Adolescence can be a tumultuous period with numerous threats to self‐integrity. A 3‐year field experiment tested whether repeated affirmations of self‐integrity can help lessen the impact of ...psychological threat on adolescent (11–14 years old) students’ core course GPA over time. A diverse cohort of students (N = 163) was randomly assigned to a control condition or to an affirmation condition, in which teachers repeatedly administered classroom writing exercises that affirmed students’ personal values. Results showed that affirmation lessened a downward trajectory of GPA over time. In contrast to previous research, this effect occurred among all ethnic groups rather than only among stereotype‐threatened ethnic minority groups. Affirmation did not reduce self‐reported psychological threat, but it severed its relationship with performance: Among control students, psychological threat predicted lower GPA. Among affirmed students, psychological threat was unrelated to performance. Beyond their practical implications, these results make two theoretical contributions. First, affirmation can have broader benefits than those previously documented among negatively stereotyped groups, if timed to co‐occur with different sources of threat that emerge over a long developmental window. Second, the effect of affirmation may not be so much to reduce threat as to disrupt its adverse cognitive and motivational effects.
For almost 50 years, psychologists have been theorizing about and measuring religiosity essentially the way Gordon Allport did, when he distinguished between intrinsic and extrinsic religiosity. ...However, there is a historical debate regarding what this scale actually measures, which items should be included, and how many factors or subscales exist. To provide more definitive answers, we estimated a series of confirmatory factor analysis models comparing four competing theories for how to score Gorsuch and McPherson’s commonly used measure of intrinsic and extrinsic religiosity. We then formally investigated measurement invariance across U.S. Protestants, Irish Catholics, and Turkish Muslims and across U.S. Protestants, Catholics, and Muslims. We provide evidence that a five-item version of intrinsic religiosity is invariant across the U.S. samples and predicts less warmth toward atheists and gay men/lesbians, validating the scale. Our results suggest that a variation of Gorsuch and McPherson’s measure may be appropriate for some but not all uses in cross-cultural research.
Currently, the gadolinium retention in the brain after the use of contrast agents is studied by T
-weighted magnetic resonance imaging (MRI) (T
w) and T
mapping. The former does not provide easily ...quantifiable data and the latter requires prolonged scanning and is sensitive to motion. T
mapping may provide an alternative approach. Animal studies of gadolinium retention are complicated by repeated intravenous (IV) dosing, whereas intraperitoneal (IP) injections might be sufficient.
T
mapping will detect the changes in the rat brain due to gadolinium retention, and IP administration is equivalent to IV for long-term studies.
Prospective longitudinal.
A total of 31 Sprague-Dawley rats administered gadodiamide IV (N = 8) or IP (N = 8), or saline IV (N = 6) or IP (N = 9) 4 days per week for 5 weeks.
A 7 T, T
w, and T
mapping.
T
relaxation and image intensities in the deep cerebellar nuclei were measured pre-treatment and weekly for 5 weeks. Then brains were assessed for neuropathology (N = 4) or gadolinium content using inductively coupled plasma mass spectrometry (ICP-MS, N = 12).
Repeated measures analysis of variance with post hoc Student-Newman-Keuls tests and Hedges' effect size.
Gadolinium was detected by both approaches; however, T
mapping was more sensitive (effect size 2.32 for T
vs. 0.95 for T
w), and earlier detection (week 3 for T
vs. week 4 for T
w). ICP-MS confirmed the presence of gadolinium (3.076 ± 0.909 nmol/g in the IV group and 3.948 ± 0.806 nmol/g in the IP group). There was no significant difference between IP and IV groups (ICP-MS, P = 0.109; MRI, P = 0.696). No histopathological abnormalities were detected in any studied animal.
T
relaxometry detects gadolinium retention in the rat brain after multiple doses of gadodiamide irrespective of the route of administration.
1 TECHNICAL EFFICACY: Stage 1.
From surviving fraction to tumour curability, definitions of tumour radioresistance may vary depending on the view angle. Yet, mechanisms of radioresistance have been identified and involve ...tumour-specific oncogenic signalling pathways, tumour metabolism and proliferation, tumour microenvironment/hypoxia, genomics. Correlations between tumour biology (histology) and imaging allow theragnostic approaches that use non-invasive biological imaging using tracer functionalization of tumour pathway biomarkers, imaging of hypoxia, etc. Modelling dose prescription function based on their tumour radio-resistant factor enhancement ratio, related to metabolism, proliferation, hypoxia is an area of investigation. Yet, the delivery of dose painting by numbers/voxel-based radiotherapy with low lineal energy transfer particles may be limited by the degree of modulation complexity needed to achieve the doses needed to counteract radioresistance. Higher lineal energy transfer particles or combinations of different particles, or combinations with drugs and devices such as done with radioenhancing nanoparticles may be promising.
