bluuebunny/crossref_metadata_2025_split huggingface dataset:
CEO Hedging Opportunities and the Weighting of Performance Measures in Compensation Contracts
Authors: Hung Shengmin , Pan Hunghua , Wang Taychang 
Published: May 2019

ABSTRACTThis study examines the rather controversial practice of managerial hedging, which allows CEOs to delink their compensation from stock price performance. We presume that boards are aware of these practices and adjust the weights placed on accounting‐based and stock‐based performance measures in executive compensation contracts to mitigate the problem. Empirically, we find that, in the presence of managerial hedging opportunities, accounting‐based performance measures receive more weight, whereas stock‐based performance measures receive less weight in determining executive compensation. Moreover, these results are more pronounced when managerial hedging needs are high. Regarding the effects of earnings management resulting from accounting‐based incentives, we find that good auditing and strong governance mechanisms strengthen the benefit of placing more weight on accounting‐based performance measures. Taken together, our findings suggest that corporate boards shift the relative weights of performance measures in compensation contracts in response to managerial hedging opportunities, which is consistent with optimal contracting.
Genetic Epidemiology of Liability for Alcohol‐Induced Blacking and Passing Out
Authors: Davis Christal N. , Slutske Wendy S. , Martin Nicholas G. , Agrawal Arpana , Lynskey Michael T. 
Published: May 2019

BackgroundIndividuals differ in their sensitivity to alcohol's physiological effects, including blacking and passing out. Blackouts are periods of impaired memory formation when an individual engages in activities they later cannot recall, while passing out results in loss of consciousness.MethodsThe sample consisted of 3,292 adult twins from the Australian Twin Registry. Univariate twin analyses were conducted to examine the contributions of genetic and environmental influences to blacking and passing out occurrence and susceptibility (accounting for frequency of intoxication). Evidence for shared etiology of susceptibility to blacking and passing out was examined using bivariate twin analyses.ResultsAlthough blacking and passing out were strongly associated (odds ratio (OR) = 4.45, 95% confidence interval (CI): [3.85, 5.14]), the genetic epidemiology was quite different. Genetic (43%) and nonshared environmental (57%) influences contributed to liability for blackout occurrence. For passing out occurrence, there was evidence of sex differences. Among men, genetic (32%) and nonshared environmental (68%) influences contributed, whereas among women, there were shared (29%) and nonshared environmental (72%) influences. After accounting for frequency of intoxication, genetic influences on blackout susceptibility remained significant; in contrast, only nonshared environmental influences were significant for passing out susceptibility. There was evidence for overlapping genetic and nonshared environmental factors influencing susceptibility to blacking and passing out among men; among women, there were overlapping nonshared environmental influences.ConclusionsBlacking and passing out are 2 common sedative‐like effects of heavy drinking, and people differ considerably in their susceptibility to these effects. This study suggests that differences in blackout susceptibility can be explained by genetic factors in both men and women, while differences in susceptibility to pass out after consuming alcohol may be attributable to environmental influences, particularly among women. These environmental factors may include changing social and cultural norms about alcohol use, drinking context, and the type(s) of alcohol consumed.
Metabolic syndrome in rural Australia: An opportunity for primary health care
Authors: Jancey Jonine , James Anthony , Lee Andy , Howat Peter , Hills Andrew P. , Anderson Annie S. , Bordin Cassandra , Blackford Krysten 
Published: May 2019

AbstractObjectiveTo measure the impact of a 6‐month home‐based behaviour change intervention on reducing the risk of chronic disease as determined by metabolic syndrome status and cardiovascular risk score, and discuss implications for primary care in rural areas.DesignA two‐arm randomised controlled trial of rural adults.SettingThe rural town of Albany in the Great Southern region of Western Australia.ParticipantsParticipants (n = 401) aged 50‐69 years who were classified with or at risk of metabolic syndrome and randomly assigned to intervention (n = 201) or waitlisted control (n = 200) group.InterventionsA 6‐month intervention program incorporating goal setting, self‐monitoring and feedback, with motivational interviewing was conducted.Main outcome measuresChange in metabolic syndrome status and cardiovascular risk.ResultsSignificant improvements in metabolic syndrome status and cardiovascular disease risk score (−0.82) were observed for the intervention group relative to control group from baseline to post‐test.ConclusionThis home‐based physical activity and nutrition intervention reduced participants' risk of experiencing a cardiovascular event in the next 5 years by 1%. Incorporating such prevention orientated approaches in primary care might assist in reducing the burden of long‐term chronic diseases. However, for realistic application in this setting, hurdles such as current national health billing system and availability of resources will need to be considered.
Involvement of p38 mitogen‐activated protein kinase in altered expressions of AQP1 and AQP4 after carbon monoxide poisoning in rat astrocytes
Authors: Li Jinlan , Jia Min , Chen Guiqin , Nie Shuke , Zheng Cong , Zeng Weiqi , Xu Yan , Wang Congping , Cao Xuebing , Liu Qunhui 
Published: May 2019

