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Frascati international research criteria for HIV-associated neurocognitive disorders (HAND) are controversial; some investigators have argued that Frascati criteria are too liberal, resulting in a high false positive rate. Meyer et al. recommended more conservative revisions to HAND criteria, including exploring other commonly used methodologies for neurocognitive impairment (NCI) in HIV including the global deficit score (GDS). This study compares NCI classifications by Frascati, Meyer, and GDS methods, in relation to neuroimaging markers of brain integrity in HIV.
Two hundred forty-one people living with HIV (PLWH) without current substance use disorder or severe (confounding) comorbid conditions underwent comprehensive neurocognitive testing and brain structural magnetic resonance imaging and magnetic resonance spectroscopy. Participants were classified using Frascati criteria versus Meyer criteria: concordant unimpaired [Frascati(Un)/Meyer(Un)], concordant impaired [Frascati(Imp)/Meyer(Imp)], or discordant [Frascati(Imp)/Meyer(Un)] which were impaired via Frascati criteria but unimpaired via Meyer criteria. To investigate the GDS versus Meyer criteria, the same groupings were utilized using GDS criteria instead of Frascati criteria.
When examining Frascati versus Meyer criteria, discordant Frascati(Imp)/Meyer(Un) individuals had less cortical gray matter, greater sulcal cerebrospinal fluid volume, and greater evidence of neuroinflammation (i.e., choline) than concordant Frascati(Un)/Meyer(Un) individuals. GDS versus Meyer comparisons indicated that discordant GDS(Imp)/Meyer(Un) individuals had less cortical gray matter and lower levels of energy metabolism (i.e., creatine) than concordant GDS(Un)/Meyer(Un) individuals. In both sets of analyses, the discordant group did not differ from the concordant impaired group on any neuroimaging measure.
The Meyer criteria failed to capture a substantial portion of PLWH with brain abnormalities. These findings support continued use of Frascati or GDS criteria to detect HIV-associated CNS dysfunction.
Objectives: Studies of neurocognitively elite older adults, termed SuperAgers, have identified clinical predictors and neurobiological indicators of resilience against age-related neurocognitive decline. Despite rising rates of older persons living with HIV (PLWH), SuperAging (SA) in PLWH remains undefined. We aimed to establish neuropsychological criteria for SA in PLWH and examined clinically relevant correlates of SA. Methods: 734 PLWH and 123 HIV-uninfected participants between 50 and 64 years of age underwent neuropsychological and neuromedical evaluations. SA was defined as demographically corrected (i.e., sex, race/ethnicity, education) global neurocognitive performance within normal range for 25-year-olds. Remaining participants were labeled cognitively normal (CN) or impaired (CI) based on actual age. Chi-square and analysis of variance tests examined HIV group differences on neurocognitive status and demographics. Within PLWH, neurocognitive status differences were tested on HIV disease characteristics, medical comorbidities, and everyday functioning. Multinomial logistic regression explored independent predictors of neurocognitive status. Results: Neurocognitive status rates and demographic characteristics differed between PLWH (SA=17%; CN=38%; CI=45%) and HIV-uninfected participants (SA=35%; CN=55%; CI=11%). In PLWH, neurocognitive groups were comparable on demographic and HIV disease characteristics. Younger age, higher verbal IQ, absence of diabetes, fewer depressive symptoms, and lifetime cannabis use disorder increased likelihood of SA. SA reported increased independence in everyday functioning, employment, and health-related quality of life than non-SA. Conclusions: Despite combined neurological risk of aging and HIV, youthful neurocognitive performance is possible for older PLWH. SA relates to improved real-world functioning and may be better explained by cognitive reserve and maintenance of cardiometabolic and mental health than HIV disease severity. Future research investigating biomarker and lifestyle (e.g., physical activity) correlates of SA may help identify modifiable neuroprotective factors against HIV-related neurobiological aging. (JINS, 2019, 25, 507–519)
The seventh-century AD switch from gold to silver currencies transformed the socio-economic landscape of North-west Europe. The source of silver, however, has proven elusive. Recent research, integrating ice-core data from the Colle Gnifetti drill site in the Swiss Alps, geoarchaeological records and numismatic and historical data, has provided new evidence for this transformation. Annual ice-core resolution data are combined with lead pollution analysis to demonstrate that significant new silver mining facilitated the change to silver coinage, and dates the introduction of such coinage to c. AD 660. Archaeological evidence and atmospheric modelling of lead pollution locates the probable source of the silver to mines at Melle, in France.
