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This article is a clinical guide which discusses the “state-of-the-art” usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (more than 70 international expert endorsers), based on 6 decades of experience, for the recommendations herein exposited. They are based on empirical evidence and expert opinion—this guide is presented as a new specialist-consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy—while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward “bridging” methods that may be used to transition simply and safely from other antidepressants to MAOIs.
A multiproxy oxygen and carbon isotope (δ13C and δ18O), growth rate, and trace element stalagmite paleoenvironmental record is presented for the Early Holocene from Ethiopia. The annually laminated stalagmite grew from 10.6 to 10.4 ka and from 9.7 to 9.0 ka with a short hiatus at ~9.25 ka. Statistically significant and coherent spectral frequencies in δ13C and δ18O are observed at 15–25 and 19–23 years, respectively. The observed ~1‰ amplitude variability in stalagmite δ18O is likely forced by nonequilibrium deposition, due to kinetic effects during the progressive degassing of CO2 from the water film during stalagmite formation. These frequencies are similar to the periodicity reported for other Holocene stalagmite records from Ethiopia, suggesting that multidecadal variability in stalagmite δ18O is typical. Several processes can lead to this multidecadal variability and operate in different directions. A hydroclimate forcing is likely the primary control on the extent of the partial evaporation of soil and shallow epikarst water and associated isotopic fractionation. The resulting oxygen isotope composition of percolation water is subsequently modulated by karst hydrology. Further isotopic fractionation is possible in-cave during nonequilibrium stalagmite deposition. Combined with possible recharge biases in drip-water δ18O, these processes can generate multidecadal δ18O variability.
The coronavirus disease 2019 (COVID-19) pandemic has significantly increased depression rates, particularly in emerging adults. The aim of this study was to examine longitudinal changes in depression risk before and during COVID-19 in a cohort of emerging adults in the U.S. and to determine whether prior drinking or sleep habits could predict the severity of depressive symptoms during the pandemic.
Participants were 525 emerging adults from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA), a five-site community sample including moderate-to-heavy drinkers. Poisson mixed-effect models evaluated changes in the Center for Epidemiological Studies Depression Scale (CES-D-10) from before to during COVID-19, also testing for sex and age interactions. Additional analyses examined whether alcohol use frequency or sleep duration measured in the last pre-COVID assessment predicted pandemic-related increase in depressive symptoms.
The prevalence of risk for clinical depression tripled due to a substantial and sustained increase in depressive symptoms during COVID-19 relative to pre-COVID years. Effects were strongest for younger women. Frequent alcohol use and short sleep duration during the closest pre-COVID visit predicted a greater increase in COVID-19 depressive symptoms.
The sharp increase in depression risk among emerging adults heralds a public health crisis with alarming implications for their social and emotional functioning as this generation matures. In addition to the heightened risk for younger women, the role of alcohol use and sleep behavior should be tracked through preventive care aiming to mitigate this looming mental health crisis.
Constant-load creep tests were performed at −10°C at various compressive stresses from 0.05 to 0.75 MPa on specimens taken every 10 m along a firn core extracted at Summit, Greenland in June 2017. The microstructures before and after creep testing were examined using both X-ray microtomography (micro-CT) and optical images from thin sections. An Andrade-like equation was used to describe the primary creep behavior and yielded the time exponent k of 0.17–0.76. The onset of secondary creep occurred at strains of ~0.5–3% but was sometimes not observed at all in shallow firn specimens and at stresses ⩽0.43 MPa even for strain up to 32%. For the 50–80 m firn crept at stresses ⩾0.55 MPa, secondary creep occurred at strains of 2.6 ± 0.28%, and the stress exponent, n, in Glen's law, was found to range from 4.1 to 4.6, similar to those observed for fully dense ice. Micro-CT observations of crept specimens showed that in most cases, the specific surface area, the total porosity and the structure model index decreased, while the structure thickness increased with increasing density. These microstructural characteristics are consistent with the densification of the firn. Optical images from thin sections showed that recrystallization occurred in some specimens that had undergone secondary creep.
Medical residents are an important group for antimicrobial stewardship programs (ASPs) to target with interventions aimed at improving antibiotic prescribing. In this study, we compared antimicrobial prescribing practices of 2 academic medical teams receiving different ASP training approaches along with a hospitalist control group.
Retrospective cohort study comparing guideline-concordant antibiotic prescribing for 3 common infections among a family medicine (FM) resident service, an internal medicine (IM) resident service, and hospitalists.
Community teaching hospital.
Adult patients admitted between July 1, 2016, and June 30, 2017, with a discharge diagnosis of pneumonia, cellulitis, and urinary tract infections were reviewed.
All 3 medical teams received identical baseline ASP education and daily antibiotic prescribing audit with feedback via clinical pharmacists. The FM resident service received an additional layer of targeted ASP intervention that included biweekly stewardship-focused rounds with an ASP physician and clinical pharmacist leadership. Guideline-concordant prescribing was assessed based on the institution’s ASP guidelines.
