bluuebunny/crossref_metadata_2025_split huggingface dataset:
Copenhagen Prospective Personalized Oncology (CoPPO)—Clinical Utility of Using Molecular Profiling to Select Patients to Phase I Trials
Authors: Tuxen Ida Viller , Rohrberg Kristoffer Staal , Oestrup Olga , Ahlborn Lise Barlebo , Schmidt Ane Yde , Spanggaard Iben , Hasselby Jane P. , Santoni-Rugiu Eric , Yde Christina Westmose , Mau-Sørensen Morten , Nielsen Finn Cilius , Lassen Ulrik 
Published: October 2018

Abstract

Purpose:
We evaluated the clinical benefit of tumor molecular profiling to select treatment in the phase I setting.

Experimental Design:
Patients with advanced solid cancers and exhausted treatment options referred to a phase I unit were included in a prospective, single-center, single-arm open-label study (NCT02290522). Tumor biopsies were obtained for comprehensive genomic analysis including whole-exome sequencing and RNA sequencing. When possible, patients were treated with regimen matched to the genomic profile. Primary endpoint was progression-free survival (PFS).

Results:
From May 2013 to January 2017, a total of 591 patients were enrolled, with 500 patients undergoing biopsy. Genomic profiles were obtained in 460 patients and a potential actionable target was identified in 352 (70%) of 500 biopsied patients. A total of 101 patients (20%) received matched treatment based on either gene mutations or RNA expression levels of targets available in early clinical trials or off-label treatment. Objective response according to RECIST1.1 was observed in 15 of 101 patients (0% complete response, 15% partial response), with a median PFS of 12 weeks (95% confidence interval, 9.9–14.4).

Conclusions:
Our study supports the feasibility of genomic profiling to select patients in the phase I setting and suggests that genomic matching can be beneficial for a minor subset of patients with no other treatment options. Randomized studies may validate this assumption.
See related commentary by Ratain, p. 1136
Tumor Sidedness and Enriched Gene Groups for Efficacy of First-line Cetuximab Treatment in Metastatic Colorectal Cancer
Authors: Sunakawa Yu , Mogushi Kaoru , Lenz Heinz-Josef , Zhang Wu , Tsuji Akihito , Takahashi Takehiro , Denda Tadamichi , Shimada Ken , Kochi Mitsugu , Nakamura Masato , Kotaka Masahito , Segawa Yoshihiko , Tanioka Hiroaki , Negoro Yuji , Moran Miriana , Astrow Stephanie H. , Hsiang Jack , Stephens Craig , Fujii Masashi , Ichikawa Wataru 
Published: October 2018

Abstract
Molecular differences in tumor locations may contribute to the sidedness-specific response to cetuximab in metastatic colorectal cancer (mCRC). We investigated genes associated with the response to cetuximab treatment depending on tumor sidedness. Our study included 77 patients with mCRC (13/63, right/left) with KRAS exon 2 wild-type tumors from phase II trials of first-line therapy with cetuximab. Expression levels of 2,551 genes were measured in tissue samples by HTG EdgeSeq Oncology Biomarker Panel. Univariate Cox regression analysis using log2 values of counts per million (CPM) was conducted in each sidedness to assess associations with clinical outcomes, and to define the optimal cut-off point for clinically significant genes. In addition, a gene set enrichment analysis (GSEA) was performed to identify significant gene pathways in each sidedness. Sixty-nine patients were assessable for gene expression data. Overexpression of BECN1 [log2(CPM) ≥ 6.8] was associated with favorable survival, regardless of tumor sidedness. High expression of NOTCH1 [log2(CPM) ≥ 7.5] predicted significantly longer progression-free survival (PFS; median 14.7 vs. 11.1 months, HR 0.43, P = 0.01) and overall survival (OS; median 42.8 vs. 26.5 months, HR 0.35, P = 0.01) in left side but not in right side. The GSEA showed that regulation of DNA replication gene set correlated with favorable survival in the left, whereas the subcellular component and leukocyte migration gene sets were associated with good survival in the right. In conclusion, genes contributing to the efficacy of cetuximab treatment may differ according to the sidedness in mCRC. NOTCH1 may potentially discriminate favorable responders to cetuximab in patients with left-sided tumors.
Daily Precipitation Fields Modeling across the Great Lakes Region (Canada) by Using the CFSR Reanalysis
Authors: Khedhaouiria Dikra , Mailhot Alain , Favre Anne-Catherine 
Published: October 2018

