Conflicting Objectives in Decisions

This book deals with quantitative approaches in making decisions when conflicting objectives are present. This problem is central to many applications of decision analysis, policy analysis, operational research, etc. in a wide range of fields, for example, business, economics, engineering, psychology, and planning. The book surveys different approaches to the same problem area and each approach is discussed in considerable detail so that the coverage of the book is both broad and deep. The problem of conflicting objectives is of paramount importance, both in planned and market economies, and this book represents a cross-cultural mixture of approaches from many countries to the same class of problem

Negative Affect-Associated USV Acoustic Characteristics Predict Future Excessive Alcohol Drinking and Alcohol Avoidance in Male P and NP Rats

BACKGROUND: Negative emotional status and adverse emotional events increase vulnerability to alcohol abuse. Ultrasonic vocalizations (USVs) emitted by rats are a well-established model of emotional status that can reflect positive or negative affective responses in real time. Most USV studies assess counts, yet each USV is a multidimensional data point characterized by several acoustic characteristics that may provide insight into the neurocircuitry underlying emotional response. METHODS: USVs emitted from selectively bred alcohol-naïve and alcohol-experienced alcohol-preferring and nonpreferring rats (P and NP rats) were recorded during 4-hour sessions on alternating days over 4 weeks. Linear mixed modeling (LMM) and linear discriminant analysis (LDA) were applied to USV acoustic characteristics (e.g., frequency, duration, power, and bandwidth) of negative affect (22 to 28 kilohertz [kHz])- and positive (50 to 55 kHz) affect-related USVs. RESULTS: Hundred percent separation between alcohol-naïve P and NP rats was achieved through a linear combination (produced by LDA) of USV acoustic characteristics of 22- to 28-kHz USVs, whereas poor separation (36.5%) was observed for 50- to 55-kHz USVs. 22- to 28-kHz LDA separation was high (87%) between alcohol-experienced P and NP rats, but was poor for 50- to 55-kHz USVs (57.3%). USV mean frequency and duration were the highest weighted characteristics in both the naïve and experienced 22- to 28-kHz LDA representations suggesting that alcohol experience does not alter the representations. LMM analyses of 22- to 28-kHz USV acoustic characteristics matched the LDA results. Poor LDA separation was observed between alcohol-naïve and alcohol-experienced P rats for both 22- to 28-kHz and 50- to 55-kHz USVs. CONCLUSIONS: Advanced statistical analysis of negative affect-associated USV data predicts future behaviors of excessive alcohol drinking and alcohol avoidance in selectively bred rats. USV characteristics across rat lines reveal affect-related motivation to consume alcohol and may predict neural pathways mediating emotional response. Further characterization of these differences could delineate particular neurocircuitry and methods to ameliorate dysregulated emotional states often observed in human alcohol abusers

Vicarious experience affects patients' treatment preferences for depression

Purpose: Depression is common in primary care but often under-treated. Personal experiences with depression can affect adherence to therapy, but the effect of vicarious experience is unstudied. We sought to evaluate the association between a patient's vicarious experiences with depression (those of friends or family) and treatment preferences for depressive symptoms. Methods: We sampled 1054 English and/or Spanish speaking adult subjects from July through December 2008, randomly selected from the 2008 California Behavioral Risk Factor Survey System, regarding depressive symptoms and treatment preferences. We then constructed a unidimensional scale using item analysis that reflects attitudes about antidepressant pharmacotherapy. This became the dependent variable in linear regression analyses to examine the association between vicarious experiences and treatment preferences for depressive symptoms. Results: Our sample was 68% female, 91% white, and 13% Hispanic. Age ranged from 18-94 years. Mean PHQ-9 score was 4.3; 14.5% of respondents had a PHQ-9 score >9.0, consistent with active depressive symptoms. Analyses controlling for current depression symptoms and socio-demographic factors found that in patients both with (coefficient 1.08, p = 0.03) and without (coefficient 0.77, p = 0.03) a personal history of depression, having a vicarious experience (family and friend, respectively) with depression is associated with a more favorable attitude towards antidepressant medications. Conclusions: Patients with vicarious experiences of depression express more acceptance of pharmacotherapy. Conversely, patients lacking vicarious experiences of depression have more negative attitudes towards antidepressants. When discussing treatment with patients, clinicians should inquire about vicarious experiences of depression. This information may identify patients at greater risk for non-adherence and lead to more tailored patient-specific education about treatment

