Preferences of Monkeys for Automatically Dispensable Rewards

1964 ◽  
Vol 15 (1) ◽  
pp. 55-64 ◽  
Author(s):  
V. J. Polidora ◽  
Ira J. Schneider
Keyword(s):  
Rhesus Monkeys ◽  
Response Rate ◽  
Paired Comparison ◽  
Comparison Method ◽  
Operant Response ◽  
Initial Preference

Initial and long-term preferences of 6 rhesus monkeys for 14 automatically dispensable rewards were determined by paired-comparison and operant response rate procedures. Initial preference for sugar pellets, dextrose or sucrose, was at least as high as that for any other single reward studied. Reward “cocktails,” composed of mixtures of several different rewards, were preferred after several hundred rewards had been consumed. It was concluded that the paired-comparison method provided a better estimate of initial preference than did the operant response rate procedure.

4-Jahres-Update der Murano-Studie bestätigt den Stellenwert von Venetoclax in der 2. Therapielinie der CLL

2021 ◽  
pp. 77-79
Author(s):  
Maximilian Schmutz ◽  
Sebastian Sommer
Keyword(s):  
Response Rate ◽  
Residual Disease ◽  
Gene Mutations ◽  
Progression Free Survival ◽  
Lymphocytic Leukemia ◽  
Fixed Duration ◽  
Genetic Characteristics ◽  
Genomic Complexity ◽  
End Of Treatment

<b>Purpose:</b> In previous analyses of the MURANO study, fixed-duration venetoclax plus rituximab (VenR) resulted in improved progression-free survival (PFS) compared with bendamustine plus rituximab (BR) in patients with relapsed or refractory chronic lymphocytic leukemia (CLL). At the 4-year follow-up, we report long-term outcomes, response to subsequent therapies, and the predictive value of molecular and genetic characteristics. <b>Patients and methods:</b> Patients with CLL were randomly assigned to 2 years of venetoclax (VenR for the first six cycles) or six cycles of BR. PFS, overall survival (OS), peripheral-blood minimal residual disease (MRD) status, genomic complexity (GC), and gene mutations were assessed. <b>Results:</b> Of 389 patients, 194 were assigned to VenR and 195 to BR. Four-year PFS and OS rates were higher with VenR than BR, at 57.3% and 4.6% (hazard ratio [HR], 0.19; 95% CI, 0.14 to 0.25), and 85.3% and 66.8% (HR, 0.41; 95% CI, 0.26 to 0.65), respectively. Undetectable MRD (uMRD) at end of combination therapy (EOCT) was associated with superior PFS compared with low MRD positivity (HR, 0.50) and high MRD positivity (HR, 0.15). Patients in the VenR arm who received ibrutinib as their first therapy after progression (n = 12) had a reported response rate of 100% (10 of 10 evaluable patients); patients subsequently treated with a venetoclax-based regimen (n = 14) had a reported response rate of 55% (six of 11 evaluable patients). With VenR, the uMRD rate at end of treatment (EOT) was lower in patients with GC than in those without GC (<i>P</i> = 0.042); higher GC was associated with shorter PFS. Higher MRD positivity rates were seen with <i>BIRC3</i> and <i>BRAF</i> mutations at EOCT and with <i>TP53, NOTCH1, XPO1,</i> and <i>BRAF</i> mutations at EOT. <b>Conclusion:</b> Efficacy benefits with fixed-duration VenR are sustained and particularly durable in patients who achieve uMRD. Salvage therapy with ibrutinib after VenR achieved high response rates. Genetic mutations and GC affected MRD rates and PFS. <b>Trial registration:</b> ClinicalTrials.gov NCT02005471.

scholarly journals Withdrawal from long-term methamphetamine self-administration ‘normalizes’ neurometabolites in rhesus monkeys: a1H MR spectroscopy study

2013 ◽  
Vol 20 (1) ◽  
pp. 69-79 ◽  
Author(s):  
Shaolin Yang ◽  
Annabelle M. Belcher ◽  
Svetlana Chefer ◽  
D. Bruce Vaupel ◽  
Charles W. Schindler ◽  
...  
Keyword(s):  
Mr Spectroscopy ◽  
Rhesus Monkeys ◽  
Spectroscopy Study ◽  
Self Administration

Anterior displacement of the mandible in adult rhesus monkeys: Long-term observations

1971 ◽  
Vol 26 (5) ◽  
pp. 517-531 ◽  
Author(s):  
Sigurd P. Ramfjord ◽  
Randall D. Enlow
Keyword(s):  
Rhesus Monkeys ◽  
Anterior Displacement

scholarly journals Sequential transarterial chemoembolization and early radiofrequency ablation improves clinical outcomes for early-intermediate hepatocellular carcinoma in a 10-year single-center comparative study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Liangliang Yan ◽  
Yanqiao Ren ◽  
Kun Qian ◽  
Xuefeng Kan ◽  
Hongsen Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Radiofrequency Ablation ◽  
Combination Therapy ◽  
Clinical Outcomes ◽  
Transarterial Chemoembolization ◽  
Response Rate ◽  
Multivariable Analysis ◽  
Complication Rates ◽  
Tace Treatment

