A web-based intervention for users of amphetamine-type stimulants: 3-month outcomes of randomized controlled trial

Background: Among illicit drugs, the prevalence of amphetamine-type stimulant (ATS) use is second only to cannabis. Currently, there are no approved pharmacotherapies for ATS problems, but some face-to-face psychotherapies are effective. Web-based interventions have proven to be effective for some substance use problems, but none has specifically targeted ATS users. Objective: The objective of the study was to evaluate the effectiveness of a Web-based intervention for ATS problems on a free-to-access site compared with a waitlist control group. Methods: We used a randomized controlled trial design. The primary outcome measure was self-reported ATS use in the past three months assessed using the Alcohol, Smoking, Substance Involvement Screening Test (ASSIST). Other measures included quality of life (EUROHIS score), psychological distress (K-10 score), days out of role, poly-drug use, general help-seeking intentions, actual help-seeking, and “readiness to change”. The intervention consisted of three fully automated, self-guided modules based on cognitive behavioral therapy and motivation enhancement. The analysis was an intention-to-treat analysis using generalized estimating equation models, with a group by time interaction as the critical assessment.Results: We randomized 160 people (intervention n=81, control n=79). At three months, 35/81 (43%) intervention and 45/79 (57%) control participants provided follow-up data. In the intervention group, 51/81 (63%) completed at least one module. The only significant group by time interaction was for days out of role. The pre/post change effect sizes showed small changes (range d=0.14 to 0.40) favoring the intervention group for poly-drug use, distress, actual help-seeking, and days out of role. In contrast, the control group was favored by reductions in ATS use, improvements in quality of life, and increases in help-seeking intentions (range d=0.09 to 0.16). Conclusions: This Web-based intervention for ATS use produced few significant changes in outcome measures. There were moderate, but nonsignificant reductions in poly-drug use, distress, days partially out of role, and increases in help-seeking. However, high levels of participant attrition, plus low levels of engagement with the modules, preclude firm conclusions being drawn on the efficacy of the intervention and emphasize the problems of engaging this group of clients in a fully automated program

The reaction coordinate mapping in quantum thermodynamics

We present an overview of the reaction coordinate approach to handling strong system-reservoir interactions in quantum thermodynamics. This technique is based on incorporating a collective degree of freedom of the reservoir (the reaction coordinate) into an enlarged system Hamiltonian (the supersystem), which is then treated explicitly. The remaining residual reservoir degrees of freedom are traced out in the usual perturbative manner. The resulting description accurately accounts for strong system-reservoir coupling and/or non-Markovian effects over a wide range of parameters, including regimes in which there is a substantial generation of system-reservoir correlations. We discuss applications to both discrete stroke and continuously operating heat engines, as well as perspectives for additional developments. In particular, we find narrow regimes where strong coupling is not detrimental to the performance of continuously operating heat engines.Comment: 17 pages, 2 tables, 7 figures. As a chapter of: F. Binder, L. A. Correa, C. Gogolin, J. Anders, and G. Adesso (eds.), "Thermodynamics in the quantum regime - Recent Progress and Outlook", (Springer International Publishing

The Cotton Centromere Contains a Ty3-gypsy-like LTR Retroelement

The centromere is a repeat-rich structure essential for chromosome segregation; with the long-term aim of understanding centromere structure and function, we set out to identify cotton centromere sequences. To isolate centromere-associated sequences from cotton, (Gossypium hirsutum) we surveyed tandem and dispersed repetitive DNA in the genus. Centromere-associated elements in other plants include tandem repeats and, in some cases, centromere-specific retroelements. Examination of cotton genomic survey sequences for tandem repeats yielded sequences that did not localize to the centromere. However, among the repetitive sequences we also identified a gypsy-like LTR retrotransposon (Centromere Retroelement Gossypium, CRG) that localizes to the centromere region of all chromosomes in domestic upland cotton, Gossypium hirsutum, the major commercially grown cotton. The location of the functional centromere was confirmed by immunostaining with antiserum to the centromere-specific histone CENH3, which co-localizes with CRG hybridization on metaphase mitotic chromosomes. G. hirsutum is an allotetraploid composed of A and D genomes and CRG is also present in the centromere regions of other AD cotton species. Furthermore, FISH and genomic dot blot hybridization revealed that CRG is found in D-genome diploid cotton species, but not in A-genome diploid species, indicating that this retroelement may have invaded the A-genome centromeres during allopolyploid formation and amplified during evolutionary history. CRG is also found in other diploid Gossypium species, including B and E2 genome species, but not in the C, E1, F, and G genome species tested. Isolation of this centromere-specific retrotransposon from Gossypium provides a probe for further understanding of centromere structure, and a tool for future engineering of centromere mini-chromosomes in this important crop species

