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To test the age, cohort, and period effect on past-year use trends in psychedelic drugs and ecstasy.Data were from a repeated cross-sectional nationally representative household survey in Australia conducted every three years between 2001 and 2019. An age-period-cohort model was used to test the effect of age, birth cohort, and period on past year psychedelic and ecstasy use. Participants were between 18 and 80 years old at the time of the survey. The total sample size was 149,296 (Mean age = 45.8; 56% female). Past-year use of psychedelics and ecstasy were the key outcome variables. There were six birth cohorts that were derived in each survey: 1936-50, 1951-60, 1961-70, 1971-80, 1981-90, and 1991-2001. There were seven periods that coincided with survey years: 2001, 2004, 2007, 2010, 2013, 2016 and 2019. Age was treated as continuous.Past-year use of both psychedelics and ecstasy decreased with age, b = -0.87, 95% CI [-1.14, -0.61] and b = -0.84, 95% CI [-1.08, -0.60]. For ecstasy, while there was significant variation across periods (p .001), there was no obvious trend. There was a significant birth cohort effect (p .001), with prevalence increasing from the 1936-50 cohort, peaking in the 1971-80 cohort and then decreasing in the 1991-2001 cohort. For psychedelics, there was significant variation across periods (p .001) with an upward trend. There was a significant birth cohort effect (p .001), with prevalence increasing from the 1936-50 cohort to similarly high prevalence for the three most recent cohorts (1971-80, 1981-90, 1991-2001).There were strong cohort and period effects in trends in the use of psychedelic and ecstasy.

Background There is substantial evidence for a cumulative dose-related response to ionizing radiation in the form of cancer development years after initial exposure. Therefore, this study focused on effective dose, a quantity with direct correlations to biologic risk from dental x-ray exposures. Objective The purpose of this study was to measure doses and to calculate the effective doses (E) resulting from exposure parameters that are used for stationary intraoral tomosynthesis (s-IOT) and conventional imaging for adult posterior bitewing examinations of the dentition. Additionally, this study sought to evaluate the effect of sensor attenuation on patient dose. Materials and Methods To meet these aims, a human tissue equivalent adult phantom and optically stimulated luminescent (Landauer, Inc., Glenwood, IL) dosimeters were used to measure dose produced during simulated posterior bitewing examinations (n = 4). Optically stimulated luminescent dosimeters were used to measure x-ray dose at 24 head and neck tissue/organ sites of interest. Dosimetry was acquired by using a tissue equivalent phantom simulating the anatomy of an average adult male (AtomMax Model 711 HN,CIRS Inc., Norfolk, VA). Exposure parameters used were 70 kV/7 mA (0.7 mAs) and 0.12 mAs for s-IOT and conventional (KaVo FOCUS, Charlotte, NC), respectively. Analysis of variance (ANOVA) and Tukey’s HSD (“honest significant difference”) statistics on dose were utilized to demonstrate significant data relationships. Results Effective dose by modality (μSv) Modality Dose (μSv) Rectangular Conventional with Sensor 1.1 Rectangular Conventional without sensor 4.6 s-IOT with sensor 5.9 s-IOT without sensor 11.9 Circular Conventional with sensor 8.2 Circular Conventional without sensor 15.7 Sensor-present doses were significantly lower than sensor-absent for all modalities (P = .0001). Significant differences in E were found for all modality combinations with the exception of s-IOT sensor-present modalities vs conventional rectangular sensor-absent modalities (P = .0482). Discussion Unadjusted s-IOT dose was 26% less than conventional-circular exposures and 61% greater than conventional-rectangular for sensor-absent exposures. Unadjusted sensor-present s-IOT dose was 28% less than conventional-circular exposures and 81% greater than conventional-rectangular exposures. Despite a 4-fold increase in mAs for s-IOT imaging compared with conventional imaging, E from s-IOT imaging was at least 26% less than the current most commonly implemented bitewing technique, conventional-circular, while providing substantially greater diagnostic yield in the form of 3-dimensional (3-D) information.

