Approximately Strategyproof Tournament Rules in the Probabilistic Setting

We consider the manipulability of tournament rules which map the results of $\binom{n}{2}$ pairwise matches and select a winner. Prior work designs simple tournament rules such that no pair of teams can manipulate the outcome of their match to improve their probability of winning by more than $1/3$, and this is the best possible among any Condorcet-consistent tournament rule (which selects an undefeated team whenever one exists) [Schneider et al., 2017, Schvartzman et al., 2020]. These lower bounds require the manipulators to know precisely the outcome of all future matches. We take a beyond worst-case view and instead consider tournaments which are "close to uniform": the outcome of all matches are independent, and no team is believed to win any match with probability exceeding $1/2+\varepsilon$. We show that Randomized Single Elimination Bracket [Schneider et al., 2017] and a new tournament rule we term Randomized Death Match have the property that no pair of teams can manipulate the outcome of their match to improve their probability of winning by more than $\varepsilon/3 + 2\varepsilon^2/3$, for all $\varepsilon$, and this is the best possible among any Condorcet-consistent tournament rule. Our main technical contribution is a recursive framework to analyze the manipulability of certain forms of tournament rules. In addition to our main results, this view helps streamline previous analysis of Randomized Single Elimination Bracket, and may be of independent interest.Comment: 18 pages, 0 figures, ITCS 202

Pediatric High Risk Leukemia — Molecular Insights

Acute leukemia comprises of 31% of all cancers in children making it the most common childhood malignancy. Significant strides have been made in treatment, partly through risk stratification and intensified therapy. A number of subtypes remain at high risk for relapse and poor outcome, despite current therapies. Here we describe risk stratification and molecular diagnosis used to identify high risk leukemias and guide treatment. Specific cytogenetic alterations that contribute to high risk B and T cell acute lymphoblastic leukemia (ALL), as well as infant leukemia are discussed. Particular attention is given to genetic alterations in IKZF1, CRLF2, and JAK, that have been identified by whole genome sequencing and recently associated with Ph-like ALL. Ongoing studies of disease mechanisms and challenges in developing pre-clinical patient-derived xenograft models to evaluate therapies are discussed

Pregnancy and Infant Development (PRIDE)—a preliminary observational study of maternal adversity and infant development

Background Children from socioeconomically disadvantaged families have a markedly elevated risk for impaired cognitive and social-emotional development. Children in poverty experience have a high risk for developmental delays. Poverty engenders disproportionate exposure to psychological adversity which may contribute to impaired offspring development; however the effect may be mitigated by social support and other aspects of resilience. Our objective was to determine the association between maternal stress, adversity and social support and early infant neurobehavior and child behavior at two and three years. Methods We conducted a longitudinal mother-infant cohort study nested within a regional home visiting program in Cincinnati, Ohio. Four home study visits were completed to collect measures of maternal stress, adversity and social support and infant and child behavior. A measure of infant neurobehavior (‘high-arousal’ infant) was derived from the NICU Network Neurobehavioral Scale (NNNS) at 1 month and externalizing and internalizing symptoms were measured by the Child Behavior Checklist (CBCL) at 24 and 36 months. Linear and logistic regression identified associations between maternal risk/protective factors and infant and child behavioral measures. We used stratification and multiplicative interaction terms to examine potential interactions. Results We enrolled n = 55 pregnant mothers and follow 53 mother–offspring dyads at 1 month, 40 dyads at 24 months and 27 dyads at 36 months. Maternal adversity and protective factors were not associated with neurobehavior at one month. However, maternal depression and measures of distress in pregnancy were significantly associated with internalizing and externalizing symptoms at 24 and 36 months. Conclusions This pilot study established the feasibility of conducting longitudinal research within a community intervention program. In addition, although there were no statistically significant associations between maternal psychosocial factors in pregnancy and infant neurobehavior, there were several associations at 24 months, primarily internalizing symptoms, which persisted through 36 months. Future work will replicate findings within a larger study as well as explore mediators and modifiers of these associations

Social Determinants of Health in People Living with Psychiatric Disorders: The Role of Pharmacists.

INTRODUCTION: Social determinants of health (SDOH) affect outcomes of people living with psychiatric disorders, including substance use disorders. As experts in medication optimization, pharmacists play a vital role in identifying and addressing medication-related problems associated with SDOH. However, there is a paucity of literature on how pharmacists can be part of the solution. OBJECTIVE: The purpose of this article is to provide a narrative review and commentary on the intersection between SDOH, medication-related outcomes in people living with psychiatric disorders, and the role of pharmacists in addressing them. METHOD: The American Association of Psychiatric Pharmacists appointed an expert panel to research the issue, identify barriers, and develop a framework for including pharmacists in addressing medication therapy problems associated with SDOH in people with psychiatric disorders. The panel used Healthy People 2030 as the framework and sought input from public health officials to propose solutions for their commentary. RESULTS: We identified potential connections between SDOH and their impact on medication use in people with psychiatric disorders. We provide examples of how comprehensive medication management can afford opportunities for pharmacists to mitigate medication-related problems associated with SDOH. CONCLUSION: Public health officials should be aware of the vital role that pharmacists play in addressing medication therapy problems associated with SDOH to improve health outcomes and to incorporate them in health promotion programs

Overexpression of a Prefoldin β subunit gene reduces biomass recalcitrance in the bioenergy crop Populus.

