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The dendrite morphologies of the cast nickel-based superalloy CMSX-4® (CMSX-4® is registered trademarks of the Cannon-Muskegon Corporation) and the austenitic stainless steel HP microalloy have been obtained via an automated serial-sectioning process which allows three-dimensional (3D) microstructural characterization. The dendrite arm spacing, volume fraction of segregation, and fraction of porosity have been determined. This technique not only increases the depth, scope, and level of detailed microstructural characterization but also delivers microstructural data for modeling and simulation.
Cariprazine is a potent dopamine D3 and D2 receptor partial agonist with preferential binding to D3 receptors.
Summarize data from two Phase III, randomized, double-blind, placebo-controlled, flexible-dose, 3-week trials of cariprazine 3-12mg/d (NCT01058096) and cariprazine 3-6mg/d or 6-12mg/d (NCT01058668) in adults with bipolar I disorder and acute manic or mixed episodes.
Evaluate the efficacy, safety, and tolerability of cariprazine in mania associated with bipolar I disorder.
Primary and secondary efficacy parameters were change from baseline to Week 3 on the Young Mania Rating Scale (YMRS) and Clinical Global Impressions-Severity (CGI-S), respectively, and were analyzed using a mixed-effects model for repeated measures.
Randomized patient populations: 312 (NCT01058096; 154 placebo, 158 cariprazine 3–12mg/d) and 497 (NCT01058668; 161 placebo, 167 cariprazine 3–6mg/d, 169 cariprazine 6–12mg/d). Improvement from baseline to Week 3 on YMRS was significantly greater for each cariprazine group vs placebo (P<0.001): least square mean difference (LSMD) was −4.3 (3–12mg/d), −6.1 (3–6mg/d) and −5.9 (6–12mg/d). For each cariprazine group, significantly more patients met YMRS response and remission criteria vs placebo. Cariprazine also was significantly superior to placebo on the CGI-S: LSMD was −0.4 (3–12mg/d, P=.0027), −0.6 (3–6mg/d, P<.001), −0.6 (6–12mg/d, P<.001). The only common cariprazine-related TEAEs (≥5% and twice rate of placebo) that occurred in both studies were akathisia and tremor. Changes in metabolic parameters were small and similar to placebo in both studies.
Cariprazine was effective and generally well tolerated in the treatment of bipolar mania.
Cariprazine is a potent dopamine D3 and D2 receptor partial agonist with preferential binding to D3 receptors.
Summarize data from 2 Phase III, randomized, double-blind (6-week), placebo-controlled trials of fixed-dose cariprazine (3mg/d and 6mg/d, NCT01104766) and flexible-dose cariprazine (3–6mg/d and 6–9mg/d, NCT01104779) in adults with acute exacerbation of schizophrenia.
Evaluate the efficacy, safety, and tolerability of cariprazine in schizophrenia.
Primary and secondary efficacy parameters were change from baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impressions-Severity (CGI-S), respectively, and were analyzed using a mixed-effects model for repeated measures.
Randomized patient populations: 617 (NCT01104766; 153 placebo, 155 cariprazine 3mg/d, 157 cariprazine 6mg/d, 152 aripiprazole) and 446 (NCT01104779; 147 placebo, 151 cariprazine 3–6mg/d, 148 cariprazine 6–9mg/d). Improvement from baseline to Week 6 on PANSS total scores was significantly greater with cariprazine vs placebo: least square mean difference (LSMD) was −6.0 (3mg/d, P=.0044), −6.8 (3–6mg/d, P=.0029), −8.8 (6mg/d, P<.0001), and −9.9 (6–9mg/d, P<.0001). Cariprazine was significantly superior to placebo on CGI-S: LSMD was −0.4 (3mg/d, P=.0044), −0.3 (3–6mg/d, P=.0115), −0.5 (6mg/d, P<.0001), and −0.5 (6–9mg/d, P=.0002). Aripiprazole (active control, NCT01104766) was superior to placebo on both measures (LSMD: PANSS=−7.0, P=.0008; CGI-S=−0.4, P=.0001). The only common cariprazine-related TEAE (≥5% and twice rate of placebo) that occurred in both studies was akathisia. Changes in metabolic parameters were small and similar to placebo in both studies.
Cariprazine was effective and generally well tolerated in the treatment of schizophrenia.
To investigate a Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak event involving multiple healthcare facilities in Riyadh, Saudi Arabia; to characterize transmission; and to explore infection control implications.
