Abstract Objective To identify clinical and neurocognitive predictors of long-term functional outcome in patients with bipolar disorder Methods A total of 32 subjects who met criteria for bipolar I ...or II disorder were recruited from the Barcelona Bipolar Disorder Program and were assessed clinically and neuropsychologically at baseline. After an average 4-year follow-up, they were interviewed with the Functioning Assessment Short Test (FAST) to assess functional outcome. Multivariate analyses were applied to identify clinical and neurocognitive predictors of functional outcome. Results The main regression model for predictors of overall psychosocial functioning identified subclinical depressive symptoms ( ß = 0.516, t = 3.51, p = 0.002), and free delayed recall in a verbal memory task ( ß = − 0.314, t = − 2.144, p = 0.041), accounting for 36% of the variance. Specific predictors of occupational functioning were, again, subthreshold depression ( ß = 0.435, t = 2.8, p = 0.009) and a measure of executive function, digits backwards ( ß = − 0.347, t = − 2.23, p = 0.034). This model explained around 28% of the variance (corrected R2 = 0.28; F = 6.38, gl = 2, p = 0.004). Conclusions Subdepressive symptomatology together with neurocognitive impairments related to verbal memory and executive functions are predictor variables of long-term functional outcome in bipolar disorder.
Flow cytometry has become a highly valuable method to monitor minimal residual disease (MRD) and evaluate the depth of complete response (CR) in bone marrow (BM) of multiple myeloma (MM) after ...therapy. However, current flow-MRD has lower sensitivity than molecular methods and lacks standardization. Here we report on a novel next generation flow (NGF) approach for highly sensitive and standardized MRD detection in MM. An optimized 2-tube 8-color antibody panel was constructed in five cycles of design-evaluation-redesign. In addition, a bulk-lysis procedure was established for acquisition of ⩾10
cells/sample, and novel software tools were constructed for automatic plasma cell gating. Multicenter evaluation of 110 follow-up BM from MM patients in very good partial response (VGPR) or CR showed a higher sensitivity for NGF-MRD vs conventional 8-color flow-MRD -MRD-positive rate of 47 vs 34% (P=0.003)-. Thus, 25% of patients classified as MRD-negative by conventional 8-color flow were MRD-positive by NGF, translating into a significantly longer progression-free survival for MRD-negative vs MRD-positive CR patients by NGF (75% progression-free survival not reached vs 7 months; P=0.02). This study establishes EuroFlow-based NGF as a highly sensitive, fully standardized approach for MRD detection in MM which overcomes the major limitations of conventional flow-MRD methods and is ready for implementation in routine diagnostics.
Four different antioxidant tests (ABTS
+, DPPH, ORAC, β-carotene–linoleate model system) were used to determine the free-radical scavenging activity of 39 extra virgin olive oils (EVOO) and compare ...the total phenol content by the Folin–Ciocalteu method. The correlation between the total phenols and antioxidant capacities measured by the four methods was very high, and highest with ABTS
+ (
R
2
=
0.9905). Some of these methods of measurement were applied to olive-oil samples (OO), with approximately a 50% decrease in the value of the antioxidant capacity in comparison with values found for EVOO. In conclusion, the results show that all the methods tested were suitable for determining the antioxidant capacity of olive oil. The Picual variety of extra-virgin olive oil showed high antioxidant activity.
is the principal mosquito vector for many arboviruses that increasingly infect millions of people every year. With an escalating burden of infections and the relative failure of traditional control ...methods, the development of innovative control measures has become of paramount importance. The use of gene drives has sparked significant enthusiasm for genetic control of mosquitoes; however, no such system has been developed in
. To fill this void, here we develop several CRISPR-based split gene drives for use in this vector. With cleavage rates up to 100% and transmission rates as high as 94%, mathematical models predict that these systems could spread anti-pathogen effector genes into wild populations in a safe, confinable and reversible manner appropriate for field trials and effective for controlling disease. These findings could expedite the development of effector-linked gene drives that could safely control wild populations of
to combat local pathogen transmission.
ABSTRACT
We present an improved measurement of the Hubble constant (H0) using the ‘inverse distance ladder’ method, which adds the information from 207 Type Ia supernovae (SNe Ia) from the Dark ...Energy Survey (DES) at redshift 0.018 < z < 0.85 to existing distance measurements of 122 low-redshift (z < 0.07) SNe Ia (Low-z) and measurements of Baryon Acoustic Oscillations (BAOs). Whereas traditional measurements of H0 with SNe Ia use a distance ladder of parallax and Cepheid variable stars, the inverse distance ladder relies on absolute distance measurements from the BAOs to calibrate the intrinsic magnitude of the SNe Ia. We find H0 = 67.8 ± 1.3 km s−1 Mpc−1 (statistical and systematic uncertainties, 68 per cent confidence). Our measurement makes minimal assumptions about the underlying cosmological model, and our analysis was blinded to reduce confirmation bias. We examine possible systematic uncertainties and all are below the statistical uncertainties. Our H0 value is consistent with estimates derived from the Cosmic Microwave Background assuming a ΛCDM universe.
To assess the quality of antifungal use, to propose a point score for this evaluation and to estimate the potential economic savings of an antifungal stewardship programme.
From December 2010 to ...January 2011, we identified 100 adult inpatients receiving systemic antifungals. Antifungal use was evaluated by means of a predefined score that considered indication, drug selection, dosage, adjustments after microbiology results, switching to an oral agent and length of treatment. Total antifungal prescriptions in defined daily doses (DDDs) and days of therapy (DOTs) and potential cost savings were calculated.