AbstractCerebral oedema is a major pathological change of acute carbon monoxide (CO) poisoning, the pathogenesis of which is still unclear. In the aquaporin (AQP) water channel family, AQP1 and AQP4 play critical roles in the progress of cerebral oedema of various neuropathological events. However, their functions in CO poisoning have not been demonstrated. In this study, we investigated the expressions of AQPs and associated mechanisms of brain injury in an acute CO poisoning rat model. Compared with the control injected intraperitoneally with equal volume of air, the dry weight/wet weight (DW/WW) ratio of brain water content, levels of AQP1, AQP4, phosph‐p38 mitogen‐activated protein kinase (p‐p38 MAPK) and astrocyte marker, glial fibrillary acidic protein (GFAP) in the frontal cortex and hippocampal CA1 of acute CO poisoning group significantly increased at 6, 12, 24 hours after CO injection. Intracerebroventricular injection with a p38 MAPK inhibitor, SB203580 (200 µmol/L/kg/d), before CO injection reduced water content in the brain tissues and significantly decreased levels of AQP1, AQP4, p‐p38 MAPK and GFAP. Therefore, our study showed that the overexpressions of AQP1 and AQP4 were involved in the development of CO poisoning‐induced cerebral oedema, which could be attenuated by inhibition of p‐p38 MAPK signalling. Manipulation of AQPs and p38 MAPK may be a new therapeutic strategy for acute CO poisoning.
Larval experience of stable fly, Stomoxys calcitrans Linneaus, 1758 (Diptera: Muscidae) does not influence oviposition preference in gravid females
Authors: Baleba Steve B.S. , Weldon Christopher W. , Masiga Daniel , Torto Baldwyn , Getahun Merid N. 
Published: May 2019

1. Hopkins' host selection principle (HHSP) proposes that, in holometabolous insects, gravid females prefer to oviposit on their developmental substrate. This hypothesis is widely explored in phytophagous insects, but few studies have considered blood‐feeding insects. In this study, the HHSP was tested using the haematophagous stable fly, Stomoxys calcitrans (Diptera: Muscidae). Using no‐choice and two‐choice tests, the study first sought to demonstrate whether S. calcitrans larvae recognise their rearing substrate.2. It was found that when a rearing substrate is offered to S. calcitrans larvae singly (no‐choice) or associated with a non‐rearing substrate (two‐choice), they were able to recognise the substrate in which they developed. This ability disappeared when larvae were transferred to another substrate for 5 h.3. Next, using oviposition bioassays, it was investigated whether information gathered by pre‐imaginal stages during their development can persist into the adult stages after metamorphosis. It was hypothesised that gravid females emerging from clean and uncleaned pupae reared on sheep and camel dung would still prefer to lay on their rearing substrate. The results revealed that gravid females did not prefer to oviposit on their developmental substrate. In addition, failure to recognise and prefer their developmental substrate was found in gravid females that had emerged from puparia that were cleaned as well as those contaminated with sheep dung.4. It is concluded that S. calcitrans adult preference is not influenced by their offspring's experience. Overall, the HHSP was not supported by our study, suggesting that this principle may not apply to generalist insects characterised by high plasticity in oviposition substrate acceptance.
Evaluating Mean Level and Within‐Person Consistency in Migraine Pain Intensity and Migraine‐Related Disability for AVP‐825 vs Oral Sumatriptan: Results from the COMPASS Study, A Randomized Trial
Authors: McGinley James S. , Buse Dawn C. , Shulman Kenneth J. , Wirth R. J. , Hugentobler Emmanuelle , Lipton Richard B. 
Published: May 2019