Introduction: In many rural and remote communities in BC, family physicians who are providing excellent primary and emergency care would like to access useful, timely, and collegial support to ensure the highest quality of health services for their patients. We undertook a real-time virtual support project in Robson Valley, located in northern BC, to evaluate the use of digital technologies such as videoconferencing for on demand consultation between family physicians at rural sites and emergency physicians at a regional site. Telehealth consults also occurred between rural sites with nurses at community emergency rooms consulting with local on-call physicians. Our aim was to use telehealth to facilitate timely access to high quality, comprehensive, coordinated team-based care. An evaluation framework, based on the Triple Aim sought to: 1) Identify telehealth use cases and assess impact on patient outcomes, patient and health professional experience, and cost of health care delivery; and 2) Assess the role of relationships among care team members in progressing from uptake to normalization of telehealth into routine usage. Methods: Using a participatory approach, all members of the pilot project were involved in shaping the pilot including the co-development of the evaluation itself. Evaluation was used iteratively throughout implementation for ongoing quality improvement via regular team meetings, sharing and reflecting on findings, and adjusting processes as required. Mixed methods were used including: interviews with family physicians, nurses, and patients at rural sites, and emergency physicians at regional site; review of records such as technology use statistics; and stakeholder focus groups. Results: From November 2016 to July 2017, 26 cases of telehealth use were captured and evaluated. Findings indicate that telehealth has positively impacted care team, patients, and health system. Benefits for care team at the rural sites included confidence in diagnoses through timely access to advice and support, while emergency physicians at the regional site gained deeper understanding of the practice settings of rural colleagues. Nevertheless, telehealth has complicated the emergency department work flow and increased physician workload. Findings demonstrated efficiencies for the health system, including reducing the need for patient transfer. Patients expressed confidence in the physicians and telehealth system; by receiving care closer to home, they experienced personal cost savings. Implementation saw a move away from scheduled telehealth visits to real use of technology for timely access. Conclusion: Evidence of the benefits of telehealth in emergency settings is needed to support stakeholder engagement to address issues of workflow and capacity. This pilot has early indications of significant local impact and will inform the expansion of emergency telehealth in all emergency settings in BC.
Little is known about the association of cortical Aβ with depression and anxiety among cognitively normal (CN) elderly persons.
We conducted a cross-sectional study derived from the population-based Mayo Clinic Study of Aging in Olmsted County, Minnesota; involving CN persons aged ≥ 60 years that underwent PiB-PET scans and completed Beck Depression Inventory-II (BDI-II) and Beck Anxiety Inventory (BAI). Cognitive diagnosis was made by an expert consensus panel. Participants were classified as having abnormal (≥1.4; PiB+) or normal PiB-PET (<1.4; PiB−) using a global cortical to cerebellar ratio. Multi-variable logistic regression analyses were performed to calculate odds ratios (OR) and 95% confidence intervals (95% CI) after adjusting for age and sex.
Of 1,038 CN participants (53.1% males), 379 were PiB+. Each one point symptom increase in the BDI (OR = 1.03; 1.00–1.06) and BAI (OR = 1.04; 1.01–1.08) was associated with increased odds of PiB-PET+. The number of participants with BDI > 13 (clinical depression) was greater in the PiB-PET+ than PiB-PET- group but the difference was not significant (OR = 1.42; 0.83–2.43). Similarly, the number of participants with BAI > 10 (clinical anxiety) was greater in the PiB-PET+ than PiB-PET− group but the difference was not significant (OR = 1.77; 0.97–3.22).
As expected, depression and anxiety levels were low in this community-dwelling sample, which likely reduced our statistical power. However, we observed an informative albeit weak association between increased BDI and BAI scores and elevated cortical amyloid deposition. This observation needs to be tested in a longitudinal cohort study.
