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Objectives/Goals: We describe the prevalence of individuals with household exposure to SARS-CoV-2, who subsequently report symptoms consistent with COVID-19, while having PCR results persistently negative for SARS-CoV-2 (S[+]/P[-]). We assess whether paired serology can assist in identifying the true infection status of such individuals. Methods/Study Population: In a multicenter household transmission study, index patients with SARS-CoV-2 were identified and enrolled together with their household contacts within 1 week of index’s illness onset. For 10 consecutive days, enrolled individuals provided daily symptom diaries and nasal specimens for polymerase chain reaction (PCR). Contacts were categorized into 4 groups based on presence of symptoms (S[+/-]) and PCR positivity (P[+/-]). Acute and convalescent blood specimens from these individuals (30 days apart) were subjected to quantitative serologic analysis for SARS-CoV-2 anti-nucleocapsid, spike, and receptor-binding domain antibodies. The antibody change in S[+]/P[-] individuals was assessed by thresholds derived from receiver operating characteristic (ROC) analysis of S[+]/P[+] (infected) versusS[-]/P[-] (uninfected). Results/Anticipated Results: Among 1,433 contacts, 67% had ≥1 SARS-CoV-2 PCR[+] result, while 33% remained PCR[-]. Among the latter, 55% (n = 263) reported symptoms for at least 1 day, most commonly congestion (63%), fatigue (63%), headache (62%), cough (59%), and sore throat (50%). A history of both previous infection and vaccination was present in 37% of S[+]/P[-] individuals, 38% of S[-]/P[-], and 21% of S[+]/P[+] (P<0.05). Vaccination alone was present in 37%, 41%, and 52%, respectively. ROC analyses of paired serologic testing of S[+]/P[+] (n = 354) vs. S[-]/P[-] (n = 103) individuals found anti-nucleocapsid data had the highest area under the curve (0.87). Based on the 30-day antibody change, 6.9% of S[+]/P[-] individuals demonstrated an increased convalescent antibody signal, although a similar seroresponse in 7.8% of the S[-]/P[-] group was observed. Discussion/Significance of Impact: Reporting respiratory symptoms was common among household contacts with persistent PCR[-] results. Paired serology analyses found similar seroresponses between S[+]/P[-] and S[-]/P[-] individuals. The symptomatic-but-PCR-negative phenomenon, while frequent, is unlikely attributable to true SARS-CoV-2 infections that go missed by PCR.
Major depression is associated with changes in plasma L-carnitine and acetyl-L-carnitine. But its association with acylcarnitines remains unclear. The aim of this study was to assess metabolomic profiles of 38 acylcarnitines in patients with major depression before and after treatment compared to healthy controls (HCs).
Methods
Metabolomic profiles of 38 plasma short-, medium-, and long-chain acylcarnitines were performed by liquid chromatography-mass spectrometry in 893 HCs from the VARIETE cohort and 460 depressed patients from the METADAP cohort before and after 6 months of antidepressant treatment.
Results
As compared to HCs, depressed patients had lower levels of medium- and long-chain acylcarnitines. After 6 months of treatment, increased levels of medium- and long-chain acyl-carnitines were observed that no longer differed from those of controls. Accordingly, several medium- and long-chain acylcarnitines were negatively correlated with depression severity.
Conclusions
These medium- and long-chain acylcarnitine dysregulations argue for mitochondrial dysfunction through fatty acid β-oxidation impairment during major depression.
Major depressive disorder (MDD) is the main cause of disability worldwide, its outcome is poor, and its underlying mechanisms deserve a better understanding. Recently, peripheral acetyl-l-carnitine (ALC) has been shown to be lower in patients with major depressive episodes (MDEs) than in controls. l-Carnitine is involved in mitochondrial function and ALC is its short-chain acetyl-ester. Our first aim was to compare the plasma levels of l-carnitine and ALC, and the l-carnitine/ALC ratio in patients with a current MDE and healthy controls (HCs). Our second aim was to assess their changes after antidepressant treatment.
