiogenic, dopaminergic, neurotrophic, kynurenine, and cytokine‐related biological pathways moderate the relationship between birth weight and ADHD symptom severity. A total of 398 youth from two multi‐site, family‐based studies of ADHD were included in the analysis. The sample consisted of 360 ADHD probands, 21 affected siblings, and 17 unaffected siblings. A set of 164 SNPs from 31 candidate genes, representing five biological pathways, were included in our analyses. Birth weight and gestational age data were collected from a state birth registry, medical records, and parent report. Generalized Estimating Equations tested for main effects and interactions between individual SNPs and birth weight centile in predicting ADHD symptom severity. SNPs within neurotrophic (NTRK3) and cytokine genes (CNTFR) were associated with ADHD inattentive symptom severity. There was no main effect of birth weight centile on ADHD symptom severity. SNPs within angiogenic (NRP1 & NRP2), neurotrophic (NTRK1 & NTRK3), cytokine (IL16 & S100B), and kynurenine (CCBL1 & CCBL2) genes moderate the association between birth weight centile and ADHD symptom severity. The SNP main effects and SNP × birth weight centile interactions remained significant after adjusting for multiple testing. Genetic variability in angiogenic, neurotrophic, and inflammatory systems may moderate the association between restricted prenatal growth, a proxy for an adverse prenatal environment, and risk to develop ADHD. © 2014 Wiley Periodicals, Inc.
Curvilinear association of CGG repeats and age at menopause in women with FMR1 premutation expansions
Authors: Mailick Marsha R. , Hong Jinkuk , Greenberg Jan , Smith Leann , Sherman Stephanie
Published: October 2014

In a sample of post‐menopausal premutation carrier mothers of children with the full mutation of fragile X syndrome (n = 88), this study examined the co‐occurrence of the reproductive and psychiatric phenotypes associated with FMR1 premutations. Mean age at menopause was 43.1 years, and 35.2% of premutation carriers reported cessation of menses prior to age 40 (premature ovarian failure), but only 18% of carriers had been medically diagnosed by a physician as having Fragile X‐associated Primary Ovarian Insufficiency. There was a significant curvilinear association between CGG repeat length and age at menopause, with women who had mid‐range repeats having the earliest menopause, similar to the pattern that has been found for the psychiatric phenotype of the FMR1 premutation. © 2014 Wiley Periodicals, Inc.
Ionizable Amphiphilic Dendrimer‐Based Nanomaterials with Alkyl‐Chain‐Substituted Amines for Tunable siRNA Delivery to the Liver Endothelium In Vivo
Authors: Khan Omar F. , Zaia Edmond W. , Yin Hao , Bogorad Roman L. , Pelet Jeisa M. , Webber Matthew J. , Zhuang Iris , Dahlman James E. , Langer Robert , Anderson Daniel G.
Published: October 2014

A library of dendrimers was synthesized and optimized for targeted small interfering RNA (siRNA) delivery to different cell subpopulations within the liver. Using a combinatorial approach, a library of these nanoparticle‐forming materials was produced wherein the free amines on multigenerational poly(amido amine) and poly(propylenimine) dendrimers were substituted with alkyl chains of increasing length, and evaluated for their ability to deliver siRNA to liver cell subpopulations. Interestingly, two lead delivery materials could be formulated in a manner to alter their tissue tropism within the liver—with formulations from the same material capable of preferentially delivering siRNA to 1) endothelial cells, 2) endothelial cells and hepatocytes, or 3) endothelial cells, hepatocytes, and tumor cells in vivo. The ability to broaden or narrow the cellular destination of siRNA within the liver may provide a useful tool to address a range of liver diseases.
Cationic Gold(III) Alkyl Complexes: Generation, Trapping, and Insertion of Norbornene
Authors: Rekhroukh Feriel , Brousses Rémy , Amgoune Abderrahmane , Bourissou Didier
Published: October 2014

Migratory insertion of alkenes into gold–carbon bonds, a fundamental yet unprecedented organometallic transformation, has been investigated from a discrete (P,C) cyclometalated gold(III) dimethyl complex. Methide abstraction by B(C6F5)3 is shown to generate a highly reactive cationic AuIII complex that evolves spontaneously by C6F5 transfer from boron. In the presence of norbornene, migratory insertion into the AuC bond proceeds readily. The resulting norbornyl complex is efficiently trapped with pyridines or chloride to give stable four‐coordinate adducts.
Kinetics of drug release from drug carrier of polymer/TiO2 nanotubes composite—pH dependent study
Authors: Jia Huiying , Kerr Lei L.
Published: October 2014

This study was to investigate the kinetics of drug release from polymer/TiO2 nanotubes composite. Lidocaine and carprofen were selected as model drugs to represent weak base and weak acid drugs, respectively. Mathematical models used to fit the in vitro drug release experimental data indicate that at higher pH, the drug release was first order diffusion controlled. At lower pH, the release of the two drugs exhibits two staged controlled release mechanism. The first phase is due to drug diffusion and the second stage is a result of poly(lactic‐co‐glycolic acid) (PLGA) polymer degradation. The rate of drug release from polymer/TiO2 nanotubes drug carrier was mainly controlled by three pH dependent factors: the solubility of the drug, the degree of polymer swelling/degradation, and the electrostatic force between polymer and drug. This study suggests that controlled release could be achieved for polymer/TiO2 nanotubes drug carrier via the modulation of pKa values of polymers and drug solubility. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41570.
Synergistic effect between silicone‐containing macromolecular charring agent and ammonium polyphosphate in flame retardant polypropylene
Authors: Lai Xuejun , Yin Changyu , Li Hongqiang , Zeng Xingrong
Published: October 2014

