Studies suggest a relationship between hypertension and outcome in bevacizumab-treated patients with metastatic colorectal cancer (mCRC). We performed a retrospective analysis of two phase II studies ...(BECA and BECOX) to determine if hypertension and proteinuria predict outcome in elderly patients with mCRC treated with bevacizumab.
Patients ≥ 70 years of age received either capecitabine 1250 mg/m(2) bid days 1-14 + bevacizumab 7.5 mg/kg day 1 every 21 days (BECA study) or capecitabine 1000 mg/m(2) bid days 1-14 with bevacizumab 7.5 mg/kg and oxaliplatin 130 mg/m(2) day 1 (BECOX study). The primary objective was to correlate hypertension and proteinuria with overall response rate (ORR), time to progression (TTP) and overall survival (OS). Secondary objectives included identification of risk factors associated with the development of hypertension and proteinuria and determining whether development of hypertension or proteinuria in the first 2 cycles was related to ORR, disease-control rate (DCR), TTP or OS.
In total, 127 patients (median age 75.5 years) were included in the study. Hypertension correlated with DCR and OS; proteinuria correlated with ORR and DCR. Proteinuria or hypertension in the first 2 cycles did not correlate with efficacy. Risk factors for hypertension were female gender (odds ratio OR 0.241; P = 0.011) and more bevacizumab cycles (OR 1.112; P = 0.002); risk factors for proteinuria were diabetes (OR 3.869; P = 0.006) and more bevacizumab cycles (OR 1.181; P<0.0001). Multivariate analysis identified as having prognostic value: baseline lactate dehydrogenase, haemoglobin, number of metastatic lesions and DCR.
This analysis of two phase II studies suggests that hypertension is significantly correlated with OS but not with ORR and TTP, whereas proteinuria is correlated with ORR but not with OS and TTP. Both hypertension and proteinuria are associated with the duration of bevacizumab treatment and do not represent an independent prognostic factor.
Temperate reefs are superb tractable systems for testing hypotheses in ecology and evolutionary biology. Accordingly there is a rich history of research stretching back over 100 years, which has made ...major contributions to general ecological and evolutionary theory as well as providing better understanding of how littoral systems work by linking pattern with process. A brief resumé of the history of temperate reef ecology is provided to celebrate this rich heritage. As a community, temperate reef ecologists generally do well designed experiments and test well formulated hypotheses. Increasingly large datasets are being collected, collated and subjected to complex meta-analyses and used for modelling. These datasets do not happen spontaneously – the burgeoning subject of macroecology is possible only because of the efforts of dedicated natural historians whether it be observing birds, butterflies, or barnacles. High-quality natural history and old-fashioned field craft enable surveys or experiments to be stratified (i.e. replicates are replicates and not a random bit of rock) and lead to the generation of more insightful hypotheses. Modern molecular approaches have led to the discovery of cryptic species and provided phylogeographical insights, but natural history is still required to identify species in the field. We advocate a blend of modern approaches with old school skills and a fondness for temperate reefs in all their splendour.
Hydrogen fuel cells based on proton exchange membrane fuel cell (PEMFC) technology are promising as a source of clean energy to power a decarbonized future. However, PEMFCs are limited by a number of ...major inefficiencies; one of the most significant is hydrogen crossover. In this work, we comprehensively study the effects of two-dimensional (2D) materials applied to the anode side of the membrane as H2 barrier coatings on Nafion to reduce crossover effects on hydrogen fuel cells, while studying adverse effects on conductivity and catalyst performance in the beginning of life testing. The barrier layers studied include graphene, hexagonal boron nitride (hBN), amorphous boron nitride (aBN), and varying thicknesses of molybdenum disulfide (MoS2), all chosen due to their expected stability in a fuel cell environment. Crossover mitigation in the materials studied ranges from 4.4% (1 nm MoS2) to 46.1% (graphene) as compared to Nafion 211. Effects on proton conductivity are also studied, suggesting high areal proton transport in materials previously thought to be effectively nonconductive, such as 2 nm MoS2 and amorphous boron nitride under the conditions studied. The results indicate that a number of 2D materials are able to improve crossover effects, with those coated with 8 nm MoS2 and 1 L graphene able to achieve greater crossover reduction while minimizing conductivity penalty.
