341 research outputs found
Instrumentation design study for testing a hypersonic ramjet engine on the x-15 a-2. volume 2- preliminary design of in-flight thrust/drag measuring device
Inflight thrust and drag measuring device for hypersonic ramjet engine on X-15A-2 aircraf
On the Permissibility of Homicidal Violence: Perspectives from Former U.S. White Supremacists
Drawing upon in-depth life-history interviews with 91 North American-based former white supremacists, we examine how participants perceive homicidal violence as either an appropriate or inappropriate political strategy. Based on the current findings, participants considered homicidal violence as largely inappropriate due to moral concerns and its politically ineffective nature but also discussed how homicidal violence could be an appropriate defensive measure in RAHOWA (Racial Holy War) or through divine mandate. Capturing how white supremacists frame the permissibility of homicidal violence is a step toward better understanding the āupper limitā or thresholds for violence among members who are trying to construct and negotiate a collective identity that involves violent and aggressive worldviews
PROTOCOL: The Effects of Medical Cannabis on Pain and Quality of Life in Individuals with Parkinsonās Disease and/or Chronic Pain
Background: The opioid epidemic has led medical professionals to research alternative methods of pain reduction. There is limited evidence concerning the usage of medical cannabis and its effect on the symptoms associated with Parkinsonās disease and/or reduction of chronic pain. Pain is subjective and neurologically derived, therefore, an association of quality of life differentiation upon individuals with chronic illnesses such as Parkinsonās disease and chronic pain can add to the research of whether medical cannabis is an appropriate alternative treatment to influence pain perception.
Objective: The aim of this study is to identify a correlation between medical cannabis and Parkinsonās disease and/or Chronic pain.
Design: This is a descriptive design study carried out through means of an electronic survey. Paper copies of the survey will also be made available for participants who prefer a paper copy.
Setting: The participants will be obtained from customers that shop at Ethos Cannabis Dispensary in Wilkes Barre, Pennsylvania. Analysis will be performed at Misericordia University in Dallas, Pennsylvania.
Participants: We hope to obtain 100 participants to complete our survey that are current prescription medical cannabis users and have been diagnosed with Parkinsonās disease and/or Chronic pain.
Measurements: The primary outcome measures included in our survey are the LISAT-11 and the Wong-Baker Pain Faces Scale. The LISAT-11 is a quality of life questionnaire and the Wong-Baker Pain Faces Scale is a pain questionnaire. Participants will be asked to rank their current quality of life using medical cannabis as well as their pain perceptions both before and after medical cannabis usage.
Limitations: Limitations include a small sample size of participants to complete the survey and knowledge of any other means of pain reduction the individual may be utilizing paired with Medical Cannabis.
Conclusion: This study will describe differences in quality of life and pain perceived by medical cannabis users with Parkinsonās disease and/or Chronic pain at Ethos Dispensary before and after they started using medical cannabis.https://digitalcommons.misericordia.edu/research_posters2021/1008/thumbnail.jp
DNA repair deficiency biomarkers and the 70-gene ultra-high risk signature as predictors of veliparib/carboplatin response in the I-SPY 2 breast cancer trial.