A novel silicone‐containing macromolecular charring agent (Si‐MCA) was synthesized via polycondensation, and it was combined with ammonium polyphosphate (APP) to flame retard polypropylene (PP). The results showed that Si‐MCA exhibited a good synergistic effect with APP in flame retardant PP. When the content of APP was 18.7 wt % and Si‐MCA was 6.3 wt %, the limiting oxygen index value of the PP/APP/Si‐MCA composite was 33.5%, and the vertical burning (UL 94) test classed a V‐0 rating. The peak heat release rate, total heat release, average mass loss rate, and total smoke production of the composite were also decreased significantly. Moreover, the PP/APP/Si‐MCA composite showed an outstanding water resistance. After soaking in 70°C water for 168 h, the PP/APP/Si‐MCA composite could still reach a UL 94 V‐0 rating at 20.0 wt % IFR loading, whereas the PP/APP/PER composite failed to pass the UL 94 test even at 25.0 wt % IFR loading. Thermogravimetric analysis, thermogravimetry‐Fourier transform infrared spectrometry, and scanning electron microscopy‐energy dispersive X‐ray spectrometry results revealed that a compact and thermostable intumescent char was formed by APP/Si‐MCA during burning, thus effectively improved the flame retardancy of PP. The possible synergistic mechanism between APP and Si‐MCA was also discussed. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41580.
Biological evaluation of chitosan‐based in situ‐forming hydrogel with low phase transition temperature
Authors: Dang Qi Feng , Yan Jing Quan , Lin Hong , Liu Cheng Sheng , Chen Xi Guang , Ji Qiu Xia , Li Jing , Liu Ya
Published: October 2014

The aims of current study were to choose a method for preparing sterile chitosan‐α,β‐glycerophosphate (CS‐α,β‐GP) in situ‐forming hydrogel which had potential applications in tissue engineering and evaluated its biocompatibility and degradation characteristics. The results of sterilization stability tests indicated that sterile formulations could be obtained by ultraviolet irradiation of CS powders, 0.22 µm filtration of α,β‐GP and lactic acid solutions, and sterile preparation of CS‐α,β‐GP formulations. The obtained sterile CS‐α,β‐GP formulations showed low hemolysis rates and low BSA adsorption at physiological conditions. When injected in vivo the CS‐α,β‐GP sol turned into gel implant in situ and could be degraded gradually. A minimal inflammatory reaction which could not be found by macroscopic evaluation was induced after injection and new capillary formation was found around the hydrogel humps, making the CS‐α,β‐GP hydrogel worthwhile to be considered for tissue engineering and biomedical applications. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41594.
Retinal Anatomy of the New Zealand Kiwi: Structural Traits Consistent With Their Nocturnal Behavior
Authors: Corfield Jeremy R. , Parsons Stuart , Harimoto Yoshitetsu , Acosta Monica L.
Published: October 2014

Kiwi (Apteryx spp.) have a visual system unlike that of other nocturnal birds, and have specializations to their auditory, olfactory, and tactile systems. Eye size, binocular visual fields and visual brain centers in kiwi are proportionally the smallest yet recorded among birds. Given the many unique features of the kiwi visual system, we examined the laminar organization of the kiwi retina to determine if they evolved increased light sensitivity with a shift to a nocturnal niche or if they retained features of their diurnal ancestor. The laminar organization of the kiwi retina was consistent with an ability to detect low light levels similar to that of other nocturnal species. In particular, the retina appeared to have a high proportion of rod photoreceptors as compared to diurnal species, as evidenced by a thick outer nuclear layer, and also numerous thin photoreceptor segments intercalated among the conical shaped cone photoreceptor inner segments. Therefore, the retinal structure of kiwi was consistent with increased light sensitivity, although other features of the visual system, such as eye size, suggest a reduced reliance on vision. The unique combination of a nocturnal retina and smaller than expected eye size, binocular visual fields, and brain regions make the kiwi visual system unlike that of any bird examined to date. Whether these features of their visual system are an evolutionary design that meets their specific visual needs or are a remnant of a kiwi ancestor that relied more heavily on vision is yet to be determined. Anat Rec, 298:771–779, 2015. © 2014 Wiley Periodicals, Inc.
The ROX coupler: Creation of a fixed iliac arteriovenous anastomosis for the treatment of uncontrolled systemic arterial hypertension, exploiting the physical properties of the arterial vasculature
Authors: Foran John P. , Jain Ajay K. , Casserly Ivan P. , Kandzari David E. , Rocha‐Singh Krishna J. , Witkowski Adam , Katzen Barry T. , Deaton David , Balmforth Peter , Sobotka Paul A.
Published: October 2014

