bluuebunny/crossref_metadata_2025_split huggingface dataset:
Jekyll and Hyde of chemotherapy treatment: Method for patient‐specific dosing of chemotherapy medications
Authors: Tatlow Dean 
Published: November 2017

SummaryCurrently chemotherapy dosing is determined by a patient's weight, height and renal function. Dosing chemotherapy based on these parameters is generally effective, assuming all other physiological conditions are normal. In hypoalbuminaemia patients a decrease in albumin often results in more severe side‐effects, since this may lead to higher chemotherapy free drug levels. A new method to dose chemotherapy based on a patients albumin will maintain the same effective free drug levels as in patients with normal albumin. This can reduce the severity of chemotherapy side‐effects and may: ensure better outcomes for patients since it allows them to complete their course of chemotherapy without interruption, decrease the cost and complications associated with severe side‐effects, and will allow for enhanced treatment options.
Serum mast cell tryptase measurements: Sensitivity and specificity for a diagnosis of anaphylaxis in emergency department patients with shock or hypoxaemia
Authors: Francis Abbie , Fatovich Daniel M , Arendts Glenn , Macdonald Stephen PJ , Bosio Erika , Nagree Yusuf , Mitenko Hugh MA , Brown Simon GA 
Published: November 2017

AbstractObjectiveClinical diagnosis of anaphylaxis is principally based on symptoms and signs. However, particularly for patients with atypical symptoms, laboratory confirmation of anaphylaxis would be useful. This study investigated the utility of mast cell tryptase, an available clinical biomarker, for differentiating anaphylaxis from other causes of critical illness, which can also involve mast cell activation.MethodsTryptase was measured (ImmunoCAP) in serum from patients with anaphylaxis and non‐anaphylactic critical illness (controls) at ED arrival, and after 1–2, 3–4 and 12–24 h. Differences in both peak and delta (difference between highest and lowest) tryptase concentrations between groups were investigated using linear regression models, and diagnostic ability was analysed using Receiver Operating Characteristic curve analysis.ResultsPeak tryptase was fourfold (95% CI: 2.9, 5.5) higher in anaphylaxis patients (n = 67) than controls (n = 120) (P < 0.001). Delta‐tryptase was 5.1‐fold (95% CI: 2.9, 8.9) higher in anaphylaxis than controls (P < 0.001). Optimal test characteristics (sensitivity: 72% [95% CI: 59, 82] and specificity: 72% [95%CI: 63, 80]) were observed when peak tryptase concentrations were >11.4 ng/mL and/or delta‐tryptase ≥2.0 ng/mL. For hypotensive patients, peak tryptase >11.4 ng/mL had improved test characteristics (sensitivity: 85% [95% CI: 65, 96] and specificity: 92% [95% CI: 85, 97]); the use of delta‐tryptase reduced test specificity.ConclusionWhile peak and delta tryptase concentrations were higher in anaphylaxis than other forms of critical illness, the test lacks sufficient sensitivity and specificity. Therefore, mast cell tryptase values alone cannot be used to establish the diagnosis of anaphylaxis in the ED. In particular, tryptase has limited utility for differentiating anaphylactic from non‐anaphylactic shock.
Does willingness to pay increase with the number and strictness of sustainability labels?
Authors: Tebbe Eva , von Blanckenburg Korbinian 
Published: November 2017

AbstractLabels signaling sustainable product attributes are gaining importance, although uncertainty concerning the environmental, micro‐ and macroeconomic benefits of such labels persist. One of the questions still incompletely answered is whether Willingness To Pay (WTP) varies with a gradually increasing number of labels on a food product. In order to answer this question, we conducted a laboratory experiment with 191 student respondents, testing consumer valuations of different labeling strategies. Using the Becker‐DeGroot‐Marschak mechanism, WTP for 15 food products was measured. The products were endowed with up to six different sustainability labels, such that each grocery item was available in eight product versions. For perishable, nonperishable, and plant‐based products, the results indicate that participants are prone to allocating WTP‐premiums to labeled products, more than to unlabeled products. For animal products, however, labels do not influence WTP significantly. Furthermore, the premiums do not vary with an increasing number of labels, irrespective of whether the labels signal substitute or complementary sustainability information. The results are not entirely in line with normative notions of magnitude variation, but rather with the behavioral economic concept of embedding effects.
Parent‐of‐origin‐environment interactions in case‐parent triads with or without independent controls
Authors: Gjerdevik Miriam , Haaland Øystein A. , Romanowska Julia , Lie Rolv T. , Jugessur Astanand , Gjessing Håkon K. 
Published: November 2017

