bluuebunny/crossref_metadata_2025_split huggingface dataset:
High melphalan exposure is associated with improved overall survival in myeloma patients receiving high dose melphalan and autologous transplantation
Authors: Nath Christa E. , Trotman Judith , Tiley Campbell , Presgrave Peter , Joshua Douglas , Kerridge Ian , Kwan Yiu Lam , Gurney Howard , McLachlan Andrew J. , Earl John W. , Nivison‐Smith Ian , Zeng Lihua , Shaw Peter J. 
Published: February 2016

AimHigh dose melphalan (HDM) and autologous stem cell transplantation (ASCT) retains a central role in the treatment of myeloma. The aim of this study was to determine whether HDM exposure (area under the concentration vs. time curve, AUC), is significantly associated with transplant outcomes.MethodsMelphalan concentrations were measured in six to 11 plasma samples collected after HDM (median 192 mg m–2) to determine melphalan AUC for a total of 114 patients. Binary logistic regression was used to assess whether melphalan AUC was associated with severe (≥ grade 3) oral mucositis. Multivariate Cox regression was used to assess whether melphalan AUC was significantly associated with time to progression, progression‐free survival and overall survival (OS).ResultsMelphalan AUC ranged from 4.9 to 24.6 mg l–1 h, median 12.84 mg l–1 h. Melphalan AUC above the median was a risk factor for severe mucositis (HR 1.21, 95% CI 1.06, 1.38, P = 0.004) but was also associated with significantly improved overall survival (OS) (HR 0.40, 95% CI 0.20, 0.81, P = 0.001), with an estimated median survival of 8.50 years vs. 5.38 years for high vs. low AUC groups. Multivariate analysis did not identify melphalan AUC as being significantly associated with time to progression or progression‐free survival.ConclusionsThis large scale pharmacodynamic analysis of HDM demonstrates that high melphalan exposure is associated with improved survival, with an acceptable increase in transplant toxicity. These results suggest studies targeting a higher AUC are warranted in patients undergoing HDM and ASCT for myeloma.
Initial experience of an algorithm‐based protocol for the community follow‐up of men with prostate cancer
Authors: Goodall Philip P. , Little Jessica , Robinson Eleanor , Trimble Ian , Cole Owen J. , Walton Thomas J. 
Published: February 2016

ObjectiveTo evaluate the implementation of a novel algorithm‐based discharge programme for the community follow‐up of men with prostate cancer.Patients and MethodsMen with prostate cancer considered suitable for discharge were identified from consultant‐led and clinical nurse‐specialist telephone clinics at Nottingham University Hospitals National Health Service Trust. Patients were discharged on to one of four discharge pathways: watchful waiting, androgen‐deprivation therapy (ADT), post‐prostatectomy, and post‐radiotherapy. Primary care providers were asked to adhere to specific surveillance measures and refer patients back to secondary care after breach of pre‐defined prostate‐specific antigen (PSA) level threshold criteria. Reasons for non‐compliance, re‐referral, and cause of death were determined for all discharged men.ResultsIn all, 573 men were discharged across all four pathways; 169 on the watchful‐waiting pathway, 229 on the ADT pathway, 95 on the post‐prostatectomy pathway, and 80 on the post‐radiotherapy pathway. All patients had ≥12 months of follow‐up. In all, 48 of 54 (88.9%) men were re‐referred promptly after a PSA‐threshold breach. Of the remaining six patients there were three refusals, one unrelated death before referral, and two late referrals at 4 months. Three patients were lost to follow‐up due to database non‐registration and were subsequently recalled, none of whom had a PSA‐threshold breach. There were three unexpected deaths attributed to prostate cancer: two were community deaths with no biochemical or clinical evidence of prostate cancer progression, while one was due to a likely progressive PSA non‐secreting tumour.ConclusionInitial results suggest the algorithm‐based protocol is a viable, effective, and oncologically safe method for the controlled discharge of men from secondary to primary care. Longer‐term follow‐up, patient satisfaction and cost‐effectiveness data are required to assess the true impact of the initiative.
Target the Source: Optimal Spatiotemporal Resource Allocation for Invasive Species Control
Authors: Baker Christopher M. 
Published: February 2016