Si les définitions de la radiorésistance des tumeurs peuvent varier selon l’angle de vue, radiobiologique ou clinique, les mécanismes de la radiorésistance sont partiellement identifiés. Ils impliquent des voies de signalisation oncogènes spécifiques aux tumeurs, le métabolisme et la prolifération des tumeurs, le microenvironnement tumoral/hypoxie, et peuvent reposer sur une génomique somatique spécifique. Les corrélations entre la biologie des tumeurs (histologie) et l’imagerie permettent des approches théragnostiques qui utilisent une imagerie biologique non invasive (fonctionnalisation de traceurs des biomarqueurs des voies tumorales, imagerie de l’hypoxie, etc). La modélisation de la fonction de prescription des doses en fonction de leur rapport d’amélioration d’un facteur de radiorésistance des tumeurs, lié au métabolisme, à la prolifération, à l’hypoxie est un domaine en cours d’investigations. Pourtant, la délivrance d’une irradiation très modulée, voxel par voxel, avec des particules à faible transfert d’énergie linéal, peut être limitée par le degré de complexité de la modulation nécessaire pour obtenir les doses requises pour contrer la radiorésistance tumorale. Des particules à transfert d’énergie linéal plus élevé ou des combinaisons de différentes particules, ou des combinaisons avec des médicaments et dispositifs comme celles réalisées avec des nanoparticules améliorant la radioprotection peuvent être envisagées.
Transcriptional responses to the appropriate temporal pattern of action potential firing are essential for long-term adaption of neuronal properties to the functional activity of neural circuits and ...environmental experience. However, standard transcriptome analysis methods can be too limited in identifying critical aspects that coordinate temporal coding of action potential firing with transcriptome response. A Pearson correlation analysis was applied to determine how pairs of genes in the mouse dorsal root ganglion (DRG) neurons are coordinately expressed in response to stimulation producing the same number of action potentials by two different temporal patterns. Analysis of 4728 distinct gene-pairs related to calcium signaling, 435,711 pairs of transcription factors, 820 pairs of voltage-gated ion channels, and 86,862 pairs of calcium signaling genes with transcription factors indicated that genes become coordinately activated by distinct action potential firing patterns and this depends on the duration of stimulation. Moreover, a measure of expression variance revealed that the control of transcripts abundances is sensitive to the pattern of stimulation. Thus, action potentials impact intracellular signaling and the transcriptome in dynamic manner that not only alter gene expression levels significantly (as previously reported) but also affects the control of their expression fluctuations and profoundly remodel the transcriptional networks.
Background
Currently, the gadolinium retention in the brain after the use of contrast agents is studied by T1‐weighted magnetic resonance imaging (MRI) (T1w) and T1 mapping. The former does not ...provide easily quantifiable data and the latter requires prolonged scanning and is sensitive to motion. T2 mapping may provide an alternative approach. Animal studies of gadolinium retention are complicated by repeated intravenous (IV) dosing, whereas intraperitoneal (IP) injections might be sufficient.
Hypothesis
T2 mapping will detect the changes in the rat brain due to gadolinium retention, and IP administration is equivalent to IV for long‐term studies.
Study Type
Prospective longitudinal.
Animal Model
A total of 31 Sprague–Dawley rats administered gadodiamide IV (N = 8) or IP (N = 8), or saline IV (N = 6) or IP (N = 9) 4 days per week for 5 weeks.
Field strength/sequences
A 7 T, T1w, and T2 mapping.
Assessment
T2 relaxation and image intensities in the deep cerebellar nuclei were measured pre‐treatment and weekly for 5 weeks. Then brains were assessed for neuropathology (N = 4) or gadolinium content using inductively coupled plasma mass spectrometry (ICP‐MS, N = 12).
Statistical tests
Repeated measures analysis of variance with post hoc Student–Newman–Keuls tests and Hedges' effect size.
Results
Gadolinium was detected by both approaches; however, T2 mapping was more sensitive (effect size 2.32 for T2 vs. 0.95 for T1w), and earlier detection (week 3 for T2 vs. week 4 for T1w). ICP‐MS confirmed the presence of gadolinium (3.076 ± 0.909 nmol/g in the IV group and 3.948 ± 0.806 nmol/g in the IP group). There was no significant difference between IP and IV groups (ICP‐MS, P = 0.109; MRI, P = 0.696). No histopathological abnormalities were detected in any studied animal.
