bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic review of the association of venous oxygenation and outcome in adult hospitalized patients
Authors: Chemtob R. A. , Eskesen T. G. , Moeller‐Soerensen H. , Perner A. , Ravn H. B. 
Published: September 2016

BackgroundAdequate tissue oxygenation is necessary to maintain organ function. Low venous oxygen saturation may reflect impaired tissue oxygenation, and may be used as a predictive tool and a therapeutic target to improve the care of critically ill patients. We therefore conducted a systematic review of the existing literature reflecting these aspects.MethodsWe searched electronic databases in January 2016 for relevant studies on venous oxygen saturation for treatment guidance and patient outcome. We sub‐grouped results based on patient groups and setting.ResultsThe search resulted in 5590 papers of which 42 studies were deemed relevant. The majority of the studies in cardiac and abdominal surgery patients showed associations between low venous oxygen saturation and increased mortality and morbidity, in particular increased length of intensive care. However, the cut‐off level for low venous oxygen saturation varied between < 55 and 70% and all studies had high risk of bias. In patients with septic shock, recent randomized trials showed no benefit of early resuscitation guided by venous oxygen saturation.ConclusionLow venous oxygen saturation may be associated with increased mortality, morbidity and length of intensive care in patients following cardiac or abdominal surgery. However, the wide range of cut‐off levels and low quality of evidence hampers the clinical application. In patients with septic shock, the present evidence does not support goal‐directed therapy using venous oxygen saturation during early resuscitation.
Evidence of positive selection and concerted evolution in the rapidly evolving PRDM9 zinc finger domain in goats and sheep
Authors: Ahlawat S. , Sharma P. , Sharma R. , Arora R. , Verma N. K. , Brahma B. , Mishra P. , De S. 
Published: September 2016

SummaryMeiotic recombination contributes to augmentation of genetic diversity, exclusion of deleterious alleles and proper segregation of chromatids. PRDM9 has been identified as the gene responsible for specifying the location of recombination hotspots during meiosis and is also the only known vertebrate gene associated with reproductive isolation between species. PRDM9 encodes a protein with a highly variable zinc finger (ZF) domain that varies between as well as within species. In the present study, the ZF domain of PRDM9 on chromosome 1 was characterized for the first time in 15 goat breeds and 25 sheep breeds of India. A remarkable variation in the number and sequence of ZF domains was observed. The number of ZF repeats in the ZF array varied from eight to 12 yielding five homozygous and 10 heterozygous genotypes. The number of different ZF domains was 84 and 52 producing 36 and 26 unique alleles in goats and sheep respectively. The posterior mean of dN/dS or omega values were calculated using the codeml tool of pamlx to identify amino acids that are evolving positively in goats and sheep, as positions −1, +3 and +6 in the ZF domain have been reported to experience strong positive selection across different lineages. Our study identified sites −5, −1, +3, +4 and +6 to be experiencing positive selection. Small ruminant zinc fingers were also found to be evolving under concerted evolution. Our results demonstrate the existence of a vast diversity of PRDM9 in goats and sheep, which is in concert with reports in many metazoans.
Predicting and Interpolating State‐Level Polls Using Twitter Textual Data
Authors: Beauchamp Nicholas 
Published: September 2016

AbstractSpatially or temporally dense polling remains both difficult and expensive using existing survey methods. In response, there have been increasing efforts to approximate various survey measures using social media, but most of these approaches remain methodologically flawed. To remedy these flaws, this article combines 1,200 state‐level polls during the 2012 presidential campaign with over 100 million state‐located political tweets; models the polls as a function of the Twitter text using a new linear regularization feature‐selection method; and shows via out‐of‐sample testing that when properly modeled, the Twitter‐based measures track and to some degree predict opinion polls, and can be extended to unpolled states and potentially substate regions and subday timescales. An examination of the most predictive textual features reveals the topics and events associated with opinion shifts, sheds light on more general theories of partisan difference in attention and information processing, and may be of use for real‐time campaign strategy.
Clinical risk scores in the current era of neoadjuvant chemotherapy for colorectal liver metastases
Authors: Kumar Rohan , Dennison Ashley R. , Robertson Vaux , Jones Michael J. , Neal Christopher P. , Garcea Giuseppe 
Published: September 2016

