bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase 1/2 study assessing the safety and efficacy of dabrafenib and trametinib combination therapy in Japanese patients with BRAF V600 mutation‐positive advanced cutaneous melanoma
Authors: Yamazaki Naoya , Tsutsumida Arata , Takahashi Akira , Namikawa Kenjiro , Yoshikawa Shusuke , Fujiwara Yutaka , Kondo Shunsuke , Mukaiyama Akihira , Zhang Fanghong , Kiyohara Yoshio 
Published: February 2018

AbstractThe combination of dabrafenib and trametinib demonstrated encouraging antitumor activity and tolerability, at initial analysis, in Japanese patients with BRAF V600 mutant advanced melanoma warranting further investigation. This study evaluated the safety and tolerability, pharmacokinetics (PK) and preliminary efficacy of dabrafenib 150 mg b.i.d. plus trametinib 2 mg q.d. in Japanese patients with BRAF V600E/K mutant solid tumors (phase 1) and melanoma (phase 2). Phase 1 was primarily intended to assess safety and tolerability as assessed by adverse events (AE), and the primary end‐point in phase 2 was to assess confirmed overall response rate (ORR). The secondary end‐points in phase 1 included PK, confirmed/unconfirmed ORR and duration of response (DOR). The secondary end‐points in phase 2 were PK, unconfirmed ORR, DOR, safety and tolerability. A total of 12 cutaneous melanoma patients were enrolled in the study (six in phase 1 and six in phase 2) and received the combination therapy of dabrafenib and trametinib. Common AE (≥50.0%) included pyrexia (75%), increased aspartate aminotransferase (67%), peripheral edema (50%) and nasopharyngitis (50%). The investigator‐assessed ORR was reported in five patients (83%) in phase 1 and was also reported in five patients (83%; 95% confidence interval, 35.9–99.6; P < 0.0001) in phase 2. Plasma concentrations of both dabrafenib and trametinib seemed to a reach steady state by week 3. Overall, efficacy and PK properties for the dabrafenib plus trametinib combination in Japanese patients were comparable with those seen in global studies.
Efficacy of oral cholecalciferol on rhododendrol‐induced vitiligo: A blinded randomized clinical trial
Authors: Watabe Akiko , Yamasaki Kenshi , Asano Masayuki , Kanbayashi Yumi , Nasu‐Tamabuchi Mei , Terui Hitoshi , Furudate Sadanori , Kakizaki Aya , Tsuchiyama Kenichiro , Kimura Yutaka , Ito Yumiko , Kikuchi Katsuko , Aiba Setsuya 
Published: February 2018

AbstractRhododendrol (RD), 4‐(4‐hydroxyphenyl)‐2‐butanol, inhibits melanin synthesis and has been used for skin‐whitening cosmetic products. RD has been very effective in lightening skin pigmentation, but some persons have developed so‐called RD vitiligo, in which vitiligo starts on the face, neck and hands where topical RD has been applied and even extended over skin areas where RD has not been applied. RD vitiligo lesions in some patients have lasted for years and have been resistant to conventional vitiligo treatments. We examined the effects of cholecalciferol on RD vitiligo in a blinded randomized clinical trial. Forty‐eight female RD vitiligo patients were recruited for the trial and were randomized into two groups: the vitamin D (VD)‐intervention group that received daily 5000 IU cholecalciferol for 5 months and the control group. Three blinded investigators scored vitiligo improvement by comparing photographic images of baseline and at 5‐month observation. Serum 25(OH)D3 of RD vitiligo patients was not significantly different from age‐matched healthy volunteers. Twenty‐two in the VD‐intervention group and 23 in the control group completed the 5‐month observation. Serum 25(OH)D3 levels were significantly increased after the 5‐month VD intervention, while the control group did not change. The improvement scores were significantly higher in the VD‐intervention group than the control group. The improvement scores were positively correlated with the serum 25(OH)D3 levels after the 5‐month intervention period but not before the treatment. This blinded randomized clinical trial showed favor in administrating 5000 IU cholecalciferol daily to RD vitiligo patients.
Spatial prioritisation of EU's LIFE‐Nature programme to strengthen the conservation impact of Natura 2000
Authors: Hermoso Virgilio , Villero Dani , Clavero Miguel , Brotons Lluís 
Published: February 2018

Abstract

Despite advances in conservation efforts within Europe during recent decades, assessments highlight a need for adequate financing mechanisms to support the Natura 2000 network, the centrepiece of the EU's Biodiversity Strategy. Besides the need for greater investment (currently only covering a fifth of the estimated cost of the network), better planning for this investment could help better achieve conservation goals.

