Статті в журналах з теми "Skipped cycles"
Щоб переглянути інші типи публікацій з цієї теми, перейдіть за посиланням: Skipped cycles.
Оформте джерело за APA, MLA, Chicago, Harvard та іншими стилями
Ознайомтеся з топ-50 статей у журналах для дослідження на тему "Skipped cycles".
Біля кожної праці в переліку літератури доступна кнопка «Додати до бібліографії». Скористайтеся нею – і ми автоматично оформимо бібліографічне посилання на обрану працю в потрібному вам стилі цитування: APA, MLA, «Гарвард», «Чикаго», «Ванкувер» тощо.
Також ви можете завантажити повний текст наукової публікації у форматі «.pdf» та прочитати онлайн анотацію до роботи, якщо відповідні параметри наявні в метаданих.
Переглядайте статті в журналах для різних дисциплін та оформлюйте правильно вашу бібліографію.
1
Burlon, S., H. Mroueh, and J. P. Cao. "‘Skipped cycles’ method for studying cyclic loading and soil–structure interface." Computers and Geotechnics 61 (September 2014): 209–20. http://dx.doi.org/10.1016/j.compgeo.2014.05.007.
2
Cucco, Marco, Marco Grenna, and Irene Pellegrino. "Egg Characteristics in Relation to Skipped Days of Laying in the Grey Partridge." Avian Biology Research 10, no. 4 (November 2017): 231–40. http://dx.doi.org/10.3184/175815617x15036738758853.
Анотація:
Birds sometimes skip a day along the sequence of egg laying, which may vary the mass or the composition of delayed eggs compared with those that were laid consecutively. Our literature review shows that this has been interpreted as a short-term adaptation that enables females to overcome energetic constraints during the laying period, but other hypotheses implying the influence of weather, pollution, or hormonal cycles have also been proposed. We collected freshly laid Grey Partridge Perdix perdix eggs to determine the effects of laying gaps on egg characteristics. Egg shape, as well as egg components (beta-carotene, avidin and lysozyme concentrations) did not vary in relation to skipped days. Eggs were slightly heavier when one or two days were skipped (0.72% and 0.45%, respectively). However, when examining the hatching rate, we found a significant decrease in relation to skipped days, hence eggs following laying gaps showed a lower hatching rate than other eggs. The pattern observed could indicate the presence of some physiological stress that caused females to skip one or two days and to lay eggs that hatched less.
3
Mäeorg, Uno, Andi Kipper, Indrek Kalvet, Kaido Tämm, Lauri Sikk, Peeter Burk, and Kuldar Kõiv. "Synthesis of Unprotected CH2-Skipped Piperazine-Pyridine Alternating Cycles with Azide End-Group." HETEROCYCLES 90, no. 1 (2015): 625. http://dx.doi.org/10.3987/com-14-s(k)12.
4
Cui, X., and C. Q. Doe. "The role of the cell cycle and cytokinesis in regulating neuroblast sublineage gene expression in the Drosophila CNS." Development 121, no. 10 (October 1, 1995): 3233–43. http://dx.doi.org/10.1242/dev.121.10.3233.
Анотація:
The precise temporal control of gene expression is critical for specifying neuronal identity in the Drosophila central nervous system (CNS). A particularly interesting class of genes are those expressed at stereotyped times during the cell lineage of identified neural precursors (neuroblasts): these are termed ‘sublineage’ genes. Although sublineage gene function is vital for CNS development, the temporal regulation of this class of genes has not been studied. Here we show that four genes (ming, even-skipped, unplugged and achaete) are expressed in specific neuroblast sublineages. We show that these neuroblasts can be identified in embryos lacking both neuroblast cytokinesis and cell cycle progression (string mutants) and in embryos lacking only neuroblast cytokinesis (pebble mutants). We find that the unplugged and achaete genes are expressed normally in string and pebble mutant embryos, indicating that temporal control is independent of neuroblast cytokinesis or counting cell cycles. In contrast, neuroblasts require cytokinesis to activate sublineage ming expression, while a single, identified neuroblast requires cell cycle progression to activate even-skipped expression. These results suggest that neuroblasts have an intrinsic gene regulatory hierarchy controlling unplugged and achaete expression, but that cell cycle- or cytokinesis-dependent mechanisms are required for ming and eve CNS expression.
5
Rahman, Nayem. "Saving DBMS Resources While Running Batch Cycles in Data Warehouses." International Journal of Technology Diffusion 1, no. 2 (April 2010): 42–55. http://dx.doi.org/10.4018/jtd.2010040102.
Анотація:
In a large data warehouse, thousands of jobs run during each cycle in dozens of subject areas. Many of the data warehouse tables are quite large and they need to be refreshed at the right time, several times a day, to support strategic business decisions. To enable cycles to run more frequently and keep the data warehouse environment stable the database system’s resource utilization must be optimal. This paper discusses refreshing data warehouses using a metadata model to make sure jobs under batch cycles run on an as-needed basis. The metadata model limits execution of the stored procedures in different analytical subject areas to source data changes in the source staging subject area tables, and then implements refreshes of analytical tables for which new data has arrived from the operational databases. The load is skipped if source data has not changed. Skipping unnecessary loads via this metadata driven approach enables significant database resources savings. The resource savings statistics based on an actual production data warehouse demonstrate an excellent reduction of computing resources consumption achieved by the proposed techniques.
6
Tonini, G., B. Vincenzi, E. Vasile, V. Catalano, V. Virzì, A. Fontana, S. Intagliata, G. Catalano, A. Falcone, and D. Santini. "Phase II capecitabine and gemcitabine fixed dose rate (FDR) in patients with advanced pancreatic cancer." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): e15530-e15530. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.e15530.
Анотація:
e15530 Background: The aims of this phase II trial are to determine the activity and the safety of the new combination modality with Gemcitabine fixed dose rate (FDR) infusion and Capecitabine in patients with advanced pancreatic cancer. Methods: Patients with unresectable pancreatic cancer who had pathologically confirmed adenocarcinoma, no prior chemotherapy, ECOG PS < 2 and measurable disease were enrolled. Gemcitabine (800 mg/mq IV infused in 80 minutes on days 1 and 8) and Capecitabine (650 mg/mq orally twice daily for 14 days) were administered and repeated every 21 days. Results: 47 patients were enrolled between January 2004 and October 2008. Median age was 66 (range: 37–79), 18 female and 29 male. A total of 299 cycles were administered, median cycles for patient were 6 (range: 1–17). CR was observed in one patient (2.1 %) and 10 patients achieved PR (21.3 %) giving an overall response rate of 23.4 % in intention-to-treat population. 22 pts (46.8 %) had stable disease obtaining an overall tumour control of 70.2 %. The median time to progression was 5.2 months (95 % CI, 2.4–7.6); the median overall survival was 8.4 months (95 % CI, 5.5–20). Grade 3–4 neutropenia was observed in 29.8 % of subjects, thrombocytopenia in 6.4 %. Grade 1–2 non-hematological toxicities were asthenia (61.7 %), diarrhea (29.8%), stomatitis (29.8 %) and hand foot syndrome (2.1 %). There were no treatment-related deaths. Gemcitabine was skipped at least once/reduced in 51/10.6 % of the patients, respectively. Capecitabine was skipped at least once/reduced in 16/8 % of the patients, respectively. Conclusions: The combination of FDR Gemcitabine and Capecitabine with this modality of infusion is feaseble, safe and seems to be active. No significant financial relationships to disclose.
7
Stark, Lloyd R. "Skipped reproductive cycles and extensive sporophyte abortion in the desert moss Tortula inermis correspond to unusual rainfall patterns." Canadian Journal of Botany 80, no. 5 (May 1, 2002): 533–42. http://dx.doi.org/10.1139/b02-053.
Анотація:
A phenological assessment of Tortula inermis (Brid.) Mont. populations in the Mojave Desert, Nevada, U.S.A., over a period of 4 years revealed that the sporophyte cohort initiated in early 1995 remained dormant until early 1998, by which time approximately 66% of the sporophytes had aborted. The viable sporophytes of this cohort were significantly shorter in length and had significantly less biomass than the previous cohort of sporophytes. In the intervening years 1996 and 1997, the sexual reproductive cycle was skipped altogether. The absence of sporophyte initiation in these two years was attributed to reduced winterspring rainfall. The majority of abortive sporophytes aborted in the late embryonic and seta elongation phenophases. The 1997 and 1998 summers were characterized by unusually heavy rains. Following the heavy summer rain events of 1997, sporophyte abortion in the 1995 cohort increased from 9 to 43%, and abortive sporophytes in this cohort further increased to 66% following the summer rains of 1998. Abortive sporophyte biomass averaged 49 µg or 33% of the mean biomass of the viable sporophytes in the cohort at maturity. These data suggest that the summer rain events precipitated two waves of sporophyte abortion, possibly through heavy membrane damage associated with rapid drying and high temperatures while hydrated.Key words: sporophyte abortion, bryophyte, desert, Tortula, desiccation.
8
Li, Zhaoxia, Jie Tang, Diane C. Bassham, and Stephen H. Howell. "Daily temperature cycles promote alternative splicing of RNAs encoding SR45a, a splicing regulator in maize." Plant Physiology 186, no. 2 (March 10, 2021): 1318–35. http://dx.doi.org/10.1093/plphys/kiab110.
Анотація:
Abstract Elevated temperatures enhance alternative RNA splicing in maize (Zea mays) with the potential to expand the repertoire of plant responses to heat stress. Alternative RNA splicing generates multiple RNA isoforms for many maize genes, and here we observed changes in the pattern of RNA isoforms with temperature changes. Increases in maximum daily temperature elevated the frequency of the major modes of alternative splices (AS), in particular retained introns and skipped exons. The genes most frequently targeted by increased AS with temperature encode factors involved in RNA processing and plant development. Genes encoding regulators of alternative RNA splicing were themselves among the principal AS targets in maize. Under controlled environmental conditions, daily changes in temperature comparable to field conditions altered the abundance of different RNA isoforms, including the RNAs encoding the splicing regulator SR45a, a member of the SR45 gene family. We established an “in protoplast” RNA splicing assay to show that during the afternoon on simulated hot summer days, SR45a RNA isoforms were produced with the potential to encode proteins efficient in splicing model substrates. With the RNA splicing assay, we also defined the exonic splicing enhancers that the splicing-efficient SR45a forms utilize to aid in the splicing of model substrates. Hence, with rising temperatures on hot summer days, SR45a RNA isoforms in maize are produced with the capability to encode proteins with greater RNA splicing potential.
9
Mobarak, Ahmed Mushfiq, and Maira Emy Reimão. "Seasonal Poverty and Seasonal Migration in Asia." Asian Development Review 37, no. 1 (March 2020): 1–42. http://dx.doi.org/10.1162/adev_a_00139.
Анотація:
Four in five poor people in the Asia and Pacific region live in rural areas. Crop cycles in agrarian areas create periods of seasonal deprivation, or preharvest “lean seasons,” when work is scarce and skipped meals become frequent. In this paper, we document this phenomenon of seasonal poverty and discuss existing formal mechanisms for coping with it. We then focus on seasonal migration from rural to urban areas as a potential coping strategy and review the evidence on the effects of encouraging seasonal migration through transport subsidies. Over the past 10 years, we have conducted a series of randomized control trials in Bangladesh and Indonesia that provided rural agricultural workers with small migration subsidies to pay for the cost of round-trip travel to nearby areas in search of work. This paper summarizes the lessons learned from this multicountry, multiyear series of seasonal migration trials, the implications of these results for spatial misallocation, urbanization, and growth, and the replicability and relevance of this and other policies encouraging domestic migration more broadly for other areas in the Asia and Pacific region.
10
Santini, D., B. Vincenzi, E. Vasile, V. Catalano, V. Virzì, G. Masi, S. Intagliata, G. Catalano, A. Falcone, and G. Tonini. "Fixed dose rate (FDR) gemcitabine (G) and capecitabine (C) in patients with metastatic biliary tract cancer (BTC): Final results of phase II trial." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): e15510-e15510. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.e15510.
Анотація:
e15510 Background: The combination of fixed dose rate (FDR) gemcitabine (C) and capecitabine (G) has been demonstrated to be well tolerated in patients with advanced cancers. To determine the activity and safety of this combination in metastatic metastatic biliary tract cancer patients, a phase II trial was conducted. Methods: Patients with unresectable BTC who had pathologically confirmed adenocarcinoma, no prior chemotherapy, ECOG PS < 2 and measurable disease were enrolled. Treatment consisted of FDR G at 800 mg/m(2) infused in 80 minutes on days 1 and 8 every 21 days with C administered orally bid in equal doses (650 mg/m2 bid) for 14 days (28 doses). Results: Between Feb 2005 and Sept 2008, 30 pts were enrolled. Median age was 67 (45–86) with 14 males. 30 pts were evaluable for response and toxicity. A total of 219 cycles were administered (median, 8; range, 2–16). One patient achieved CR and 8 pts achieved PR giving an overall response rate of 30.0% in intention-to-treat population (95% CI, 19.2–42.6%). And 11 pts (36.6%) had stable disease. The median time to progression of all patients was 7.4 months (mo) (95% CI, 3.2–19.5). The median overall survival was 15.3 mo (95% CI, 4.6–27.9). Grade 3/4 neutropenia and thrombocytopenia were noted in 13.3% and 6.6% of the pts, respectively. Grade 2/3 non-hematologic toxicities were asthenia (50.0 % of pts), diarrhea (16.6%), stomatitis (23.3%) and hand-foot syndrome (6.6%). There was no treatment-related death. Gemcitabine was skipped at least once/reduced in 20%/15% of the patients, respectively. Capecitabine was skipped at least once/reduced in 20%/25% of the patients, respectively. Conclusions: The combination of FDR gemcitabine and capecitabine in this three week cycle is safe and seems to have advantages in activity over other regimens in advanced biliary cancer. No significant financial relationships to disclose.
11
Sikov, William M., Donald A. Berry, Charles M. Perou, Baljit Singh, Constance T. Cirrincione, Sara M. Tolaney, Charles S. Kuzma, et al. "Impact of the Addition of Carboplatin and/or Bevacizumab to Neoadjuvant Once-per-Week Paclitaxel Followed by Dose-Dense Doxorubicin and Cyclophosphamide on Pathologic Complete Response Rates in Stage II to III Triple-Negative Breast Cancer: CALGB 40603 (Alliance)." Journal of Clinical Oncology 33, no. 1 (January 1, 2015): 13–21. http://dx.doi.org/10.1200/jco.2014.57.0572.
