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Stratigraphic records extending to Marine Oxygen Isotope Stage (MIS) 3 (57,000–29,000 cal yr BP) or older in Beringia are extremely rare. Three stratigraphic sections in interior western Alaska show near continuous sedimentological and environmental progressions extending from at least MIS 3, if not older, through MIS 1 (14,000 cal yr BP–present). The Kolmakof, Sue Creek, and VABM (vertical angle bench mark) Kuskokwim sections along the central Kuskokwim River, once a highland landscape at the fringe of central and eastern Beringia, contain aeolian deposition and soil sequences dating beyond 50,000 14C yr BP. Thick peaty soil, shallow lacustrine, and tephra deposits represent the MIS 3 interstade (or older). Sand sheet and loess deposits, wedge cast development, and very thin soil development mark the later MIS 3 period and the transition into the MIS 2 stade (29,000–14,000 cal yr BP). Loess accumulation with thicker soil development occurred between ~16,000–13,500 cal yr BP at the MIS 2 and MIS 1 transition. After ~13,500 cal yr BP, loess accumulation waned and peat development increased throughout MIS 1. These stratigraphic sequences represent transitions between a warm and moist period during MIS 3, to a cooler and more arid period during MIS 2, then a return to warmer and moister climates in MIS 1.
We sampled individual growth rings from three ancient remnant bald cypress (Taxodium distichum) trees from a massive buried deposit at the mouth of the Altamaha River on the Georgia Coast to determine the best technique for radiocarbon (14C) dating pretreatment. The results of our comparison of traditional ABA pretreatment and holocellulose and α-cellulose fractions show no significant differences among the pretreatments (<1 sigma) thereby suggesting that ABA pretreatment will prove sufficient for the development of a high-resolution 14C tree-ring chronology based on these ancient bald cypresses which will indicate whether the U.S. Southeast is subject to a regional radiocarbon offset.
First-degree relatives of patients with psychotic disorder have higher levels of polygenic risk (PRS) for schizophrenia and higher levels of intermediate phenotypes.
We conducted, using two different samples for discovery (n = 336 controls and 649 siblings of patients with psychotic disorder) and replication (n = 1208 controls and 1106 siblings), an analysis of association between PRS on the one hand and psychopathological and cognitive intermediate phenotypes of schizophrenia on the other in a sample at average genetic risk (healthy controls) and a sample at higher than average risk (healthy siblings of patients). Two subthreshold psychosis phenotypes, as well as a standardised measure of cognitive ability, based on a short version of the WAIS-III short form, were used. In addition, a measure of jumping to conclusion bias (replication sample only) was tested for association with PRS.
In both discovery and replication sample, evidence for an association between PRS and subthreshold psychosis phenotypes was observed in the relatives of patients, whereas in the controls no association was observed. Jumping to conclusion bias was similarly only associated with PRS in the sibling group. Cognitive ability was weakly negatively and non-significantly associated with PRS in both the sibling and the control group.
The degree of endophenotypic expression of schizophrenia polygenic risk depends on having a sibling with psychotic disorder, suggestive of underlying gene–environment interaction. Cognitive biases may better index genetic risk of disorder than traditional measures of neurocognition, which instead may reflect the population distribution of cognitive ability impacting the prognosis of psychotic disorder.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
In this article we document Canada’s trade policy response to late nineteenth and early twentieth century globalization by linking newly digitized annual productspecific data on the value of Canadian imports and duties paid from 1870–1913, to establishment-specific production and location information drawn from the manuscripts of the 1871 industrial census. We find evidence of a highly selective move towards protectionism following the adoption of the National Policy in 1879. Changes in the Canadian tariff schedule narrowly targeted manufactured import products that had close substitutes produced by relatively large, urban, politically influential domestic manufacturers.
This is a copy of the slides presented at the meeting but not formally written up for the volume.