BackgroundConsistency of response across multiple attacks is typically measured as the proportion of study participants who achieve a categorical endpoint over a specified number of attacks (ie, 2‐hour pain‐free response in 2 of 3 attacks). We applied a novel analytic approach for measuring consistency of response in the acute treatment of episodic migraine using data from the COMPASS study.MethodsThe COMPASS study (NCT01667679) was a multiple attack crossover study which compared AVP‐825, a Breath Powered® intranasal delivery system for low‐dose sumatriptan powder (22 mg), with 100‐mg oral sumatriptan tablets in the acute treatment of migraine. Participants were 18–65 years old, met ICHD‐2 criteria for migraine with or without aura, and had migraine for ≥1 year prior to screening. They were instructed to treat up to 5 migraine attacks with each treatment and recorded migraine pain intensity and disability data at pre‐dose and 10, 15, 30, 45, 60, 90, and 120 minutes post‐dose for each attack. We explored the mean level and within‐person variability (WPV; a measure of consistency) in migraine pain intensity and migraine‐related disability across multiple attacks after treatment with AVP‐825 (22 mg) vs oral sumatriptan (100 mg) using location scale mixed‐effects models (LSMEMs). LSMEMs controlled for pre‐dose pain/disability, demographics, treatment sequence, and treatment period.ResultsThe mean age was 40 and the sample was 84.6% women. Participants (N = 259) treated an average of 6.8 attacks each during the course of the study. Attacks treated with AVP‐825 showed significantly lower mean pain intensity and mean disability from 10 to 90 minutes post‐dose (effect sizes ranged from −0.09 to −0.29 and P values ranged from P < .0001 to P = .01). WPV was significantly greater at 10–15 minutes (WPV ratios ranged from 1.20 to 1.58 and P values ranged from P < .0001 to P = .04) but significantly reduced from 45 to 120 minutes for attacks treated with AVP‐825 compared to oral sumatriptan (WPV ratios ranged from 0.67 to 0.81 and P values ranged from P < .0001 to P = .03).ConclusionsLSMEMs demonstrate that treatment with AVP‐825 is associated with lower average migraine pain intensity and disability from 10 to 90 minutes and greater within‐person consistency across multiple migraine attacks (reduced WPV) from 45 to 120 minutes post‐dose compared to oral sumatriptan. These findings may reflect the more rapid and consistent absorption of sumatriptan using AVP‐825. Increased WPV with AVP‐825 in the first 15 minutes likely reflects the earlier onset of treatment effects with the device compared to oral sumatriptan. LSMEMs show promise as a novel approach for assessing and comparing consistency of treatment response in migraine trials.
IWRM and the Nexus Approach: Versatile Concepts for Water Resources Education
Authors: Grigg Neil S. 
Published: May 2019

AbstractIntegrated Water Resources Management (IWRM) and the nexus approach are tools to identify solutions for water problems across interdependent sectors with interacting social and natural systems. Although both tools aim at solutions for complex water issues using an interdisciplinary approach, IWRM is a management process and the nexus approach is a systems tool to characterize problems. By clarifying their attributes and providing examples, instructors can use them to explain broad social problems and offer practical frameworks for problem‐solving. Given their breadth, IWRM and the nexus approach can seem vague and attract criticism, but if they are replaced, the need for them will endure. The concepts are explained, and similarities between them are explored in the paper. Case study sources for them are identified, and the cases are classified by the processes of water resources management as applied across related sectors. How the concepts and their corresponding case studies can be used will vary by context. Suggestions are made for interdisciplinary instruction and discussions in disciplinary settings.
Water Scavenging from Roadside Springs in Appalachia
Authors: Krometis Leigh‐Anne , Patton Hannah , Wozniak Austin , Sarver Emily 
Published: May 2019

AbstractSignificant challenges in the provision of safe drinking water and appropriate, effective sanitation remain in the United States, particularly among communities with few financial resources and/or situated in challenging terrain. Though previous formal research is limited, anecdotal reports suggest that some households in Appalachia may rely on untreated, unregulated roadside “springs” as a primary source of potable water. This effort monitored the water quality at twenty‐one of these springs in Central Appalachia and identified potential motivations for this behavior through volunteer surveys in order to better define community challenges and to establish communication for future outreach. The majority (>80%) of spring samples collected were positive for E. coli, indicating a potential risk of exposure to waterborne pathogens; measured concentrations of metals and nutrients were generally in accordance with USEPA recommendations for drinking water. Survey respondents generally had a piped source of in‐home water available yet primarily collected the water due to “taste” and “quality/health” and used it directly for drinking. Multiple respondents included extra written information indicating that they either did not trust their in‐home water source or considered it unreliable. Collectively these results suggest that these roadside springs do serve as a regular source of household water for some communities though they generally do not meet federal drinking water standards. Future efforts are encouraged to work with local municipal water authorities to rebuild community trust and/or to determine whether on‐site treatment at these springs is practicable.
Whole‐genome analysis identifying candidate genes of altitude adaptive ecological thresholds in yak populations
Authors: E Guang‐Xin , Basang Wang‐Dui , Zhu Yan‐Bin 
Published: May 2019

