Value of Knowing: Health-Related Behavior Changes following Amyloid PET Results Disclosure in Mild Cognitive Impairment.

BACKGROUND: Growing evidence supports the clinical utility of amyloid PET, however, whether patients at risk for dementia use knowledge of their brain amyloid status to alter their health behaviors remains unclear. OBJECTIVES: To explore the effect of amyloid PET results disclosure on self-reported health behaviors in patients with mild cognitive impairment. DESIGN: Self-reported health behaviors were a secondary outcome of the Return of Amyloid Imaging Scan Results (RAISR) randomized clinical trial of amyloid PET results disclosure for individuals with mild cognitive impairment. SETTING: Academic medical center. PARTICIPANTS: RAISR study participants included 82 patients with mild cognitive impairment who were 92% non-Hispanic white, 59% male, and, on average, 73 ± 8.61 years old with 16.25 ± 2.49 years of education. INTERVENTION: Participants were assigned to a scan group with the opportunity to have an amyloid PET scan and learn their results or to a control group consisting only of a mild cognitive impairment education session and no opportunity for an amyloid PET scan. MEASUREMENTS: A 14-item health behavior questionnaire supplemented with qualitative data from the open-ended text entries to describe "other" health behaviors and follow-up semi-structured interviews. Baseline assessments were conducted prior to group assignment. For the present analysis, 71 participants had available data and scan group participants were divided by amyloid status, creating three groups for comparison: amyloid positive, amyloid negative, and control (no scan). RESULTS: Over 12 months of follow-up, no significant differences were observed in lifestyle, vitamin/supplement use, stress reduction activities, cognitive stimulation, or advance directive completion. Amyloid-negative participants were less likely than controls to consider long-term care insurance (63.6% vs. 89.2%; P = .025), and to endorse behaviors classified as "other" (36.4% vs. 64.9%; P = 0.037). After adjusting for education level, gender, and Mini-Mental State Exam score, logistic regression showed that amyloid-negative patients were 74% less likely than controls to report "other" behaviors (OR = 0.26, 95% CI [0.08, 0.85], P = 0.025), and 78% less likely to consider long-term care insurance (OR= 0.22, 95% CI [0.06, 0.86], P = 0.03). Qualitative analysis of open-ended questionnaire data and supplemental interviews with scan group participants revealed "other" activities to include changes in areas like employment, driving, and residential status, and engagement in other non-medical activities (e.g., pursuing bucket lists). CONCLUSIONS: This exploratory analysis of health-related behavior changes following amyloid PET disclosure suggests that the value of knowing one's brain amyloid status may differ by scan result and encompass actions that focus more on maximizing quality of life than promoting cognitive health.

US Adults' Likelihood to Participate in Dementia Prevention Drug Trials: Results from the National Poll on Healthy Aging.