The role of insulin receptor substrate 2 in hypothalamic and β cell function

Insulin receptor substrate 2 (Irs2) plays complex roles in energy homeostasis. We generated mice lacking Irs2 in β cells and a population of hypothalamic neurons (RIPCreIrs2KO), in all neurons (NesCreIrs2KO), and in proopiomelanocortin neurons (POMCCreIrs2KO) to determine the role of Irs2 in the CNS and β cell. RIPCreIrs2KO mice displayed impaired glucose tolerance and reduced β cell mass. Overt diabetes did not ensue, because β cells escaping Cre-mediated recombination progressively populated islets. RIPCreIrs2KO and NesCreIrs2KO mice displayed hyperphagia, obesity, and increased body length, which suggests altered melanocortin action. POMCCreIrs2KO mice did not display this phenotype. RIPCreIrs2KO and NesCreIrs2KO mice retained leptin sensitivity, which suggests that CNS Irs2 pathways are not required for leptin action. NesCreIrs2KO and POMCCreIrs2KO mice did not display reduced β cell mass, but NesCreIrs2KO mice displayed mild abnormalities of glucose homeostasis. RIPCre neurons did not express POMC or neuropeptide Y. Insulin and a melanocortin agonist depolarized RIPCre neurons, whereas leptin was ineffective. Insulin hyperpolarized and leptin depolarized POMC neurons. Our findings demonstrate a critical role for IRS2 in β cell and hypothalamic function and provide insights into the role of RIPCre neurons, a distinct hypothalamic neuronal population, in growth and energy homeostasis

On the multiplicity of the O-star Cyg OB2 #8A and its contribution to the gamma-ray source 3EG J2033+4118

We present the results of an intensive spectroscopic campaign in the optical waveband revealing that Cyg OB2 #8A is an O6 + O5.5 binary system with a period of about 21.9 d. Cyg OB2 #8A is a bright X-ray source, as well as a non-thermal radio emitter. We discuss the binarity of this star in the framework of a campaign devoted to the study of non-thermal emitters, from the radio waveband to gamma-rays. In this context, we attribute the non-thermal radio emission from this star to a population of relativistic electrons, accelerated by the shock of the wind-wind collision. These relativistic electrons could also be responsible for a putative gamma-ray emission through inverse Compton scattering of photospheric UV photons, thus contributing to the yet unidentified EGRET source 3EG J2033+4118.Comment: 8 pages, 4 figures, conference on "The Multiwavelength Approach to Gamma-Ray Sources", to appear in Ap&S

Associations between blood sex steroid concentrations and risk of major adverse cardiovascular events in healthy older women in Australia: a prospective cohort substudy of the ASPREE trial

Background: Blood testosterone concentrations in women decline during the reproductive years and reach a nadir in the seventh decade, after which concentrations increase and are restored to those of reproductive-aged women early in the eighth decade. We aimed to establish the association between the concentration of testosterone in the blood and risk of major adverse cardiovascular events (MACE) and all-cause mortality in healthy older women. Methods: SHOW was a prospective cohort substudy of the longitudinal randomised ASPREE trial. Eligible participants were women aged at least 70 years from Australia with unimpaired cognition, no previous MACE, and a life expectancy of at least 5 years. Participants who were receiving hormonal or steroid therapy were ineligible for inclusion. We measured serum concentrations of sex steroids with liquid chromatography–tandem mass spectrometry and of SHBG with immunoassay. We compared lower concentrations of sex hormones with higher concentrations using four quartiles. Primary endpoints were risk of MACE and all-cause mortality, the associations of which with sex steroid concentrations were assessed using Cox proportional hazards regression that included age, body-mass index, smoking status, alcohol consumption, diabetes, hypertension, dyslipidaemia, impaired renal function, and treatment allocation in the ASPREE trial (aspirin vs placebo). ASPREE is registered with ClinicalTrials.gov, NCT01038583. Findings: Of the 9180 women recruited to the ASPREE trial between March 10, 2010, and Dec 31 2014, 6358 participants provided sufficient biobank samples at baseline and 5535 were included in the final analysis. Median age at entry was 74·0 years (IQR 71·7–77·7). During a median 4·4 years of follow-up (24 553 person-years), 144 (2·6%) women had a first MACE (incidence 5·9 per 1000 person-years). During a median 4·6 years of follow-up (3·8–5·6), 200 women died (7·9 per 1000 person-years). In the fully adjusted models, higher concentrations of testosterone were associated with a lower incidence of MACE (quartile 4 vs quartile 1: hazard ratio 0·57 [95% CI 0·36–0·91]; p=0·02), as were higher concentrations of DHEA (quartile 4 vs quartile 1: 0·61 [0·38–0·97]; p=0·04). For oestrone, a lower risk of MACE was seen for concentrations in quartile 2 only, compared with quartile 1 (0·55 [0·33–0·92]; p=0·02). In fully adjusted models, no association was seen between SHBG and MACE, or between any hormone or SHBG and all-cause mortality. Interpretation: Blood concentrations of testosterone and DHEA above the lowest quartile in older women were associated with a reduced risk of a first-ever MACE. Given that the physiological effects of DHEA are mediated through its steroid metabolites, if the current findings were to be replicated, trials investigating testosterone therapy for the primary prevention of ischaemic cardiovascular disease events in older women would be warranted. Funding: The National Health and Medical Research Council of Australia, US National Institute on Aging, the Victorian Cancer Agency, the Commonwealth Scientific and Industrial Research Organisation, and Monash University