Objectives: Uncontrolled hypertension, whether due to drug resistance or poor adherence and persistence, remains a problem in many patients. The ROX coupler is a novel technology designed to reduce arterial blood pressure consequent to the predicted physical effects of reducing vascular resistance and improving arterial compliance. This article describes the technical aspects of the device and implantation procedure, results from a preclinical study, patient selection criteria, and potential complications of this therapy for uncontrolled hypertension. Background: The coupler is a self‐expanding, stent‐like device that exploits the mechanical effects of the creation of a low‐resistance, high‐compliance venous segment to the central arterial tree, and can be implanted in a standard catheterization laboratory under fluoroscopic guidance. Methods: Preclinical studies were conducted in sheep with acute or chronic hypertension. The devices were implanted in the aorta for up to 12 months. The anastomoses were evaluated for patency, healing, conformation into the artery and vein, and complications. Results: Deployment of the anastomotic device in ovine aortas for up to 12 months showed optimal anastomotic patency in all animals with proper healing and conformation of the device into the artery and the vein. There was no significant residual mural thrombus and minimal to moderate intimal thickening at the vein outflow, consistent with expected arterialization. Conclusions: A novel arteriovenous coupler for percutaneous placement in the iliac vasculature is under clinical investigation as a potential treatment modality for selected patients with uncontrolled hypertension. Initial results from patients with uncontrolled hypertension are expected in Autumn 2014. © 2014 Wiley Periodicals, Inc.
Lignin‐based Microporous Materials as Selective Adsorbents for Carbon Dioxide Separation
Authors: Meng Qing Bo , Weber Jens
Published: October 2014

Suitable solid adsorbents are demanded for carbon capture and storage (CCS) processes. In this work, a novel microporous polymer is developed by hypercrosslinking of organosolv lignin, which is a renewable resource. Reaction with formaldehyde dimethyl acetal (FDA) via Friedel–Crafts reaction gives microporous networks, with moderate capacity of carbon dioxide but excellent selectivity towards CO2/N2 mixture as predicted on the basis of ideal adsorption–solution theory (IAST). Pyrolysis of pure organosolv lignin results in microporous carbon powders, while pyrolysis of hypercrosslinked organosolv lignin yields shape‐persistent materials with increased CO2 capacity while maintaining very good selectivity.
Birth weight and two possible types of maternal effects on male sexual orientation: A clinical study of children and adolescents referred to a Gender Identity Service
Authors: VanderLaan Doug P. , Blanchard Ray , Wood Hayley , Garzon Luisa C. , Zucker Kenneth J.
Published: October 2014

This study tested predictions regarding two hypothesized maternal immune responses influencing sexual orientation: one affecting homosexual males with high fraternal birth order and another affecting firstborn homosexual individuals whose mothers experience repeated miscarriage after the birth of the first child. Low birth weight was treated as a marker of possible exposure to a maternal immune response during gestation. Birth weight was examined relative to sibship characteristics in a clinical sample of youth (N = 1,722) classified as heterosexual or homosexual based on self‐reported or probable sexual orientation. No female sexual orientation differences in birth weight were found. Homosexual, compared to heterosexual, males showed lower birth weight if they had one or more older brothers—and especially two or more older brothers—or if they were an only‐child. These findings support the existence of two maternal immune responses influencing male sexual orientation and possibly also cross‐gender behavior and identity. © 2014 Wiley Periodicals, Inc. Dev Psychobiol 57: 25–34, 2015.
Population structure and phylogeography reveal pathways of colonization by a migratory marine reptile (Chelonia mydas) in the central and eastern Pacific
Authors: Dutton Peter H. , Jensen Michael P. , Frey Amy , LaCasella Erin , Balazs George H. , Zárate Patricia , Chassin‐Noria Omar , Sarti‐Martinez Adriana Laura , Velez Elizabeth
Published: October 2014

Climate, behavior, ecology, and oceanography shape patterns of biodiversity in marine faunas in the absence of obvious geographic barriers. Marine turtles are an example of highly migratory creatures with deep evolutionary lineages and complex life histories that span both terrestrial and marine environments. Previous studies have focused on the deep isolation of evolutionary lineages (>3 mya) through vicariance; however, little attention has been given to the pathways of colonization of the eastern Pacific and the processes that have shaped diversity within the most recent evolutionary time. We sequenced 770 bp of the mtDNA control region to examine the stock structure and phylogeography of 545 green turtles from eight different rookeries in the central and eastern Pacific. We found significant differentiation between the geographically separated nesting populations and identified five distinct stocks (FST = 0.08–0.44, P < 0.005). Central and eastern Pacific Chelonia mydas form a monophyletic group containing 3 subclades, with Hawaii more closely related to the eastern Pacific than western Pacific populations. The split between sampled central/eastern and western Pacific haplotypes was estimated at around 0.34 mya, suggesting that the Pacific region west of Hawaii has been a more formidable barrier to gene flow in C. mydas than the East Pacific Barrier. Our results suggest that the eastern Pacific was colonized from the western Pacific via the Central North Pacific and that the Revillagigedos Islands provided a stepping‐stone for radiation of green turtles from the Hawaiian Archipelago to the eastern Pacific. Our results fit with a broader paradigm that has been described for marine biodiversity, where oceanic islands, such as Hawaii and Revillagigedo, rather than being peripheral evolutionary “graveyards”, serve as sources and recipients of diversity and provide a mechanism for further radiation.
The prevalence and burden of behavioural and psychological symptoms of dementia in rural Tanzania
Authors: Paddick S.‐M. , Kisoli A. , Longdon A. , Dotchin C. , Gray W. K. , Chaote P. , Teodorczuk A. , Walker R.
Published: October 2014

Objectives

Behavioural and psychological symptoms (BPS) in dementia are common in high‐income countries, but there are few data from sub‐Saharan Africa. Our aim was to estimate the prevalence and pattern of BPS and associated caregiver distress in rural Tanzania.