Анотація:
Purpose One third of patients with triple-negative breast cancer (TNBC) achieve pathologic complete response (pCR) with standard neoadjuvant chemotherapy (NACT). CALGB 40603 (Alliance), a 2 × 2 factorial, open-label, randomized phase II trial, evaluated the impact of adding carboplatin and/or bevacizumab. Patients and Methods Patients (N = 443) with stage II to III TNBC received paclitaxel 80 mg/m2 once per week (wP) for 12 weeks, followed by doxorubicin plus cyclophosphamide once every 2 weeks (ddAC) for four cycles, and were randomly assigned to concurrent carboplatin (area under curve 6) once every 3 weeks for four cycles and/or bevacizumab 10 mg/kg once every 2 weeks for nine cycles. Effects of adding these agents on pCR breast (ypT0/is), pCR breast/axilla (ypT0/isN0), treatment delivery, and toxicities were analyzed. Results Patients assigned to either carboplatin or bevacizumab were less likely to complete wP and ddAC without skipped doses, dose modification, or early discontinuation resulting from toxicity. Grade ≥ 3 neutropenia and thrombocytopenia were more common with carboplatin, as were hypertension, infection, thromboembolic events, bleeding, and postoperative complications with bevacizumab. Employing one-sided P values, addition of either carboplatin (60% v 44%; P = .0018) or bevacizumab (59% v 48%; P = .0089) significantly increased pCR breast, whereas only carboplatin (54% v 41%; P = .0029) significantly raised pCR breast/axilla. More-than-additive interactions between the two agents could not be demonstrated. Conclusion In stage II to III TNBC, addition of either carboplatin or bevacizumab to NACT increased pCR rates, but whether this will improve relapse-free or overall survival is unknown. Given results from recently reported adjuvant trials, further investigation of bevacizumab in this setting is unlikely, but the role of carboplatin could be evaluated in definitive studies, ideally limited to biologically defined patient subsets most likely to benefit from this agent.
12
Mirza, M. R., B. Lund, K. Bertelsen, J. Lindegaard, N. Keldsen, A. Mellemgaard, and R. Depont. "Pegylated liposomal doxorubicin (PLD) and gemcitabine (GEM) in combination in the salvage treatment of epithelial ovarian cancer (OC)—a Danish Gynaecologic Cancer Group (DGC) study." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 5094. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.5094.
Анотація:
5094 Background: Ovarian cancer patients (pts) recurring with a short treatment-free interval (TFI) after prior chemotherapy (PCT) have a bad prognosis. DGC has conducted a phase II study of PLD-GEM in combination in OC pts recurring with a TFI of less than 12 months (mo). Methods: All pts must have received at least one platinum-paclitaxel containing regimen; no PCT with GEM or anthracyclines. Regimen: GEM 800mg/m2 day 1+8 and PLD 25mg/m2 day 1, q 21 days. GEM dose escalation to 1g/m2 day 1+8 from 2. cycle in the absence of grade 3–4 toxicity. Primary end point: OS, secondary: PFS, response and toxicity. Pts were grouped according to their response to PCT. Group 1: pts with CR on PCT and TFI 3–12 mo; group 2: pts with CR on PCT and TFI 0–3 mo; group 3: pts with PR/SD on PCT and TFI 0–12 mo. 35 pts with ≥2 prior number of treatments. Results: 82 pts were enrolled (May 2003-Aug 2005); the median age was 59 yrs (range 31 to 77 yrs); 15 pts were entered with rising CA125 only (GCIG criteria). Groups according to their response to PCT: group 1: 44 pts; group 2: 5 pts; group 3: 33 pts. TFI ≤ 6 mo 33 pts, TFI > 6 to ≤ 12 mo 49 pts. To date data on 330 cycles (mean 4.7 cycles) is available; 45 pts are evaluable for PFS and OS; 62 pts are evaluable for response and 71 pts for toxicity. Grade 3–4 toxicity: PPE 6/330 cycles; mucosites 8/330 cycles; febrile neutropenia 4%; treatment delay 9%. No dose reductions performed for PLD. GEM dose escalation to 1000 mg/m2 in 31 pts; dose reduction to 650 mg/m2 at any time in 21 pts; skipped dose day 8 in 44 cycles. Response (RESIST): CR 3 pts; PR 17 pts (CR+PR 32%); SD 39 pts; PD 2 pts. Median PFS 212 days, Median OS 234 days. Conclusions: PLD-GEM in combination in the salvage setting is well tolerated, with acceptable toxicity and clear activity. No significant financial relationships to disclose.
13
Mirzaghaderi, Ghader, and Elvira Hörandl. "The evolution of meiotic sex and its alternatives." Proceedings of the Royal Society B: Biological Sciences 283, no. 1838 (September 14, 2016): 20161221. http://dx.doi.org/10.1098/rspb.2016.1221.
Анотація:
Meiosis is an ancestral, highly conserved process in eukaryotic life cycles, and for all eukaryotes the shared component of sexual reproduction. The benefits and functions of meiosis, however, are still under discussion, especially considering the costs of meiotic sex. To get a novel view on this old problem, we filter out the most conserved elements of meiosis itself by reviewing the various modifications and alterations of modes of reproduction. Our rationale is that the indispensable steps of meiosis for viability of offspring would be maintained by strong selection, while dispensable steps would be variable. We review evolutionary origin and processes in normal meiosis, restitutional meiosis, polyploidization and the alterations of meiosis in forms of uniparental reproduction (apomixis, apomictic parthenogenesis, automixis, selfing) with a focus on plants and animals. This overview suggests that homologue pairing, double-strand break formation and homologous recombinational repair at prophase I are the least dispensable elements, and they are more likely optimized for repair of oxidative DNA damage rather than for recombination. Segregation, ploidy reduction and also a biparental genome contribution can be skipped for many generations. The evidence supports the theory that the primary function of meiosis is DNA restoration rather than recombination.
14
Balduzzi, Francesco, Luca Romani, Lorenzo Bosi, and Giovanni Ferrara. "Intermittent Injection for a Two-Stroke Direct Injection Engine." SAE International Journal of Advances and Current Practices in Mobility 2, no. 2 (January 24, 2020): 1013–21. http://dx.doi.org/10.4271/2019-32-0524.
Анотація:
<div class="section abstract"><div class="htmlview paragraph">Cycle-to-cycle variation is one of the main factors for high fuel consumption and emissions of a two-stroke engine during the low-load and low-speed running. The increase of residual gas ratio due to the lower delivered amount of fresh scavenging air leads to a lower flame front speed and, therefore, to a slow combustion or even misfiring. The consequence is a very high level of unburnt hydrocarbons, since a large amount of fuel does not take part in the combustion process.</div><div class="htmlview paragraph">The use of a direct injection system allows a more flexible management of the injection of fuel over subsequent engine cycles. Under a low-load condition, the low request in terms of brake mean effective pressure (BMEP) can be achieved by performing a load control based on an intermittent injection, thus reducing the need for intake throttling and avoiding the loss of fresh fuel resulting from cycles without combustion. In more detail, the supply of fuel to the combustion chamber can be skipped for one or more cycles, thus performing a number of consecutive scavenging cycles with only fresh air. As a result, the fresh air is less diluted by the residual gas and the combustion efficiency increases.</div><div class="htmlview paragraph">This paper presents the results of a preliminary experimental activity on the use of an intermittent injection strategy with a Low Pressure Direct Injection (LPDI) system. In more detail, the effect of skipping one cycle - thus operating the two-stroke engine in a four-stroke-like mode - was investigated at part load conditions by considering four BMEP levels (i.e. from 1.0 bar to 2.5 bar). The benefits of such strategy were evaluated at the test bench and compared with the performance of the standard operation mode. In particular, the cycle-to-cycle variation was drastically reduced and the combustion misfire was avoided with the intermittent injection, thus leading to a strong reduction of both hydrocarbon emissions and brake specific fuel consumption.</div></div>
15
Dej, K. J., and A. C. Spradling. "The endocycle controls nurse cell polytene chromosome structure during Drosophila oogenesis." Development 126, no. 2 (January 15, 1999): 293–303. http://dx.doi.org/10.1242/dev.126.2.293.
Анотація:
Polytene chromosomes exhibit intricate higher order chromatin structure that is easily visualized due to their precisely aligned component strands. However, it remains unclear if the same factors determine chromatin organization in polyploid and diploid cells. We have analyzed one such factor, the cell cycle, by studying changes in Drosophila nurse cell chromosomes throughout the 10 to 12 endocycles of oogenesis. We find that nurse cells undergo three distinct types of endocycle whose parameters are correlated with chromosome behavior. The first four endocycles support complete DNA replication; poorly banded polytene euchromatin progressively condenses during the late S phases to produce blob-like chromosomes. During the unique fifth endocycle, an incomplete late S phase is followed by a mitosis-like state during which the 64C chromosomes dissociate into 32 chromatid pairs held together by unreplicated regions. All the subsequent endocycles lack any late S phase; during these cycles a new polytene chromosome grows from each 2C chromatid pair to generate 32-ploid polytene nuclei. These observations suggest that euchromatin begins to condense during late S phase and that nurse cell polytene chromosome structure is controlled by regulating whether events characteristic of late S and M phase are incorporated or skipped within a given endocycle.
16
Sukhinov, Alexander, Yulia Belova, Natalia Panasenko, and Valentina Sidoryakina. "Research of the Solutions Proximity of Linearized and Nonlinear Problems of the Biogeochemical Process Dynamics in Coastal Systems." Mathematics 11, no. 3 (January 21, 2023): 575. http://dx.doi.org/10.3390/math11030575.
Анотація:
The article considers a non-stationary three-dimensional spatial mathematical model of biological kinetics and geochemical processes with nonlinear coefficients and source functions. Often, the step of analytical study in models of this kind is skipped. The purpose of this work is to fill this gap, which will allow for the application of numerical modeling methods to a model of biogeochemical cycles and a computational experiment that adequately reflects reality. For this model, an initial-boundary value problem is posed and its linearization is carried out; for all the desired functions, their final spatial distributions for the previous time step are used. As a result, a chain of initial-boundary value problems is obtained, connected by initial–final data at each step of the time grid. To obtain inequalities that guarantee the convergence of solutions of a chain of linearized problems to the solution of the original nonlinear problems, the energy method, Gauss’s theorem, Green’s formula, and Poincaré’s inequality are used. The scientific novelty of this work lies in the proof of the convergence of solutions of a chain of linearized problems to the solution of the original nonlinear problems in the norm of the Hilbert space L2 as the time step τ tends to zero at the rate O(τ).
17
Le Gouill, Steven, Krimo Bouabdallah, Guillaume Cartron, Remy Gressin, Thierry Lamy, Bertrand Coiffier, Catherine Thieblemont, et al. "T3 : A Multicenter Phase IB Dose Escalation Study to Evaluate the Safety, Feasibility and Efficacy of the Temsirolimus (Torisel™)-CHOP-Rituximab (T-R-CHOP), Temsirolimus (Torisel™)-FC-Rituximab (T-R-FC) and Temsirolimus (Torisel™)- DHA-Rituximab (T-R-DHA) for the Treatment of Patients with Relapsed/Refractory Mantle Cell Lymphoma (MCL), a Lysa Study." Blood 124, no. 21 (December 6, 2014): 4426. http://dx.doi.org/10.1182/blood.v124.21.4426.4426.
Анотація:
Abstract The T3 trial is a multicenter Phase IB dose escalation study that evaluates the safety, feasibility and efficacy of three Temsirolimus-based chemotherapy regimens: Temsirolimus(Torisel™)-CHOP-Rituximab (T-R-CHOP), Temsirolimus(Torisel™)-FC-Rituximab (T-R-FC) and Temsirolimus(Torisel™)-Dexamethasone-aracytine-Rituximab (T-R-DHA) for the treatment of patients with relapsed/refractory Mantle Cell Lymphoma (MCL). The choice of the chemotherapy regimen was left to the decision of local investigator. The primary objective of the T3 was to assess the feasibility and incidence of dose limiting toxicities (DLT) during the two first cycles for each chemotherapy regimen in order to determine the maximal tolerate dose (MTD) in a 3+3 dose escalating design. Dose levels of Temsirolimus (administrated at D2, 8 and 15) were as followed: 25mg level 1; 50mg level 2 and 75mg level 3 and 15 mg in level -1. Patients were planned to receive at least 4 cycles. After 4 cycles, response was evaluated and then patients could continue treatment for 2 additional cycles or receive another treatment according to investigator’s decision. The T3 trial started in November 2011 and so far 38 patients have been enrolled (32 patients are evaluable to date; median age of 69y; range 56 -79). Before inclusion into the T3 trial, patients had received a median of 1 (range 1-3) line of treatment including autologous stem cell transplantation in 15 cases. Nine patients were included in the R-CHOP group (ORR after 4 cycles was 55,6%). In level 1, two patients out of 3 experimented DLT (grade 3: lymphopenia and GI hemorrhage). In level -1 (n=6), one DLT has been reported (grade 3 thrombocytopenia). In the T-R-FC group (n=12; ORR after 4 cycles was 41,7%), 6 patients were included in level 1 and 3 experimented DLT (grade 3: thrombocytopenia and leukopenia). In cohort -1 (n=6), 4 DLTs were reported. Eleven patients were included in the T-R-DHA group (ORR after 4 cycles was 80%). One DLT was suspected during toxicity review in level 1 (n=3) and was not confirmed as a DLT by the Safety Committee, hence the decision to pass to superior dose level. Then 6 patients (3+3) were included in level 2 (50mg) where 1 DLT was reported. However, only one patient received complete schema of temsirolimus with 3 injections because of hematology toxicity. Thus, it has been decided to add 3 additional patients at level 1 (25mg). These patients are currently under treatment. In conclusion, hematological toxicity grade 3 was the major concern of the three temsirolimus-based chemotheprapy regimen. Administration of Temsirolimus at D15 was frequently skipped. However, 51,6% of patients reached at least a PR after 4 cycles and the T-R-DHA group was the safest, in which, 50% of patients reached CR after 4 cycles. Thus, Temsirolimus plus high dose aracytine based-chemotherapy regimens provides good disease control with an acceptable tolerability profile for patients with relapsed MCL. Disclosures Le Gouill: pfizer: Honoraria; mundipharma: Honoraria; roche: Honoraria; celgene: Consultancy, Honoraria; janssen-cilag: Honoraria. Coiffier:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees.
