418 research outputs found
sj-pdf-1-ctj-10.1177_17407745231222018 – Supplemental material for Hierarchical Bayesian modelingof heterogeneous outcome variancein cluster randomized trials
No full textSupplemental material, sj-pdf-1-ctj-10.1177_17407745231222018 for Hierarchical Bayesian modelingof heterogeneous outcome variancein cluster randomized trials by Guangyu Tong, Jiaqi Tong, Yi Jiang, Denise Esserman, Michael O Harhay and Joshua L Warren in Clinical Trials</p
Major histocompatibility complex class II transcriptional platform: assembly of nuclear factor Y and regulatory factor X (RFX) on DNA requires RFX5 dimers
No full textMajor histocompatibility complex class II (MHC-II) genes are regulated in a B-cell-specific and gamma
interferon-inducible manner. Conserved upstream sequences (CUS) in their compact promoters bind nuclear
factor Y (NFY) and regulatory factor X (RFX) complexes. These DNA-bound proteins form a platform that
attracts the class II transactivator, which initiates and elongates MHC-II transcription. In this report, we
analyzed the complex assembly of these DNA-bound proteins. First, we found that NFY can interact with RFX
in cells. In particular, NFYA and NFYC bound RFXANK/B in vitro. Next, RFX5 formed dimers in vivo and in
vitro. Within a leucine-rich stretch N-terminal to the DNA-binding domain in RFX5, the leucine at position 66
was found to be critical for this self-association. Mutant RFX5 proteins that could not form dimers also did
not support the formation of higher-order DNA-protein complexes on CUS in vitro or MHC-II transcription
in vivo. We conclude that the MHC-II transcriptional platform begins to assemble off CUS and then binds DNA
via multiple, spatially constrained interactions. These findings offer one explanation of why in the Bare
Lymphocyte Syndrome, which is a congenital severe combined immunodeficiency, MHC-II promoters are bare
when any subunit of RFX is mutated or missing
MHC class II enhanceosome: how is the class II transactivator recruited to DNA-bound activators?
No full textMHC class II (MHCII) determinants play a crucial role in the immune response by presenting
antigenic peptides to T cells. Their expression is controlled from compact promoters at the
transcriptional level. Pre-assembled regulatory factor X (RFX) and nuclear factor Y (NFY)
complexes form a platform on DNA. The class II transactivator (CIITA) can then be recruited
through multiple protein±protein interactions. In this report, we de®ned domains of CIITA that
are responsible for its interactions with these DNA-bound factors. Furthermore, using DNA-af®nity
precipitation, we demonstrated that although CIITA binds at least ®ve activators, RFX5, RFXAP,
RFXANK/B, NFYB and NFYC, its assembly on the promoter requires the addition of nuclear
extracts. We conclude that not only does the platform bind DNA via multiple, spatially
constrained nteractions, but that it can recruit only modi®ed and/or complexed CIITA to MHCII
promoters
Data record for the article: TriggerPoint Injection for Post-Mastectomy Pain: A Simple Intervention with High Rate of Long-Term Relief
No full textThis
data record provides details of the data supporting the claims of the related article:
“TriggerPoint Injection for
Post-Mastectomy Pain: A Simple Intervention with High Rate of Long-Term Relief”.
The
related study aimed to assess the rate of long-term resolution of post-mastectomy
pain syndrome (PMPS) after trigger point injections to relieve neuropathic
pain.
Type of data:
Participant characteristics; outcomes from the intervention
Subject of
data: Women presenting with clinical symptoms consistent with PMPS.
Sample size:
52 patients
Population
characteristics: Women (aged 31-92) who underwent partial mastectomy with
reduction mammoplasty or mastectomy with or without reconstruction.
Recruitment:
Patients from a breast surgery practice at the University of California San
Francisco Breast Care Center
Date of data
collection: August 2010 to April 2018
Geographic
location: United States of America
Trial
registration number: none
Data
access
De-identified participant
data showing
1.
study participant characteristics
2.
surgery interventions and
complications
3.
comparisons between sample
characteristics and primary outcome
are openly
available as part of this figshare metadata
record in the file ‘Khoury_PainInjectionPatients_NewCodedDatabase_Deidentified.xlsx’.
Corresponding author(s) for this study
Laura
J. Esserman ([email protected]).
Study approval
None</p
School of Law takes third place in international VIS pre-moot tournament
No full textCongratulations to second-year students Hanna M. Esserman, Sandon X. Fernandes, Yekaterina Kat Ko and Benjamin K. Ben Price for finishing in third place overall in the ILS Richard DeWitt Memorial VIS Pre-Moot. The Florida Bar\u27s International Law Section hosted the competition for American schools before the teams head to Vienna, Austria, for the international rounds of the 2023 Willem C. Vis International Commercial Arbitration Moot competition next month. The team is led by Dean Peter B. Bo Rutledge. Third-year students Emily K. Crowell and Savannah L. Grant serve as team coaches, with support from Collin Douglas and A. Ligon Fant
Practice implications of the high false negative rate of sentinel lymph node biopsy reported in NSABP-32
No full textAbstract P4-12-03: Tailoring screening to individual risk decreases the cost and improves the value of screening
No full textAbstract
Introduction:
Health care spending rose from 5% to 17.8% of GDP between 1960 and 2015. Clinicians and researchers must engage in increasing health care value – better outcomes at less cost. Personalized screening is one such opportunity. The Patient Centered Outcomes Research Institute recently funded WISDOM (Women Informed to Screen Depending On Measures of risk), a randomized trial to tests the safety and efficacy of basing starting age, stopping age, frequency and modality of breast cancer screening on individual risk (Clinical Trials Identifier NCT02620852). The personalized arm of WISDOM integrates genetic testing into the risk algorithm. Funding for the clinical services of WISDOM (genetic test, risk assessment, high-risk counseling) are expected to be covered ( health plans, insurers). Risk determines the frequency, time to initiate screening and drives cost of downstream screening services. The cost of genetic testing is now less than 215 per participant. Based on current trial enrollment, we estimated that 30 per 1,000 health plan enrollees would join, resulting in an upfront cost of 600 in ongoing costs after Year 1. However, the health plan would save on mammogram and work up costs as participants would receive an average of 2-3 fewer mammograms over five years. Savings are sensitive to the age of participants, cost of mammograms, and savings increase over time. Per participant, five-year savings of 35 for those aged 40-49 and 65-74 respectively, and increased costs of 6,000 per 1,000 health plan enrollees (30 participants) yields $3,800 in five-year savings.