AbstractDetermining how to cost‐effectively allocate resources for managing invasive species is a notoriously difficult problem. Invasive species control problems are always spatiotemporal, but much of the current theory about control strategies is either spatial or temporal. This article uses a deterministic spatiotemporal model of invasive species dynamics and identifies the optimal management strategy across a range of situations. The optimal solution points a principle of targeting the source of the population, which in many cases is the region of the landscape where the invader is most abundant. The analysis presented here is the first capable of solving for optimal strategies for invasive species over large and irregular environments. Thus, it is an important step forward for both the understanding of control strategies and the application to management scenarios.
Lactic acidosis: relationship between metformin levels, lactate concentration and mortality
Authors: Boucaud‐Maitre D. , Ropers J. , Porokhov B. , Altman J.‐J. , Bouhanick B. , Doucet J. , Girardin E. , Kaloustian E. , Lassmann Vague V. , Emmerich J. 
Published: February 2016

AbstractAimThe role of metformin in lactic acidosis is regularly questioned. Arguments against a causal role for metformin in lactic acidosis occurrence are the lack of correlation between plasma metformin and lactate levels, as well as between metformin plasma levels and mortality. We aim to analyse these correlations in a large series of lactic acidosis cases recorded in the French nationwide pharmacovigilance database.MethodsAll cases of lactic acidosis spontaneously reported between 1985 and October 2013 associated with metformin exposure were extracted from the pharmacovigilance database. We assessed the statistical correlations between prescribed daily doses of metformin, plasma concentrations of metformin and lactate, pH and plasma creatinine, as well as the relationship between mortality and these variables.ResultsSeven hundred and twenty‐seven cases of lactic acidosis were reported during the period. Metformin plasma concentration was documented for 260 patients, lactate plasma concentration for 556 patients, pH for 502 patients, creatinine for 397 patients and the vital outcome for 713 patients. Metformin plasma concentration, lactate concentration, pH and plasma creatinine were all correlated (P < 0.001). There were significant differences between surviving and deceased patients in terms of metformin plasma levels (25.2 vs. 37.4 mg/l, P = 0.002) and lactate concentrations (10.8 vs. 16.3 mmol/l, P < 0.001). Thirty per cent of patients died when metformin concentration was > 5 mg/l compared with 11% for patients with concentration < 5 mg/l (P = 0.003).ConclusionsOur data suggest that metformin accumulation contributes to the pathogenesis and prognosis of lactic acidosis.
Soluble galectin‐3 is associated with premature myocardial infarction
Authors: Winter Max‐Paul , Wiesbauer Franz , Alimohammadi Arman , Blessberger Hermann , Pavo Noemi , Schillinger Martin , Huber Kurt , Wojta Johann , Lang Irene M. , Maurer Gerald , Goliasch Georg 
Published: February 2016

AbstractBackgroundInflammatory responses are pivotal in the initiation and development of premature atherosclerotic lesions. Galectin‐3 represents a valuable biomarker for both progression and destabilization of atherosclerotic lesions. This study aims to assess the involvement of galectin‐3 in premature myocardial infarction.DesignIn this multicentre case–control study, we assessed circulating galectin‐3 levels in 144 patients comprising 72 consecutive survivors of acute myocardial infarction (≤ 40 years) and 72 hospital controls frequency matched for age, gender and centre.ResultsPatients with acute myocardial infarction showed significantly higher galectin‐3 levels as compared to controls in the acute phase of acute myocardial infarction (2552 ± 1992 vs. 1666 ± 829 pg/mL; P < 0·001) as well as in the stable phase 1 year after the index event (3692 ± 1774 vs. 1666 ± 829 pg/mL; P < 0·001). Circulating galectin‐3 was significantly and independently associated with premature myocardial infarction in the logistic regression analysis (acute phase: adj. OR per 1‐SD change 2·03, 95% CI 1·30−3·19; P = 0·002; stable phase: adj. OR of 6·54 (95% CI 2·56−16·68; P < 0·001). Moreover, we observed a significant correlation between circulating galectin‐3 and leucocyte count (r = 0·35, P < 0·001), non‐HDL cholesterol (r = 0·23, P = 0·014) and HDL cholesterol (r = −0·29, P = 0·002).ConclusionWe demonstrated that elevated levels of circulating galectin‐3 are strongly associated with premature myocardial infarction. Galectin‐3 might serve as link between dyslipidaemia as driving force of plaque formation with inflammation as initiator of plaque rupture in patients with premature acute myocardial infarction.
The interrelationships of birthweight, inflammation and body composition in healthy adults
Authors: Kofler Thomas , Bossard Matthias , Aeschbacher Stefanie , Tabord Alexandra , Ruperti Repilado Francisco Javier , van der Lely Stéphanie , Berger Sebastian , Risch Martin , Risch Lorenz , Conen David 
Published: February 2016

