University of Florida Health

Moving Average and Autoregressive Processes. Introduction to Fourier Analysis. Spectral Theory and Filtering. Some Large Sample Theory. Estimation of the Mean and Autocorrelations. The Periodogram, Estimated Spectrum. Parameter Estimation. Regression, Trend, and Seasonality. Unit Root and Explosive Time Series. Bibliography. Index.

Colored photographic pictures that varied widely across the affective dimensions of valence (pleasant-unpleasant) and arousal (excited-calm) were each viewed for a 6-s period while facial electromyographic (zygomatic and corrugator muscle activity) and visceral (heart rate and skin conductance) reactions were measured. Judgments relating to pleasure, arousal, interest, and emotional state were measured, as was choice viewing time. Significant covariation was obtained between (a) facial expression and affective valence judgments and (b) skin conductance magnitude and arousal ratings. Interest ratings and viewing time were also associated with arousal. Although differences due to the subject's gender and cognitive style were obtained, affective responses were largely independent of the personality factors investigated. Response specificity, particularly facial expressiveness, supported the view that specific affects have unique patterns of reactivity. The consistency of the dimensional relationships between evaluative judgments (i.e., pleasure and arousal) and physiological response, however, emphasizes that emotion is fundamentally organized by these motivational parameters.

BACKGROUND: Patients who have residual invasive breast cancer after receiving neoadjuvant chemotherapy plus human epidermal growth factor receptor 2 (HER2)-targeted therapy have a worse prognosis than those who have no residual cancer. Trastuzumab emtansine (T-DM1), an antibody-drug conjugate of trastuzumab and the cytotoxic agent emtansine (DM1), a maytansine derivative and microtubule inhibitor, provides benefit in patients with metastatic breast cancer that was previously treated with chemotherapy plus HER2-targeted therapy. METHODS: We conducted a phase 3, open-label trial involving patients with HER2-positive early breast cancer who were found to have residual invasive disease in the breast or axilla at surgery after receiving neoadjuvant therapy containing a taxane (with or without anthracycline) and trastuzumab. Patients were randomly assigned to receive adjuvant T-DM1 or trastuzumab for 14 cycles. The primary end point was invasive disease-free survival (defined as freedom from ipsilateral invasive breast tumor recurrence, ipsilateral locoregional invasive breast cancer recurrence, contralateral invasive breast cancer, distant recurrence, or death from any cause). RESULTS: At the interim analysis, among 1486 randomly assigned patients (743 in the T-DM1 group and 743 in the trastuzumab group), invasive disease or death had occurred in 91 patients in the T-DM1 group (12.2%) and 165 patients in the trastuzumab group (22.2%). The estimated percentage of patients who were free of invasive disease at 3 years was 88.3% in the T-DM1 group and 77.0% in the trastuzumab group. Invasive disease-free survival was significantly higher in the T-DM1 group than in the trastuzumab group (hazard ratio for invasive disease or death, 0.50; 95% confidence interval, 0.39 to 0.64; P<0.001). Distant recurrence as the first invasive-disease event occurred in 10.5% of patients in the T-DM1 group and 15.9% of those in the trastuzumab group. The safety data were consistent with the known safety profile of T-DM1, with more adverse events associated with T-DM1 than with trastuzumab alone. CONCLUSIONS: Among patients with HER2-positive early breast cancer who had residual invasive disease after completion of neoadjuvant therapy, the risk of recurrence of invasive breast cancer or death was 50% lower with adjuvant T-DM1 than with trastuzumab alone. (Funded by F. Hoffmann-La Roche/Genentech; KATHERINE ClinicalTrials.gov number, NCT01772472 .).

ENNEKING, WILLIAM F. M.D.; SPANIER, SUZANNE S. M.D.; GOODMAN, MARK A. M.D.Editor(s): SMITH, CHADWICK F. M.D.; MONSEN, DAVID C. G. M.D. Author Information

Emotions are action dispositions--states of vigilant readiness that vary widely in reported affect, physiology, and behavior. They are driven, however, by only 2 opponent motivational systems, appetitive and aversive--subcortical circuits that mediate reactions to primary reinforcers. Using a large emotional picture library, reliable affective psychophysiologies are shown, defined by the judged valence (appetitive/pleasant or aversive/unpleasant) and arousal of picture percepts. Picture-evoked affects also modulate responses to independently presented startle probe stimuli. In other words, they potentiate startle reflexes during unpleasant pictures and inhibit them during pleasant pictures, and both effects are augmented by high picture arousal. Implications are elucidated for research in basic emotions, psychopathology, and theories of orienting and defense. Conclusions highlight both the approach's constraints and promising paths for future study.