Of 1,572 patients, 295 (18.8%) were eligible for inclusion (FM, 96; IM, 69; hospitalist, 130). The percentage of patients receiving guideline-concordant antibiotic selection empirically was similar between groups for all diagnoses (FM, 87.5%; IM, 87%; hospitalist, 83.8%; P = .702). No differences were observed in appropriate definitive antibiotic selection among groups (FM, 92.4%; IM, 89.1%; hospitalist, 89.9%; P = .746). The FM resident service was more likely to prescribe a guideline-concordant duration of therapy across all diagnoses (FM, 74%; IM, 56.5%; hospitalist, 44.6%; P < .001).
Adding dedicated stewardship-focused rounds into the graduate medical curriculum demonstrated increased guideline adherence specifically to duration of therapy recommendations.
A verified instrumental calibration of annually resolved δ18O for a stalagmite from Gümüşhane in northeast Turkey is presented and cross-validated using a ‘leave-one-out’ technique. The amount of late autumn to winter precipitation is negatively correlated with stalagmite δ18O between AD 1938 and 2004. The observed relationship is extrapolated back to ~ AD 1500 leading to the first long winter precipitation reconstruction for this region. Modern day October to January precipitation is linked to pressure fields in Western Russia. Anomalously lower reconstructed rainfall is recorded in AD 1540–1560 at which time higher pressure over the Caspian Sea region is inferred.
In North America, terrestrial records of biodiversity and climate change that span Marine Oxygen Isotope Stage (MIS) 5 are rare. Where found, they provide insight into how the coupling of the ocean–atmosphere system is manifested in biotic and environmental records and how the biosphere responds to climate change. In 2010–2011, construction at Ziegler Reservoir near Snowmass Village, Colorado (USA) revealed a nearly continuous, lacustrine/wetland sedimentary sequence that preserved evidence of past plant communities between ~140 and 55 ka, including all of MIS 5. At an elevation of 2705 m, the Ziegler Reservoir fossil site also contained thousands of well-preserved bones of late Pleistocene megafauna, including mastodons, mammoths, ground sloths, horses, camels, deer, bison, black bear, coyotes, and bighorn sheep. In addition, the site contained more than 26,000 bones from at least 30 species of small animals including salamanders, otters, muskrats, minks, rabbits, beavers, frogs, lizards, snakes, fish, and birds. The combination of macro- and micro-vertebrates, invertebrates, terrestrial and aquatic plant macrofossils, a detailed pollen record, and a robust, directly dated stratigraphic framework shows that high-elevation ecosystems in the Rocky Mountains of Colorado are climatically sensitive and varied dramatically throughout MIS 5.
Recent studies have suggested a physical link between Ca++ ions and an increase in the ductility or ‘softening’ of polycrystalline ice. In order to investigate the potential effects of Ca++ on deformation, we created sets of both undoped and CaSO4-doped specimens of polycrystalline ice for testing in uniaxial tension or compression. Deformation tests in tension were carried out under a constant load at an initial stress of 0.75 MPa and a temperature of −6°C. Compression tests were carried out at −10 and −20°C at constant strain rates of 1×10−4 s−1, 1 × 10−5 s−1 and 1 × 10−6 s−1 and taken to 5% strain. Our results show that CaSO4 increases the strength of polycrystalline ice at higher strain rates and lower temperatures, an effect that decreases with decreasing strain rate and higher temperatures. A microstructural analysis of the post-test compression specimens reveals mean grain diameters much larger in the CaSO4-doped specimens tested at the lowest applied strain rate of 1 × 10−6 s−1. Precipitates were found to have formed along grain boundaries in some doped specimens and evidence of intergranular fracture was observed in all specimens tested at 1 × 10−4 and 1 × 10−5 s−1. In tension-tested specimens, there was no difference in the mean grain diameter between doped and undoped specimens at 25% strain.
The study examined whether cardiovascular responses to active or passive coping tasks and single or multiple tasks predicted changes in resting blood pressure (BP) over a ten-month period. Heart rate (HR), BP, cardiac output (CO), and total peripheral resistance (TPR) were measured at rest, and during mental stress tests (mental arithmetic, speech, and cold pressor tasks). A total of 104 eligible participants participated in the initial study, and 77 (74.04%) normotensive adult participants’ resting BP were re-evaluated at ten-month follow-up. Regression analyses indicated that after adjustment for baseline BP, initial age, gender, body mass index, family history of cardiovascular disease, and current cigarette smoking, heighted systolic blood pressure (SBP) and HR responses to an active coping task (mental arithmetic) were associated with increased future SBP (ΔR2 = .060, ΔR2 = .045, respectively). Further, aggregated SBP responsivity (over the three tasks) to the predictor models resulted in significant, but smaller increases in ΔR2 accounting for .040 of the variance of follow-up SBP. These findings suggest that cardiovascular responses to active coping tasks predict future SBP. Further, compared with single tasks, the findings revealed that SBP responses to three tasks were less predictive compared to an individual task (i.e., mental arithmetic). Of importance, hemodynamic reactivity (namely CO and TPR) did not predict future BP suggesting that more general psychophysiological processes (e.g., inflammation, platelet aggregation) may be implicated, or that BP, but not hemodynamic reactivity may be a marker of hypertension.