Voltage-gated sodium (Na$_\mathrm{v}$) channels are responsible for the depolarizing phase of the action potential in most nerve cells, and Na$_\mathrm{v}$ channel localization to the axon initial segment is vital to action potential initiation. Na$_\mathrm{v}$ channels in the soma play a role in the transfer of axonal output information to the rest of the neuron and in synaptic plasticity, although little is known about Na$_\mathrm{v}$ channel localization and dynamics within this neuronal compartment. This study uses single-particle tracking and photoactivation localization microscopy to analyze cell-surface Na$_\mathrm{v}$1.6 within the soma of cultured hippocampal neurons. Mean-square displacement analysis of individual trajectories indicated that half of the somatic Na$_\mathrm{v}$1.6 channels localized to stable nanoclusters $\sim$230 nm in diameter. Strikingly, these domains were stabilized at specific sites on the cell membrane for >30 min, notably via an ankyrin-independent mechanism, indicating that the means by which Na$_\mathrm{v}$1.6 nanoclusters are maintained in the soma is biologically different from axonal localization. Nonclustered Na$_\mathrm{v}$1.6 channels showed anomalous diffusion, as determined by mean-square-displacement analysis. High-density single-particle tracking of Na$_\mathrm{v}$ channels labeled with photoactivatable fluorophores in combination with Bayesian inference analysis was employed to characterize the surface nanoclusters. A subpopulation of mobile Na$_\mathrm{v}$1.6 was observed to be transiently trapped in the nanoclusters. Somatic Na$_\mathrm{v}$1.6 nanoclusters represent a new, to our knowledge, type of Na$_\mathrm{v}$ channel localization, and are hypothesized to be sites of localized channel regulation.

Apoptosis Signal-Regulating Kinase-1 (ASK1) is a known member of the Mitogen-Activated Protein Kinase Kinase Kinase (MAP3K) family and upon stimulation will activate the p38- and JNK-pathways leading to cardiac apoptosis, fibrosis, and hypertrophy. Using Structure-Based Drug Design (SBDD) in parallel with deconstruction of a published compound, a novel series of ASK1 inhibitors was optimized, which incorporated a saturated heterocycle proximal to the hinge-binding motif. This yielded a unique chemical series with excellent selectivity across the broader kinome, and desirable drug-like properties. The lead compound (10) is highly soluble and permeable, and exhibits a cellular EC50 = 24 nM and Kd 5000 structures in the Protein Data Bank, potentially conferring the selectivity seen in this series.

Background There is substantial evidence for a cumulative dose-related response to ionizing radiation in the form of cancer development years after initial exposure. Therefore, this study focused on effective dose (E), a quantity with direct correlations to biologic risk from dental x-ray exposures. Objectives The purpose of this study was to measure doses and calculate (E) from adult full-mouth examinations (FMXs) by using handheld and conventional wall-mounted x-ray sources with both circular and rectangular collimation (RC). Materials and Methods A human tissue-equivalent phantom and optically stimulated luminescent dosimeters were used to measure dose from simulated FMXs (n = 18) at 24 head/neck tissue sites. The parameters were 70 kV/7 mA (0.84 mAs and 1.34 mAs) for Conventional Circular and RC handheld device; 60 kV/2.5 mA (2.16 mAs) for NOMAD Circular and RC handheld device; and 60 kV/2.0 mA (1.98 mAs) for Xray2 Go Circular (XTG) handheld device. Analysis of variance (ANOVA) and Tukey’s HSD (“honest significant difference”) statistics demonstrated significant relationships. Results The FMX E (µSv) values were: NOMAD RC (6.9); XTG (16.7); NOMAD Circular (17.4); and Conventional Circular (26.3). For circular techniques, the handheld device E was significantly lower than the conventional unit for both devices (P Discussion Handheld device E was at least 34% less than conventional circular and as much as 74% less with the use of RC. Operator exposure to the groin can increase significantly from overangulating the handheld sources; however, the addition of RC can reduce this exposure by as much as 76%.