Complex oxides exhibit various physical properties such as ferromagnetism, dielectricity, and superconductivity. The nature of these physical properties is determined by very small characteristic length scales. Future heteroepitaxial devices based on such oxides have great potential for applications provided that the growth can be controlled on an atomic level.Currently, in-situ growth morphology characterization is mostly performed by diffraction techniques such as Reflection High Energy Electron Diffraction (RHEED). We have now realized a system, in which Atomic Force Microscopy (AFM) can be performed during Pulsed Laser Deposition (PLD). Deposition and force microscopy are performed in one vacuum chamber and via a fast transfer (in the order of seconds) the surface of a sample can be scanned. In our system we take advantage of the pulsed deposition process, because microscopy measurements can be carried out between the pulses. This provides real-time morphology information on the microscopic scale during growth. The transfer mechanism allows switching between microscopy and deposition with a re-position accuracy of ±500 nm which gives new opportunities to study growth processes. This system is especially useful to study crystal growth, phase transitions, diffusion processes and nanoparticle formation. Furthermore, it will provide information if RHEED is not possible, for example during amorphous and polycrystalline growth. In this contribution, we will present the results obtained with a few model systems on oxide surfaces. We have used treated SrTiO3 (001) oxide substrates with 0.4 nm high substrate steps which are ideal for these experiments. Several materials are currently investigated, such as Au, SrRuO3, PbTiO3 and transparent conducting indium tin oxide. The in-situ AFM has been used to study the initial growth of these materials at various deposition conditions. The physical properties of these materials are correlated with the growth conditions, such as deposition pressure, fluency and substrate temperature. Besides showing the growth results obtained with the AFM, the latest equipment developments will be presented. To scan at elevated temperatures, small heaters have been developed. These small thermal mass heaters are designed in such a way to obtain stable monitoring settings at temperatures >973K in a high pressure environment or even ambient pressure. With high temperature microscopy, growth characterization at typical deposition conditions of complex oxides becomes feasible.
In coastal and island archaeology, carbonate mollusk shells are often among the most abundant materials available for radiocarbon (14C) dating. The marsh periwinkle (Littorina irrorata) is one of these such species, ubiquitously found along the Atlantic and Gulf coasts of the United States in both modern and archaeological contexts. This paper presents a novel approach to dating estuarine mollusks where rather than attempting to characterize the size and variability of reservoir effects to “correct” shell carbonate dates, we describe a compound-specific approach that isolates conchiolin, the organic matter bound with the shell matrix of the L. irrorata. Conchiolin typically constitutes <5% of shell weight. In L. irrorata, it is derived from the snail’s terrestrial diet and is thus not strongly influenced by marine, hardwater, or other carbon reservoir effects. We compare the carbon isotopes (δ13C and Δ14C) of L. irrorata shell carbonate, conchiolin, and bulk soft tissue from six modern, live-collected specimens from Apalachicola Bay, Florida, with samples that represent possible sources of carbon within their environment including surface sediments, marsh plant tissues, and dissolved inorganic carbon (DIC) in water. Ultimately, this paper demonstrates that samples obtained from wet chemical oxidation of L. irrorata conchiolin produces accurate 14C dates.
The 22q11.2 deletion syndrome (22q11DS) is caused by a deletion on chromosome 22 locus q11.2. This copy number variant results in haplo-insufficiency of the catechol-O-methyltransferase (COMT) gene, and is associated with a significant increase in the risk for developing cognitive impairments and psychosis. The COMT gene encodes an enzyme that primarily modulates clearance of dopamine (DA) from the synaptic cleft, especially in the prefrontal cortical areas. Consequently, extracellular DA levels may be increased in prefrontal brain areas in 22q11DS, which may underlie the well-documented susceptibility for cognitive impairments and psychosis in affected individuals. This study aims to examine DA D2/3 receptor binding in frontal brain regions in adults with 22q11DS, as a proxy of frontal DA levels.
The study was performed in 14 non-psychotic, relatively high functioning adults with 22q11DS and 16 age- and gender-matched healthy controls (HCs), who underwent DA D2/3 receptor [18F]fallypride PET imaging. Frontal binding potential (BPND) was used as the main outcome measure.
BPND was significantly lower in adults with 22q11DS compared with HCs in the prefrontal cortex and the anterior cingulate gyrus. After Bonferroni correction significance remained for the anterior cingulate gyrus. There were no between-group differences in BPND in the orbitofrontal cortex and anterior cingulate cortex.