AbstractReanalyses, generated by numerical weather prediction methods assimilating past observations, provide consistent and continuous meteorological fields for a specific period. In regard to precipitation, reanalyses cannot be used as a climate proxy of the observed precipitation, as biases and scale mismatches exist between the datasets. In the present study, a stochastic model output statistics (SMOS) approach combined with meta-Gaussian spatiotemporal random fields was employed to cope with these caveats. The SMOS is based on the generalized linear model (GLM) and the vector generalized linear model (VGLM) frameworks to model the precipitation occurrence and intensity, respectively. Both models use the Climate Forecast System Reanalysis (CFSR) precipitation as covariate and were locally calibrated at 173 sites across the Great Lakes region. Combined with meta-Gaussian random fields, the GLM and VGLM models allowed for the generation of spatially coherent daily precipitation fields across the region. The results indicated that the approach corrected systematic biases and provided an accurate spatiotemporal structure of daily precipitation. Performances of selected precipitation indicators from the joint Commission for Climatology (CCl)/CLIVAR/JCOMM Expert Team on Climate Change Detection and Indices (ETCCDI) were good and were systematically improved when compared to CFSR.
The Growth and Saturation of Submesoscale Instabilities in the Presence of a Barotropic Jet
Authors: Stamper Megan A. , Taylor John R. , Fox-Kemper Baylor 
Published: October 2018

AbstractMotivated by recent observations of submesoscales in the Southern Ocean, we use nonlinear numerical simulations and a linear stability analysis to examine the influence of a barotropic jet on submesoscale instabilities at an isolated front. Simulations of the nonhydrostatic Boussinesq equations with a strong barotropic jet (approximately matching the observed conditions) show that submesoscale disturbances and strong vertical velocities are confined to a small region near the initial frontal location. In contrast, without a barotropic jet, submesoscale eddies propagate to the edges of the computational domain and smear the mean frontal structure. Several intermediate jet strengths are also considered. A linear stability analysis reveals that the barotropic jet has a modest influence on the growth rate of linear disturbances to the initial conditions, with at most a ~20% reduction in the growth rate of the most unstable mode. On the other hand, a basic state formed by averaging the flow at the end of the simulation with a strong barotropic jet is linearly stable, suggesting that nonlinear processes modify the mean flow and stabilize the front.
The NCAR–FAA Snow Machine: An Artificial Snow-Generation System
Authors: Landolt Scott D. , Rasmussen Roy M. , Hills Alan J. , Underwood Warren , Knight Charles A. , Jachcik Albert , Schwartz Andrew 
Published: October 2018

AbstractThe National Center for Atmospheric Research (NCAR) developed an artificial snow-generation system designed to operate in a laboratory cold chamber for testing aircraft anti-icing fluids under controlled conditions. Flakes of ice are produced by shaving an ice cylinder with a rotating carbide bit; the resulting artificial snow is dispersed by turbulent airflows and falls approximately 2.5 m to the bottom of the device. The resulting fine ice shavings mimic snow in size, distribution, fall velocity, density, and liquid water equivalent (LWE) snowfall rate. The LWE snowfall rate can be controlled using either a mass balance or a precipitation gauge, which measures the snowfall accumulation over time, from which the computer derives the LWE rate. LWE snowfall rates are calculated every 6 s, and the rate the ice cylinder is fed into the carbide bit is continually adjusted to ensure that the LWE snowfall rate matches a user-selected value. The system has been used to generate LWE snowfall rates ranging from 0 to 10 mm h−1 at temperatures from −2 to −30°C and densities of approximately 0.1–0.5 g cm−3. Comparisons of the snow-machine fluid tests with the outdoor fluid tests have shown that the snow machine can mimic natural outdoor rates under a broad range of conditions.
Comparing the Hedging Effectiveness of Weather Derivatives Based on Remotely Sensed Vegetation Health Indices and Meteorological Indices
Authors: Möllmann Johannes , Buchholz Matthias , Musshoff Oliver 
Published: October 2018