18
Kamaraju, Sailaja, Saranya Chumsri, Blaise Bayer, Mingjin Chang, William Williams, Charles L. Wiseman, and Giuseppe Del Priore. "Differential efficacy of SV-BR-1-GM in inducing intracranial metastasis regression." Journal of Clinical Oncology 42, no. 16_suppl (June 1, 2024): e13119-e13119. http://dx.doi.org/10.1200/jco.2024.42.16_suppl.e13119.
Анотація:
e13119 Background: Breast cancer metastasis to the central nervous system (CNS) and intracranial area often leads to severe morbidity and mortality. While systemic treatments manage systemic tumors, their impact on CNS/intracranial metastases is limited. Cell based therapies like SV-BR-1-GM may overcome this limitation. SV-BR-1-GM is a GM-CSF secreting, antigen-presenting immortalized breast cancer cell line. We report its efficacy on CNS tumor regression. Methods: Post-hoc analysis of a subset of all advanced MBC patients with CNS/intracranial metastases from previous phase 1, 2, and an ongoing randomized phase 2, trials (n=7 subjects) of SV-BR-1-GM. Bria-IMT monotherapy (intradermal SV-BR-1-GM + cyclophosphamide 300 mg/m2, +interferon-alpha) was administered q3wks to 2 subjects; an immune checkpoint inhibitor (ICI) was administered with each cycle in the combination setting (n=5). Results: There were 7 patients with intracranial metastases at baseline of whom 5 had intracranial tumor responses. Of the 5 responders, median pt age = 66 (range 58-70), median prior lines = 5.5 (3-13), and median time from initial diagnosis = 7.5 years (3-10). 4/5 pts had ≥1 HLA class match with SV-BR-1-GM. 3 were HR + and 1 HER2 +. Pt A002 (ER+/PR+, HER2-) received 6/6 planned cycles, achieving an 83% reduction in breast lesions; after 3 months off therapy, imaging revealed multiple brain metastases and recurrence of right breast lesions. Following 3 additional cycles there was marked regression in both brain and breast lesions. Pt 02-003 (ER-/PR-, HER2 1+ (IHC)) received 5 cycles of SV-BR-1-GM and observed a 60% reduction (5mm -> 2mm) in a left parietal periventricular lesion, and complete resolution (CR) of a left parietal lobe. Pt 06-005 (ER+/PR-, HER2 1+) demonstrated a 56% (9mm -> 4mm) reduction in the thickness of a dural lesion overlying the left anterior temporal lobe after 6 cycles of SV-BR-1-GM + ICI. After 2 additional cycles of SV-BR-1-GM + ICI and 1 cycle of SV-BR-1-GM (ICI skipped on final cycle due to grade 2 AE), patient achieved CR of a left orbital mass observed at baseline (24mm -> 0m). Pt06-007’s (ER-/PR-, HER2 1+) CNS lesions showed a median reduction of 49% compared to baseline after 3 cycles. Pt 11-018 (ER+/PR-, HER2 +) showed standard progression (SD) at initial restaging; 14% increase in sum of diameters of intracranial metastasis. Subsequent imaging, after 3 cycles, showed significant orbital tumor reduction along with reported improvement in eye pain. Conclusions: This post-hoc analysis demonstrated promising efficacy of the Bria-IMT regimen either alone or in combination with ICIs in CNS/intracranial metastasis. The CNS/intracranial regression seen across all breast cancer subtypes among heavily pretreated patients highlights the potential of SV-BR-1-GM in managing CNS metastasis. Ongoing trials will further evaluate the efficacy of the Bria-IMT regimen in patients with CNS/intracranial metastasis. Clinical trial information: NCT03328026 .
19
Saxena, Shreya, Sridevi V. Sarma, and Munther Dahleh. "Performance Limitations in Sensorimotor Control: Trade-Offs Between Neural Computation and Accuracy in Tracking Fast Movements." Neural Computation 32, no. 5 (May 2020): 865–86. http://dx.doi.org/10.1162/neco_a_01272.
Анотація:
The ability to move fast and accurately track moving objects is fundamentally constrained by the biophysics of neurons and dynamics of the muscles involved. Yet the corresponding trade-offs between these factors and tracking motor commands have not been rigorously quantified. We use feedback control principles to quantify performance limitations of the sensorimotor control system (SCS) to track fast periodic movements. We show that (1) linear models of the SCS fail to predict known undesirable phenomena, including skipped cycles, overshoot and undershoot, produced when tracking signals in the “fast regime,” while nonlinear pulsatile control models can predict such undesirable phenomena, and (2) tools from nonlinear control theory allow us to characterize fundamental limitations in this fast regime. Using a validated and tractable nonlinear model of the SCS, we derive an analytical upper bound on frequencies that the SCS model can reliably track before producing such undesirable phenomena as a function of the neurons' biophysical constraints and muscle dynamics. The performance limitations derived here have important implications in sensorimotor control. For example, if the primary motor cortex is compromised due to disease or damage, the theory suggests ways to manipulate muscle dynamics by adding the necessary compensatory forces using an assistive neuroprosthetic device to restore motor performance and, more important, fast and agile movements. Just how one should compensate can be informed by our SCS model and the theory developed here.
20
Hess, D., S. Boehm, A. Delmonte, E. Gallerani, P. Barbieri, S. Pace, P. Carminati, S. Marsoni, N. Coceani, and C. Sessa. "Clinical development of namitecan (ST1968), a novel camptothecin derivative with high antitumor activity: Phase I clinical data." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): 2570. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.2570.
Анотація:
2570 Background: Namitecan is a new water-soluble camptothecin analogue which showed high antitumor activity in preclinical models. Aim of this trial was to determine safety, PK profile and activity in adult patients with advanced solid tumors. Methods: The dose escalation started at 2.5 mg i.v. on days 1 and 8 of a 21 day cycle (D1, D8 Q21D) and increased according to 3+3 cohort design depending on the observed toxicity. Dose limiting toxicity (DLT) definitions were: ANC <0.5x109/L for >5 days; PLT ≥ Grade 3 (CTC V3); grade ≥2 liver/renal toxicity not recovered by D22; any non-hematologic toxicity ≥ Grade 3; D8 dose skipping due to toxicity. Maximum tolerated dose (MTD) and recommended dose (RD) were the primary end-points. Blood and urine samples were collected at cycle 1 for PK evaluation. Results: 31 pts (11 endometrial ca., 5 CRC, 5 ovarian ca., 2 NSCLC, 8 other) have been included, with 6 dose levels evaluated (2.5; 5; 10; 15; 17.5 and 20 mg). 17.5 mg was introduced later when 2/7 DLTs at 20 mg were observed (ANC G4>5days, one with D8 skipping). At 17.5mg 2/4 pts experienced DLTs (ANC G4; D8 skipped). Uncomplicated neutropenia and thrombocytopenia were the most relevant G3/4 hematological toxicities. Other toxicities were mild or moderate asthenia, fatigue and alopecia. The MTD was defined at 17.5 mg and the RD was 15 mg. Stable disease ≥ 6 cycles was recorded in 6 pts (2 stable diseases ≥ 10 cycles). PK was linear and data suggest an entero-hepatic recirculation. No metabolites were found in plasma and the product resulted poorly excreted into urine. Conclusions: The MTD and RD of D1, D8 Q21D schedule have been identified. The study will continue with the evaluation of MTD and RD of a single administration per cycle (D1 Q21D), to optimize the schedule of treatment. [Table: see text]
21
Kamaraju, Sailaja, Blaise Bayer, Mingjin Chang, William Williams, Charles Wiseman, and Giuseppe Del Priore. "Abstract CT204: Efficacy of Bria-IMT regimen in inducing CNS metastasis regression." Cancer Research 84, no. 7_Supplement (April 5, 2024): CT204. http://dx.doi.org/10.1158/1538-7445.am2024-ct204.
Анотація:
Abstract Objectives: Breast cancer metastasis to the central nervous system (CNS) often leads to severe morbidity and mortality, and while systemic treatments manage primary tumors, their impact on CNS metastases is limited. This retrospective analysis evaluates the efficacy of Bria-IMT as a monotherapy or in combination with an immune checkpoint inhibitor (ICI) on CNS tumor regression. Methods: Post-hoc analysis of a subset of advanced MBC patients with CNS metastases from previous phase 1 and 2, and ongoing randomized phase 2 trials involving SV-BR-1-GM. SV-BR-1-GM is a GM-CSF secreting, antigen-presenting immortalized breast cancer cell line. Bria-IMT (SV-BR-1-GM ~20x106 cells, intradermally 48-72 hours after cyclophosphamide 300 mg/m2, followed by interferon-alpha at the inoculation sites 2 days later) was administered q3wks. In the combination setting, an ICI was administered with each cycle. Patients A002 and 02-003 received Bria-IMT as monotherapy. Patients 06-005 and 06-007 received Bria-IMT in combination with an ICI. Results: Median pt age of 65 (range 58-70). All pts had ≥1 HLA match with SV-BR-1-GM. Significant CNS tumor regression was observed in all pts. Pt A002 (ER+/PR+, HER2-) received 6 cycles, achieving an 83% reduction in breast lesions. ~3 months after the last cycle, imaging revealed the onset of multiple brain metastases and recurrence of right breast lesions. Following 3 additional cycles, marked measurable regression in both brain metastases and breast lesions was noted. Pt 02-003 (ER-/PR-, HER2 1+ (IHC)) received 5 cycles and observed a 60% reduction (5mm ->2mm) in a left parietal periventricular lesion, and complete resolution (CR) of a left parietal lobe lesion. Pt 06-005 (ER+/PR-, HER2 1+(IHC)) demonstrated a 56% (9mm -> 4mm) reduction in the thickness of a dural lesion overlying the left anterior temporal lobe after 6 cycles of SV-BR-1-GM + ICI (pembrolizumab). After 2 additional cycles of SV-BR-1-GM + ICI (retifanlimab) and 1 cycle of SV-BR-1-GM (ICI was skipped on final cycle due to grade 2 AE), patient achieved CR of a left orbital mass observed at baseline (24mm -> 0m). Circulating cancer-associated macrophage-like cells (CAMLs) varied throughout the treatment, with levels ranged from a baseline of 90 to 24 by Cycle 13. Pt 06-007 (ER-/PR-, HER2 1+ (IHC)) demonstrated significant reductions in CNS lesions after 3 cycles of SV-BR-1-GM + ICI (pembrolizumab): a 67% reduction in a right frontal lobe lesion, 29% in the right parietal, 30% in the right thalamus, and 67% in the right precentral gyrus lesions. CAML levels remained low throughout treatment. Conclusions: This review consolidates evidence for the efficacy of the Bria-IMT regimen in CNS metastasis regression, both alone and with ICIs. The consistent regression seen across all breast cancer subtypes among heavily pretreated patients highlights the potential of SV-BR-1-GM in managing CNS metastasis. Ongoing trials will determine the full extent. Citation Format: Sailaja Kamaraju, Blaise Bayer, Mingjin Chang, William Williams, Charles Wiseman, Giuseppe Del Priore. Efficacy of Bria-IMT regimen in inducing CNS metastasis regression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT204.
22
Lindberg, Kurt R., William C. Daniels, Isla S. Castañeda, and Julie Brigham-Grette. "Biomarker proxy records of Arctic climate change during the Mid-Pleistocene transition from Lake El'gygytgyn (Far East Russia)." Climate of the Past 18, no. 3 (March 30, 2022): 559–77. http://dx.doi.org/10.5194/cp-18-559-2022.
Анотація:
Abstract. The Mid-Pleistocene Transition (MPT) is a widely recognized global climate shift occurring between approximately 1250 and 700 ka. At this time, Earth's climate underwent a major transition from dominant 40 kyr glacial–interglacial cycles to quasi-100 kyr cycles. The cause of the MPT remains a puzzling aspect of Pleistocene climate. Presently, there are few, if any, continuous MPT records from the Arctic, yet understanding the role and response of the high latitudes to the MPT is required to better evaluate the causes of this climatic shift. Here, we present new continental biomarker records of temperature and vegetation spanning 1142 to 752 ka from Lake El'gygytgyn (Far East Russia). We reconstruct warm-season temperature variations across the MPT based on branched glycerol dialkyl glycerol tetraethers (brGDGTs). The new Arctic temperature record does not display an overall cooling trend during the MPT but does exhibit strong glacial–interglacial cyclicity. Spectral analysis demonstrates persistent obliquity and precession pacing over the study interval and reveals substantial sub-orbital temperature variations at ∼900 ka during the first “skipped” interglacial. Interestingly, Marine Isotope Stage (MIS) 31, which is widely recognized as a particularly warm interglacial, does not exhibit exceptional warmth in the Lake El'gygytgyn brGDGT record. Instead, we find that MIS 29, 27, and 21 were as warm or warmer than MIS 31. In particular, MIS 21 (∼870 to 820 ka) stands out as an especially warm and long interglacial in the continental Arctic while MIS 25 is a notably cold interglacial. Throughout the MPT, Lake El'gygytgyn pollen data exhibit a long-term drying trend, with a shift to an increasingly open landscape noted after around 900 ka (Zhao et al., 2018), which is also reflected in our higher plant leaf wax (n-alkane) distributions. Although the mechanisms driving the MPT remain a matter of debate, our new climate records from the continental Arctic exhibit some similarities to changes noted around the North Pacific region. Overall, the new organic geochemical data from Lake El'gygytgyn contribute to expanding our knowledge of the high-latitude response to the MPT.
23
Calatayud, N. E., D. M. Shier, R. R. Swaisgood, and B. S. Durrant. "119 HORMONE-ASSISTED REPRODUCTION IN A CAPTIVE MOUNTAIN YELLOW-LEGGED FROG POPULATION." Reproduction, Fertility and Development 28, no. 2 (2016): 189. http://dx.doi.org/10.1071/rdv28n2ab119.
