Pushing the Limits: Cognitive, Affective, and Neural Plasticity Revealed by an Intensive Multifaceted Intervention.

Scientific understanding of how much the adult brain can be shaped by experience requires examination of how multiple influences combine to elicit cognitive, affective, and neural plasticity. Using an intensive multifaceted intervention, we discovered that substantial and enduring improvements can occur in parallel across multiple cognitive and neuroimaging measures in healthy young adults. The intervention elicited substantial improvements in physical health, working memory, standardized test performance, mood, self-esteem, self-efficacy, mindfulness, and life satisfaction. Improvements in mindfulness were associated with increased degree centrality of the insula, greater functional connectivity between insula and somatosensory cortex, and reduced functional connectivity between posterior cingulate cortex (PCC) and somatosensory cortex. Improvements in working memory and reading comprehension were associated with increased degree centrality of a region within the middle temporal gyrus (MTG) that was extensively and predominately integrated with the executive control network. The scope and magnitude of the observed improvements represent the most extensive demonstration to date of the considerable human capacity for change. These findings point to higher limits for rapid and concurrent cognitive, affective, and neural plasticity than is widely assumed

Pharmacogenomic testing and outcome among depressed patients in a tertiary care outpatient psychiatric consultation practice

The authors tested the hypothesis that pharmacogenomic genotype knowledge is associated with better clinical and cost outcomes in depressed patients, after controlling for other factors that might differentiate tested and non-tested patients. Medical records of 251 patients, seen in the Mayo Clinic Rochester outpatient psychiatric practice, who had patient health questionnaire-9 (PHQ-9) scores before and after consultation, were reviewed. Comparisons of differences in pre-consultation and post-consultation depression scores and slopes between tested and non-tested patients and between genotype categories of tested patients, were evaluated, along with healthcare cost and utilization comparisons between tested and non-tested patients, using Kruskal–Wallis tests, Wilcoxon rank-sum tests and group mean comparisons, controlling for significant univariate demographic and clinical differences. Tested patients had significantly higher depression diagnosis frequency, baseline PHQ-9 scores, family history of depression, psychiatric hospitalization history, and higher numbers of antidepressant, mood stabilizer and antipsychotic medication trials. After controlling for these differences, there were no differences between tested and non-tested patients in post-baseline depression scores or slopes for CYP genotype categories. For patients with 5-HTTLPR testing, there was significantly more depression score improvement for patients with the long/long genotype at time 4 (N=55, χ2-value=8.0492, P=0.018) and at time 5 (N=44, χ2-value=6.1492, P=0.046). For a subgroup (n=46) with ⩾two pre- and ⩾two post-baseline PHQ-9 scores, the mean difference between pre-baseline and post-baseline PHQ-9 score slopes for tested patients was −0.08 (median −0.01; range −1.20 to 0.15) compared with 0.13 (median 0.02; range −0.18 to 2.16) for non-tested patients (P=0.03). Among genotype categories, mean differences between pre-consultation and post-consultation slopes were significantly better for poor CYP2D6 metabolizers than intermediate or extensive metabolizers (P=0.04); there was a trend for slope differences to be better for 5-HTTLPR long/long genotype patients (P=0.06). Subsets of local tested and consultant-adjusted non-tested controls (n=19), who had 8 years of longitudinal care within the health system, had similar overall mean healthcare costs before and after testing; however, tested patients on average had significantly fewer time-adjusted post-baseline psychiatric admissions (0.8 vs 3.8, P=0.04) and fewer time-adjusted psychiatric consultations and comprehensive mental health-specialty evaluations (4.2 vs 9.9, P=0.03). Prospective study is indicated as to whether and how pharmacogenomic testing in a psychiatric consultation practice may improve clinical and cost outcomes

Human Vault Nanoparticle Targeted Delivery of Antiretroviral Drugs to Inhibit Human Immunodeficiency Virus Type 1 Infection.

"Vaults" are ubiquitously expressed endogenous ribonucleoprotein nanoparticles with potential utility for targeted drug delivery. Here, we show that recombinant human vault nanoparticles are readily engulfed by certain key human peripheral blood mononuclear cells (PBMC), predominately dendritic cells, monocytes/macrophages, and activated T cells. As these cell types are the primary targets for human immunodeficiency virus type 1 (HIV-1) infection, we examined the utility of recombinant human vaults for targeted delivery of antiretroviral drugs. We chemically modified three different antiretroviral drugs, zidovudine, tenofovir, and elvitegravir, for direct conjugation to vaults. Tested in infection assays, drug-conjugated vaults inhibited HIV-1 infection of PBMC with equivalent activity to free drugs, indicating vault delivery and drug release in the cytoplasm of HIV-1-susceptible cells. The ability to deliver functional drugs via vault nanoparticle conjugates suggests their potential utility for targeted drug delivery against HIV-1

Insulation for Daydreams: A Role for Tonic Norepinephrine in the Facilitation of Internally Guided Thought

Although consciousness can be brought to bear on both perceptual and internally generated information, little is known about how these different cognitive modes are coordinated. Here we show that between-participant variance in thoughts unrelated to the task being performed (known as task unrelated thought, TUT) is associated with longer response times (RT) when target presentation occurs during periods when baseline Pupil Diameter (PD) is increased. As behavioral interference due to high baseline PD can reflect increased tonic activity in the norepinephrine system (NE), these results might implicate high tonic NE activity in the facilitation of TUTs. Based on these findings, it is hypothesised that high tonic mode NE leads to a generalised de-amplification of task relevant information that prioritses internally generated thought and insulates it from the potentially disruptive events taking place in the external environment