AbstractWith case–parent triad data, one can frequently deduce parent of origin of the child's alleles. This allows a parent‐of‐origin (PoO) effect to be estimated as the ratio of relative risks associated with the alleles inherited from the mother and the father, respectively. A possible cause of PoO effects is DNA methylation, leading to genomic imprinting. Because environmental exposures may influence methylation patterns, gene–environment interaction studies should be extended to allow for interactions between PoO effects and environmental exposures (i.e., PoOxE). One should thus search for loci where the environmental exposure modifies the PoO effect.We have developed an extensive framework to analyze PoOxE effects in genome‐wide association studies (GWAS), based on complete or incomplete case–parent triads with or without independent control triads. The interaction approach is based on analyzing triads in each exposure stratum using maximum likelihood estimation in a log‐linear model. Interactions are then tested applying a Wald‐based posttest of parameters across strata. Our framework includes a complete setup for power calculations. We have implemented the models in the R software package Haplin.To illustrate our PoOxE test, we applied the new methodology to top hits from our previous GWAS, assessing whether smoking during the periconceptional period modifies PoO effects on cleft palate only.
The Mendacity of Reconciliation in an Age of Resentment
Authors: McIvor David W. 
Published: November 2017

AbstractThe political ideal of reconciliation has gained increased prominence in recent decades, in part due to political experiments such as the South African Truth and Reconciliation Commission and other formal or informal truth or reconciliation processes. Here, I argue that there is a fundamental mendacity to reconciliation, given stubborn asymmetries of social power and disrespect. Reconciliation as an ideal carries an impetus towards resolution that covers over the necessary role that conflict plays in political struggles—including the role that conflict plays within struggles for reconciliation. Nevertheless, despite the mendacity of reconciliation, its meaning still holds political value. Reconciliation implies an orientation towards social repair, which even the strongest critics of reconciliation cannot bring themselves to reject. Some lies are worse than others, and some lies might be noble or necessary. Reconciliation is the latter—a fiction that is less pernicious than its absence. In this light, the task is to locate means of political reconciliation that do not obscure the conflicts and asymmetries of social life but enable social actors to face up to these conflicts and to discover novel ways to repair the damage that they can do.
Plant recolonization of reclamation areas from patches of salvaged forest floor material
Authors: Jones Caren E. , Landhäusser Simon M. 
Published: November 2017

AbstractQuestionUnderstorey development is a great challenge in the restoration of many forest sites, particularly when sources of vegetation propagules are scarce. Can placement of propagule‐rich soil patches within reclaimed landscapes otherwise covered with propagule‐poor material promote the dispersal of vegetation from the patches into the surrounding areas?LocationLarge reclamation site in the Canadian (Alberta) boreal forest.MethodPatches of propagule‐rich forest floor material were placed within a matrix of propagule‐poor peat material. Vegetation assessments (cover estimates, seed rain) were done surrounding these patches in the third and fourth growing seasons.ResultsThere was significant egress of species from the patches into the peat after four growing seasons, and overall species associated with the patches had higher cover in the peat than species that were associated with the peat itself. While wind‐dispersed herbaceous species from the patches were found at the leading edge of the egressing community, most species used vegetative propagation, resulting in short egress distances. Several patch‐associated species were found in seed rain collected on the peat areas but were not observed in this material, suggesting seedbed limitations.ConclusionDespite the relatively short distance of egress, this experiment suggests that placement of propagule‐rich soil material within reclaimed landscapes will promote egress into adjacent propagule‐poor soil material.
Reader Reaction: A Note on Testing and Estimation in Marker-set Association Study Using Semiparametric Quantile Regression Kernel Machine
Authors: Zhan Xiang , Wu Michael C. 
Published: November 2017

Summary
Kong et al. (2016, Biometrics72, 364–371) presented a quantile regression kernel machine (QRKM) test for robust analysis of genetic marker-set association studies. A potential limitation of QRKM is the permutation-based test design may be unscalable for the massive sizes of modern datasets. In this article, we present an alternative strategy for p-value calculation of QRKM, which is capable of speeding up the QRKM testing procedure dramatically while maintaining the same testing performance as QRKM. The effectiveness of our approach is demonstrated via simulation studies.
Data-driven Confounder Selection via Markov and Bayesian Networks
Authors: Häggström Jenny 
Published: November 2017