Overall, 43% of prescriptions came from medical departments, 25% from haematology/oncology and 17% from intensive care units. The main reasons for starting antifungals were empirical (42%), pre-emptive (20%) and targeted treatment (20%). Antifungals were unnecessary in 16% of cases. Inadequacies in other aspects of antifungal prescription were: drug selection, 31%; dosing, 16%; no switch from intravenous to oral administration, 20%; no adjustment after microbiological results, 35%; and length of therapy, 27%. The number of antifungal DDDs per 1000 patient-days was 65.1. The total number of DOTs was 1556, which added a direct cost of €219 364. Only 51.3% of DOTs were considered optimal. The potential estimated savings would be €50 536.
Major efforts should be made to improve the selection and duration of antifungal therapy. Our study demonstrated the potential cost savings that could be achieved by optimizing antifungal therapy. A stewardship programme should include an instrument to objectively evaluate the adequacy of antifungal use.
A search for mixing between active neutrinos and light sterile neutrinos has been performed by looking for muon neutrino disappearance in two detectors at baselines of 1.04 and 735 km, using a ...combined MINOS and MINOS+ exposure of 16.36×10^{20} protons on target. A simultaneous fit to the charged-current muon neutrino and neutral-current neutrino energy spectra in the two detectors yields no evidence for sterile neutrino mixing using a 3+1 model. The most stringent limit to date is set on the mixing parameter sin^{2}θ_{24} for most values of the sterile neutrino mass splitting Δm_{41}^{2}>10^{-4} eV^{2}.
The high impact of air quality on environmental and human health justifies the increasing research activity regarding its measurement, modelling, forecasting and anomaly detection. Raw data offered ...by sensors usually makes the mentioned time series disciplines difficult. This is why the application of techniques to improve time series processing is a challenge. In this work, Singular Spectral Analysis (SSA) is applied to air quality analysis from real recorded data as part of the Help Responder research project. Authors evaluate the benefits of working with SSA processed data instead of raw data for modelling and estimation of the resulting time series. However, what is more relevant is the proposal to detect indoor air quality anomalies based on the analysis of the time derivative SSA signal when the time derivative of the noisy original data is useless. A dual methodology, evaluating level and dynamics of the SSA signal variation, contributes to identifying risk situations derived from air quality degradation.
Alcohol drinking and nicotine vaping often co-occur and dependence on both substances is common. However, the impact of nicotine vaping on alcohol consumption is not fully understood.
We examined the ...effects of nicotine vaping on ethanol drinking in female and male C57BL/6 J mice using an electronic nicotine delivery system and intermittent access two-bottle choice (IA-2BC) drinking. Mice were exposed to electronic nicotine vapor (3%) or propylene glycol/vegetable glycerol (PG/VG) control for 3 h sessions daily for 4 weeks and voluntary alcohol consumption was monitored. Nicotine vapor exposure was stopped and voluntary alcohol drinking was measured for a 2 week abstinence period. We also examined the effects of alcohol and nicotine on locomotion, temperature, and nicotine metabolism.
Following acute nicotine vapor exposure, alcohol drinking was increased in males but not in females. Thermoregulation was disrupted following nicotine vapor exposure and voluntary drinking. Male and female mice displayed increased locomotor activity immediately following chronic nicotine vapor exposure, and an anxiolytic effect was seen in males. In nicotine vapor abstinence, female mice displayed increased alcohol consumption. Locomotor activity and anxiolytic effects remained elevated in male but not female mice. Female mice displayed higher levels of serum nicotine and hydroxycotinine, suggesting impaired metabolism following chronic drinking and nicotine vapor exposure.
Collectively, these results suggest that while both male and female ethanol-drinking mice experience the stimulatory effects of nicotine vapor, only in males is there a parallel increase in ethanol drinking and only females display impairments in nicotine metabolism after drinking.
•Acute nicotine vaping increases short-term alcohol drinking in male mice•Chronic nicotine vaping does not affect long-term drinking in male and female mice•Nicotine vapor promotes locomotion in males and females and is anxiolytic in males•Female mice displayed higher levels of serum nicotine and hydroxycotinine•Nicotine vapor abstinence does not impact drinking or locomotor effects in males
When a qubit or spin interacts with others under a many-body Hamiltonian, the information it contains progressively scrambles. Here, nuclear spins of an adamantane crystal are used as a quantum ...simulator to monitor such dynamics through out-of-time-order correlators, while a Loschmidt echo (LE) asses how weak perturbations degrade the information encoded in these increasingly complex states. Both observables involve the implementation of a time-reversal procedure which, in practice, involves inverting the sign of the effective Hamiltonian. Our protocols use periodic radio frequency pulses to modulate the natural dipolar interaction implementing a Hamiltonian that can be scaled down at will. Meanwhile, experimental errors and strength of perturbative terms remain constant and can be quantified through the LE. For each scaling factor, information spreading occurs with a timescale, T_{2}, inversely proportional to the local second moment of the Hamiltonian. We find that, when the reversible interactions dominate over the perturbations, the information scrambled among up to 10^{2} spins can still be recovered. However, we find that the LE decay rate cannot become smaller than a critical value 1/T_{3}≈(0.15±0.02)/T_{2}, which only depends on the interactions themselves, and not on the perturbations. This result shows the emergence of a regime of intrinsic irreversibility in accordance to a central hypothesis of irreversibility, hinted from previous experiments.
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