Emotional reactions are organized by underlying motivational states--defensive and appetitive--that have evolved to promote the survival of individuals and species. Affective responses were measured while participants viewed pictures with varied emotional and neutral content. Consistent with the motivational hypothesis, reports of the strongest emotional arousal, largest skin conductance responses, most pronounced cardiac deceleration, and greatest modulation of the startle reflex occurred when participants viewed pictures depicting threat, violent death, and erotica. Moreover, reflex modulation and conductance change varied with arousal, whereas facial patterns were content specific. The findings suggest that affective responses serve different functions-mobilization for action, attention, and social communication-and reflect the motivational system that is engaged, its intensity of activation, and the specific emotional context.

IMPORTANCE: The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) provided systematic estimates of incidence, morbidity, and mortality to inform local and international efforts toward reducing cancer burden. OBJECTIVE: To estimate cancer burden and trends globally for 204 countries and territories and by Sociodemographic Index (SDI) quintiles from 2010 to 2019. EVIDENCE REVIEW: The GBD 2019 estimation methods were used to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life years (DALYs) in 2019 and over the past decade. Estimates are also provided by quintiles of the SDI, a composite measure of educational attainment, income per capita, and total fertility rate for those younger than 25 years. Estimates include 95% uncertainty intervals (UIs). FINDINGS: In 2019, there were an estimated 23.6 million (95% UI, 22.2-24.9 million) new cancer cases (17.2 million when excluding nonmelanoma skin cancer) and 10.0 million (95% UI, 9.36-10.6 million) cancer deaths globally, with an estimated 250 million (235-264 million) DALYs due to cancer. Since 2010, these represented a 26.3% (95% UI, 20.3%-32.3%) increase in new cases, a 20.9% (95% UI, 14.2%-27.6%) increase in deaths, and a 16.0% (95% UI, 9.3%-22.8%) increase in DALYs. Among 22 groups of diseases and injuries in the GBD 2019 study, cancer was second only to cardiovascular diseases for the number of deaths, years of life lost, and DALYs globally in 2019. Cancer burden differed across SDI quintiles. The proportion of years lived with disability that contributed to DALYs increased with SDI, ranging from 1.4% (1.1%-1.8%) in the low SDI quintile to 5.7% (4.2%-7.1%) in the high SDI quintile. While the high SDI quintile had the highest number of new cases in 2019, the middle SDI quintile had the highest number of cancer deaths and DALYs. From 2010 to 2019, the largest percentage increase in the numbers of cases and deaths occurred in the low and low-middle SDI quintiles. CONCLUSIONS AND RELEVANCE: The results of this systematic analysis suggest that the global burden of cancer is substantial and growing, with burden differing by SDI. These results provide comprehensive and comparable estimates that can potentially inform efforts toward equitable cancer control around the world.

Increasingly, consumers engage in health information seeking via the Internet. Taking a communication perspective, this review argues why public health professionals should be concerned about the topic, considers potential benefits, synthesizes quality concerns, identifies criteria for evaluating online health information and critiques the literature. More than 70 000 websites disseminate health information; in excess of 50 million people seek health information online, with likely consequences for the health care system. The Internet offers widespread access to health information, and the advantages of interactivity, information tailoring and anonymity. However, access is inequitable and use is hindered further by navigational challenges due to numerous design features (e.g. disorganization, technical language and lack of permanence). Increasingly, critics question the quality of online health information; limited research indicates that much is inaccurate. Meager information-evaluation skills add to consumers' vulnerability, and reinforce the need for quality standards and widespread criteria for evaluating health information. Extant literature can be characterized as speculative, comprised of basic 'how to' presentations, with little empirical research. Future research needs to address the Internet as part of the larger health communication system and take advantage of incorporating extant communication concepts. Not only should research focus on the 'net-gap' and information quality, it also should address the inherently communicative and transactional quality of Internet use. Both interpersonal and mass communication concepts open avenues for investigation and understanding the influence of the Internet on health beliefs and behaviors, health care, medical outcomes, and the health care system.