This study is the first to demonstrate lower frontal D2/3 receptor binding in adults with 22q11DS. It suggests that a 22q11.2 deletion affects frontal dopaminergic neurotransmission.
Healthcare organizations are required to provide workers with respiratory protection (RP) to mitigate hazardous airborne inhalation exposures. This study sought to better identify gaps that exist between RP guidance and clinical practice to understand issues that would benefit from additional research or clarification.
Buprenorphine/samidorphan (BUP/SAM), a combination of BUP (a µ-opioid receptor partial agonist and κ-antagonist) and SAM (a sublingually bioavailable µ-opioid antagonist), is an investigational opioid system modulator for depression. BUP/SAM has shown efficacy versus placebo as an adjunctive treatment for major depressive disorder (MDD) and a consistent safety profile in previously reported, placebo-controlled clinical studies.1,2
1. To characterize the safety profile following long-term treatment with BUP/SAM
2. To explore depression symptoms and remission rates in patients with MDD following long-term treatment with BUP/SAM
FORWARD-2 (Clinicaltrials.gov ID: NCT02141399) enrolled patients who had participated in 1 of 4 controlled studies as well as de novo patients. All patients had a confirmed diagnosis of MDD, had a history of inadequate response to standard antidepressant therapies (ADTs), and had been treated with an adequate dose of an established ADT for ≥8weeks before BUP/SAM initiation. ADT dosage could be titrated, but the ADT could not be changed. During the study, patients received open-label, sublingual BUP/SAM 2mg/2mg as adjunctive treatment for up to 52weeks. Safety (primary objective) was assessed via adverse events (AEs), vital signs, laboratory analytes, and electrocardiography. Suicidal ideation or behavior (SIB) was evaluated by the Columbia Suicide Severity Rating Scale. Abuse potential, dependence, and withdrawal were assessed by AEs and the Clinical Opiate Withdrawal Scale. Exploratory efficacy endpoints included mean Montgomery–Åsberg Depression Rating Scale (MADRS) scores and remission rate (MADRS ≤10).
Of 1454 total patients, 49% completed the 52-week study, 11% discontinued due to an AE, and 40% discontinued because of other reasons as of the interim data cutoff date (April 30, 2017). Most AEs were of mild/moderate severity. Serious AEs were reported in 3.2% of patients. AEs occurring in ≥10% of patients were nausea, headache, constipation, dizziness, and somnolence. There was no evidence of increased risk of SIB with BUP/SAM. Incidence of euphoria-related events was low (1.2%). After abrupt discontinuation of BUP/SAM, there was little evidence of withdrawal. BUP/SAM was not associated with meaningful changes in laboratory or metabolic parameters or in bodyweight. The mean MADRS score decreased from 22.9 (±9.7) at baseline to 9.8 (±8.8) after 52weeks. The remission rate at 52weeks was 52.5%.
Long-term treatment with BUP/SAM did not reveal any new safety findings and confirmed that the risk of abuse and dependence with BUP/SAM was low. BUP/SAM maintained an antidepressant effect for up to 52weeks of treatment in patients with MDD.
Here we present the synthesis of porous platinum–palladium macrobeams templated from high aspect ratio Magnus’ salt needle derivatives. The combination of [PtCl4]2− and/or [PdCl4]2− with [Pt(NH3)4]2+ ions results in salt needles ranging from 15 to 300 µm in length. Electrochemical reduction of the salt templates results in porous macrobeams with a square cross-section. Porous side wall texture and elemental composition was controlled with initial platinum to palladium salt ratio. Macrobeam free-standing films exhibited a specific capacitance up to 11.73 F/g and a solvent accessible surface area of 26.6 m2/g. These salt-templated porous platinum–palladium macrobeams offer a promising material for fuel cell catalysis.
To determine the efficacy in eradicating Staphylococcus aureus (SA) carriage of a 5-day preoperative decolonization bundle compared to 2 disinfectant soap showers, with both regimens self-administered at home.
Open label, single-center, randomized clinical trial.