Methods
l-Carnitine and ALC levels and the carnitine/ALC ratio were measured in 460 patients with an MDE in a context of MDD and in 893 HCs. Depressed patients were re-assessed after 3 and 6 months of antidepressant treatment for biology and clinical outcome.
Results
As compared to HC, depressed patients had lower ALC levels (p < 0.00001), higher l-carnitine levels (p < 0.00001) and higher l-carnitine/ALC ratios (p < 0.00001). ALC levels increased [coefficient: 0.18; 95% confidence interval (CI) 0.12–0.24; p < 0.00001], and l-carnitine levels (coefficient: −0.58; 95% CI −0.75 to −0.41; p < 0.00001) and l-carnitine/ALC ratios (coefficient: −0.41; 95% CI −0.47 to −0.34; p < 0.00001), decreased after treatment. These parameters were completely restored after 6 months of antidepressant. Moreover, the baseline l-carnitine/ALC ratio predicted remission after 3 months of treatment (odds ratio = 1.14; 95% CI 1.03–1.27; p = 0.015).
Conclusions
Our data suggest a decreased mitochondrial metabolism of l-carnitine into ALC during MDE. This decreased mitochondrial metabolism is restored after a 6-month antidepressant treatment. Moreover, the magnitude of mitochondrial dysfunction may predict remission after 3 months of antidepressant treatment. New strategies targeting mitochondria should be explored to improve treatments of MDD.
It is unclear whether olfactory deficits improve after remission in depressed patients. Therefore, we aimed to assess in drug-free patients the olfactory performance of patients with major depressive episodes (MDE) and its change after antidepressant treatment.
Methods
In the DEP-ARREST-CLIN study, 69 drug-free patients with a current MDE in the context of major depressive disorder (MDD) were assessed for their olfactory performances and depression severity, before and after 1 (M1) and 3 (M3) months of venlafaxine antidepressant treatment. They were compared to 32 age- and sex-matched healthy controls (HCs). Olfaction was assessed with a psychophysical test, the Sniffin’ Sticks test (Threshold: T score; Discrimination: D score; Identification: I score; total score: T + D + I = TDI score) and Pleasantness (pleasantness score: p score; neutral score: N score; unpleasantness score: U score).
Results
As compared to HCs, depressed patients had lower TDI olfactory scores [mean (s.d.) 30.0(4.5) v. 33.3(4.2), p < 0.001], T scores [5.6(2.6) v. 7.4(2.6), p < 0.01], p scores [7.5(3.0) v. 9.8(2.8), p < 0.001)] and higher N scores [3.5(2.6) v. 2.1(1.8), p < 0.01]. T, p and N scores at baseline were independent from depression and anhedonia severity. After venlafaxine treatment, significant increases of T scores [M1: 7.0(2.6) and M3: 6.8(3.1), p < 0.01] and p scores [M1: 8.1(3.0) and M3: 8.4(3.3), p < 0.05] were evidenced, in remitters only (T: p < 0.01; P: p < 0.01). Olfaction improvement was mediated by depression improvement.
Conclusions
The olfactory signature of MDE is restored after venlafaxine treatment. This olfaction improvement is mediated by depression improvement.
This study investigated the latent factor structure of the NIH Toolbox Cognition Battery (NIHTB-CB) and its measurement invariance across clinical diagnosis and key demographic variables including sex, race/ethnicity, age, and education for a typical Alzheimer’s disease (AD) research sample.
Method:
The NIHTB-CB iPad English version, consisting of 7 tests, was administered to 411 participants aged 45–94 with clinical diagnosis of cognitively unimpaired, dementia, mild cognitive impairment (MCI), or impaired not MCI. The factor structure of the whole sample was first examined with exploratory factor analysis (EFA) and further refined using confirmatory factor analysis (CFA). Two groups were classified for each variable (diagnosis or demographic factors). The confirmed factor model was next tested for each group with CFA. If the factor structure was the same between the groups, measurement invariance was then tested using a hierarchical series of nested two-group CFA models.