Cases presented in 4 healthcare facilities in Riyadh, Saudi Arabia: a tertiary-care hospital, a specialty pulmonary hospital, an outpatient clinic, and an outpatient dialysis unit.
Contact tracing and testing were performed following reports of cases at 2 hospitals. Laboratory results were confirmed by real-time reverse transcription polymerase chain reaction (rRT-PCR) and/or genome sequencing. We assessed exposures and determined seropositivity among available healthcare personnel (HCP) cases and HCP contacts of cases.
In total, 48 cases were identified, involving patients, HCP, and family members across 2 hospitals, an outpatient clinic, and a dialysis clinic. At each hospital, transmission was linked to a unique index case. Moreover, 4 cases were associated with superspreading events (any interaction where a case patient transmitted to ≥5 subsequent case patients). All 4 of these patients were severely ill, were initially not recognized as MERS-CoV cases, and subsequently died. Genomic sequences clustered separately, suggesting 2 distinct outbreaks. Overall, 4 (24%) of 17 HCP cases and 3 (3%) of 114 HCP contacts of cases were seropositive.
We describe 2 distinct healthcare-associated outbreaks, each initiated by a unique index case and characterized by multiple superspreading events. Delays in recognition and in subsequent implementation of control measures contributed to secondary transmission. Prompt contact tracing, repeated testing, HCP furloughing, and implementation of recommended transmission-based precautions for suspected cases ultimately halted transmission.
Lymphatic filariasis is a neglected tropical disease caused by roundworm parasites such as Brugia malayi that spread via a mosquito vector. In vitro culture of these parasites provides controlled conditions to understand parasite biology and provides a cheaper way to screen potential micro- and macrofilaricides. Published studies have used a wide array of approaches and metrics regarding in vitro cultures of B. malayi; as a result, drawing comparisons and identifying the reasons why inability to reproduce outcomes are difficult. This study sought to determine conditions that ensure reproducible outcomes and used evaluation metrics that are easily measured and can be automated to ensure objectivity. We found culturing B. malayi third-stage larvae (L3) in endothelial basal media supplemented with 20% fetal bovine serum and 75 µm ascorbic acid in a temperature- and humidity-controlled incubator produced better survival and molting rates as well as longer and more motile parasites than previously reported. The benefit of ascorbic acid seemed to be unique to L3 parasites, as the addition of ascorbic acid to adult parasites had no significant impact on survival or motility. The methods reported in this study will help in designing experiments for both parasite behaviour studies and drug screening applications for disease eradication.
Epitaxial Ge films are useful as a substrate for high-efficiency solar cell applications. It is possible to grow epitaxial Ge films on low cost, cube textured Ni(001) sheets using CaF2(001) as a buffer layer. Transmission electron microscopy (TEM) analysis indicates that the CaF2(001) lattice has a 45o in-plane rotation relative to the Ni(001) lattice. The in-plane epitaxy relationships are CaF2//Ni and CaF2[$\bar 1$10]//Ni. Energy dispersive spectroscopy (EDS) shows a sharp interface between Ge/CaF2 as well as between CaF2/Ni. Electron backscatter diffraction (EBSD) shows that the Ge(001) film has a large grain size (∼50 μm) with small angle grain boundaries (< 8o). The epitaxial Ge thin film has the potential to be used as a substrate to grow high quality III-V and II-VI semiconductors for optoelectronic applications.
Loess deposits in the Vojvodina region, northern Serbia, are among the oldest and most complete loess-paleosol sequences in Europe to date. These thick sequences contain a detailed paleoclimatic record from the late Early Pleistocene. Based on the correlation of detailed magnetic susceptibility (MS) records from Vojvodina with the Chinese loess record and deep-sea isotope stratigraphy we here reconfirm and expand on a stratigraphic model of the Vojvodinian loess-paleosol chronostratigraphic sequence following the Chinese loess stratigraphic system.
Variations in MS, dust accumulation rates, and the intensity of pedogenesis demonstrate evidence for a Middle Pleistocene climatic and environmental transition. The onset of loess deposition in Vojvodina also indicates a direct link between dust generation in Europe and that in the interior of Eurasia since the Early Pleistocene. The youngest part of the Early Pleistocene and oldest part of the Middle Pleistocene is characterised by relatively uniform dust accumulation and soil formation rates as well as relatively high magnetic susceptibility values. In contrast, the last five interglacial-glacial cycles are characterised by sharp environmental differences between high dust accumulation rates during the glacials and low rates observed during soil development. The data presented in this study demonstrate the great potential of Vovjodina's loess archives for accurate reconstruction of continental Eurasian Pleistocene climatic and environmental evolution.