Maize tassel inflorescence architecture is relevant to efficient production of F₁ seed and yield performance of F₁ hybrids. The objectives of this study were to identify genetic relationships among ...seven measured tassel inflorescence architecture traits and six calculated traits in a maize backcross population derived from two lines with differing tassel architectures, and identify Quantitative Trait Loci (QTL) involved in the inheritance of those tassel inflorescence architecture traits. A Principal Component (PC) analysis was performed to examine relationships among correlated traits. Traits with high loadings for PC1 were branch number and branch number density, for PC2 were spikelet density on central spike and primary branch, and for PC3 were lengths of tassel and central spike. We detected 45 QTL for individual architecture traits and eight QTL for the three PCs. For control of inflorescence architecture, important QTL were found in bins 7.02 and 9.02. The interval phi034--ramosa1 (ral) in bin 7.02 was associated with six individual architecture trait QTL and explained the largest amount of phenotypic variation (17.3%) for PC1. Interval bnlg344-phi027 in bin 9.02 explained the largest amount of phenotypic variation (14.6%) for PC2. Inflorescence architecture QTL were detected in regions with candidate genes fasciated ear2, thick tassel dwarf1, and ral. However, the vast majority of QTL mapped to regions without known candidate genes, indicating positional cloning efforts will be necessary to identify these genes.
Abstract Globally, forests are net carbon sinks that partly mitigates anthropogenic climate change. However, there is evidence of increasing weather-induced tree mortality, which needs to be better ...understood to improve forest management under future climate conditions. Disentangling drivers of tree mortality is challenging because of their interacting behavior over multiple temporal scales. In this study, we take a data-driven approach to the problem. We generate hourly temperate weather data using a stochastic weather generator to simulate 160,000 years of beech, pine, and spruce forest dynamics with a forest gap model. These data are used to train a generative deep learning model (a modified variational autoencoder) to learn representations of three-year-long monthly weather conditions (precipitation, temperature, and solar radiation) in an unsupervised way. We then associate these weather representations with years of high biomass loss in the forests and derive weather prototypes associated with such years. The identified prototype weather conditions are associated with 5–22% higher median biomass loss compared to the median of all samples, depending on the forest type and the prototype. When prototype weather conditions co-occur, these numbers increase to 10–25%. Our research illustrates how generative deep learning can discover compounding weather patterns associated with extreme impacts.
Background:
Comorbidities and extra-articular manifestations (EAMs) substantially increase disease burden and mortality risk in patients (pts) with ankylosing spondylitis (AS).
1,2
Tumour necrosis ...factor inhibitors (TNFi) are highly efficacious and effective in AS treatment (tx), and are used after inadequate response to non-steroidal anti-inflammatory drugs.
3,4
However, the impact of TNFi on the incidence of comorbidities and EAMs in pts with AS is unknown.
5
Objectives:
To determine the incidence of comorbidities and EAMs in TNFi vs non-TNFi treated pts with AS in the US.
Methods:
This was a retrospective, observational cohort study using data from 3 healthcare insurance claims databases: Multi-Payer Claims Database (MPCD Optum Insight; 2007–2010), Truven MarketScan
®
(2010–2014) and US Medicare Fee-for-Service Claims database (2006–2014). Eligible pts: ≥20 years (yrs) for MarketScan/MPCD or ≥65 yrs for Medicare, had an AS diagnosis (≥2 International Classification of Disease, 9
th
version ICD-9 diagnosis codes of 720.0 from a rheumatologist) and ≥12 months’ continuous medical and pharmacy enrolment prior to AS diagnosis (AS index date). Pts with AS not receiving tx were excluded. Tx exposure was reported from the first date of a new prescription/administration of an AS tx (no prior exposure) after the AS index date. Crude incidence rates (IR; shown as cases/100 pt-yrs) were calculated for EAMs (uveitis, psoriasis PSO, psoriatic arthritis PsA, inflammatory bowel disease IBD), with follow-up until the earliest of: death, lost medical/pharmacy coverage, study period end, first outcome occurrence, tx switch/discontinuation. Hazard ratios (HRs) of comorbidities (hospitalised infection, solid cancers) and EAMs for propensity score (PS)-matched pt groups were calculated using Cox proportional hazard regression models. Pts with the specific comorbidity/EAM of interest prior to AS index date were excluded. PS analyses assessed probability of TNFi initiation vs non-TNFi tx and adjusted for factors including comorbidities and demographics. HRs with confidence intervals crossing 1 are not reported.