BACKGROUND: Recruitment to dementia prevention clinical trials is challenging, and participants are not representative of US adults at risk. A better understanding of the general public's interest in dementia prevention research participation is needed to inform future recruitment strategies. OBJECTIVE: To examine US adults' characteristics associated with self-reported likelihood to participate in dementia prevention clinical trials. DESIGN: We conducted a cross-sectional survey using the October 2018 wave of the University of Michigan National Poll on Healthy Aging. SETTING: The National Poll on Healthy Aging is a nationally representative survey of adults using KnowledgePanel (Ipsos Public Affairs LLC), a probability-based panel of the civilian, noninstitutionalized US population. PARTICIPANTS: We analyzed data from 1,028 respondents, ages 50 to 64 years, who completed a web survey module on brain health. MEASUREMENTS: We used logistic regression models to examine associations between sociodemographic and dementia-related factors (e.g., family history) and self-reported likelihood to participate in a dementia prevention clinical trial of a new medicine ("very" or "somewhat likely" vs. "not likely" survey responses). Among respondents not likely to participate, we examined frequency of reasons endorsed for this decision, stratified by age, sex, and race and ethnicity. RESULTS: Of the 1,028 respondents, half were female, 68% Non-Hispanic White, 13% Hispanic, and 12% Non-Hispanic Black. Twelve percent of respondents reported being very likely to participate in a dementia prevention trial, 32% somewhat likely, and 56% not likely. Factors associated with higher likelihood to participate were higher perceived risk of dementia [OR, 2.17 (95% CI, 1.61, 2.93)], a positive family history of dementia [OR, 1.75 (95% CI, 1.27, 2.43)], and having discussed dementia prevention with a doctor [OR, 2.20 (95% CI, 1.10, 4.42)]. There were no differences in likelihood to participate by sociodemographic characteristics. Among 570 respondents not likely to participate, 39% said they did not want to be a guinea pig, 23% thought dementia would not affect them, 22% thought there would be too high a chance for harm, 15% indicated study participation would take too much time, and 5% reported fear of learning information about oneself. There were no differences across age, sex, and racial and ethnic groups. CONCLUSIONS: In this study, perceived risk of dementia, family history, and discussion of prevention with a doctor were associated with likelihood to participate in a dementia prevention clinical trial, whereas sociodemographic factors including race and ethnicity were not. Findings suggest that recruitment interventions focused on increasing knowledge of dementia risk and prevention trials and involving healthcare providers may be effective tools to improve enrollment rates, regardless of target community.

Determining the prevalence of tuberculosis in emergency departments in the Eastern Cape region of South Africa and the utility of the World Health Organization tuberculosis screening tool.

BACKGROUND: South Africa (SA) faces a significant tuberculosis (TB) burden complicated by high rates of HIV-TB co-infection. In SA, emergency departments (EDs) play an important role in screening for TB. OBJECTIVES: To determine the prevalence of TB in the ED and the effectiveness of the World Health Organization (WHO) TB screening tool. METHODS: This was a cross-sectional observational study, conducted in the ED at Livingstone Hospital, Port Elizabeth, from 4 June to 15 July 2018. All patients aged >18 years and able to consent were administered the WHO TB screening questions and underwent a point-of-care HIV test and demographic data collection. Patients were followed up for 1 year and tracked in the National Health Laboratory Service database to determine TB status using laboratory testing. RESULTS: Over the study period, 790 patients were enrolled. Overall, 121 patients (15.3%) were TB-positive, with 46 (38.0%) diagnosed after presenting to the ED and 75 (62.0%) with a previous TB history determined by self-report or confirmed laboratory testing. A greater proportion of the TB-positive patients were HIV-positive (49.6%) compared with the TB-negative population (24.8%). TB-positive individuals were more likely to present to the ED with a chief complaint of shortness of breath (SoB) (18.2%) compared with the TB-negative population (10.5%). Overall, the WHO TB screening tool had poor sensitivity (46.5%) and specificity (62.5%) for identifying TB-positive patients in the ED. A multiple logistic regression analysis, controlled for age and sex, showed HIV status (odds ratio (OR) 2.81; p<0.001) and SoB (OR 2.19; p<0.05) to be significant predictors of TB positivity. Adding positive HIV status and a presenting complaint of SoB increased sensitivity to 78.3%. CONCLUSIONS: EDs in SA face a high burden of TB. While WHO screening guidelines identify some of these patients, including routine HIV testing in the ED could significantly affect the number of TB diagnoses made.

EMR documentation of physician-patient communication following genomic counseling for actionable complex disease and pharmacogenomic results.

