To see the other types of publications on this topic, follow the link: Restricted estimator (RE).
Journal articles on the topic 'Restricted estimator (RE)'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Restricted estimator (RE).'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Preuß, M., and A. Ziegler. "A Simplification and Implementation of Random-effects Meta-analyses Based on the Exact Distribution of Cochran’s Q." Methods of Information in Medicine 53, no. 01 (2014): 54–61. http://dx.doi.org/10.3414/me13-01-0073.
Full textAbstract:
SummaryBackground: The random-effects (RE) model is the standard choice for meta-analysis in the presence of heterogeneity, and the stand ard RE method is the DerSimonian and Laird (DSL) approach, where the degree of heterogeneity is estimated using a moment-estimator. The DSL approach does not take into account the variability of the estimated heterogeneity variance in the estimation of Cochran’s Q. Biggerstaff and Jackson derived the exact cumulative distribution function (CDF) of Q to account for the variability of Ť 2.Objectives: The first objective is to show that the explicit numerical computation of the density function of Cochran’s Q is not required. The second objective is to develop an R package with the possibility to easily calculate the classical RE method and the new exact RE method.Methods: The novel approach was validated in extensive simulation studies. The different approaches used in the simulation studies, including the exact weights RE meta-analysis, the I 2 and T 2 estimates together with their confidence intervals were implemented in the R package metaxa.Results: The comparison with the classical DSL method showed that the exact weights RE meta-analysis kept the nominal type I error level better and that it had greater power in case of many small studies and a single large study. The Hedges RE approach had inflated type I error levels. Another advantage of the exact weights RE meta-analysis is that an exact confidence interval for T 2is readily available. The exact weights RE approach had greater power in case of few studies, while the restricted maximum likelihood (REML) approach was superior in case of a large number of studies. Differences between the exact weights RE meta-analysis and the DSL approach were observed in the re-analysis of real data sets. Application of the exact weights RE meta-analysis, REML, and the DSL approach to real data sets showed that conclusions between these methods differed.Conclusions: The simplification does not require the calculation of the density of Cochran’s Q, but only the calculation of the cumulative distribution function, while the previous approach required the computation of both the density and the cumulative distribution function. It thus reduces computation time, improves numerical stability, and reduces the approximation error in meta-analysis. The different approaches, including the exact weights RE meta-analysis, the I 2 and T 2estimates together with their confidence intervals are available in the R package metaxa, which can be used in applications.
2
Latimer, NR, IR White, KR Abrams, and U. Siebert. "Causal inference for long-term survival in randomised trials with treatment switching: Should re-censoring be applied when estimating counterfactual survival times?" Statistical Methods in Medical Research 28, no. 8 (June 25, 2018): 2475–93. http://dx.doi.org/10.1177/0962280218780856.
Full textAbstract:
Treatment switching often has a crucial impact on estimates of effectiveness and cost-effectiveness of new oncology treatments. Rank preserving structural failure time models (RPSFTM) and two-stage estimation (TSE) methods estimate ‘counterfactual’ (i.e. had there been no switching) survival times and incorporate re-censoring to guard against informative censoring in the counterfactual dataset. However, re-censoring causes a loss of longer term survival information which is problematic when estimates of long-term survival effects are required, as is often the case for health technology assessment decision making. We present a simulation study designed to investigate applications of the RPSFTM and TSE with and without re-censoring, to determine whether re-censoring should always be recommended within adjustment analyses. We investigate a context where switching is from the control group onto the experimental treatment in scenarios with varying switch proportions, treatment effect sizes, treatment effect changes over time, survival function shapes, disease severity and switcher prognosis. Methods were assessed according to their estimation of control group restricted mean survival that would be observed in the absence of switching, up to the end of trial follow-up. We found that analyses which re-censored usually produced negative bias (i.e. underestimating control group restricted mean survival and overestimating the treatment effect), whereas analyses that did not re-censor consistently produced positive bias which was often smaller in magnitude than the bias associated with re-censored analyses, particularly when the treatment effect was high and the switching proportion was low. The RPSFTM with re-censoring generally resulted in increased bias compared to the other methods. We believe that analyses should be conducted with and without re-censoring, as this may provide decision-makers with useful information on where the true treatment effect is likely to lie. Incorporating re-censoring should not always represent the default approach when the objective is to estimate long-term survival times and treatment effects.
3
Sekulić, Jovana, and Feđa Netjasov. "Modelling of runway excursions using Fault Tree Analysis." Tehnika 76, no. 4 (2021): 475–82. http://dx.doi.org/10.5937/tehnika2104475s.
Full textAbstract:
Runway excursion (RE) is recognized as one of the main Airport Safety Issues. It can be defined as an event in which an aircraft veers-off or overruns the runway surface during either takeoff or landing. In this paper an application of Fault Tree Analysis (FTA) method on RE events is presented. FTA belongs to quantitative class of causal methods. It estimates the risk of incident or accident according to estimation of probability of occurrence of each cause of an event. It might be restricted to pure statistical analysis based on the available data or combine these data with expert judgment on the accident causes. The aim of this paper is to identify potential causal factors. In order to illustrate FTA application on RE, two models were developed: one for landing and other for take-off. Application of FTA has shown what are the most critical causal factors whose knowledge allows developing certain measures to reduce the risk of RE.
4
Chen, Shiyi, and Amelia U. Santos-Paulino. "Energy consumption restricted productivity re-estimates and industrial sustainability analysis in post-reform China." Energy Policy 57 (June 2013): 52–60. http://dx.doi.org/10.1016/j.enpol.2012.08.060.
Full text
5
Mortimer, Suzanne I., and J. W. James. "Changes in genetic parameters under restricted index selection." Genetical Research 49, no. 2 (April 1987): 129–34. http://dx.doi.org/10.1017/s0016672300026926.
Full textAbstract:
SummaryThe ability of restricted selection indices to prevent genetic change in a restricted trait over several generations of selection was studied using deterministic computer models. Four loci, two affecting each trait independently, and two pleiotropic loci, one affecting each trait in the same direction, and one with opposite effects, were modelled. In general, continued effectiveness of the restriction was achieved only when the restricted trait was affected by only one locus. In some conditions (equal gene frequencies), an independent locus and one pleiotropic locus affecting the restricted trait allowed maintenance of the restriction. The results suggest that long-term restriction may be very difficult without re-estimation of parameters.
6
Kitamura, Nobutaka, Shinya Ohkouchi, Ryushi Tazawa, Haruyuki Ishii, Toshinori Takada, Takuro Sakagami, Takahiro Tanaka, and Koh Nakata. "Incidence of autoimmune pulmonary alveolar proteinosis estimated using Poisson distribution." ERJ Open Research 5, no. 1 (February 2019): 00190–2018. http://dx.doi.org/10.1183/23120541.00190-2018.
Full textAbstract:
The incidence and prevalence of autoimmune pulmonary alveolar proteinosis in Japan were previously estimated to be 0.49 and 6.2 per million, respectively. Thereafter, an increase in serological diagnosis forced a re-estimation of the incidence based on more contemporaneous data using more robust methods.Sera of 702 patients were positive for granulocyte-macrophage colony-stimulating factor autoantibody during the 2006–2016 period (group A). Of these patients, 43 were actively surveyed in Niigata prefecture (group B) for estimation of the incidence. To estimate the survival period, 103 patients (group C) were investigated retrospectively for the 1999–2017 period using restricted mean survival time.In group A, the number of patients diagnosed in each prefecture was closely correlated with the corresponding population, indicating no regional integration of onset. In group B, a total of 43 patients were diagnosed, the annual number followed a Poisson distribution and the incidence was thus estimated to be 1.65 per million. In group C, the retrospective cohort study revealed the mean survival period to be 16.1 years. Taken together, the prevalence was estimated to be 26.6 per million, indicating that the previous data for incidence and prevalence was an underestimation.
7
Miranda, Judith C., José M. León, Camillo Pieramati, Mayra M. Gómez, Jesús Valdés, and Cecilio Barba. "Estimation of Genetic Parameters for Peak Yield, Yield and Persistency Traits in Murciano-Granadina Goats Using Multi-Traits Models." Animals 9, no. 7 (July 1, 2019): 411. http://dx.doi.org/10.3390/ani9070411.
Full textAbstract:
This paper studies parameters of a lactation curve such as peak yield (PY) and persistency (P), which do not conform to the usual selection criteria in the Murciano-Granadina (MG) breed, but are considered to be an alternative to benefit animal welfare without reducing production. Using 315,663 production records (of 122,883 animals) over a period of 24 years (1990–2014), genetic parameters were estimated with uni-, bi- and multivariate analysis using multiple trait derivative free restricted maximum likelihood (MTDFREML). The heritability (h2)/repeatability (re) of PY, yield (Y) and P was estimated as 0.13/0.19, 0.16/0.25 and 0.08/0.09 with the uni-trait and h2 of bi- and multi-traits analysis ranging from 0.16 to 0.17 of Y, while that of PY and Y remained constant. Genetic correlations were high between PY–Y (0.94 ± 0.011) but low between PY–P (–0.16 ± 0.054 to –0.17 ± 0.054) and between Y–P (–0.06 ± 0.058 to –0.05 ± 0.058). Estimates of h2/re were low to intermediate. The selection for Y–PY or both can be implemented given the genetic correlation between these traits. PY–P and Y–P showed low to negligible correlation values indicating that if these traits are implemented in the early stages of evaluation, they would not be to the detriment of PY–Y. The combination of estimated breeding values (EBVs) for all traits would be a good criterion for selection.
8
Schoeman, S. J., and G. G. Jordaan. "Animal x testing environment interaction on postweaning liveweight gains of young bulls." Australian Journal of Agricultural Research 49, no. 4 (1998): 607. http://dx.doi.org/10.1071/a97102.
Full textAbstract:
Postweaning liveweight gain records of 1610 young bulls obtained both in feedlot and under pasture were used to estimate (co)variance components using a multivariate restricted maximum likelihood analysis. The pedigree file included 3477 animals. Heritability estimates for liveweights and gain in both environments correspond to most previously reported estimates. The genetic correlation of gain between the 2 environments was -0·12, suggesting a large genotype testing environment interaction and re-ranking of animal breeding values across environments. Results of this analysis suggest the need for environment-specific breeding values for postweaning gain.
9
BAI, XIUQIN, and WEIXING SONG. "Comparison study on the confidence intervals in linear regression models with restricted parameter space." Journal of Statistical Research 52, no. 2 (March 11, 2019): 115–27. http://dx.doi.org/10.47302/jsr.2018520201.
Full textAbstract:
This paper proposes an empirical likelihood confidence region for the regression coefficients in linear regression models when the regression coefficients are subjected to some equality constraints. The shape of the confidence set does not depend on the re-parametrization of the regression model induced by the equality constraint. It is shown that the asymptotic coverage rate attains the nominal confidence level and the Bartlett correction can successfully reduce the coverage error rate from $O(n^{-1})$ to $O(n^{-2})$, where n denotes the sample size. Simulation studies are conducted to evaluate the finite sample performance of the proposed empirical likelihood empirical confidence estimation procedure. Finally, a comparison study is conducted to compare the finite sample performance of the proposed and the classical ellipsoidal confidence sets based on normal theory.
10
Fajardo, Gladys, and H. Hörnicke. "Problems in estimating the extent of coprophagy in the rat." British Journal of Nutrition 62, no. 3 (November 1989): 551–61. http://dx.doi.org/10.1079/bjn19890057.
Full textAbstract:
The quantity of re-ingested faeces was calculated by comparing faecal dry matter of unrestricted rats and coprophagy-restricted rats after correcting for differences in food intake. Due to high day-to-day variations of produced and re-ingested faeces it was not possible to calculate precisely the extent of coprophagy of an individual rat at a particular day with this difference method. Reliable quantitative estimates require at least two rats and a collection period of 7 d. When fed on a nutritionally complete diet, rats re-ingested 0-11 % of their faeces. When fed on low-protein diets (66 g egg albumin/kg) or diets diluted with 200 g cellulose/kg, coprophagy was not significantly increased. A high re-ingestion rate (6–25 %) was observed with thiamin and pantothenic acid deficiencies. After re-ingestion of faeces had been prevented for 1 week, the amount of faeces re-ingested during the subsequent week without tail-cups was increased twofold. It is concluded that rats are able to regulate the amount of faeces eaten precisely according to their requirements.
11
Pacheco-Rios, D., D. D. S. Mackenzie, and W. C. McNabb. "Comparison of two variants of the Fick principle for estimation of mammary blood flow in dairy cows fed two levels of dry matter intake." Canadian Journal of Animal Science 81, no. 1 (March 1, 2001): 57–63. http://dx.doi.org/10.4141/a00-035.
Full textAbstract:
The estimation of the mammary blood flow (MBF) is an important component of studies of the utilization of metabolites by the mammary gland of lactating animals. Although there are several flow meters available to measure MBF by direct contact with the vessels perfusing the mammary gland, their use is limited mainly by the surgical preparation required for their implantation. For that reason, the application of the Fick principle was assessed as a mean to estimate MBF as part of a study on amino acid utilization by the mammary gland in three pasture-fed dairy cows at either ad libitum or restricted dry matter intakes. Two methods based on the Fick principle were assessed, namely, arterio-venous differences of amino acids (methionine: Met or phenylalanine+tyrosine: Phe + Tyr) and tritiated water (TOH). The estimated MBF was not significantly different for the Met and Phe + Tyr methods (average of 8.1 and 8.8 L min–1, respectively). The TOH method yielded a significantly lower (P < 0.05) estimate of blood flow (average of 5.3 L min–1). Using the Met and Phe+Tyr methods, the MBF was lower during the period of dietary restriction compared with the ad libitum treatment (average of 9.4 and 7.5 L min–1, respectively). In contrast, the TOH method resulted in a numerically higher MBF for the restricted group (5.7 vs. 4.9 L min–1). The short sampling period a nd the loss of indicator in the TOH method appear to be a disadvantage for extrapolating the estimated values to balance studies with lactating cows involving longer periods of time. The estimated values obtained using the Met or Phe + Tyr appear to be re presentative of the MBF during the experimental period. Therefore, any of these methods (Met, Phe + Tyr) may be used alone or in combination as an alternative to flow meters in studies of mammary metabolism. Key words: Dairy cows, mammary blood flow, Fick principle
12
Ellin, Fredrik, Knut B. Smeland, Tove Wästerlid, Jacob H. Christensen, Judit Jørgensen, Pär L. Josefsson, Harald Holte, et al. "Inferior Outcomes for Older Patients in the Adolescent and Young Adult (AYA) Population with Burkitt Lymphoma Treated with Intensive Immunochemotherapy: An International Study of 108 Patients." Blood 134, Supplement_1 (November 13, 2019): 4113. http://dx.doi.org/10.1182/blood-2019-127995.