Gauge symmetry and the EMC spin effect

We emphasise the EMC spin effect as a problem of symmetry and discuss the renormalisation of the $C=+1$ axial tensor operators. This involves the generalisation of the Adler-Bell-Jackiw anomaly to each of these operators. We find that the contribution of the axial anomaly to the spin dependent structure function $g_1 (x, Q^2)$ scales at $O(\alpha_s)$. This means that the anomaly can be a large $x$ effect in $g_1$. Finally we discuss the jet signature of the anomaly.Comment: 17 pages, Latex, Cavendish preprint HEP 93/

Future Directions in Parity Violation: From Quarks to the Cosmos

I discuss the prospects for future studies of parity-violating (PV) interactions at low energies and the insights they might provide about open questions in the Standard Model as well as physics that lies beyond it. I cover four types of parity-violating observables: PV electron scattering; PV hadronic interactions; PV correlations in weak decays; and searches for the permanent electric dipole moments of quantum systems.Comment: Talk given at PAVI 06 workshop on parity-violating interactions, Milos, Greece (May, 2006); 10 page

Local Hidden Variables Underpinning of Entanglement and Teleportation

Entangled states whose Wigner functions are non-negative may be viewed as being accounted for by local hidden variables (LHV). Recently, there were studies of Bell's inequality violation (BIQV) for such states in conjunction with the well known theorem of Bell that precludes BIQV for theories that have LHV underpinning. We extend these studies to teleportation which is also based on entanglement. We investigate if, to what extent, and under what conditions may teleportation be accounted for via LHV theory. Our study allows us to expose the role of various quantum requirements. These are, e.g., the uncertainty relation among non-commuting operators, and the no-cloning theorem which forces the complete elimination of the teleported state at its initial port.Comment: 24 pages, 1 figure, accepted Found. Phy

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC)

Head and neck cancers, including those of the lip and oral cavity, nasal cavity, paranasal sinuses, oropharynx, larynx and nasopharynx represent nearly 700,000 new cases and 380,000 deaths worldwide per annum, and account for over 10,000 annual deaths in the United States alone. Improvement in outcomes are needed for patients with recurrent and or metastatic squamous cell carcinoma of the head and neck (HNSCC). In 2016, the US Food and Drug Administration (FDA) granted the first immunotherapeutic approvals - the anti-PD-1 immune checkpoint inhibitors nivolumab and pembrolizumab - for the treatment of patients with recurrent squamous cell carcinoma of the head and neck (HNSCC) that is refractory to platinum-based regimens. The European Commission followed in 2017 with approval of nivolumab for treatment of the same patient population, and shortly thereafter with approval of pembrolizumab monotherapy for the treatment of recurrent or metastatic HNSCC in adults whose tumors express PD-L1 with a 65 50% tumor proportion score and have progressed on or after platinum-containing chemotherapy. Then in 2019, the FDA granted approval for PD-1 inhibition as first-line treatment for patients with metastatic or unresectable, recurrent HNSCC, approving pembrolizumab in combination with platinum and fluorouracil for all patients with HNSCC and pembrolizumab as a single agent for patients with HNSCC whose tumors express a PD-L1 combined positive score 65 1. These approvals marked the first new therapies for these patients since 2006, as well as the first immunotherapeutic approvals in this disease. In light of the introduction of these novel therapies for the treatment of patients with head and neck cancer, The Society for Immunotherapy of Cancer (SITC) formed an expert committee tasked with generating consensus recommendations for emerging immunotherapies, including appropriate patient selection, therapy sequence, response monitoring, adverse event management, and biomarker testing. These consensus guidelines serve as a foundation to assist clinicians' understanding of the role of immunotherapies in this disease setting, and to standardize utilization across the field for patient benefit. Due to country-specific variances in approvals, availability and regulations regarding the discussed agents, this panel focused solely on FDA-approved drugs for the treatment of patients in the U.S