Objectives: Human immunodeficiency virus (HIV) disproportionately affects Hispanics/Latinos in the United States, yet little is known about neurocognitive impairment (NCI) in this group. We compared the rates of NCI in large well-characterized samples of HIV-infected (HIV+) Latinos and (non-Latino) Whites, and examined HIV-associated NCI among subgroups of Latinos. Methods: Participants included English-speaking HIV+ adults assessed at six U.S. medical centers (194 Latinos, 600 Whites). For overall group, age: M=42.65 years, SD=8.93; 86% male; education: M=13.17, SD=2.73; 54% had acquired immunodeficiency syndrome. NCI was assessed with a comprehensive test battery with normative corrections for age, education and gender. Covariates examined included HIV-disease characteristics, comorbidities, and genetic ancestry. Results: Compared with Whites, Latinos had higher rates of global NCI (42% vs. 54%), and domain NCI in executive function, learning, recall, working memory, and processing speed. Latinos also fared worse than Whites on current and historical HIV-disease characteristics, and nadir CD4 partially mediated ethnic differences in NCI. Yet, Latinos continued to have more global NCI [odds ratio (OR)=1.59; 95% confidence interval (CI)=1.13–2.23; p<.01] after adjusting for significant covariates. Higher rates of global NCI were observed with Puerto Rican (n=60; 71%) versus Mexican (n=79, 44%) origin/descent; this disparity persisted in models adjusting for significant covariates (OR=2.40; CI=1.11–5.29; p=.03). Conclusions: HIV+ Latinos, especially of Puerto Rican (vs. Mexican) origin/descent had increased rates of NCI compared with Whites. Differences in rates of NCI were not completely explained by worse HIV-disease characteristics, neurocognitive comorbidities, or genetic ancestry. Future studies should explore culturally relevant psychosocial, biomedical, and genetic factors that might explain these disparities and inform the development of targeted interventions. (JINS, 2018, 24, 163–175)
Isotope tracer studies, particularly radiocarbon measurements, play a key role in biological, nutritional, and environmental research. Accelerator mass spectrometry (AMS) is now the most sensitive detection method for 14C, but AMS is not widely used in kinetic studies of humans. Part of the reason is the expense, but costs would decrease if AMS were used more widely. One component in the cost is sample preparation for AMS. Biological and environmental samples are commonly reduced to graphite before they are analyzed by AMS. Improvements and mechanization of this multistep procedure is slowed by a lack of organized educational materials for AMS sample preparation that would allow new investigators to work with the technique without a substantial outlay of time and effort. We present a detailed sample preparation protocol for graphitizing biological samples for AMS and include examples of nutrition studies that have used this procedure.
Tuberous sclerosis complex (TSC) is associated with intellectual disability, but the risk pathways are poorly understood.
The Tuberous Sclerosis 2000 Study is a prospective longitudinal study of the natural history of TSC. One hundred and twenty-five UK children age 0–16 years with TSC and born between January 2001 and December 2006 were studied. Intelligence was assessed using standardized measures at ≥2 years of age. The age of onset of epilepsy, the type of seizure disorder, the frequency and duration of seizures, as well as the response to treatment was assessed at interview and by review of medical records. The severity of epilepsy in the early years was estimated using the E-Chess score. Genetic studies identified the mutations and the number of cortical tubers was determined from brain scans.
TSC2 mutations were associated with significantly higher cortical tuber count than TSC1 mutations. The extent of brain involvement, as indexed by cortical tuber count, was associated with an earlier age of onset and severity of epilepsy. In turn, the severity of epilepsy was strongly associated with the degree of intellectual impairment. Structural equation modelling supported a causal pathway from genetic abnormality to cortical tuber count to epilepsy severity to intellectual outcome. Infantile spasms and status epilepticus were important contributors to seizure severity.
The findings support the proposition that severe, early onset epilepsy may impair intellectual development in TSC and highlight the potential importance of early, prompt and effective treatment or prevention of epilepsy in tuberous sclerosis.
To determine the potential epidemiologic and economic value of the implementation of a multifaceted Clostridium difficile infection (CDI) control program at US acute care hospitals
Markov model with a 5-year time horizon
Patients whose data were used in our simulations were limited to hospitalized Medicare beneficiaries ≥65 years old.
CDI is an important public health problem with substantial associated morbidity, mortality, and cost. Multifaceted national prevention efforts in the United Kingdom, including antimicrobial stewardship, patient isolation, hand hygiene, environmental cleaning and disinfection, and audit, resulted in a 59% reduction in CDI cases reported from 2008 to 2012.
Our analysis was conducted from the federal perspective. The intervention we modeled included the following components: antimicrobial stewardship utilizing the Antimicrobial Use and Resistance module of the National Healthcare Safety Network (NHSN), use of contact precautions, and enhanced environmental cleaning. We parameterized our model using data from CDC surveillance systems, the AHRQ Healthcare Cost and Utilization Project, and literature reviews. To address uncertainty in our parameter estimates, we conducted sensitivity analyses for intervention effectiveness and cost, expenditures by other federal partners, and discount rate. Each simulation represented a cohort of 1,000 hospitalized patients over 1,000 trials.
In our base case scenario with 50% intervention effectiveness, we estimated that 509,000 CDI cases and 82,000 CDI-attributable deaths would be prevented over a 5-year time horizon. Nationally, the cost savings across all hospitalizations would be $2.5 billion (95% credible interval: $1.2 billion to $4.0 billion).
The potential benefits of a multifaceted national CDI prevention program are sizeable from the federal perspective.