We demonstrate a method that could be used to identify priority Natura 2000 sites, and species therein, that could guide investment in the future. We first used the lists of key species associated with each Natura 2000 site to map the distribution of all priority species covered by the Birds and Habitats Directives. We then used Marxan software to prioritise allocation of conservation funds among all Natura 2000 sites, while trying to mimic the observed conservation effort implemented under the LIFE programme, the main financial tool of the EU's Biodiversity Strategy, in the period 1992–2013.

Some Natura 2000 sites show exceptional value, holding species that either do not, or only very rarely, occur elsewhere in the network. These priority sites were concentrated mainly on islands and in the south western, eastern and northern extremes of Europe's mainland, thus reflecting patterns in species richness and endemism.

We found a poor relationship between the priorities identified here and the way funds had been distributed in previous LIFE‐Nature programmes.

Policy implications. We propose that prioritisation exercises like the one shown here could be used to inform a top‐down EU regulation mechanism by providing lists of site and species priorities that better reflect European conservation needs. These recommendations, performed at continental scale, could then help guide LIFE project proposals from the Member States and fill the current gap in the coverage of priority species. This top‐down control mechanism could be integrated in the current system of budget distribution, rather than replacing it completely, to enhance the efficiency of conservation investment in the EU and achievement of continental goals.
Early repeat computed tomographic imaging in transferred trauma and neurosurgical patients: Incidence, indications and impact
Authors: Blazak Penni , Hacking Craig , Presneill Jeffrey , Reade Michael 
Published: February 2018

AbstractIntroductionComputed tomographic (CT) imaging is widely available in Australian rural and remote hospitals and is often performed prior to patient transfer to definitive tertiary hospital care. We hypothesised that critically ill trauma and neurosurgical patients might have CT scans repeated after interhospital transfer and that the utility of this practice might be low in relation to the additional financial cost and radiation exposure.MethodsWe conducted a retrospective review of clinical records to determine the proportion of trauma and neurosurgical patients transferred to our tertiary ICU from other hospitals between 1 June 2013 and 30 June 2014 who underwent a repeat CT scan. The additional effective radiation dose was estimated using the dose length product method and the Australian Medicare Benefits Schedule was used to estimate the associated cost.ResultsOf the 247 patients transferred for trauma and neurosurgical indications, many (144; 58%) had undergone CT imaging at the referring hospital. Repeat scans were performed in 60 (42%) already imaged patients (24% of all transferred patients), most frequently for changed clinical indications. While in 11 (18%) of those 60 already imaged patients the repeat scan led to an identifiable change in management, for another 13 (22%) patients the repeat scans appeared to be potentially avoidable. The median cost of a repeat scan was AU$250 and the median additional effective radiation dose was 2.74 mSv per patient.ConclusionRepeat CT scans for patients already imaged prior to transfer were relatively common, occurring mostly for apparently valid clinical reasons. However, the additional radiation risk and financial cost of these repeat scans appeared on retrospective audit to be potentially avoidable in approximately one in five cases.
Correlation analysis of mesenchymal–epithelial transition factor protein and human epidermal growth receptor 2 protein expression in 1479 cases of lung adenocarcinoma in China
Authors: Yang Lin , Che Yiqun , Guo Lei , Zheng Bo , Wang Bingning , Yang Zhenxi , Zhu Yixiang , Li Junling 
Published: February 2018

BackgroundTo investigate the correlation between mesenchymal–epithelial transition factor (C‐Met) and human epidermal growth receptor 2 (HER2) protein expression in primary lung adenocarcinoma tissues.MethodA total of 1479 resected primary lung adenocarcinoma patients were enrolled in the present study for detecting of C‐Met and HER2 protein by immunohistochemistry, and correlation analysis was made between the above two biomarkers and related clinicopathological features.ResultBoth C‐Met and HER2 proteins were found to stain highly positive in lung adenocarcinomas, and a positive correlation was found between them (χ2 = 118.5, P = 2.707 × 10−21). In addition, HER2 protein expression was correlated with sex, pathological stage, lymph node metastasis, and major subtypes; and C‐Met was correlated with sex (P < 0.05).ConclusionThe expression of C‐Met and HER2 protein in lung adenocarcinoma is highly correlated, and whether it is synergistic in the targeted therapy of lung adenocarcinoma deserves further study.
Multi‐level mixed models for evaluating factors affecting the mortality and weaning weight of piglets in large‐scale commercial farms in central China
Authors: Liu Ze‐Xue , Wei Hong‐Kui , Zhou Yuan‐Fei , Peng Jian 
Published: February 2018