Abstract Background Transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) are effective treatment methods for unresectable hepatocellular carcinoma (HCC). However, there is still a lack of clinical research on whether early sequential RFA, compared with late combination therapy, can improve the long-term efficacy of initial TACE treatment. Methods This retrospective study investigated a cohort of patients who underwent combination therapy using TACE and RFA (TACE followed by RFA) from January 2010 to January 2020 at our medical centre. A total of 96 patients underwent TACE combined with early RFA (usually during the first hospitalization), which was called TACE + eRFA. Thirty-four patients received 1–2 palliative TACE treatments first and then underwent TACE treatment combined with late RFA (TACE + lRFA). All patients continued to receive palliative TACE treatments after intrahepatic lesion progression until reaching intolerance. The overall survival (OS) rate, time to tumour progression (TTP), tumour response rate and major complication rates were compared between the two groups. Results There were significant differences in the median OS (46 months vs 33 months; P = 0.013), median TTP (28 months vs 14 months; P < 0.00), objective response rate (ORR) (89.6% vs 61.8%, P = 0.000) and disease control rate (DCR) (94.8% vs 73.5% P = 0.002) between the two groups. Multivariable analysis revealed that the Barcelona Clinic Liver Cancer stage was an independent risk factor for OS. Meanwhile, multivariable analysis revealed that TACE + eRFA was associated with an enhanced TTP. Conclusion Early sequential RFA treatment in patients with early-intermediate HCC can improve local tumour control and clinical outcomes while reducing the frequency of TACE treatment. In clinical practice, in HCC patients initially treated with TACE, it is recommended to combine RFA as soon as possible to obtain long-term survival.

EXTH-77. POLIO VIROTHERAPY OF MURINE BRAIN TUMORS INDUCES MICROGLIA PROLIFERATION AND INFLAMMATION THAT IS POTENTIATED BY IMMUNE CHECKPOINT BLOCKADE

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi181-vi181
Author(s):  
Yuanfan Yang ◽  
Michael Brown ◽  
Kevin Stevenson ◽  
Giselle lopez ◽  
Reb Kornahrens ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Checkpoint ◽  
Response Rate ◽  
Cd8 T Cell ◽  
Gene Set Enrichment Analysis ◽  
Type I ◽  
Acute Type ◽  
Type I Ifn ◽  
Term Survival

Abstract Immunotherapy with polio:rhinovirus recombinant (PVSRIPO) has shown evidence of efficacy in a phase I clinical trial for recurrent GBM, resulting in durable radiographic responses and 21% long-term survival at 36 months. Ongoing research aims to enhance the clinical response rate by resolving the mechanisms of action and therapy resistance in vivo, thereby devising more effective therapies. Mouse glioma (CT2A) cells were intracranially implanted (day 0) in transgenic mice carrying poliovirus receptor CD155, and treated with intratumor PVSRIPO (5×105 pfu; day 6) to dissect early and late events following therapy. A blinded pathological review of 45 post-treatment tumors was performed. On day 8, a histological response, featured by tumor dissociation and shrinkage, with inflammation and microglia enrichment in the treated hemisphere, was common in PVSRIPO group (6/7) compared to controls (0/4). However, the response rate fell over time (7/12 on day 12; 1/7 on day 15) and the therapy was overcome by aggressive tumor regrowth. RNAseq was performed and Gene Set Enrichment Analysis of the tumor microenvironment revealed an acute type-I interferon (IFN)-related inflammation, correlating with the histological findings of profound proinflammatory engagement of microglia (Iba1+) widespread in the treated hemisphere. Microglia proliferation (Ki67+) was observed in the treated hemisphere, likely resulting from PVSRIPO infection, in CT2A and B16 intracranial models. This suggests an association of adaptive antitumor immunity—elicited by immediate intratumor type-I IFN-dominant inflammation—with tumor regression. Thus, buttressing type-I IFN directed antitumor CD8+T cell immunity, e.g. with blockade of the PD1:PD-L1 immune checkpoint, might contribute to tumor remission. Indeed, combination therapy with αPD-L1 antibody in the CT2A model showed longer median survival and higher long-term remission rate compared to monotherapy alone; CD8 T cell depletion can completely abrogate this efficacy with this therapy combination, confirming the role of anti-tumor immunity in this approach.

