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.
Archimedes screw generators are a small-scale, eco-friendly hydropower technology. Despite their promise as a sustainable energy technology, the design specifics of the technology are not well documented in the published literature. Existing performance prediction models often fail to accurately forecast power loss, particularly as it relates to the outlet of the screw generator. To address this, a comprehensive computational fluid dynamic model was developed and evaluated using both laboratory-scale experiments and real-world data. This yielded an extensive dataset that covered wide variations in design parameters. The dataset was then used to inform the development and evaluation of an outlet power loss prediction model. The resulting model significantly improved the accuracy of overall performance predictions, reducing average error to 13.68 % compared with nominal experimental data – a substantial improvement over previous models, which averaged around 42.55 % error for the same test cases. Notably, the new model achieved an absolute error of 5 % or less in over 26 % of comparison points, marking a remarkable advancement by predicting outlet power loss by more than 28.8 %.
We study the exact Hausdorff and packing dimensions of the prime Cantor set, $\Lambda _P$, which comprises the irrationals whose continued fraction entries are prime numbers. We prove that the Hausdorff measure of the prime Cantor set cannot be finite and positive with respect to any sufficiently regular dimension function, thus negatively answering a question of Mauldin and Urbański (1999) and Mauldin (2013) for this class of dimension functions. By contrast, under a reasonable number-theoretic conjecture we prove that the packing measure of the conformal measure on the prime Cantor set is in fact positive and finite with respect to the dimension function $\psi (r) = r^\delta \log ^{-2\delta }\log (1/r)$, where $\delta $ is the dimension (conformal, Hausdorff, and packing) of the prime Cantor set.
Schmidt games and the Cantor winning property give alternative notions of largeness, similar to the more standard notions of measure and category. Being intuitive, flexible, and applicable to recent research made them an active object of study. We survey the definitions of the most common variants and connections between them. A new game called the Cantor game is invented and helps with presenting a unifying framework. We prove surprising new results such as the coincidence of absolute winning and $1$ Cantor winning in metric spaces, and the fact that $1/2$ winning implies absolute winning for subsets of $\mathbb {R}$. We also suggest a prototypical example of a Cantor winning set to show the ubiquity of such sets in metric number theory and ergodic theory.
The clay mineral textures, assemblages, formation mechanisms, and controlling geological parameters relating to alteration of silicic volcanic rocks by hydrothermal solutions, in core samples from the Broadlands-Ohaaki hydrothermal system, New Zealand, were investigated using X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission and analytical electron microscopy (TEM/AEM). Mineralogical and textural relations of this active hydrothermal system, for which temperatures and fluid relations are well known, are equivalent to those in the Golden Cross hydrothermal gold deposit as described in Part 1.
XRD data show a sequence of clay minerals from smectite to a range of interstratified I-S to mica with increasing depth and temperature, on average. TEM observations are in general agreement with XRD data, especially with respect to relative proportions of illite (I)- and smectite (S)- like layers. TEM data also show that: (1) Smectite packets contain no discrete illite-like layers in samples identified as (Reichweite, R = 0) I-S by XRD. They coexist with separate packets of (R = 1) I-S. (2) A continuous range in I-S occurs from (R = 1) I-S with increasing proportion of illite-like layers, but at high illite-like layer contents there is a gap between I-S and illite. (3) 1M and 2M1 polytypes of mica coexist in separate packets, but the rare 1M polytype has a larger VIMg content.
The data imply that clay minerals formed by dissolution and neocrystallization directly from volcanic phases, although multiple reaction events can not be ruled out. Such “episodic” alteration produces a sequence of clay minerals identical to those of prograde diagenesis of pelitic sediments. This result implies that the presence of a continuous sequence is not definitive proof of continuous sequences of transformation as a function of time and continuous burial. Reaction progress of the clay-mineral sequence is in general accord with the known temperature gradient, but with significant and common exceptions. High porosity and permeability, both inherent in rock texture and local structure, are inferred to foster local reaction progress, as consistent with metastability of phases and the Ostwald step rule.