Genomic risk information for potentially actionable complex diseases and pharmacogenomics communicated through genomic counseling (GC) may motivate physicians and patients to take preventive actions. The Ohio State University-Coriell Personalized Medicine Collaborative is a randomized trial to measure the effects of in-person GC on chronic disease patients provided with multiplex results. Nine personalized genomic risk reports were provided to patients through a web portal, and to physicians via electronic medical record (EMR). Active arm participants (98, 39% female) received GC within 1 month of report viewing; control arm subjects (101, 54% female) could access counseling 3-months post-report viewing. We examined whether GC affected documentation of physician-patient communication by reviewing the first clinical note following the patient's GC visit or report upload to the EMR. Multivariable logistic regression modeling estimated the independent effect of GC on physician-patient communication, as intention to treat (ITT) and per protocol (PP), adjusted for physician educational intervention. Counselees in the active arm had more physician-patient communications than control subjects [ITT, odds ratio (OR): 3.76 (95% confidence interval (CI): 1.38-10.22, p < 0.0094); PP, OR: 5.53 (95% CI: 2.20-13.90, p = 0.0017). In conclusion, GC appreciably affected physician-patient communication following receipt of potentially actionable genomic risk information.

Counselees' Perspectives of Genomic Counseling Following Online Receipt of Multiple Actionable Complex Disease and Pharmacogenomic Results: a Qualitative Research Study.

Genomic applications raise multiple challenges including the optimization of genomic counseling (GC) services as part of the results delivery process. More information on patients' motivations, preferences, and informational needs are essential to guide the development of new, more efficient practice delivery models that capitalize on the existing strengths of a limited genetic counseling workforce. Semi-structured telephone interviews were conducted with a subset of counselees from the Coriell Personalized Medicine Collaborative following online receipt of multiple personalized genomic test reports. Participants previously had either in-person GC (chronic disease cohort, n = 20; mean age 60 years) or telephone GC (community cohort, n = 31; mean age 46.8 years). Transcripts were analyzed using a Grounded Theory framework. Major themes that emerged from the interviews include 1) primary reasons for seeking GC were to clarify results, put results into perspective relative to other health-related concerns, and to receive personalized recommendations; 2) there is need for a more participant driven approach in terms of mode of GC communication (in-person, phone, video), and refining the counseling agenda pre-session; and 3) there was strong interest in the option of follow up GC. By clarifying counselees' expectations, views and desired outcomes, we have uncovered a need for a more participant-driven GC model when potentially actionable genomic results are received online.

The impact of multiplex genetic testing on disease risk perceptions.

This study assessed the effects of multiplex genetic testing on disease risk perceptions among 216 healthy adults. Participants, aged 25-40, were recruited through the Multiplex Initiative, which offered a genetic susceptibility test for eight common diseases. Participants completed baseline telephone and web-based surveys prior to making the testing decision. Three months after the receipt of mailed test results, participants completed a follow-up telephone survey. Risk perceptions for the eight diseases were measured at baseline and follow-up, along with beliefs about genetic causation of those diseases. The main results were: (i) mean risk perceptions were considerably stable from baseline to follow-up; (ii) the best predictors of follow-up risk perceptions were the corresponding baseline perceptions and family history; and (iii) within-individuals, most participants increased or decreased their risk perceptions for specific diseases in concordance with the number of risk markers they carry, their family history and their beliefs about genetic causality of diseases. In conclusion, participants presented a vigilant approach to the interpretation of genetic test results, which provides reassurance with regard to a potential inflation of risk perceptions in the population because of multiplex genetic testing.

Strategic retrieval processing and the impact of knowing when a memory was first created.