Conclusion:
Personalized screening could provide cost savings and has the potential to increase health care value. Enrollment in the Wisdom study is ongoing and results will be reported in 5 years.
Citation Format: Wimmer K, Stover Fiscalini A, Eklund M, DiGiorgio K, Naeim A, Athena and Wisdom Investigators, Esserman L. Tailoring screening to individual risk decreases the cost and improves the value of screening [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-12-03.</jats:p
Recognising the benefits and harms of breast cancer screening: an opportunity to target improvement
No full textAbstract P3-09-02: Risk stratification using clinical risk factors and genetic variants in a personalized screening trial
No full textAbstract
Introduction: Tailoring breast cancer screening according to individual risk may represent an improvement over the current practice of age-based screening. WISDOM (Women Informed to Screen Depending on Measures of Risk) is an ongoing randomized trial comparing the safety, efficacy, cost, and patient acceptability of personalized versus annual screening. Women in the personalized arm receive screening recommendations based on sequencing of 9 genes associated with hereditary breast cancer and a 5-year risk estimate from the Breast Cancer Surveillance Consortium (BCSC) risk model modified by a polygenic risk score (PRS) comprised of 75 single nucleotide polymorphisms. WISDOM represents the first-ever use of a PRS to prospectively modify risk estimates and allows comparison of risk model performance in a population-based setting. Thus, we evaluated the risk estimates generated by: 1) the Breast Cancer Risk Assessment Tool (BCRAT) based on the Gail model, 2) the BCSC model, and 3) the BCSC model modified by the PRS (BCSC-PRS).
Methods: We analyzed participants in the personalized screening arm of the WISDOM Study (NCT02620852). The trial opened in October 2016 and is enrolling participants aged 40-74 years. Participants' self-reported demographic and risk factor information were collected through an online portal. Genotyping of participants in the personalized arm was done using a custom panel from Color Genomics. 5-year risk estimates were generated using the BCRAT (2011 version), BCSC, and BCSC-PRS models. In the latter, the PRS was used as a Bayesian likelihood ratio to modify the BCSC 5-year risk estimate. We compared the distributions of BCRAT, BCSC, and BCSC-PRS risk estimates around a low-risk (&lt;1%) and moderately high-risk (≥3%) threshold using a paired statistical test (McNemar).
Results: To date, WISDOM has enrolled 2,065 participants, of whom 1,157 are in the personalized arm and 830 have completed risk assessment. The median age was 57 years (interquartile range, IQR 49-64). 83% were Caucasian, 2% African-American, and 7% Asian. 8% self-reported as Hispanic. The median 5-year risk was 1.7% (IQR 1.1-2.3%) using the BCRAT, 1.6% (IQR 1.1-2.3%) using the BCSC model, and 1.5% (IQR 0.9-2.7%) using the BCSC-PRS model. The BCSC-PRS model classified more women into the low (&lt;1%) and moderately high (≥3%) risk categories compared with the BCRAT (p &lt; 0.001) and BCSC model (p &lt; 0.001), Table.
5-year risk classification according to the BCRAT, BCSC and BCSC-PRS models &lt;1%1-3%≥3% n (%)n (%)n (%)Gail161 (19)556 (67)113 (14)BCSC159 (19)568 (68)103 (12)BCSC-PRS275 (33)379 (46)176 (21)
Discussion: Adding a PRS to the BCSC model categorized significantly more women below the low-risk threshold and above the moderately high-risk threshold compared with the BCSC model and BCRAT. Furthermore, the BCSC and BCRAT generated similar distributions of risk estimates. Follow-up with incident breast cancer data is needed to determine whether the reclassification provided by the PRS improves risk stratification and clinical outcomes. However, our preliminary findings suggest that incorporating genetic variants into a validated clinical model is feasible and could enhance risk prediction.
Citation Format: Shieh Y, Ziv E, Eklund M, Sabacan L, Firouzian R, Madlensky L, Anton-Culver H, Borowsky A, LaCroix A, Naeim A, Parker B, van't Veer L, Esserman L, Tice J, WISDOM Study and Athena Network Investigators WS. Risk stratification using clinical risk factors and genetic variants in a personalized screening trial [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-09-02.</jats:p
How Well Does the WTO Settle Disputes?
No full textLast fall, a judicial panel of the WorldTrade Organization (WTO) issued a controversial ruling in a high-stakes corporate tax dispute between the United States and the European Union. Paying scant attention to the complexities of the case, the panel authorized Brussels to implement retaliatory sanction of $4 billion - an unprecedented sum - against Washington. Notably, around the same time the United States and its European allies were also making headlines with another fierce legal battle: over the authority of the International Criminal Court to prosecute American soldiers for alleged misdeeds committed abroad
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