The past decade witnessed a wide range of industrial relations reforms in Australia. Employee participation and industrial democracy was espoused by the Labor government (1983–96) as a key element in its workplace reform program. It was also embraced by the trade union movement and, to a lesser extent, by leading employers and their associations. A case study of employee participation in the Ford Motor Company is used to illustrate the process of workplace reform in Australia during this period While Ford Australia provides a positive example of workplace change, it is argued that the promise of employee participation has not generally been fulfilled in Australian industry. Contributing factors identified in the paper include economic recession, the decline of trade union membership and a lack of ‘people’ skills in managerial ranks.
A combination of olanzapine and the opioid receptor antagonist samidorphan (OLZ/SAM) has been approved in the United States for the treatment of adults with schizophrenia or adults with bipolar I disorder. In a phase 3 study in adults with schizophrenia (ENLIGHTEN-2), OLZ/SAM treatment was associated with significantly less weight gain compared with olanzapine. Prespecified subgroup analyses explored the consistency of the weight mitigation effect of OLZ/SAM vs olanzapine across demographic subgroups in ENLIGHTEN-2.
Methods
The multicenter, randomized, double-blind ENLIGHTEN-2 study (NCT02694328) included outpatients aged 18–55 years with a diagnosis of schizophrenia based on DSM-5 criteria, a body mass index (BMI) of 18 to 30 kg/m2, and stable body weight (self-reported change ≤5% for ≥3 months before study entry). Patients were randomized 1:1 to receive OLZ/SAM or olanzapine for 24 weeks. Co-primary endpoints (previously reported) were percent change in body weight and proportion of patients with at least 10% weight gain from baseline at week 24. Prespecified exploratory subgroup analyses by sex, age, self-reported race, and baseline BMI were conducted.
Results
At week 24, treatment with OLZ/SAM resulted in numerically less percent weight gain than with olanzapine across all subgroups evaluated. The proportion of patients with at least 10% weight gain was smaller in each subgroup treated with OLZ/SAM vs olanzapine.
Conclusion
In these exploratory subgroup analyses from the ENLIGHTEN-2 study, weight-mitigating effects of OLZ/SAM vs olanzapine were observed consistently across patient subgroups and were in line with results from the overall study population.
The coronavirus disease 2019 (COVID-19) pandemic has resulted in shortages of personal protective equipment (PPE), underscoring the urgent need for simple, efficient, and inexpensive methods to decontaminate masks and respirators exposed to severe acute respiratory coronavirus virus 2 (SARS-CoV-2). We hypothesized that methylene blue (MB) photochemical treatment, which has various clinical applications, could decontaminate PPE contaminated with coronavirus.
Design:
The 2 arms of the study included (1) PPE inoculation with coronaviruses followed by MB with light (MBL) decontamination treatment and (2) PPE treatment with MBL for 5 cycles of decontamination to determine maintenance of PPE performance.
Methods:
MBL treatment was used to inactivate coronaviruses on 3 N95 filtering facepiece respirator (FFR) and 2 medical mask models. We inoculated FFR and medical mask materials with 3 coronaviruses, including SARS-CoV-2, and we treated them with 10 µM MB and exposed them to 50,000 lux of white light or 12,500 lux of red light for 30 minutes. In parallel, integrity was assessed after 5 cycles of decontamination using multiple US and international test methods, and the process was compared with the FDA-authorized vaporized hydrogen peroxide plus ozone (VHP+O3) decontamination method.
Results:
Overall, MBL robustly and consistently inactivated all 3 coronaviruses with 99.8% to >99.9% virus inactivation across all FFRs and medical masks tested. FFR and medical mask integrity was maintained after 5 cycles of MBL treatment, whereas 1 FFR model failed after 5 cycles of VHP+O3.
Conclusions:
MBL treatment decontaminated respirators and masks by inactivating 3 tested coronaviruses without compromising integrity through 5 cycles of decontamination. MBL decontamination is effective, is low cost, and does not require specialized equipment, making it applicable in low- to high-resource settings.