Chronic hepatitis C (non-A, non-B hepatitis) is a common and often progressive viral liver disease. To assess the efficacy of therapy with the antiviral agent interferon alfa, we randomly assigned 166 patients with chronic hepatitis C to treatment with either 3 million or 1 million units of recombinant interferon alfa three times weekly for 24 weeks, or to no treatment. The probability of normalization or near normalization of the serum alanine aminotransferase levels after six months of interferon therapy was 46 percent in patients treated with 3 million units of interferon (P less than 0.001) and 28 percent in those treated with 1 million units (P less than 0.02), but only 8 percent in untreated patients. The serum alanine aminotransferase level became completely normal in 22 of the 26 patients (85 percent) who responded to treatment with 3 million units of interferon and 9 of the 16 patients (56 percent) who responded to treatment with 1 million units. The patients who received 3 million units of interferon had histologic improvement because of the regression of lobular and periportal inflammation. Relapse within six months after the completion of treatment occurred in 51 percent of the patients treated with 3 million units of interferon and 44 percent of those treated with 1 million units. We conclude that a 24-week course of interferon therapy is effective in controlling disease activity in many patients with hepatitis C, although relapse after the cessation of treatment is common.

Rice is the staple food for over half the world's population. Approximately 480 million metric tons of milled rice is produced annually. China and India alone account for ∼50% of the rice grown and consumed. Rice provides up to 50% of the dietary caloric supply for millions living in poverty in Asia and is, therefore, critical for food security. It is becoming an important food staple in both Latin America and Africa. Record increases in rice production have been observed since the start of the Green Revolution. However, rice remains one of the most protected food commodities in world trade. Rice is a poor source of vitamins and minerals, and losses occur during the milling process. Populations that subsist on rice are at high risk of vitamin and mineral deficiency. Improved technologies to fortify rice have the potential to address these deficiencies and their associated adverse health effects. With the rice industry consolidating in many countries, there are opportunities to fortify a significant share of rice for distribution or for use in government safety net programs that target those most in need, especially women and children. Multisectoral approaches are needed for the promotion and implementation of rice fortification in countries.

BACKGROUND: The authors designed a prospective longitudinal study to investigate the hypothesis that advancing age is a risk factor for postoperative cognitive dysfunction (POCD) after major noncardiac surgery and the impact of POCD on mortality in the first year after surgery. METHODS: One thousand sixty-four patients aged 18 yr or older completed neuropsychological tests before surgery, at hospital discharge, and 3 months after surgery. Patients were categorized as young (18-39 yr), middle-aged (40-59 yr), or elderly (60 yr or older). At 1 yr after surgery, patients were contacted to determine their survival status. RESULTS: At hospital discharge, POCD was present in 117 (36.6%) young, 112 (30.4%) middle-aged, and 138 (41.4%) elderly patients. There was a significant difference between all age groups and the age-matched control subjects (P < 0.001). At 3 months after surgery, POCD was present in 16 (5.7%) young, 19 (5.6%) middle-aged, and 39 (12.7%) elderly patients. At this time point, the prevalence of cognitive dysfunction was similar between age-matched controls and young and middle-aged patients but significantly higher in elderly patients compared to elderly control subjects (P < 0.001). The independent risk factors for POCD at 3 months after surgery were increasing age, lower educational level, a history of previous cerebral vascular accident with no residual impairment, and POCD at hospital discharge. Patients with POCD at hospital discharge were more likely to die in the first 3 months after surgery (P = 0.02). Likewise, patients who had POCD at both hospital discharge and 3 months after surgery were more likely to die in the first year after surgery (P = 0.02). CONCLUSIONS: Cognitive dysfunction is common in adult patients of all ages at hospital discharge after major noncardiac surgery, but only the elderly (aged 60 yr or older) are at significant risk for long-term cognitive problems. Patients with POCD are at an increased risk of death in the first year after surgery.

One of the puzzles regarding initial public offerings (IPOs) is that issuers rarely get upset about leaving substantial amounts of money on the table, defined as the number of shares sold times the difference between the first-day closing market price and the offer price. The average IPO leaves $9.1 million on the table. This number is approximately twice as large as the fees paid to investment bankers and represents a substantial indirect cost to the issuing firm. We present a prospect theory model that focuses on the covariance of the money left on the table and wealth changes. Our reasoning also provides an explanation for a second puzzling pattern: much more money is left on the table following recent market rises than after market falls. This results in an explanation of hot issue markets. We also offer a new explanation for why IPOs are underpriced.