Prefoldin (PFD) is a group II chaperonin that is ubiquitously present in the eukaryotic kingdom. Six subunits (PFD1-6) form a jellyfish-like heterohexameric PFD complex and function in protein folding and cytoskeleton organization. However, little is known about its function in plant cell wall-related processes. Here, we report the functional characterization of a PFD gene from Populus deltoides, designated as PdPFD2.2. There are two copies of PFD2 in Populus, and PdPFD2.2 was ubiquitously expressed with high transcript abundance in the cambial region. PdPFD2.2 can physically interact with DELLA protein RGA1_8g, and its subcellular localization is affected by the interaction. In P. deltoides transgenic plants overexpressing PdPFD2.2, the lignin syringyl/guaiacyl ratio was increased, but cellulose content and crystallinity index were unchanged. In addition, the total released sugar (glucose and xylose) amounts were increased by 7.6% and 6.1%, respectively, in two transgenic lines. Transcriptomic and metabolomic analyses revealed that secondary metabolic pathways, including lignin and flavonoid biosynthesis, were affected by overexpressing PdPFD2.2. A total of eight hub transcription factors (TFs) were identified based on TF binding sites of differentially expressed genes in Populus transgenic plants overexpressing PdPFD2.2. In addition, several known cell wall-related TFs, such as MYB3, MYB4, MYB7, TT8 and XND1, were affected by overexpression of PdPFD2.2. These results suggest that overexpression of PdPFD2.2 can reduce biomass recalcitrance and PdPFD2.2 is a promising target for genetic engineering to improve feedstock characteristics to enhance biofuel conversion and reduce the cost of lignocellulosic biofuel production

Cyanidin-3-Glucoside inhibits ethanol-induced invasion of breast cancer cells overexpressing ErbB2

<p>Abstract</p> <p>Background</p> <p>Ethanol is a tumor promoter. Both epidemiological and experimental studies suggest that ethanol may enhance the metastasis of breast cancer cells. We have previously demonstrated that ethanol increased the migration/invasion of breast cancer cells expressing high levels of ErbB2. Amplification of ErbB2 is found in 20-30% of breast cancer patients and is associated with poor prognosis. We sought to identify agents that can prevent or ameliorate ethanol-induced invasion of breast cancer cells. Cyanidin-3-glucoside (C3G), an anthocyanin present in many vegetables and fruits, is a potent natural antioxidant. Ethanol exposure causes the accumulation of intracellular reactive oxygen species (ROS). This study evaluated the effect of C3G on ethanol-induced breast cancer cell migration/invasion.</p> <p>Results</p> <p>C3G attenuated ethanol-induced migration/invasion of breast cancer cells expressing high levels of ErbB2 (BT474, MDA-MB231 and MCF7^ErbB2) in a concentration dependent manner. C3G decreased ethanol-mediated cell adhesion to the extracellular matrix (ECM) as well as the amount of focal adhesions and the formation of lamellipodial protrusion. It inhibited ethanol-stimulated phosphorylation of ErbB2, cSrc, FAK and p130^Cas, as well as interactions among these proteins. C3G abolished ethanol-mediated p130^Cas/JNK interaction.</p> <p>Conclusions</p> <p>C3G blocks ethanol-induced activation of the ErbB2/cSrc/FAK pathway which is necessary for cell migration/invasion. C3G may be beneficial in preventing/reducing ethanol-induced breast cancer metastasis.</p

SAHA Enhances Synaptic Function and Plasticity In Vitro but Has Limited Brain Availability In Vivo and Does Not Impact Cognition

Suberoylanilide hydroxamic acid (SAHA) is an inhibitor of histone deacetylases (HDACs) used for the treatment of cutaneous T cell lymphoma (CTCL) and under consideration for other indications. In vivo studies suggest reducing HDAC function can enhance synaptic function and memory, raising the possibility that SAHA treatment could have neurological benefits. We first examined the impacts of SAHA on synaptic function in vitro using rat organotypic hippocampal brain slices. Following several days of SAHA treatment, basal excitatory but not inhibitory synaptic function was enhanced. Presynaptic release probability and intrinsic neuronal excitability were unaffected suggesting SAHA treatment selectively enhanced postsynaptic excitatory function. In addition, long-term potentiation (LTP) of excitatory synapses was augmented, while long-term depression (LTD) was impaired in SAHA treated slices. Despite the in vitro synaptic enhancements, in vivo SAHA treatment did not rescue memory deficits in the Tg2576 mouse model of Alzheimer’s disease (AD). Along with the lack of behavioral impact, pharmacokinetic analysis indicated poor brain availability of SAHA. Broader assessment of in vivo SAHA treatment using high-content phenotypic characterization of C57Bl6 mice failed to demonstrate significant behavioral effects of up to 150 mg/kg SAHA following either acute or chronic injections. Potentially explaining the low brain exposure and lack of behavioral impacts, SAHA was found to be a substrate of the blood brain barrier (BBB) efflux transporters Pgp and Bcrp1. Thus while our in vitro data show that HDAC inhibition can enhance excitatory synaptic strength and potentiation, our in vivo data suggests limited brain availability may contribute to the lack of behavioral impact of SAHA following peripheral delivery. These results do not predict CNS effects of SAHA during clinical use and also emphasize the importance of analyzing brain drug levels when interpreting preclinical behavioral pharmacology