Conclusion
T2 relaxometry detects gadolinium retention in the rat brain after multiple doses of gadodiamide irrespective of the route of administration.
Evidence Level
1
Technical Efficacy
Stage 1
Leiomyosarcoma is the second most frequent soft-tissue sarcoma. Tumor lymphocytic infiltration (TIL) and programed cell death ligand-1 (PD-L1) have been associated with prognosis in different ...malignancies while DNA mismatch-repair deficiency (MMR-D) has been associated with response to check-point inhibitors. In this pilot study, we sought to examine TIL, PD-L1 and mismatch-repair (MMR) protein expression in 11 leiomyosarcoma and its association with outcome as potential biomarkers for adjuvant treatment. Eleven primary leiomyosarcoma archived-tissues were analyzed for expression of MMR proteins (MSH2, MLH1, MSH6 and PSM2), PD-L1 expression and PD-1, CD3 or CD8. MMR-D was detected in tumor tissue from 2/11 leiomyosarcoma patients. CD3 T-cells were present in all samples, whereas CD8 staining was positive in all but one. PDL-1 was positive in 4/11 and PD-L1 in 6/11. Interestingly, the three patients with the poorest outcome had strongly positive staining for PD-L1 and CD8 while in the two patients who are alive and recurrence-free, both PD-L1 and CD8 infiltration were lacking. We found an association between tumor infiltrating CD8 cytotoxic lymphocytes, strong PD-L1 staining and survival; suggesting a role as biomarkers for treatment decisions regarding peri-operative chemotherapy. We also identified MMR-D in two patients with leiomyosarcoma comprising 18% of our sample.
Summary
Background
LY3022855 is a recombinant, immunoglobulin, human monoclonal antibody targeting the colony-stimulating factor-1 receptor. This phase 1 trial determined the safety, ...pharmacokinetics, and antitumor activity of LY3022855 in combination with durvalumab or tremelimumab in patients with advanced solid cancers who had received standard anti-cancer treatments.
Methods
In Part A (dose-escalation), patients received intravenous (IV) LY3022855 25/50/75/100 mg once weekly (QW) combined with durvalumab 750 mg once every two weeks (Q2W) IV or LY3022855 50 or 100 mg QW IV with tremelimumab 75/225/750 mg once every four weeks. In Part B (dose-expansion), patients with non-small cell lung cancer (NSCLC) or ovarian cancer (OC) received recommended phase 2 dose (RP2D) of LY3022855 from Part A and durvalumab 750 mg Q2W.
Results
Seventy-two patients were enrolled (median age 61 years): Part A = 33, Part B = 39. In Part A, maximum tolerated dose was not reached, and LY3022855 100 mg QW and durvalumab 750 mg Q2W was the RP2D. Four dose-limiting equivalent toxicities occurred in two patients from OC cohort. In Part A, maximum concentration, area under the concentration-time curve, and serum concentration showed dose-dependent increase over two cycles of therapy. Overall rates of complete response, partial response, and disease control were 1.4%, 2.8%, and 33.3%. Treatment-emergent anti-drug antibodies were observed in 21.2% of patients.
Conclusions
LY3022855 combined with durvalumab or tremelimumab in patients with advanced NSCLC or OC had limited clinical activity, was well tolerated. The RP2D was LY3022855 100 mg QW with durvalumab 750 mg Q2W.
ClinicalTrials.gov
ID:
NCT02718911
(Registration Date: May 3, 2011).
The two studies reported here tested whether a classroom-based psychological intervention that benefited a few African American 7th graders could trigger emergent ecological effects that benefited ...their entire classrooms. Multilevel analyses were conducted on data that previously documented the benefits of values affirmations on African American students' grades. The density of African American students who received the intervention in each classroom (i.e., treatment density) was used as an independent predictor of grades. Within a classroom, the greater the density of African American students who participated in the intervention exercise, the higher the grades of all classmates on average, regardless of their race or whether they participated in the intervention exercise. Benefits of treatment density were most pronounced among students with a history of poor performance. Results suggest that the benefits of psychological intervention do not end with the individual. Changed individuals can improve their social environments, and such improvements can benefit others regardless of whether they participated in the intervention. These findings have implications for understanding the emergence of ecological consequences from psychological processes.
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