Abstract
Weather derivatives are considered a promising agricultural risk management tool. Station-based meteorological indices typically provide the data underlying these instruments. However, the main shortcoming of these weather derivatives is an imperfect correlation between the weather index and the yield of the insured crop, called basis risk. This paper considers three available remotely sensed vegetation health (VH) indices, namely, the vegetation condition index (VCI), the temperature condition index (TCI), and the vegetation health index (VHI), as indices for weather derivatives in a German case study. We investigated the correlation and period of highest correlation with winter wheat yield. Moreover, we analyzed whether the use of remotely sensed VH indices for weather derivatives can reduce basis risk and thus improve the performance of weather derivatives. The two commonly used meteorological indices, precipitation and temperature sums, were employed as benchmarks. Quantile regression and index value simulation were used for the design and pricing of the weather derivatives. The analysis for the selected farms and corresponding counties in northeastern Germany revealed that, on average, the VHI resulted in the highest correlation with winter wheat yield, and VHI-based weather derivatives were also superior in terms of the hedging effectiveness. The total periods of the highest correlations ranged from the beginning of April to the end of July. VHI- and VCI-based weather derivatives led to statistically significant reductions of basis risk, compared to the benchmarks. Our results indicate that the VHI-based weather derivatives can be useful alternatives to meteorological indices, especially in regions with sparser weather station networks.
Mapping Discourses of Climate Change Adaptation in the United Kingdom
Authors: Cotton Matthew , Stevens Emma 
Published: October 2018

AbstractThe concept of adaptation is becoming part of mainstream public discourse on climate change. Yet the diversity, complexity, and novelty of the adaptation concept itself leads to interpretive flexibility, differing public understanding of (and engagement with) adaptation strategies, and hence differentiated policy responses. The boundary work of communicative practices and public understanding of the adaptation concept therefore requires empirical analysis in different cases and contexts. This study employs Q-methodology (a combined quantitative–qualitative social research method) to reveal the typologies of perspectives that emerge around the adaptation concept among a diverse group of citizen-stakeholders in the United Kingdom. Four such typologies are identified under the labels 1) top-down climate action, 2) collective action on climate change, 3) optimistic, values-focused adaptation, and 4) adaptation skepticism. The division between these perspectives reveals a perceived “responsibility gap” between the governmental–institutional and/or individual–community levels. Across the emergent discourses we find a consensual call for a multisector, multiscalar, and multistakeholder-led approach that posits adaptation as a contemporary, intragenerational problem, with a strong emphasis upon managing extreme weather events, and not as an abstract future problem. By attending to these public discourses in climate policy, this presents a potential means to lessen such a responsibility gap.
Effects of meal replacement therapy on metabolic outcomes in Thai patients with type 2 diabetes: A randomized controlled trial
Authors: Boonyavarakul Apussanee , Leelawattana Rattana , Pongchaiyakul Chatlert , Buranapin Supawan , Phanachet Pariya , Pramyothin Pornpoj 
Published: October 2018

Background: A meal replacement (MR) with a low glycemic index (GI) is possibly beneficial for glycemic control. However, the effects of MR on diabetes mellitus have not been studied among Thai patients with type 2 diabetes (T2DM). Aim: To compare metabolic outcomes between T2DM patients receiving the new MR formula (ONCE PRO) and normal controlled diets. Methods: A multicenter, open-labeled, randomized controlled trial was conducted. Eligible patients received either ONCE PRO for one meal daily with controlled diets or only controlled diets for 3 months. The differences in metabolic profile between the baseline and end point of each group and between groups were measured. Results: 110 participants were enrolled; the mean difference and standard deviation in hemoglobin A1C (HbA1c) (%) from baseline were –0.21 ± 0.78 ( p = 0.060) and –0.27 ± 0.60 ( p = 0.001) in the MR and control groups, respectively; however, there was no significant difference between groups ( p = 0.637). Patients consuming a MR instead of breakfast had a significant decrease in HbA1c ( p = 0.040). Body weight (BW) and body mass index (BMI) were significantly reduced in both groups. There were no significant change in waist circumference, fasting plasma glucose, total cholesterol and triglycerides. Low-density lipoprotein cholesterol (LDL-C) was significantly decreased in the MR group compared with the control group ( p = 0.049). Conclusions: Short-term conventional diet control and the low-GI MR product were associated with a decreased BW and BMI. Changes in the other metabolic outcomes, HbA1c, total cholesterol and triglycerides, were comparable despite ONCE PRO as the MR having a better effect on LDL-C lowering.
Systemic therapy of metastatic renal cell carcinoma: Review of the current literature
Authors: Zerdes Ioannis , Tolia Maria , Tsoukalas Nikolaos , Mitsis Michail , Kardamakis Dimitrios , Pistevou-Gombaki Kyriaki , Tsekeris Perikles , Kyrgias George 
Published: October 2018