Ambulatory orthopedic, urologic, neurologic, colorectal, cardiovascular, and general surgery clinics at a tertiary-care referral center in the United States.
Patients at the University of Minnesota Medical Center planning to have elective surgery and not on antibiotics.
Consenting participants were screened for SA colonization using nasal, throat, axillary, and perianal swab cultures. Carriers of SA were randomized, stratified by methicillin resistance status, to a decolonization bundle group (5 days of nasal mupirocin, chlorhexidine gluconate [CHG] bathing, and CHG mouthwash) or control group (2 preoperative showers with antiseptic soap). Colonization status was reassessed preoperatively. The primary endpoint was absence of SA at all 4 screened body sites.
Of 427 participants screened between August 31, 2011, and August 9, 2016, 127 participants (29.7%) were SA carriers. Of these, 121 were randomized and 110 were eligible for efficacy analysis (57 decolonization bundle group, 53 control group). Overall, 90% of evaluable participants had methicillin-susceptible SA strains. Eradication of SA at all body sites was achieved for 41 of 57 participants (71.9%) in the decolonization bundle group and for 13 of 53 participants (24.5%) in the control group, a difference of 47.4% (95% confidence interval [CI], 29.1%–65.7%; P<.0001).
An outpatient preoperative antiseptic decolonization bundle aimed at 4 body sites was significantly more effective in eradicating SA than the usual disinfectant showers (ie, the control).
Background: Central neuropathic pain syndromes are a result of central nervous system injury, most commonly related to stroke, traumatic spinal cord injury, or multiple sclerosis. These syndromes are distinctly less common than peripheral neuropathic pain, and less is known regarding the underlying pathophysiology, appropriate pharmacotherapy, and long-term outcomes. The objective of this study was to determine the long-term clinical effectiveness of the management of central neuropathic pain relative to peripheral neuropathic pain at tertiary pain centers. Methods: Patients diagnosed with central (n=79) and peripheral (n=710) neuropathic pain were identified for analysis from a prospective observational cohort study of patients with chronic neuropathic pain recruited from seven Canadian tertiary pain centers. Data regarding patient characteristics, analgesic use, and patient-reported outcomes were collected at baseline and 12-month follow-up. The primary outcome measure was the composite of a reduction in average pain intensity and pain interference. Secondary outcome measures included assessments of function, mood, quality of life, catastrophizing, and patient satisfaction. Results: At 12-month follow-up, 13.5% (95% confidence interval [CI], 5.6-25.8) of patients with central neuropathic pain and complete data sets (n=52) achieved a ≥30% reduction in pain, whereas 38.5% (95% CI, 25.3-53.0) achieved a reduction of at least 1 point on the Pain Interference Scale. The proportion of patients with central neuropathic pain achieving both these measures, and thus the primary outcome, was 9.6% (95% CI, 3.2-21.0). Patients with peripheral neuropathic pain and complete data sets (n=463) were more likely to achieve this primary outcome at 12 months (25.3% of patients; 95% CI, 21.4-29.5) (p=0.012). Conclusion: Patients with central neuropathic pain syndromes managed in tertiary care centers were less likely to achieve a meaningful improvement in pain and function compared with patients with peripheral neuropathic pain at 12-month follow-up.
Energetic particle effects in magnetic confinement fusion devices are commonly studied by hybrid kinetic-fluid simulation codes whose underlying continuum evolution equations often lack the correct energy balance. While two different kinetic-fluid coupling options are available (current coupling and pressure coupling), this paper applies the Euler–Poincaré variational approach to formulate a new conservative hybrid model in the pressure-coupling scheme. In our case the kinetics of the energetic particles are described by guiding center theory. The interplay between the Lagrangian fluid paths and phase space particle trajectories reflects an intricate variational structure which can be approached by letting the four-dimensional guiding center trajectories evolve in the full six-dimensional phase space. Then, the redundant perpendicular velocity is integrated out to recover a four-dimensional description. A second equivalent variational approach is also reported, which involves the use of phase space Lagrangians. Not only do these variational structures confer on the new model a correct energy balance, but also they produce a cross-helicity invariant which is lost in the other pressure-coupling schemes reported in the literature.