Pathogenic Huntingtin Repeat Expansions in Patients with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis.

We examined the role of repeat expansions in the pathogenesis of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) by analyzing whole-genome sequence data from 2,442 FTD/ALS patients, 2,599 Lewy body dementia (LBD) patients, and 3,158 neurologically healthy subjects. Pathogenic expansions (range, 40-64 CAG repeats) in the huntingtin (HTT) gene were found in three (0.12%) patients diagnosed with pure FTD/ALS syndromes but were not present in the LBD or healthy cohorts. We replicated our findings in an independent collection of 3,674 FTD/ALS patients. Postmortem evaluations of two patients revealed the classical TDP-43 pathology of FTD/ALS, as well as huntingtin-positive, ubiquitin-positive aggregates in the frontal cortex. The neostriatal atrophy that pathologically defines Huntington's disease was absent in both cases. Our findings reveal an etiological relationship between HTT repeat expansions and FTD/ALS syndromes and indicate that genetic screening of FTD/ALS patients for HTT repeat expansions should be considered

Unconventional mass enhancement around the Dirac nodal loop in ZrSiS

The topological properties of fermions arise from their low-energy Dirac-like band dispersion and associated chiralities. Initially confined to points, extensions of the Dirac dispersion to lines and even loops have now been uncovered and semimetals hosting such features have been identified. However, experimental evidence for the enhanced correlation effects predicted to occur in these topological semimetals has been lacking. Here, we report a quantum oscillation study of the nodal loop semimetal ZrSiS in high magnetic fields that reveals significant enhancement in the effective mass of the quasiparticles residing near the nodal loop. Above a threshold field, magnetic breakdown occurs across gaps in the loop structure with orbits that enclose different windings around its vertices, each winding accompanied by an additional \pi-Berry phase. The amplitudes of these breakdown orbits exhibit an anomalous temperature dependence. These findings demonstrate the emergence of novel, correlation-driven physics in ZrSiS associated with the Dirac-like quasiparticles.Comment: 20 pages, 4 figure

Identification and characterization of trimethylamine N-oxide (TMAO) demethylase and TMAO permease in Methylocella silvestris BL2

Methylocella silvestris, an alphaproteobacterium isolated from a forest soil, can grow on trimethylamine N-oxide (TMAO) as a sole nitrogen source, however, the molecular and biochemical mechanisms underpinning its growth remain unknown. Marker-exchange mutagenesisenabled the identification of several genes involved in TMAO metabolism, including Msil_3606, a permease of the amino acids-polyamine (APC) superfamily, and Msil_3603, consisting of anN-terminal domain of unknown function (DUF1989) and a C-terminal tetrahydrofolate-binding domain. Null mutants of Msil_3603 and Msil_3606 can no longer grow on TMAO. Purified Msil_3603 from recombinant Escherichia coli can convert TMAO to dimethylamine and formaldehyde (1 TMAO [RIGHTWARDS ARROW] 1 dimethylamine + 1 formaldehyde), confirming that it encodes a bona fide TMAO demethylase (Tdm). Tdm of M. silvestrisand eukaryotic TMAO demethylases have no sequence homology and contrasting characteristics. Recombinant Tdm of M. silvestris appears to be hexameric, has a high affinity for TMAO (Km= 3.3 mM; Vmax=21.7 nmolmin-1mg-1) and only catalyses demethylation of TMAO and a structural homologue, dimethyldodecylamine N-oxide. Our study has contributed to the understanding of the genetic and biochemical mechanisms for TMAO degradation in M. silvestris