Unveiling the intruder deformed 02+^+_2 state in 34^{34}Si

The 0$^+_2$ state in $^{34}$Si has been populated at the {\sc Ganil/Lise3} facility through the $\beta$-decay of a newly discovered 1$^+$ isomer in $^{34}$Al of 26(1) ms half-life. The simultaneous detection of $e^+e^-$ pairs allowed the determination of the excitation energy E(0$^+_2$)=2719(3) keV and the half-life T$_{1/2}$=19.4(7) ns, from which an electric monopole strength of $\rho^2$(E0)=13.0(0.9)$\times10^{-3}$ was deduced. The 2$^+_1$ state is observed to decay both to the 0$^+_1$ ground state and to the newly observed 0$^+_2$ state (via a 607(2) keV transition) with a ratio R(2$^+_1$$\rightarrow0^+_1/2^+_1$$\rightarrow0^+_2$)=1380(717). Gathering all information, a weak mixing with the 0$^+_1$ and a large deformation parameter of $\beta$=0.29(4) are found for the 0$^+_2$ state, in good agreement with shell model calculations using a new {\sc sdpf-u-mix} interaction allowing \textit{np-nh} excitations across the N=20 shell gap.Comment: 5 pages, 3 figures, accepted for publication in Physical Review Letter

Automated diffeomorphic registration of anatomical structures with rigid parts: application to dynamic cervical MRI.

International audienceWe propose an iterative two-step method to compute a diffeomorphic non-rigid transformation between images of anatomical structures with rigid parts, without any user intervention or prior knowledge on the image intensities. First we compute spatially sparse, locally optimal rigid transformations between the two images using a new block matching strategy and an efficient numerical optimiser (BOBYQA). Then we derive a dense, regularised velocity field based on these local transformations using matrix logarithms and M-smoothing. These two steps are iterated until convergence and the final diffeomorphic transformation is defined as the exponential of the accumulated velocity field. We show our algorithm to outperform the state-of-the-art log-domain diffeomorphic demons method on dynamic cervical MRI data

Generalized methods and solvers for noise removal from piecewise constant signals. II. New methods

Removing noise from signals which are piecewise constant (PWC) is a challenging signal processing problem that arises in many practical scientific and engineering contexts. In the first paper (part I) of this series of two, we presented background theory building on results from the image processing community to show that the majority of these algorithms, and more proposed in the wider literature, are each associated with a special case of a generalized functional, that, when minimized, solves the PWC denoising problem. It shows how the minimizer can be obtained by a range of computational solver algorithms. In this second paper (part II), using this understanding developed in part I, we introduce several novel PWC denoising methods, which, for example, combine the global behaviour of mean shift clustering with the local smoothing of total variation diffusion, and show example solver algorithms for these new methods. Comparisons between these methods are performed on synthetic and real signals, revealing that our new methods have a useful role to play. Finally, overlaps between the generalized methods of these two papers and others such as wavelet shrinkage, hidden Markov models, and piecewise smooth filtering are touched on

Measurement of the 20 and 90 keV resonances in the 18O(p,α)15{}^{18}{\rm O}(p,\alpha){}^{15}N reaction via THM

The $^{18}{\rm O}(p,\alpha)^{15}{\rm N}$ reaction is of primary importance in several astrophysical scenarios, including fluorine nucleosynthesis inside AGB stars as well as oxygen and nitrogen isotopic ratios in meteorite grains. Thus the indirect measurement of the low energy region of the $^{18}{\rm O}(p,\alpha)^{15}{\rm N}$ reaction has been performed to reduce the nuclear uncertainty on theoretical predictions. In particular the strength of the 20 and 90 keV resonances have been deduced and the change in the reaction rate evaluated.Comment: 4 pages, 4 figures, submitted to PR

Search for new resonant states in 10C and 11C and their impact on the cosmological lithium problem

The observed primordial 7Li abundance in metal-poor halo stars is found to be lower than its Big-Bang nucleosynthesis (BBN) calculated value by a factor of approximately three. Some recent works suggested the possibility that this discrepancy originates from missing resonant reactions which would destroy the 7Be, parent of 7Li. The most promising candidate resonances which were found include a possibly missed 1- or 2- narrow state around 15 MeV in the compound nucleus 10C formed by 7Be+3He and a state close to 7.8 MeV in the compound nucleus 11C formed by 7Be+4He. In this work, we studied the high excitation energy region of 10C and the low excitation energy region in 11C via the reactions 10B(3He,t)10C and 11B(3He,t)11C, respectively, at the incident energy of 35 MeV. Our results for 10C do not support 7Be+3He as a possible solution for the 7Li problem. Concerning 11C results, the data show no new resonances in the excitation energy region of interest and this excludes 7Be+4He reaction channel as an explanation for the 7Li deficit.Comment: Accepted for publication in Phys. Rev. C (Rapid Communication

Prolate-Spherical Shape Coexistence at N=28 in 44^{44}S

The structure of $^{44}$S has been studied using delayed $\gamma$ and electron spectroscopy at \textsc{ganil}. The decay rates of the 0$^+_2$ isomeric state to the 2$^+_1$ and 0$^+_1$ states have been measured for the first time, leading to a reduced transition probability B(E2~:~2$^{+}_1$$\rightarrow$0$^{+}_2)$= 8.4(26)~e$^2$fm$^4$ and a monopole strength $\rho^2$(E0~:~0$^{+}_2$$\rightarrow$0$^{+}_1)$ =~8.7(7)$\times$10$^{-3}$. Comparisons to shell model calculations point towards prolate-spherical shape coexistence and a phenomenological two level mixing model is used to extract a weak mixing between the two configurations.Comment: 5 pages, 3 figures, accepted for publication in Physical Review Letter