Miracle-dz/UniFAR-FTUs huggingface dataset:
Simulation-based power analysis could improve the design of clinical trials in Alzheimer's disease

Clinical trials of new treatments in different progressive diseases use power analysis to determine the sample size needed for a trial to obtain a statistically significant estimate for an anticipated treatment effect. In trials with parallel designs, the standard power analysis approach is based on a two-sample t-test. For example, the standard t-test approach was used in determining the sample size for the Phase 3 trials of aducanumab, the first drug approved by the United States Food and Drug Administration (FDA) to potentially slow cognitive decline in early-stage Alzheimer's disease. However, t-tests contain normality assumptions, and t-test-based power analyses do not implicitly factor in the uncertainty about anticipated treatment effects that arises due to inter-subject heterogeneity in disease progression. These limitations may lead to recommended sample sizes that are too small, potentially making a trial blind to a treatment effect that is truly present if the cohort's endpoints are not normally distributed and/or the anticipated treatment effect is overestimated. To address these issues, we present a novel power analysis method that (1) simulates clinical trials in a progressive disease using real-world data, (2) accounts for inter-subject heterogeneity in disease progression, and (3) does not depend on normality assumptions. As a showcase example, we used our method to calculate power for a range of sample sizes and treatment effects in simulated trials similar to the Phase 3 aducanumab trials EMERGE and ENGAGE. As expected, our results show that power increases with number of subjects and treatment effect (here defined as the cohort-level percent reduction in the rate of cognitive decline in treated subjects vs. controls). However, inclusion of realistic inter-subject heterogeneity in cognitive decline trajectories leads to increased sample size recommendations compared to a standard t-test power analysis. These results suggest that the sample sizes recommended by the t-test power analyses in the EMERGE and ENGAGE Statistical Analysis Plans were possibly too small to ensure a high probability of detecting the anticipated treatment effect. Insufficient sample sizes could partly explain the statistically significant effect of aducanumab being detected only in EMERGE. We also used our method to analyze power in simulated trials similar the Phase 3 lecanemab trial Clarity AD. Our results suggest that Clarity AD was adequately powered, and that power may be influenced by a trial's number of analysis visits and the characteristics of subgroups within a cohort. By using our simulation-based power analysis approach, clinical trials of treatments in Alzheimer's disease and potentially in other progressive diseases could obtain sample size recommendations that account for heterogeneity in disease progression and uncertainty in anticipated treatment effects. Our approach avoids the limitations of t-tests and thus could help ensure that clinical trials are more adequately powered to detect the treatment effects they seek to measure.
Silencing TLR4 using an ultrasound-targeted microbubble destruction-based shRNA system reduces ischemia-induced seizures in hyperglycemic rats

Abstract The toll-like receptor 4 (TLR4) pathway is involved in seizures. We investigated whether ultrasound-targeted microbubble destruction (UTMD)-mediated delivery of short hairpin RNA (shRNA) targeting the TLR4 gene (shRNA-TLR4) can reduce ischemia-induced seizures in rats with hyperglycemia. A total of 100 male Wistar rats were randomly assigned to five groups: (1) Sham; (2) normal saline (NS); (3) shRNA-TLR4, where rats were injected with shRNA-TLR4; (4) shRNA-TLR4 + US, where rats were injected with shRNA-TLR4 followed by ultrasound (US) irradiation; and (5) shRNA-TLR4 + microbubbles (MBs) + US, where rats were injected with shRNA-TLR4 mixed with MBs followed by US irradiation. Western blot and immunohistochemical staining were used to measure TLR4-positive cells. Half of the rats in the NS group developed tonic-clonic seizures, and TLR4 expression in the CA3 region of the hippocampus was increased in these rats. In addition, the NS group showed an increased number of TLR4-positive cells compared with the Sham group, while there was a decreased number of TLR4-positive cells in the shRNA, shRNA + US, and shRNA + MBs + US groups. Our findings indicate that the TLR4 pathway is involved in the pathogenesis of ischemia-induced seizures in hyperglycemic rats and that UTMD technology may be a promising strategy to treat brain diseases.
Assimilation of radar‐derived rain rates into the convective‐scale model COSMO‐DE at DWD