BackgroundClinical risk scores (CRS) within the context of neoadjuvant chemotherapy for colorectal liver metastases (CRLM) has not been validated. The predictive value of clinical risk scoring in patients administered neoadjuvant chemotherapy prior to liver surgery for CRLM is evaluated.MethodsA prospective database over a 15‐year period (April 1999 to March 2014) was analysed. We identified two groups: A, neoadjuvant chemotherapy prior to CRLM surgery; and B, no neoadjuvant chemotherapy.ResultsOverall median survival in groups A and B were 36 (2–137) months and 33 (2–137) months. In group A, nodal status, size, number of metastases and carcinoembryonic antigen levels were not found to be independent predictors of overall survival (OS). However, patients with a shorter disease‐free interval of less than 12 months had an increased OS (P = 0.0001). Multivariate analysis of high‐ and low‐risk scores compared against survival in group B (P < 0.05) confirms the applicability of the scoring system in traditional settings.ConclusionTraditional CRS are not a prognostic predictive tool when applied to patients receiving neoadjuvant chemotherapy for CRLM. Disease‐free interval may be one independent variable for use in future risk score systems specifically developed for the neoadjuvant chemotherapy era.
Prevalence of non‐union and delayed union in proximal humeral fractures
Authors: Papakonstantinou Maritsa K. , Hart Melissa J. , Farrugia Richard , Gosling Cameron , Kamali Moaveni Afshin , van Bavel Dirk , Page Richard S. , Richardson Martin D. 
Published: September 2016

BackgroundLittle is known about the prevalence of proximal humeral non‐union. There is disagreement on what constitutes union, delayed union and non‐union. Our aim was to determine the prevalence of these complications in proximal humeral fractures (PHFs) admitted to trauma hospitals.MethodsThe Victorian Orthopaedic Trauma Outcomes Registry identified 419 cases of PHFs, of which 306 were analysed. Three upper limb orthopaedic surgeons used X‐rays to classify fractures according to the Neer classification and determine union. Twelve‐item Short Form Health Survey scores were used to assess patient health and wellbeing.ResultsOf 306 cases, 49.4% reached union. Median time to union was 100 days (confidence interval 90–121). Of these, 17.0% united by 60 days, 8.5% united by 89 days and 23.9% united after 90 days, demonstrating ‘prolonged delayed union’. There were 25 non‐unions with a prevalence of 8.2%, most occurring in two‐part surgical neck fractures.ConclusionOur cohort of largely displaced PHFs admitted to trauma hospitals had a non‐union prevalence of 8.2% and an overall delayed union prevalence of 32.4%. Consensus is required on definitions of non‐union and delayed union timeframes.
Microtubule destabilising agents: far more than just antimitotic anticancer drugs
Authors: Bates Darcy , Eastman Alan 
Published: September 2016

Vinca alkaloids have been approved as anticancer drugs for more than 50 years. They have been classified as cytotoxic chemotherapy drugs that act during cellular mitosis, enabling them to target fast growing cancer cells. With the evolution of cancer drug development there has been a shift towards new “targeted” therapies to avoid the side effects and general toxicities of “cytotoxic chemotherapies” such as the vinca alkaloids. Due to their original classification, many have overlooked the fact that vinca alkaloids, taxanes and related drugs do have a specific molecular target: tubulin. They continue to be some of the most effective anticancer drugs, perhaps because their actions upon the microtubule network extend far beyond the ability to halt cells in mitosis, and include the induction of apoptosis at all phases of the cell cycle. In this review, we highlight the numerous cellular consequences of disrupting microtubule dynamics, expanding the textbook knowledge of microtubule destabilising agents and providing novel opportunities for their use in cancer therapy.
Pharmacokinetics and pharmacodynamics of PF‐05190457: The first oral ghrelin receptor inverse agonist to be profiled in healthy subjects
Authors: Denney William S. , Sonnenberg Gabriele E. , Carvajal‐Gonzalez Santos , Tuthill Theresa , Jackson V. Margaret 
Published: September 2016

