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phase response curve

Vanessa Trieu, Harlan Pinto, Jonathan W Riess, Ruth Lira, Richard Luciano, Jessie Coty, Derek Boothroyd, A Dimitrios Colevas
LESSONS LEARNED: Chemotherapy for recurrent, metastatic squamous cell carcinoma of the head and neck need not be known for extreme toxicity.The weekly regimen studied here has been demonstrated to be tolerable and effective. BACKGROUND: The objective of this study was to establish the response rate, progression-free survival (PFS) and overall survival (OS), and safety profile of weekly docetaxel, platinum, and cetuximab (TPC) in patients with relapsed or metastatic squamous cell carcinoma of the head and neck (SCCHN)...
March 14, 2018: Oncologist
Matthew K Doherty, Tao Ding, Charlie Koumpouras, Shannon E Telesco, Calixte Monast, Anuk Das, Carrie Brodmerkel, Patrick D Schloss
The fecal microbiota is a rich source of biomarkers that have previously been shown to be predictive of numerous disease states. Less well studied is the effect of immunomodulatory therapy on the microbiota and its role in response to therapy. This study explored associations between the fecal microbiota and therapeutic response of Crohn's disease (CD) patients treated with ustekinumab (UST; Stelara) in the phase 2 CERTIFI study. Using stool samples collected over the course of 22 weeks, the composition of these subjects' fecal bacterial communities was characterized by sequencing the 16S rRNA gene...
March 13, 2018: MBio
Łukasz Szeleszczuk, Dariusz Maciej Pisklak, Monika Zielińska-Pisklak
The aim of this study was to determine whether the periodic density functional theory (DFT) calculations can be used for accurate prediction of the influence of the increased pressure on crystal structure and stability of molecular solids. To achieve this goal a series of geometry optimization and thermodynamic parameters calculations were performed for γ-glycine and δ-glycine structures at different pressure values using CASTEP program. In order to perform most accurate geometry optimization various exchange-correlation functionals defined within generalized gradient approximation (GGA): PBE, PW91, RPBE, WC, PBESOL as well as defined within local density approximation (LDA), i...
March 12, 2018: Journal of Computational Chemistry
Kilian Gladiné, Joris J J Dirckx
For the validation of modelling results or the comparison of middle ear interventions, such as prostheses placement, average responses of middle ear vibrations are needed. One such response is the amplitude and phase of the vibration of the stapes footplate as a function of frequency. Average responses and their standard deviation are commonly obtained by calculating the mean of a number of measured responses at each frequency. A typical middle ear magnitude response curve shows a number of distinct peaks, and the location of these peaks varies between ears...
February 24, 2018: Hearing Research
Chia-Ming Chang, Yi-Hsin Lin, Abhishek Kumar Srivastava, Vladimir Grigorievich Chigrinov
Photobiomodulation or low-level light therapy (LLLT) has extensive applications based on light-induced effects in biological systems. Photobiomodulation remains controversial because of a poorly understood biochemical mechanism limited by the well-known biphasic dose response or Arndt-Schulz curve. The Arndt-Schulz curve states that an optimal dose of light is a key factor for realizing a therapeutic effect. In this report, we demonstrate a tunable optical system for photobiomodulation to aid physicians in overcoming the constraints of light due to biphasic dose response...
March 9, 2018: Scientific Reports
Hyungwoo Cho, Dok Hyun Yoon, Kyu-Pyo Kim, Kyun-Seop Bae, Won Seog Kim, Hyeon-Seok Eom, Jin Seok Kim, Jung Yong Hong, Seok Jin Kim, Hyewon Lee, Soo-Jeong Kim, Cheolwon Suh
Background The objective of this study was to assess the safety, dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), pharmacokinetics, and anti-tumor efficacy of CKD-581, a novel pan-histone deacetylase inhibitor, in patients with lymphoma or multiple myeloma (MM) refractory to standard therapy. Methods In this phase I study, CKD-581 was intravenously administered on days 1, 8, and 15 of a 28-day cycle. A standard 3 + 3 cohort design was used to determine the MTD. Acetylated histones H3 and H4 in peripheral blood mononuclear cells were measured for pharmacodynamic assessment in a subpopulation of patients...
March 9, 2018: Investigational New Drugs
Asuka Mogi, Ryo Yomoda, Syunya Kimura, Chisato Tsushima, Jun Takouda, Miho Sawauchi, Tomoko Maekawa, Hidenobu Ohta, Satoshi Nishino, Masatake Kurita, Nariyasu Mano, Noriko Osumi, Takahiro Moriya
The mitotic activity of certain tissues in the body is closely associated with circadian clock function. However, the effects of growth factors on the molecular clockwork are not fully understood. Stimulation of neural stem cells (NSCs) with epidermal growth factor (EGF), a well-known mitogen, is known to cause synchronized cell cycle progression with a period of approximately 24 h, closely associated with the Per2 gene expression rhythm. Here, we examined the effects of EGF on the molecular clockwork of NSCs...