Results:
A two-factor model capturing fluid cognition (executive function, processing speed, and memory) versus crystalized cognition (language) fit well for the whole sample and each group except for those with age < 65. This model generally had measurement invariance across sex, race/ethnicity, and education, and partial invariance across diagnosis. For individuals with age < 65, the language factor remained intact while the fluid cognition was separated into two factors: (1) executive function/processing speed and (2) memory.
Conclusions:
The findings mostly supported the utility of the battery in AD research, yet revealed challenges in measuring memory for AD participants and longitudinal change in fluid cognition.
The effect of an externally applied electric field on the motion of an interface between two viscous dielectric fluids is investigated. We first develop a powerful, efficient and widely applicable boundary integral method to compute the interface dynamics in a general multiphysics model comprising coupled Laplace and Stokes flow problems in a periodic half-space. In particular, we exploit the relevant Stokes and Laplace Green's functions to reduce the problem to one defined on the interfacial part of the domain alone. Secondly, motivated by recent experimental work that seeks to underpin the development of switchable liquid optical devices, we concentrate on a fluid–air interface and derive asymptotic approximations suitable to describe the behaviour of a thin film of fluid above an array of electrodes. In this case, the problem is reduced to a single nonlinear partial differential equation describing the film height, coupled to the electrostatic problem via suitable numerical solution or via an asymptotic formula for electrostatic forcing. Comparison against numerical simulations of the full problem shows that the reduced models successfully capture key features of the film dynamics in appropriate regimes; all three approaches are shown to reproduce experimental results.
Objectives: Prior research has identified numerous genetic (including sex), education, health, and lifestyle factors that predict cognitive decline. Traditional model selection approaches (e.g., backward or stepwise selection) attempt to find one model that best fits the observed data, risking interpretations that only the selected predictors are important. In reality, several predictor combinations may fit similarly well but result in different conclusions (e.g., about size and significance of parameter estimates). In this study, we describe an alternative method, Information-Theoretic (IT) model averaging, and apply it to characterize a set of complex interactions in a longitudinal study on cognitive decline. Methods: Here, we used longitudinal cognitive data from 1256 late–middle aged adults from the Wisconsin Registry for Alzheimer’s Prevention study to examine the effects of sex, apolipoprotein E (APOE) ɛ4 allele (non-modifiable factors), and literacy achievement (modifiable) on cognitive decline. For each outcome, we applied IT model averaging to a set of models with different combinations of interactions among sex, APOE, literacy, and age. Results: For a list-learning test, model-averaged results showed better performance for women versus men, with faster decline among men; increased literacy was associated with better performance, particularly among men. APOE had less of an association with cognitive performance in this age range (∼40–70 years). Conclusions: These results illustrate the utility of the IT approach and point to literacy as a potential modifier of cognitive decline. Whether the protective effect of literacy is due to educational attainment or intrinsic verbal intellectual ability is the topic of ongoing work. (JINS, 2019, 25, 119–133)
Objectives: A major challenge in cognitive aging is differentiating preclinical disease-related cognitive decline from changes associated with normal aging. Neuropsychological test authors typically publish single time-point norms, referred to here as unconditional reference values. However, detecting significant change requires longitudinal, or conditional reference values, created by modeling cognition as a function of prior performance. Our objectives were to create, depict, and examine preliminary validity of unconditional and conditional reference values for ages 40–75 years on neuropsychological tests. Method: We used quantile regression to create growth-curve–like models of performance on tests of memory and executive function using participants from the Wisconsin Registry for Alzheimer’s Prevention. Unconditional and conditional models accounted for age, sex, education, and verbal ability/literacy; conditional models also included past performance on and number of prior exposures to the test. Models were then used to estimate individuals’ unconditional and conditional percentile ranks for each test. We examined how low performance on each test (operationalized as <7th percentile) related to consensus-conference–determined cognitive statuses and subjective impairment. Results: Participants with low performance were more likely to receive an abnormal cognitive diagnosis at the current visit (but not later visits). Low performance was also linked to subjective and informant reports of worsening memory function. Conclusions: The percentile-based methods and single-test results described here show potential for detecting troublesome within-person cognitive change. Development of reference values for additional cognitive measures, investigation of alternative thresholds for abnormality (including multi-test criteria), and validation in samples with more clinical endpoints are needed. (JINS, 2019, 25, 1–14)
New analyses of a garnet-clinopyroxene rock (‘eclogite’) and its constituent minerals from the Sittampundi complex of India are presented. The rock has a composition comparable with an alkali-poor tholeiite and this composition, as well as the garnet (Py 51·5 %; Alm 32·7 %) and pyroxene (Jd 7·4 %; Ts 10·8 %) are very similar to those from South Harris.