AbstractThis study investigated the factors affecting piglet mortality (square root of mortality, SQRM) and average weaning weight (AWW) in commercial farms in central China. Information on sow diets, management and climate from 2478 weaning batches completed in 16 pig farms was collected from 2009 to 2013. Multi‐level mixed models, which included batch level (level 1) and farm level (level 2), were used to analyze the factors associated with SQRM and AWW. The mean values of SQRM and AWW were 2.52% (SD = 0.96) and 7.31 (SD = 0.77), respectively. Lactation sow diets supplemented with oregano essential oils (OEOs) decreased the SQRM (P < 0.05) and increased the AWW of piglets (P < 0.01). The SQRM was lower in period 2 (June to September, hot) than in period 1 (February to May, warm) and period 3 (October to January, cold; P < 0.05 and 0.001, respectively). The AWW was lower in periods 2 and 3 than in period 1 (P < 0.01). In conclusion, supplying OEOs to lactation diets can increase the weaning weight and reduce the mortality of piglets. The sources of variations in SQRM and AWW are of greater concern in the warm season than in the hot season.
Big Data Opportunities for Accounting and Finance Practice and Research
Authors: Cockcroft Sophie , Russell Mark 
Published: February 2018

AbstractWe examine the research opportunities for the use of ‘big data’ in accounting and finance. The purpose of the study is to present a snapshot of big data academic research in information systems, accounting and finance, and to highlight areas for further research in accounting and finance. The research question addressed in this work is: What are the major themes in existing research in big data and where are the resulting gaps in the accounting and finance literature? An analysis is presented of 47 accounting, finance and information systems journals from 2007–2016. We identify and sample the relevant literature to derive a taxonomy of themes. These themes are presented as a conceptual matrix in which the themes from the taxonomy are used as concepts, and the matrix identifies where they appear, and where there are potential areas for further research. Prior research in big data in accounting, finance and information systems falls into six themes. The six under‐researched areas of big data in accounting and finance are risk and security, data visualisation and predictive analytics, data management and data quality. Increased research in these areas will lead to improvements in industry practices, and opportunities for cross‐disciplinary research.
Threats to global antimicrobial resistance control: Centrally approved and unapproved antibiotic formulations sold in India
Authors: McGettigan Patricia , Roderick Peter , Kadam Abhay , Pollock Allyson 
Published: February 2018

AimsRising antimicrobial resistance (AMR) is a global health crisis. India has among the highest resistance rates and antibiotic consumption internationally. Extensive use of fixed‐dose combination (FDC) antibiotics and of unapproved formulations are claimed contributory factors but there has been no systematic examination of formulations or volumes sold. The aim of the present study was to investigate the regulatory approval status and sales volumes of systemic antibiotics marketed in India.MethodsThis was an ecological study using regulatory records in India, the UK and the US to determine the approval status in each country of systemic antibiotic FDCs and single‐drug formulations (SDFs) sold in India. Pharmatrac® sales data were used to determine the formulations and volumes sold (2007–2012), branded‐product numbers and manufacturers.ResultsOf 118 systemic antibiotic FDC formulations sold in India, 43 (36%) were approved but 75 (64%) had no record of regulatory approval; four (3%) formulations were approved in the UK and/or US. Almost half of formulations (58/118; 49%) comprised dual antimicrobials, most unapproved in India (43/58; 74%), and many were pharmacologically problematic. In contrast, 80/86 (93%) SDFs were approved in India and over two‐thirds in the UK and/or US. Total antibiotic sales increased by 26%, from 2056 million units (2007–08) to 2583 million units (2011–12). FDC sales rose by 38% vs. 20% for SDFs. By 2011–12, FDCs comprised one‐third of sales (872 million units). Over one‐third of FDCs sold (300.26 million units; 34.5%) were of unapproved formulations. Multinational companies manufactured unapproved formulations and accounted for 19% of all FDC and SDF sales annually.ConclusionsSales in India of antibiotic FDCs, including unapproved formulations, are rising. In the context of increasing AMR rates nationally and globally, unapproved antibiotic FDCs undermine India's national AMR strategy and should be banned from sale.
Factors affecting the structure of Coleoptera assemblages on bracket fungi (Basidiomycota) in a Brazilian forest
Authors: Graf Letícia V. , Barbieri Fabrícia , Sperb Edilena , Soares Rivaldo Daniela , de A. Moura Luciano , B. da Silveira Rosa Mara , A. Reck Mateus , Nogueira‐de‐Sá Flávia 
Published: February 2018