AbstractThe domestic yak (Bos grunniens) is an iconic symbol of animal husbandry on the Qinghai–Tibet Plateau. Long‐term domestication and natural selection have led to a wide distribution of yak, forming many ecological populations to adapt to the local ecological environment. High altitude is closely related to oxygen density, and it is an important environmental ecological factor for biological survival and livestock production. The aim of the present study was to perform a preliminary analysis to identify the candidate genes of altitude distribution adapted ecological thresholds in yak using next‐generation sequence technology. A total of 15,762,829 SNPs were obtained from 29 yaks with high‐ and low‐altitude distribution by genome‐wide sequencing. According to the results of the selective sweep analysis with FST and ZHp, 21 candidate genes were identified. 14 genes (serine/threonine protein kinase TNNI3K, TEN1, DYM, ITPR1, ZC4H2, KNTC1, ADGRB3, CLYBL, TANGO6, ASCC3, KLHL3, PDE4D, DEPDC1B and AGBL4) were grouped into 32 Gene Ontology terms, and four genes (RPS6KA6, ITPR1, GNAO1 and PDE4D) annotated in 35 pathways, including seven environmental information processing and one environmental adaptation. Therefore, the novel candidate genes found in the current study do not only support new theories about high‐altitude adaptation, but also further explain the molecular mechanisms of altitude adaptation threshold in yaks.
Reassessing False Discoveries in Mutual Fund Performance: Skill, Luck, or Lack of Power?
Authors: ANDRIKOGIANNOPOULOU ANGIE , PAPAKONSTANTINOU FILIPPOS 
Published: May 2019

ABSTRACTBarras, Scaillet, and Wermers propose the false discovery rate (FDR) to separate skill (alpha) from luck in fund performance. Using simulations with parameters informed by the data, we find that this methodology is conservative and underestimates the proportion of nonzero‐alpha funds. For example, 65% of funds with economically large alphas of are misclassified as zero alpha. This bias arises from the low signal‐to‐noise ratio in fund returns and the resulting low statistical power. Our results question FDR's applicability in performance evaluation and other domains with low power, and can materially change the conclusion that most funds have zero alpha.
The next‐generation BET inhibitor, PLX51107, delays melanoma growth in a CD8‐mediated manner
Authors: Erkes Dan A. , Field Conroy O. , Capparelli Claudia , Tiago Manoela , Purwin Timothy J. , Chervoneva Inna , Berger Adam C. , Hartsough Edward J. , Villanueva Jessie , Aplin Andrew E. 
Published: May 2019

AbstractEpigenetic agents such as bromodomain and extra‐terminal region inhibitors (BETi) slow tumor growth via tumor intrinsic alterations; however, their effects on antitumor immunity remain unclear. A recent advance is the development of next‐generation BETi that are potent and display a favorable half‐life. Here, we tested the BETi, PLX51107, for immune‐based effects on tumor growth in BRAF V600E melanoma syngeneic models. PLX51107 delayed melanoma tumor growth and increased activated, proliferating, and functional CD8+ T cells in tumors leading to CD8+ T‐cell‐mediated tumor growth delay. PLX51107 decreased Cox2 expression, increased dendritic cells, and lowered PD‐L1, FasL, and IDO‐1 expression in the tumor microenvironment. Importantly, PLX51107 delayed the growth of tumors that progressed on anti‐PD‐1 therapy; a response associated with decreased Cox2 levels, decreased PD‐L1 expression on non‐immune cells, and increased intratumoral CD8+ T cells. Thus, next‐generation BETi represent a potential first‐line and secondary treatment strategy for metastatic melanoma by eliciting effects, at least in part, on antitumor CD8+ T cells.
Acral bullous lichen sclerosus intolerant to UVA‐1 successfully treated with narrowband ultraviolet B phototherapy
Authors: Herz‐Ruelas Maira Elizabeth , Barboza‐Quintana Oralia , Cuéllar‐Barboza Adrián , Cárdenas‐de la Garza Jesús Alberto , Gómez‐Flores Minerva 
Published: May 2019