Full textAbstract:
Introduction: Non-endemic Burkitt lymphoma (BL) is a rare and highly aggressive B-cell malignancy, of whom a substantial number are adolescents and young adults (AYAs). In this particular group of patients, the balance between efficacy and long-term toxicities is of major concern, due to the long expected remaining lifetime. In this study, we investigated the outcomes for AYA patients treated with intensive immunochemotherapy. Patients and methods: Patients were identified through queries to clinic based and population-based lymphoma registries from six countries (Australia, Canada, Denmark, Norway, Sweden, and USA). All diagnoses were confirmed by local investigators; patients with classical BL histology plus detectable MYC translocation, were included. Patients between 18 and 39 years of age at diagnosis treated with intensive immunochemotherapy (DA-EPOCH-R or more intensively) were evaluated in pre-specified age groups. All treatment protocols included rituximab. Overall survival (OS) was defined as the time from diagnosis until death from any cause or censoring, while event-free survival (EFS) was defined as the time from diagnosis until unplanned re-treatment, progression/relapse, death, or censoring, whichever came first. Response evaluation was assessed using established response criteria based on CT and/or PET/CT imaging. Survival curves were computed using the Kaplan-Meier estimator. The cumulative incidence of relapse in patients reaching complete remission (CR) or CR unconfirmed (CRu) was computed by Aalen-Johansen estimator. The 5-year restricted loss of lifetime (RLOL) was defined as the area between the patient and general population survival curves until 5-years. The general population survival was retrieved from publicly available lifetables stratified on age, sex, calendar year, and country. Results: In total, 108 AYA BL patients were included. The median age was 30 years, ranging between 18 and 39 and 82% were male. The majority had advanced stage disease (Ann Arbor stage III-IV, 76%), extranodal involvement (87%), and elevated LDH (67%). Seven patients (6%) had CNS involvement at the time of diagnosis. The chemotherapy regimens used were CODOX-M/IVAC (51%), BFM/GMALL (34%), hyper-CVAD (7%), DA-EPOCH (5%), and others (3%). Among 74 patients for whom data on tumor lysis were available, 10 (14%) developed clinical tumor lysis upon start of chemotherapy, all presenting with advanced stage and extranodal disease. The response rate was 91% (89 in CR/CRu and 2% in partial remission). At a median follow-up of 53 months, 15 had an event and 10 died. The 2-year OS and EFS for the total population was 92% (87-97%, Figure 1) and 88% (82-94%), respectively. For 13 patients aged 18-21 2-year OS and EFS were both 100%, while 2-year OS and EFS for 43 patients aged 22-30 were 98% (93-100%) and 93% (85-100%), respectively. The 2-year OS and EFS for patients aged 31-39 were 86% (76-96%) and 80% (69-91%), respectively. For patients in CR/CRu and available date of response evaluation, the 2-year post-remission OS was 99% (97-100%) and the 2-year relapse risk was 2% (0-5%), with no relapses after 6 months. Compared to the general population, the RLOL was 0.8 months (-0.5-2.2 months). Nine patients did not respond to primary treatment (SD or PD), all which belonged to the age group 31-40 years (P<0.001 versus age group 18-30 years). The oldest age group had an inferior OS compared to younger patients (P=0.008), largely due to non-responders having poor subsequent survival with a 1-year OS of 33%. Conclusion: The outcomes of AYA BL patients following intensive immunochemotherapy are excellent with high remission rates and low risk of relapse in general. However, even among young patients age remained prognostic, with patients 31 years or older having inferior OS and lower response rate to first-line treatment. In patients achieving CR, survival was similar to that of the general population over the median follow-up of 4.5 years, illustrating the need to focus on survivorship issues in these individuals. Figure 1: Overall survival for BL patients following intensive immunochemotherapy for all patients and for age groups (18-21, 22-30, and 31-39 years). Figure 1 Disclosures Jørgensen: Gilead: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees. Holte:Novartis: Honoraria, Other: Advisory board. Molin:Roche Holding AG: Honoraria; Merck & Co., Inc.: Honoraria; Bristol-Myers Squibb: Honoraria; Takeda Pharmaceuticals: Honoraria. Ekstroem Smedby:Takeda: Honoraria, Other: Grant funding, Research Funding; Celgene: Honoraria, Other: Grant funding, Research Funding; Janssen Cilag: Honoraria, Other: Grant funding, Research Funding. Song:Takeda: Honoraria; Celgene: Honoraria, Research Funding; Janssen: Honoraria; Amgen: Honoraria. Gerrie:Lundbeck, Seattle Genetics: Consultancy, Honoraria. Cheah:Roche, Janssen, MSD, Gilead, Loxo Oncology, Acerta, BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Other: Travel expenses; Celgene, Roche, Abbvie: Research Funding. El-Galaly:Roche: Employment, Other: Travel support; Takeda: Other: Travel support.
13
Thistle, Harold W., Milton E. Teske, Brian Richardson, and Tara M. Strand. "Technical Note: Model Physics and Collection Efficiency in Estimates of Pesticide Spray Drift Model Performance." Transactions of the ASABE 63, no. 6 (2020): 1939–45. http://dx.doi.org/10.13031/trans.14024.
Full textAbstract:
HighlightsRecent large field programs are re-examined in the context of model development.Details of plant canopy wind fields are discussed.Collection efficiency of rotorods is discussed in detail, and the theory is used to re-examine field data.The approach used in the AGDISP model to simulate canopy wind fields is discussed in detail.Abstract. Recent field studies provided data to evaluate the performance of the aerial spray deposition algorithm in AGDISP. Those studies provided data for forest canopy settings that are either outside the stated domain of AGDISP or where assumptions in the model greatly impact the model performance. The two data sets were collected with the intention of providing input to drive model upgrades, but data limitations restricted that objective. Rather, this technical note shows that collection efficiency (CE) must always be considered (the model currently adjusts for CE only if the modeled output is canopy capture). One of the previous studies showed that the model substantially overpredicted droplet flux 65 m downwind of the spray line. Consideration of CE resolves some of this overprediction, but the model physics employed in AGDISP remain a substantial simplification of the complex flows that transport droplets in the atmospheric boundary layer near and in deep, three-dimensionally varying forest canopies. Keywords: Aerial application, AGDISP, Model, Spray drift.
14
Yan, Guiping, Richard W. Smiley, Patricia A. Okubara, Andrea M. Skantar, and Catherine L. Reardon. "Developing a Real-Time PCR Assay for Detection and Quantification of Pratylenchus neglectus in Soil." Plant Disease 97, no. 6 (June 2013): 757–64. http://dx.doi.org/10.1094/pdis-08-12-0729-re.
Full textAbstract:
Pratylenchus neglectus is one of the most widespread and economically important nematodes that invades plant roots and restricts wheat productivity in the Pacific Northwest. It is challenging to quantify P. neglectus using microscopic methods for studies that require large-scale sampling, such as assessment of rotation crops, wheat cultivars, and other management practices. A real-time quantitative polymerase chain reaction (qPCR) assay was developed to detect and quantify P. neglectus from DNA extracts of soil. The primers, designed from the internal transcribed spacer region of rDNA, showed high specificity with a single melt curve peak to DNA from eight isolates of P. neglectus but did not amplify DNA from 28 isolates of other plant-parasitic and non-plant-parasitic nematodes. A standard curve (R2 = 0.96; P < 0.001) was generated by amplifying DNA extracted from soil to which nematodes were added. The soil standard curve was validated using sterilized soil inoculated with lower numbers of P. neglectus. A significant positive relationship (R2 = 0.66; P < 0.001) was observed for nematode numbers quantified from 15 field soils using qPCR and the Whitehead tray and microscopic method but the qPCR generally tended to provide higher estimates. Real-time PCR potentially provides a useful platform for efficient detection and quantification of P. neglectus directly from field soils.
15
Misiewicz, T. M., and N. C. Zerega. "PHYLOGENY, BIOGEOGRAPHY AND CHARACTER EVOLUTION OF DORSTENIA (MORACEAE)." Edinburgh Journal of Botany 69, no. 3 (October 18, 2012): 413–40. http://dx.doi.org/10.1017/s096042861200025x.
Full textAbstract:
Dorstenia, the second largest genus (105 species) within the Moraceae, is the only genus in the family with woody, herbaceous and succulent species. All but one species of Dorstenia are restricted to the Neotropics or Africa, and it is the only genus in the family with an almost equal transatlantic distribution. This work presents the first molecular phylogeny and the first evolutionary study to examine origin and diversification within the genus. We inferred the phylogeny with ITS sequence data using Bayesian and maximum likelihood approaches. We tracked the evolution of distinct morphological characters and tested for correlated evolution in multiple characters. Time and place of Dorstenia’s origin were estimated to test a post-Gondwanan versus a Gondwanan origin hypothesis using fossil calibrations, Bayesian molecular dating, and maximum likelihood-based ancestral range reconstructions. Our phylogenetic analysis supports the monophyly of Dorstenia; previous subgeneric classifications are polyphyletic and must be re-evaluated. Woody habit, phanerophytic life form, macrospermy, and lack of storage organs are ancestral traits found in African Dorstenia. Evolution of woodiness and macrospermy are correlated. Dorstenia appears to have originated in Africa, radiated into the Neotropics and subsequently re-colonised Africa. Whether or not the extant distribution is the result of vicariance or dispersal is equivocal.
16
Rosa, Ierecê Lucena, Tacyana P. R. Oliveira, André L. C. Castro, Luiz E. de Souza Moraes, Josias H. A. Xavier, Mara C. Nottingham, Thelma L. P. Dias, et al. "Population characteristics, space use and habitat associations of the seahorse Hippocampus reidi (Teleostei: Syngnathidae)." Neotropical Ichthyology 5, no. 3 (September 2007): 405–14. http://dx.doi.org/10.1590/s1679-62252007000300020.
Full textAbstract:
This paper provides a case study of a threatened seahorse species, Hippocampus reidi, highlighting the importance of using ecological information to assist conservation and management initiatives. Underwater visual sighting data (50 x 2m transect) gathered along the NE, SE and S portions of the Brazilian coast revealed an unequal distribution across localities, perhaps related to harvesting pressure, and a mean density of 0.026 ind.m-2. Our findings suggest some restricted spatial use by H. reidi, which was consistent with its estimated home range, and with re-sighting of specimens. Reproduction was recorded year-round, however productive peaks may exist. Components of habitat structure mostly used as anchoring points were mangrove plants, macroalgae, cnidarians, seagrass, sponges, and bryozoans. Conservation recommendations include: further characterization and mapping of habitats; assessment of availability and condition of microhabitats in selected areas, and studies on dispersal routes during initial life stages.
17
van der Kuyl, Antoinette C. "Contemporary Distribution, Estimated Age, and Prehistoric Migrations of Old World Monkey Retroviruses." Epidemiologia 2, no. 1 (February 3, 2021): 46–67. http://dx.doi.org/10.3390/epidemiologia2010005.
Full textAbstract:
Old World monkeys (OWM), simians inhabiting Africa and Asia, are currently affected by at least four infectious retroviruses, namely, simian foamy virus (SFV), simian immunodeficiency virus (SIV), simian T-lymphotropic virus (STLV), and simian type D retrovirus (SRV). OWM also show chromosomal evidence of having been infected in the past with four more retroviral species, baboon endogenous virus (BaEV), Papio cynocephalus endogenous virus (PcEV), simian endogenous retrovirus (SERV), and Rhesus endogenous retrovirus-K (RhERV-K/SERV-K1). For some of the viruses, transmission to other primates still occurs, resulting, for instance, in the HIV pandemic. Retroviruses are intimately connected with their host as they are normally spread by close contact. In this review, an attempt to reconstruct the distribution and history of OWM retroviruses will be made. A literature overview of the species infected by any of the eight retroviruses as well as an age estimation of the pathogens will be given. In addition, primate genomes from databases have been re-analyzed for the presence of endogenous retrovirus integrations. Results suggest that some of the oldest retroviruses, SERV and PcEV, have travelled with their hosts to Asia during the Miocene, when a higher global temperature allowed simian expansions. In contrast, younger viruses, such as SIV and SRV, probably due to the lack of a primate continuum between the continents in later times, have been restricted to Africa and Asia, respectively.
18
Young, Mark T., Stéphane Hua, Lorna Steel, Davide Foffa, Stephen L. Brusatte, Silvan Thüring, Octávio Mateus, et al. "Revision of the Late Jurassic teleosaurid genus Machimosaurus (Crocodylomorpha, Thalattosuchia)." Royal Society Open Science 1, no. 2 (October 2014): 140222. http://dx.doi.org/10.1098/rsos.140222.
Full textAbstract:
Machimosaurus was a large-bodied genus of teleosaurid crocodylomorph, considered to have been durophagous/chelonivorous, and which frequented coastal marine/estuarine ecosystems during the Late Jurassic. Here, we revise the genus based on previously described specimens and revise the species within this genus. We conclude that there were three European Machimosaurus species and another taxon in Ethiopia. This conclusion is based on numerous lines of evidence: craniomandibular, dental and postcranial morphologies; differences in estimated total body length; geological age; geographical distribution; and hypothetical lifestyle. We re-diagnose the type species Machimosaurus hugii and limit referred specimens to only those from Upper Kimmeridgian–Lower Tithonian of Switzerland, Portugal and Spain. We also re-diagnose Machimosaurus mosae , demonstrate that it is an available name and restrict the species to the uppermost Kimmeridgian–lowermost Tithonian of northeastern France. We re-diagnose and validate the species Machimosaurus nowackianus from Harrar, Ethiopia. Finally, we establish a new species, Machimosaurus buffetauti , for the Lower Kimmeridgian specimens of France and Germany (and possibly England and Poland). We hypothesize that Machimosaurus may have been analogous to the Pliocene–Holocene genus Crocodylus in having one large-bodied taxon suited to traversing marine barriers and additional, geographically limited taxa across its range.
19
Wilson, J. D., A. Ridgwell, and S. Barker. "Can organic matter flux profiles be diagnosed using remineralisation rates derived from observed tracers and modelled ocean transport rates?" Biogeosciences 12, no. 18 (September 30, 2015): 5547–62. http://dx.doi.org/10.5194/bg-12-5547-2015.