Methods

Prevalent cases of dementia (aged 70 and over) were identified during a community‐based door‐to‐door study in six rural villages in Tanzania. Following cognitive screening, a stratified sample (over‐sampled for people with dementia) of cases underwent a detailed clinical assessment including the brief 12 item neuropsychiatric inventory (NPI‐Q), which assesses BPS and associated caregiver distress over the preceding 30 days.

Results

Of 78 people with dementia, at least one current BPS was reported by 69 (88.4%), with 40 (51.3%) reporting 3 or more symptoms. In 172 people with no cognitive impairment, 110 (64.0%) reported at least one symptom and 48 (27.9%) reported 3 or more. In dementia cases, the most frequent symptoms reported were anxiety (47.4%), agitation/aggression (38.5%), night‐time behavioural disturbance (34.6%), irritability (33.3%) and depression (33.3%).

Conclusion

The frequency of BPS in dementia in this rural Tanzanian population is high and comparable to that reported in prevalence studies from high income countries. Symptoms were also common, although to a lesser degree, amongst cognitively intact subjects. BPS are likely to have a significant impact on quality of life for elderly persons and their carers in low‐income settings. Low‐cost interventions, such as community‐based therapy and education, are needed. Copyright © 2014 John Wiley & Sons, Ltd.
Retinoic acid‐related orphan receptor alpha reprograms glucose metabolism in glutamine‐deficient hepatoma cells
Authors: Byun Jun‐Kyu , Choi Yeon‐Kyung , Kang Yu Na , Jang Byoung Kuk , Kang Koo Jeong , Jeon Yong Hyun , Lee Ho‐Won , Jeon Jae‐Han , Koo Seung‐Hoi , Jeong Won‐Il , Harris Robert A. , Lee In‐Kyu , Park Keun‐Gyu
Published: October 2014

The metabolism of glutamine and glucose is recognized as a promising therapeutic target for the treatment of cancer; however, targeted molecules that mediate glutamine and glucose metabolism in cancer cells have not been addressed. Here, we show that restricting the supply of glutamine in hepatoma cells, including HepG2 and Hep3B cells, markedly increased the expression of retinoic acid‐related orphan receptor alpha (RORα). Up‐regulation of RORα in glutamine‐deficient hepatoma cells resulted from an increase in the level of cellular reactive oxygen species and in the nicotinamide adenine dinucleotide phosphate/nicotinamide adenine dinucleotide phosphate reduced (NADP+/NADPH) ratio, which was consistent with a reduction in the glutathione/glutathione disulfide (GSH/GSSG) ratio. Adenovirus (Ad)‐mediated overexpression of RORα (Ad‐RORα) or treatment with the RORα activator, SR1078, reduced aerobic glycolysis and down‐regulated biosynthetic pathways in hepatoma cells. Ad‐RORα and SR1078 reduced the expression of pyruvate dehydrogenase kinase 2 (PDK2) and inhibited the phosphorylation of pyruvate dehydrogenase and subsequently shifted pyruvate to complete oxidation. The RORα‐mediated decrease in PDK2 levels was caused by up‐regulation of p21, rather than p53. Furthermore, RORα inhibited hepatoma growth both in vitro and in a xenograft model in vivo. We also found that suppression of PDK2 inhibited hepatoma growth in a xenograft model. These findings mimic the altered glucose utilization and hepatoma growth caused by glutamine deprivation. Finally, tumor tissue from 187 hepatocellular carcinoma patients expressed lower levels of RORα than adjacent nontumor tissue, supporting a potential beneficial effect of RORα activation in the treatment of liver cancer. Conclusion: RORα mediates reprogramming of glucose metabolism in hepatoma cells in response to glutamine deficiency. The relationships established here between glutamine metabolism, RORα expression and signaling, and aerobic glycolysis have implications for therapeutic targeting of liver cancer metabolism. (Hepatology 2015;61:953–964)
Crucial roles of mixed‐lineage leukemia 3 and 4 as epigenetic switches of the hepatic circadian clock controlling bile acid homeostasis in mice
Authors: Kim Dae‐Hwan , Rhee Jennifer Chiyeon , Yeo Sujeong , Shen Rongkun , Lee Soo‐Kyung , Lee Jae W. , Lee Seunghee
Published: October 2014

The histone H3‐lysine‐4 methyltransferase mixed‐lineage leukemia 3 (MLL3) and its closest homolog, MLL4 (aka KMT2D), belong to two homologous transcriptional coactivator complexes, named MLL3 and MLL4 complexes, respectively. MLL3 plays crucial roles in multiple metabolic processes. However, the physiological roles of MLL4 in metabolism and the relationship between MLL3 and MLL4 in metabolic gene regulation are unclear. To address these issues, we analyzed the phenotypes of newly generated MLL4 mutant mice, along with MLL3 mutant and MLL3;MLL4 compound mutant mice. We also performed comparative genome‐wide transcriptome analyses in livers of MLL3, MLL4, and MLL3;MLL4 mutant mice. These analyses revealed that MLL3 and MLL4 complexes are key epigenetic regulators of common metabolic processes and the hepatic circadian clock. Subsequent mechanistic analyses uncovered that MLL3/4 complexes function as pivotal coactivators of the circadian transcription factors (TFs), retinoid‐related orphan receptor (ROR)‐α and ‐γ, in the hepatic circadian clock. Consistent with disturbed hepatic clock gene expression in MLL4 mutant mice, we found that rhythmic fluctuation of hepatic and serum bile acid (BA) levels over the circadian cycle is abolished in MLL4 mutant mice. Our analyses also demonstrate that MLL4 primarily impinges on hepatic BA production among several regulatory pathways to control BA homeostasis. Together, our results provide strong in vivo support for important roles of both MLL3 and MLL4 in similar metabolic pathways. Conclusion: Both MLL3 and MLL4 complexes act as major epigenetic regulators of diverse metabolic processes (including circadian control of bile acid homeostasis) and as critical transcriptional coactivators of the circadian TFs, RORs. (Hepatology 2015;61:1012–1023)
Derivation of human health‐based ambient water quality criteria: A consideration of conservatism and protectiveness goals
Authors: Tatum Vickie , Wiegand Paul , Stratton Steve , Louch Jeffrey , Ebert Ellen , Anderson Paul
Published: October 2014

