201 research outputs found
Bounds on R-parity violating supersymmetric couplings from leptonic and semi-leptonic meson decays
We present a comprehensive update of the bounds on R-Parity violating
supersymmetric couplings from lepton-flavour- and lepton-number-violating decay
processes. We consider tau and mu decays as well as leptonic and semi-leptonic
decays of mesons. We present several new bounds resulting from tau, eta and
Kaon decays and correct some results in the literature concerning B-meson
decays.Comment: 30 pages; changed title, updated some bounds from the literature from
different references, added reference
Respiratory Health Effects of In Vivo Sub-Chronic Diesel and Biodiesel Exhaust Exposure
Biodiesel, which can be made from a variety of natural oils, is currently promoted as a sustainable, healthier replacement for commercial mineral diesel despite little experimental data supporting this. The aim of our research was to investigate the health impacts of exposure to exhaust generated by the combustion of diesel and two different biodiesels. Male BALB/c mice (n = 24 per group) were exposed for 2 h/day for 8 days to diluted exhaust from a diesel engine running on ultra-low sulfur diesel (ULSD) or Tallow or Canola biodiesel, with room air exposures used as control. A variety of respiratory-related end-point measurements were assessed, including lung function, responsiveness to methacholine, airway inflammation and cytokine response, and airway morphometry. Exposure to Tallow biodiesel exhaust resulted in the most significant health impacts compared to Air controls, including increased airway hyperresponsiveness and airway inflammation. In contrast, exposure to Canola biodiesel exhaust resulted in fewer negative health effects. Exposure to ULSD resulted in health impacts between those of the two biodiesels. The health effects of biodiesel exhaust exposure vary depending on the feedstock used to make the fuel
Systematic identification of functionally relevant risk alleles to stratify aggressive versus indolent prostate cancer
Novel approaches for classification, including molecular features, are needed to direct therapy for men with low-grade prostate cancer (PCa), especially men on active surveillance. Risk alleles identified from genome-wide association studies (GWAS) could improve prognostication. Those risk alleles that coincided with genes and somatic copy number aberrations associated with progression of PCa were selected as the most relevant for prognostication. In a systematic literature review, a total of 698 studies were collated. Fifty-three unique SNPs residing in 29 genomic regions, including 8q24, 10q11 and 19q13, were associated with PCa progression. Functional studies implicated 21 of these single nucleotide polymorphisms (SNPs) as modulating the expression of genes in the androgen receptor pathway and several other oncogenes. In particular, 8q24, encompassing MYC, harbours a high density of SNPs conferring unfavourable pathological characteristics in low-grade PCa, while a copy number gain of MYC in low-grade PCa was associated with prostate-specific antigen recurrence after radical prostatectomy. By combining GWAS data with gene expression and structural rearrangements, risk alleles were identified that could provide a new basis for developing a prognostication tool to guide therapy for men with early prostate cancer
T-cell receptor determinants of response to chemoradiation in locally-advanced HPV16-driven malignancies
BackgroundThe effect of chemoradiation on the anti-cancer immune response is being increasingly acknowledged; however, its clinical implications in treatment responses are yet to be fully understood. Human papillomavirus (HPV)-driven malignancies express viral oncogenic proteins which may serve as tumor-specific antigens and represent ideal candidates for monitoring the peripheral T-cell receptor (TCR) changes secondary to chemoradiotherapy (CRT).MethodsWe performed intra-tumoral and pre- and post-treatment peripheral TCR sequencing in a cohort of patients with locally-advanced HPV16-positive cancers treated with CRT. An in silico computational pipeline was used to cluster TCR repertoire based on epitope-specificity and to predict affinity between these clusters and HPV16-derived epitopes.ResultsIntra-tumoral repertoire diversity, intra-tumoral and post-treatment peripheral CDR3β similarity clustering were predictive of response. In responders, CRT triggered an increase peripheral TCR clonality and clonal relatedness. Post-treatment expansion of baseline peripheral dominant TCRs was associated with response. Responders showed more baseline clustered structures of TCRs maintained post-treatment and displayed significantly more maintained clustered structures. When applying clustering by TCR-specificity methods, responders displayed a higher proportion of intra-tumoral TCRs predicted to recognise HPV16 peptides.ConclusionsBaseline TCR characteristics and changes in the peripheral T-cell clones triggered by CRT are associated with treatment outcome. Maintenance and boosting of pre-existing clonotypes are key elements of an effective anti-cancer immune response driven by CRT, supporting a paradigm in which the immune system plays a central role in the success of CRT in current standard-of-care protocols