Introduction: Renal cell carcinoma represents a neoplasm with usually aggressive behavior. Due to its nature, it is often diagnosed in an advanced stage or when metastatic dissemination has been occurred. The aim of this review is to provide an overview of the current management of metastatic renal cell carcinoma and briefly discuss the potential new therapeutic strategies for this disease. Methods: Review of the literature was performed in PubMed/MEDLINE, Cochrane, and EMBASE and we included English articles up to February 2018. Results: Over the past years, many efforts have been made in the context of confronting metastatic disease and led to the introduction of targeted therapies. More available agent options, including various tyrosine kinase inhibitors and mammalian target of rapamycin inhibitors, can be served nowadays as the first-, second-, and third-line therapy in the metastatic setting of the disease providing better outcomes. Discussion: Moreover, regarding the recent advances in the field of cancer immunotherapy, the landscape of metastatic renal cell carcinoma management is being shaped toward novel immunotherapeutic interventions alone or in combination with other types of therapy.
Target Temperature Management May Not Improve Clinical Outcomes of Extracorporeal Cardiopulmonary Resuscitation
Authors: Kim Young Su , Cho Yang Hyun , Sung Kiick , Ryu Jeong-Am , Chung Chi Ryang , Suh Gee Young , Yang Jeong Hoon , Yang Ji-Hyuk 
Published: October 2018

Purpose: Target temperature management (TTM) and extracorporeal cardiopulmonary resuscitation (ECPR) have been established as important interventions during cardiopulmonary arrest. However, the impact of combined TTM and ECPR on clinical outcomes has not been studied in detail. Methods: We reviewed the records of 245 patients who received extracorporeal life support (ECLS) between January 2012 and June 2015. Exclusion criteria were as follows: Extracorporeal life support performed for reasons other than cardiac arrest, age less than 18 years, and death within 24 hours. A total of 101 patients were finally included in the study. Twenty-five patients underwent TTM, and 76 patients did not. Results: The patients’ mean age was 55 ± 16.7 years. The mean cardiac arrest time was 44.6 ± 33.5 minutes. There were 84 patients whose cardiac arrest was due to a cardiac cause (83.2%) and 79 patients with in-hospital cardiac arrest (78.2%). There was a significant difference in average body temperature during the first 24 hours following ECPR (33.4°C vs 35.6°C; P = .001). The overall favorable neurological outcome rate was 34% and hospital survival rate was 47%. There was no difference in favorable neurological outcomes and hospital survival between the TTM and non-TTM groups ( P = .91 and .84, respectively). On multivariate analysis of neurological outcomes and hospital survival, TTM was not a significant prognostic factor. Conclusion: We did not observe any benefits of TTM in patients undergoing ECPR. Natural hypothermia or normothermia related to ECLS may explain this result. Further research is needed to understand the role of TTM in ECPR.
Surviving Disasters by Suppressing Political Storms: Participation as Knowledge Transfer in Community-Based Disaster Governance
Authors: Curato Nicole , Calamba Septrin John 
Published: October 2018

The small island of San Francisco, Cebu in the Philippines has gained global recognition for its community-based disaster management program. By institutionalizing the purok system—a sub-village level of organization—citizens are empowered to plan and implement disaster preparedness programs that fit their specific needs and geographical context.We interrogate the logics that underpin this prize-winning governance innovation. We find that San Francisco—the island where all survive even after the most devastating of disasters—functions through the modality of participation as knowledge transfer. It is underpinned the ethos of solidarity over conflict and takes place in a predetermined rather than citizen-driven space for participatory politics. We situate our arguments in the recent literature on public participation to understand the precise character of participatory politics in the field of disaster response.
Expression of peripheral blood monocyte human leukocyte antigen DR in patients with cardiac arrest and its clinical significance
Authors: Zhang Junli , Wang Yanjuan , Gu Wei 
Published: October 2018