BACKGROUND: The role of walking, as compared with vigorous exercise, in the prevention of cardiovascular disease remains controversial. Data for women who are members of minority racial or ethnic groups are particularly sparse. METHODS: We prospectively examined the total physical-activity score, walking, vigorous exercise, and hours spent sitting as predictors of the incidence of coronary events and total cardiovascular events among 73,743 postmenopausal women 50 to 79 years of age in the Women's Health Initiative Observational Study. At base line, participants were free of diagnosed cardiovascular disease and cancer, and all participants completed detailed questionnaires about physical activity. We documented 345 newly diagnosed cases of coronary heart disease and 1551 total cardiovascular events. RESULTS: An increasing physical-activity score had a strong, graded, inverse association with the risk of both coronary events and total cardiovascular events. There were similar findings among white women and black women. Women in increasing quintiles of energy expenditure measured in metabolic equivalents (the MET score) had age-adjusted relative risks of coronary events of 1.00, 0.73, 0.69, 0.68, and 0.47, respectively (P for trend, <0.001). In multivariate analyses, the inverse gradient between the total MET score and the risk of cardiovascular events remained strong (adjusted relative risks for increasing quintiles, 1.00, 0.89, 0.81, 0.78, and 0.72, respectively; P for trend <0.001). Walking and vigorous exercise were associated with similar risk reductions, and the results did not vary substantially according to race, age, or body-mass index. A brisker walking pace and fewer hours spent sitting daily also predicted lower risk. CONCLUSIONS: These prospective data indicate that both walking and vigorous exercise are associated with substantial reductions in the incidence of cardiovascular events among postmenopausal women, irrespective of race or ethnic group, age, and body-mass index. Prolonged sitting predicts increased cardiovascular risk.

Cells constantly generate reactive oxygen species (ROS) during aerobic metabolism. The ROS generation plays an important protective and functional role in the immune system. The cell is armed with a powerful antioxidant defense system to combat excessive production of ROS. Oxidative stress occurs in cells when the generation of ROS overwhelms the cells' natural antioxidant defenses. ROS and the oxidative damage are thought to play an important role in many human diseases including cancer, atherosclerosis, other neurodegenerative diseases and diabetes. Thus, establishing their precise role requires the ability to measure ROS accurately and the oxidative damage that they cause. There are many methods for measuring free radical production in cells. The most straightforward techniques use cell permeable fluorescent and chemiluminescent probes. 2'-7'-Dichlorodihydrofluorescein diacetate (DCFH-DA) is one of the most widely used techniques for directly measuring the redox state of a cell. It has several advantages over other techniques developed. It is very easy to use, extremely sensitive to changes in the redox state of a cell, inexpensive and can be used to follow changes in ROS over time.

This article reviews the literature from 1996 to 2007 to update the 1998 Brestan and Eyberg report on evidence-based psychosocial treatments (EBTs) for child and adolescent disruptive behavior, including oppositional defiant disorder and conduct disorder. Studies were evaluated using criteria for EBTs developed by the task force on promotion and dissemination of psychological procedures (Chambless et al., 1998 Chambless , D. L. , Baker , M. J. , Baucom , D. , Beutler , L. E. , Calhoun , K. S. , et al. . ( 1998 ). Update on empirically validated therapies: II . The Clinical Psychologist , 51 , 3 – 16 . [Google Scholar]; Chambless et al., 1996 Chambless , D. L. , Sanderson , W. C. , Shoham , V. , Bennet Johnson , S. , Pope , K. S. , et al. . ( 1996 ). An update on empirically validated therapies . Clinical Psychologist , 49 , 5 – 18 . [Google Scholar]). Sixteen EBTs were identified in this review, up from 12 in the earlier report, and 9 “possibly efficacious” treatments (Chambless & Hollon, 1998 Chambless , D. L. , & Hollon , S. D. ( 1998 ). Defining empirically supported therapies . Journal of Consulting and Clinical Psychology , 66 ( 1 ), 7 – 18 .[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]) were identified as well. This article describes the EBTs and their evidence base and covers research on moderators and mediators of treatment outcome, as well as the clinical representativeness and generalizability of the studies. Best practice recommendations from the current evidence base also are offered, as well as calls for future research that increases understanding of the moderators and mechanisms of change for children and adolescents with disruptive behavior disorders.

These recommendations provide a data-supported approach to establishing guidelines. They are based on the following: (1) a

This chapter is primarily devoted to experiments that compare 2 treatments with respect to an outcome measure. Six design scenarios are discussed: (a) completely randomized designs (treatments are assigned completely at random); (b) randomized block designs (experimental units are subdivided into blocks of like subjects, with one subject in each block randomly assigned to each treatment); (c) stratified designs (subjects are categorized into subpopulations called strata, and within each stratum, a completely randomized design is conducted); (d) crossover designs (each subject gets both treatments, but order is completely at random); (e) 2 x 2 factorial designs [design can be in any of the formats (a)-(d) but there are 4 not 2 treatments representing 2 types of treatment interventions, each with 2 levels]; and (f) randomized designs with "random" effects. This is much like the stratified design, except there is only 1 sample, at least conceptually, from the strata. Examples might be litters of laboratory animals, surgical practices, or batches of a therapeutic agent. The desire is to make inferences about treatments in the population as a whole, not just in the strata that were actually sampled.