March 5, 2018: Neuroscience
Ravi Kumar Narayanasamy, Carlos Alberto Castañón-Sanchez, Juan Pedro Luna-Arias, Guillermina García-Rivera, Bartolo Avendaño-Borromeo, María Luisa Labra-Barrios, Jesús Valdés, María Esther Herrera-Aguirre, Esther Orozco
BACKGROUND: Entamoeba histolytica is the protozoan parasite responsible for human amebiasis. It causes up to 100,000 deaths worldwide each year. This parasite has two closely related basal transcription factors, the TATA-box binding protein (EhTBP) and the TBP-related factor 1 (EhTRF1). TBP binds to the canonical TATTTAAA-box, as well as to different TATA variants. TRF1 also binds to the TATTTAAA-box. However, their binding capacity to diverse core promoter elements, including the GAAC-element, and their role in gene regulation in this parasite remains unknown...
March 7, 2018: Parasites & Vectors
Jin Wu, Fred Racine, Michael K Wismer, Katherine Young, Donna M Carr, Jing C Xiao, Ravi Katwaru, Qian Si, Paul Harradine, Mary Motyl, Pratik R Bhagunde, Matthew L Rizk
Resistance to antibiotics among bacterial pathogens is rapidly spreading and therapeutic options against multidrug-resistant bacteria are limited. There is an urgent need for new drugs, especially those that can circumvent the broad array of resistance pathways that bacteria have evolved. In this study, we assessed the pharmacokinetic/pharmacodynamic relationship of the novel β-lactamase inhibitor relebactam (MK-7655; REL) in a hollow fiber infection model. REL is intended for use with the carbapenem β-lactam antibiotic imipenem for the treatment of Gram-negative bacterial infections...
March 5, 2018: Antimicrobial Agents and Chemotherapy
Yuanming Luo, Zhiwei Fan, Stephen Baek, Jia Lu
Machine learning was applied to classify tension-strain curves harvested from inflation tests on ascending thoracic aneurysm samples. The curves were classified into rupture and non-rupture groups using pre-rupture response features. Two groups of features were used as the basis for classification. The first was the constitutive parameters fitted from the tension-strain data and the second was geometric parameters extracted from the tension-strain curve. Based on the importance scores provided by the machine learning, implications of some features were interrogated...
March 4, 2018: International Journal for Numerical Methods in Biomedical Engineering
Sibylle Loibl, Joyce O'Shaughnessy, Michael Untch, William M Sikov, Hope S Rugo, Mark D McKee, Jens Huober, Mehra Golshan, Gunter von Minckwitz, David Maag, Danielle Sullivan, Norman Wolmark, Kristi McIntyre, Jose J Ponce Lorenzo, Otto Metzger Filho, Priya Rastogi, W Fraser Symmans, Xuan Liu, Charles E Geyer
BACKGROUND: Although several randomised trials in patients with triple-negative breast cancer have shown that the addition of carboplatin, with or without poly(ADP-ribose) polymerase (PARP) inhibitors, to neoadjuvant chemotherapy increases the likelihood of achieving a pathological complete response, the use of these therapies in this setting has remained controversial. The BrighTNess trial was designed to assess the addition of the PARP inhibitor veliparib plus carboplatin or carboplatin alone to standard neoadjuvant chemotherapy in triple-negative breast cancer...
February 28, 2018: Lancet Oncology
Xinran Wang, Shupeng Yang, Yi Li, Jinzhen Zhang, Yue Jin, Wen Zhao, Yongxin Zhang, Jingping Huang, Peng Wang, Cuiling Wu, Jinhui Zhou
A robust and sensitive method of solid-phase extraction followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was established and performed for the simultaneous determination of eleven aminoglycosides (AGs) in royal jelly and honey. After sample extraction by a phosphate buffer containing trichloroacetic acid (TCA) and ethylenediaminetetracetic acid disodium salt (Na2 EDTA), the extraction solution was subjected to a parallel solid-phase extraction for clean-up prior to the LC-MS/MS analysis...
February 19, 2018: Journal of Chromatography. A
Takahiro Kobayashi, Masatomo Miura, Takenori Niioka, Maiko Abumiya, Fumiko Ito, Isuzu Kobayashi, Sho Ikeda, Tomoko Yoshioka, Yoshihiro Kameoka, Naoto Takahashi
BACKGROUND: The authors conducted a phase II clinical trial of lenalidomide and dexamethasone combination therapy in Japanese elderly patients with newly diagnosed multiple myeloma to evaluate its safety and efficacy and to determine whether safety and efficacy correlate with the plasma concentration of lenalidomide. METHODS: Forty patients received oral lenalidomide on days 1-21 of a 28-day cycle in addition to weekly doses of dexamethasone. Plasma concentrations of lenalidomide were measured, and the area under the concentration-time curve from 0 to 24 h (AUC0-24) of lenalidomide was predicted using a formula the authors previously reported in this journal...