SummaryTo unbiasedly estimate a causal effect on an outcome unconfoundedness is often assumed. If there is sufficient knowledge on the underlying causal structure then existing confounder selection criteria can be used to select subsets of the observed pretreatment covariates, X, sufficient for unconfoundedness, if such subsets exist. Here, estimation of these target subsets is considered when the underlying causal structure is unknown. The proposed method is to model the causal structure by a probabilistic graphical model, for example, a Markov or Bayesian network, estimate this graph from observed data and select the target subsets given the estimated graph. The approach is evaluated by simulation both in a high-dimensional setting where unconfoundedness holds given X and in a setting where unconfoundedness only holds given subsets of X. Several common target subsets are investigated and the selected subsets are compared with respect to accuracy in estimating the average causal effect. The proposed method is implemented with existing software that can easily handle high-dimensional data, in terms of large samples and large number of covariates. The results from the simulation study show that, if unconfoundedness holds given X, this approach is very successful in selecting the target subsets, outperforming alternative approaches based on random forests and LASSO, and that the subset estimating the target subset containing all causes of outcome yields smallest MSE in the average causal effect estimation.
Population-based Clinical Practice Research Datalink study using algorithm modelling to identify the true burden of hidradenitis suppurativa
Authors: Ingram J.R. , Jenkins-Jones S. , Knipe D.W. , Morgan C.L.I. , Cannings-John R. , Piguet V. 
Published: November 2017

Summary

Background
Epidemiology data regarding hidradenitis suppurativa (HS) are conflicting and prevalence estimates vary 80-fold, from 0·05% in a population-based study to 4%.

Objectives
To assess the hypothesis that previous population-based studies underestimated true HS prevalence by missing undiagnosed cases.

Methods
We performed a population-based observational and case–control study using the U.K. Clinical Practice Research Datalink (CPRD) linked to hospital episode statistics data. Physician-diagnosed cases in the CPRD were identified from specific Read codes. Algorithms identified unrecognized ‘proxy’ cases, with at least five Read code records for boils in flexural skin sites. Validation of proxy cases was undertaken with general practitioner (GP) questionnaires to confirm criteria-diagnosed cases. A case–control study assessed disease associations.

Results
On 30 June 2013, 23 353 physician-diagnosed HS cases were documented in 4 364 308 research-standard records. In total, 68 890 proxy cases were identified, reduced to 10 146 criteria-diagnosed cases after validation, extrapolated from 107 completed questionnaires (61% return rate). Overall point prevalence was 0·77% [95% confidence interval (CI) 0·76–0·78%]. An additional 18 417 cases had a history of one to four flexural skin boils. In physician-diagnosed cases, odds ratios (ORs) for current smoker and obesity (body mass index &gt; 30 kg m-2) were 3·61 (95% CI 3·44–3·79) and 3·29 (95% CI 3·14–3·45). HS was associated with type 2 diabetes, Crohn disease, hyperlipidaemia, acne and depression, and not associated with ulcerative colitis or polycystic ovary syndrome.

Conclusions
Contrary to results of previous population-based studies, HS is relatively common, with a U.K. prevalence of 0·77%, one-third being unrecognized, criteria-diagnosed cases using the most stringent disease definition. If individuals with probable cases are included, HS prevalence rises to 1·19%.
RANDOM SHOCK UNCERTAINTY AND INVESTMENT REVERSIBILITY: REAL OPTION FRAMEWORK
Authors: Cui Xue , Shibata Takashi 
Published: November 2017

ABSTRACTThis paper examines, in the presence of random shock, how changes in reversibility of investment affect a firm's optimal investment strategies including the investment timing (trigger) and quantity. Existing results do not consider random shock, where the quantity is independent of the degree of reversibility and the investment trigger is always decreasing with the degree of reversibility. In contrast, we show that with random shock, the quantity exhibits an inverse U‐shape, and the investment trigger is not always monotonically decreasing with the degree of reversibility. Additionally, we show that the firm undertakes a smaller quantity with random shock than without random shock for any degree of reversibility. Finally, we find that the presence of random shock decreases firm value, which implies that random shock is costly for firms.
Fluoxetine induces autophagic cell death via eEF2K‐AMPK‐mTOR‐ULK complex axis in triple negative breast cancer
Authors: Sun Dejuan , Zhu Lingjuan , Zhao Yuqian , Jiang Yingnan , Chen Lixia , Yu Yang , Ouyang Liang 
Published: November 2017