The apparent distribution coefficient (K′Fe/Mg) for the garnet-clinopyroxene pair suggests a temperature of equilibration near 850 °C. Projection of the experimental data of Green and Ringwood (1967) down to this temperature suggests a pressure of about 7–8 kb. This is well below the pressure of the granulite-eclogite transition.
The effects of temperature and the annual growth cycle on the formation of root suckers were determined by propagating root cuttings of black locust (Robinia pseudoacacia L.). The percentage of cuttings which formed suckers in an air temperature of 60 F was significantly lower than that of cuttings at 70 to 80 F. In the annual growth cycle experiment, cuttings removed in June formed significantly fewer suckers than those removed during January, March, August, or November.
Isostatic response of the Earth to changes in Quaternary Times of ice and water loads is partly elastic, and partly involves viscous mantle flow. The relaxation spectrum of the Earth, critical for estimation of the mantle flow component, is estimated from published determinations of Fennoscandian and Laurentide rebound, and of the nontidal acceleration of the Earth's rotation. The spectrum is consistent with an asthenosphere viscosity around 1021P, and a viscosity around 1023P below 400 km depth. Calculation of relaxation effects is done by convoluting the load history with the response function in spherical harmonics for global effects, and in rectangular or cylindrical transforms for smaller regional effects. Broad-scale deformation of the globe, resulting from the last deglaciation and sea level rise, is calculated to have involved an average depression of ocean basins of about 8 m, and mean upward movement of continents of about 16 m, relative to the center of the Earth, in the last 7000 yr. Deflection in the ocean margin “hinge zone” varies with continental shelf geometry and rigidity of the underlying lithosphere: predictions are made for different model cases. The computational methods is checked by predicting Fennoscandian and Laurentide postglacial warping, from published estimates of icecap histories, with good results. The depth variations of shorelines formed around 17,000 BP (e.g., North America, 90–130 m; Australia, 130–170 m), are largely explainable in terms of combined elastic and relaxation isostasy. Differences between Holocene eustatic records from oceanic islands (Micronesia, Bermuda), and continental coasts (eastern North America, Australia), are largely but not entirely explained in the same terms.
Quaternary paleotemperatures and sea level records, from both deep sea cores and dated shorelines, provide the basis for testing the Milankovitch hypothesis of climatic change. The longest and most detailed records include (1) oxygen isotope analyses of Caribbean and Atlantic deep sea cores, (2) paleoecological analyses of the same cores, and (3) radiometrically dated raised coral reefs from New Guinea and elsewhere, representing times of relatively high Quaternary sea levels. Time-domain and frequency-domain analysis of these records, shows with a high degree of certainty that Quaternary climatic changes are strongly influenced by the obliquity perturbations and precession of the Earth's orbit. The same analyses also suggest that the time scale adopted by Emiliani for deep sea cores may be more nearly correct than alternative time scales of other workers.