An open-label extension study (NCT02873208) evaluated the long-term tolerability, safety, and efficacy of combination olanzapine/samidorphan (OLZ/SAM) treatment in patients with schizophrenia. This qualitative sub study explored perceptions of benefit, burden, and satisfaction with previous medications and OLZ/SAM.
Methods
Semi-structured interviews (60 minutes; audio-recorded) were conducted. Interviewer sensitivity training, senior interviewer oversight, and a list of common medications to aid recall supported data collection. Interview transcripts were content coded and analyzed (NVivo v11.0).
Results
All 41 patients reported a lifetime burden with schizophrenia adversely impacting employment, relationships, emotional health, social activities, and daily tasks. Hospitalization for schizophrenia management was another reported aspect of disease burden. Although most (n=32) patients reported previous medication benefits, side effects affecting physical, emotional/behavioral, and cognitive functioning were reported by all (n=41). Following OLZ/SAM treatment, 39/41 patients (95%) reported improvements in symptoms including hallucinations, paranoia, depression, sleep, and concentration. Furthermore, patients described improvements in self-esteem, social activities, relationships, and daily activities. Twenty-three patients (56%) reported side effects attributed to OLZ/SAM; lack of energy (n=12 [29%]) and dry mouth (n= 5 [12%]) were most common. Twenty-four (59%) patients were “very satisfied” with OLZ/SAM; most (n=35 [85%]) preferred to continue OLZ/SAM vs switching to another medication. As most substudy patients (n=40; 98%) completed the extension study, satisfied patients may be overrepresented in this analysis.
Conclusion
This qualitative interview approach provided valuable insight into patients’ experiences with previous medications and OLZ/SAM. Overall, most patients reported treatment satisfaction and improvements in symptoms, function, and health-related quality of life with OLZ/SAM.
Olanzapine effectively treats schizophrenia and bipolar I disorder (BD-I); however, its use is hindered by significant weight gain. A combination of olanzapine and samidorphan (OLZ/SAM) is in development to provide the efficacy of olanzapine while mitigating olanzapine-associated weight gain through opioid-receptor blockade. Here, we summarize OLZ/SAM clinical data.
Methods
The OLZ/SAM development program consists of 18 phase 1–3 clinical studies evaluating antipsychotic and weight mitigation efficacy of OLZ/SAM, along with pharmacokinetics, safety, and tolerability. Safety evaluation also included metabolic laboratory assessments.
Results
OLZ/SAM significantly improved psychotic symptoms (measured by Positive and Negative Syndrome Scale); improvements were similar to that observed with olanzapine vs placebo. OLZ/SAM resulted in significantly less weight gain than olanzapine. Additionally, 2 long-term phase 3 extension studies confirmed the durability of antipsychotic effect, as well as stabilization of weight and metabolic parameters in those continuing treatment. Supporting the potential use of OLZ/SAM in BD-I, OLZ/SAM or olanzapine resulted in bioequivalent olanzapine plasma concentrations, and OLZ/SAM did not affect lithium or valproate pharmacokinetics. OLZ/SAM treatment had no clinically relevant effects on ECG parameters (including QTc interval). OLZ/SAM and olanzapine safety were similar, except for reduced weight gain with OLZ/SAM; no additional safety risks were identified.
Conclusion
Data across 18 OLZ/SAM studies in >1600 subjects support an antipsychotic efficacy and safety profile for OLZ/SAM that is similar to olanzapine, with significantly less weight gain than olanzapine. OLZ/SAM is a potential new treatment for schizophrenia and BD-I patients needing efficacious long-term treatment with reduced risk of weight gain.
We study the dynamical Borel–Cantelli lemma for recurrence sets in a measure-preserving dynamical system
$(X, \mu , T)$
with a compatible metric d. We prove that under some regularity conditions, the
$\mu $
-measure of the following set
obeys a zero–full law according to the convergence or divergence of a certain series, where
$\psi :\mathbb {N}\to \mathbb {R}^+$
. The applications of our main theorem include the Gauss map,
$\beta $
-transformation and homogeneous self-similar sets.