Анотація:
Severe declines of the mountain yellow-legged frog (MYLF, Rana muscosa) led to establishment of a captive population at the San Diego Zoo Institute for Conservation Research. With less than 200 adults estimated to remain in the wild, the Institute’s MYLF colony currently holds approximately 30% of the entire gene pool. Simulating natural seasonality by artificial brumation and manipulation of atmospheric temperature and light cycles is an integral part of this species’ management in captivity. However, over 5 years, the number of females that have oviposited has decreased from 80% in 2011 to 28% in 2014. It is unclear if changes in reproduction are related to husbandry or a lack of information regarding the natural reproductive cycles of these animals. Therefore, we examined the effects of hormone treatments on reproduction in the MYLF captive population. Prior to breeding, 21 females and 18 males were evenly assigned to either a control group (IP injection of PBS) or hormone-treated group [IP injection of gonadotropic releasing hormone (GnRH, D-Ala6, des-GLy10 ethylamide LHRH derivative) at 0.4 µg g–1 of body weight and metoclopramide (dopamine inhibitor) at 10 µg g–1 of body weight]. Males and females were housed in groups of 3 males and 3 females and allowed to choose their mate. Once a male had amplexed a female they were housed in pairs until oviposition occurred or until males ceased amplexus. Responses recorded during this study included amplexus, spermiation, oviposition, and embryonic cleavage. There was no significant difference in the number of eggs deposited by females treated with hormones and untreated controls (P = 0.1949) nor were there any differences between groups in the number of embryos that cleaved (P = 0.673) or survived to tadpole stage (P = 0.629). No significant differences were detected between the numbers of males that amplexed in the control or treated groups (P = 0.1120). Urine collected from 10/18 amplexed males (7 hormone-treated and 3 controls) indicated that 57% percent of hormone-treated males and 67% of control males were spermiating at the time of collection. Therefore, hormone treatments did not increase the number of eggs oviposited or the number of males spermiating or amplexing. Closer analysis of individual female reproductive histories indicated that 48% of captive female MYLF oviposited just once in 5 years, 40% in 2 consecutive years, 8% oviposited eggs in 2 consecutive years, skipped a year, and then oviposited again in 2 consecutive years, and 4% oviposited in 3 consecutive years. The number of females ovipositing in 2015 was significantly higher than 2012 (P = 0.0002), 2013 (P = 0.0001), and 2014 (P = 0.0026), but not 2011 (P = 0.0885), suggesting breeding may not occur annually in females. Understanding the breeding cycles of MYLF females will enable managers to determine if and when hormone administration is efficacious in captive amphibian breeding populations.
24
Long, Rong, Xiaohui Fan, Kai Wei, Junxuan Bai, and Shanpeng Xiao. "Internet-of-Things object model." Digital Twin 2 (April 12, 2022): 5. http://dx.doi.org/10.12688/digitaltwin.17562.1.
Анотація:
Background: With the advancement of communication technology and advanced sensors, there are massive demands for Internet-of-Things (IoT) applications in buildings, communities, factories, parks, etc. Accessing IoT devices provides convenience for scene management and monitoring, ameliorating production and life intelligently. However, due to the lack of a unified model for IoT devices, data is often skipped over IoT platforms and transmitted to applications directly. This leads to the fact that each manufacturer needs to produce its devices and develop its customized software, which hugely increases the development cycle. On the other hand, it is difficult to convey information between different systems, limiting cross- system control. Moreover, digital twin relies on large amounts of heterogeneous data, and it is impracticable to provide enough data without a unified model for device description. Methods: First, we illustrate the motivation, design goals, and design principles for creating the Internet-of-Things Object Model (IoT-OM). Then we propose a unified description to define IoT devices. The proposed concept has been accepted by several companies, and we analyse one platform that adopts the model. To demonstrate the effectiveness of the model, we introduce two projects based on the platform. One project is an intelligent fire protection system, and another project is an intelligent air quality monitoring system. Results: We measured the time taken by five companies when developing IoT devices and their applications, including the development cycle duration without utilizing the proposed model and the duration using the model at China Mobile’s OneNET platform. The results prove that the proposed model can significantly shorten the development cycle. Conclusions: This paper proposes a model for IoT devices, which helps to unify heterogeneous data among different manufacturers and helps to shorten the development cycles for developers.
25
Lacombe, D. A., F. Caponigro, A. Anthoney, J. Bauer, A. Govaerts, A. Milano, S. Marréaud, and C. Twelves. "A phase I study of bortezomib in combination with 5FU/LV plus oxaliplatin in patients (pts) with advanced colorectal cancer (CRC): EORTC 16029." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 4090. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.4090.
Анотація:
4090 Background: Bortezomib is a potent and reversible inhibitor of the ubiquitin-mediated proteasome pathway, whose inhibition results in the stabilization of p53, p21Cip1, p27Kip1, Bax, in cell-cycle dysregulation and, finally, apoptosis. A phase I study of the combination of 5FU/LV and bortezomib has shown a significant stable disease rate in advanced CRC (Iqbal, ASCO 2004). Methods: In this phase I study bortezomib was given as an IV push over 3 to 5 seconds on days 1, 8 and 15 in combination with standard FOLFOX-4 every 28 days in chemo-naïve pts with advanced CRC. Bortezomib starting dose level was 1.3 mg/m2. A 3+3 study design was utilized at predefined dose levels (DL). Dose-limiting-toxicity (DLT) was assessed during cycle 1. Exploratory pharmacogenetics research was conducted. Results: 15 pts were treated and 46 cycles given. At DL2 (1.6 mg/m2), 2/4 pts experienced a DLT: G3 febrile neutropenia causing treatment delay and bortezomib dose reduction in 1pt and one bortezomib dose skipped due to persistent G2 peripheral neuropathy and myalgia in 1pt. At DL1 (1.3 mg/m2), 2/6 pts had a DLT. Both pts experienced a G3 neutropenia on day 15, which prevented treatment from being given as scheduled. DL-1 (1 mg/m2) was therefore investigated and no DLT was observed among 5 pts. The most frequently reported toxicities in cycle 1 were γGT (64%), nausea, fatigue and sensory neuropathy (53%), pain (33%), diarrhea and fever (27%), vomiting (20%), anorexia, dyspnea and mucositis (13%) and neutropenia 29% (G2,3). 12 pts are currently evaluable for response; 6 had a partial response, 3 stable disease and 3 disease progression. Conclusion: The toxicity profile of this combination is predictable and early evidence of clinical activity has been observed. The recommended bortezomib dose for further investigation within this regimen is 1 mg/m2. No significant financial relationships to disclose.
26
Lu, Jiaying, Yuanjie Chen, Zihan Wang, Feng Zhao, Yisen Zhong, Cong Zeng, and Ling Cao. "Larval Dispersal Modeling Reveals Low Connectivity among National Marine Protected Areas in the Yellow and East China Seas." Biology 12, no. 3 (March 2, 2023): 396. http://dx.doi.org/10.3390/biology12030396.
Анотація:
Marine protected areas (MPAs) are vital for protecting biodiversity, maintaining ecosystem integrity, and tackling future climate change. The effectiveness of MPA networks relies on connectivity, yet connectivity assessments are often skipped in the planning process. Here we employed a multi-species biophysical model to examine the connectivity patterns formed among the 21 national MPAs in the Yellow and East China Seas. We simulated the potential larval dispersal of 14 oviparous species of five classes. Larvae of non-migratory species with pelagic larval duration (PLD) were assumed to be passive floating particles with no explicit vertical migration. A total of 217,000 particles were released according to spawning period, living depth, and species distribution, and they were assumed to move with currents during the PLD. Most larvae were dispersed around the MPAs (0–60 m isobaths) and consistent with the currents. Larval export increased with PLD and current velocity, but if PLD was too long, few larvae survived due to high daily mortality during pelagic dispersal. The overall connectivity pattern exhibited a north-to-south dispersal trend corresponding to coastal currents. Our results indicated that the national MPAs in the Yellow and East China Seas did not form a well-connected network and nearly 30% of them were isolated. These MPAs formed three distinct groups, one in the Yellow Sea ecoregion and two in the East China Sea ecoregion. Four MPAs (all in coastal Zhejiang) emerged as key nodes for ensuring multi-generational connectivity. Under the pressure of future climate change, high self-recruitment and low connectivity present significant challenges for building well-connected MPA networks. We suggest adding new protected areas as stepping stones for bioecological corridors. Focused protection of the Yellow Sea ecoregion could have a good effect on the southern part of the population recruitment downstream. Conservation management should be adjusted according to the life cycles and distributions of vulnerable species, as well as seasonal changes in coastal currents. This study provides a scientific basis for improving ecological connectivity and conservation effectiveness of MPAs in the Yellow and East China Seas.
27
Gorelik, Gennady Bencianovich, Anatoly Nikolaevich Sobolenko, and Sergey Vital'evich Pastukhov. "Prospects for the diesel fuel equipment development in the near future." Vestnik of Astrakhan State Technical University. Series: Marine engineering and technologies 2024, no. 1 (February 29, 2024): 58–63. http://dx.doi.org/10.24143/2073-1574-2024-1-58-63.
Анотація:
The analysis of the positive qualities of Common Rail (CR) fuel equipment widely used in diesels today is given. The possibility of optimal diesel control, high injection pressure, elimination of repeated fuel injections, improvement of fuel efficiency, reduction of the difference in the amplitude of torque fluctuations in the cylinders, very precise regulation of the beginning of fuel supply, a high degree of diagnosability of fuel equipment, the possibility of precise regulation of the uniformity of fuel supply through the cylinders, the ability to ensure optimal regulation of the turbocharger are noted, the ability to turn off a number of cylinders and ensure that cycles are skipped when operating under partial loading conditions. Disadvantages are also presented, in particular, a large number of various elements and sensors, activators and other controls are included in the injection system, as well as the increased demands of CR-type fuel equipment on the purity and quality of diesel fuel. When operating in low-flow modes, the injection pressure is significantly reduced to a value of 60-80 MPa, which leads to fuel overspending, the cost of fuel equipment is about twice as much as classical fuel equipment, the starting properties of diesel (as evidenced by operation) decrease sharply after 500-800 hours of operation, problems arise with maintaining high pressure in the ramp (battery), possible ruptures and leakages of the high-pressure system lead to increased fire hazard of the engine. The reasons for increased carbon formation and loss of operational efficiency and reliability are listed. Using the methods of relative penalty points, the quality of traditional fuel equipment and CR-type equipment was compared. Based on the analysis, a conclusion is made about the scope of application of this new system and traditional classical fuel equipment in the near future. The operating conditions, the qualifications of the maintenance personnel, modern requirements of standards for noise, toxicity of diesel engines and their reliability indicators were taken into account.
28
Weigmann, K., and C. F. Lehner. "Cell fate specification by even-skipped expression in the Drosophila nervous system is coupled to cell cycle progression." Development 121, no. 11 (November 1, 1995): 3713–21. http://dx.doi.org/10.1242/dev.121.11.3713.
Анотація:
The correct specification of defined neurons in the Drosophila central nervous system is dependent on even-skipped. During CNS development, even-skipped expression starts in the ganglion mother cell resulting from the first asymmetric division of neuroblast NB 1–1. This first division of NB 1–1 (and of the other early neuroblasts as well) is temporally controlled by the transcriptional regulation of string expression, which we have manipulated experimentally, even-skipped expression still occurs if the first neuroblast division is delayed, but not if the division is prohibited. Moreover, even-skipped expression is also dependent on progression through S phase which follows immediately after the first division. However, cytokinesis during the first NB division is not required for even-skipped expression as revealed by observations in pebble mutant embryos. Our results demonstrate therefore that even-skipped expression is coupled to cell cycle progression, presumably in order to prevent a premature activation of expression by a positive regulator which is produced already in the neuroblast during G2 and segregated asymmetrically into the ganglion mother cell during mitosis.
29
Cui, Jiujie, Haiyan Yang, Jiong Hu, Jiayu Yao, Yu Wang, Yiyi Liang, Yongchao Wang, et al. "Anti-PD-1 antibody combined with albumin-bound paclitaxel and gemcitabine (AG) as first-line therapy and Anti-PD-1 monotherapy as maintenance in metastatic pancreatic ductal adenocarcinoma (PDAC)." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): e16218-e16218. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e16218.
Анотація:
e16218 Background: Two studies in ASCO 2018 showed the preliminary efficacy of PD-1 inhibitor and AG as first-line therapy for advanced pancreatic cancer, the disease control rate (DCR) was up to 100%. However, in a phase 1 study of nivolumab plus nab-paclitaxel and gemcitabine in advanced PDAC, the objective response rate (ORR) was only 18%, and the progression-free survival (PFS)/overall survival (OS) were 5.5/9.9 months, which was quite different from what had been reported before in ASCO. All the patients received continuous chemotherapy, and the tolerance was poor. Recently, maintenance therapy on pancreatic cancer was widely investigated in clinical trials. The present study explored the camrelizumab (anti-PD-1 antibody) combined with AG as the first-line treatment, and camrelizumab as maintenance therapy for metastatic PDAC (mPDAC) among Chinese patients. Methods: In this single-arm, single-center, exploratory study, patients who were pathologically or cytologically diagnosed as mPDAC and had not received systemic treatment before, with an ECOG performance status of 0-1 would receive: albumin-bound paclitaxel 125 mg/m2 plus gemcitabine 1000 mg/m2 (days 1, 8), and camrelizumab, 200mg (day 1) for a 21-day cycle. After six cycles, if there was no evidence of disease progression, camrelizumab (200mg, every 21 days) monotherapy as maintenance therapy would be given. Primary endpoint was ORR assessed according to RECIST 1.1. The secondary endpoint was DCR, PFS, OS, etc. Safety was also assessed. Results: From July 3, 2019 to July 1, 2020, twenty patients were enrolled and received the study treatment. The median age was 63 years (range 33-78). Sixteen participants (80%) were male. Eleven patients (55%) received six cycles of camrelizumab combined with AG and subsequential maintenance therapy. Nineteen patients received at least one imaging evaluation, one patient (5%) achieved complete response, eleven (55%) patients achieved partial response, five (25%) patients were assessed as stable disease, and progressive disease was observed in two patients (10%) who died within 2 months. The ORR (primary endpoint) and DCR were 60% and 85%, respectively. The data of PFS and OS were immature. The most common AEs (all grade, grade≥3) were erythropenia (55%, 0%), leukopenia (45%, 10%), neutropenia (40%, 15%), anemia (30%, 5%), thrombocytopenia (30%, 5%). One patient received day 1 camrelizumab plus AG, and the day 8 therapy was skipped due to thrombocytopenia. During the second cycle, he presented with jaundice due to disease progression and died rapidly. Conclusions: The ORR and DCR of chemotherapy-naive mPDAC patients receiving camrelizumab plus AG were high. Safety findings were consistent with previous data observed from camrelizumab or AG treatment; with no unexpected safety signals. Clinical trial information: NCT04181645.