AbstractBackgroundLower birthweight is associated with an increased risk of cardiovascular diseases and diabetes. We hypothesized that inflammation and body fat may be potential mediators for these inverse relationships.Materials and methodsHealthy adults aged 25–41 years were enrolled in a prospective population‐based cohort study in the Principality of Liechtenstein. Main exclusion criteria were diabetes, overt cardiovascular disease or a body mass index > 35 kg/m2. Birthweight was self‐reported by the study participants. White blood cell (WBC) count and high‐sensitivity C‐reactive protein (hs‐CRP) levels were assayed from fresh blood samples. Body composition was determined by bioelectrical impedance analysis. Multivariable linear regression models were constructed to assess the relationships between birthweight, inflammation and body composition.ResultsOur sample consisted of 1774 participants (53·4% females) with a median age of 37 years. Median birthweight was 3355 g. In multivariable models, we found an inverse relationship of birthweight with hs‐CRP levels (β −0·010 (95% CI −0·02; −0·002), P = 0·01) and WBC count (β −0·002 (95% CI −0·004; −0·0002), P = 0·03). Additional adjustment for body fat mass attenuated these relationships (β −0·008 (95% CI −0·02; 0·0003), P = 0·06 for hs‐CRP levels and (β −0·002 (95% CI −0·004; 0·0006), P = 0·16 for WBC count. Body fat mass itself was strongly associated with birthweight (β −0·06 (95% CI −0·10; −0·03), P < 0·0001).ConclusionBirthweight is inversely associated with inflammation in adulthood. This relationship may be mediated by an elevated body fat mass among individuals with lower birthweight.
The importance of diurnal and nocturnal activity and interspecific interactions for space use by ants in clear‐cuts
Authors: ŻMIHORSKI MICHAŁ , ŚLIPIŃSKI PIOTR 
Published: February 2016

1. Full sunlight conditions in open clear‐cuts may limit the activity of ants as soil surface temperatures reach lethal levels. Therefore, differences may be expected between the diurnal and nocturnal activity of ants, and in the interactions between ant species. These predictions, however, have been poorly investigated so far.2. The circadian activity of ants in clear‐cuts in managed forests in Poland was investigated. Repeated counts of ants were performed during the day and the following night at the clear‐cut edge and in the clear‐cut interior. Interspecific interactions and the effect of plant coverage were also considered.3. Abundances of Formica fusca Linnaeus and red wood ants were higher during the day, whereas Myrmica were more common at night. Formica fusca, Lasius and red wood ants were more common at the clear‐cut edge than in the interior. Myrmica showed the opposite pattern, but at night, its numbers increased at the edge. Plant coverage positively affected F. fusca and red wood ants.4. Red wood ants tended to be negatively associated with Lasius, whereas they were neutral for F. fusca. The negative association of red wood ants and Myrmica was stronger during the day compared to night.5. The time of day was a strong driver of ant activity in the clear‐cuts, whereas the distribution of red wood ants was of lesser importance. It is concluded that circadian activity may substantially contribute to niche separation between coexisting species, therefore, studies performed exclusively during the day cannot reflect the real structure of the community.
Pro‐ and anticoagulant factors facilitate thrombin generation and balance the haemostatic response to FEIBA® in prophylactic therapy
Authors: Varadi K. , Tangada S. , Loeschberger M. , Montsch P. , Schrenk G. , Ewenstein B. , Turecek P. L. 
Published: February 2016