AimTo evaluate safety, tolerability and pharmacokinetics of oral PF‐05190457, an oral ghrelin receptor inverse agonist, in healthy adults.MethodsSingle (SAD) and multiple ascending dose (MAD) studies were randomised, placebo‐controlled, double‐blind studies. Thirty‐five healthy men (age 38.2 ± 10.4 years; body mass index 24.8 ± 3.1 kg m–2 [mean ± standard deviation]) received ≥1 dose (2, 10, 40 [divided], 50, 100, 150, and 300 [single or divided] mg) of PF‐05190457 and/or placebo in the SAD. In the MAD study, 35 healthy men (age 39.7 ± 10.1 years; body mass index 25.9 ± 3.3 kg m–2) received ≥1 dose (2, 10, 40 and 100 mg twice daily) of PF‐05190457 and/or placebo daily for 2 weeks.ResultsPF‐05190457 absorption was rapid with a Tmax of 0.5–3 hours and a half‐life between 8.2–9.8 hours. PF‐05190457 dose‐dependently blocked ghrelin (1 pmol kg–1 min–1)‐induced growth hormone (GH) release with (mean [90% confidence interval]) 77% [63–85%] inhibition at 100 mg. PF‐05190457 (150 mg) delayed gastric emptying lag time by 30% [7–58%] and half emptying time by 20% [7–35%] with a corresponding decrease in postprandial glucose by 9 mg dL–1. The most frequent adverse event reported by 30 subjects at doses ≥50 mg was somnolence. PF‐05190457 plasma concentrations also increased heart rate up to 13.4 [4.8–58.2] beats min–1 and, similar to the effect on glucose and ghrelin‐induced GH, was lost within 2 weeks.ConclusionsPF‐05190457 is a well‐tolerated first‐in‐class ghrelin receptor inverse agonist with acceptable pharmacokinetics for oral daily dosing. Blocking ghrelin receptors inhibits ghrelin‐induced GH, and increases heart rate, effects that underwent tachyphylaxis with chronic dosing. PF‐051940457 has the potential to treat centrally‐acting disorders such as insomnia.
CRISPR‐Cas9 technology and its application in haematological disorders
Authors: Zhang Han , McCarty Nami 
Published: September 2016

SummaryThe recent advent of the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)‐CRISPR associated protein 9 (Cas9) system for precise genome editing has revolutionized methodologies in haematology and oncology studies. CRISPR‐Cas9 technology can be used to remove and correct genes or mutations, and to introduce site‐specific therapeutic genes in human cells. Inherited haematological disorders represent ideal targets for CRISPR‐Cas9‐mediated gene therapy. Correcting disease‐causing mutations could alleviate disease‐related symptoms in the near future. The CRISPR‐Cas9 system is also a useful tool for delineating molecular mechanisms involving haematological malignancies. Prior to the use of CRISPR‐Cas9‐mediated gene correction in humans, appropriate delivery systems with higher efficiency and specificity must be identified, and ethical guidelines for applying the technology with controllable safety must be established. Here, the latest applications of CRISPR‐Cas9 technology in haematological disorders, current challenges and future directions are reviewed and discussed.
Disclosure policy in Tullock contests with asymmetric stochastic entry
Authors: Fu Qiang , Lu Jingfeng , Zhang Jun 
Published: September 2016