The temperature dependent structural evolutions of RbxC60 (x = 3, 5, 6) and K4C60 were studied using both in-house andsynchrotron x-ray powder diffraction and thermal analysis techniques over a temperature range of 10K - 673K. The superconducting face centered-cubic (fcc) Rb3C60 and the body centered-tetragonal (bct) M4C60(M = K, Rb) phases are found to be line compounds in this temperature range, while the body centered-cubic (bcc) phase forms a solid solution in which the solubility of vacant M sites increases with temperature. The orientation of the C60 molecules in the K4C60 phase was analyzed. A crystalline fcc Rb1C60 phase is stable only above room temperature.
Diamond thin films were grown on a scratched silicon crystal surface by a novel CVD technique. The substrate was exposed to a bombardment of sputtered carbon atoms from a graphite target in a helium DC glow discharge, and subsequently exposed to atomic hydrogen generated by a hot tungsten filament. The resulting diamond films were characterized by Raman spectroscopy and SEM. Deposited film quality, and growth rate are presented as a function of carbon flux, and atomic hydrogen flux. The observed increase in growth rate with atomic hydrogen indicates that a surface reaction mechanism may be responsible for growth. The saturation of the utilization of carbon confirms that the diamond growth is probably a surface reaction. Based on this work we propose that the growth of diamond films in the sequential CVD reactor is most likely governed by surface reactions, and that the necessity of gas phase precursors can be precluded.
Fullerene (C60 and C70) synthesis by combustion of ethylene and benzene in a flat flame burner was investigated. This method of fullerene synthesis is particularly attractive because of its potential of scale up. Also the ability to change the flame conditions andcontrol the yield of C60 and C70 makes this method versatile. No fullerenes were found in soot samples collected from the ethylene flame. However, fullerenes were formed in a benzene flame with C/O = 0.88 and operated at 40 torr, with cold gas velocity of 25.3 cm/s (273 K) and containing 10% argon. The concentration of fullerenes in this flame was found to depend strongly on the height above the burner surface. It exhibited a strong maxima at about 1.0 cm above the burner height suggesting the presence of both growth and destruction mechanisms.
We report angle-resolved photoemission data from single crystals of C60 cleaved in UHV. Unlike the other forms of pure carbon, the valence band spectrum of C60 consists of many sharp features that can be essentially accounted for by the quantum chemical calculations describing individual molecules. This suggests that the electronic structure of solid C60 is mainly determined by the bonding interactions within the individual molecules. We also observe remarkable intensity modulations of the photoemission features as a function of photon energy, suggesting strong final state effects. Finally, we address the issue of the band width of the HOMO state of C60. We assert that the width of the photoemission peak of C60 does not reflectthe intrinsic band width.
In a series of experiments on solid C60, the low-energy rotational dynamics of the molecules, the higher-energy vibrational spectra, and aspects of disorder in the static structure, have been studied. The nearly spherical shape of the C60 molecule, and the occurrence of an orientational phase transition at Tc=256 K, make the C60 solid an excellent system for investigations of orientational dynamics. Coherent quasi-elastic neutron scattering above Tc is described quantitatively by a rotational diffusion model. Below Tc, inelastic scattering froma soft librational mode is observed between 2 and 3 meV. Models of the strong, temperaturedependent diffuse scattering due to orientational disorder are discussed. Finally, measurements of the density of states for the intramolecular ( E ≥ 33 meV) vibrational modes are also presented.
We have used a first principles molecular dynamics technique to find the relaxed atomic geometry and the corresponding electronic structure of a simple novel form of threecoordinated solid carbon, which we name polybenzene. The polybenzene structure is found to have a substantially lower energy per atom (by 0.23 eV) than C60, yet contains only 24 atoms per unit cell. In addition we have calculated the zero wavevector vibrational spectrum for this novel carbon structure.
A study was performed on polycrystalline copper versus that of Si(100) utilizing a negative substrate bias to enhance diamond nucleation. The biasing pretreatment and subsequent growth of the diamond were performed via microwave plasma chemical vapor deposition and the initial stages of nucleation were characterized by in-vacuo surface analysis. The biasing pretreatment step proved to have a tremendous influence on the nucleation density pertaining to Si(100) substrates, however, the nucleation density on polycrystalline copper was only increased slightly. A highly graphitic surface coverage of roughly 10A was evident on the copper substrates prior to the detection of diamond and was quite stable in thickness in as early as 15 minutes of biasing. The Si(100) substrates, however, were characterized by the formation of a carbide with some form of nondiamond carbon present on the surface throughout the biasing pretreatment.