Numerical weather prediction (NWP) models often parameterise aerosols to reduce computational needs, while aiming to accurately capture their impact adequately. Increasingly, aerosols are monitored in-situ directly and/or indirectly (e.g. by automatic lidars and ceilometers, ALC). ALC measure the aerosol optical characteristic of attenuated backscatter. This can also be estimated using forward models that combine forecast aerosol and relative humidity to parameterise aerosol physical and optical characteristics. The aerFO is one such forward model, designed to use Met Office NWP model output and parameterisations from the MURK visibility scheme. Given the aerFO-MURK scheme link, assessing the aerFO and its output could therefore be used to inform future developments of the MURK scheme. To identify which parameterised physical and optical aerosol characteristics in the scheme are the most critical in urban settings, aerFO is driven with different in-situ aerosol observations at a background site in central London. Estimated attenuated backscatter is then assessed against ALC observations. It is shown that the original MURK scheme parameterisation underestimates the variance of both dry mean volume radius and total number concentration. Representing both the accumulation and coarse mode aerosols in the aerFO reduces the median bias error of estimated attenuated backscatter by 69.1 %. Providing more realistic temporal (monthly to hourly) variability of relative mass for different species leads to little improvement, compared to using monthly climatological means. Numerical experiments show that having more realistic estimates of number concentration is more important than providing more accurate values of the dry mean volume radius for the accumulation mode. Hence, improving the parameterisations for number concentration should be a main focus for further development of the MURK scheme. To estimate aerosol attenuated backscatter, the aerFO requires an extinction to backscatter ratio (i.e. the lidar ratio). In addition to forward modelling, the lidar ratio can also be used with ALC attenuated backscatter to calculate aerosol properties estimated in aerosol forecasts. Here, a model is developed that estimates the ratio using in-situ observations of the number size distribution and speciated aerosol masses. The values of lidar ratio derived at the London background site (14 – 80 sr across selected common lidar wavelengths) compare well to the literature. However, the modelled lidar ratio is unexpectedly correlated to relative humidity. Further, a stronger dependence exists at shorter wavelengths (355 and 532 nm) compared to longer wavelengths (905 and 1064 nm), and is due to the critical relation of lidar wavelength to aerosol size.\ud \ud Keywords: urban aerosols; lidar forward operator; automatic lidar and ceilometers; urban observation network; lidar ratio

Does the Supreme Court care what the public thinks? For decades, articles in leading political science journals have consistently answered in the affirmative. They regularly report a significant, positive relationship between public opinion and Supreme Court output. Given this accepted empirical fact, attention has turned to how or when public opinion affects the Court. Theories that attempt to answer these questions, however, face unresolved challenges: the mechanisms are left unexplained, and the studies are mutually contradictory. We advance this literature by showing that the empirical “fact” driving the search for a workable theory is actually ephemeral. To be clear, we do not attempt to prove the Court does not respond to public opinion. We do demonstrate, however, that contrary to twenty-five years of scholarship, there is no good empirical evidence suggesting it does. Doing so returns the field to the central question of whether opinion matters.

Background Selecting heart failure (HF) patients for intensive management to reduce readmissions requires effective targeting. However, available prediction scores are only modestly effective. We sought to develop a prediction score for 30-day all-cause rehospitalization or death in HF with the use of nonclinical and clinical data. Methods and Results This statewide data linkage included all patients who survived their 1st HF admission (with either reduced or preserved ejection fraction) to a Tasmanian public hospital during 2009–2012. Nonclinical data (n = 1,537; 49.5% men, median age 80 y) included administrative, socioeconomic, and geomapping data. Clinical data before discharge were available from 977 patients. Prediction models were developed and internally and externally validated. Within 30 days of discharge, 390 patients (25.4%) died or were rehospitalized. The nonclinical model (length of hospital stay, age, living alone, discharge during winter, remoteness index, comorbidities, and sex) had fair discrimination (C-statistic 0.66 [95% confidence interval (CI) 0.63–0.69]). Clinical data (blood urea nitrogen, New York Heart Association functional class, albumin, heart rate, respiratory rate, diuretic use, angiotensin-converting enzyme inhibitor use, arrhythmia, and troponin) provided better discrimination (C-statistic 0.72 [95% CI 0.68–0.76]). Combining both data sources best predicted 30-day rehospitalization or death (C-statistic 0.76 [95% CI 0.72–0.80]). Conclusions Clinical data are stronger predictors than nonclinical data, but combining both best predicts 30-day rehospitalization or death among HF patients.