Full textAbstract:
Abstract. The average depth in the ocean at which the majority of sinking organic matter particles remineralise is a fundamental parameter in the ocean's role in regulating atmospheric CO2. Observed spatial patterns in sinking fluxes and relationships between the fluxes of different particles in the modern ocean have widely been used to invoke controlling mechanisms with important implications for CO2 regulation. However, such analyses are limited by the sparse spatial sampling of the available sediment trap data. Here we explore whether model ocean circulation rates, in the form of a transport matrix, can be used to derive remineralisation rates and infer sinking particle flux curves from the much more highly resolved observations of dissolved nutrient concentrations. Initially we show an example of the method using a transport matrix from the MITgcm model and demonstrate that there are a number of potential uncertainties associated with the method. We then use the Earth system model GENIE to generate a synthetic tracer data set to explore the method and its sensitivity to key sources of uncertainty arising from errors in the tracer observations and in the model circulation. We use a 54-member ensemble of different, but plausible, estimates of the modern circulation to explore errors associated with model transport rates. We find that reconstructed re-mineralisation rates are very sensitive to both errors in observations and model circulation rates, such that a simple inversion cannot provide a robust estimate of particulate flux profiles. Estimated remineralisation rates are particularly sensitive to differences between the "observed" and modelled circulation because remineralisation rates are 3–4 magnitudes smaller than transport rates. We highlight a potential method of constraining the uncertainty associated with using modelled circulation rates, although its success is limited by the observations currently available. Finally, we show that there are additional uncertainties when inferring particle flux curves from reliable estimates of remineralisation rates due to processes that are not restricted to the vertical water column transport, such as the cycling of dissolved organic matter.
20
Gelderblom, Oscar, and Regina Grafe. "The Rise and Fall of the Merchant Guilds: Re-thinking the Comparative Study of Commercial Institutions in Premodern Europe." Journal of Interdisciplinary History 40, no. 4 (April 2010): 477–511. http://dx.doi.org/10.1162/jinh.2010.40.4.477.
Full textAbstract:
Although the importance of merchant guilds for the commercial development of Europe is beyond doubt, scholars do not agree about why they emerged, persisted, and ultimately declined between the eleventh and eighteenth centuries. Historical studies usually focus on individual cases and idiosyncratic circumstances that restrict comparisons, whereas economic approaches based on game or contract theory often impose narrow assumptions on their models that tend to neglect two key features of these institutions: In imperfect markets, merchants used more than one institution to solve a given problem, and individual institutions often addressed more than one problem. However, a new methodological approach (maximum likelihood estimation) permits rigorous comparative analysis of the probability that merchants, under a given set of market and political circumstances, will delegate control of their dealings. This model requires only one assumption—that merchants relinquished such control only when they expected a positive return.
21
Kim, Youngboo, and Eun-Chan Park. "An Efficient Relayed Broadcasting based on the Duplication Estimation Model for IoT Applications." Sensors 19, no. 9 (April 30, 2019): 2038. http://dx.doi.org/10.3390/s19092038.
Full textAbstract:
In this paper, we consider relay-based broadcasting in wireless ad hoc networks, which can enable various emerging services in the Internet of Things (IoT). In this kind of traffic dissemination scheme, also known as flooding, all the nodes not only receive frames but also rebroadcast them. However, without an appropriate relay suppression, a broadcast storm problem arises, i.e., the transmission may fail due to severe collisions and/or interference, many duplicate frames are unnecessarily transmitted, and the traffic dissemination time increases. To mitigate the broadcast storm problem, we propose a reasonable criterion to restrict the rebroadcasting named the duplication ratio. Based on this, we propose an efficient mechanism consisting of duplication suppression and re-queuing schemes. The former discards duplicate frames proactively in a probabilistic manner to decrease the redundancy whereas the latter provides a secondary transmission opportunity reactively to compensate for the delivery failure. Moreover, to apply the duplication ratio practically, we propose a simple method to approximate it based on the number of adjacent nodes. The simulation study confirms that the proposed mechanism tightly ensured the reliability and decreased the traffic dissemination time by up to 6-fold compared to conventional mechanisms.
22
Willis, D. M., J. Robin Singh, and K. S. C. Freeman. "Uncertainties in field-line tracing in the magnetosphere. Part II: the complete internal geomagnetic field." Annales Geophysicae 15, no. 2 (February 28, 1997): 181–96. http://dx.doi.org/10.1007/s00585-997-0181-4.
Full textAbstract:
Abstract. The discussion in the preceding paper is restricted to the uncertainties in magnetic-field-line tracing in the magnetosphere resulting from published standard errors in the spherical harmonic coefficients that define the axisymmetric part of the internal geomagnetic field (i.e. gn0 ± δgn0). Numerical estimates of these uncertainties based on an analytic equation for axisymmetric field lines are in excellent agreement with independent computational estimates based on stepwise numerical integration along magnetic field lines. This comparison confirms the accuracy of the computer program used in the present paper to estimate the uncertainties in magnetic-field-line tracing that arise from published standard errors in the full set of spherical harmonic coefficients, which define the complete (non-axisymmetric) internal geomagnetic field (i.e. gnm ± δgnm and hnm ± δhnm). An algorithm is formulated that greatly reduces the computing time required to estimate these uncertainties in magnetic-field-line tracing. The validity of this algorithm is checked numerically for both the axisymmetric part of the internal geomagnetic field in the general case (1 ≤ n ≤ 10) and the complete internal geomagnetic field in a restrictive case (0 ≤ m ≤ n, 1 ≤ n ≤ 3). On this basis it is assumed that the algorithm can be used with confidence in those cases for which the computing time would otherwise be prohibitively long. For the complete internal geomagnetic field, the maximum characteristic uncertainty in the geocentric distance of a field line that crosses the geomagnetic equator at a nominal dipolar distance of 2 RE is typically 100 km. The corresponding characteristic uncertainty for a field line that crosses the geomagnetic equator at a nominal dipolar distance of 6 RE is typically 500 km. Histograms and scatter plots showing the characteristic uncertainties associated with magnetic-field-line tracing in the magnetosphere are presented for a range of illustrative examples. Finally, estimates are given for the maximum uncertainties in the locations of the conjugate points of selected geophysical observatories. Numerical estimates of the uncertainties in magnetic-field-line tracing in the magnetosphere, including the associated uncertainties in the locations of the conjugate points of geophysical observatories, should be regarded as "first approximations'' in the sense that these estimates are only as accurate as the published standard errors in the full set of spherical harmonic coefficients. As in the preceding paper, however, all computational techniques developed in this paper can be used to derive more realistic estimates of the uncertainties in magnetic-field-line tracing in the magnetosphere, following further progress in the determination of more accurate standard errors in the spherical harmonic coefficients.
23
Halmos, Balazs, Thomas Burke, Chrysostomos Kalyvas, Ralph Insinga, Kristel Vandormael, Andrew Frederickson, and Bilal Piperdi. "A Matching-Adjusted Indirect Comparison of Pembrolizumab + Chemotherapy vs. Nivolumab + Ipilimumab as First-Line Therapies in Patients with PD-L1 TPS ≥1% Metastatic NSCLC." Cancers 12, no. 12 (December 4, 2020): 3648. http://dx.doi.org/10.3390/cancers12123648.
Full textAbstract:
Background: In the absence of head-to-head trials, this study indirectly compared the effectiveness of pembrolizumab + chemotherapy vs nivolumab + ipilimumab for the first-line treatment of metastatic stage IV NSCLC patients with PD-L1 tumor proportion score (TPS) ≥1%. Methods: An anchored matching-adjusted indirect comparison (MAIC) was conducted using pooled individual patient data (IPD) from the ITT population in KEYNOTE-021G, KEYNOTE-189 and KEYNOTE-407 (n = 816) and published aggregate data of nivolumab + ipilimumab from CheckMate 227 Part 1A (n = 793). To adjust for cross-trial differences in baseline characteristics, data from KEYNOTE-021G/KEYNOTE-189/KEYNOTE-407 were re-weighted to match the baseline characteristics of CheckMate 227 Part 1A. Outcomes included OS, PFS and ORR. Base case analyses were restricted to patients with PD-L1 TPS ≥1%, with sub-group analyses in PD-L1 TPS ≥50% and 1–49%. Results: The estimated HR (95% CI) of pembrolizumab + chemotherapy vs nivolumab + ipilimumab was 0.80 (0.59,1.09) and 0.53 (0.41,0.68) for OS and PFS, respectively. For ORR, the estimated risk ratio was 1.8 (1.3,2.4) for pembrolizumab + chemotherapy vs nivolumab + ipilimumab and the risk difference was 25.5% (15.0,36.0). PD-L1 TPS ≥50% and 1–49% sub-groups showed an OS HR of 0.89 (0.58,1.36) and 0.68 (0.46,1.01), respectively. Conclusion: These MAIC results suggest that pembrolizumab + chemotherapy leads to a greater clinical benefit vs nivolumab + ipilimumab in patients with PD-L1 TPS ≥1% across multiple endpoints.
24
Hernlund, Emma, Josefine Redig, Åsa Rangert Derolf, Bjorn Paulsson, Martin Höglund, Simona Vertuani, and Gunnar Juliusson. "Costs per Treatment Phase for AML Patients Receiving High-Dose Chemoterapy in Sweden." Blood 134, Supplement_1 (November 13, 2019): 2154. http://dx.doi.org/10.1182/blood-2019-127957.
Full textAbstract:
Introduction: AML affects all ages with an incidence rate of 5 per 100,000, but is much more frequent in older population. The overall lifetime risk of AML is estimated to be 0.5-1%. Long-term overall survival in younger (age < 60 years) is about 50%, but much worse among older population. Although AML therapy is one of the most resource-intensive cancer treatments, there are few estimates of the resource use and economic burden by treatment phase. Methods: This study was a retrospective database study performed on Swedish national data. Adult patients (age ≥18 years) diagnosed with AML in Sweden between 2007 and 2015 were identified in the Swedish Cancer Registry, along with vital status. Data on resource use were collected from national registers for inpatient- and outpatient specialized care and prescribed drugs. Information on diagnostics and treatment was accessed from the Swedish national AML Registry (SwAMLR). Data on sick leave (SL) and early retirement (ER) came from the Swedish Social Insurance Agency (absent days costed with the mean salary in Sweden). Hospital care resource use was costed using diagnosis-related group (DRG) remunerations, and include cost of inpatient drugs. The mean cost from the defined start of the treatment phase until the end of the treatment phase was divided by the mean number of days for the corresponding treatment phase to estimate the mean cost per day. The defined treatment phases were restricted to a maximum of 5 years. All costs are represented in US$. Results: Of the 2,954 patients identified in the Swedish Cancer Registry, 1,772 patients with a median age of 64 years were identified in the SwAMLR as fit for receiving high-dose chemotherapy . Of these, 1,243 were recorded with both curative intent of treatment and dates for achieving complete remission. Mean costs from the first AML-related hospital admission until the date of complete remission amount to $27,244. The mean number of days for the corresponding period were 45.16, resulting in a mean cost per day of $603 from first admission to first complete remission. The corresponding cost per day for patients recorded with curative intent but no complete remission (n=428) are $494. Time was counted from first AML-related admission until 90 days after first admission, or SCT or death, whichever occurred first. Costs after complete remission to either relapse, SCT, death or re-induction (n=1,237) amount to $50,793 for a mean of 438.63 days ($116/day). This treatment phase includes long-term survivors, whereas the costs from SCT, relapse or re-induction are not included. From relapse to death, the total cost is almost twofold for patients with re-induction (n=350) compared to palliative treatment (n=254). Cost per day amount to $179 for patients with palliative treatment and $256 for patients with re-induction treatment, respectively. The cost per day from date of SCT to death (n=511) is estimated to $192, incurred over a long period of time (mean number of days 844.02). The age of transplant recipients ranged between 18-71 years, with a median of 52 years. Conclusions: Costs of AML up to remission are feasible to estimate through DRG-costing methods, and studies have shown these costs are intense. Indeed this study shows that the highest cost per day is observed from first admission to complete remission. In addition results from our study show that there are high costs incurred also in the long-term, i.e. after remission. Of the included treatment phases the total cost from date of SCT to death is the largest, amounting to over $160,000. Approximately 20% are due to SL/ER, which is the second largest cost component after inpatient costs accounting for 60% of the total costs. Table. Disclosures Hernlund: ICON: Employment. Redig:ICON: Employment. Paulsson:Novartis: Employment. Vertuani:Novartis: Employment.
25
Ruban, A. I., T. Bernots, and D. Pryce. "Receptivity of the boundary layer to vibrations of the wing surface." Journal of Fluid Mechanics 723 (April 16, 2013): 480–528. http://dx.doi.org/10.1017/jfm.2013.119.
Full textAbstract:
AbstractIn this paper we study the generation of Tollmien–Schlichting waves in the boundary layer due to elastic vibrations of the wing surface. The subsonic flow regime is considered with the Mach number outside the boundary layer $M= O(1)$. The flow is investigated based on the asymptotic analysis of the Navier–Stokes equations at large values of the Reynolds number, $\mathit{Re}= {\rho }_{\infty } {V}_{\infty } L/ {\mu }_{\infty } $. Here $L$ denotes the wing section chord; and ${V}_{\infty } $, ${\rho }_{\infty } $ and ${\mu }_{\infty } $ are the free stream velocity, air density and dynamic viscosity, respectively. We assume that in the spectrum of the wing vibrations there is a harmonic that comes in to resonance with the Tollmien–Schlichting wave on the lower branch of the stability curve; this happens when the frequency of the harmonic is a quantity of the order of $({V}_{\infty } / L){\mathit{Re}}^{1/ 4} $. The wavelength, $\ell $, of the elastic vibrations of the wing is assumed to be $\ell \sim L{\mathit{Re}}^{- 1/ 8} $, which has been found to represent a ‘distinguished limit’ in the theory. Still, the results of the analysis are applicable for $\ell \gg L{\mathit{Re}}^{- 1/ 8} $ and $\ell \ll L{\mathit{Re}}^{- 1/ 8} $; the former includes an important case when $\ell = O(L)$. We found that the vibrations of the wing surface produce pressure perturbations in the flow outside the boundary layer, which can be calculated with the help of the ‘piston theory’, which remains valid provided that the Mach number, $M$, is large as compared to ${\mathit{Re}}^{- 1/ 4} $. As the pressure perturbations penetrate into the boundary layer, a Stokes layer forms on the wing surface; its thickness is estimated as a quantity of the order of ${\mathit{Re}}^{- 5/ 8} $. When $\ell = O({\mathit{Re}}^{- 1/ 8} )$ or $\ell \gg {\mathit{Re}}^{- 1/ 8} $, the solution in the Stokes layer appears to be influenced significantly by the compressibility of the flow. The Stokes layer on its own is incapable of producing the Tollmien–Schlichting waves. The reason is that the characteristic wavelength of the perturbation field in the Stokes layer is much larger than that of the Tollmien–Schlichting wave. However, the situation changes when the Stokes layer encounters a wall roughness, which are plentiful in real aerodynamic flows. If the longitudinal extent of the roughness is a quantity of the order of ${\mathit{Re}}^{- 3/ 8} $, then efficient generation of the Tollmien–Schlichting waves becomes possible. In this paper we restrict our attention to the case when the Stokes layer interacts with an isolated roughness. The flow near the roughness is described by the triple-deck theory. The solution of the triple-deck problem can be found in an analytic form. Our main concern is with the flow behaviour downstream of the roughness and, in particular, with the amplitude of the generated Tollmien–Schlichting waves.