Results:
20,460 pts with AS were eligible (MPCD: 2,384; MarketScan: 9,032; Medicare: 9,044). In all databases, crude IR of EAMs were higher for TNFi vs non-TNFi treated pts (
Figure 1
). In the PS-matched cohort, incidences of hospitalised infections were lower in TNFi vs non-TNFi treated pts from the MarketScan and Medicare databases (
Figure 2
). Higher incidences of solid cancers and EAMs were observed in TNFi vs non-TNFi treated pts; Medicare data (
Figure 2
). A higher risk of PsA and PSO was seen in TNFi vs non-TNFi treated pts; MarketScan data (
Figure 2
). PS-matched cohort data from the MPCD database were non-significant.
Conclusion:
Despite strong efficacy in treating AS-related signs and symptoms, similar incidence of comorbidities and increased incidence of some EAMs (IBD, PSO/PsA, uveitis) was seen in TNFi vs non-TNFi treated pts in the PS-matched analyses. This may be due to channelling of pts with more severe AS to receive TNFi, despite the PS-matched analysis aiming to overcome this. Moreover, prior medical history of Medicare pts may not be captured in the database, as pts are typically older with longer disease durations. While these results confirm previous findings,
6
a prospective observational study is required to generalise to pts outside the US.
References:
1Stolwijk C. Ann Rheum Dis 2015;74:1373–8;
2Bremander A. Arthritis Care Res 2011;63:550–6;
3Braun J. Scand J Rheumatol 2005;34:178–90;
4Ji X. Front Pharmacol 2019;10:1476;
5Maxwell LJ. Cochrane Database Syst Rev 2015:CD005468;
6Walsh J. J Pharm Health Serv Res 2018;9:115–21.
Acknowledgments:
This study was funded by UCB Pharma. Editorial services were provided by Costello Medical.
Disclosure of Interests:
Atul Deodhar Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Kevin Winthrop Grant/research support from: Bristol-Myers Squibb, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead, GSK, Pfizer Inc, Roche, UCB, Rhonda Bohn Consultant of: UCB Pharma, Benjamin Chan: None declared, Robert Suruki Employee of: UCB Pharma, Jeffrey Stark Employee of: UCB Pharma, Huifeng Yun Grant/research support from: Bristol-Myers Squibb and Pfizer, Sarah Siegel: None declared, Lang Chen: None declared, Jeffrey Curtis Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Corona, Crescendo, Genentech, Janssen, Pfizer, Roche and UCB Pharma, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Corona, Crescendo, Genentech, Janssen, Pfizer, Roche and UCB Pharma
Parasitism is a consequence of complex interactions between host, parasite, and their shared environment, and host behavior can influence parasite risk. Animal personality (i.e., consistent ...behavioral differences that are repeatable across time and context) can influence parasitism with more explorative individuals typically hosting greater parasite loads. Host “sociality” is known to impact parasite risk with more social individuals typically at higher risk of acquiring or transmitting parasites, but other behaviors could also be important. We quantified personality in least chipmunks (Tamias minimus), including repeatability of behavioral traits, and determined whether these personality traits affected ectoparasite prevalence and abundance. We measured personality using standardized hole‐board tests and quantified ectoparasitism of 39 least chipmunks over 2 years at a site in southeastern Manitoba, Canada. We found that activity and exploration were repeatable within the context of the hole‐board test for least chipmunks, which suggests that these traits reflect personality. More exploratory individuals hosted a greater abundance of ectoparasites compared to less exploratory individuals. Our results are consistent with past studies implicating personality as a factor in host–parasite dynamics and suggest that exploration may be an important behavioral correlate of parasite acquisition.