Retrieval orientation refers to a process where participants strategically alter how a memory cue is processed in response to different task demands. In the present study we explored whether retrieval orientation is influenced by knowing when an old stimulus was first encoded. Participants completed separate remember/know test blocks for old items from a recent delay (40min) and old items from a remote delay (48h). Manipulations at encoding ensured that performance levels were matched between these two blocks, thus avoiding confounds with differences in retrieval effort. Importantly, a third test block comprised old items from both delays randomly intermixed. As the nature of the old items varies unpredictably in the mixed block, it should not be possibly to adopt a specific retrieval orientation and the mixed block therefore acts as a control condition. Participants saw the words "mixed," "recent" or "remote" prior to each test block. Comparing ERPs from the recent and remote blocks permitted an investigation of whether participants alter their retrieval orientation in response to the specific length of the retention interval. Comparing ERPs from the pure (recent and remote) test blocks to ERPs from the mixed block permitted an investigation of whether delay information per se led to differences in retrieval strategy. Analysis of the ERP data found no differences between the recent and remote blocks. However, ERPs from these pure blocks were significantly less positive than ERPs from the mixed block from 200ms towards the end of the epoch. The findings suggest that the delay information was useful in a general sense and encouraged retrieval strategies distinct from those engaged in the mixed block. We speculate that such strategies might relate to whether or not the retrieval search is specific and constrained and/or whether processes that serve to reinstate the original encoding context are engaged.

The electrophysiological correlates of recent and remote recollection.

Research using event related potentials (ERPs) to explore recognition memory has linked late parietal old/new effects to the recollection of episodic information. In the vast majority of these studies, the retrieval phase immediately follows encoding and consequently, very little is known about the ERP correlates of long term recollection. This is despite the fact that in other areas of the memory literature there is considerable interest in consolidation theories and the way episodic memory changes over time. The present study explored the idea that consolidation and forgetting processes operating over a moderate retention interval can alter the ERP markers of recollection memory. A remember/know test probed memory for stimuli studied either 15 minutes (recent memory) or 1 week (remote memory) prior to the test phase. Results revealed an attenuated late parietal effect for remote compared to recent remember responses, a finding that remained significant even when these recognition judgments were matched for reaction time. Experiments 2a and 2b identified characteristic differences between recent and remote recognition at the behavioural level. The 1 week delay produced an overall decline in recognition confidence and a dramatic loss of episodic detail. These behavioural changes are thought to underlie the ERP effects reported in the first experiment. The results highlight that although the neural basis of memory may exhibit significant changes as the length of the retention interval increases, it is important to consider the extent to which this is a direct effect of time or an indirect effect due to changes in memory quality, such as the amount of detail that can be recollected.

Suppression of Zeeman splitting of the energy levels of exciton-polariton condensates in semiconductor microcavities in an external magnetic field.

A key property of equilibrium exciton-polariton condensates in semiconductor microcavities is the suppression of the Zeeman splitting under a magnetic field. By studying magnetophotoluminescence spectra from a GaAs microcavity, we show experimentally that a similar effect occurs in a nonequilibrium polariton condensate arising from polariton parametric scattering. In this case, the quenching of Zeeman splitting is related to a phase synchronization of spin-up and spin-down polarized polariton condensates caused by a nonlinear coupling via the coherent pump state.

Using Alzheimer's disease as a model for genetic risk disclosure: implications for personal genomics.

Susceptibility testing for common, complex adult-onset diseases is projected to become more commonplace as the rapid pace of genomic discoveries continues, and evidence regarding the potential benefits and harms of such testing is needed to inform medical practice and health policy. Apolipoprotein E (APOE) testing for risk of Alzheimer's disease (AD) provides a paradigm in which to examine the process and impact of disclosing genetic susceptibility for a prevalent, severe and incurable neurological condition. This review summarizes findings from a series of multi-site randomized clinical trials examining psychological and behavioral responses to various methods of genetic risk assessment for AD using APOE disclosure. We discuss challenges involved in disease risk estimation and communication and the extent to which participants comprehend and perceive utility in their genetic risk information. Findings on the psychological impact of test results are presented (e.g. distress), along with data on participants' health behavior and insurance purchasing responses (e.g. long-term care). Finally, we report comparisons of the safety and efficacy of intensive genetic counseling approaches to briefer models that emphasize streamlined processes and educational materials. The implications of these findings for the emerging field of personal genomics are discussed, with directions identified for future research.