AbstractWe examine how disclosure policy can be optimally designed to incentivize contestants when their participation is exogenously stochastic. In a generalized Tullock contest setting with two players who are asymmetric in both their values and entry probabilities, we fully characterize the necessary and sufficient conditions under which no disclosure dominates full disclosure. We find that the comparison depends solely on a balance effect exercised by entry probabilities on the expected total effort. The optimal disclosure policy must better balance the competition. These conditions continue to hold when the precisionrof Tullock contests is endogenously chosen by the designer.
The effects of wrongful discharge protection on foreign multinationals: Evidence from transaction‐level data
Authors: Kandilov Ivan T. , Senses Mine Z. 
Published: September 2016

AbstractUsing detailed micro‐level data from 1977 to 1994, we analyze the impact of employment protection measures adopted across US states on the number and the value of new inbound foreign direct investment (FDI) transactions completed by foreign‐owned companies. Our findings point to a robust negative association between the implementation of employment protection laws and both the extensive and the intensive margins of FDI in the US. When states adopt regulations that increase employers’ firing costs, FDI transactions by foreign multinational companies become less frequent and decrease in value, with stronger negative impacts in more labour‐intensive industries. There is also some evidence of diversion and spillover effects from the adoption of these measures by neighbouring states.
Exporters and the environment
Authors: Holladay J. Scott 
Published: September 2016

AbstractThis paper documents a relationship between international trade and environmental performance at the plant level. Using a panel of establishment‐level data from 1990–2006, I estimate the relationship between export orientation, import competition and pollution emissions. I find a robust relationship between international trade and pollution levels. Exporters emit 9% to 13% less after controlling for output, but there is significant heterogeneity across industries. Import competition is associated with the exit of the smallest, most pollution‐intensive plants. There is no evidence that this result is caused by polluting firms relocating to countries with low levels of environmental regulation and importing back into the US.
Consumption, housing collateral and the Canadian business cycle
Authors: Christensen Ian , Corrigan Paul , Mendicino Caterina , Nishiyama Shin‐Ichi 
Published: September 2016

AbstractHow important are collateral constraints for reproducing salient features of the data? To address this question, we estimate two nested versions of a New Keynesian model: one with collateralized household debt and the frictionless version of the same model. Both versions of the model are fit to Canadian data using Bayesian methods. We argue that the presence of collateral constraints improves the performance of the model in terms of overall goodness of fit. Housing collateral helps to generate a positive correlation between consumption and house prices. Moreover, housing collateral induced spillovers boosted consumption growth during the housing market boom‐bust cycles of the late 1980s and early 2000s.
Internal trade, productivity and interconnected industries: A quantitative analysis
Authors: Albrecht Lukas , Tombe Trevor 
Published: September 2016

AbstractDoes trade within a country affect welfare and productivity? What are the magnitude and consequences of costs to such trade? To answer these questions, we exploit unique Canadian data to measure internal trade costs in a variety of ways—they are large and vary across sectors and provinces. To quantify their consequences for welfare and productivity, we use a recent multi‐sector trade model featuring rich input–output relationships. We find interprovincial trade is an important contributor to Canada's GDP and welfare, though there are significant costs to such trade. Reducing interprovincial trade costs by 10% yields aggregate gains of 0.9%; eliminating our preferred estimates of costs, gains average between 3% and 7%—equivalent to real GDP gains between $50 billion and $130 billion. Finally, as policy reforms are often sector specific, we liberalize sectors one at a time and find gains are largest in highly interconnected industries.
Payment choice in international trade: Theory and evidence from cross‐country firm‐level data
Authors: Hoefele Andreas , Schmidt‐Eisenlohr Tim , Yu Zhihong 
Published: September 2016

AbstractWhen trading across borders, firms choose between different payment contracts. Theoretically, this should allow firms to trade‐off differences in financing costs and enforcement across countries. This paper provides evidence for this hypothesis employing firm‐level data from a large number of developing countries. As predicted, international transactions are more likely paid after delivery when financing costs in the source country are high and when contract enforcement is low. We extend the theory and also show empirically that the more complex an industry is, the more important is contract enforcement and the less important are financing costs for the contract choice.
The impact of autism services on mothers' psychological wellbeing
Authors: Hodgetts S. , McConnell D. , Zwaigenbaum L. , Nicholas D. 
Published: September 2016