Acute activation and inactivation of macaque frontal eye field with GABA-related drugs

1995 ◽  
Vol 74 (6) ◽  
pp. 2744-2748 ◽  
Author(s):  
E. C. Dias ◽  
M. Kiesau ◽  
M. A. Segraves
Keyword(s):  
Injection Site ◽  
Rhesus Monkeys ◽  
Frontal Eye Field ◽  
Surgical Removal ◽  
Gamma Aminobutyric Acid ◽  
Eye Field ◽  
Distribution Of Points ◽  
Direction Opposite ◽  
Voluntary Saccades

1. This project tests the behavioral effects of reversible activation and inactivation of sites within the frontal eye field of rhesus monkeys with microinjections of the gamma-aminobutyric acid (GABA)-related drugs bicuculline and muscimol. 2. Muscimol injections impaired the monkeys' ability to make both visually and memory-guided saccades to targets at the center of the area represented by the injection site. The latencies of saccades to targets in regions flanking the injection were increased. For memory-guided saccades, saccades in the direction opposite to that represented by the injection site, were made with shorter latency than controls and often occurred before the movement cue. 3. Bicuculline injections produced irrepressible saccades equivalent to the saccade vector represented by the injection site, often in a staircase of several closely spaced movements. 4. Both substances decreased the accuracy of fixation of a central light. The distribution of points of fixation on different trials was diffuse, and the angle of gaze tended to deviate towards the side of the injection. 5. The results of these acute injections are similiar to those observed in the superior colliculus and are much more substantial than the effects observed in the long term after surgical removal of the frontal eye field. The results of this study promote a central role for the frontal eye field in the generation of all voluntary saccades and in the control of fixation.

Sucrose Concentration as Reinforcement for Lever Pressing by Monkeys

1956 ◽  
Vol 2 (3) ◽  
pp. 381-384 ◽  
Author(s):  
Donald G. Conrad ◽  
Murray Sidman
Keyword(s):  
Food Deprivation ◽  
Rhesus Monkeys ◽  
Response Rate ◽  
Sucrose Concentration ◽  
Variable Interval ◽  
Variable Interval Schedule ◽  
Interval Schedule ◽  
Satiation Effect ◽  
Low Concentrations ◽  
Lever Pressing

3 rhesus monkeys were given various concentrations of sucrose for lever pressing on a variable interval schedule of reinforcement. 7 sucrose concentrations were studied at 2 levels of food deprivation. The response rates accelerated rapidly with increasing concentrations, and then declined after reaching a maximum, generally between 15 and 30% sucrose concentration. The decline was attributed to a satiation effect. The higher level of food deprivation tended to increase the response rate at all but the extreme high and low concentrations.

scholarly journals Waning Humoral Response 3 to 6 Months after Vaccination with the SARS-COV-2 BNT162b2 mRNA Vaccine in Dialysis Patients

2021 ◽  
Vol 11 (1) ◽  
pp. 64
Author(s):  
Noa Berar-Yanay ◽  
Sarit Freiman ◽  
Maʹanit Shapira ◽  
Amer Saffoury ◽  
Ameer Elemy ◽  
...  
Keyword(s):  
Response Rate ◽  
Vaccine Dose ◽  
Humoral Response ◽  
Albumin Level ◽  
High Response Rate ◽  
Control Group ◽  
Dialysis Patients ◽  
Serious Adverse Events ◽  
Antibody Levels

Background and objectives: The short-term reported antibody response to SARS-COV-2 vaccination in dialysis patients is high, with a seroconversion response rate up to 97%. Data on the long-term durability of this response are scarce. Our objective was to characterize the long-term anti-spike antibody level in dialysis patients. Design, setting, participants, and measurements: In an observational study, we measured SARS-COV-2 anti-spike antibody levels in dialysis patients who completed 2 doses of the BNT162b2 mRNA SAR S-COV-2 vaccine at 1, 3 and 6 months after the second vaccine dose. We compared the response to dialysis patients who were infected with COVD-19 and to a control group of healthcare-employees. Results: One hundred and forty-two dialysis patients who had been vaccinated (ages 64 ± 11.9 years, 61% male), 33 dialysis patients who had COVID-19 infection (ages 54 ± 14.3 years, 55% male) and 104 individuals in the control group (ages 50 ± 12.2 years, 44% male) were included. The response rate in the vaccinated dialysis patients was 94%, 78% and 73% at 1, 3 and 6 months after the second vaccine dose. In the COVID-19 infected dialysis group and in the control group, the response rate remained at 100% over 6 months. The percentage of change in antibody levels between one and 6 months was −66% in the vaccinated dialysis group, −28% in the control group (p < 0.001) and +48% in dialysis patients who had been infected with COVID-19 (p < 0.001). A non-responder status at 6 months was associated with a lower albumin level. No serious adverse events following vaccination were reported. In conclusion: the initially high response rate to the BNT162b2 vaccine in dialysis patients decreases rapidly. Our results indicate that an early booster (3rd) dose, at three months after the second dose, may be advised for this population to preserve the humoral immunity.

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