Dark matter scenarios in the minimal SUSY B-L model
We perform a study of the dark matter candidates of a constrained version of
the minimal R-parity-conserving supersymmetric model with a gauged
. It turns out that there are four additional candidates for dark
matter in comparison to the MSSM: two kinds of neutralino, which either
correspond to the gaugino of the or to a fermionic bilepton, as
well as "right-handed" CP-even and -odd sneutrinos. The correct dark matter
relic density of the neutralinos can be obtained due to different mechanisms
including new co-annihilation regions and resonances. The large additional
Yukawa couplings required to break the radiatively often lead to
large annihilation cross sections for the sneutrinos. The correct treatment of
gauge kinetic mixing is crucial to the success of some scenarios. All
candidates are consistent with the exclusion limits of Xenon100.Comment: 45 pages, 22 figures; v2: extended discussion of direct detection
cross section, matches published versio
SUSY parameter determination at the LHC using cross sections and kinematic edges
We study the determination of supersymmetric parameters at the LHC from a
global fit including cross sections and edges of kinematic distributions. For
illustration, we focus on a minimal supergravity scenario and discuss how well
it can be constrained at the LHC operating at 7 and 14 TeV collision energy,
respectively. We find that the inclusion of cross sections greatly improves the
accuracy of the SUSY parameter determination, and allows to reliably extract
model parameters even in the initial phase of LHC data taking with 7 TeV
collision energy and 1/fb integrated luminosity. Moreover, cross section
information may be essential to study more general scenarios, such as those
with non-universal gaugino masses, and distinguish them from minimal,
universal, models.Comment: 22 pages, 8 figure
Managed Aquifer Recharge as a Tool to Enhance Sustainable Groundwater Management in California
A growing population and an increased demand for water resources have resulted in a global trend of groundwater depletion. Arid and semi-arid climates are particularly susceptible, often relying on groundwater to support large population centers or irrigated agriculture in the absence of sufficient surface water resources. In an effort to increase the security of groundwater resources, managed aquifer recharge (MAR) programs have been developed and implemented globally. MAR is the approach of intentionally harvesting and infiltrating water to recharge depleted aquifer storage. California is a prime example of this growing problem, with three cities that have over a million residents and an agricultural industry that was valued at 47 billion dollars in 2015. The present-day groundwater overdraft of over 100 km3 (since 1962) indicates a clear disparity between surface water supply and water demand within the state. In the face of groundwater overdraft and the anticipated effects of climate change, many new MAR projects are being constructed or investigated throughout California, adding to those that have existed for decades. Some common MAR types utilized in California include injection wells, infiltration basins (also known as spreading basins, percolation basins, or recharge basins), and low-impact development. An emerging MAR type that is actively being investigated is the winter flooding of agricultural fields using existing irrigation infrastructure and excess surface water resources, known as agricultural MAR. California therefore provides an excellent case study to look at the historical use and performance of MAR, ongoing and emerging challenges, novel MAR applications, and the potential for expansion of MAR. Effective MAR projects are an essential tool for increasing groundwater security, both in California and on a global scale. This chapter aims to provide an overview of the most common MAR types and applications within the State of California and neighboring semi-arid regions
Locked down apps versus the social media ecology : why do young people and educators disagree on the best delivery platform for digital sexual health entertainment education?