AbstractBackgroundFamilies with a child diagnosed with autism spectrum disorder (ASD) often utilize a variety of professional services. The provision of these services has many potential benefits for families; however, these services also place demands on parents, particularly mothers, to access, navigate and participate. Little is known about how involvement with these services and service systems influences the psychological wellbeing of mothers of children diagnosed with ASD. We examined the relationship between professional services and psychological wellbeing for mothers of children diagnosed with ASD.MethodsMothers (n = 119) of children (mean child age 10.1 years; range 2–24 years) diagnosed with ASD anonymously completed a comprehensive survey. The survey included data related to maternal psychological wellbeing, professional services received and perceptions of these services, and child, mother and household characteristics.ResultsRegression analyses revealed that maternal psychological wellbeing was positively associated with the perceived continuity of services, and negatively associated with the number of professionals involved. Child and maternal age, and household income were also statistically significant predictors of maternal psychological wellbeing.ConclusionsThe study findings draw attention to the potentially negative impact of systems‐level challenges, especially fragmentation of services, on maternal psychological wellbeing, despite positive front‐line services. In particular, our data suggest that psychological wellbeing among mothers of children with ASD may vary more as a function of service system variables than practitioner‐level or child‐level variables.
Double‐barrelled wet colostomy formation after pelvic exenteration for locally advanced or recurrent rectal cancer
Authors: Bloemendaal A. L. A. , Kraus R. , Buchs N. C. , Hamdy F. C. , Hompes R. , Cogswell L. , Guy R. J. 
Published: September 2016

AbstractAimIn advanced pelvic cancer it may be necessary to perform a total pelvic exenteration. In such cases urinary tract reconstruction is usually achieved with the creation of an ileal conduit with a urinary stoma on the right side of the patient's abdomen and an end colostomy separately on the left. The potential morbidity from a second stoma may be avoided by the use of a double‐barrelled wet colostomy (DBWC), as a single stoma. Another advantage is the possibility of using a vertical rectus abdominis muscle flap for perineal reconstruction.MethodAll patients undergoing formation of a DBWC were included.ResultA DBWC was formed in 10 patients. One patient underwent formation of a double‐barrelled wet ileostomy.ConclusionsIn this technical note we present our early experience in 11 cases and a video of DBWC formation in a male patient.
Oncological results of extended resection for locally advanced rectal cancer: the value of postirradiation MRI in predicting local recurrence
Authors: Räsänen M. , Ristimäki A. , Savolainen R. , Renkonen‐Sinisalo L. , Lepistö A. 
Published: September 2016

AbstractAimThe primary purpose of this study was to analyse the overall survival and local recurrence rate after extended resection of locally advanced rectal cancer. The second aim was to determine the ability of the response to radiological irradiation to predict R0 resection.MethodA retrospective study was performed of 94 consecutive patients with locally advanced rectal cancer operated on at the Helsinki University Hospital, Helsinki, Finland between 2005 and 2013. Data were collected from patient records. All patients were treated with an en bloc resection. Sixty‐two patients received preoperative long‐term chemoradiotherapy.ResultsThe 30‐day mortality was 3.2%. Local recurrence occurred in 10 (10.6%) patients. The cumulative 1‐, 3‐ and 5‐year overall survival to each year was 89.4%, 68.3% and 51.8%. The most important prognostic factor for both local recurrence (P = 0.006) and survival (P = 0.003) was an R0 resection. A poor or no response seen on posttreatment MRI predicted local recurrence (P = 0.045) and decreased disease‐free survival in patients treated curatively (P = 0.052). The histological tumour regression grade was not associated with local recurrence or survival.ConclusionMultivisceral resection offers a 5‐year survival of over 50% and local control of advanced rectal cancer in nearly 90% of carefully selected patients.