The question of whether insolation changes arising from orbital perturbations can generate ice ages, has been disputed by climatologists. It is shown here that orbital perturbations cannot affect climate indirectly through agencies originating within the Earth, such as vulcanism, and that the primary climatic control is therefore through variation of insolation distribution, as Milankovitch suggested. The conclusion is that climatologic theory must accommodate these facts.
As many as six levels of emerged Holocene coral terraces occur along 40 km of coastline on the Huon Peninsula, Papua New Guinea, recording uplift history since culmination of the postglacial transgression. The Holocene reef crest, ca. 6000 yr B.P., is tilted down to the northwest, parallel to the coast and concordant with the deformation of the last interglacial coral reef terrace, and descends from 23 to 12 m in the study area. The pattern and rate of deformation have been uniform in the late Quaternary because average uplift rates have remained the same since the last interglaciation. The Holocene terraces described here are erosional features with regressive encrusting corals, developed upon the Holocene transgressive reef. The multiple levels represent episodic, probably coseismic uplift, which has occurred repeatedly in the last ca. 6000 yr. Significant longshore variation in the age of the lowest terrace, from 1700 to 2500 yr B.P., suggests independent coseismic uplift on different sectors of the coast. This is supported by age-height relationships of the higher Holocene terraces. Nonlinear uplift during the Holocene, with recurrence intervals increasing toward the present, is clearly recorded by the regressive terraces in each subregion. Some of the Holocene regressive terraces grade laterally into fluvial terraces capped with debris-flow deposits, probably reflecting seismically triggered mass movement.
The late-type stellar population in the Galactic Center was first predicted to reside in a dynamically relaxed cusp (power law slope ranging from 3/2 to 7/4). However, other works - which rely on models to correct for projection effects - have suggested a flat distribution instead. The need for this correction is due to the lack of information regarding the line-of-sight distances. With a two decade long baseline in astrometric measurements, we are now able to measure significant projected radial accelerations, six of which are newly reported here, which directly constrain line-of-sight distances. Here we present a statistical approach to take advantage of this information and more accurately constrain the shape of the radial density profile of the late-type stellar population in the Galactic Center.
In this paper, we show a second-order (four-resonator) absorptive bandstop filter circuit topology which gives a larger bandwidth compared to a first-order topology. Due to the absorptive characteristic, it creates a large attenuation at the center frequency using low-Q resonators. Since low-Q resonators can be used in generating a large attenuation, small-size resonators can be employed in bandstop filter design. Analytic design equations are provided so that a higher-order absorptive bandstop filter can be designed analytically. It is also shown that the second-order filter topology exhibits a better frequency selectivity having a same bandwidth. The proposed filter topology has been applied to a design of a miniaturized low-temperature co-fired ceramic bandstop filter with low-Q resonators. The Q-factor of the lumped-element resonators has been chosen to be 5 for demonstration.
In this paper, the benefits of adaptive preselect filtering are investigated by analyzing mote-to-mote throughput in the presence of interference. In a city-wide deployment of a sensor network, of the 150 wireless sensor nodes deployed in our urban test system, five nodes were electrically “lost”. Surprisingly, the limiting factor was not the signal strength, but the neighboring cell towers that caused nearby interference. Therefore, we explored the effect of an adaptive front end to mitigate these nearby interferers. The sensor motes operated at a fixed band, the unlicenced band of 902 to 928 MHz, and did not have the frequency adaptability of future cognitive radios. However, the effect was demonstrative of the potential benefits of adaptive preselect filtering. The measured result shows substantial improvements over the fixed band system by even slight tuning of the bandwidth and/or the center frequency of the preselect filter. Experimentally and numerically, we show that both tuning in the filter bandwidth and/or center frequency can significantly improve the packet reception rate. Guidelines for achieving an optimized filtering technique are given to provide a broad understanding of how the adaptable preselect filtering can be utilized.