This article reports on focus groups exploring the best way to reach young men with vulgar comedy videos that provide sexual health information. Young people reported that they found the means by which the material was presented - as a locked down app - to be problematic, and that it would better be delivered through social media platforms such as YouTube. This would make it more 'spreadable'. By contrast, adult sex education stakeholders thought the material should be contained within a locked down, stand-alone app - otherwise it might be seen by children who are too young, and/or young people might misunderstand the messages. We argue that the difference in approach represented by these two sets of opinions represents a fundamental stumbling block for attempts to reach young people with digital sexual health materials, which can be understood through the prism of different cultural forms - education versus entertainment
Overall Survival With Palbociclib And Fulvestrant in Women With HR+/HER2– ABC: Updated Exploratory Analyses of PALOMA-3, a Double-Blind, Phase 3 Randomized Study
Purpose: To conduct an updated exploratory analysis of overall survival (OS) with a longer
median follow-up of 73.3 months and evaluate the prognostic value of molecular analysis by
circulating tumor DNA (ctDNA).
Patients and methods: Patients with hormone receptor−positive/human epidermal growth
factor receptor 2−negative (HR+/HER2−) advanced breast cancer (ABC) were randomized 2:1 to
receive palbociclib (125 mg orally/d; 3/1 week schedule) and fulvestrant (500 mg
intramuscularly) or placebo and fulvestrant. This OS analysis was performed when 75% of
enrolled patients died (393 events in 521 randomized patients). ctDNA analysis was performed
among patients who provided consent.
Results: At the data cutoff (August 17, 2020), 258 and 135 deaths occurred in the palbociclib
and placebo groups, respectively. The median OS (95% CI) was 34.8 months (28.8−39.9) in the
palbociclib group and 28.0 months (23.5−33.8) in the placebo group (stratified hazard ratio
0.81; 95% CI, 0.65−0.99). The 6-year OS rate (95% CI) was 19.1% (14.9−23.7) and 12.9%
(8.0−19.1) in the palbociclib and placebo groups, respectively. Favorable OS with palbociclib
plus fulvestrant compared with placebo plus fulvestrant was observed in most subgroups,
particularly in patients with endocrine-sensitive disease, no prior chemotherapy for ABC, low
circulating tumor fraction, and regardless of ESR1, PIK3CA, or TP53 mutation status. No new
safety signals were identified.
Conclusions: The clinically meaningful improvement in OS associated with palbociclib plus
fulvestrant was maintained with >6 years of follow-up in patients with HR+/HER2− ABC,
supporting palbociclib plus fulvestrant as a standard of care in these patients.
Trial Registration: ClinicalTrials.gov Identifer: NCT0194213
Overall Survival with Palbociclib and Fulvestrant in Women with HR+/HER2− ABC: Updated Exploratory Analyses of PALOMA-3, a Double-blind, Phase III Randomized Study
Purpose: To conduct an updated exploratory analysis of overall
survival (OS) with a longer median follow-up of 73.3 months and
evaluate the prognostic value of molecular analysis by circulating
tumor DNA (ctDNA).
Patients and Methods: Patients with hormone receptor–positive/
human epidermal growth factor receptor 2–negative (HRþ/HER2)
advanced breast cancer (ABC) were randomized 2:1 to receive
palbociclib (125 mg orally/day; 3/1 week schedule) and fulvestrant
(500 mg intramuscularly) or placebo and fulvestrant. This OS
analysis was performed when 75% of enrolled patients died (393
events in 521 randomized patients). ctDNA analysis was performed
among patients who provided consent.
Results: At the data cutoff (August 17, 2020), 258 and 135 deaths
occurred in the palbociclib and placebo groups, respectively.
The median OS [95% confidence interval (CI)] was 34.8 months
(28.8–39.9) in the palbociclib group and 28.0 months (23.5–33.8)
in the placebo group (stratified hazard ratio, 0.81; 95% CI, 0.65–
0.99). The 6-year OS rate (95% CI) was 19.1% (14.9–23.7) and
12.9% (8.0–19.1) in the palbociclib and placebo groups, respectively. Favorable OS with palbociclib plus fulvestrant compared
with placebo plus fulvestrant was observed in most subgroups,
particularly in patients with endocrine-sensitive disease, no prior
chemotherapy for ABC and low circulating tumor fraction and
regardless of ESR1, PIK3CA, or TP53 mutation status. No new
safety signals were identified.
Conclusions: The clinically meaningful improvement in OS
associated with palbociclib plus fulvestrant was maintained with
>6 years of follow-up in patients with HRþ/HER2 ABC, supporting palbociclib plus fulvestrant as a standard of care in these patients
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