Veliparib combined with carboplatin (VC) was an experimental regimen evaluated in the biomarker-rich neoadjuvant I-SPY 2 trial for breast cancer. VC showed improved efficacy in the triple negative signature. However, not all triple negative patients achieved pathologic complete response and some HR+HER2- patients responded. Pre-specified analysis of five DNA repair deficiency biomarkers (BRCA1/2 germline mutation; PARPi-7, BRCA1ness, and CIN70 expression signatures; and PARP1 protein) was performed on 116 HER2- patients (VC: 72 and concurrent controls: 44). We also evaluated the 70-gene ultra-high risk signature (MP1/2), one of the biomarkers used to define subtype in the trial. We used logistic modeling to assess biomarker performance. Successful biomarkers were combined using a simple voting scheme to refine the 'predicted sensitive' group and Bayesian modeling used to estimate the pathologic complete response rates. BRCA1/2 germline mutation status associated with VC response, but its low prevalence precluded further evaluation. PARPi-7, BRCA1ness, and MP1/2 specifically associated with response in the VC arm but not the control arm. Neither CIN70 nor PARP1 protein specifically predicted VC response. When we combined the PARPi-7 and MP1/2 classifications, the 42% of triple negative patients who were PARPi7-high and MP2 had an estimated pCR rate of 75% in the VC arm. Only 11% of HR+/HER2- patients were PARPi7-high and MP2; but these patients were also more responsive to VC with estimated pathologic complete response rates of 41%. PARPi-7, BRCA1ness and MP1/2 signatures may help refine predictions of VC response, thereby improving patient care
Cyclophosphamide- metabolizing enzyme polymorphisms and survival outcomes after adjuvant chemotherapy for node-positive breast cancer: a retrospective cohort study
Abstract Introduction Cyclophosphamide-based adjuvant chemotherapy is a mainstay of treatment for women with node-positive breast cancer, but is not universally effective in preventing recurrence. Pharmacogenetic variability in drug metabolism is one possible mechanism of treatment failure. We hypothesize that functional single nucleotide polymorphisms (SNPs) in drug metabolizing enzymes (DMEs) that activate (CYPs) or metabolize (GSTs) cyclophosphamide account for some of the observed variability in disease outcomes. Methods We performed a retrospective cohort study of 350 women enrolled in a multicenter, randomized, adjuvant breast cancer chemotherapy trial (ECOG-2190/INT-0121). Subjects in this trial received standard-dose cyclophosphamide, doxorubicin and fluorouracil (CAF), followed by either observation or high-dose cyclophosphamide and thiotepa with stem cell rescue. We used bone marrow stem cell-derived genomic DNA from archival specimens to genotype CYP2B6, CYP2C9, CYP2D6, CYP3A4, CYP3A5, GSTM1, GSTT1, and GSTP1. Cox regression models were computed to determine associations between genotypes (individually or in combination) and disease-free survival (DFS) or overall survival (OS), adjusting for confounding clinical variables. Results In the full multivariable analysis, women with at least one CYP3A4 *1B variant allele had significantly worse DFS than those who were wild-type *1A/*1A (multivariate hazard ratio 2.79; 95% CI 1.52, 5.14). CYP2D6 genotype did not impact this association among patients with estrogen receptor (ER) -positive tumors scheduled to receive tamoxifen. Conclusions These data support the hypothesis that genetic variability in cyclophosphamide metabolism independently impacts outcome from adjuvant chemotherapy for breast cancer
Overall Survival with Palbociclib and Fulvestrant in Advanced Breast Cancer
BACKGROUND
The cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor palbociclib, in combination with fulvestrant therapy, prolongs progression-free survival among patients
with hormone-receptorāpositive, human epidermal growth factor receptor 2
(HER2)ānegative advanced breast cancer. We report the results of a prespecified
analysis of overall survival.
METHODS
We randomly assigned patients with hormone-receptorāpositive, HER2-negative
advanced breast cancer who had progression or relapse during previous endocrine
therapy to receive palbociclib plus fulvestrant or placebo plus fulvestrant. We analyzed overall survival; the effect of palbociclib according to the prespecified
stratification factors of presence or absence of sensitivity to endocrine therapy,
presence or absence of visceral metastatic disease, and menopausal status; the efficacy of subsequent therapies after disease progression; and safety.
RESULTS
Among 521 patients who underwent randomization, the median overall survival
was 34.9 months (95% confidence interval [CI], 28.8 to 40.0) in the palbociclibā
fulvestrant group and 28.0 months (95% CI, 23.6 to 34.6) in the placeboāfulvestrant group (hazard ratio for death, 0.81; 95% CI, 0.64 to 1.03; P=0.09; absolute
difference, 6.9 months). CDK4/6 inhibitor treatment after the completion of the
trial regimen occurred in 16% of the patients in the placeboāfulvestrant group.