30
Zilioli, Vittorio Ruggero, Periana Minga, Lara Crucitti, Erika Meli, Monica Luigia Torretta, Anna Esposito, Chiara Rusconi, and Roberto Cairoli. "NEPA (netupitant + palonosetron) Administration Is Safe and Effective in cHL Patients Receiving ABVD Regimen: A Single-Center Real Life Experience." Blood 132, Supplement 1 (November 29, 2018): 5374. http://dx.doi.org/10.1182/blood-2018-99-116543.
Анотація:
Abstract BACKGROUND In the setting of cHL, ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) is the most widely used first line chemotherapeutic treatment and it is well known that this regimen is associated with a high emetic risk (HEC). Palonosetron (PALO) currently represents one of the most effective and implemented drug for CINV prevention, but after many ABVD cycles patients (pts) frequently need to add other antiemetic drugs to obtain a good control of their symptoms. Netupitant (NETU) is the NK1-RA (neurokinin receptor antagonist) component of NEPA, the first antiemetic drug available as oral fixed combination: NETU (300mg) + PALO (0.5mg). Both ABVD drugs and NETU are metabolized by cytochrome P-450 isoform 3A4 (CYP3A4), but respect to other NK1-receptor antagonist available, NETU has demonstrated to have no clinical relevant interaction with chemotherapy drugs like etoposide, cyclophosphamide and docetaxel. However, no data are currently available about the safety profile of NETU in the setting of ABVD treatment; for that reason we started the use of this drug as salvage therapy after PALO failure. METHODS We retrospectively analyzed the cHL pts treated with ABVD at our Center from September 2016 to January 2018. We used PALO + dexamethasone as first-line anti-CINV prophylaxis, while NEPA was introduced as salvage drug for those pts with inadequately controlled CINV. We collected data regarding demographics; diagnosis; planned chemotherapeutic treatment; performed chemotherapeutic treatment; acute, delayed and anticipatory CINV (before and after NEPA); laboratory findings including transaminases, creatinine and electrolytes (before and after NEPA); adverse reactions (before and after NEPA). The primary endpoint of the study was safety of NEPA in ABVD treated pts, while CINV control (no nausea or vomiting) was the secondary endpoint. NEPA-related safety data have been compared to the same data collected at the moment of the last previous PALO-containing regimen. RESULTS Among the 32 pts treated with ABVD during the study period, 13 (41%) received NEPA. Three pts were males and 10 females, and median age was 33 years (range 18-61). According to disease characteristics at diagnosis the planned ABVD administrations were 12 (6 cycles) in 9 pts, 8 (4 cycles) in 3 pts and 4 (2 cycles) in 1 pt. Nine pts completed the planned chemotherapy, 1 pt skipped the last cycle for personal decision, 3 pts are ongoing treatment at the time of analysis. Reasons for shift to NEPA are as follows: acute (grade 2) CINV alone in 3/13 pts; late (grade 2) CINV alone in 3/13 pts; combined acute (4 grade 2, 1 grade 1) and late (4 grade 2, 1 grade 1) CINV in 5/13 pts; combined anticipatory (grade 1), acute (grade 1) and late (grade 2) CINV in 2/13 pts. NEPA was started after a median of 4 ABVD administrations (range 1-10). Globally 53 NEPA administrations were delivered during subsequent cycles (median number of 3 NEPA administrations for each pt, range 1-11). With regard to the primary endpoint, the observed adverse events are listed in Table 1. With regard to the secondary endpoint, anticipatory, acute and delayed CINV were detected in 15%, 77%, 77%, of PALO pts and 15%, 46% and 15% of NEPA pts, respectively (see Table 2) CONCLUSION In our experience NETU did not show drug-drug interaction with ABVD chemotherapy agents, and NEPA administration was globally well tolerated with mild and transient adverse events. Furthermore, in cHL ABVD treated pts who experienced nausea and/or vomiting after failure of PALO + dexamethasone antiemetic prophylaxis, NEPA has demonstrated to be effective in CINV control. In 4 out of 13 cases, after an initial improvement in CINV control, pts subsequently required to shift to anti-CINV third line treatments. On the other hand, the 9 pts who continued on NEPA administration could experience an optimal CINV control immediately after the first administration. At our knowledge no data have been published regarding NEPA toxicities in the ABVD setting. Our safety and efficacy data come from a real life experience of consecutive pts treated homogeneously at a single center and would suggest the use of NEPA as primary anti-CINV prophylaxis in previously untreated cHL pts. Disclosures Rusconi: Celgene: Research Funding.
31
Sailo, Lalrintlingi, Apurba Sarkar, and Suresh Babu. "A STUDY ON STATUS OF URINARY HYDROXYPROLINE IN POST MENOPAUSAL WOMEN." International Journal of Advanced Research 9, no. 03 (March 31, 2021): 136–46. http://dx.doi.org/10.21474/ijar01/12566.
Анотація:
Introduction: WHO and the Stages of Reproductive Aging Workshop have defined menopausal transition as the time of an increase in follicle-stimulating hormone and either increased variability in menstrual cycle length, two skipped menstrual cycles with 60 days or more of amenorrhea, or both. It concludes with the final menstrual period. Post-menopause begins at that time, although it is not recognized until after 12 months of amenorrhea. During menopause, women face various physiological, psychological, and biochemical changes. Laboratory medicine has given a new background to overcome the clinicianÂÂs diagnostic dilemma. Hydroxyproline is mainly found in collagen and accounts for 13% of total amino acid content and derived from proline by post-translational hydroxylation. Hydroxyproline is derived from another amino acid such as proline. Direct urinary assay of hydroxyproline to measure bone resorption have clinical applications as part of screening programs to assess the risk of osteoporotic fractures. Method: A total of seventy patients with regular medical follow-up records, The Patients were pre and post-menopausal women (35 each) recruited for this study. Patient details like body mass index, education, smoking, alcohol intake, dietary habits, and family history were considered before selecting the patients. Analytical Methods: Urinary Hydroxyproline and Urinary creatinine was estimated by Modified Neumann et al and Spectrophotometric JaffeÂÂs reaction respectively. Result: The study population consisted of 70 participants of premenopausal (n=35) and postmenopausal women (n=35), mean age of 38.11 ± 4.3 and 54.40 ± 4.6 respectively. The bone mineralization marker urinary total hydroxyproline was quantified in pre and post-menopausal women, which is 80.3 ± 75mg/L and 136 ± 103mg/L respectively. The urinary creatinine level in pre and post-menopausal women was 53.7 ± 14.2mg/dL and 37.0 ± 27.3 respectively. The hydroxyproline: creatinine ratio (HCR) was 41% to 69% against the normal reference interval in pre and post-menopausal women. Conclusion: The obtained normative data for the premenopausal woman population would be a new reference range in Indian sub-population or otherwise general population normative reference range commonly being used as a reference interval in all kind of pathophysiological disorders. Hence, the derived parameter confirmed that HCR is the most prognostic significant diagnostic marker in pre and post-menopausal patients.
32
Yoshino, S., M. Oka, S. Hazama, R. Shimizu, and T. Yamamoto. "A combination phase I study of biweekly docetaxel and 5’-DFUR in patients with unresectable or recurrent gastric cancer." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 14115. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.14115.
Анотація:
14115 Background: Docetaxel (DOC) and 5’-DFUR (an intermetamolite of capecitabine) have single-agent activity in gastric cancer and have distinct mechanisms of action and no overlap of key toxicities. Synergistic interaction between DOC and 5’-DFUR is mediated by taxane-induced up-regulation of thymidine phosphorylase. The objectives of this study were to determine the maximum tolerated dose (MTD), the dose limiting toxicity (DLT) and the recommended dose (RD) of the combination therapy of biweekly DOC and 5’-DFUR. The DLT was set in low grade to treat the patients in the outpatient clinic. Methods: Eligibility criteria included patients with histologically proven unresectable or recurrent gastric cancer, no requirement of prior chemotherapy, a performance status of 0–2, adequate organ function and written informed consent. DOC was administered by 1-hour intravenous infusion (level 1, 2, 3, 4: 30, 35, 40, 45 mg/m2) biweekly for 4 weeks. 5’-DFUR was administered orally at a fixed dose of 600mg/body everyday. Toxicity and efficacy were evaluated during the 2 cycles for 8 weeks. Three or 6 patients were enrolled at each dose level. Administration of DOC was skipped in the event of grade 2 hematologic toxicity. DLT was defined as grade 3 hematologic toxicity, grade 2 non-hematologic toxicity. The MTD was defined as the dose level at which at least two of three patients or three of six patients presented with DLT. Results: Twelve patients with a median age of 58 years (range, 29 to 75) were enrolled in this study. Five patients have received prior chemotherapy. Eight patients were unresectable and 4 had recurrent tumors. At level 1 (n=3), 2 (n=3), 3 (n=3), no patients developed DLT. Two patients developed DLT at level 4 (n=3). All DLT was neutropenia. Only 1 developed grade 4 neutropenia at level 4. Non-hematological toxicity was uncommon. Level 4 was determined as the MTD. Of 8 evaluable patients, responses included 4 PR, 3 SD and 1 PD for an overall response rate of 50%. Conclusions: The MTD of DOC in this combination is 45 mg/m2 and the RD is 40 mg/m2. This regimen is well-tolerated with high response rate in outpatient setting. A phase II study is necessary to evaluate the response of this regimen. No significant financial relationships to disclose.
33
Spira, A. I., N. O. Iannotti, M. A. Savin, M. Neubauer, N. Y. Gabrail, R. Yanagihara, K. K. Datta, E. A. Zang, S. Z. Fields, and A. Das. "Phase II study of eribulin mesylate (E7389), a mechanistically novel inhibitor of microtubule dynamics, in patients with advanced non-small cell lung cancer (NSCLC)." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 7546. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.7546.
Анотація:
7546 Background: Eribulin is a structurally-simplified, fully synthetic analog of the marine sponge natural product halichondrin B. Eribulin inhibits microtubule dynamics via a mechanistically novel mode of action. Methods: An open-label, single-arm, Phase II study of eribulin was conducted in patients with advanced NSCLC (ECOG of 0 or 1) who were treated with platinum-based doublet chemotherapy and stratified by prior taxane exposure. A total of 103 patients (83 with prior taxanes and 20 taxane naïve) were treated with eribulin (1.4 mg/m2), administered as a bolus infusion over 2 –5 minutes on Days 1, 8, and 15 of a 28-day cycle (N=77). Due to delays or skipped doses secondary to myelosuppression at Day 15 with recovery by Day 21, the protocol was amended to a schedule of Days 1 and 8 of a 21-day cycle (N=26). The primary efficacy endpoint was objective response rate. Independent radiologic review was used to confirm responses. Results: Of 106 enrolled patients, 103 received eribulin. Median age was 65 years and median number of prior therapies was 2, including taxanes (81%), gemcitabine (40%), pemetrexed (23%), and EGFR inhibitors (34%). Median number of cycles administered was 3 (range 1–15). Drug related toxicities included neutropenia grade 3 (23%) and 4 (26%), febrile neutropenia (4%), grade 3 fatigue (11%), grade 3 nausea (2%), and peripheral neuropathy grade 1/2 (37%) and 3 (2%). Based on RECIST criteria, the overall response rate (all partial responses) was 9.7% (95% CI: 4.0–15.4 %), with 10.8% PR in taxane pre-treated, and 5% PR in taxane naïve patients. Overall disease control rate (PR + SD) was 55.3%. 12-week progression free survival (PFS) rate was 53.0% (95% CI: 42.6–63.3%) and median PFS was 102 days (range 1–408+). Median duration of response was 176 days (range 50–291+), and median overall survival was 287 days (range 16–423+). The one year survival rate was 46.4% (95% CI: 34.9–58.0%). Conclusions: In this group of NSCLC patients who were treated with a median of two prior therapies, consisting in the majority of cases of two cytotoxic regimens, eribulin demonstrated an overall PR rate of 9.7% (10.8% in the taxane pre-treated) and 9.6 months median survival. No significant financial relationships to disclose.
34
Liu, Ting, Pu Kuang, Tian Dong, Bing Xiang, Jianjun Li, Xinchuan Chen, Chuan He, et al. "Imatinib 400mg Daily Combined with Vindesine and Dexamethasone As Induction and Maintenance Therapy for Philadelphia Chromosome-Positive Acute Lymphocytic Leukemia." Blood 118, no. 21 (November 18, 2011): 4243. http://dx.doi.org/10.1182/blood.v118.21.4243.4243.