Mild cognitive impairment in clinical care: a survey of American Academy of Neurology members.

OBJECTIVE: To assess how neurologists view mild cognitive impairment (MCI) as a clinical diagnosis and how they treat patients with mild cognitive symptoms. METHODS: Members of the American Academy of Neurology with an aging, dementia, or behavioral neurology practice focus were surveyed by self-administered questionnaire. RESULTS: Survey respondents were 420 providers (response rate 48%), and 88% reported at least monthly encounters with patients experiencing mild cognitive symptoms. Most respondents recognize MCI as a clinical diagnosis (90%) and use its diagnostic code for billing purposes (70%). When seeing these patients, most respondents routinely provide counseling on physical (78%) and mental exercise (75%) and communicate about dementia risk (63%); fewer provide information on support services (27%) or a written summary of findings (15%). Most (70%) prescribe cholinesterase inhibitors at least sometimes for this population, with memantine (39%) and other agents (e.g., vitamin E) prescribed less frequently. Respondents endorsed several benefits of a diagnosis of MCI: 1) involving the patient in planning for the future (87%); 2) motivating risk reduction activities (85%); 3) helping with financial planning (72%); and 4) prescribing medications (65%). Some respondents noted drawbacks, including 1) too difficult to diagnose (23%); 2) better described as early Alzheimer disease (21%); and 3) diagnosis can cause unnecessary worry (20%). CONCLUSIONS: Patients with mild cognitive symptoms are commonly seen by neurologists, who view MCI as a useful diagnostic category. Information and treatments provided to patients with MCI vary significantly, suggesting a need for practice guidelines and further research on clinical decision-making with this population.

Understandings of basic genetics in the United States: results from a national survey of black and white men and women.

AIM: This study examined understandings of basic genetic concepts among Americans. METHOD: In a national telephone survey of 1,200 Americans with equal representation among Black and White men and women, subjects responded to 8 items developed by a multidisciplinary team of experts that assessed understanding of basic concepts in multiple domains, including inheritance, genetics and race, and genetics and behavior. RESULTS: Over 70% of subjects responded correctly on items about the genetic similarity of identical twins and siblings. Less than half of subjects responded correctly on all other items. Understanding of genetics was lowest in three areas: types/locations of genes in the body (29% correct), a genetic basis for race (25% correct), and the influence of single genes on behaviors (24% correct). Logistic regression models controlling for age and education showed some differences by race and gender on specific items but also showed that understandings are generally similar across these groups. CONCLUSION: Misunderstandings about genetics are common among Black and White American men and women. Responses appear to reflect personal experiences, group values and interests. These findings emphasize the need for initiatives to improve the public's genetic literacy as well as a need for further investigation in this domain.

Processing tangerine tomatoes: effects on lycopene-isomer concentrations and profile.

Because lycopene is a powerful biological antioxidant, its delivery to humans is of major concern. cis-Lycopene isomers are more bioavailable than the all-trans isomers and thus more efficiently absorbed. Tangerine tomatoes, whose lycopene isomeric content is almost all tetra-cis, provide a useful food source for comparing cis- and trans-isomer absorption. Tangerine tomatoes were processed into sauce in the Univ. of California, Davis Pilot Plant for subsequent use in a human feeding study described in another publication. Samples were taken at several stages during processing and carotenoids extracted and analyzed for carotenoid-isomer profiles and concentrations. Analyses showed that total lycopene concentration decreased considerably during the 1st step of processing, which included heating and juicing operations. Processing resulted in a large decrease in tetra-cis lycopene concentration accompanied by increases in trans- and other cis-lycopene isomers.

Ultrasound pasteurization: the effects of temperature, soluble solids, organic acids and pH on the inactivation of Escherichia coli ATCC 25922.