IntroductionFEIBA® consists of zymogens and traces of activated forms of procoagulant factors II, VII, IX, X, anticoagulants protein C and TFPI, and small amounts of cofactors FV, FVIII and protein S, in a balanced ratio. As shown previously, FII‐FXa complex plays a key role in FEIBA's mode of action (MoA).MethodsThrombin generation (TG) was measured by spiking coagulation factors, cofactors and inhibitors to high titer FVIII inhibitor plasma, and in plasma samples from patients in a phase 3 clinical study evaluating the safety and efficacy of FEIBA prophylaxis in haemophilia A patients with inhibitors.ResultsIncreasing the FXa/FII ratio improved TG, while adding coagulation enzyme components had a negligible effect. Adding FX, FIX, and FVII increased the peak thrombin and decreased the lag time. The presence of FV and phospholipids led to faster TG, while protein C and protein S reduced the amount of peak thrombin. TFPI appeared to have no effect. Patients on prophylaxis with FEIBA® showed higher peak thrombin and AUC with elevated FII, FX, FIX, FVIIa, and protein C levels, and experienced significantly less bleeding episodes than those receiving on‐demand treatment.ConclusionThese experiments showed that although the FII‐FXa complex induced immediate thrombin formation on the activated platelet surface, other procoagulant components of FEIBA were necessary to achieve an optimal thrombin burst. The presence of the pro‐ and anti‐coagulants in FEIBA provides a haemostatic balance, and is thus expected to prevent thrombotic events. Recent clinical data verified the postulated MoA of FEIBA in prophylaxis treatment.
Length time bias in surveillance for hepatocellular carcinoma and how to avoid it
Authors: Cucchetti Alessandro , Garuti Francesca , Pinna Antonio Daniele , Trevisani Franco ,   for the Italian Liver Cancer (ITA.LI.CA) group
Published: February 2016

AimLength time bias is a selection bias which can lead to an overestimation of survival of screening‐detected cases caused by the relative excess of slower‐growing tumors detected with respect to symptomatic cases. This leads to the incorrect perception that screening improves outcomes when it only selects tumors with a favorable biology. Data regarding this bias in surveillance for hepatocellular carcinoma (HCC) have never been provided.MethodsA semi‐Markov model was developed to investigate this issue. An exponential tumor growth was applied. During its growth, tumor diagnosis “at surveillance appointments” was made when tumor attained a size equal to or above the size of tumors diagnosed in surveilled patients obtained from pertinent published reports, or “in‐between appointments” (due to the development of symptoms) if tumor size attained the size of symptomatic diagnosis, derived from published reports; otherwise the tumor continued to grow until the time horizon had been reached. Tumor doubling time (DT) values were recorded according to the method of diagnosis.ResultsIn a theoretical cohort of 1000 patients submitted to semiannual surveillance, 72.5% will be diagnosed at a surveillance appointment and 18% because of symptom development, although under surveillance. Patients diagnosed with HCC at a surveillance appointment had a median tumor DT of 100 days (interquartile range, 68–143 days), whereas those diagnosed because of symptoms had a median DT of 42 days (interquartile range, 29–58 days) although under surveillance.ConclusionThe surveillance propensity to detect slower‐growth tumors is relevant, and practical suggestions to minimize this bias in longitudinal studies are provided.
Functional properties of protein hydrolysates from Riceberry rice bran
Authors: Thamnarathip Parichart , Jangchud Kamolwan , Jangchud Anuvat , Vardhanabhuti Bongkosh 
Published: February 2016