Background: In the early period of spontaneous circulation (ROSC), the body may show severe immunosuppression and excessive activation of inflammatory response, This is very similar to sepsis in many ways. Objective: The aim of this study is to observe changes of the early expression of monocyte human leukocyte antigen DR in patients with cardiac arrest, so as to explore the clinical significance of the related immune assessment and prognosis prediction. Methods: A total of 43 patients with cardiac arrest who have been treated in the emergency department of Beijing Chaoyang Hospital from January 2015 to February 2018 are selected. By taking the survival rate on the 28th day of hospitalization as the end of observation, the patients are divided into the survival group and the death group. Changes of APACHE-II scores and monocyte human leukocyte antigen DR levels on the first, second, and third day after admission are analyzed. Results: On the first, second, and third day after onset, cardiac arrest patients show significantly decreased levels of monocyte human leukocyte antigen DR which are obviously lower in the death group than in the survival group. In addition, human leukocyte antigen DR levels were significantly negatively correlated with APACHE-II scores. Conclusion: The expression of monocyte human leukocyte antigen DR is proven to be an ideal indicator to evaluate the immune function and prognosis of cardiac arrest patients. A constantly low expression of human leukocyte antigen DR indicates impaired immune function and increased mortality of patients.
Accuracy of biometric formulae in hypermetropic patients undergoing cataract surgery
Authors: Mustafa Mohammad Z , Khan Ashraf A , Bennett Harry , Tatham Andrew J , Wright Mark 
Published: October 2018

Purpose: To audit and analyse the accuracy of current biometric formulae on refractive outcomes following cataract surgery in patients with axial length less than 22 mm. Methods: A total of 84 eyes from 84 patients with axial length <22 mm were identified from consecutive patients undergoing cataract surgery retrospectively at a single university hospital. All subjects had biometry using the IOLMaster (Carl Zeiss Meditec, Inc, Dublin, CA, USA) and a Sensar AR40 intraocular lens implant (Abbott Medical Optics, CA, USA). One eye from each patient was randomly selected for inclusion. Prediction errors were calculated by comparing expected refraction from optimized formulas (SRK/T, Hoffer Q, Haigis and Holladay 1) to postoperative refraction. A national survey of ophthalmologists was conducted to ascertain biometric formula preference for small eyes. Results: The mean axial length was 21.00 ± 0.55 mm. Mean error was greatest for Hoffer Q at −0.57 dioptres. There was no significant difference in mean absolute error between formulae. SRK/T achieved the highest percentage of outcomes within 0.5 dioptres (45.2%) and 1 dioptre (76.2%) of target. Shallower anterior chamber depth was associated with higher mean absolute error for SRK/T (p = 0.028), Hoffer Q (p = 0.003) and Haigis (p = 0.016) but not Holladay (p = 0.111). Conclusion: SRK/T had the highest proportion of patients achieving refractive results close to predicted outcomes. However, there was a significant association between a shallower anterior chamber depth and higher mean absolute error for all formulae except Holladay 1. This suggests that anterior chamber depth with axial length should be considered when counselling patients about refractive outcome.
One-step management of post-traumatic triple dialysis using two rings
Authors: Gupta Shikha , Selvan Harathy , Shakrawal Jyoti , Gupta Viney 
Published: October 2018

Purpose: To report a case that presented with post blunt trauma cataract, zonular dialysis, cyclodialysis and iridodialysis and its successful single-sitting management. Methods: After lens aspiration, a capsular tension ring and multipiece intraocular lens were placed in the bag to support the zonules, a single eyelet Cionni ring was fixed in the sulcus to provide endocyclotamponade, and iridodialysis repair was done using the ‘stroke and dock technique’. Result: Successful centration of the intraocular lens, closure of the cleft and apposition of the iris root to its base were achieved at the end of the surgery. Conclusion: A single-sitting surgery correcting all the three dialysis can curtail the burden of repeated surgeries and their complications, providing early visual recovery and cost-effectivity.