The objectives of this research were to study the effects of temperature, sugar concentration (8, 12, and 16 g/100ml), organic acids (citric and malic acids) and pH (2.5 and 4.0) on ultrasound pasteurization. The model organism used for the research was Escherichia coli ATCC 25922, and ultrasound treatment times were conducted to achieve a 5 log (base 10) reduction. Ultrasound generates heat, therefore the study involved removing the heat using a jacketed beaker with refrigerant (-30 degrees C) to maintain processing temperature at or below 30 degrees C and eliminate the thermal inactivation effects. Overall, ultrasound increased the sensitivity of E. coli to thermal inactivation. The presence of soluble solids had a protective effect where the sonication time requirement increased. Similar to heat sensitivity, the lower pH environment resulted in E. coli having less resistance to sonication. The type of organic acid had the least significant effect on ultrasound inactivation of E. coli.

Dominant effect of polariton-polariton interactions on the coherence of the microcavity optical parametric oscillator.

The importance of interaction effects in determining the temporal coherence of spectrally and spatially isolated single modes of the microcavity optical parametric oscillator (OPO) is demonstrated. As a function of macroscopic occupancy, the coherence time (tau c) first increases linearly and then exhibits saturation behavior, reaching maximum values of up to 500 ps. Good agreement is found with a model including fluctuations in polariton number and polariton-polariton interactions between the OPO states. tau c is a property of the coupled OPO system, a result confirmed by the finding of equal coherence times for signal and idler, even though the idler is subject to strong additional scattering.

Enhanced all-optical tuning of leaky eigenmodes in photonic crystal waveguides.

We demonstrate all-optical switching in an active two-dimensional photonic crystal waveguide, observing as large as 16 nm blueshifts of a leaky eigenmode at 839 nm and switching ratios of almost 70%. These results are larger than those previously observed in similar experiments performed on passive photonic crystal waveguides; the enhancement is due to resonant photogeneration of carriers by In(0.12)Al(0.2)Ga(0.68)As quantum wells in the core of the waveguide. The effective change in the refractive index of the structure is approximately10(-2), with a rise time of approximately1 ps and a decay time of approximately10 ps, potentially allowing high-speed switching and fast modulation rates.

The influence of inhaled nitric oxide on cerebral blood flow and metabolism in a child with traumatic brain injury.

IMPLICATIONS: The effects of inhaled nitric oxide (INO) on cerebrovascular hemodynamics are not well established. We report no adverse cerebral effects with INO therapy in a child with traumatic brain injury.

Posttreatment results of combining naltrexone with cognitive-behavior therapy for the treatment of alcoholism.

Naltrexone, an opiate antagonist medication, has been reported to be efficacious in the treatment of alcohol dependence when added to psychosocial treatments. Although the within-treatment efficacy of naltrexone has received primary attention, there has been little published on the outcome of individuals once the medication is discontinued. Animal studies have led to concern regarding a quick rebound to heavy drinking. This report extends the data previously reported by evaluating the outcome in alcoholic subjects during the 14 weeks after a 12-week treatment with naltrexone or placebo in conjunction with cognitive behavioral therapy. Of the 131 subjects evaluated during the treatment phase, 124 (95%) had up to 14 weeks of posttreatment drinking data available for analysis. Measures of craving and blood markers of heavy drinking were also evaluated. By the end of treatment, naltrexone demonstrated significantly greater efficacy than placebo. However, once the medication was discontinued, there was a gradual increase in relapse rates, heavy drinking days, and drinks per drinking day, and fewer days of abstinence were reported. By the end of the 14-week follow-up period, although naltrexone-treated subjects were, on average, still doing better than control subjects, the effectiveness of naltrexone was no longer statistically significant. There was no evidence that naltrexone subjects had an immediate return to heavy alcohol use as suggested in animals. These data suggest that, for a number of alcoholic subjects, continued treatment with naltrexone, or perhaps psychosocial intervention, for longer than 3 months is indicated. Future research should identify which alcohol-dependent individuals may need prolonged treatment to improve treatment success in the long term.