26
Neves, Maria Luciana Menezes Wanderley, Antonia Sherlânea Chaves Véras, Evaristo Jorge Oliveira de Souza, Marcelo De Andrade Ferreira, Sebastião De Campos Valadares Filho, Gabriel Santana da Silva, Francisco Fernando Ramos de Carvalho, Diogo José Gomes de Oliveira, Edine Roberta de Lima, and Ligia Maria Gomes Barreto. "Energy and protein requirements of crossbred cattle in feedlot." Semina: Ciências Agrárias 37, no. 2 (April 26, 2016): 1029. http://dx.doi.org/10.5433/1679-0359.2016v37n2p1029.
Full textAbstract:
The objective of this study is to predict the energy and protein requirements of crossbred dairy cattle in feedlot. The study was conducted at the Unidade Acadêmica de Serra Talhada, Universidade Federal Rural de Pernambuco, Brazil with 30 bulls with a body weight of 339.1 ± 35.4 kg. Five animals were slaughtered at the end of the adaptation period to serve as the reference group; the remainder of the animals was slaughtered after 112 days. The latter group was randomly allocated to receive five treatments: 0, 17, 34, 51 and 68% of concentrate in the feed using a completely randomized design. The dietary intake of the animals that were not given concentrate was restricted to 1.5% of their body weight; these animals composed the group fed for maintenance. The body composition and empty body weight (EBW) were estimated by means of the comparative slaughter method and full dissection of a half-carcass. The results showed that for crossbred dairy bulls in confinement, the net and metabolizable energy requirements were 86.49 and 138 kcal EBW-0.75 day-1, respectively, and the efficiency of use of metabolizable energy for maintenance and gain were 62.67% and 31.67%, respectively. The net energy (NEg) and net protein (NPg) requirements for gain can be estimated using the following equations, respectively: NEg= 0.0392*EBW0.75*EBWG1.0529 and NPg= 242.34 x EBWG - 23.09 x RE. The efficiency of use of metabolizable protein for gain was 25.8%, and the protein requirement for maintenance was 2.96 g EBW-0.75 day-1. The rumen degradable protein can supply 62.44% of the crude protein requirements of feedlot dairy crossbred bulls with a body weight of 450 kg while gaining 1 kg day-1.
27
Mueller, Jakob C., Heiner Kuhl, Stefan Boerno, Jose L. Tella, Martina Carrete, and Bart Kempenaers. "Evolution of genomic variation in the burrowing owl in response to recent colonization of urban areas." Proceedings of the Royal Society B: Biological Sciences 285, no. 1878 (May 16, 2018): 20180206. http://dx.doi.org/10.1098/rspb.2018.0206.
Full textAbstract:
When a species successfully colonizes an urban habitat it can be expected that its population rapidly adapts to the new environment but also experiences demographic perturbations. It is, therefore, essential to gain an understanding of the population structure and the demographic history of the urban and neighbouring rural populations before studying adaptation at the genome level. Here, we investigate populations of the burrowing owl ( Athene cunicularia ), a species that colonized South American cities just a few decades ago. We assembled a high-quality genome of the burrowing owl and re-sequenced 137 owls from three urban–rural population pairs at 17-fold median sequencing coverage per individual. Our data indicate that each city was independently colonized by a limited number of founders and that restricted gene flow occurred between neighbouring urban and rural populations, but not between urban populations of different cities. Using long-range linkage disequilibrium statistics in an approximate Bayesian computation approach, we estimated consistently lower population sizes in the recent past for the urban populations in comparison to the rural ones. The current urban populations all show reduced standing variation in rare single nucleotide polymorphisms (SNPs), but with different subsets of rare SNPs in different cities. This lowers the potential for local adaptation based on rare variants and makes it harder to detect consistent signals of selection in the genome.
28
HIRATA, M., E. KUNIEDA, and M. TOBISA. "Short-term ingestive behaviour of cattle grazing tropical stoloniferous grasses with contrasting growth forms." Journal of Agricultural Science 148, no. 5 (June 25, 2010): 615–24. http://dx.doi.org/10.1017/s0021859610000353.
Full textAbstract:
SUMMARYRelationships between sward height and short-term ingestive behaviour of cattle were examined for two tropical stoloniferous grasses with contrasting growth forms: centipede grass (Eremochloa ophiuroides(Munro) Hack.; (CG); strongly prostrate) and bahia grass (Paspalum notatumFlügge; (BG); more erect). Turves (500×500 mm) were extracted from field monoculture swards of each grass after the varying duration of re-growth, and presented to animals for a short period (10 bites) to measure bite dimensions (area, depth and volume), bite mass, time per bite and intake rate. In the same re-growth period, CG was always shorter and denser than BG. Bite dimensions, the bite mass and the intake rate of animals increased at a declining rate as the sward height increased for both grasses, showing a tendency for a steeper initial increase, an earlier plateau and a lower maximum in CG than in BG. Due to the difference in the shape of the intake rate response, animals on BG were estimated to require a longer grazing time than those on CG to attain the same daily herbage intake, when the sward is shorter than about 200 mm. The sward height below which the daily intake of animals may be restricted was lower for CG (61–70 mm) than for BG (71–92 mm). The results indicate an advantage of strongly prostrated, highly dense grasses (e.g. CG) over more erect, less dense grasses (e.g. BG) when grazed at a relatively low height (<200 mm). In relation to increasing bite mass, the time per bite pooled over CG and BG was constant until the bite mass reached a critical value (0·55 g dry matter (DM)) and thereafter increased linearly with the bite mass, confirming that cattle are able to perform compound jaw movements that gather herbage into the mouth (manipulative jaw movement) and chew herbage already in the mouth (chewing jaw movement) within one cycle of opening and closing of the jaws.
29
Johnson, Wendy, Ian J. Deary, and Thomas J. Bouchard. "Have Standard Formulas Correcting Correlations for Range Restriction Been Adequately Tested?: Minor Sampling Distribution Quirks Distort Them." Educational and Psychological Measurement 78, no. 6 (October 26, 2017): 1021–55. http://dx.doi.org/10.1177/0013164417736092.
Full textAbstract:
Most study samples show less variability in key variables than do their source populations due most often to indirect selection into study participation associated with a wide range of personal and circumstantial characteristics. Formulas exist to correct the distortions of population-level correlations created. Formula accuracy has been tested using simulated normally distributed data, but empirical data are rarely available for testing. We did so in a rare data set in which it was possible: the 6-Day Sample, a representative subsample of 1,208 from the Scottish Mental Survey 1947 of cognitive ability in 1936-born Scottish schoolchildren (70,805). 6-Day Sample participants completed a follow-up assessment in childhood and were re-recruited for study at age 77 years. We compared full 6-Day Sample correlations of early-life variables with those of the range-restricted correlations in the later-participating subsample, before and after adjustment for direct and indirect range restriction. Results differed, especially for two highly correlated cognitive tests; neither reproduced full-sample correlations well due to small deviations from normal distribution in skew and kurtosis. Maximum likelihood estimates did little better. To assess these results’ typicality, we simulated sample selection and made similar comparisons using the 42 cognitive ability tests administered to the Minnesota Study of Twins Reared Apart, with very similar results. We discuss problems in developing further adjustments to offset range-restriction distortions and possible approaches to solutions.
30
Liu, Caixia, Xiaolu Zhou, Xiangdong Lei, Huabing Huang, Carl Zhou, Changhui Peng, and Xiaoyi Wang. "Separating Regressions for Model Fitting to Reduce the Uncertainty in Forest Volume-Biomass Relationship." Forests 10, no. 8 (August 5, 2019): 658. http://dx.doi.org/10.3390/f10080658.
Full textAbstract:
The method of forest biomass estimation based on a relationship between the volume and biomass has been applied conventionally for estimating stand above- and below-ground biomass (SABB, t ha−1) from mean growing stock volume (m3 ha−1). However, few studies have reported on the diagnosis of the volume-SABB equations fitted using field data. This paper addresses how to (i) check parameters of the volume-SABB equations, and (ii) reduce the bias while building these equations. In our analysis, all equations were applied based on the measurements of plots (biomass or volume per hectare) rather than individual trees. The volume-SABB equation is re-expressed by two Parametric Equations (PEs) for separating regressions. Stem biomass is an intermediate variable (parametric variable) in the PEs, of which one is established by regressing the relationship between stem biomass and volume, and the other is created by regressing the allometric relationship of stem biomass and SABB. A graphical analysis of the PEs proposes a concept of “restricted zone,” which helps to diagnose parameters of the volume-SABB equations in regression analyses of field data. The sampling simulations were performed using pseudo data (artificially generated in order to test a model) for the model test. Both analyses of the regression and simulation demonstrate that the wood density impacts the parameters more than the allometric relationship does. This paper presents an applicable method for testing the field data using reasonable wood densities, restricting the error in field data processing based on limited field plots, and achieving a better understanding of the uncertainty in building those equations.
31
Wilson, Crispen, and Matthew Linkie. "The Panglima Laot of Aceh: a case study in large-scale community-based marine management after the 2004 Indian Ocean tsunami." Oryx 46, no. 4 (October 2012): 495–500. http://dx.doi.org/10.1017/s0030605312000191.
Full textAbstract:
AbstractDespite dating back over 400 years the relevance of traditional fisheries management in Aceh, Indonesia, still remains high. Aceh was, however, greatly affected by the December 2004 Indian Ocean tsunami that claimed an estimated 167,000 lives, including 14,000 fishermen and 59 of the 193 traditional marine leaders (Panglima Laot). This tragic loss of life was accompanied by a substantial loss of local knowledge, such as the locations of hazardous fishing grounds. In this study we describe an innovative project that sought to rebuild a post-tsunami fisheries sector by re-engaging and empowering the Panglima Laot. During April–June 2008 GPS (global positioning system) sounding devices were installed on 53 local fishing boats and hazardous fishing areas mapped based on local knowledge, and shared amongst fishermen. During July–December 2008 nearly five million GPS data points were collected, from which detailed bathymetric maps were produced and shared between fishermen and Aceh government officials. Significant project outputs included a map of fishing areas over 20,000 km2, which included three new seamounts, one of which expanded Aceh's provincial boundary by > 1.3 million ha, and a Panglima Laot decree that reduced fishing in hazardous areas of high coral density by 23.3%. Our findings have wide applicability. Locally, the introduction of GPS technology and sharing of traditional knowledge resulted in fishermen developing and implementing their own management strategies and demonstrating their ability to stay out of restricted areas. Provincially, this project provided a framework through which government agencies and academic institutions could effectively engage with local customary leaders and their fishing communities.
32
Demicco, Robert V., and Tim K. Lowenstein. "When “evaporites” are not formed by evaporation: The role of temperature and pCO2 on saline deposits of the Eocene Green River Formation, Colorado, USA." GSA Bulletin 132, no. 7-8 (November 4, 2019): 1365–80. http://dx.doi.org/10.1130/b35303.1.
Full textAbstract:
Abstract Halite precipitates in the Dead Sea during winter but re-dissolves above the thermocline upon summer warming, “focusing” halite deposition below the thermocline (Sirota et al., 2016, 2017, 2018). Here we develop an “evaporite focusing” model for evaporites (nahcolite + halite) preserved in a restricted area of the Eocene Green River Formation in the Piceance Creek Basin of Colorado, USA. Nahcolite solubility is dependent on partial pressure of carbon dioxide (pCO2) as well as temperature (T), so these models covary with both T and pCO2. In the lake that filled the Piceance Creek Basin, halite, nahcolite or mixtures of both could have precipitated during winter cooling, depending on the CO2 content in different parts of the lake. Preservation of these minerals occurs below the thermocline (>∼25 m) in deeper portions of the basin. Our modeling addresses both: (1) the restriction of evaporites in the Piceance Creek Basin to the center of the basin without recourse to later dissolution and (2) the variable mineralogy of the evaporites without recourse to changes in lake water chemistry. T from 20 to 30 °C and pCO2 between 1800 and 2800 ppm are reasonable estimates for the conditions in the Piceance Creek Basin paleolake. Other evaporites occur in the center of basins but do not extend out to the edges of the basin. Evaporite focusing caused by summer-winter T changes in the solubility of the minerals should be considered for such deposits and variable pCO2 within the evaporating brines also needs to be considered if pCO2 sensitive minerals are found.
33
Rodger, Yael S., Alexandra Pavlova, Steve Sinclair, Melinda Pickup, and Paul Sunnucks. "Evolutionary history and genetic connectivity across highly fragmented populations of an endangered daisy." Heredity 126, no. 5 (February 19, 2021): 846–58. http://dx.doi.org/10.1038/s41437-021-00413-0.
Full textAbstract:
AbstractConservation management can be aided by knowledge of genetic diversity and evolutionary history, so that ecological and evolutionary processes can be preserved. The Button Wrinklewort daisy (Rutidosis leptorrhynchoides) was a common component of grassy ecosystems in south-eastern Australia. It is now endangered due to extensive habitat loss and the impacts of livestock grazing, and is currently restricted to a few small populations in two regions >500 km apart, one in Victoria, the other in the Australian Capital Territory and nearby New South Wales (ACT/NSW). Using a genome-wide SNP dataset, we assessed patterns of genetic structure and genetic differentiation of 12 natural diploid populations. We estimated intrapopulation genetic diversity to scope sources for genetic management. Bayesian clustering and principal coordinate analyses showed strong population genetic differentiation between the two regions, and substantial substructure within ACT/NSW. A coalescent tree-building approach implemented in SNAPP indicated evolutionary divergence between the two distant regions. Among the populations screened, the last two known remaining Victorian populations had the highest genetic diversity, despite having among the lowest recent census sizes. A maximum likelihood population tree method implemented in TreeMix suggested little or no recent gene flow except potentially between very close neighbours. Populations that were more genetically distinctive had lower genetic diversity, suggesting that drift in isolation is likely driving population differentiation though loss of diversity, hence re-establishing gene flow among them is desirable. These results provide background knowledge for evidence-based conservation and support genetic rescue within and between regions to elevate genetic diversity and alleviate inbreeding.