In recent years, a variety of efforts have been made in political science to enable, encourage, or require scholars to be more open and explicit about the bases of their empirical claims and, in turn, make those claims more readily evaluable by others. While qualitative scholars have long taken an interest in making their research open, reflexive, and systematic, the recent push for overarching transparency norms and requirements has provoked serious concern within qualitative research communities and raised fundamental questions about the meaning, value, costs, and intellectual relevance of transparency for qualitative inquiry. In this Perspectives Reflection, we crystallize the central findings of a three-year deliberative process—the Qualitative Transparency Deliberations (QTD)—involving hundreds of political scientists in a broad discussion of these issues. Following an overview of the process and the key insights that emerged, we present summaries of the QTD Working Groups’ final reports. Drawing on a series of public, online conversations that unfolded at www.qualtd.net, the reports unpack transparency’s promise, practicalities, risks, and limitations in relation to different qualitative methodologies, forms of evidence, and research contexts. Taken as a whole, these reports—the full versions of which can be found in the Supplementary Materials—offer practical guidance to scholars designing and implementing qualitative research, and to editors, reviewers, and funders seeking to develop criteria of evaluation that are appropriate—as understood by relevant research communities—to the forms of inquiry being assessed. We dedicate this Reflection to the memory of our coauthor and QTD working group leader Kendra Koivu.1
We present a new method of proving the Diophantine extremality of various dynamically defined measures, vastly expanding the class of measures known to be extremal. This generalizes and improves the celebrated theorem of Kleinbock and Margulis [Logarithm laws for flows on homogeneous spaces. Invent. Math.138(3) (1999), 451–494] resolving Sprindžuk’s conjecture, as well as its extension by Kleinbock, Lindenstrauss, and Weiss [On fractal measures and Diophantine approximation. Selecta Math.10 (2004), 479–523], hereafter abbreviated KLW. As applications we prove the extremality of all hyperbolic measures of smooth dynamical systems with sufficiently large Hausdorff dimension, and of the Patterson–Sullivan measures of all nonplanar geometrically finite groups. The key technical idea, which has led to a plethora of new applications, is a significant weakening of KLW’s sufficient conditions for extremality. In the first of this series of papers [Extremality and dynamically defined measures, part I: Diophantine properties of quasi-decaying measures. Selecta Math.24(3) (2018), 2165–2206], we introduce and develop a systematic account of two classes of measures, which we call quasi-decaying and weakly quasi-decaying. We prove that weak quasi-decay implies strong extremality in the matrix approximation framework, as well as proving the ‘inherited exponent of irrationality’ version of this theorem. In this paper, the second of the series, we establish sufficient conditions on various classes of conformal dynamical systems for their measures to be quasi-decaying. In particular, we prove the above-mentioned result about Patterson–Sullivan measures, and we show that equilibrium states (including conformal measures) of nonplanar infinite iterated function systems (including those which do not satisfy the open set condition) and rational functions are quasi-decaying.
Combination olanzapine and samidorphan (OLZ/SAM), in development for schizophrenia and bipolar I disorder, is intended to provide the efficacy of olanzapine while mitigating olanzapine-associated weight gain. OLZ/SAM safety, tolerability, and efficacy from a 52-week open-label extension study in patients with schizophrenia are reported.
Methods
Patients previously completing the 4-week, double-blind ENLIGHTEN-1 study switched from OLZ/SAM, olanzapine, or placebo to OLZ/SAM. Assessments included adverse events (AEs), weight, vital signs, Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression-Severity (CGI-S) scores. Baseline was prior to first dose of OLZ/SAM in the extension study.
Results
In total, 281 patients enrolled, 277 received ≥1 OLZ/SAM dose, and 183 (66.1%) completed 52 weeks. Reasons for discontinuation included patient withdrawal (15.5%), loss to follow-up (6.9%), AEs (5.8%), and lack of efficacy (1.8%). AEs were reported in 136 (49.1%) patients; increased weight (13%) and somnolence (8%) were most common. Ten serious AEs were reported in eight patients (2.9%); none were considered treatment related. There were no deaths. Mean (SD) baseline weight was 79.1 (17.8) kg. Mean weight change from baseline to week 52 was 1.86 kg (2.79% increase). PANSS total and CGI-S scores continued to decline over 52 weeks (mean [95% CI] changes from baseline to week 52: −16.2 [−18.5, −14.0] and −0.9 [−1.0, −0.8], respectively).