Among 410 patients with sensitivity to previous endocrine therapy, the median
overall survival was 39.7 months (95% CI, 34.8 to 45.7) in the palbociclibāfulvestrant group and 29.7 months (95% CI, 23.8 to 37.9) in the placeboāfulvestrant
group (hazard ratio, 0.72; 95% CI, 0.55 to 0.94; absolute difference, 10.0 months).
The median duration of subsequent therapy was similar in the two groups, and
the median time to the receipt of chemotherapy was 17.6 months in the palbociclibā
fulvestrant group, as compared with 8.8 months in the placeboāfulvestrant group
(hazard ratio, 0.58; 95% CI, 0.47 to 0.73; P<0.001). No new safety signals were
observed with 44.8 months of follow-up.
CONCLUSIONS
Among patients with hormone-receptorāpositive, HER2-negative advanced breast
cancer who had sensitivity to previous endocrine therapy, treatment with palbociclibāfulvestrant resulted in longer overall survival than treatment with placeboā
fulvestrant. The differences in overall survival in the entire trial group were not
significant. (Funded by Pfizer; PALOMA-3 ClinicalTrials.gov number, NCT01942135.
A Case for Humans-in-the-Loop: Decisions in the Presence of Erroneous Algorithmic Scores
The increased use of algorithmic predictions in sensitive domains has been
accompanied by both enthusiasm and concern. To understand the opportunities and
risks of these technologies, it is key to study how experts alter their
decisions when using such tools. In this paper, we study the adoption of an
algorithmic tool used to assist child maltreatment hotline screening decisions.
We focus on the question: Are humans capable of identifying cases in which the
machine is wrong, and of overriding those recommendations? We first show that
humans do alter their behavior when the tool is deployed. Then, we show that
humans are less likely to adhere to the machine's recommendation when the score
displayed is an incorrect estimate of risk, even when overriding the
recommendation requires supervisory approval. These results highlight the risks
of full automation and the importance of designing decision pipelines that
provide humans with autonomy.Comment: Accepted at ACM Conference on Human Factors in Computing Systems (ACM
CHI), 202
Genetic risk for schizophrenia and psychosis in Alzheimer disease
Psychotic symptoms, defined as the occurrence of delusions or hallucinations, are frequent in Alzheimer disease (AD), affecting ~40 to 60% of individuals with AD (AD with psychosis (AD+P)). In comparison with AD subjects without psychosis, AD+P subjects have more rapid cognitive decline and poor outcomes. Prior studies have estimated the heritability of psychosis in AD at 61%, but the underlying genetic sources of this risk are not known. We evaluated a Discovery Cohort of 2876 AD subjects with (N=1761) or without psychosis (N=1115). All subjects were genotyped using a custom genotyping array designed to evaluate single-nucleotide polymorphisms (SNPs) with evidence of genetic association with AD+P and include SNPs affecting or putatively affecting risk for schizophrenia and AD. Results were replicated in an independent cohort of 2194 AD subjects with (N=734) or without psychosis (N=1460). We found that AD+P is associated with polygenic risk for a set of novel loci and inversely associated with polygenic risk for schizophrenia. Among the biologic pathways identified by the associations of schizophrenia SNPs with AD+P are endosomal trafficking, autophagy and calcium channel signaling. To the best of our knowledge, these findings provide the first clear demonstration that AD+P is associated with common genetic variation. In addition, they provide an unbiased link between polygenic risk for schizophrenia and a lower risk of psychosis in AD. This provides an opportunity to leverage progress made in identifying the biologic effects of schizophrenia alleles to identify novel mechanisms protecting against more rapid cognitive decline and psychosis risk in AD
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