34
Brigolin, Daniele, Christophe Rabouille, Bruno Bombled, Silvia Colla, Salvatrice Vizzini, Roberto Pastres, and Fabio Pranovi. "Modelling biogeochemical processes in sediments from the north-western Adriatic Sea: response to enhanced particulate organic carbon fluxes." Biogeosciences 15, no. 5 (March 5, 2018): 1347–66. http://dx.doi.org/10.5194/bg-15-1347-2018.
Full textAbstract:
Abstract. This work presents the result of a study carried out in the north-western Adriatic Sea, by combining two different types of biogeochemical models with field sampling efforts. A longline mussel farm was taken as a local source of perturbation to the natural particulate organic carbon (POC) downward flux. This flux was first quantified by means of a pelagic model of POC deposition coupled to sediment trap data, and its effects on sediment bioirrigation capacity and organic matter (OM) degradation pathways were investigated constraining an early diagenesis model by using original data collected in sediment porewater. The measurements were performed at stations located inside and outside the area affected by mussel farm deposition. Model-predicted POC fluxes showed marked spatial and temporal variability, which was mostly associated with the dynamics of the farming cycle. Sediment trap data at the two sampled stations (inside and outside of the mussel farm) showed average POC background flux of 20.0–24.2 mmol C m−2 d−1. The difference of organic carbon (OC) fluxes between the two stations was in agreement with model results, ranging between 3.3 and 14.2 mmol C m−2 d−1, and was primarily associated with mussel physiological conditions. Although restricted, these changes in POC fluxes induced visible effects on sediment biogeochemistry. Observed oxygen microprofiles presented a 50 % decrease in oxygen penetration depth (from 2.3 to 1.4 mm), accompanied by an increase in the O2 influx at the station below the mussel farm (19–31 versus 10–12 mmol O2 m−2 d−1) characterised by higher POC flux. Dissolved inorganic carbon (DIC) and NH4+ concentrations showed similar behaviour, with a more evident effect of bioirrigation underneath the farm. This was confirmed through constraining the early diagenesis model, of which calibration leads to an estimation of enhanced and shallower bioirrigation underneath the farm: bioirrigation rates of 40 yr−1 and irrigation depth of 15 cm were estimated inside the shellfish deposition footprint versus 20 yr−1 and 20 cm outside. These findings were confirmed by independent data on macrofauna composition collected at the study site. Early diagenesis model results indicated a larger organic matter mineralisation below the mussel farm (11.1 versus 18.7 mmol m−2 d−1), characterised by similar proportions between oxic and anoxic degradation rates at the two stations, with an increase in the absolute values of oxygen consumed by OM degradation and reduced substances re-oxidation underneath the mussel farm.
35
Bailey-Watts, A. E., and A. Kirika. "A re-assessment of phosphorus inputs to Loch Leven (Kinross, Scotland): rationale and an overview of results on instantaneous loadings with special reference to runoff." Transactions of the Royal Society of Edinburgh: Earth Sciences 78, no. 4 (1987): 351–67. http://dx.doi.org/10.1017/s0263593300011299.
Full textAbstract:
ABSTRACTConcern over the effects of eutrophication of Loch Leven led to an assessment of the phosphorus (P) loading and the contributions from runoff (from a catchment area of 145 km2), rain on the loch, roosting wildfowl, treated sewage effluent and P-rich industrial waste. Integrated programmes of flow gauging and nutrient analyses on twelve stream systems were carried out at eight-day intervals from January 1985 to February 1986. The paper concentrates on runoff and is restricted largely to total phosphorus (TP) loadings estimated from instantaneous flow and concentration data. The potential for deriving continuous loadings is discussed; examination of instantaneous and continuous discharge figures for a major inflow suggests that the present sampling regime has characterised its hydrological behaviour well. Nearly 90% of the water enters the loch in four streams of 0·1–1·0 m3 s−1 mean flow. The total input of water was high in 1985–134·4 × 106 m3 which is equivalent to a flushing rate of 2·6 (loch volumes); the effect on the loading results of the unusually wet study period is discussed.Inflow concentrations of TP ranged from <10μg 1−1 to c. 4 mg 1−1; they generally increased with increasing flow but co-efficients of determination (r2 values) were only ≦0·57. Rating curves based on log load/log flow gave, for most waters, r2 values of 0·85, suggesting that load-flow, rather than concentration-flow models, will prove more favourable for predicting loads on non-sampling dates.The total TP loading in runoff in 1985 was 9·4 tonnes, 38% of which was in soluble reactive form (SRP). Losses of P varied between sub-catchments, with 0·41–1·67 kg TP ha−1 yr−1 and typically <0·25 kg SRP ha−1 yr−1—representing only 5% of the annual agricultural applications of P. Initial calculations of inputs from sewage treatment works and industry suggest that these point-sources together contribute at least as much TP as in runoff, and twice the SRP in runoff. The significance of these findings for P control is discussed.
36
Winter, Kate, Emily A. Hill, G. Hilmar Gudmundsson, and John Woodward. "Subglacial topography and ice flux along the English Coast of Palmer Land, Antarctic Peninsula." Earth System Science Data 12, no. 4 (December 17, 2020): 3453–67. http://dx.doi.org/10.5194/essd-12-3453-2020.
Full textAbstract:
Abstract. Recent satellite data have revealed widespread grounding line retreat, glacier thinning, and associated mass loss along the Bellingshausen Sea sector, leading to increased concern for the stability of this region of Antarctica. While satellites have greatly improved our understanding of surface conditions, a lack of radio-echo sounding (RES) data in this region has restricted our analysis of subglacial topography, ice thickness, and ice flux. In this paper we analyse 3000 km of 150 MHz airborne RES data collected using the PASIN2 radar system (flown at 3–5 km line spacing) to investigate the subglacial controls on ice flow near the grounding lines of Ers, Envisat, Cryosat, Grace, Sentinel, Lidke, and Landsat ice streams as well as Hall and Nikitin glaciers. We find that each outlet is topographically controlled, and when ice thickness is combined with surface velocity data from MEaSUREs (Mouginot et al., 2019a), these outlets are found to discharge over 39.25 ± 0.79 Gt a−1 of ice to floating ice shelves and the Southern Ocean. Our RES measurements reveal that outlet flows are grounded more than 300 m below sea level and that there is limited topographic support for inland grounding line re-stabilization in a future retreating scenario, with several ice stream beds dipping inland at ∼ 5∘ km−1. These data reinforce the importance of accurate bed topography to model and understand the controls on inland ice flow and grounding line position as well as overall mass balance and sea level change estimates. RES data described in this paper are available through the UK Polar Data Centre: https://doi.org/10.5285/E07D62BF-D58C-4187-A019-59BE998939CC (Corr and Robinson, 2020).
37
FLORES, D. A., L. E. PHILLIP, D. M. VEIRA, and M. IVAN. "DIGESTION IN THE RUMEN AND AMINO ACID SUPPLY TO THE DUODENUM OF SHEEP FED ENSILED AND FRESH ALFALFA." Canadian Journal of Animal Science 66, no. 4 (December 1, 1986): 1019–27. http://dx.doi.org/10.4141/cjas86-112.
Full textAbstract:
A study was conducted with six sheep equipped with rumen and duodenal re-entrant cannulae to investigate differences in duodenal amino acid supply with fresh and ensiled alfalfa. The experiment was conducted as a cross-over design with two 12-d periods consisting of an adaptation phase (5 d) followed by feces collection (5 d), and finally on day 12, 24 h continuous collection of duodenal digesta and sampling of rumen fluid. During the experiment the sheep were restricted on feed to 52 g DM d−1 kg−0.75. Analyses of the forages revealed extensive breakdown of threonine, lysine and other basic amino acids, and high degree of preservation of branched chain amino acids. Relative to the amount consumed, there was a net loss of amino acids at the duodenum with fresh alfalfa but a net gain with silage. The relationship between intake of individual essential amino acids and duodenal recovery was inconsistent. Duodenal recovery of total essential amino acids was 28% higher with fresh than with ensiled alfalfa, a difference which was most pronounced with threonine and lysine. Digestion of organic matter and fiber was unaffected (P > 0.05) by ensiling of alfalfa. Estimates of ruminal pH were higher (P < 0.05) for silage than fresh forage (6.9 vs. 6.7) but VFA concentrations were lower (P < 0.05) for silage (52.1 vs. 64.1 mmol L−1). Rumen ammonia levels were similar for the two forages. The deficit in duodenal supply of essential amino acids with silage is discussed in relation to the problem of silage intake in ruminants. Key words: Alfalfa silage, duodenal amino acids, sheep, rumen digestion
38
Ohngemach, Sibylle, Gabi Hagel, and Frank Schaeffel. "Concentrations of biogenic amines in fundal layers in chickens with normal visual experience, deprivation, and after reserpine application." Visual Neuroscience 14, no. 3 (May 1997): 493–505. http://dx.doi.org/10.1017/s0952523800012153.
Full textAbstract:
AbstractPrevious experiments in chickens have shown that dopamine released from the retina may be one of the messengers controlling the growth of the underlying sclera. It is also possible, however, that the apparent relationship between dopamine and myopia is secondary and artifactual. We have done experiments to assess this hypothesis. Using High Pressure Liquid Chromatography with electrochemical detection (HPLC-ED), we have asked whether changes in dopamine metabolism are restricted to the local retinal regions in which myopia was locally induced. Furthermore, we have measured the concentrations of biogenic amines separately in different fundal layers (vitreous, retina, choroid, and sclera) to find out how changes induced by “deprivation” (= removal of high spatial frequencies from the retinal image by translucent eye occluders which produce “deprivation myopia”) are transmitted through these layers. Finally, we have repeated the deprivation experiments after intravitreal application of the irreversible dopamine re-uptake blocker reserpine to see how suppression of dopaminergic transmission affects these changes. We found that (1) Alterations in retinal dopamine metabolism were indeed restricted to the retinal areas in which myopia was induced. (2) The retina was the major source of dopamine release with a steep gradient both to the vitreal and choroidal side. Vitreal content was about one-tenth, choroidal content about one-third, and scleral content about one-twentieth of that of the retina. (3) There was a drop by about 40% in vitreal dopamine, DOPAC (3,4-dihydroxyphenylacetic acid) and HVA (homovanilic acid) concentrations following deprivation which occurred already at a time where little changes could yet be seen in their total retinal contents. (4) Choroidal and scleral dopamine levels were not affected by deprivation, indicating that other messengers must relay the information to the sclera. (5) A single intravitreal injection of reserpine lowered dopamine and HVA levels in retina and vitreous for at least 10 days in a dose-dependent fashion and diminished or suppressed further effects of deprivation on these compounds. DOPAC levels continued to change upon deprivation even after reserpine injection (Fig. 3). Our results suggest that the release rates of dopamine from retinal amacrine cells can be estimated from vitreal dopamine concentrations; furthermore, they are in line with the hypothesis that there is an inverse relationship between dopamine release and axial eye growth rates. Although our experiments do not ultimately prove that dopamine has a functional role in the visual control of eye growth, they are in line with this notion.
39
Nikkilä, Atte, Olli Lohi, Ólafur Gísli Jónsson, Bendik Lund, Jonas Abrahamsson, Goda Elizabeta Vaitkeviciene, Kaie Pruunsild, et al. "Intensive Chemotherapy for High-Risk ALL in Children - the Nordic Collaborative Approach." Blood 134, Supplement_1 (November 13, 2019): 742. http://dx.doi.org/10.1182/blood-2019-122914.
Full textAbstract:
OS for childhood ALL is now >90%, but high-risk (HR) cases still need to improve. The NOPHO ALL2008 protocol restricted very intensive HR chemotherapy to patients with an inferior early minimal residual disease (MRD) response or HR genetics, and we here report the results for this subset. HR patients had WBC >100K at diagnosis and/or T-ALL; and an MRD of either >25% day 15 or >0.1% day 29; and/or a KMT2A-re or hypodiploidy (<45 chr). MRD was assessed by flow cytometry (BCP) or PCR (T-ALL). If no marker was found with one, the alternative method was used. Thus, >98% had a suitable MRD marker. All HR patients received a 3-drug induction chemotherapy (VCR 2 mg/m2 x5), DOX (40 mg/m2 x2), PRED (60 mg/m2/d for 4 weeks for BCP-ALL with WBC <100K) or DEXA (10 mg/m2/d for 3 weeks for all others). This was followed by 9 (A1-B1-C1-A2-B2-C2-A3-B3-C3) or 7 (if MRD after 1st HR block <0.1%; C2/C3 deleted) blocks, 60 weeks of interim maintenance with oral 6MP/MTX and HD-MTX x3 (5g/m2/d), delayed intensification, and maintenance therapy until a total of 2.5 years from diagnosis. Post-induction, a total of 12 doses of i.m. Peg-asp (1,000 IU/m2) was given (Toft, Leukemia 2018). A-blocks included cyclophosphamide (440 mg/m2/d x5), etoposide (100 mg/m2/d x5), and Peg-asp (1000 IU/m2). B-blocks consisted of HD-MTX (5g/m2), HD-AraC (2x2g/m2 /d x2), 6MP (100 mg/m2/d x5), DEXA (20 mg/m2/d x5), VCR (2 mg/m2 x2), Peg-asp (1000 IU/m2). C-blocks included idarubicin (8 mg/m2), fludarabine (30 mg/m2/d x5), HD-AraC (2g/m2 /d x5), Peg-asp (1000 IU/m2). Patients were allocated to hSCT if MRD >5% at end of induction, or >0.1% after 2 HR-blocks or ~3 months of LR-chemotherapy. HSCT-patients are not included here. Data on 18 toxic adverse events was prospectively collected at three-month intervals. The Kaplan-Meier method was used for OS and EFS analyses. CI of Rel (CIR) and TRM (CITRM) were estimated accounting for competing events. Cox-models were used to compute hazard ratios and proportional hazard assumptions were evaluated using Schoenfeld residuals. 132 subjects 1-≤18 years of age at diagnosis were eligible for HR chemotherapy accounting for 16% of the study cohort with a median age of 6.6 years as compared to 4.6 years in the entire cohort. Of the HR chemotherapy subjects 26% received PRED in induction. Five-year EFS was 67% (95% CI, 59-76%) and OS was 74% (95% CI, 67-82%) in the HR chemo cohort. CIR at five years was 18% (95% CI, 11-24%). We found no difference in EFS by cell lineage (BCP-ALL: 69%, 95% CI, 59-80% vs. T-ALL 65%, 95% CI 52-77%). KMT2A-re occurred in 34 patients, 62% of whom had MRD <0.1% after induction. Their five-year EFS and OS were 88% (95% CI, 77-99%). KMT2A-re patients with a leukocyte count <100K and EOI MRD <0.1% had no relapses, but toxic deaths resulting in a 5-year EFS of 80% (95% CI, 55-100%). Hypodiploid patients had a five-year EFS and OS of 55% (95% CI, 34%-76%) and 58% (95% CI, 39-78%), respectively. Strikingly, KMT2A-re and hypodiploid patients with a negative MRD at EOI, suffered no relapses. 29 patients shifted to HR-blocks at day 15 due to MRD >25% (T-ALL (N=17), BCP with WBC >100K (N=7), KMT2A-re (N=4), or hypodiploid ALL (N=1). Their five-year EFS was 47% (95% CI, 21-73%) and CIR 44% (95% CI, 18-70%). During the HR chemotherapy blocks, 70% (N=93) of patients encountered at least one toxic event beyond bacteremia and febrile neutropenia, the most common of which was fungal infections (25%), referral to intensive care (23%), and asparaginase associated anaphylaxis (21%). The NOPHO ALL2008 stratification strategy led to allocation of 16% of patients to the HR arm with an EFS of 67% and OS of 74%. Due to the intensity of chemotherapy a significant risk of toxic death was encountered, and the risks of toxic death and relapse were very similar. Patients with rearranged KMT2A and a low EOI MRD could be candidates for future reduction of treatment intensity. These findings are integrated into the upcoming European ALLTogether1 protocol opening in 14 European countries early 2020, where the use of the NOPHO ALL2008 HR blocks will be restricted to the 3% of patients with the poorest prognosis. Figure - EFS with 95% Cis, CITRM (short dash) and CIR (long dash) for the NOPHO ALL-2008 high-risk chemotherapy patients Disclosures No relevant conflicts of interest to declare.