Reviews psychosocial interventions for child and adolescent conduct problems, including oppositional defiant disorder and conduct disorder, to identify empirically supported treatments. Eighty-two controlled research studies were evaluated using the criteria developed by the Division 12 (Clinical Psychology) Task Force on Promotion and Dissemination of Psychological Procedures. The 82 studies were also examined for specific participant, treatment, and methodological characteristics to describe the treatment literature for child and adolescent conduct problems. Two interventions were identified that met the stringent criteria for well-established treatments: videotape modeling parent training program (Spaccarelli, Cotler, & Penman, 1992; Webster-Stratton, 1984, 1994) and parent-training programs based on Patterson and Gullion's (1968) manual Living With Children (Alexander & Parsons, 1973; Bernal, Klinnert, & Schultz, 1980; Wiltz & Patterson, 1974). Twenty of the 82 studies were identified as supporting the efficacy of probably efficacious treatments.

Neural stem cells from neurogenic regions of mammalian CNS are clonogenic in an in vitro culture system exploiting serum and anchorage withdrawal in medium supplemented with methyl cellulose and the pleiotropic growth factors EGF, FGF2, and insulin. The aim of this study was to test whether cortical glial tumors contain stem-like cells capable, under this culture system, of forming clones showing intraclonal heterogeneity in the expression of neural lineage-specific proteins. The high frequencies of clone-forming cells (about 0.1-10 x 10(-3)) in clinical tumor specimens with mutated p53, and in neurogenic regions of normal human CNS, suggest that the ability to form clones in this culture system is induced epigenetically. RT-PCR analyses of populations of normal brain- and tumor-derived sister clones revealed transcripts for nestin, neuron-specific enolase, and glial fibrillary acidic protein (GFAP). However, the tumor-derived clones were different from clones derived from neurogenic regions of normal brain in the expression of transcripts specific for genes associated with neural cell fate determination via the Notch-signaling pathway (Delta and Jagged), and cell survival at G2 or mitotic phases (Survivin). Moreover, the individual glioma-derived clones contain cells immunopositive separately for GFAP or neuronal beta-III tubulin, as well as single cells coexpressing both glial and neuronal markers. The data suggest that the latent critical stem cell characteristics can be epigenetically induced by growth conditions not only in cells from neurogenic regions of normal CNS but also in cells from cortical glial tumors. Moreover, tumor stem-like cells with genetically defective responses to epigenetic stimuli may contribute to gliomagenesis and the developmental pathological heterogeneity of glial tumors.

OBJECTIVES: To determine the effects of cognitive training on cognitive abilities and everyday function over 10 years. DESIGN: Ten-year follow-up of a randomized, controlled single-blind trial (Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE)) with three intervention groups and a no-contact control group. SETTING: Six U.S. cities. PARTICIPANTS: A volunteer sample of 2,832 persons (mean baseline age 73.6; 26% African American) living independently. INTERVENTION: Ten training sessions for memory, reasoning, or speed of processing; four sessions of booster training 11 and 35 months after initial training. MEASUREMENTS: Objectively measured cognitive abilities and self-reported and performance-based measures of everyday function. RESULTS: Participants in each intervention group reported less difficulty with instrumental activities of daily living (IADLs) (memory: effect size = 0.48, 99% confidence interval (CI) = 0.12-0.84; reasoning: effect size = 0.38, 99% CI = 0.02-0.74; speed of processing: effect size = 0.36, 99% CI = 0.01-0.72). At a mean age of 82, approximately 60% of trained participants, versus 50% of controls (P < .05), were at or above their baseline level of self-reported IADL function at 10 years. The reasoning and speed-of-processing interventions maintained their effects on their targeted cognitive abilities at 10 years (reasoning: effect size = 0.23, 99% CI = 0.09-0.38; speed of processing: effect size = 0.66, 99% CI = 0.43-0.88). Memory training effects were no longer maintained for memory performance. Booster training produced additional and durable improvement for the reasoning intervention for reasoning performance (effect size = 0.21, 99% CI = 0.01-0.41) and the speed-of-processing intervention for speed-of-processing performance (effect size = 0.62, 99% CI = 0.31-0.93). CONCLUSION: Each Advanced Cognitive Training for Independent and Vital Elderly cognitive intervention resulted in less decline in self-reported IADL compared with the control group. Reasoning and speed, but not memory, training resulted in improved targeted cognitive abilities for 10 years.