This paper draws on the work of Dror Paley et al and describes the basic principles of clinical and radiographic assessment of coronal plane lower limb deformity. It covers concepts of mechanical axis deviation and of the Centre of Rotation of Angulation (CORA) which influence the choice of corrective osteotomy shape and its location.

The uppermost Pliensbachian-Lower Toarcian sediments recovered from Llanbedr (Mochras Farm) Borehole (North Wales, UK) were deposited in the Cardigan Bay Basin and mainly consist of alternating marls and marly limestones. The current study analyses the foraminiferal assemblages from the cored interval (143 m) that has been assigned to the Spinatum Zone (Upper Pliensbachian) to the lower part of the Bifrons Zone (Middle Toarcian). The foraminiferal assemblages are dominated by the suborders Lagenina and Robertinina. Four main ecostratigraphic intervals have been identified, based on changes in the foraminiferal assemblages that occurred before, during and after the Toarcian Oceanic Anoxic Event (T-OAE). Ecostratigraphic interval I (upper part of the Spinatum Zone) is characterized by a diverse assemblage with specialist, opportunist and intermediate forms. This assemblage is interpreted to represent a phase that pre-dates the biotic crisis. The ecostratigraphic interval II (Tenuicostatum Zone) shows an abrupt increase in opportunist forms such as the genus Reinholdella, and a facultative opportunist such as Paralingulina tenera, which was tolerant to oxygen depleted conditions. This second interval represents the initial biotic crisis phase, in response to decreasing oxygenation. The ecostratigraphic interval III is considered the peak of the biotic crisis, coincident with the negative carbon isotopic excursion (at the base of the Serpentinum Zone) and characterized by the dominance of the opportunist Reinholdella (87–97% of the assemblage) and low diversity. The ecostratigraphic interval IV (upper part of Serpentinum Zone and lower part of Bifrons Zone) is characterized by an increase of diversity and an abrupt decrease in Reinholdella. This assemblage is interpreted to reflect the increased availability of oxygen from deep-infaunal to epifaunal microhabitats and the return to normal conditions at the sea bottom. Ecostratigraphic fluctuations in the Mochras foraminiferal assemblages across the T-OAE event are comparable with those from other parts of the UK, the Lusitanian Basin (Portugal), the Umbria Marche Basin (Italy) and the Atlassic Basin (North Africa). In addition, a foraminiferal turnover is evident across the Pliensbachian-Toarcian boundary and the T-OAE, and reflects the effects of the Early Jurassic biotic crisis on benthic foraminifera. Controlling factors of the biotic crisis are discussed, regarding that anoxic conditions do not necessarily have a lethal effect on all foraminiferal species and other oceanographic and environmental factors need consideration (fragmentation of epicontinental platforms, sea-level changes, crisis of carbonate productivity and temperature changes).

The importance of the priming of the lung environment by past infections is being increasingly recognized. Exposure to any given antigen can either improve or worsen the outcome of subsequent lung infections, depending on the immunological history of the host. Thus, an ability to impart transient alterations in the lung environment in anticipation of future insult could provide an important novel therapy for emerging infectious diseases. In this study, we show that nasal administration of virus-like particles (VLPs) before, or immediately after, lethal challenge with methicillin-resistant Staphylococcus aureus (MRSA) of mice i) ensures complete recovery from lung infection and near absolute clearance of bacteria within 12 hours of challenge, ii) reduces host response-induced lung tissue damage, iii) promotes recruitment and efficient bacterial clearance by neutrophils and CD11c(+) cells, and iv) protects macrophages from MRSA-induced necrosis. VLP-mediated protection against MRSA relied on innate immunity. Complete recovery occurred in VLP-dosed mice with severe combined immunodeficiency, but not in wild-type mice depleted of either Ly6G(+) or CD11c(+) cells. Early IL-13 production associated with VLP-induced CD11c(+) cells was essential for VLP-induced protection. These results indicate that VLP-induced alteration of the lung environment protects the host from lethal MRSA pneumonia by enhancing phagocyte recruitment and killing and by reducing inflammation-induced tissue damage via IL-13-dependent mechanisms.