Conclusion
OLZ/SAM was generally well tolerated in this extension study; most patients completed the 52-week treatment period with sustained improvement in schizophrenia symptoms. Mean increases in weight stabilized by week 6 with limited subsequent change through end of treatment.
Opioid antagonists may mitigate medication-associated weight gain and/or metabolic dysregulation. ENLIGHTEN-2 evaluated a combination of olanzapine and the opioid antagonist samidorphan (OLZ/SAM) vs olanzapine for effects on weight gain and metabolic parameters over 24 weeks in adults with stable schizophrenia.
METHODS:
This phase 3, double-blind study (ClinicalTrials.gov: NCT02694328) enrolled adults 18–55 yo with stable schizophrenia, randomized 1:1 to once-daily OLZ/SAM or olanzapine. Co-primary endpoints were percent change from baseline in body weight and proportion of patients with ≥10% weight gain at week 24. Waist circumference and fasting metabolic parameters were also measured. Completers could enter a 52-week open-label safety extension.
RESULTS:
561 patients were randomized: 550 were dosed, 538 had ≥1 post-baseline weight assessment, and 352 (64%) completed; 10.9% discontinued due to AEs. At week 24, least squares mean (SE) percent weight change from baseline was 4.21 (0.68)% with OLZ/SAM and 6.59 (0.67)% with olanzapine (difference, −2.38 [0.76]%; P=0.003). Fewer patients treated with OLZ/SAM (17.8%) had ≥10% weight gain vs olanzapine (29.8%; odds ratio=0.50; P=0.003). The change from baseline in waist circumference was significantly smaller with OLZ/SAM (P<0.001). Common AEs (≥10%) with OLZ/SAM and olanzapine were weight increased (24.8%, 36.2%), somnolence (21.2%, 18.1%), dry mouth (12.8%, 8.0%), and increased appetite (10.9%, 12.3%), respectively. Metabolic parameter changes were generally small and remained stable with long-term OLZ/SAM treatment.
DISCUSSION:
OLZ/SAM treatment limited weight gain associated with olanzapine. Metabolic parameter changes were generally small, similar between groups over 24 weeks, and remained stable over an additional 52 weeks of open-label OLZ/SAM treatment.
Background: ALKS 3831, a combination of olanzapine and samidorphan (OLZ/SAM), is in development for the treatment of schizophrenia and is intended to provide the antipsychotic efficacy of olanzapine while mitigating olanzapine-associated weight gain. We report the safety, tolerability, and efficacy of OLZ/SAM in patients with schizophrenia in a phase 3, 52-week, open-label extension study.
Methods:
Patients aged 18–70 years who completed a previous phase 3, 4-week, inpatient acute efficacy study were switched from OLZ/SAM, olanzapine, or placebo to OLZ/SAM. Study assessments included adverse events (AEs), weight, clinical laboratory testing, and Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-Severity (CGI-S) scores.
Results:
281 patients were enrolled; 277 (mean age, 41.4 years) received ≥1 dose of study drug, and 183 (66.1%) completed the extension study. The most common reasons for discontinuation were withdrawal by patient (15.5%), loss to follow-up (6.9%), and AEs (5.8%). AEs were reported in 136 (49.1%) patients; most were mild in severity. The most common AEs were increased weight (13.4%), somnolence (8.3%), nasopharyngitis (4.0%), and headache (4.0%). Mean weight increase from baseline in patients completing 52 weeks of treatment was 1.86 kg, a 2.79% increase. No clinically significant changes in mean laboratory parameters were observed. Mean (SD) changes from baseline to week 52 in PANSS total score and CGI-S score were –16.2 (15.41) and –0.9 (0.92), respectively (both P<0.001).
Discussion:
OLZ/SAM was generally well tolerated with a safety profile that supports long-term treatment. During this 52-week extension study, there were improvements in schizophrenia symptoms.