Methods for near-real-time monitoring of new drugs in electronic healthcare data are needed.
In a novel application, we prospectively monitored ischemic, bleeding, and mortality outcomes among ...patients initiating prasugrel versus clopidogrel in routine care during the first 2 years following the approval of prasugrel.
Using the HealthCore Integrated Research Database, we conducted a prospective cohort study comparing prasugrel and clopidogrel initiators in the 6 months following the introduction of prasugrel and every 2 months thereafter. We identified patients who initiated antiplatelets within 14 days following discharge from hospitalizations for myocardial infarction (MI) or acute coronary syndrome. We matched patients using high-dimensional propensity scores (hd-PSs) and followed them for ischemic (i.e., MI and ischemic stroke) events, bleed (i.e., hemorrhagic stroke and gastrointestinal bleed) events, and all-cause mortality. For each outcome, we applied sequential alerting algorithms.
We identified 1,282 eligible new users of prasugrel and 8,263 eligible new users of clopidogrel between September 2009 and August 2011. In hd-PS matched cohorts, the overall MI rate difference (RD) comparing prasugrel with clopidogrel was -23.1 (95 % confidence interval CI -62.8-16.7) events per 1,000 person-years and RDs were -0.5 (-12.9-11.9) and -2.8 (-13.2-7.6) for a composite bleed event outcome and death from any cause, respectively. No algorithms generated alerts for any outcomes.
Near-real-time monitoring was feasible and, in contrast to the key pre-marketing trial that demonstrated the efficacy of prasugrel, did not suggest that prasugrel compared with clopidogrel was associated with an increased risk of gastrointestinal and intracranial bleeding.
Last October, the nuclear medicine departments were informed of the closure of the chromium-51 production line for clinical use. This radionuclide has different diagnostic indications in nephrology ...and hematology. It was therefore essential to set up alternative exploration protocols to overcome this production stoppage.
Chromium-51 EDTA has been replaced by technetium-99m DTPA for the determination of glomerular filtration rates. Sodium chromate was substituted by sodium pertechnetate for the determination of globular volumes. A retrospective analysis of the chromium-51 data was performed followed by a prospective study, from January to December 2019 for technetium tracers.
One hundred and forty-four patients were included in the study. Forty-two EDTA-
Cr and 30 DTPA-
Tc exams were conducted and compared. There were no significant differences between the methods used to assess renal function (P=0.355). For the determination of blood cell and plasma volumes, 47 tests with
Cr and
I and 25 tests with
Tc and
I were performed and compared. There were no significant differences in the determination of total (P=0.325) and globular (P=0.148) volumes.
The study carried out shows that there is no significant difference between the results obtained with chromium-51 and technetium tracers. As a result, clinical activity was maintained in good conditions.
Anadromous Arctic charr
Salvelinus alpinus
is a cold-adapted salmonid that is vulnerable to climate warming and anthropogenic activities including salmon farming, hydropower regulation, and ...pollution, which poses a multiple-stressor scenario that influences or threatens populations. We studied the horizontal and vertical behaviour of Arctic charr tagged with acoustic transmitters (n = 45, mean fish length: 22 cm) in a pristine, subarctic marine area to provide insights into the behaviour of first-time migrants. Tagged fish spent up to 78 d at sea, with high marine survival (82% returned to their native watercourse). While at sea, they utilized mostly near-shore areas, up to 45 km away from their native river. Arctic charr showed large variation in migration distance (mean ± SD: 222 ± 174 km), and the migration distance increased with body size. Although the fish displayed a strong fidelity to surface waters (0-3 m), spatiotemporal variation in depth use was evident, with fish utilizing deeper depths during the day and in late July. These results represent baseline data on Arctic charr’s marine behaviour in a pristine fjord system and highlight the importance of near-shore surface water as feeding areas for first-time migrants. Furthermore, the observed dependency on coastal areas implies a vulnerability to increasing human-induced perturbations, on top of impacts by large-scale climate change in marine and freshwater habitats.
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