Background Magnetic resonance imaging (MRI) of pacemaker patients is contraindicated due to documented potential risks to the patient from hazardous interactions between the MRI and pacemaker system. Objective The purpose of this prospective, randomized, controlled, worldwide clinical trial was to evaluate the safety and effectiveness of a pacemaker system designed for safe use in MRI for any bradycardia indicated patient. Methods Patients (n = 464) were randomized to undergo an MRI scan between 9 and 12 weeks postimplant (MRI group, n=258) or not to undergo MRI (control group, n=206) after successful implantation of the specially designed dual-chamber pacemaker and leads. Patients were monitored for arrhythmias, symptoms, and pacemaker system function during 14 nonclinically indicated relevant brain and lumbar MRI sequences. Sequences were performed at 1.5 T and included scans with high radiofrequency power deposition and/or high gradient dB/dt exposure. Clinical evaluation of the pacemaker system function occurred immediately before and after MRI, 1 week and 1 month post-MRI, and at corresponding times for the control group. Primary endpoints for safety analyzed the MRI procedure complication-free rate and for effectiveness compared capture and sensing performance between MRI and control groups. Results No MRI-related complications occurred during or after MRI, including sustained ventricular arrhythmias, pacemaker inhibition or output failures, electrical resets, or other pacemaker malfunctions. Pacing capture threshold and sensed electrogram amplitude changes were minimal and similar between study groups. Conclusion This trial documented the ability of this pacemaker system to be exposed in a controlled fashion to MRI in a 1.5 T scanner without adverse impact on patient outcomes or pacemaker system function.

The correct identification of the time series path of non-renewable energy resources has far reaching consequences for economists and policymakers alike. This study builds on the existing literature by employing a data series that includes a sample period of institutional change and recently developed unit root testing procedures. Besides crude oil, natural gas and coal prices are also examined, aiming to further the knowledge of non-renewable energy resource time paths in order to inform future research and update the conclusions of past studies. The unit root tests allow for structural breaks and are based on the procedures developed by Zivot and Andrews (1992), Lumsdaine and Papell (1997) and Lee and Strazicich (2003). Finally, we investigate whether the trend changes signs in the regimes which are bounded by the structural breaks and quantify the prevalence of the trends over the sample period considered. The results show that the trend is not well represented by a single positive or negative trend. The variability of the trend suggests that forecasting energy prices should not typically occur about a single trend.

Introduction A novel thermomechanical processing procedure has been developed that yields a superelastic (SE) nickel-titanium (NiTi) wire (M-Wire) that laboratory testing shows has improved mechanical properties compared with conventional SE austenitic NiTi wires used for manufacture of rotary instruments. The objective of this study was to determine the origin of the improved mechanical properties. Method Specimens from 2 batches of M-Wire prepared under different processing conditions and from 1 batch of standard-processed SE wire for rotary instruments were examined by scanning transmission electron microscopy, temperature-modulated differential scanning calorimetry, micro–x-ray diffraction, and scanning electron microscopy with x-ray energy-dispersive spectrometric analyses. Results The processing for M-Wire yields a microstructure containing martensite, that the proportions of NiTi phases depend on processing conditions, and that the microstructure exhibits pronounced evidence of alloy strengthening. Conclusions The presence of Ti 2 Ni precipitates in both microstructures indicates that M-Wire and the conventional SE wire for rotary instruments are titanium-rich.

Sway was examined during standing on a rotating platform. Sway increased significantly when standing on a firm rotating platform and increased further if standing on a compliant rotating platform. Medio-lateral (ML) sway was smaller than anterio-posterior (AP) sway when not rotating. When rotating, ML sway increased to similar levels as AP sway. Findings suggested that vestibular feedback is significantly impaired when the body is rotating. Conclusions Sway is increased when standing on a rotating platform, with the greatest increase seen in ML sway, mostly due to impaired vestibular sensory function.

A sealer, stainless steel files, and thermally plasticized gutta-percha were used in a filling technique to obtain a three-dimensional obturation of the root canal system. The technique eliminates the fitting of a master cone and does not require the special skills that are needed in other techniques for the apical placement of master cones.

An elderly man was seen with hemolytic anemia due to the urinary tract analgesic, phenazopyridine hydrochloride. The mechanisms underlying this toxic reaction are presented. Cautious use of this drug in elderly patients and in those with renal insufficiency is emphasized.