Under the terms of the Clean Water Act, criteria for the protection of human health (Human Health Ambient Water Quality Criteria [HHWQC]) are traditionally derived using equations recommended by the US Environmental Protection Agency (USEPA) that include parameters for exposure assessment. To derive “adequately protective” HHWQC, USEPA proposes the use of default values for these parameters that are a combination of medians, means, and percentile estimates targeting the high end (90th percentile) of the general population. However, in practice, in nearly all cases, USEPA's recommended default assumptions represent upper percentiles. This article considers the adequacy of the exposure assessment component of USEPA‐recommended equations to yield criteria that are consistent with corresponding health protection targets established in USEPA recommendations or state policies, and concludes that conservative selections for exposure parameters can result in criteria that are substantially more protective than the health protection goals for HHWQC recommended by USEPA, due in large part to the compounding effect that occurs when multiple conservative factors are combined. This situation may be mitigated by thoughtful selection of exposure parameter values when using a deterministic approach, or by using a probabilistic approach based on data distributions for many of these parameters. Integr Environ Assess Manag 2015;11:298–305. © 2014 SETAC
Effects of coal fly ash on tree swallow reproduction in Watts Bar Reservoir, Tennessee
Authors: Walls Suzanne J , Meyer Carolyn B , Iannuzzi Jacqueline , Schlekat Tamar H
Published: October 2014

Coal-fly ash was released in unprecedented amounts (4.1 × 106 m3) into the Emory River from the Tennessee Valley Authority Kingston Fossil Plant on Watts Bar Reservoir in Tennessee. Tree swallows were exposed to ash-related constituents at the ash release via their diet of emergent aquatic insects, whose larval forms can accumulate constituents from submerged river sediments. Reproduction of tree swallow colonies was assessed over a 2-year period by evaluating whether 1) ash constituent concentrations were elevated in egg, eggshell, and nestling tissues at colonies near ash-impacted river reaches compared to reference colonies, 2) production of fledglings per nesting female was significantly lower in ash-impacted colonies versus reference colonies, and 3) ash constituent concentrations or diet concentrations were correlated with nest productivity measures (clutch size, hatching success, and nestling survival, and fledglings produced per nest). Of the 26 ash constituents evaluated, 4 (Se, Sr, Cu, and Hg) were significantly elevated in tissues potentially from the ash, and 3 (Se, Sr, and Cu) in tissues or in swallow diet items were weakly correlated to at least one nest-productivity measure or egg weight. Tree swallow hatching success was significantly reduced by 12%, but fledgling production per nest was unaffected due to larger clutch sizes in the impacted than reference colonies. Bioconcentration from the ash to insects in the diet to tree swallow eggs appears to be low. Overall, adverse impacts of the ash on tree swallow reproduction were not observed, but monitoring is continuing to further ensure Se from the residual ash does not adversely affect tree swallow reproduction over time. Integr Environ Assess Manag 2015;11:56–66. © 2014 SETAC

Key Points

Tree swallow hatching success was significantly reduced at colonies exposed to coal fly ash. Some selenium concentrations in eggs exceeded a toxic threshold of 7.7 mg/kg dw. Productivity was not significantly correlated to selenium. Adverse impacts of ash to tree swallow reproduction were minor.
Application of ecological risk assessment in managing residual fly ash in TVA's Watts Bar Reservoir, Tennessee
Authors: Carriker Neil E , Jones Daniel S , Walls Suzanne J , Stojak Amber R
Published: October 2014

The Tennessee Valley Authority conducted a Baseline Ecological Risk Assessment (BERA) for the Kingston Fossil Plant ash release site to evaluate potential effects of residual coal ash on biota in Watts Bar Reservoir, Tennessee. The BERA was in response to a release of 4.1 million m3 of coal ash on December 22, 2008. It used multiple lines of evidence to assess risks for 17 different ecological receptors to approximately 400 000 m3 of residual ash in the Emory and Clinch rivers. Here, we provide a brief overview of the BERA results and then focus on how the results were used to help shape risk management decisions. Those decisions included selecting monitored natural recovery for remediation of the residual ash in the Emory and Clinch rivers and designing a long-term monitoring plan that includes adaptive management principles for timely adjustment to changing conditions. This study demonstrates the importance of site-specific ecological data (e.g., tissue concentrations for food items, reproductive data, and population data) in complex ecological risk assessments. It also illustrates the value of the US Environmental Protection Agency's (USEPA) data quality objectives process in building consensus and identifying multiple uses of results. The relatively limited adverse effects of this likely worst-case scenario for ash-related exposures in a lotic environment provide important context for the USEPA's new coal combustion residue disposal rules. Integr Environ Assess Manag 2015;11:80–87. © 2014 SETAC