40
Cammell, S. B., D. J. Thomson, D. E. Beever, M. J. Haines, M. S. Dhanoa, and M. C. Spooner. "The efficiency of energy utilization in growing cattle consuming fresh perennial ryegrass (Lolium perenne cv. Melle) or white clover (Trifolium repens cv. Blanca)." British Journal of Nutrition 55, no. 3 (May 1986): 669–80. http://dx.doi.org/10.1079/bjn19860073.
Full textAbstract:
1. Twenty Friesian steers (225 kg live weight) were fed on mid- (M) (June-July) and late- (L) (August- September) season crops of either fresh perennial ryegrass (Loliumperenne cv. Melle) (G) or white clover (Trifolium repens cv. Blanca) (C). Each of the forage diets was offered at three restricted planes of nutrition above main- tenance to compare the effect of forage species on the efficiency of energy utilization. All diets were harvested daily from swards of regrowth forage of intended equivalent digestibility.2. Faecal and urine excretions were measured for 7 and 5 d respectively, followed by two consecutive 24 h measurements of methane, carbon dioxide and oxygen exchange in open-circuit respiration chambers.3. The apparent digestibility of the energy in perennial ryegrass (0.759) was marginally higher (P < 0.01) than that in white clover (0.748);the mid- and late-season forages were of similar (P > 0.05)digestibilities. Metabolizable energy (ME):digestible energy (DE) in diet G (0.837) was significantly (P < 0,001) different from that in diet C (0.812). The partition of energy losses when expressed as MJ/GJ gross energy intake (GEI) indicated that energy lost as methane was not significantly different (P > 0.05) either between forages (G 62.8, C 63.4) or between seasons (M 63.2, L 63.1). Energy excretion in urine was higher for cattle fed on diet C (77.5) compared with diet G (60.5)(P < 0.001). Heat production was similar (P 0.05) between forages (G 480, C 478), but lower (P < 0.01) for L (471) compared with M(486). Energy retention (by difference) was lower (P < 0.001) for diet C (132) than G (156) and for M (138) than L (149) (P < 0.05).4. Parallel-line analysis of unscaled ME intake (MEI) in relation to retained energy (RE; MJ/d) indicated that the efficiency of utilization (kr) was similar (P > 0.05) between perennial ryegrass (0.42) and white clover (0.46). Linear extrapolation of the values to zero energy retention indicated that maintenance requirements of ME (Em MJ/d) were 23.3 for diet G and 28.8 for diet C. The extrapolated Emwhen expressed in relation to a measured fasting heat production (FHP) of 22.8 (MJ/d) resulted in a derived efficiency of utilization of ME for maintenance (km) of 0.97 (G) and 0.79 (C), suggesting an underestimate of Em for diet G.5. Asymptotic exponential curves (representing the law ofdiminishing returns) were fitted to the unscaled values, ME1 and RE (MJ/d), and extrapolated to zero energy retention and zero energy intake. The derived estimates of FHP (MJ/d) 18.0 (G) and 22.0 (C) were not significantly different (P > 0.05) from the observed value of 22.8 MJ/d. Using the measured FHP as additional data points, the exponential model accounted for significantly more variance (P < 0,001) compared with the linear regression method of analysis. Exponential analysis resulted in estimates of Em (MJ/d) of 29.04 for diet G and 31.80 for C. The k, for each forage was calculated, assuming linearity of response, as 0.78 (G) and 0.72 (C). The calculation of k, at fixed positions on the exponential curve related to ME1 (expressed as multiples of Em)indicated that above 1.65 Em, kt was significantly higher for C than G (P < 0.05). With increasing plane of nutrition kf declined from 0.53 to 0.29 (G) and 0.55 to 0.36 (C) over the ME1 range measured during the experiment.
41
Cohen, Adam D., Suzanne Trudel, Peter A. Forsberg, Rafael Fonseca, Amrita Y. Krishnan, Andrew Spencer, Jesus G. Berdeja, et al. "GO39775: A multicenter phase I trial evaluating the safety, pharmacokinetics, and activity of BFCR4350A, a FcRH5/CD3 T-cell dependent bispecific antibody, in patients with relapsed or refractory multiple myeloma." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): TPS8551. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.tps8551.
Full textAbstract:
TPS8551 Background: Multiple myeloma (MM) remains an incurable disease, with estimated median survival of 8–9 months in patients with relapsed or refractory (R/R) disease (Kumar et al. 2014; Usmani et al. 2016). There is no uniform standard of care for R/R MM, and combinations used in later lines have diminishing responses, especially after re-exposure to previously received classes of therapy (Gandhi et al. 2019). New targets and treatment modalities are needed. Fragment crystallizable receptor-like 5 (FcRH5) is expressed on myeloma cells across lines of therapy, and is overexpressed by myeloma cells with 1q21 gain; expression in healthy tissue is restricted to the B-cell lineage, and is retained in plasma cells (Li et al. 2017). BFCR4350A is an IgG-based T-cell-dependent bispecific antibody that was specifically engineered to target the most membrane-proximal domain of FcRH5 on myeloma cells and cluster of differentiation 3 (CD3) on T cells, with dual binding resulting in efficient immune synapse formation and T-cell killing of myeloma cells. BFCR4350A demonstrates potent killing of plasma cells and patient-derived myeloma cells (including those with low levels of FcRH5 expression) in vitro, and complete depletion of bone marrow plasma cells in primates, without severe or prolonged cytokine release (Li et al. 2017). GO39775 (NCT03275103) is an open-label, multicenter Phase I dose-escalation and dose-expansion trial evaluating the safety, pharmacokinetics (PK), and activity of BFCR4350A monotherapy in patients with R/R MM. Methods: Patients must be aged ≥18 years and must have R/R MM for which no established therapies are available or appropriate, or be intolerant to those therapies. Patients with prior CAR-T therapy and/or prior BCMA-directed therapy are not excluded. BFCR4350A is administered by intravenous infusion, and q3w dosing with Cycle 1 single-step or multi-step dosing is being investigated in dose-escalation (Arms A and B, respectively). Enrolment into both arms is ongoing, with patients receiving up to 17 cycles of treatment until disease progression or unacceptable toxicity. Primary objectives are to evaluate safety (including the maximum tolerated dose and dose-limiting toxicities) and to identify a recommended Phase II dose. Secondary objectives include assessment of PK, activity, immunogenicity, and pharmacodynamic biomarkers. Clinical trial information: NCT03275103 .
42
de Ruijter, W. J., and Sharma Renu. "Precise on-line Measurement of Lattice Vectors." Proceedings, annual meeting, Electron Microscopy Society of America 48, no. 1 (August 12, 1990): 530–31. http://dx.doi.org/10.1017/s0424820100181403.
Full textAbstract:
Established methods for measurement of lattice spacings and angles of crystalline materials include x-ray diffraction, microdiffraction and HREM imaging. Structural information from HREM images is normally obtained off-line with the traveling table microscope or by the optical diffractogram technique. We present a new method for precise measurement of lattice vectors from HREM images using an on-line computer connected to the electron microscope. It has already been established that an image of crystalline material can be represented by a finite number of sinusoids. The amplitude and the phase of these sinusoids are affected by the microscope transfer characteristics, which are strongly influenced by the settings of defocus, astigmatism and beam alignment. However, the frequency of each sinusoid is solely a function of overall magnification and periodicities present in the specimen. After proper calibration of the overall magnification, lattice vectors can be measured unambiguously from HREM images.Measurement of lattice vectors is a statistical parameter estimation problem which is similar to amplitude, phase and frequency estimation of sinusoids in 1-dimensional signals as encountered, for example, in radar, sonar and telecommunications. It is important to properly model the observations, the systematic errors and the non-systematic errors. The observations are modelled as a sum of (2-dimensional) sinusoids. In the present study the components of the frequency vector of the sinusoids are the only parameters of interest. Non-systematic errors in recorded electron images are described as white Gaussian noise. The most important systematic error is geometric distortion. Lattice vectors are measured using a two step procedure. First a coarse search is obtained using a Fast Fourier Transform on an image section of interest. Prior to Fourier transformation the image section is multiplied with a window, which gradually falls off to zero at the edges. The user indicates interactively the periodicities of interest by selecting spots in the digital diffractogram. A fine search for each selected frequency is implemented using a bilinear interpolation, which is dependent on the window function. It is possible to refine the estimation even further using a non-linear least squares estimation. The first two steps provide the proper starting values for the numerical minimization (e.g. Gauss-Newton). This third step increases the precision with 30% to the highest theoretically attainable (Cramer and Rao Lower Bound). In the present studies we use a Gatan 622 TV camera attached to the JEM 4000EX electron microscope. Image analysis is implemented on a Micro VAX II computer equipped with a powerful array processor and real time image processing hardware. The typical precision, as defined by the standard deviation of the distribution of measurement errors, is found to be <0.003Å measured on single crystal silicon and <0.02Å measured on small (10-30Å) specimen areas. These values are ×10 times larger than predicted by theory. Furthermore, the measured precision is observed to be independent on signal-to-noise ratio (determined by the number of averaged TV frames). Obviously, the precision is restricted by geometric distortion mainly caused by the TV camera. For this reason, we are replacing the Gatan 622 TV camera with a modern high-grade CCD-based camera system. Such a system not only has negligible geometric distortion, but also high dynamic range (>10,000) and high resolution (1024x1024 pixels). The geometric distortion of the projector lenses can be measured, and corrected through re-sampling of the digitized image.
43
Weber, K. J., and Hans Dronkert. "Screening Criteria to Evaluate the Development Potential of Remaining Oil in Mature Fields." SPE Reservoir Evaluation & Engineering 2, no. 05 (October 1, 1999): 405–11. http://dx.doi.org/10.2118/57873-pa.
Full textAbstract:
Summary Continuing reservoir management at mature stages often concentrates on delineating pockets of remaining mobile oil. This is becoming a major task for reservoir geologists and petrophysicists. Many old fields are coming up for reactivation as investment opportunities and there is an overall expectation that modern techniques can lead to additional recovery of between 10 and 20%. In this article we will discuss the screening criteria related to reservoir architecture, accumulation condition and production history. The mobile oil remaining can be found in a number of predictable locations in reservoirs depending on their structural style and facies. Attic oil along faults is perhaps the most simple configuration but sizeable volumes of remaining oil can also occur as a function of reservoir stratification and lateral discontinuity. A systematic overview of the different play types has been compiled based on structural or stratigraphic lateral continuity and vertical reservoir connectivity. Screening criteria have been derived on the basis of field examples and models for four play types. The screening criteria specify minimum conditions which may lead to economic re-development with horizontal sidetracks from existing wells. In addition recommendations are given with respect to data gathering to confirm the presence of economically viable targets. Introduction Numerous oil fields that have been in production for many years are currently being reviewed to evaluate options for increasing their ultimate recovery. The task involves determination of the volume and location of remaining mobile oil and subsequently the technical and economic assessment of methods to recover this oil. The first part of this task is often difficult because of the poor quality of the data often associated with old fields. Nevertheless, certain basic data are usually available and the purpose of this article is to provide first round screening criteria based on these data in order to select those reservoirs for which re-development schemes are more likely to be economical. For the reservoirs selected, further study and some additional data acquisition will be warranted. The data that may be expected to be present consist of well logs, limited core measurements, basic facies descriptions, original oil-in-place and cumulative production figures, structure maps and well positions. Having access to well completion data is also essential. Individual well performance data are often difficult to obtain. The proposed screening scheme is based on a classification of the types of remaining oil configurations. Once such a potential oil pocket has been recognized, an attempt is made to assess its economic value by estimating a number of parameters with a limited degree of accuracy. Dip, original accumulation conditions, bedding thickness, reservoir profile, porosity distribution and original oil saturation can often be determined satisfactorily. More detailed reservoir architecture and particularly permeability distributions are more difficult to obtain. The classification scheme for mobile remaining oil pockets consists of a division into reservoirs with either high or low vertical permeability/connectivity and a further subdivision into types with a high and low horizontal connectivity. In this article four major types of mobile remaining oil configurations, representing the four combinations of high and low vertical and horizontal conductivity, are discussed. The screening criteria presented are based on re-development with pairs of horizontal sidetracks from existing wells. A cost of $1,000,000 has been assumed per job for re-entering the hole, milling the casing and drilling and completion of the two sidetracks each of 300 m length. This is based on a variety of cost estimates obtained for land operations. The economic analysis based on this method and on the cost level shows a remarkably large scope for re-development of reservoirs with oil rims, attic oil cases in faulted reservoirs and layer cake reservoirs with beds of contrasting permeability. Fluvial labyrinth type reservoirs1 are much more difficult to re-develop but a number of observations are made to suggest more favorable configurations. Classification of Remaining Mobile Oil Configurations The retention of mobile oil in sufficiently large volumes to allow economic re-development is largely controlled by the presence of heterogeneous pressure distribution and the fluid density and viscosity contrasts. This article is restricted to sandstone reservoirs containing light oil that have been developed with vertical wells and produced under reasonable draw-down conditions. In view of the potential for recompletion and infill drilling, the most important heterogeneities are faults, boundaries of genetic units, large permeability contrasts and baffles to flow such as shale intercalations. Following the subdivisions of clastic reservoirs into layer cake, jigsaw puzzle and labyrinth types one can already predict a number of typical oil displacement patterns. By considering major large scale heterogeneities we can subdivide the reservoirs into types with a high vertical conductivity and those in which stratification and low permeable intercalations result in low vertical conductivity. Next we can make a further distinction between layer cake reservoirs with a high degree of lateral continuity of the beds and reservoirs where the lateral continuity is limited by faults or pinchouts of the sand bodies. This leads to the scheme shown in Fig. 1. To the first category, A, we can attribute oil-rim reservoirs with a high vertical conductivity in which unproducible oil columns are left between the vertical wells as a result of cusping and coning. Poor lateral continuity can be formed by a normal fault (B1) which, even when nonsealing over the juxtaposed reservoir interval, traps oil in the up-thrown block against the caprock in the down-thrown block. Depending on the throw of the fault, the structural dip and the distance of the vertical wells from the fault, a volume of oil will remain when the well water runs out. In labyrinth reservoirs one finds updip stratigraphic traps (B2) especially in low net/gross (N/G) cases. In such cases we also encounter poor sweep efficiency unless the well spacing is small (D). Poor sweep can also result from stratification with large permeability contrast between the beds, particularly when these are separated by impermeable intercalations (C). This situation is quite common in layer cake reservoirs. Even without impermeable separations crossflow may be limited if the vertical permeability of the low permeability layer is low. This situation frequently occurs in fluvial labyrinth reservoirs and this can occur in combination with configurations B1 and D.