AbstractObjectivesTriple negative breast cancer (TNBC) is a complex and intrinsically aggressive tumour with poor prognosis, and the discovery of targeted small‐molecule drugs for TNBC treatment still remains in its infancy. In this study, we aimed to discover a small‐molecule agent for TNBC treatment and illuminate its potential mechanisms.Materials and methodsCell viability was detected by using methylthiazoltetrazolium (MTT) assay. Electron microscopy, GFP‐LC3 transfection, monodansylcadaverine staining and apoptosis assay were performed to determine Fluoxetine‐induced autophagy and apoptosis. Western blotting and siRNA transfection were carried out to investigate the mechanisms of Fluoxetine‐induced autophagy. iTRAQ‐based proteomics analysis was used to explore the underlying mechanisms.ResultsWe have demonstrated that Fluoxetine had remarkable anti‐proliferative activities and induced autophagic cell death in MDA‐MB‐231 and MDA‐MB‐436 cells. The mechanism for Fluoxetine‐induced autophagic cell death was associated with inhibition of eEF2K and activation of AMPK‐mTOR‐ULK complex axis. Further iTRAQ‐based proteomics and network analyses revealed that Fluoxetine‐induced mechanism was involved in BIRC6, BNIP1, SNAP29 and Bif‐1.ConclusionsThese results demonstrate that Fluoxetine induces apoptosis and autophagic cell death in TNBC, which will hold a promise for the future TNBC therapy.
Molecular testing of BRAF, RAS and TERT on thyroid FNAs with indeterminate cytology improves diagnostic accuracy
Authors: Decaussin‐Petrucci M. , Descotes F. , Depaepe L. , Lapras V. , Denier M.‐L. , Borson‐Chazot F. , Lifante J.‐C. , Lopez J. 
Published: November 2017

ObjectiveLiquid‐based (LB)‐FNA is widely recognized as a reliable diagnostic method to evaluate thyroid nodules. However, up to 30% of LB‐FNA remain indeterminate according to the Bethesda system. Use of molecular biomarkers has been recommended to improve its pathological accuracy but implementation of these tests in clinical practice may be difficult. Here, we evaluated feasibility and performance of molecular profiling in routine practice by testing LB‐FNA for BRAF, N/HRAS and TERT mutations.MethodsWe studied a large prospective cohort of 326 cases, including 61 atypia of undetermined significance, 124 follicular neoplasms, 72 suspicious for malignancy and 69 malignant cases. Diagnosis of malignancy was confirmed by histology on paired surgical specimen.ResultsMutated LB‐FNAs were significantly associated with malignancy regardless of the cytological classification. Overall sensitivity was 60% and specificity 89%. Importantly, in atypia of undetermined significance and follicular neoplasm patients undergoing surgery according to the Bethesda guidelines, negative predictive values were 85.4% and 90% respectively. TERT promoter mutation was rare but very specific for malignancy (5.5%) suggesting that it could be of interest in patients with indeterminate cytology.ConclusionsMutation profiling can be successfully performed on thyroid LB‐FNA without any dedicated sample in a pathology laboratory. It is an easy way to improve diagnostic accuracy of routine LB‐FNA and may help to better select patients for surgery and to avoid unnecessary thyroidectomies.
Prevalence and severity of non‐alcoholic fatty liver disease are underestimated in clinical practice: impact of a dedicated screening approach at a large university teaching hospital
Authors: Marjot T. , Sbardella E. , Moolla A. , Hazlehurst J. M. , Tan G. D. , Ainsworth M. , Cobbold J. F. L. , Tomlinson J. W. 
Published: November 2017