Key Points

Ecological risks of residual ash in the river system were found to be at most moderate and generally low or negligible. Risk-management was deemed necessary for benthic invertebrates and birds that consume them, due to ash, arsenic, and selenium. These results contrast starkly with the catastrophic predictions by respected researchers and others The results were critical to the selection of monitored natural recovery as the remedy and are important benchmarks for the ongoing debate about coal combustion residuals disposal regulations.
Assessing ecological risks to the fish community from residual coal fly ash in Watts Bar Reservoir, Tennessee
Authors: Rigg David K , Wacksman Mitch N , Iannuzzi Jacqueline , Baker Tyler F , Adams Marshall , Greeley Mark S
Published: October 2014

Extensive site-specific biological and environmental data were collected to support an evaluation of risks to the fish community in Watts Bar Reservoir from residual ash from the December 2008 Tennessee Valley Authority (TVA) Kingston ash release. This article describes the approach used and results of the risk assessment for the fish community, which consists of multiple measurement endpoints (measures of exposure and effects) for fish. The lines of evidence included 1) comparing postspill annual fish community assessments with nearby prespill data and data from other TVA reservoirs, 2) evaluating possible effects of exposures of fish eggs and larval fish to ash in controlled laboratory toxicity tests, 3) evaluating reproductive competence of field-exposed fish, 4) assessing individual fish health through physical examination, histopathology, and blood chemistry, 5) comparing fish tissue concentrations with literature-based critical body residues, and 6) comparing concentrations of ash-related contaminants in surface waters with US Environmental Protection Agency's (USEPA) Ambient Water Quality Standards for Fish and Aquatic Life. These measurement endpoints were treated as independent lines of evidence that were integrated into an overall weight-of-evidence estimate of risk to the fish community. Collectively, the data and analysis presented here indicate that ash and ash-related constituents pose negligible risks to the fish communities in Watts Bar Reservoir. This conclusion contradicts the predictions by some researchers immediately following the ash release of devastating effects on the aquatic ecology of Watts Bar Reservoir. The information presented in this article reaffirms the wisdom of carefully evaluating the evidence before predicting probable ecological effects of a major event such as the TVA Kingston ash release. This study demonstrates that a thorough and detailed investigation using multiple measurement endpoints is needed to properly evaluate ecological effects. Integr Environ Assess Manag 2015;11:88–101. © 2014 SETAC

Key Points

The manuscript describes a weight-of-evidence approach to evaluate multiple lines of evidence for fish, including detailed fish community, fish toxicity, and fish reproduction studies. The results indicate that levels of some ash-related constituents exceeded water quality criteria in surface waters and critical body residues in fish tissues. However, given the uncertainty using comparisons with these literature-derived effects values contribute little to the overall assessment of risks to fish. Conversely, the lack of effects observed for the community surveys, toxicity tests, and reproductive competence evaluations suggest that ash and ash-related constituents pose negligible risks to the fish communities in the Watts Bar Reservoir.
Cancer incidence and mortality among members of the Danish resistance movement deported to German concentration camps: 65‐Year follow‐up
Authors: Olsen Maja Halgren , Nielsen Henrik , Dalton Susanne Oksbjerg , Johansen Christoffer
Published: October 2014

The widespread belief that a stressful life event increases cancer incidence and mortality was investigated in a unique cohort of all Danish male political prisoners, who survived the extremely stressful experience of life in German concentration camps between 1943 and 1945. A virtually complete cohort of all 1,322 Danish male political prisoners who survived deportation to German concentration camps were followed up for cancer incidence and all‐cause and cancer‐specific mortality from 1946 through 2010. Standardized ratios and 95% confidence intervals were calculated from the observed and expected numbers of cancers or deaths, the latter based on national rates. We observed slightly increased standardized cancer incidence ratio (SIR 1.16; 95% CI, 1.06–1.27), particularly of smoking‐ or alcohol‐related cancers (SIR 1.31; 95% CI, 1.15–1.49) and nonsignificantly increased SIR of immune system‐ and hormone‐related cancers (SIR 1.17; 95% CI, 0.80–1.65 and 1.05; 95% CI, 0.81–1.34 respectively). Both the standardized all‐cause mortality ratio (SMR 1.11; 95% CI, 1.05–1.18) and cancer specific mortality ratio (SCMR 1.17; 95% CI, 1.01–1.26) were slightly increased, particularly from smoking‐ or alcohol‐related cancers (SCMR 1.25; 95% CI, 1.06–1.45). The minor increased cancer incidence and cancer mortality among the survivors is probably not directly associated with exposure to this extreme stressful event, but may be indirectly mediated through behavioral responses to psychological stress, as reflected in the increased incidence of and mortality from tobacco‐ and alcohol‐related cancers.
Triaging HPV‐positive women with normal cytology by p16/Ki‐67 dual‐stained cytology testing: Baseline and longitudinal data
Authors: Uijterwaal Margot H. , Polman Nicole J. , Witte Birgit I. , van Kemenade Folkert J. , Rijkaart Dorien , Berkhof Johannes , Balfoort‐van der Meij G.A.M.A. , Ridder Ruediger , Snijders Peter J.F. , Meijer Chris J.L.M.
Published: October 2014