February 27, 2018: Therapeutic Drug Monitoring
Walburga Engel-Riedel, Jamie Lowe, Paulette Mattson, J Richard Trout, Richard D Huhn, Michele Gargano, Myra L Patchen, Richard Walsh, My My Trinh, Mariève Dupuis, Folker Schneller
BACKGROUND: BTH1677, a beta-glucan pathogen-associated molecular pattern molecule, drives an anti-cancer immune response in combination with oncology antibody therapies. This phase II study explored the efficacy, pharmacokinetics (PK), and safety of BTH1677 combined with bevacizumab/carboplatin/paclitaxel in patients with untreated advanced non-small cell lung cancer (NSCLC). METHODS: Patients were randomized to the BTH1677 arm (N = 61; intravenous [IV] BTH1677, 4 mg/kg, weekly; IV bevacizumab, 15 mg/kg, once each 3-week cycle [Q3W]; IV carboplatin, 6 mg/mL/min Calvert formula area-under-the-curve, Q3W; and IV paclitaxel, 200 mg/m2 , Q3W) or Control arm (N = 31; bevacizumab/carboplatin/paclitaxel as above)...
February 27, 2018: Journal for Immunotherapy of Cancer
Flavio Finger, Enrico Bertuzzo, Francisco J Luquero, Nathan Naibei, Brahima Touré, Maya Allan, Klaudia Porten, Justin Lessler, Andrea Rinaldo, Andrew S Azman
BACKGROUND: Cholera prevention and control interventions targeted to neighbors of cholera cases (case-area targeted interventions [CATIs]), including improved water, sanitation, and hygiene, oral cholera vaccine (OCV), and prophylactic antibiotics, may be able to efficiently avert cholera cases and deaths while saving scarce resources during epidemics. Efforts to quickly target interventions to neighbors of cases have been made in recent outbreaks, but little empirical evidence related to the effectiveness, efficiency, or ideal design of this approach exists...
February 2018: PLoS Medicine
Haoyu Sun, Yongzheng Pan, Yue Gu, Zhifen Lin
Cross-phenomenon in which the concentration-response curve (CRC) for a mixture crosses the CRC for the reference model has been identified in many studies, expressed as a heterogeneous pattern of joint toxic action. However, a mechanistic explanation of the cross-phenomenon has thus far been extremely insufficient. In this study, a time-dependent cross-phenomenon was observed, in which the cross-concentration range between the CRC for the mixture of sulfamethoxypyridazine (SMP) and (Z-)-4-Bromo-5-(bromomethylene)-2(5H)-furanone (C30) to the bioluminescence of Aliivibrio fischeri (A...
February 19, 2018: Science of the Total Environment
Rodney A Kennedy, David Drake
Kennedy, RA and Drake, D. Dissociated time course of recovery between strength and power after isoinertial resistance loading in rugby union players. J Strength Cond Res 32(3): 748-755, 2018-There is a substantial amount of research on the responses to isometric and eccentric loading. However, only a paucity of literature exists on the responses to isoinertial loading, especially in trained athletic populations using realistic loading protocols. The purpose of this study was to examine the acute neuromuscular response to a bout of isoinertial resistance loading in elite rugby players...
March 2018: Journal of Strength and Conditioning Research
Reinhard Lipowsky
Aqueous two-phase systems and water-in-water emulsions have attracted much recent interest. Here, we theoretically study the interactions of such systems with biomimetic membranes and giant unilamellar vesicles (GUVs). For partial wetting, the water-water interface and the membrane form a three-phase contact line that partitions the membrane into two distinct segments with different tensions and different curvature-elastic properties. On the nanometer scale, the capillary forces arising from the water-water interface lead to a smoothly curved membrane that forms an intrinsic contact angle with the interface...
February 21, 2018: Journal of Physical Chemistry. B
Kathleen N Moore, Todd M Bauer, Gerald S Falchook, Swapan Chowdhury, Chirag Patel, Rachel Neuwirth, Aaron Enke, Fabian Zohren, Manish R Patel
Background: Sapanisertib (TAK-228) is an investigational, orally available, potent and highly selective mTORC1/2 inhibitor demonstrating promise in numerous malignancies. This phase I study (NCT02412722) evaluated the safety, tolerability, pharmacokinetics and antitumour activity of single-agent TAK-228 (milled capsules), administered daily (QD) or weekly (QW) and in combination with paclitaxel in patients with advanced solid tumours. Pharmacokinetic comparisons of milled versus unmilled TAK-228 and the impact of food were also investigated...
2018: ESMO Open
Ji-Hae Choi, Seung-Hoon Jhi
Group-VIIB transition metal dichalcogenides (TMDCs) are known to be stabilized solely in a distorted 1T phase termed as 1T″ phase, which is compared to many stable or metastable phases in other TMDCs. Using first-principles calculations, we study the structural origin of 1T″ phase group-VIIB TMDCs. We find that quasi 1D Peierls-like instability is responsible for the transition to the 1T″ phase ReS2 monolayer from the 1T' phase, another distorted 1T phase. Two half-filled bands in 1T'-ReS2 make sharp peaks in the Lindhard function that prompt the charge density wave (CDW) phase with large band gap opening...
February 19, 2018: Journal of Physics. Condensed Matter: An Institute of Physics Journal
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