AbstractAimsTo define the attitudes and current clinical practice of diabetes specialists with regard to non‐alcoholic fatty liver disease and, based on the results, implement an evidenced‐based pathway for non‐alcoholic fatty liver disease assessment.MethodsAn online survey was disseminated to diabetes specialists. Based on findings from this survey, we sought a local solution by launching an awareness campaign and implementing a screening algorithm across all diabetes clinics at a secondary/tertiary referral centre.ResultsA total of 133 diabetes specialists responded to the survey. Fewer than 5% of responders correctly assessed the prevalence and severity of advanced fibrotic non‐alcoholic fatty liver disease in people with diabetes as 50–75%. Whilst most clinicians performed liver function tests, only 5.7% responded stating that they would use, or had used, a non‐invasive algorithm to stage the severity of non‐alcoholic fatty liver disease. Implementing a local non‐alcoholic fatty liver disease awareness campaign and screening strategy using pre‐printed blood request forms, we ensured that 100% (n=395) of all people with Type 1 and Type 2 diabetes mellitus attending secondary/tertiary care diabetes clinics over a 6‐month period were appropriately screened for advanced fibrotic non‐alcoholic fatty liver disease using the Fib‐4 index; 17.9% required further investigation or assessment.ConclusionsThe prevalence and severity of non‐alcoholic fatty liver disease are underestimated among diabetes specialists. The Fib‐4 index can easily be incorporated into clinical practice in secondary/tertiary care to identify those individuals at risk of advanced fibrosis who require further assessment and who may benefit from a dedicated multidisciplinary approach to their management.
A Retrospective Nested Cohort Study of Emergency Department Revisits for Migraine in New York City
Authors: Minen Mia T. , Boubour Alexandra , Wahnich Amanda , Grudzen Corita , Friedman Benjamin W. 
Published: November 2017

ObjectiveMigraine causes more than 1.2 million visits to US emergency departments (EDs) annually. Many of these visits are revisits among patients who had already been treated in an ED for migraine. The goal of this analysis was to determine the frequency of headache revisits among patients who present to an ED for management of migraine and sociodemographic factors associated with the revisit.MethodsUsing the New York City Department of Health and Mental Hygiene Syndromic Surveillance database, we conducted a retrospective nested cohort study. We analyzed visits from 18 NYC EDs with discharge diagnoses in the first 6 months of 2015. We conducted descriptive analyses to determine the frequency of headache revisit within 6 months of an index ED visit for migraine and the elapsed time to revisit. Using multivariable logistic regression, we assessed associations between age, sex, poverty, and revisit.ResultsOf 1052 ED visits with an ED discharge diagnosis of migraine during the first 6 months of 2015, 277 (26.3%) had a headache revisit within 6 months of their initial migraine visit and 131 (12.5%) had two or more revisits at the same hospital. Of the revisits for headache, 9% occur within 72 hours and 46% occur within 90 days of the initial migraine visit. Sex, age, and poverty level were not associated with an ED revisit.ConclusionMore than a quarter of initial ED visits for migraine are followed by headache revisits in <6 months. Future work should target interventions to decrease the frequency of headache revisits.
Food insecurity may lead to incomplete HIV viral suppression and less immune reconstitution among HIV/hepatitis C virus‐coinfected people
Authors: Aibibula W , Cox J , Hamelin A‐M , Moodie EEM , Naimi AI , McLinden T , Klein MB , Brassard P 
Published: November 2017

ObjectivesThe aim of this study was to determine the impact of food insecurity (FI) on HIV viral load and CD4 count among people coinfected with HIV and hepatitis C virus (HCV).MethodsThis study was conducted using data from the Food Security & HIV‐HCV Sub‐Study of the Canadian Co‐Infection Cohort study. FI was measured using the adult scale of Health Canada's Household Food Security Survey Module and was classified into three categories: food security, moderate food insecurity and severe food insecurity. The association between FI, HIV viral load, and CD4 count was assessed using a stabilized inverse probability weighted marginal structural model.ResultsA total of 725 HIV/HCV‐coinfected people with 1973 person‐visits over 3 years of follow‐up contributed to this study. At baseline, 23% of participants experienced moderate food insecurity and 34% experienced severe food insecurity. The proportion of people with undetectable HIV viral load was 75% and the median CD4 count was 460 [interquartile range (IQR): 300–665] cells/μL. People experiencing severe food insecurity had 1.47 times [95% confidence interval (CI): 1.14, 1.88] the risk of having detectable HIV viral load and a 0.91‐fold (95% CI: 0.84, 0.98) increase in CD4 count compared with people who were food secure.ConclusionsThese findings provide evidence of the negative impact of food insecurity on HIV viral load and CD4 count among HIV/HCV‐coinfected people.