44
Raup, David M. "Large-body impact: the least unlikely cause of pulsed extinction." Paleontological Society Special Publications 6 (1992): 240. http://dx.doi.org/10.1017/s2475262200008005.
Full textAbstract:
In the past year, a strong consensus in the geological community has developed in favor of comet or asteroid impact as the ultimate cause of the K-T mass extinction, although many paleontologists remain doubtful. The discovery of tektites and craters with argon-argon ages matching the K-T boundary has finally removed the “smoking gun” problem. It is important, therefore, to evaluate large-body impact as a possible cause of other Phanerozoic extinctions, and to do so as carefully as possible before enthusiasm for the K-T success overwhelms objectivity in this research area.Approximately 60% of all species extinctions in the Phanerozoic occurred in “pulsed” extinctions, defined as ecologically and geographically pervasive episodes in which the number of species going extinct in a geologically short interval far exceeds any reasonable estimate based on chance coincidence of independent events. In addition to the well-known mass extinctions, pulsed extinctions often mark system, series, and stage boundaries, and probably some zonal boundaries.To be plausible, any proposed cause of pulsed extinctions must be (1) geographically pervasive (regional or global), (2) effective in diverse habitats, and (3) relatively quick-acting (to inhibit survival of species by migration or adaptation). The stresses causing the extinctions must be sufficiently severe and rare to be beyond the reach of natural selection, so that species do not have prior opportunity to evolve defenses.These requirements severely limit the possibilities to phenomena that occur on time scales of one million to tens of millions of years, far longer than the tens or hundreds of years available for study by traditional actualistic approaches. In view of the Phanerozoic record, it is not surprising that the earth has not experienced a pulsed extinction in historic times (excluding human influences). This suggests that extinction is one case where the present is a not the key to the past, and a full exploration of the problem will require a substantial re-ordering of thinking.Furthermore, because pulsed extinctions involve geographically widespread species (as well as restricted taxa), and because extinction of widespread species may be qualitatively different from that of local endemics, the common extrapolation from studies of extinction in local populations is risky.Of the many phenomena suggested as causes of pulsed extinction, large-body impact is the one that most nearly satisfies the requirements, and is therefore the least unlikely of the candidates. Temporal distribution is especially critical. Currently accepted flux estimates for comet and asteroid impacts are in the appropriate frequency range to explain the extinction record, but testing the hypothesis will depend on better radiometric dating of the 100+ craters and other confirmed impact events.
45
Heyland, Daren, Christian Stoppe, Luis A. Ortiz, and Andrew G. Day. "669 The Validation of a Novel Outcome Measure in Severe Burns- the Persistent Organ Dysfunction (POD)+Death: Results from a Multicentre Evaluation." Journal of Burn Care & Research 41, Supplement_1 (March 2020): S179—S180. http://dx.doi.org/10.1093/jbcr/iraa024.285.
Full textAbstract:
Abstract Introduction Very few burn care interventions have been rigorously evaluated with adequately powered randomized clinical trials (RCTs) focusing on long-term clinically relevant outcomes. There is a need to improve the efficiency of RCTs in burn care so that more definitive high quality RCTs can be completed with the available resources. Persistent Organ Dysfunction (POD) plus death is a novel endpoint that has been previously validated in general ICU patients. The objective of this study was to validate and demonstrate the utility of POD+death for clinical trials of burn patients. Methods We performed a secondary analysis of a dataset from a RCT of enteral glutamine (the RE-ENERGIZE Trial) involving 60 Intensive Care Units (ICUs) around the world. Enrolled patients were followed for 6 months documenting hospital and 6 months outcomes including quality of life. For the purposes of this analysis, we restricted inclusion to patients with >20% burn size. We define POD as requiring supportive technologies during critical illness and is present when a patient has ongoing requirement for vasopressors, dialysis, or mechanical ventilation at the outcome assessments time points. We evaluated the data for the prevalence of POD and its association with outcome. We hypothesized that patients alive with POD, compared to those alive without POD, would have worse clinical outcomes and that by combining POD+death, we would gain statistical efficiencies. Results Five hundred thirty-nine patients were involved in this analysis. At 28 days, 4.6% of patients were estimated to have circulatory failure, 6.3% had renal failure, 17.1% had respiratory failure, and 8.9% had died, for an overall prevalence of POD+death=27%. Of survivors at day 28, those with POD, compared to those without POD, had a higher mortality rate in the follow up period, had longer ICU and hospital stays, and a reduced quality of life on many of the domains at 6 months (see Tables). Using our observed 28 day rates, to achieve 80% power at a two-sided alpha=0.05 to determine a 25% RRR in mortality, we would require 2246 patient per group to detect a 25% RRR in mortality from 9% to 6.75%, but only 573 patients per group to detect a 25% RRR in mortality+POD from 27% to 20% Conclusions POD+death may be a valid composite outcome measure and compared to historically used endpoints, POD may reduce the sample size requirements of clinical trials of severe burns patients. Further validation in larger clinical trials is required. Applicability of Research to Practice To improve the efficiency of RCTs in burn settings.
46
Davidoff, Amy J., Xuehua Ke, Maria R. Baer, Sheila R. Weiss Smith, Dan Zandberg, Franklin Hendrick, Masayo Sato, Peter L. Greenberg, and Steven D. Gore. "Do Erythropoiesis-Stimulating Agents (ESAs) Affect Survival in Anemic Patients with Myelodysplastic Syndromes (MDS)?" Blood 118, no. 21 (November 18, 2011): 2794. http://dx.doi.org/10.1182/blood.v118.21.2794.2794.
Full textAbstract:
Abstract Abstract 2794 ESAs play an important role in the amelioration of MDS-related anemia with Phase II trials demonstrating a 20–40% erythroid response rate. Randomized trials in breast, non-small cell lung, and head and neck cancers have suggested a deleterious effect of ESAs on progression-free and overall survival. In contrast, the single Phase III trial randomizing between ESA administration and supportive care in lower- risk MDS patients (E1996) demonstrated no differences in overall survival or in the incidence of acute myeloid leukemia (AML) transformation (Blood 2009). Retrospective analyses of MDS studies have also suggested no such negative impact of ESAs. To further examine the impact of ESA administration on progression to AML or death (ie, progression-free survival, PFS), we combined data on MDS patients from two sources: the International MDS Risk Assessment Workshop (IMRAW) pooled data on ESA untreated patients from 7 historical registries accrued when ESAs were not commercially available (Blood 1997) and Surveillance Epidemiology and End Results (SEER) registries from 2001–2005 linked to Medicare claims including ESA treated and untreated patients. Conceptually, comparison of these groups could function as an “historical experiment” comparing cohorts which differ primarily in the widespread availability of ESAs. Because IMRAW included baseline hemoglobin measurements but did not indicate transfusion use, while SEER-Medicare documents transfusion use but not hemoglobin, we identified MDS patients with a high likelihood of transfusion need as follows: IMRAW patients with hemoglobin <8.5, and SEER-Medicare with at least one transfusion within 3 months pre-or post-diagnosis. Patients were selected and grouped by risk (IMRAW: IPSS low and intermediate-1 versus intermediate-2 and high risk; SEER: WHO classification of refractory anemia, refractory anemia with ring sideroblasts, refractory cytopenia with multilineage dysplasia or del(5q) syndrome versus refractory anemia with excess blasts). Compared to IMRAW (N=199), SEER-Medicare (N=260) had a higher proportion of MDS lower-risk (74% versus 61%), and older (78% versus 37% aged > 75 years) patients. Cox proportional hazard (PH) estimates pooling ESA treated from SEER and (non-treated) IMRAW patients, controlling for age, sex, and risk group (Model 1) failed to find an effect of ESAs (HR 0.79, p=.147) on PFS. As expected, higher MDS risk (HR 3.05, p<.001) and increasing age were associated with increased hazard of AML or death. We further compared the IMRAW (all patients with Hgb < 8.5) to SEER-Medicare (transfusion-receiving) including both ESA-treated and ESA-naïve patients (Model 2) and re-estimated both Models 1 & 2 stratified by MDS prognostic risk group. Relative to IMRAW, SEER-Medicare patients (ESA users and non-users) demonstrated an increased risk of AML/death (HR 1.34, p=.020). ESA use was not associated with a significant difference in survival when comparison of ESA-treated SEER-Medicare to IMRAW (Model 1) was restricted to either MDS-high risk or MDS-lower risk patients. Subset analysis of Model 2 by risk group (ESA treated and naïve in SEER-Medicare compared with IMRAW) indicates a somewhat larger effect among higher-risk compared to lower-risk MDS (HR 1.51, p=0.037 versus HR 1.21, p=0.264). When ESA treated and untreated in SEER-Medicare alone were compared to each other, controlling for risk group, age, race, sex, comorbid conditions, and prior cancer, a strong protective effect of ESAs was found (PH model, HR 0.63, p<.001); however this difference was not sustained when analyses controlled for potential selection bias (HR: 1.54, p=0.14). Although the SEER-Medicare cohort demonstrated inferior progression-free survival compared to the IMRAW cohort, even when age and MDS risk group were controlled for, this analysis can identify no specific negative impact of the use of ESA in this population. Disclosures: Davidoff: Cellgene: Equity Ownership, Research Funding. Off Label Use: this study examines off-label use of erythropoiesis stimulating agents in patients with myelodysplastic syndromes. Greenberg:amgen: Consultancy, Research Funding; onconova: Research Funding; glaxosmithkline: Research Funding; novartis: Consultancy, Research Funding. Gore:Celgene: Consultancy, Equity Ownership, Research Funding.
47
Chen, Clara, Philippe Armand, Basia Rogula, Karissa Johnston, Derek Peterson, Joseph M. Connors, and Greta Lozano-Ortega. "A Matching-Adjusted Indirect Comparison of Nivolumab Versus Brentuximab Vedotin for Relapsed/Refractory Classical Hodgkin Lymphoma after Failure of Autologous Hematopoietic Cell Transplantation." Blood 134, Supplement_1 (November 13, 2019): 4761. http://dx.doi.org/10.1182/blood-2019-122302.