Анотація:
Abstract Abstract 4243 [Background] Imatinib combined with intensive chemotherapy protocol markedly has markedly improved the prognosis of patients with Philadelphia chromosome-positive acute lymphocytic leukemia (Ph+ALL), and has become the standard therapy for this disease. Based on experience from patients with chronic myelogenous leukemia in blast crisis or accelerated phase, this highly specific tyrosine kinase inhibitor was given 600mg or 800mg daily in most clinical trials. However, some pilot study and case report implied that either lower dose of imatinib or less intensive chemotherapy could also achieve a satisfying remission rate. We carried out this pilot study to testify whether a lower dose of imatinib and less intensive chemotherapy could generate similar outcome, especially for patient who are unwilling to or unsuitable for allogeneic hematopoietic stem cell transplantation. [Method] Thirty six patients with de novo Ph+ALL were enrolled between Dec-2008 and Dec-2010. All patients received imatinib 400mg daily, vindesine 4 mg weekly and dexamethasone 10 mg/m2/day for 4 days per week as induction therapy. After complete remission, these patients received 3 courses chemotherapy of protocols adapted from China Acute Lymphocytic Leukemia Group (CALLG) as intensification. Those who were unwilling to receive or unsuitable for allo-HSCT received maintenance therapy with imatinib 400mg daily with chemotherapy by vindesine 4 mg on D1 and D11, dexamethasone 10mg/m2/day on D1-5 and D11-15 with or without interferon-α 3 million unit every other day. Patients over 55 year old skipped the intensification therapy. The maintenance chemotherapy was given once a month in the first year, once per 2 months in the second year, and once per 3 months in the third year. Sixteen cycles of intrathecal chemotherapy with cytarabine and dexamethasone +/− methotrexate was scheduled for central nervous system leukemia (CNSL) prophylaxis. [Result] Thirty six patients were enrolled, and the median age of this group of patients was 33.5 years (shown in table 1). All but one patients (97.2%) achieved complete remission after 4 weeks of induction therapy. One patient was loss of follow-up and one patient quit from this study because of severe hepatic dysfunction thought to be caused by imatinib. Three patients (8.3%) died of infections (pneumonia or sepsis) within intensification cycles. Three (8.3%) patients received allo-HSCT either from a sibling or an unrelated donor at CR1 after 3–4 courses of intensification therapy. The median time of follow-up was 8 months. The median overall survival was were 22.1 (shown in figure 1A.). For patients who received imatinib and chemotherapy only, the median overall survival was 20.4 months (shown in figure 1B). Although there was no evidence for CNSL at diagnosis in all patient, four (11.1%) patients had CNS relapse and three died despite of regular CNSL prophylaxis. [Conclusion] In this pilot study, our data showed that imatinib combined with less intensive chemotherapy could also achieve a over 90% remission rate in patients with de novo Ph+ALL. With the short time of follow-up, the long term effect of this strategy on survival and relapse can not determined yet, and a prospective randomized study is warranted. With reduced chemotherapy intensity, a more intensive protocol for CNS prophylaxis or new generation of TKI (e.g. dasatinib) with higher blood-brain barrier permeability may be considered. Disclosures: No relevant conflicts of interest to declare.
35
Desanti de Oliveira, Beatriz, David DeStephano, Melissa Parsons Beauchemin, Cynthia Law, Kristina `. Howard, Jason Dennis Wright, Ian Kronish, Dawn L. Hershman, and Melissa Kate Accordino. "Implementation of EHR medication-adherence screening tool in breast cancer clinic." Journal of Clinical Oncology 40, no. 28_suppl (October 1, 2022): 438. http://dx.doi.org/10.1200/jco.2022.40.28_suppl.438.
Анотація:
438 Background: Nonadherence to prescribed medications occurs frequently in patient with breast cancer (BC) and can affect BC outcomes as well as outcomes for comorbid conditions. We implemented a process to screen for medication adherence in the electronic health record (EHR) in an urban outpatient BC clinic. Methods: Plan-Do-Study-Act (PDSA) methodology was used to implement a screening process for medication adherence for all patients seen in the outpatient breast oncology clinic. At check-in (via the patient portal or clinic based kiosks), patients were asked to complete an EHR adherence screener. Two PDSA cycles were completed. During cycle one (2/16/22-5/17/22), patients were asked if they received ≥1 prescribed medication; if yes they were asked to complete the questionnaire (y/n); if yes a 3-item questionnaire was used to screen for adherence to all medications over the prior 7 days. Adherence was defined as 3 of 3 responses “none of the time” to “I have missed my medicine;” “I have skipped a dose of my medicine;” and “I did not take a dose of my medicine.” During cycle two (5/17/22-6/5/22) the screener was simplified. Patients were no longer asked to complete the survey; and the survey was modified to 1-item “I did not take a dose of my medicine”, adherence was defined as response of “none of the time”. We evaluated response rate and self-reported non-adherence rate. Results: During PDSA cycle 1 (2/16/22-5/17/22), 2840 visits occurred and 722 (25%) responses were received; 80% noted prescription of ≥1 medication, 38% agreed to complete the survey; and 87% reported adherence to all prescribed medications while 13% reported non-adherence. During PDSA cycle 2 (5/17/22-6/5/22), 512 visits occurred and 172 (33%) responses were received. Of those, 73% reported prescription of ≥1 medication; of those 66%-reported adherence to all prescribed medications, 21% reported non-adherence, and 17% preferred not to answer. Conclusions: This EHR screener is a simple and scalable tool to rapidly screen for medication adherence. Up to a quarter of patients who completed screening reported non-adherence. Further tools are needed to assess adherence among patients who lack access to the patient portal or clinic kiosk, or are uncomfortable checking in with these mechanisms. Future interventions are necessary to further screen potentially non-adherent patients and for interventions to improve adherence once vulnerable patients are identified.
36
Trneny, M., U. Jaeger, O. Belohlavek, C. Skrabs, J. Koren, A. Hanswirth, R. Pytlik, and P. Klener. "Prediction of outcome using positron emission tomography (PET) compared to standard response criteria and potential role in treatment decisions in diffuse large B-cell lymphoma (DLBCL) patients." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 7565. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.7565.
Анотація:
7565 Background: PET has been demonstrated to give valid information about viable tumor residua. There are however only limited data regarding the combination of classical response criteria with PET and there is a lack of information on the impact of additional therapy (add-Th) on the outcome of PET neg. or PET pos. pts. Methods: One hundred thirty-nine pts (median age 50y) with newly diagnosed DLBCL who were examined by PET during (after 2–4 cycles CHT - ‘early PET’) or/and at the end of therapy (‘end PET’) were analyzed retrospectively. IPI risk distribution were as follows: L 28%, LI 24%, IH 33% and H 15% pts. All pts were treated with anthracyclin based CHT. “Early PET” was performed in 84 pts. and “end PET” in 103 pts before add-Th, PET at both time points was performed in 48 pts. Add-Th (HDT with ASCT or/and radiotherapy), was given as planned or as a result of response evaluation (conventional methods - CT, trephine biopsy). No treatment modification was made on PET result only, except for 2 cases when planned RT was skipped because of PET neg. RT was performed in 59 pts (42.4%) and HDT with ASCT as consolidation in 54 pts (38.8%). Median follow up was 30 m. Results: CR or CRu was achieved after CHT in 102 (74%) pts, PR in 24 (17%) pts, stable or progress dis. in 13 (9%). ‘Early PET’ was neg. in 60% pts and ‘end PET’ was neg in 67% pts. PET neg. was achieved at least once in 97 (70%) pts, and PET pos. at least once was found in 50 pts (36%). The PFS at 30 m according to the combination of conventional and PET response was as follows: for CR PET-neg. pts 89%, for PR PET-neg. pts 90%, for CR PET-pos. pts 45% and for PR PET-pos. pts 64% (p=0.0001). OS was 93%, 63%, 90% and 83%, respect.(p=0.004). The analysis of impact of add-Th showed PFS at 30 m: for PET-neg pts with Add-Th 96%, for PET-neg. pts without Add-Th 82%. PET-pos. pts without Add-Th had a PFS of only 10% and PET-pos. pts with add-Th had PFS 58% (p=0.0001). The OS was 92%, 98%, 38% and 74% respect. (p=0.0001). Conclusions: Our data demonstrate that PET give more powerful information than standard response criteria. The second analysis support the the idea that pts with DLBCL in CR who remain PET pos. should undergo the additional therapy. Partial support: Grant MSM 0021620808 No significant financial relationships to disclose.
37
Yao, Gang, Nuno V. da Silva, Michael Warner, Di Wu, and Chenhao Yang. "Tackling cycle skipping in full-waveform inversion with intermediate data." GEOPHYSICS 84, no. 3 (May 1, 2019): R411—R427. http://dx.doi.org/10.1190/geo2018-0096.1.
Анотація:
Full-waveform inversion (FWI) is a promising technique for recovering the earth models for exploration geophysics and global seismology. FWI is generally formulated as the minimization of an objective function, defined as the L2-norm of the data residuals. The nonconvex nature of this objective function is one of the main obstacles for the successful application of FWI. A key manifestation of this nonconvexity is cycle skipping, which happens if the predicted data are more than half a cycle away from the recorded data. We have developed the concept of intermediate data for tackling cycle skipping. This intermediate data set is created to sit between predicted and recorded data, and it is less than half a cycle away from the predicted data. Inverting the intermediate data rather than the cycle-skipped recorded data can then circumvent cycle skipping. We applied this concept to invert cycle-skipped first arrivals. First, we picked up the first breaks of the predicted data and the recorded data. Second, we linearly scaled down the time difference between the two first breaks of each shot into a series of time shifts, the maximum of which was less than half a cycle, for each trace in this shot. Third, we moved the predicted data with the corresponding time shifts to create the intermediate data. Finally, we inverted the intermediate data rather than the recorded data. Because the intermediate data are not cycle-skipped and contain the traveltime information of the recorded data, FWI with intermediate data updates the background velocity model in the correct direction. Thus, it produces a background velocity model accurate enough for carrying out conventional FWI to rebuild the intermediate- and short-wavelength components of the velocity model. Our numerical examples using synthetic data validate the intermediate-data concept for tackling cycle skipping and demonstrate its effectiveness for the application to first arrivals.
38
Zhang, Jing, Qian Cong, Xiao-Ling Fan, Rongjiang Wang, Min Wang, and Nick V. Grishin. "Mitogenomes of Giant-Skipper Butterflies reveal an ancient split between deep and shallow root feeders." F1000Research 6 (March 6, 2017): 222. http://dx.doi.org/10.12688/f1000research.10970.1.
Анотація:
Background: Giant-Skipper butterflies from the genus Megathymus are North American endemics. These large and thick-bodied Skippers resemble moths and are unique in their life cycles. Grub-like at the later stages of development, caterpillars of these species feed and live inside yucca roots. Adults do not feed and are mostly local, not straying far from the patches of yucca plants. Methods: Pieces of muscle were dissected from the thorax of specimens and genomic DNA was extracted (also from the abdomen of a specimen collected nearly 60 years ago). Paired-end libraries were prepared and sequenced for 150bp from both ends. The mitogenomes were assembled from the reads followed by a manual gap-closing procedure and a phylogenetic tree was constructed using a maximum likelihood method from an alignment of the mitogenomes. Results: We determined mitogenome sequences of nominal subspecies of all five known species of Megathymus and Agathymus mariae to confidently root the phylogenetic tree. Pairwise sequence identity indicates the high similarity, ranging from 88-96% among coding regions for 13 proteins, 22 tRNAs and 2 rRNA, with a gene order typical for mitogenomes of Lepidoptera. Phylogenetic analysis confirms that Giant-Skippers (Megathymini) originate within the subfamily Hesperiinae and do not warrant a subfamily rank. Genus Megathymus is monophyletic and splits into two species groups. M. streckeri and M. cofaqui caterpillars feed deep in the main root system of yucca plants and deposit frass underground. M. ursus, M. beulahae and M. yuccae feed in the yucca caudex and roots near the ground, and deposit frass outside through a "tent" (a silk tube projecting from the center of yucca plant). M. yuccae and M. beulahae are sister species consistently with morphological similarities between them. Conclusions: We constructed the first DNA-based phylogeny of the genus Megathymus from their mitogenomes. The phylogeny agrees with morphological considerations.
39
Duke, J. H. "Do periodic consolidations of Pacific countercurrents trigger global cooling by equatorially symmetric La Niña?" Climate of the Past Discussions 6, no. 3 (May 20, 2010): 905–61. http://dx.doi.org/10.5194/cpd-6-905-2010.
Анотація:
Abstract. A sporadic phenomenon of internal tide resonance (ITR) in the western equatorial Pacific thermocline is shown to precede 11 of 12 major upturns in the Niño 3.4 index between 1992 and 2008. Observed ITR has up to 9 °C semidiurnal temperature excursions indicating thermocline heave, but is invisible in time resolution longer than one day. It is independent of westerly wind bursts (WWB). A hypothesis is advanced that (1) ITR dissipates vorticity, leading to Pacific countercurrent consolidation (PCC) by reducing the vortex stretching term in Sverdrup balance. The consequence of lost vorticity survives ephemeral ITR events; (2) The specific surface area of countercurrents is reduced by PCC, which reduces frictional opposition to zonal gradient pressure, which triggers eastward advection at El Niño onset; (3) PCC also accelerates transfer of potential energy to the "pycnostad" below the Equatorial Undercurrent. This shoals the equatorial thermocline, leading to a distinct mode of equatorially symmetric La Niña (ESLN) characterized by a winter monsoon cell above a "cold eye" that is separated from the South American continent, as in 1998; (4) Precessional southward intertropical convergence zone migration (ITCZ) is an alternate PCC trigger, but its effect is modulated by obliquity; and (5) ESLN causes global cooling in all timescales by (a) reduced Hadley cell water vapor production when its rising branch is above the cold eye, (b) equatorward shift in southern circumpolar westerlies due to Hadley cell constriction, (c) possible CO2 sequestration by increased EUC iron fertilized export production on the equator, and (d) possible adjacent cloud seeding by biogenic dimethyl sulphide. Surprising coincidences of WWB with perigean eclipses suggest a parallel atmospheric tide influence. Proposed PCC-ESLN forcing operates in multiple timescales, beginning where the annual cycle of strong equinoctial tides coincides with the minimum perigee cycle. This forcing corresponds with El Niño Southern Oscillation (ENSO) events in 1997, 2002, and 2006. Next, extreme central eclipses that perturb perigee-sysygy intervals also correspond with extreme ENSO events, notably in 1877, 1888, and 1982, and a 586 year cycle in the frequency of these eclipses corresponds with known stadial events in the past 4 thousand years. Contrast in the 586 year cycle increases with Earth eccentricity because it is the result of shorter synodic months at aphelion. Longer timescale forcing is by orbital control of the east-central Pacific ITCZ position, yielding a 10 thousand year fast ice sheet melt interval between March and September perihelion. But default ESLN is only interrupted when perihelion in March coincides with rising obliquity. A change in the phase relation between obliquity and precession from 1:2 to 3:5 or 2:5 may therefore explain skipped obliquity cycles after the mid-Pleistocene transition. A secular improvement in eclipse commensurability that parallels Cenozoic cooling is noted.