Primary human papillomavirus (HPV)‐based screening results in a 2–5% lower specificity for cervical intraepithelial neoplasia Grade 2 or worse (CIN2+) compared to Pap cytology. To identify HPV‐positive women with CIN2+, we retrospectively evaluated the cross‐sectional and longitudinal performance of p16/Ki‐67 dual‐stained cytology in HPV‐positive women with normal cytology participating in population‐based cervical screening. Conventional Pap cytology specimens of 847 of these women derived from the VUSA‐Screen study were dual‐stained for p16/Ki‐67. Cross‐sectional clinical performance in detecting CIN3 or worse (CIN3+), and CIN2+ was compared to that of baseline HPV genotyping. Moreover, 5‐year cumulative incidence risks (CIR) for CIN3+ (CIN2+) were determined. The sensitivity of p16/Ki‐67 dual‐stained cytology for CIN3+ (CIN2+) was 73.3% (68.8%) with a specificity of 70.0% (72.8%). HPV16/18 genotyping showed a sensitivity for CIN3+ (CIN2+) of 46.7% (43.8%), with a specificity of 78.3% (79.4%). The 5‐year CIR for CIN3+ in HPV‐positive women with normal cytology was 6.9%. Testing these women with p16/Ki‐67 dual‐stained cytology resulted in a significantly lower CIN3+ 5‐year CIR of 3.3% (p = 0.017) in case of a negative test result. A negative HPV16/18 genotyping test result also led to a lower 5‐year CIN3+ CIR of 3.6%. p16/Ki‐67 dual‐stained cytology detects more than 70% of underlying CIN3+ lesions in HPV‐positive women with normal cytology at baseline and is therefore suitable for triaging these women to colposcopy. Furthermore, the CIN3+ 5‐year CIR of 3.3% after a negative dual‐stain result is significantly lower compared to the 5‐year CIR of 6.9% in women without p16/Ki‐67 dual‐stained cytology triage.
Identification of HERC5 and its potential role in NSCLC progression
Authors: Wrage Michaela , Hagmann Wolfgang , Kemming Dirk , Uzunoglu Faik G. , Riethdorf Sabine , Effenberger Katharina , Westphal Manfred , Lamszus Katrin , Kim Soo‐Zin , Becker Natalia , Izbicki Jakob R. , Sandoval Juan , Esteller Manel , Pantel Klaus , Risch Angela , Wikman Harriet
Published: October 2014

For better lung cancer diagnosis and therapy, early detection markers of tumor dissemination are urgently needed, as most lung cancers do not show symptoms until extensive metastasis formation has already taken place. Our previous studies showed that in non‐small cell lung cancer (NSCLC) early tumor dissemination is associated with a loss of chromosome 4q12‐q32 and the presence of disseminated tumor cells (DTC) in the bone marrow. In order to identify the potential target gene in this region, a screen for methylation‐dependent expression was performed. Lung cancer cell lines showing a loss of 4q as well as a normal bronchial epithelial cell line as control were treated with 5‐aza‐2'‐deoxycytidine (5‐aza‐CdR) followed by expression profiling. Seven genes within the 4q target region, which have been associated with a positive DTC status before were found to be regulated by hypermethylation. QRT‐PCR in an independent sample set identified HERC5 as a potential target gene. Quantitative methylation analysis of these lung tissue samples revealed that HERC5 promoter hypermethylation was significantly associated with positive DTC status (p = 0.020) and occurrence of brain metastases (p = 0.015). In addition, hypermethylation of the HERC5 promoter in NSCLC was identified as a predictor for poor survival for Stage I adenocarcinoma patients (p = 0.022) and also for poor overall survival in metastatic lung cancer patients (p = 0.028). In conclusion, HERC5 may function as a prognostic marker and is associated with tumor dissemination in lung cancer.
Grid‐based algorithm to search critical points, in the electron density, accelerated by graphics processing units
Authors: Hernández‐Esparza Raymundo , Mejía‐Chica Sol‐Milena , Zapata‐Escobar Andy D. , Guevara‐García Alfredo , Martínez‐Melchor Apolinar , Hernández‐Pérez Julio‐M. , Vargas Rubicelia , Garza Jorge
Published: October 2014

Using a grid‐based method to search the critical points in electron density, we show how to accelerate such a method with graphics processing units (GPUs). When the GPU implementation is contrasted with that used on central processing units (CPUs), we found a large difference between the time elapsed by both implementations: the smallest time is observed when GPUs are used. We tested two GPUs, one related with video games and other used for high‐performance computing (HPC). By the side of the CPUs, two processors were tested, one used in common personal computers and other used for HPC, both of last generation. Although our parallel algorithm scales quite well on CPUs, the same implementation on GPUs runs around 10× faster than 16 CPUs, with any of the tested GPUs and CPUs. We have found what one GPU dedicated for video games can be used without any problem for our application, delivering a remarkable performance, in fact; this GPU competes against one HPC GPU, in particular when single‐precision is used. © 2014 Wiley Periodicals, Inc.
Trending Now: Digital Leadership Education Using Social Media and the Social Change Model
Authors: Ahlquist Josie
Published: October 2014