Full textAbstract:
Introduction: Historically, patients with relapsed/refractory classical Hodgkin lymphoma (R/R cHL) who relapse after autologous hematopoietic cell transplantation (auto-HCT) have poor outcomes. In the phase 2 CheckMate 205 study (NCT02181738) of patients with R/R cHL and prior auto-HCT, patients in Cohort A were brentuximab vedotin (BV) naive, and those in Cohorts B and C had prior BV exposure. Nivolumab (nivo), an anti-PD-1 immune checkpoint inhibitor monoclonal antibody, was associated with a high response rate (71% Cohorts A+B+C; 65% Cohort A) and durable remissions (median duration of response 18 and 25 months, respectively). Notably, the 2-year overall survival (OS) rates were 87% in Cohorts A+B+C and 90% in Cohort A; the median OS was not reached (median follow-up 33 months; Armand et al. ASH 2018). These results appear better than those in prior studies in this patient population. In the phase 2 pivotal trial of BV (NCT00848926), patients with R/R cHL had a 2-year OS rate of approximately 65% (Chen et al. Blood 2016). Without direct head-to-head randomized trials, cross-trial comparisons have limitations primarily due to differences in patient populations and trial design, and the survival benefits of various treatments are difficult to distinguish. We used matching-adjusted indirect comparison (MAIC) to balance patient populations and then assess the efficacy and survival benefit of nivo relative to BV in patients with R/R cHL for whom auto-HCT had failed. Methods: Individual patient data (IPD) from patients receiving nivo in the CheckMate 205 study were matched to summary data from patients in the BV pivotal trial reported by Chen et al. IPD from Cohort A and combined Cohorts A+B+C of the CheckMate 205 study were re-weighted to match relevant baseline characteristics reported for BV. Pseudo-IPD were generated for BV from KM curves applying a published algorithm. Treatment outcomes (progression-free survival [PFS] and OS) were then compared across balanced trial populations and assessed using hazard ratios (HRs) generated via Cox regression and differences in the area under the curve (ΔAUC) from best-fitting parametric curves. For nivo, 2 well-fitting OS curves were selected for comparison, which conveyed optimistic and conservative assumptions. Restricted AUC at a specific time point is identical to mean survival time at that time point, thus ΔAUC was used as a summary metric to compare survival time between groups. Confidence intervals (CIs) for AUC estimates were generated via bootstrapping. Results: Patients receiving nivo from Cohort A (unmatched n = 63) and Cohorts A+B+C (unmatched n = 243) were matched to those receiving BV (n = 102) using age, sex, performance status score, B symptoms, prior radiotherapy, primary refractory disease, and best response to the most recent prior systemic regimen (matched size: Cohort A, n = 38, Cohorts A+B+C, n = 172). For Cohort A, MAIC analysis of nivo versus BV showed statistically significant reductions in the risk of death (HR, 0.11; 95% CI, 0.12-0.53; P < 0.001) and the risk of progression/death per investigator (HR, 0.54; 95% CI, 0.32-0.91; P = 0.02). Comparing mean survival time at 15 years using AUCs, the expected OS was estimated to range from 153 months (conservative) to 165 months (optimistic) for nivo versus 69 months for BV, with ΔAUC ranging from 85 (95% CI, 51-111) to 94 (72-113) months, respectively. The PFS per investigator at 5 years was estimated to be 32 months for nivo and 22 months for BV, with ΔAUC of 11 (95% CI, −1 to 22) months. MAIC analyses of Cohorts A+B+C produced similar findings (Figure), with the HR for nivo versus BV of 0.33 (95% CI, 0.21-0.53; P < 0.001) for OS, and 0.60 (0.43-0.83; P = 0.002) for PFS per investigator. Comparing AUC at 15 years, the expected OS ranged from 114 months (conservative) to 131 months (optimistic) for nivo versus 69 months for BV, with ΔAUC ranging from 46 (95% CI, 21-71) to 61 (36-83) months, respectively. The estimated PFS per investigator at 5 years was 29 months for nivo versus 22 months for BV, with ΔAUC of 8 (95% CI, 0.4-14) months. Conclusions: MAIC of Cohort A to BV suggests that nivo may provide a favorable OS compared with BV. Additionally, MAIC of Cohorts A+B+C with BV suggests that nivo alone or adding nivo after BV in patients with R/R cHL and prior auto-HCT may provide a meaningful OS benefit compared with BV alone. MAIC of Cohorts B+C with BV is ongoing. Study support: BMS. Writing support: Janice Zhou, Caudex, funded by BMS. Disclosures Chen: Bristol-Myers Squibb: Employment. Armand:Genentech: Research Funding; Sigma Tau: Research Funding; Infinity: Consultancy; Affimed: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy; Adaptive: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; ADC Therapeutics: Consultancy; Tensha: Research Funding; Roche: Research Funding; Otsuka: Research Funding. Rogula:Broadstreet HEOR: Employment; Bristol-Myers Squibb: Other: I am an employee of Broadstreet HEOR which was contracted by Bristol-Myers Squibb for the conduct of this work.. Johnston:Broadstreet HEOR: Employment; Bristol-Myers Squibb: Other: I am an employee of Broadstreet HEOR which was contracted by Bristol-Myers Squibb for the conduct of this work.. Peterson:Bristol-Myers Squibb: Employment, Equity Ownership. Connors:Bristol-Myers Squibb: Consultancy; Takeda Pharmaceuticals: Honoraria; Seattle Genetics: Honoraria, Research Funding. Lozano-Ortega:Broadstreet HEOR: Employment; Bristol-Myers Squibb: Other: I am an employee of Broadstreet HEOR which was contracted by Bristol-Myers Squibb for the conduct of this work..
48
Bernig, Toralf, Willemijn Breunis, Nannette Brouwer, Dirk Roos, Taco W. Kuijpers, and Stephen J. Chanock. "Functional Consequences of Genetic Variation across the Entire MBL2 Locus: Possible Identification of 3′ SNPs That Could Modify Circulating Levels of MBL." Blood 104, no. 11 (November 16, 2004): 1330. http://dx.doi.org/10.1182/blood.v104.11.1330.1330.
Full textAbstract:
Abstract Mannose-binding protein (MBL) is a critical component of innate immunity and provides first-line protection against pathogens by binding to N-acetyl-glucosamine and mannose residues on the surface of microorganisms (bacteria, fungi and parasites). MBL can activate complement by the lectin pathway. Both circulating MBL serum levels and functional activity have been correlated with common genetic variants in the MBL2 gene; decreased levels and activity correlate with 3 nonsynonymous single nucleotide polymorphisms, SNPs, (known as B, C and D) in exon 1 and two linked promoter SNPs (−550 H/L and −221 Y/X) as well as a 5′UTR SNP (+4 P/Q) influence circulating levels. These components form the “secretor haplotypes”, which correlate with circulating levels. A number of studies have reported associations between MBL deficiency and recurrent or severe infections, especially in immuno-incompetent patients (i.e., BMT recipients, cancer patients, and infants) or in auto-immune disorders; however, measured MBL serum levels do not fully correlate with the “secretor haplotypes”. Based on data from a re-sequence analysis across the entire MBL2 locus, in which we revealed a probable recombination hotspot in the 3′ end of the gene dividing MBL2 into two haplotype blocks, we investigated whether the extended block structure might identify additional SNPs that contribute to MBL serum levels and activity. We analysed more than 20 common SNPs across the locus, including haplotype-tagging SNPs (htSNPs) with Taqman assays validated on the SNP500 website (http://snp500cancer.nci.nih.gov); we captured more than 95% of common haplotypes in both the 5′ and 3′ haplotype blocks. Our pilot analysis was performed in 235 DNA samples of healthy Dutch Caucasian blood donors with known MBL serum concentrations measured by ELISA. Haplotypes were deduced by maximization-estimation analysis of unphased genotypes; PHASE 2.0 (http://www.stat.washington.edu/stephens/software.html). The haplotype analysis of the results confirmed the haplotype block structure of MBL2 in the Dutch population. The additional 5′ variants tested in this study were in strong linkage to the elements of the “secretor haplotypes”; functional alleles B, C and D also lie on restricted haplotypes. As reported by others, in our study, the secretor haplotypes predicted levels in roughly 85%. Four variants in the 3′ block (Ex4–1483T>C, Ex4–1067G>A, Ex4–901G>A and Ex4–710G>A) lie in 3 common haplotypes (TAAA, CGGG and TGAA) that strongly correlate with MBL serum concentration (Kruskal-Wallis p < 0.0001); individuals with at least one TAAA allele have a higher serum concentration. Thus, it is also possible that both 5′ and the 3′ haplotypes could contribute to serum levels. This suggests that there could be a selective advantage for diversification of the 3′ region of the gene, perhaps altering expression or stability (to be analyzed in follow-up studies). Our data provide evidence that there are additional SNPs in regulatory elements of MBL2, which could influence circulating levels. These observations could improve the predictive value of locus-wide analysis of MBL2 in genetic association studies.
49
Roszkiewicz, J., D. Michałek, A. Ryk, B. Szmyd, and E. Smolewska. "FRI0452 THE IMPACT OF SINGLE NUCLEOTIDE POLYMORPHISMS IN ADORA2A AND ADORA3 ON THE EARLY RESPONSE TO METHOTREXATE AND PRESENCE OF THERAPY SIDE EFFECTS IN CHILDREN WITH JUVENILE IDIOPATHIC ARTHRITIS." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 823.1–823. http://dx.doi.org/10.1136/annrheumdis-2020-eular.4772.
Full textAbstract:
Background:Juvenile idiopathic arthritis (JIA) is the most frequent rheumatic disease in children, with an estimated prevalence between 16 and 150 per 100 000 [1]. Methotrexate (MTX) administered at the dose 10-15mg/m2is currently recommended as the first-line treatment in most of JIA subtypes [2]. Despite its widespread use in rheumatology, the mechanism of MTX immunomodulatory action remains incompletely understood [3]. Free adenosine is one of the particles possibly associated with the action of MTX, acting via three types of adenosine receptor: ADORA2A, ADORA2B, and ADORA3 [4].Objectives:The aim of our study was to determine the association between single nucleotide polymorphisms inADORA2A(rs2236624, rs2298383) andADORA3(rs3393) receptors genes on the disease activity and presence of MTX therapy side effects in patients with JIA.Methods:One hundred children with JIA of all subtypes treated with MTX were recruited to the study. Demographic and clinical parameters were collected at the baseline of MTX therapy and on a control visit 4-6 months (median 5.09 months) after starting MTX. The clinical parameters included inflammatory markers values, number of joints with active arthritis, number of joints with restricted range of movement, physician’s global assessment of disease activity, parent/patient global assessment of overall well-being, functional ability (measured by the Childhood Health Assessment Questionnaire – CHAQ) and the value of Juvenile Idiopathic Arthritis Disease Activity Score 71 (JADAS 71). Presence of MTX side effects was evaluated on the control visit. SNP genotyping was performed using genomic DNA isolated from peripheral blood samples.Results:Both polymorphic variants ofADORA2A(rs2236624, rs2298383 - CC/CT) were significantly associated with 3.5 times higher odds of gastrointestinal side effects occurrence (OR: 3.52, 95%CI: 1.12-11.03, p=0.03 and OR: 3.49, 95%CI: 0.89-13.66 p=0.07) after adjustment to age, sex, dose and route of MTX administration. In addition, children with theADORA3rs3393 polymorphic variant (CT/CC) after six months of MTX treatment had significantly lower number of joints with active arthritis (0.0 vs 1.0, p=0.04), lower JADAS 71 score (3.0 vs 5.1, p=0.16) and lower value of CRP (0.6 vs 2.4, p=0.02).Conclusion:Although future studies are needed to verify our findings, polymorphisms inADORA2AandADORA3genes may become the determinants of MTX treatment efficacy and gastrointestinal toxicity in children with JIA.References:[1]Petty RE, Southwood TR, Manners P, et al. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001.J Rheumatol. 2004;31(2):390-392.[2]Ferrara G, Mastrangelo G, Barone P, et al. Methotrexate in juvenile idiopathic arthritis: advice and recommendations from the MARAJIA expert consensus meeting.PediatrRheumatol Online J. 2018;16(1):46. Published 2018 Jul 11. doi:10.1186/s12969-018-0255-8.[3]Brown, P. M., Pratt, A. G., & Isaacs, J. D. (2016). Mechanism of action of methotrexate in rheumatoid arthritis and the search for biomarkers. Nature Reviews Rheumatology, 12(12), 731–742. doi:10.1038/nrrheum.2016.175.[4]Varani, K. et al. A2A and A3 adenosine receptor expression in rheumatoid arthritis: upregulation, inverse correlation with disease activity score and suppression of inflammatory cytokine and metalloproteinase release. Arthritis Res. Ther. 13, R197 (2011).Disclosure of Interests:None declared
50
Cavet, James, and Daniel Wiseman. "Distal Limb Infiltration by Transformed Lymphoplasmacytoid Lymphoma." Blood 108, no. 11 (November 16, 2006): 4647. http://dx.doi.org/10.1182/blood.v108.11.4647.4647.
Full textAbstract:
Abstract We report 2 cases of lymphoplasmacytoid lymphoma (LPCL) with aggressive, high-grade transformation accompanied by extensive distal lower limb skeletal disease. Case 1: a 26-year-old man with stage IVA anaplastic Ki-1+ NHL achieved durable CR1 with VAPEC-B induction, AC consolidation & mediastinal radiotherapy. In 1997 he re-presented with lymphadenopathy: biopsy & marrow showed small CD20+CD79a+ B lymphocytes with IgM(κ) light chain restriction & increased mature plasma cells, but no evidence of anaplastic NHL. He received VAD (×6) & autologous PBSCT (melphalan 200mg/m2) to CR1. Relapse in 2004 was treated with cyclophosphamide & dexamethasone, then fludarabine (×4). Ten months later he presented with B symptoms & painful right tibial swelling. MR showed multiple medullary lesions in proximal femoral shafts, tibiae & upper fibulae. CT confirmed widespread lymphadenopathy & bilateral renal deposits. Marrow had dense infiltrate of CD20+CD79a+ small lymphoid cells with additional immature CD20+CD79a+ blasts, consistent with transformation to high-grade DLBCL. New complex cytogenetics included XXY with t(14;22) (IGH rearrangement), add(1q), del(6q), del(9p) & trisomy 3. He received R-mini-BEAM (×2) & 2nd PBSCT (R-BEAM conditioning) in 2006 using residual 1997 PBSCH, acheiving CR4 with bony regression on MRI. Four months later B symptoms & right tibial pain recurred & the disease is currently being held by rituximab & steroid. Case 2 was diagnosed with WM/LPCL in 1996, aged 54, following 8 years history of IgM MGUS. He received chlorambucil (1996), CVP (×6) (1997), fludarabine (×5) (1999/2000), chlorambucil (2001) rituximab (×8), further fludarabine (×3) (June 2003) & repeated R-CVP (2004/5). In Sept 2005 he presented with lower limb & right heel pain. MR revealed diffuse abnormality within tibiae, fibulae & distal femorae: a soft tissue mass infiltrated the right talus bone, & left calcaneus, talus & anterior malleolus showed patchy involvement. Biopsy of right talus yielded small lymphocytes, lymphoplasmacytoid cells & plasma cells, strongly CD20+ & κ light chain restricted (with smaller % CD138+ cells), in keeping with lymphoplasmocytic lymphoma. Bisphosphonate exacerbated the pain & single fraction of radiotherapy had no effect. He received salvage R-CVP (×6), reducing paraprotein from 6.9 to 2.7g/L. Nevertheless, the bone deposits continue to cause significant discomfort. Transformation of WM/LPCL to high-grade lymphoma is rare but well-described. Lin et al. describe DLBCL transformation in 13% cases, at median 44 months after diagnosis & associated with poor outcome. Seven of the 12 cases had received cladrabine. Purine analogues have been implicated in pathogenesis of Richter’s syndrome, in which CLL transforms to aggressive NHL (estimated <3% CLL patients). MRI reliably demonstrates marrow involvement in WM/LPCL but changes are diffuse. In contrast to MM, focal skeletal MR abnormalities are not observed in WM/LPCL. We present 2 cases of LPCL with focal distal lower limb bone involvement. The focal nature of skeletal involvement in sites not active in adult haemopoeisis (& atypical for LPCL or MM involvement), with B symptoms & rapidly progressive NHL are unusual features. Other features include >10year disease course, multiple lines of therapy (incl. purine analogues) & high-grade transformation/behaviour. Involvement of distal bones (e.g. talus) is rare in NHL, & we could find no previous reports of focal distal lower limb LPCL. We observe that LPCL can undergo high-grade transformation (analogous to Richter’s syndrome) with distinct trophic phenotype, & postulate that purine analogues may be implicated in selecting for this behaviour.