To determine the frequency of multiple pathology [Alzheimer Disease (AD) plus Vascular Dementia and/or Dementia with Lewy Bodies] in patients enrolled in clinical trials of AD therapy, and to compare the cognitive and functional assessments between patients with pure AD and AD with multiple pathology.
We conducted a retrospective analysis of patients with a clinical diagnosis of AD who were enrolled in AD therapy clinical trials and subsequently received an autopsy for confirmation of their diagnosis from 2000 to 2009. Performance on cognitive screening tests, namely Modified Mini Mental state (3MS) exam, Mini Mental state Exam (MMSE) and Functional Rating Scale (FRS) were compared between patients with pure AD and multiple pathology.
Autopsy reports were available for 16/47 (34%) of deceased patients. Of these 16 patients, 5 (31%) had pure AD pathology, 10 (63%) had AD with other pathology, and 1 (6%) had non-AD pathology. Compared to patients with pure AD, patients with AD mixed with other pathology had poorer baseline FRS in problem-solving (p<0.01) and community affairs (p<0.02).
While the strict enrollment criteria for clinical trials identified the presence of AD pathology in the majority of cases (15/16), multiple pathology was more common than pure AD in our series of autopsied patients. Premortem biomarkers that can distinguish between pure AD and AD with multiple pathology will be beneficial in future clinical trials and dementia patient management.
Often, silver nanoparticles (AgNps) are looked at in the realm of their plasmonic effects that are characterized by unique absorptional bands in the visible spectrum. Herein, the kinetics of a simple gravity mediated sedimentation process of AgNps, in aqueous suspensions. The surface energy mismatch between the AgNps and the receiver substrate allow for the formation of irregularly shaped AgNp microclusters with interconnected microchannels with dimensions and particle density controlled by the distance between the exposed substrate surface and the water/suspension interface. An investigation of the interplay between these properties and the films’ nanoparticle density is presented.
A study of the formation mechanisms of foamy coatings on the surface of glass-ceramic substrates produced by laser ablation is presented. Three laser systems emitting at 1064, 532 and 355 nm with pulse-widths in the nanosecond range were used. In the NIR range the formation of the coating is only possible when the temperature of the surface is higher than 300 ºC. In this case, the generation is related to an increase of the layer in liquid-phase produced in the interaction zone. However, when the sample is machined at 532 or 355 nm, it is not necessary to heat the whole surface to be processed. In this case, the local temperature and the pressure exerted over the interaction zone produce the generation of this coating, obtaining the layer at room temperature. Furthermore, the coating can be produced at higher speeds. In this way, it is possible to reduce the energetic cost improving the efficiency of the process.
Morphology, microstructure, composition and thermal properties of the layer are described.
A mechanical vibration system was made by sandwiching an array of parylene-C microsprings between two flat plates of Si. This system was driven mechanically in forced oscillation using a piezo transducer attached to the bottom Si plate. An atomic force microscope was used to record the displacement of the top plate in both the contact and non-contact modes. At the resonance, the system was observed to give large vertical displacement amplitude of up to 100 nm with a Q-factor of up to 900.
Fully nonlinear electrostatic waves in a plasma containing electrons, positrons, and ions are investigated by solving the governing equations exactly. It is found that both smooth and spiky quasistationary waves exist, and large-amplitude waves necessarily have large-phase velocities, but small-amplitude waves can be both fast and slow.
Knowledge of the control of the musculoskeletal system in patients with knee osteoarthritis (OA) during gait is helpful for the development of intervention programs in the management of these patients. The current study aimed to investigate the leg and joint stiffness, aswell as the associated joint kinematics and kinetics, in patients with bilateral medial knee OA during gait. Joint angles, moments and stiffness, as well as leg stiffness from fifteen patients with bilateral knee OA and fifteen normal controls during level walking, were obtained and their values at the beginning and end of single leg stance were compared using a t-test.
Patients with knee OA were found to modulate their leg and joint stiffness through acquired specific biomechanical strategies in order to maintain normal temporal-spatial patterns of gait. During weight acceptance, they increased their leg stiffness with increased knee stiffness but unalterd hip and ankle stiffness. During weight release, they modulated their hip and ankle kinetics with increased knee and ankle stiffness to improve the control stability of the limb with unaltered leg stiffness. It is suggested that muscle strengthening exercise intervention and/or rehabilitation for patients with knee OA should focus on activities that develop and/or maintain functions not only of the knee, but also of the overall lower extremity.