Mutations in the progranulin gene (GRN) are a common cause of familial frontotemporal dementia. We used a comprehensive neuropsychological battery to investigate whether early cognitive changes could be detected in GRN mutation carriers before dementia onset. Twenty-four at-risk members from six families with known GRN mutations underwent detailed neuropsychological testing. Group differences were investigated by domains of attention, language, visuospatial function, verbal memory, non-verbal memory, working memory and executive function. There was a trend for mutation carriers (n=8) to perform more poorly than non-carriers (n=16) across neuropsychological domains, with significant between group differences for visuospatial function (p<.04; d=0.92) and working memory function (p<.02; d=1.10). Measurable cognitive differences exist before the development of frontotemporal dementia in subjects with GRN mutations. The neuropsychological profile of mutation carriers suggests early asymmetric, right hemisphere brain dysfunction that is consistent with recent functional imaging data from our research group and the broader literature. (JINS, 2014, 20, 1–10)
Two types of as-cast microstructures have been observed in a series of near-equiatomic FeNiMnAl alloys: 1) an ultrafine microstructure in Fe30Ni20Mn20Al30  and Fe25Ni25Mn20Al30, which consists of (Fe, Mn)-rich B2-ordered (ordered b.c.c.) and (Ni, Al)-rich L21-ordered (Heusler) phases aligned along <100>; and 2) a fine two-phase microstructure in Fe30Ni20Mn30Al20 and Fe25Ni25Mn30Al20, which consists of alternating (Fe, Mn)-rich f.c.c. and (Ni, Al)-rich B2-ordered platelets with an orientation relationship close to f.c.c (002) // B2 (002); f.c.c.  // B2  . The phases in Fe25Ni25Mn20Al30 coarsened upon annealing with no significant change in the chemical partitioning. The hardness behavior was studied as a function of the annealing time at 823 K. AnL21-to-B2 transition, which occurred at 573-623K, was observed using in-situ heating in a TEM. After annealing at 973 K for 100 h, needle-shaped clusters of (Fe, Mn)-rich precipitates were observed along the grain boundaries and in the matrix. The temperature dependence of the yield strength of as-cast Fe25Ni25Mn20Al30 was also studied.
Iron magnetic nanoparticles were synthesized under an inert atmosphere via the reaction between FeCl3 and NaBH4 in droplets of water in a microemulsion consisting of octane with cetyl trimethylammonium bromide and butanol as surfactants. A thin Fe3O4 layer was produced on the iron nanoparticles using slow, controlled oxidation at room temperature. A silica shell was deposited on the Fe3O4 using 3-aminopropyltrimethoxysilane following the method of Zhang et al. [Mater. Sci. Eng. C 30 (2010) 92–97]. The structure and chemistry of the resulting nanoparticles were studied using variety of methods and their magnetic properties were determined. The diameter of the iron core was typically 8-16 nm, while the thickness of the Fe3O4 shell was 2-3 nm. The presence of the silica layer was confirmed using Fourier transform infra-red spectroscopy and the number of NH2-groups on each nanoparticle was determined based on colorimetric tests using ortho-phthalaldehyde.
The pin-on-disc wear behavior of nanostructured two-phase Fe30Ni20Mn20Al30 and eutectic lamellar-structured Fe30Ni20Mn35Al15 is compared emphasizing the influence of the microstructure and mechanical properties of alloys as well as the effect of test environment. Although the wear of both alloys was greater in oxygen-containing environments, eutectic Fe30Ni20Mn35Al15 is less sensitive to oxygen than nanostructured Fe30Ni20Mn20Al30. Abrasive wear dominated during the wear in all cases, while plastic deformation also occurred during the wear of eutectic Fe30Ni20Mn35Al15. A tribolayer of zirconia, which was embedded in the surface of the wear pin, was characterized using a scanning transmission electron microscope equipped with an energy dispersive spectrometer.
The material characterization toolbox has recently experienced a number of parallel revolutionary advances, foreshadowing a time in the near future when material scientists can quantify material structure evolution across spatial and temporal space simultaneously. This will provide insight to reaction dynamics in four-dimensions, spanning multiple orders of magnitude in both temporal and spatial space. This study presents the authors’ viewpoint on the material characterization field, reviewing its recent past, evaluating its present capabilities, and proposing directions for its future development. Electron microscopy; atom probe tomography; x-ray, neutron and electron tomography; serial sectioning tomography; and diffraction-based analysis methods are reviewed, and opportunities for their future development are highlighted. Advances in surface probe microscopy have been reviewed recently and, therefore, are not included [D.A. Bonnell et al.: Rev. Modern Phys. in Review]. In this study particular attention is paid to studies that have pioneered the synergetic use of multiple techniques to provide complementary views of a single structure or process; several of these studies represent the state-of-the-art in characterization and suggest a trajectory for the continued development of the field. Based on this review, a set of grand challenges for characterization science is identified, including suggestions for instrumentation advances, scientific problems in microstructure analysis, and complex structure evolution problems involving material damage. The future of microstructural characterization is proposed to be one not only where individual techniques are pushed to their limits, but where the community devises strategies of technique synergy to address complex multiscale problems in materials science and engineering.