We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure no-reply@cambridge.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Although atypical antipsychotics have lowered the prevalence and severity of extrapyramidal symptoms (EPS), they still contribute to the overall side-effect burden of approved antipsychotics. Drugs with novel mechanisms without D2 dopamine receptor blocking activity have shown promise in treating schizophrenia without the side effects of currently available treatments. KarXT (xanomeline–trospium chloride) represents a possible alternative that targets muscarinic receptors. KarXT demonstrated efficacy compared with placebo in 3 out of 3 short-term acute studies and has not been associated with many of the side effects of D2 dopamine receptor antagonists. Here, we further characterize EPS rates with KarXT in these trials.
Methods
EMERGENT-1 (NCT03697252), EMERGENT-2 (NCT04659161), and EMERGENT-3 (NCT04738123) were 5-week, randomized, double-blind, placebo-controlled, inpatient trials in people with schizophrenia experiencing acute psychosis. Data from the safety populations, defined as all participants who received ³1 dose of trial medication, were pooled. For this analysis, we used a broader definition of EPS-related adverse events (AEs) to encompass any new onset of dystonia, dyskinesia, akathisia, or extrapyramidal disorder reported any time after the first dose of medication. Additionally, EPS were assessed by examining change from baseline to week 5 on the Simpson-Angus Scale (SAS), Barnes Akathisia Rating Scale (BARS), and Abnormal Involuntary Movement Scale (AIMS).
Results
A total of 683 participants (KarXT, n=340; placebo, n=343) were included in the analyses. The rate of treatment-emergent AEs (TEAEs) associated with EPS was 3.2% in the KarXT group vs 0.9% in the placebo group. The most commonly reported TEAE was akathisia (KarXT, 2.4%; placebo 0.9%); half of possible akathisia cases in the KarXT group (4/8 TEAEs) were from a single US site, considered by the investigator to be unrelated to trial drug, and resolved without treatment. Overall rates of akathisia TEAEs deemed related to trial drug were low (KarXT, 0.6%; placebo 0.3%). Dystonia, dyskinesia, and extrapyramidal disorder TEAEs were reported by only a single subject each (0.3%) in the KarXT arm. All reported TEAEs were mild to moderate in severity. KarXT was associated with no clinically meaningful mean±SD changes from baseline to week 5 on the SAS (-0.1±0.6), BARS (-0.1±0.9), or AIMS (0.0±0.7).
Conclusions
The incidence of EPS-related TEAEs with KarXT was low in comparison to those observed in similar trials of antipsychotics (D2 dopamine receptor antagonists), although head-to-head studies have not been completed. Moreover, KarXT was not associated with increased scores on EPS scales (SAS, BARS, AIMS) across 5 weeks of treatment. These results, combined with the robust efficacy of KarXT in trials to date, suggest that KarXT’s novel mechanism of action may provide therapeutic benefit in the absence of EPS frequently associated with currently available antipsychotics.
The use of an electronic hand hygiene monitoring system (EHHMS) decreased due to the coronavirus disease 2019 (COVID-19) pandemic. We analyzed dispenser use, hand hygiene (HH) badge use, and HH compliance to determine the effect of COVID-19 on EHHMS use and HH compliance. HH product shortages and other pandemic-induced challenges influenced EHHMS use.
Interest in electronic hand hygiene monitoring systems (EHHMSs) is now widespread throughout the infection control community. We tested 2 types of EHHMS for accuracy. The type B EHHMS captured more HH events with superior accuracy. Hospitals considering an EHHMS should assess the technology’s ability to accurately capture HH performance in the clinical workflow.
This chapter insists on the centrality of state-making in American politics of the Revolutionary era. In contrast to fairly long and distinguished traditions in the social scientific and historical literatures highlighting an early American constitutional hostility to governance and perhaps even a nascent anti-statism, this paper argues that early American independence was worked out against the background assumption of a strong state and interventionist social and economic policymaking. The chapter offers two different investigations of this phenomenon. Part I features a re-examination of the political-economic origins of the Declaration of Independence. In contrast to conventional renderings of that historic document highlighting a simple liberty against tyranny, the first part of this paper argues that most of Thomas Jefferson’s words actually described failures of British statecraft--i.e., a state doing too little--and aspired to create an alternative post-revolutionary state that would do better and far more. Part II of the chapter moves from the Declaration itself into a more general exploration of early revolutionary-era legislation in a complementary effort to demonstrate the unprecedented interventionism of the original American revolutionary state across a wide set of political-economic policy concerns.
The paper reports on the growth of group III-Sb’s on silicon, substrate preparation, optimization of AlGaSb metamorphic buffer, formation of defects (threading dislocations, microtwins and anti-phase boundaries) and their effect on the surface morphology and electrical properties of these high hole mobility materials for future III-V CMOS technology. Defect density was found to be 2-3x higher than in similar structures grown on GaAs, resulting in 2x higher roughness. Defects also result in background p-type doping well above 1017 cm-3 causing inversion of polarity from n-type to p-type in thin n-type doped GaSb. MOS Capacitors fabricated on these buffers demonstrate similar characteristics to higher quality GaSb-on-GaAs. The highest hole mobility obtained in a strained InGaSb QW MOS channel grown on silicon is ∼630 cm2/V-s which is ∼30% lower than similar channels grown on GaAs substrates.