SummaryProtein hydrolysate from pigmented Riceberry rice bran has great potential to be used in food products due to its protein content and antioxidative activities. In this study, characteristics, solubility, heat stability and emulsification properties of protein hydrolysates from the bran fraction of two rice cultivars, commercial rice bran (CBH) and Riceberry bran (RBH), were investigated. Both CBH and RBH showed the lowest solubility near their isoelectric point between pH 2 and 3. Solubility of RBH increased with increasing pH as the hydrolysates became more negatively charged; however, solubility of CBH was less dependent on pH. Heating did not significantly affect solubility of both hydrolysates which could be due to reduced aggregation of low‐molecular weight peptides and/or the exposure of charged and polar groups after hydrolysis. Oil‐in‐water emulsions stabilised by RBH were more stable compared to those stabilised by CBH. Maximum stability was achieved with RBH at pH 6 where no creaming was observed after 14 day storage. Higher stability could be due to increased surface protein coverage, more negative charge and higher viscosity of RBH‐stabilised emulsions. In addition, higher carbohydrate content and the presence of flavonoid could also contribute to an increase in stability. These results can be applied in food products using rice bran protein hydrolysate as nutritional ingredients.
Parallel effects of the inversion In(3R)Payne on body size across the North American and Australian clines in Drosophila melanogaster
Authors: Kapun M. , Schmidt C. , Durmaz E. , Schmidt P. S. , Flatt T. 
Published: February 2016

AbstractChromosomal inversions are thought to play a major role in climatic adaptation. In D. melanogaster, the cosmopolitan inversion In(3R)Payne exhibits latitudinal clines on multiple continents. As many fitness traits show similar clines, it is tempting to hypothesize that In(3R)P underlies observed clinal patterns for some of these traits. In support of this idea, previous work in Australian populations has demonstrated that In(3R)P affects body size but not development time or cold resistance. However, similar data from other clines of this inversion are largely lacking; finding parallel effects of In(3R)P across multiple clines would considerably strengthen the case for clinal selection. Here, we have analysed the phenotypic effects of In(3R)P in populations originating from the endpoints of the latitudinal cline along the North American east coast. We measured development time, egg‐to‐adult survival, several size‐related traits (femur and tibia length, wing area and shape), chill coma recovery, oxidative stress resistance and triglyceride content in homokaryon lines carrying In(3R)P or the standard arrangement. Our central finding is that the effects of In(3R)P along the North American cline match those observed in Australia: standard arrangement lines were larger than inverted lines, but the inversion did not influence development time or cold resistance. Similarly, In(3R)P did not affect egg‐to‐adult survival, oxidative stress resistance and lipid content. In(3R)P thus seems to specifically affect size traits in populations from both continents. This parallelism strongly suggests an adaptive pattern, whereby the inversion has captured alleles associated with growth regulation and clinal selection acts on size across both continents.
Effect of Nanofiller Loading on Cure Efficiency and Potential Color Change of Model Composites
Authors: de Oliveira Dayane Carvalho Ramos Salles , de Menezes Livia Rodrigues , Gatti Alexandre , Correr Sobrinho Lourenço , Ferracane Jack L. , Sinhoreti Mario Alexandre Coelho 
Published: February 2016

AbstractObjectivesTo evaluate the effect of nanofiller loading on cure efficiency and potential color change of experimental composites.Materials and MethodsFour different polymeric materials were produced using the same organic matrix blend. To this matrix, different amounts of 0.05 μm fumed silica filler were added: no filler, 13, 52, and 65wt%. Fourier transform infrared spectroscopy was used to evaluate the degree of conversion (DC) for each composite using near‐IR analysis, and spectrophotometry according to CIELab chromatic space was used to evaluate the color change.To induce color change, composites were artificially aged with exposure to cycles of UV‐B light for 300 hours. Trasmission electron microscopy was used to illustrate nanoffiler aglomeration in the resin matrix. Data were analyzed using correlation analysis (α = 0.05).ResultsThere was an excellent inverse linear correlation between filler wt% and either DC or color change. Greater changes to red (+Δa) and yellow (+Δb) were observed as the filler wt% increased.ConclusionsA higher percentage of nano‐sized filler particles in dental resin composites directly affects their cure efficiency and potential for color change.Clinical SignificanceThe increase in filler particle loading negatively affected monomer conversion and color stability of resin‐based composites. As reduced filler loading results in poorer mechanical properties, to enhance color stability, resin‐based composites should be formulated by making the refractive index of the polymeric matrix more closely match that of the filler throughout the polymerization process. (J Esthet Restor Dent, 2016)