40
Zailani, Rosilatul, Gani Priambodo, and Yohannes Sardjono. "NEUTRON AND GAMMA SPECTRUM ANALYSIS OF KARTINI RESEARCH REACTOR FOR BORON NEUTRON CAPTURE THERAPY (BNCT)." JURNAL TEKNOLOGI REAKTOR NUKLIR TRI DASA MEGA 20, no. 2 (July 19, 2018): 59. http://dx.doi.org/10.17146/tdm.2018.20.2.4067.
Анотація:
MCNPX was used to design a three-dimensional model of Kartini Research Reactor (KRR) as a neutron source and performed criticality calculation. The criticality calculation of the reactor aims to obtain the neutron and gamma spectrum by simulating the fission reaction inside the reactor core. Total source histories were 105 per cycle, when the number of cycle for criticality calcutation was 1000 cycles with 60 skipped cycles. The reactor criticality according to the simulation result is 1.00179±0.00007. The total neutron flux on ring A, B, C, D, E and F inside the reactor core are respectively 6.553×1011 n/cm2s, 4.53×1012 n/cm2s, 4.167×1012 n/cm2s, 3.751×1012 n/cm2s, 2.914×1012 n/cm2s and 3.107×1012 n/cm2s. The total gamma flux is 6.956×1011 particles/cm2s, 4.838×1012 particles/cm2s, 4.398×1012 particles/cm2s, 3.962×1012 particles/cm2s, 2.953×1012 particles/cm2s and 2.013×1012 particles/cm2s, respectively for each ring. Thermal neutron fluxes recorded on the base of radial piercing beamport were 4.678×1010 n/cm2s, with the epithermal neutron flux of 5.37×109 n/cm2s and fast neutron flux of 4.17×1010 n/cm2s. The gamma flux on that side reaches 4.22×1012 particles/cm2s. On the 92-cm-ranges from the base inside radial piercing beamport, both neutron and gamma flux decrease up to 5.11×108 n/cm2s for thermal neutron flux, 4.598×106 n/cm2s for epithermal neutron flux, 2.55×107 n/cm2s for fast neutron flux and 8.214×1010 particles/cm2s for gamma flux. In conclusion, the spectrum yield from this study can be use to define the source spectrum of the simulations and optimations prior to BNCT pre-clinical trial (in vivo/in vitro test) use KRR radial piercing beamport.Keywords: BNCT, radial piercing beamport, Kartini Research Reactor, neutron spectrum, gamma spectrum ANALISIS SPEKTRUM NEUTRON DAN GAMMA UNTUK BORON NEUTRON CAPTURE THERAPY (BNCT) DI REAKTOR KARTINI. MCNPX telah digunakan untuk memodelkan bentuk 3 dimensi dari Reaktor Kartini sebagai sumber neutron dan melakukan perhitungan kekritisan. Perhitungan kekritisan reaktor bertujuan untuk mendapatkan spektrum neutron dan gamma dengan mensimulasikan reaksi fisi yang terjadi di dalam inti reaktor. Jumlah source histories adalah 105 per iterasi, dimana banyaknya iterasi yang dilakukan dalam perhitungan kritikalisasi adalah 1000 iterasi dengan jumlah iterasi yang dilewatkan adalah 60 iterasi. Nilai kekritisan reaktor sesuai dengan hasil simulasi adalah 1,00179±0,00007. Fluks neutron total pada ring A, B, C, D, E and F di dalam inti reaktor masing-masing adalah 6,553×1011 n/cm2s, 4,53×1012 n/cm2s, 4,167×1012 n/cm2s, 3,751×1012 n/cm2s, 2,914×1012 n/cm2s and 3,107×1012 n/cm2s. Total fluks gamma adalah 6,956×1011 partikel/cm2s, 4,838×1012 partikel/cm2s, 4,398×1012 partikel/cm2s, 3,962×1012 partikel/cm2s, 2,953×1012 partikel/cm2s dan 2,013×1012 partikel/cm2s, masing-masing untuk tiap ring. Fluks neutron termal hasil perekaman pada pangkal beamport tembus radial adalah 4,678×1010 n/cm2s, dengan fluks neutron epitermal sebesar 5,37×109 n/cm2s dan fluks neutron cepat sebesar of 4,17×1010 n/cm2s. Fluks gamma pada bagian tersebut mencapai 4,22×1012 partikel/cm2s. pada jarak 92 cm dari pangkal beamport tembus radial, fluks neutron dan gamma turun mencapai 5,11×108 n/cm2s untuk fluks neutron termal, 4,598×106 n/cm2s untuk fluks neutron epitermal, 2,55×107 n/cm2s untuk fluks neutron cepat dan 8,214×1010 partikel/cm2s untuk fluks gamma. Kesimpulannya, spektrum yang dihasilkan pada studi kali ini dapat digunakan untuk mendefinisikan sumber dalam simulasi dan optimasi terutama untuk keperluan uji pre-klinis (uji in vivo/ in vitro) BNCT menggunakan beamport tembus radial Reaktor Kartini. Kata kunci: BNCT, beamport tembus radial, Reaktor Kartini, spektrum neutron, spektrum gamma
41
Pacitti, A., F. G. Casino, L. Pedrini, A. Santoro, and M. Atti. "Prescription and Surveillance of the Acetate-Free Biofiltration Sessions: The Bicarbonate Cycle." International Journal of Artificial Organs 18, no. 11 (November 1995): 722–25. http://dx.doi.org/10.1177/039139889501801107.
Анотація:
A computerized system, structured by 4 different models concerning urea depuration, and bicarbonate and sodium handling in acetate-free hemodiafiltration has been conceived for integrated use covering each step of the therapeutic cycle, from a) the prescription of the session to b) its delivery, up to c) the dose - response analysis: the system, now fully developed for the bicarbonate cycle, covers both working areas; the medical one, with a program implemented on a Personal Computer, called Skipper which deals with steps a) and c), and the nursing area, with a program built into the dialytic equipment software. The Skipper program supports the prescription step (a) testing the session schedule by bicarbonate, sodium and urea kinetics. The dialytic equipment, (step(b)) using a different program, on the basis of the scheduled parameters memorizes the end-session plasma bicarbonate level and reacts to any modifications of the parameters regarding blood flow and fluid reinfusion flow suggesting opposite changes in order to reach the scheduled results. Finally (step (c)), the Skipper system statistically evaluates the observed end session bicarbonate plasma level with an expected value with upper and lower confidence bounds obtained by a multiple regression analysis performed on a large population of patients.
42
Wesselink, Amelia K., Lauren A. Wise, Elizabeth E. Hatch, Ellen M. Mikkelsen, Henrik T. Sørensen, Anders H. Riis, Craig J. McKinnon, and Kenneth J. Rothman. "Seasonal patterns in fecundability in North America and Denmark: a preconception cohort study." Human Reproduction 35, no. 3 (January 31, 2020): 565–72. http://dx.doi.org/10.1093/humrep/dez265.
Анотація:
Abstract STUDY QUESTION To what extent does fecundability vary across seasons? SUMMARY ANSWER After accounting for seasonal patterns in pregnancy planning, we observed higher fecundability in the fall and lower fecundability in the spring, particularly at lower latitudes. WHAT IS KNOWN ALREADY In human populations, there are strong seasonal patterns of births that vary across geographic regions and time periods. However, previous studies of seasonality and fecundity are limited because they examine season of birth rather than season of conception and therefore neglect to account for seasonal variation in initiating attempts to conceive or pregnancy loss or differences in gestational length. STUDY DESIGN, SIZE, DURATION We conducted a preconception cohort study of 14 331 women residing in North America (June 2013–May 2018: n = 5827) and Denmark (June 2007–May 2018: n = 8504). Participants were attempting to conceive without fertility treatment and had been attempting pregnancy for ≤6 menstrual cycles at enrolment. PARTICIPANTS/MATERIAL, SETTING, METHODS We collected information on season of each pregnancy attempt using last menstrual period dates over the study period. Pregnancy was reported on female bi-monthly follow-up questionnaires. We fit log-binomial models with trigonometric regression to examine periodic variation in fecundability. We accounted for seasonal variation in initiation of pregnancy attempts by including indicator variables for menstrual cycle of attempt in the regression models. MAIN RESULTS AND THE ROLE OF CHANCE Initiation of pregnancy attempts peaked in September, with stronger seasonality in North America than in Denmark (48 vs. 16% higher probability initiating attempts in September compared with March). After accounting for seasonal variation in initiation of pregnancy attempts, we observed modest seasonal variation in fecundability, with a peak in the late fall and early winter in both cohorts, but stronger peak/low ratios in North America (1.16; 95% confidence interval [CI]: 1.05, 1.28) than in Denmark (1.08; 95% CI: 1.00, 1.16). When we stratified the North American data by latitude, we observed the strongest seasonal variation in the southern USA (peak/low ratio of 1.45 [95% CI: 1.14, 1.84]), with peak fecundability in late November. LIMITATIONS, REASONS FOR CAUTION We estimated menstrual cycle dates between follow-up questionnaires, which may have introduced exposure misclassification, particularly when women skipped follow-up questionnaires. We were unable to measure seasonally varying factors that may have influenced fecundability, including ambient temperature, vitamin D levels or infectious disease. WIDER IMPLICATIONS OF THE FINDINGS An understanding of how fecundability varies across seasons could help identify factors that can impair reproductive function. Neglecting to account for seasonal variation in initiation of pregnancy attempts could bias estimates of seasonal patterns in fecundability. This is the first preconception cohort study to examine seasonal variation in fecundability after accounting for seasonality in initiation of pregnancy attempts. Fecundability was highest in the fall and lowest in the spring, with stronger effects in southern latitudes of North America, suggesting that seasonal exposures may affect fecundity. STUDY FUNDING/COMPETING INTEREST(S) This research was funded by the Eunice K. Shriver National Institute of Child Health and Human Development (R21-050264, R01-HD060680, R21-HD072326 and R01-HD086742) and the Danish Medical Research Council (271-07-0338). The authors declare no conflicts of interest.
43
Gulle, S., Y. Erez, A. Karakas, T. Yüce İnel, S. B. Kocaer, T. Demirci Yildirim, G. Can, İ. Sari, M. Birlik, and F. Onen. "AB0708 HIGH DRUG RETENTION RATES DESPITE B/TSDMARD INTERRUPTIONS IN COVID-19 PANDEMIC CHAOS." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 1386.1–1386. http://dx.doi.org/10.1136/annrheumdis-2021-eular.4068.
Анотація:
Background:A significant increased risk of COVID-19 related adverse outcomes of the biological or target-directed synthetic DMARDs (b/tsDMARDs) has not yet been reported. For this reason, it is recommended to continue b/tsDMARD treatments with maximum compliance with pandemic measures.Objectives:The aim of this study was to evaluate the effects of patients using b/tsDMARDs on drug survival and rheumatic disease control during pandemic.Methods:In this study, patients diagnosed with rheumatic disease using b/tsDMARDs and who were followed up during the 12-month period (January 2020-2021) including the onset of the Covid-19 pandemic at Dokuz Eylul University Faculty of Medicine Rheumatology Clinic were evaluated. In the first 3 months of the pandemic (March-June 2020), the patients skipped at least 2 cycles of treatment with the fear of Covid-19 infection except for infection / surgical reasons was considered as a disruption of the drug. The drug retention rates of the patients on b/tsDMARDs treatments during the pandemic process and the factors affecting this situation were evaluated.Results:The rate of disrupting their b/tsDMARDs was higher in patients> 65 years of age, with a diagnosis of RA and who needed to come to the hospital for bDMARD treatment (p=0.007, p=0.015 and p=0.004, respectively).The overall 1-year b/tsDMARD retention rates was found 91%. It was determined that a history of interruption in b/tsDMARD treatments in the first 3 months of the pandemic [OR: 1.28 (CI: 1.042-8.71), p=0.014] and the need to come to the hospital to receive bDMARD [OR: 0.59 (CI: 0.64-13.11), p=0.041] caused unresponsiveness to return to the same bDMARD treatment and a significant increase in the risk of discontinuation of the biologic treatment.Conclusion:We conclude that it is important for patients to continue taking b/tsDMARD treatments without interruption in the days past abnormal periods such as pandemic conditions and to make sufficient effort for minimum dose of CS and low disease activity by determining patient-based risk.Table 1.Demographic and clinical characteristics of b/tsDMARDs patientsTotal (n=521)b/tsDMARD Continue (n=424) (82.4%)b/tsDMARD Interruption (+) (n=97) (17.6%)PMedian (Min./Max.)Median (Min./Max.)Median (Min./Max.)Age, years48 (18/86)47 (18/82)52 (21/81)0.008tDisease Duration, years11,2 (2/43.3)130 (22/490)142 (22/519)0.41tb/ts DMARD Duration, months40 (12/192)40 (12/192)40 (12/156)0.176tn (%)n (%)n (%)Female278 (53.4)225 (53.1)53 (54.6)0.826Most common rheumatic diseases AxSpa or other SpA283 (54.3)232 (54.7)51 (52.6)0.737 RA134 (25.7)100 (23.6)34 (35.1)0.015l PsA44 (8.4)40 (9.4)4 (4.1)0.109 Vasculitis32 (6.1)27 (6.4)5 (5.2)0.817 Others28 (5.4)25 (5.9)3 (3.1)0.338b/tsDMARD at Hospital/Health center140 (26.9)102 (24.1)38 (39.2)0.004l(OR: 0.59)b/tsDMARD administration route (IV)137 (26.3)100 (23.6)37 (38.1)0.005lActive/Progressive Disease92 (17.7)14 (3.3)78 (80.4)<0.001l(OR: 4.8)Start/continue with the same b/tsDMARD55 (10.6)3 (0.7)52 (53.6)<0.001pUnresponsiveness, b/tsDMARD switch16 (3.1)9 (2.1)7 (7.2)0.017pb/tsDMARD stopped permanently/deceased29 (5.6)9 (2.1)20 (20.6)<0.001ffb/tsDMARD retention (Total)474 (91)406 (95.8)68 (70.1)<0.001tIndependent Samples t Test (Bootstrap), pPearson Chi-Square Test (Monte Carlo), ffFisher freeman Halton Test (Monte Carlo), lLinear-by-Linear Association Test(Monte Carlo, Exact), SD.: Standard deviation; * OR, Odds Ratio,Disclosure of Interests:None declared
44
Pawar, V. G., and K. Pancharatna. "Annual oviduct cycle in the Indian skipper frog,Rana cyanophlyctis(Schneider 1799): a morphological study." Tropical Zoology 12, no. 1 (July 1999): 79–88. http://dx.doi.org/10.1080/03946975.1999.10539379.