The cognitive profile of early onset Parkinson’s disease (EOPD) has not been clearly defined. Mutations in the parkin gene are the most common genetic risk factor for EOPD and may offer information about the neuropsychological pattern of performance in both symptomatic and asymptomatic mutation carriers. EOPD probands and their first-degree relatives who did not have Parkinson’s disease (PD) were genotyped for mutations in the parkin gene and administered a comprehensive neuropsychological battery. Performance was compared between EOPD probands with (N = 43) and without (N = 52) parkin mutations. The same neuropsychological battery was administered to 217 first-degree relatives to assess neuropsychological function in individuals who carry parkin mutations but do not have PD. No significant differences in neuropsychological test performance were found between parkin carrier and noncarrier probands. Performance also did not differ between EOPD noncarriers and carrier subgroups (i.e., heterozygotes, compound heterozygotes/homozygotes). Similarly, no differences were found among unaffected family members across genotypes. Mean neuropsychological test performance was within normal range in all probands and relatives. Carriers of parkin mutations, whether or not they have PD, do not perform differently on neuropsychological measures as compared to noncarriers. The cognitive functioning of parkin carriers over time warrants further study. (JINS, 2011, 17, 1–10)
Metastable Intermolecular Composite (MIC) materials are comprised of a mixture of oxidizer and fuel with particle sizes in the nanometer range. Characterizing their ignition and combustion is an ongoing effort at Los Alamos. In this paper we will present some recent studies at Los Alamos aimed at developing a better understanding of ignition and combustion of MIC materials. Ignition by impact has been studied using a laboratory gas gun using nano-aluminum (Al) and nano-tantalum (Ta) as the reducing agent and bismuth (III) oxide (Bi2O3) as the oxidant. As expected from the chemical potential, the Al containing composites gave higher peak pressures. It was found, for the Al/Bi2O3 system, that impact velocity under observed conditions plays no role in the pressure output until approximately 100 m/s, below which speed, impact energy is insufficient to ignite the reaction. This makes the experiment more useful in evaluating the reactive performance. Replacing the atmosphere on impact with an inert gas reduced both the amount of light produced and the realized peak pressure. The combustion of low-density MIC powders has also been studied. To better understand the reaction mechanisms of burning MIC materials, dynamic electrical conductivity measurements have been performed on a MIC material for the first time. Simultaneous optical measurements of the wave front position have shown that the reaction and conduction fronts are coincident within 160 μm.
Obsidian hydration dating has served as one of the chronological indicators for the Hopewell Culture earthworks (ca. 200 B.C.—A.D. 500) in central Ohio. This work presents new obsidian hydration dates developed from high precision hydration layer depth profiling using secondary ion mass spectrometry (SIMS). These data suggest that long-distance exchange in obsidian occurred throughout the Hopewell period.
The local structural information around the germanium atom in boron doped SiGe alloys is important in understanding the dopant diffusion mechanisms. Epitaxial SiGe test structures with B and C markers were grown on Si substrates by using rapid thermal chemical vapor deposition (RTCVD). The local structure around the Ge atom was probed using Ge K-edge x-ray absorption fine structure spectroscopy (XAFS) to determine the effects of the B and C on the Ge sites. The concentration profiles obtained from secondary ion mass spectroscopy are correlated with the Ge XAFS results. The modifications on the local structure around the Ge atoms are revealed from the multiple scattering analyses on the Ge near-neighbors. First and second shell XAFS fits to the B doped SiGe samples indicate a direct evidence of the Ge trapping of the B atoms whereas the C is randomly distributed to the Si lattice sites.
New, non-routine metrology issues are addressed for three kinds of materials and processes that are necessary for the fabrication of ultra-high speed devices. We look at the problems and solutions for measuring both stoichiometry and dopant content of SiGe material when using Cs primary ion bombardment. We examine the challenges of determining the N content of ultra-thin SiON gate dielectrics with emphasis on what will be necessary for the measurement of 1nm thick oxides. And finally we show some promising early results of using a new protocol for measuring ULE B ion implant profiles in the top 3nm with emphasis on obtaining a more realist profile shape in this region for TCAD modeling purposes.
One of the important challenges in semiconductor industry is to sustain high concentration of dopant atoms electrically active in very small areas. In investigating the optimum post implantation treatment methods that will help to attain these conditions, the local structural information around the dopant atom is crucial. In this study, we have used secondary ion mass spectroscopy (SIMS) and x-ray absorption fine structure spectroscopy (XAFS) to obtain the concentration depth profiles and the local structural information around the Sb atom in laser thermal annealed (LTA) Sb implants in Si wafers. The Sb implant doses used in this work are 6.4x1015/cm2 and 2.0x1016/cm2. The XAFS results for the 6.4x1015/cm2 Sb dose sample do not exhibit any rhombohedral-Sb precipitation as the Fourier Transformed (FT) data can be fit successfully using only substitutional-Sb in the Si lattice sites. However, a multi-shell analysis of the Fourier Transformed (FT) data for the 2.0x1016/cm2 Sb dose sample clearly indicates there is a substantial contribution from the Sb-Sb scattering, which is a signature of precipitated form of Sb.
An early long-running federal social policy experiment was the preferential hiring of American Indians at agencies, reserations, and shools. This government employment was designed to accelerate the assimilation of the natives and to reduce their resistance to education and economic change. Instead, the program inadvertently created a form of dependency. This ironic outcome was due to the power of the natives to shape the policy according to their needs and values.
The diffusion of boron in ion implanted LPCVD polycrystalline silicon is shown to be dominated by grain boundary diffusion at low and moderate concentrations. The diffusion coefficient is 2 to 3 orders of magnitude larger than its value in crystalline silicon. In preannealed polysilicon, the boron diffusion coefficient is found to be 30% smaller than in polysilicon annealed after implantation. This reflects the effect of the grain size in the diffusion coefficient since preannealed polysilicon has larger grains and smaller density of grain boundaries per unit area.
Recommend this
Email your librarian or administrator to recommend adding this to your organisation's collection.