High potency cannabis has been associated with greater risk, and earlier onset of psychosis. However, its effect on brain structure, particularly white matter (WM), has never been explored.
Objectives and Aims
To elucidate the interplay between cannabis potency, pattern of use (frequency and age of first use) and CC microstructure; in patients with first-episode psychosis (FEP) and healthy controls.
Methods
56 FEP and 43 healthy controls underwent Diffusion-Tensor Imaging combined with WM mapping-tractography. CC was virtually dissected and segmented to calculate Fractional Anisotropy (FA), Mean Diffusivity (MD), Axial Diffusivity (AD) and Radial Diffusivity (RD) for each CC segment.
Results
High potency cannabis users had higher Total CC MD and Total CC AD than both low potency users and those who never used (p=0.009 and p=0.02 respectively). Daily users also had higher Total CC MD and Total CC AD than both occasional users and those who never used (p=0.02 and p=0.01 respectively). Furthermore, daily/highpotency users had higher Total CC MD than those who never used or used weekly [F(2,57)=4.7, p=0.01]. There was no effect of diagnosis or diagnosis X potency/patterns of use interactions; neither differences between users who started before the age of 15 and those who started later were detected, in any diffusivity measures.
Conclusions
Frequent use of high-potency cannabis significantly affects callosal microstructure, regardless of the presence of a psychotic disorder. Given the increased availability and use of high potency preparations in Europe, raising awareness about some of their detrimental effects is an important avenue to pursue.
The impact of cannabis use on brain structure, particularly white matter (WM), is poorly understood. The CC is the largest WM structure in the brain. Abnormalities revealed in the CC may underlie functional anomalies of cannabis use. This is the largest study to explore the effect of cannabis on callosal WM connectivity among first episode psychosis (FEP) and controls.
Objectives
To investigate the relationship between cannabis use and WM micro-structural integrity of the CC, in FEP and healthy controls.
Methods
We evaluated 56 FEP patients (67% current cannabis users), and 43 healthy controls (44% current cannabis users). We used Diffusion Tensor Imaging combined with a WM mapping-tractography technique to investigate the microstructural integrity of the CC.
Results
Total CC Fractional anisotropy (FA) was lower in patients than controls (p=0.05). Cannabis-using patients had lower FA of the total CC than cannabis-using controls (p=0.04). There were no differences in FA between cannabis-using patients and those who had never used. However, cannabis-using patients had higher mean diffusivity (MD) of total CC (p= 0.02), Rostral-Body (p=0.003), Anterior Mid-Body (p=0.03) and the Splenium (p=0.06) than patients who never used cannabis. There were no differences in MD between patient users who started before the age of 16 and those who started later.
Conclusion
Cannabis is associated with a significant effect on callosal WM integrity only in patients with psychosis. Disturbed callosal connectivity may explain some of the abnormalities with regard to the functional and clinical outcomes in FEP cannabis users, including measures of cognitive impairment.
Human coronavirus NL63 (HCoV-NL63) is an enveloped pathogen of the family Coronaviridae that spreads worldwide and causes up to 10% of all annual respiratory diseases. HCoV-NL63 is typically associated with mild upper respiratory symptoms in children, elderly and immunocompromised individuals. It has also been shown to cause severe lower respiratory illness. NL63 shares ACE2 as a receptor for viral entry with SARS-CoV-1 and SARS-CoV-2. Here, we present the in situ structure of HCoV-NL63 spike (S) trimer at 3.4-Å resolution by single-particle cryo-EM imaging of vitrified virions without chemical fixative. It is structurally homologous to that obtained previously from the biochemically purified ectodomain of HCoV-NL63 S trimer, which displays a three-fold symmetric trimer in a single conformation. In addition to previously proposed and observed glycosylation sites, our map shows density at other sites, as well as different glycan structures. The domain arrangement within a protomer is strikingly different from that of the SARS-CoV-2 S and may explain their different requirements for activating binding to the receptor. This structure provides the basis for future studies of spike proteins with receptors, antibodies or drugs, in the native state of the coronavirus particles.