AbstractInsect–fungal interactions are an important but understudied aspect of tropical forest ecology. Here we present the first large‐scale study of insect communities feeding on the reproductive structures of macrofungi (basidiomes) in the Neotropics. This trophic interaction is not well characterized in most ecosystems; however, beetle consumption of basidiomes is thought to be affected by fungal factors, via mechanisms analogous to those observed in plant–herbivore interactions and in some interactions with fungi as hosts in the Holarctic region. We investigated how the composition of beetle assemblages varies as a function of fungal taxonomic distance, basidiome consistency, and hyphal systems. We collected 367 basidiomes belonging to the orders Polyporales and Hymenochaetales in the subtropicalAraucaria angustifoliaforest region of southern Brazil, along with any fauna present or without it. Basidiomes were maintained individually in the laboratory in plastic containers for up to three months to allow beetles to develop to adulthood, at which point the beetles were collected. We found that 207 basidiome specimens representing 40 species were associated with beetles. We recorded 447 occurrences of Coleoptera, representing 90 morphospecies from 20 families. We found that assemblages of fungivorous Coleoptera were more similar among more closely related fungi. Furthermore, the beetle assemblages varied as a function of basidiome toughness, which is influenced by sporocarp consistency and hyphal system type. The associations between beetles and basidiomes resemble those reported previously in temperate zones, suggesting continuity in the structure of such associations across a wide latitudinal range.
Effect of length and location of edentulous area on the accuracy of prosthetic treatment plan incorporation into cone‐beam computed tomography scans
Authors: Jamjoom Faris Z. , Kim Do‐Gyoon , Lee Damian J. , McGlumphy Edwin A. , Yilmaz Burak 
Published: February 2018

AbstractBackgroundEffects of length and location of the edentulous area on the accuracy of prosthetic treatment plan incorporation into cone‐beam computed tomography (CBCT) scans has not been investigated.PurposeTo evaluate the effect of length and location of the edentulous area on the accuracy of prosthetic treatment plan incorporation into CBCT scans using different methods.Material and MethodsDirect digital scans of a completely dentate master model with removable radiopaque teeth were made using an intraoral scanner, and digital scans of stone duplicates of the master model were made using a laboratory scanner. Specific teeth were removed to simulate different clinical situations and their CBCT scans were made. Surface scans were registered onto the CBCT scans. Radiographic templates for each clinical situation were also fabricated and used during CBCT scans of the master models. Using metrology software, three‐dimensional (3D) deviation was measured on standard tesselation language (STL) files created from the CBCT scans against an STL file of the master model created from a CBCT scan. Statistical analysis was done using the MIXED procedure in a statistical software and Tukey HSD test (α =.05).ResultsThe interaction between location and method was significant (P = .009). Location had no significant effect on registration methods (P > .05), but on the radiographic templates (P = .011). Length of the edentulous area did not have any significant effect (P > .05).ConclusionsAccuracy of digital image registration methods was similar and higher than that of radiographic templates in all clinical situations. Tooth‐bound radiographic templates were significantly more accurate than the free‐end templates. The results of this study suggest using image registration instead of radiographic templates when planning dental implants, particularly in free‐end situations.
Remote limb ischemic postconditioning promotes motor function recovery in a rat model of ischemic stroke via the up‐regulation of endogenous tissue kallikrein
Authors: Liang Dan , He Xi‐Biao , Wang Zheng , Li Ce , Gao Bei‐Yao , Wu Jun‐Fa , Bai Yu‐Long 
Published: February 2018