AbstractLichen sclerosus (LS) is an uncommon, chronic, lymphocyte‐mediated, inflammatory dermatosis characterized by ivory‐white patches with scar‐like atrophy. Extragenital bullous lichen sclerosus may rarely affect palms and soles, causing severe pain and substantially impairing quality of life. We present the first case of acral bullous lichen sclerosus intolerant to UVA‐1 phototherapy successfully treated with low doses of narrowband ultraviolet B phototherapy.
Use of Statin Medications Following Diagnosis in Relation to Survival among Women with Ovarian Cancer
Authors: Harding Barbara N. , Delaney Joseph A. , Urban Renata R. , Weiss Noel S. 
Published: May 2019

Abstract

Background:
It has been suggested that the likelihood of survival among women with ovarian cancer could be increased by postdiagnosis statin use. This study examines the potential association between postdiagnosis statin use and cancer-specific mortality among women with ovarian cancer.

Methods:
This cohort study used SEER-Medicare data on women ≥66 years of age diagnosed with ovarian cancer during 2007 to 2012 who were enrolled in Medicare parts A, B, and D during the year after diagnosis. Statin use was defined as two or more fills for a statin during the year after diagnosis. Ovarian cancer–specific death was assessed starting 1 year after diagnosis. Marginal structural Cox models were used, adjusting for the inverse probability of treatment weighting and censoring weighting. Treatment weights and censoring weights were calculated using logistic regression models with a priori–defined covariates.

Results:
Among 2,195 women with ovarian cancer, 489 (22%) used statins within 1 year after their diagnosis. Over a mean follow-up of 2.2 years, 796 (36%) women died from ovarian cancer. The adjusted HR for ovarian cancer mortality comparing statin users to nonusers was 0.74 (95% confidence interval, 0.61–0.91).

Conclusions:
Findings from this and prior work suggest statin use following a diagnosis with ovarian cancer is associated with a lower risk of cancer death.

Impact:
Because, in most women, statin administration has limited side effects, a randomized trial of statins among patients with ovarian cancer may be warranted.
Mesothelin-Targeted Thorium-227 Conjugate (MSLN-TTC): Preclinical Evaluation of a New Targeted Alpha Therapy for Mesothelin-Positive Cancers
Authors: Hagemann Urs B. , Ellingsen Christine , Schuhmacher Joachim , Kristian Alexander , Mobergslien Anne , Cruciani Véronique , Wickstroem Katrine , Schatz Christoph A. , Kneip Christoph , Golfier Sven , Smeets Roger , Uran Steinar , Hennekes Hartwig , Karlsson Jenny , Bjerke Roger M. , Ryan Olav B. , Mumberg Dominik , Ziegelbauer Karl , Cuthbertson Alan S. 
Published: May 2019

Abstract

Purpose:
Targeted thorium-227 conjugates (TTC) represent a new class of molecules for targeted alpha therapy (TAT). Covalent attachment of a 3,2-HOPO chelator to an antibody enables specific complexation and delivery of the alpha particle emitter thorium-227 to tumor cells. Because of the high energy and short penetration range, TAT efficiently induces double-strand DNA breaks (DSB) preferentially in the tumor cell with limited damage to the surrounding tissue. We present herein the preclinical evaluation of a mesothelin (MSLN)-targeted thorium-227 conjugate, BAY 2287411. MSLN is a GPI-anchored membrane glycoprotein overexpressed in mesothelioma, ovarian, pancreatic, lung, and breast cancers with limited expression in healthy tissue.

Experimental Design:
The binding activity and radiostability of BAY 2287411 were confirmed bioanalytically. The mode-of-action and antitumor potency of BAY 2287411 were investigated in vitro and in vivo in cell line and patient-derived xenograft models of breast, colorectal, lung, ovarian, and pancreatic cancer.

Results:
BAY 2287411 induced DSBs, apoptotic markers, and oxidative stress, leading to reduced cellular viability. Furthermore, upregulation of immunogenic cell death markers was observed. BAY 2287411 was well-tolerated and demonstrated significant antitumor efficacy when administered via single or multiple dosing regimens in vivo. In addition, significant survival benefit was observed in a disseminated lung cancer model. Biodistribution studies showed specific uptake and retention of BAY 2287411 in tumors and enabled the development of a mechanistic pharmacokinetic/pharmacodynamic model to describe the preclinical data.

Conclusions:
These promising preclinical results supported the transition of BAY 2287411 into a clinical phase I program in mesothelioma and ovarian cancer patients (NCT03507452).