45
Sandalcı, Tarkan, Derviş Erol, Battal Doğan, and Erdal Tunçer. "Energy and exergy analyses of skipped cycle mode in a single-cylinder engine fuelled with diesel and natural gas." International Journal of Exergy 39, no. 2 (2022): 173. http://dx.doi.org/10.1504/ijex.2022.10049452.
46
Tunçer, Erdal, Battal Doğan, Tarkan Sandalcı, and Derviş Erol. "Energy and exergy analyses of skipped cycle mode in a single-cylinder engine fuelled with diesel and natural gas." International Journal of Exergy 39, no. 2 (2022): 173. http://dx.doi.org/10.1504/ijex.2022.125523.
47
Supekar, S. C., and N. P. Gramapurohit. "Does temporal variation in predation risk affect antipredator responses of larval Indian Skipper Frogs (Euphlyctis cyanophlyctis)?" Canadian Journal of Zoology 98, no. 3 (March 2020): 202–9. http://dx.doi.org/10.1139/cjz-2019-0118.
Анотація:
Predation risk varies on a moment-to-moment basis, through day and night, lunar and seasonal cycles, and over evolutionary time. Hence, it is adaptive for prey animals to exhibit environment-specific behaviour, morphology, and (or) life-history traits. Herein, the effects of temporally varying predation risk on growth, behaviour, morphology, and life-history traits of larval Indian Skipper Frogs (Euphlyctis cyanophlyctis (Schneider, 1799)) were studied by exposing them to no risk, continuous, predictable, and unpredictable risks at different time points. Our results show that larval E. cyanophlyctis could learn the temporal pattern of risk leading to weaker behavioural responses under predictable risk and stronger responses to unpredictable risk. Temporally varying predation risk had a significant impact on tadpole morphology. Tadpoles facing continuous risk had narrow tail muscles. Tadpoles facing predictable risk during the day were heavy with wide and deep tail muscles, whereas those facing predictable risk at night had long tails. Tadpoles facing unpredictable risk were heavy with narrow tail muscles. Metamorphic traits of E. cyanophlyctis were also affected by the temporal variation in predation risk. Tadpoles facing predictable risk during the day emerged at the largest size. However, tadpoles facing predictable risk at night and unpredictable risk metamorphosed earlier, whereas those facing continuous risk metamorphosed later.
48
DUERR, NATHAN, THALIA CORAHUA-ESPINOZA, QUINLYN BAINE, RAFAEL TEJEIRA, RODRIGO CCAHUANA, MARÍA MERCEDES DEL CASTILLO ESPINOZA, ERIC PERLETT, et al. "Immature stages, new host plant records and shelter structures of Troyus phyllides (Röber, 1925) and Thoon ponka Evans, 1955 in the Peruvian Amazon (Lepidoptera: Hesperiidae: Hesperiinae: Hesperiini)." Zootaxa 5200, no. 4 (October 31, 2022): 372–90. http://dx.doi.org/10.11646/zootaxa.5200.4.6.
Анотація:
We describe here for the first time the complete immature life cycles and shelter structures of two Neotropical skipper butterflies in the subtribe Moncina, Troyus phyllides (Röber, 1925) and Thoon ponka Evans 1955, along with new natural host plant records for these species at Finca Las Piedras, Madre de Dios, Peru. Four eggs and a preantepenultimate larva of T. phyllides, as well as three eggs of Thoon ponka were collected in nature and each passed through five larval instars to adulthood. Troyus phyllides fed on a herbaceous species, Lasiacis ligulata Hitchcock & Chase (Poaceae: Panicoideae: Paniceae), while T. ponka fed on two congeneric herbaceous bamboo species, Pariana lunata Nees and Pariana sp. (Poaceae: Bambusoideae: Olyreae). We present photos of all immature stages and host plants, as well as illustrations of the shelter structures and the head capsules for each of these two species.
49
Dreyling, Martin, Marco Ladetto, Jeanette K. Doorduijn, Eva Gine, Mats Jerkeman, Ulrich Mey, Michal Szymczyk, et al. "Triangle: Autologous Transplantation after a Rituximab/Ibrutinib/ara-c Containing Induction in Generalized Mantle Cell Lymphoma - a Randomized European MCL Network Trial." Blood 134, Supplement_1 (November 13, 2019): 2816. http://dx.doi.org/10.1182/blood-2019-127863.
Анотація:
Background: Mantle cell lymphoma (MCL) is a distinct subtype of lymphoma with a wide variation of clinical course. Based on randomized trials of our network, current standard of care is a cytarabine-containing immunochemotherapy induction (Hermine, Lancet 2016) followed by autologous stem cell transplantation (SCT; Zöllner, ICML 2019) and rituximab maintenance for 3 years (Le Gouill, NEJM 2018). In relapsed MCL the BTK inhibitor ibrutinib achieves high response rates and ongoing remissions (Wang, NEJM 2013; Dreyling, Lancet 2016). This approach achieved especially longer remission durations in earlier treatment lines (Rule, Hamatologica 2019). We aim to clarify whether ibrutinib added to induction and as maintenance with or without autologous stem cell transplantation might improve outcome. Study design and methods: In this international, randomized three-arm phase III trial (EudraCT-no. 2014-001363-12) young, fit patients ( up to 65 years) with histologically confirmed, untreated mantle cell lymphoma advanced stage II-IV qualify for 1:1:1 randomization after written informed consent according to ICH/EU GCP. In the control arm A, patients receive an alternating R-CHOP/R-DHAP induction followed by myeloablative consolidation (either BEAM or THAM: TBI, high dose Ara-C and melphalan). In arm A+I Ibrutinib is added to the R-CHOP cycles (560 mg day 1-19) and applied as maintenance (continuous dosing) for 2 years. In arm I the same induction and maintenance is applied but high dose consolidation and autologous SCT is skipped. A rituximab maintenance (single doses every 2 months up to 3 years) may be added in all study arms according to national clinical routine. The primary study aim is to show superiority of one of three study arms as future standard of care based on the comparison of the investigator-assessed failure-free survival (FFS), i.e. to investigate if the addition of ibrutinib improves the efficacy of standard 1st line treatment, and can even challenge the use of high-dose chemotherapy with autologous SCT. Secondary study aims include the efficacy of the three treatment arms and the safety and tolerability of ibrutinib during induction immuno-chemotherapy and maintenance. Accordingly, overall and complete response rates, progression-free and overall survival will be determined as well as adverse events during induction immuno-chemotherapy and follow-up including the cumulative incidence rates of SPMs. In addition, minimal residual disease is regularly determined based on patient-specific PCR assay according to the standardized Biomed-2 procedure. Results: As of July 30th, 511 of up to 870 patients have been randomized from 12 different European countries. In a meanwhile completed safety run-in of the initial 50 patients, feasibility of the two experimental arms was confirmed with no major differences in hematological and other toxicities and no major delays during induction. Disclosures Dreyling: Acerta: Other: Scientific advisory board; Novartis: Other: Scientific advisory board; Mundipharma: Other: Scientific advisory board, Research Funding; Janssen: Other: Scientific advisory board, Research Funding, Speakers Bureau; Gilead: Other: Scientific advisory board, Speakers Bureau; Celgene: Other: Scientific advisory board, Research Funding, Speakers Bureau; Bayer: Other: Scientific advisory board, Speakers Bureau; Sandoz: Other: Scientific advisory board; Roche: Other: Scientific advisory board, Research Funding, Speakers Bureau. Ladetto:Roche: Honoraria; AbbVie: Honoraria; J&J: Honoraria; Celgene: Honoraria; Pfizer: Honoraria, Speakers Bureau; Acerta: Honoraria, Speakers Bureau; ADC Therapeutics: Honoraria. Doorduijn:Roche: Honoraria, Research Funding. Gine:Janssen: Other: Travel expenses, Research Funding; Gilead: Other: Travel expenses, Research Funding; Roche: Other: Travel expenses, Research Funding. Jerkeman:Janssen: Honoraria, Research Funding; Gilead: Honoraria, Research Funding; Acerta: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Roche: Honoraria, Research Funding. Mey:Janssen-Cilag: Consultancy; Roche: Consultancy, Research Funding. Hutchings:Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Celgene: Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Research Funding. Kolstad:Merck: Research Funding; Nordic Nanovector: Membership on an entity's Board of Directors or advisory committees, Research Funding. Trneny:Roche: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Gilead sciences: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria. Gomes da Silva:AbbVie: Consultancy, Other: Travel support; Roche: Consultancy, Other: Travel support; Janssen-Cilag: Consultancy, Other: Travel support; Celgene: Consultancy; Gilead Siences: Other: Travel support, Research Funding. Klapper:Roche, Takeda, Amgen, Regeneron: Honoraria, Research Funding. Unterhalt:F. Hoffmann-La Roche: Research Funding. Hoster:Janssen: Research Funding; Roche Pharma AG: Other: Travel Support.
50
Terpos, Evangelos, Ioannis Ntanasis-Stathopoulos, Maria Gavriatopoulou, Panagiotis Malandrakis, Despina Fotiou, Magdalini Migkou, Foteini Theodorakakou, et al. "Evaluation of a Novel Method for the Assessment of Ocular Adverse Events and Associated Functional Impact in Transplant Ineligible Patients with Newly Diagnosed Multiple Myeloma Treated with Belantamab Mafodotin, Lenalidomide, and Dexamethasone in the Phase 1/2 Belard Trial." Blood 142, Supplement 1 (November 28, 2023): 6726. http://dx.doi.org/10.1182/blood-2023-173074.
Анотація:
Introduction Belantamab mafodotin (belamaf; GSK2857916), an antibody-drug conjugate targeting B-cell maturation antigen, has shown promising efficacy and a favorable tolerability profile in the treatment of multiple myeloma. Ocular adverse events (OAEs), manifesting as visual acuity changes, ocular symptoms, and corneal findings, are common with belamaf and the main reason for dose modifications (dose reduction, dose holds) or treatment discontinuation. Keratopathy and Visual Acuity (KVA) scale was used in most belamaf trials, including the pivotal DREAMM-2, to guide belamaf dose modifications. KVA grading is dependent on an ophthalmologist consultation prior to belamaf administration. Herein, we evaluate a novel approach to guide belamaf dosing in transplant ineligible (TI) patients (pts) with newly diagnosed multiple myeloma (NDMM), treated with an extended dosing schedule of belamaf in combination with lenalidomide and dexamethasone (Rd) in the phase 1/2 BelaRd study. Methods BelaRd (NCT04808037) is an open-label, phase 1/2 study conducted in Greece, aiming to enroll 66 TI NDMM pts. Part 1 evaluated the safety/tolerability of three belamaf doses (2.5/1.9/1.4 mg/kg) plus Rd in 36 pts and established that the recommended phase 2 dose (RP2D) is 1.9 mg/kg, initially administered q8w and, depending on toxicity, adjusted to q12w. Part 2 investigates the safety/efficacy of RP2D in Groups A and B, comprised of 15 pts each, and evaluates two different sets of guidelines for the management of OAEs. In Group A, belamaf dosing is guided by the KVA scale; in Group B, dose modifications are determined by the pts' responses on ocular symptoms and their impact on activities of daily living (ADL), captured by the Vision Related Anamnestic (VRA) tool, and by the presence of ≥Grade (Gr) 3 KVA events (BCVA reduced/corneal findings). VRA is a novel, 9-item physician administered questionnaire designed to assess the frequency of ocular symptoms and their impact on vision-related activities. Ocular exams include Snellen best corrected visual acuity (BCVA) and slit lamp corneal evaluation, while ocular symptoms are classified by CTCAE v5.0. Herein, we present the OAEs and the clinical activity of the treatment combination for both Groups of Part 2 (cut-off date 05/06/2023). Results By the cut-off date, twenty-four pts [median age: 75.5 years; male: 16 (66.7%)] had received ≥ 1 belamaf dose in Part 2 and were still on treatment. At baseline, most pts had ocular comorbidities. The median belamaf administrations and number of cycles reached were 3.0/2.0 and 6.5/5.5, for Groups A and B, respectively. A meaningful BCVA decline (BCVA <20/50) with at least 3 lines drop in the better seeing eye, was noted in 5/52 (9.6%) and 5/45 (11.1%) assessments, while BCVA ≤20/200 with at least 3 lines drop was noted in 1/59 (1.7%) and 2/51 (3.9%), respectively. Overall, no ≥Gr 3 ocular symptoms were observed, while the most frequent ≥Gr 2 ocular symptom was dry eye (57/110, 51.8%); also, no ≥Gr3 keratopathies were recorded. Among 66/59 VRA assessments, ocular symptoms and ADL impairment, manifesting for >50% of the time (substantial time) in the last 24 hours prior to belamaf administration, were noted in 2 (3.0%)/9 (15.3%) and 2 (3.0%)/7 (11.9%), respectively. Importantly, numerically similar proportions of KVA events and skipped belamaf doses were noted in both Groups (Table 1). Furthermore, although the sample size of the present analysis does not allow conclusions for the VRA test characteristics, it is notable that in all assessments where eyesight difficulties were reported for substantial time, ≥Gr2 KVA events were also recorded, suggesting a potential association between VRA responses and KVA events, that warrants further investigation. Finally, in terms of clinical activity, for the 19 response-evaluable pts (≥2 efficacy assessments), at a median follow-up of 7.4 months the ORR was 90%/100% in Groups A and B (PR/VGPR: 30%/60%; 66.7%/33.3%) with no disease progression observed. Conclusions In this preliminary descriptive analysis, the VRA tool was safe and effective in informing belamaf dose adjustments in the extended dosing schedule. Recruitment in Part 2 is ongoing and, as data accumulates, future analyses will provide further insight on the potential association of the VRA tool with KVA events, which may eliminate the need for an ophthalmic exam prior to belamaf dosing.