The current article examines social media applications as a tool for positive social change. The number of users on applications from Facebook to Twitter and Instagram continues to increase in all demographics. These tools are being integrated into our daily activities and challenging boundaries, roles, and even possibilities globally. Currently, there exists a gap in developing competent leaders capable of leading change using social media. Education leaders and leadership education programs can adapt the values of the Social Change Model to reflect and apply digital competencies to their practice. Digital leadership requires reflection on online self‐awareness and congruence, grappling with the controversy that comes with cyber civility and how to be a digital citizen prepared to inspire positive social change.
Genomic medicine for cancer diagnosis
Authors: Gordon Benjamin L. , Finnerty Brendan M. , Aronova Anna , Fahey Thomas J.
Published: October 2014

Genomic diagnostics in cancer has evolved since the completion of the Human Genome Project and the advancements made in diagnosis and therapy in chronic myelogenous leukemia. Among the diseases to achieve limited success or potentially benefit from diagnostic genetic testing are thyroid cancer, Burkitt's lymphoma, gastrointestinal stromal tumors, adrenocortical carcinoma, and colorectal cancer. With increased understanding of genomics, genetic tests should improve diagnosis and help guide medical and surgical management. J. Surg. Oncol. 2015 111:24–30. © 2014 Wiley Periodicals, Inc.
BRAF V600E mutations are frequent in dysembryoplastic neuroepithelial tumors and subependymal giant cell astrocytomas
Authors: Lee Dakeun , Cho Young Hye , Kang So Young , Yoon Nara , Sung Chang Ohk , Suh Yeon‐Lim
Published: October 2014

Background

BRAF mutation has received a great deal of attention in neuro‐oncology field, recently. This study aimed to investigate the incidence and the clinical significance of BRAFV600E in low‐grade glial tumors.

Methods

An institutional cohort of 105 brain tumors (51 dysembryoplastic neuroepithelial tumors (DNTs), 14 subependymal giant cell astrocytomas (SEGAs), 12 glioblastoma with neuronal marker expression (GBM‐N), and 28 pleomorphic xanthoastrocytomas (PXAs)) from 100 patients were investigated for the presence of BRAFV600E by direct sequencing.

Results

We found frequent BRAFV600E in DNTs (26/51, 51%), SEGAs (6/14, 42.9%), and PXAs (14/28, 50%). In DNTs, BRAFV600E was more commonly detected in tumors with extra‐temporal location (68.2% vs. 37.9%; P = 0.032). The diagnostic subgroups of tuberous sclerosis complex were not correlated with BRAFV600E in patients with SEGA (P = 0.533). One PXA case revealed a unique duplication mutation (p.Thr599dup) of codon 599. All GMB‐N cases did not carry BRAF mutation.

Conclusions

Our data indicate that BRAFV600E is a common genetic alteration in low‐grade glial tumors with neuronal component or differentiation. High frequency of BRAFV600E in DNTs and SEGAs would be useful in the differential diagnosis, and also offers a potential specific treatment targeting BRAFV600E. J. Surg. Oncol. 2015 111:359–364. © 2014 Wiley Periodicals, Inc.
Raman spectroscopy differentiates squamous cell carcinoma (SCC) from normal skin following treatment with a high‐powered CO2 laser
Authors: Fox Sara A. , Shanblatt Ashley A. , Beckman Hugh , Strasswimmer John , Terentis Andrew C.
Published: October 2014

Background and Objectives

The number of cases of non‐melanoma skin cancer (NMSC), which include squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), continues to rise as the aging population grows. Mohs micrographic surgery has become the treatment of choice in many cases but is not always necessary or feasible. Ablation with a high‐powered CO2 laser offers the advantage of highly precise, hemostatic tissue removal. However, confirmation of complete cancer removal following ablation is difficult. In this study we tested for the first time the feasibility of using Raman spectroscopy as an in situ diagnostic method to differentiate NMSC from normal tissue following partial ablation with a high‐powered CO2 laser.

Materials and Methods

Twenty‐five tissue samples were obtained from eleven patients undergoing Mohs micrographic surgery to remove NMSC tumors. Laser treatment was performed with a SmartXide DOT Fractional CO2 Laser (DEKA Laser Technologies, Inc.) emitting a wavelength of 10.6 μm. Treatment levels ranged from 20 mJ to 1200 mJ total energy delivered per laser treatment spot (350 μm spot size). Raman spectra were collected from both untreated and CO2 laser‐treated samples using a 785 nm diode laser. Principal Component Analysis (PCA) and Binary Logistic Regression (LR) were used to classify spectra as originating from either normal or NMSC tissue, and from treated or untreated tissue.

Results

Partial laser ablation did not adversely affect the ability of Raman spectroscopy to differentiate normal from cancerous residual tissue, with the spectral classification model correctly identifying SCC tissue with 95% sensitivity and 100% specificity following partial laser ablation, compared with 92% sensitivity and 60% selectivity for untreated NMSC tissue. The main biochemical difference identified between normal and NMSC tissue was high levels of collagen in the normal tissue, which was lacking in the NMSC tissue.

Conclusion

The feasibility of a combined high‐powered CO2 laser ablation, Raman diagnostic procedure for the treatment of NMSC is demonstrated since CO2 laser treatment does not hinder the ability of Raman spectroscopy to differentiate normal from diseased tissue. This combined approach could be employed clinically to greatly enhance the speed and effectiveness of NMSC treatment in many cases. Lasers Surg. Med. 46:757–772, 2014. © 2014 Wiley Periodicals, Inc.