SummaryAimsRemote ischemic conditionings, such as pre‐ and per‐conditioning, are known to provide cardioprotection in animal models of ischemia. However, little is known about the neuroprotection effect of postconditioning after cerebral ischemia. In this study, we aim to evaluate the motor function rescuing effect of remote limb ischemic postconditioning (RIPostC) in a rat model of acute cerebral stroke.MethodsLeft middle cerebral artery occlusion (MCAO) was performed to generate the rat model of ischemic stroke, followed by daily RIPostC treatment for maximum 21 days. The motor function after RIPostC was assessed with foot fault test and balance beam test. Local infarct volume was measured through MRI scanning. Neuronal status was evaluated with Nissl's, HE, and MAP2 immunostaining. Lectin immunostaining was performed to evaluate the microvessel density and area.ResultsDaily RIPostC for more than 21 days promoted motor function recovery and provided long‐lasting neuroprotection after MCAO. Reduced infarct volume, rescued neuronal loss, and enhanced microvessel density and size in the injured areas were observed. In addition, the RIPostC effect was associated with the up‐regulation of endogenous tissue kallikrein (TK) level in circulating blood and local ischemic brain regions. A TK receptor antagonist HOE‐140 partially reversed RIPostC‐induced improvements, indicating the specificity of endogenous TK mediating the neuroprotection effect of RIPostC.ConclusionOur study demonstrates RIPostC treatment as an effective rehabilitation therapy to provide motor function recovery and alleviate brain impairment in a rat model of acute cerebral ischemia. We also for the first time provide evidence showing that the up‐regulation of endogenous TK from remote conditioning regions underlies the observed effects of RIPostC.
Assessment of myocardial strain in children with risk factors for atherosclerosis with use of 3D speckle tracking echocardiography
Authors: Zhang Peixu , Li Dongqing , Su Yanzhuo , Wang Xiaona , Sun Jianping , Xu Yang , Sun Jinghui 
Published: February 2018

BackgroundThe known risk factors for atherosclerosis such as dyslipidemia, hypertension, obesity, and fasting hyperglycemia are associated with subclinical myocardial dysfunction. We assessed myocardial strain in children who had risk factors for atherosclerosis with use of 3D speckle tracking echocardiography (3DSTE).MethodsA total of 340 eligible children (mean age [±SD]: 9.5 [±1.9] years; range, 7.1–12.2; 189 males, 151 females). Levels of serum cholesterol (TC), triglyceride (TG), high‐density lipoprotein cholesterol (HDL‐C), low‐density lipoprotein cholesterol (LDL‐C), fasting blood glucose (FBG), systolic blood pressure (SBP), diastolic blood pressure (DBP), and body mass index (BMI) were investigated. The parameters of left ventricular (LV) myocardial strain including global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) were measured with use of real time 3DSTE.ResultsLeft ventricular (LV) global longitudinal strain and global circumferential strain in the groups with isolated dyslipidemia, isolated hypertension, isolated obese/overweight, and combination groups were lower than those in healthy controls (P < .01 for all). Global longitudinal strain (GLS) and GCS showed a negative correlation with the respective risk factors (TG, TC, and LDL‐C; SBP and DBP; weight and BMI) (P < .05 for all). Multiple stepwise regression analysis showed a significant negative correlation of GLS and GCS with BMI, TC, TG, and SBP. The degree of myocardial strain aggravated significantly with increase in the number of risk factors in an individual subject.
Primary education and fertility rates
Authors: Bittencourt Manoel 
Published: February 2018

AbstractUnified growth theory advances that the transition from a Malthusian regime to sustained economic growth is characterized by technological progress and, amongst other things, by an increase in demand for human capital which in turn creates incentives for lower fertility rates. Bearing that in mind, I ask the question: has southern Africa escaped the Malthusian stagnation? Specifically, I study whether primary school completion rates have played any role in total fertility rates in all countries of the Southern African Development Community (SADC) during the 1980–2009 period. Contrary to conventional wisdom, the results, based on dynamic panel time‐series methods, suggest that primary education is associated with lower fertility in the SADC, or that the community is already trading‐off quantity for quality of children. Although I do not claim causality, overall the results are significant because, in accordance with unified growth theory, they suggest that the SADC is experiencing its own transition from the Malthusian stagnation epoch into sustained growth, or that the SADC is going through its own post‐Malthusian regime.