To improve very‐short‐range forecasts particularly in convective situations, a version of the COSMO‐Model (formerly known as LM) which simulates deep convection explicitly (horizontal grid length: 2.8 km) has been developed and is now run operationally at DWD. This model uses a prognostic type of precipitation scheme accounting for the horizontal drift of falling hydrometeors. To initialise convective‐scale events, the latent heat nudging (LHN) approach has been adopted for the assimilation of surface precipitation rates derived from radar reflectivity data. It is found that a conventional LHN scheme designed for larger‐scale models with diagnostic treatment of precipitation does not perform well and leads to strong overestimation of precipitation when applied to the convective‐scale model with a prognostic treatment of precipitation. As illustrated here, surface precipitation and vertically integrated latent heating are far less correlated horizontally and temporally in such a model than with diagnostic precipitation, and this implies a violation of the basic assumption of LHN.
Transfer matrix model of the fiber grating external cavity semiconductor laser

Based on the coupled mode theory, the transfer matrix approach is presented to investigate the fiber grating external cavity semiconductor lasers (FGECSL). As a result, the P-I curve, the lasing wavelength and the side-mode-suppression-ratio (SMSR) have been investigated numerically in detail. With the length of the fiber grating increasing, the reflection spectrum of FGECSL changes obviously, the threshold current and threshold carrier density decreases, the mode distribution is irregular, and the output spectrum becomes complex. Moreover, the optical bistablility is also observed.
A coordinate free approach to score tests

This paper presents a coordinate free approach to score tests and Cα tests. This approach allows the tests to be understood by analogy to the usual linear model. The invariance propertieswith respect to changes in parametrizations are stressed. Finally, aresult of Pregibon relating score tests to the Pearson statistic is extended.
Editorial: With obesity becoming the new normal, what should we do? ‐Volume II

COPYRIGHT © 2022 Tziomalos, Kilpeläinen and Samaras. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. TYPE Editorial PUBLISHED 28 December 2022 DOI 10.3389/fendo.2022. 1119910
Translating Authentic Nursing Knowledge From One Era to Another

As time passes, concepts change. The risk to nursing theories is that concepts can shift so far away from a theorist’s originally intended meaning that future scholars might misunderstand or misuse what will become historically time-bound theories. To preserve authentic nursing knowledge, the process of conceptual matching and translation is proposed. Two thought experiments are used to demonstrate conceptual translation.
RanGTP regulates the augmin complex

Spindles are composed of microtubules that must nucleate at the right place and time during mitosis. Spindle microtubule nucleation is regulated by the GTPase Ran, which, through importin-αβ, releases a gradient of spindle assembly factors (SAFs) centered at chromosomes. Branching MT nucleation generates most spindle MTs and requires the augmin complex. In Xenopus laevis, Ran can control branching through the SAF TPX2, TPX2 is non-essential in other organisms. Thus, how Ran regulates branching MT nucleation in the absence of TPX2 is unknown. Here, we use in vitro pulldowns and TIRF microscopy to show that augmin is itself a SAF. Augmin directly interacts with both importins through two nuclear localization sequences on the Haus8 subunit, which overlap the MT binding site. Moreover, Ran controls localization of augmin to MTs in both Xenopus egg extract and in vitro. By uncovering that RanGTP directly regulates augmin, we demonstrate how Ran controls branching MT nucleation and, thereby, spindle assembly and cell division.
What doesn’t kill you makes you live longer – Longevity of a social host linked to parasite proteins

Parasites with complex lifecycles are known to manipulate the phenotype of their intermediate hosts to increase the probabil-ity of transmission to their deﬁnitive hosts. Anomotaenia brevis , a cestode that uses Temnothorax nylanderi ants as intermediate hosts, extends the lifespan of these hosts several fold and changes their behaviour, morphology, and colouration. The mechanisms behind these changes are unknown, as is whether the increased longevity is achieved through manipulation of the parasite. Here we show that the prolonged lifespan of infected ants is probably due to the secretion of antioxidants and possibly novel substances by the parasite. These parasitic proteins make up a substantial portion of the host haemolymph proteome, and thioredoxin peroxidase and superoxide dismutase, two antioxidants, exhibited the highest abundances among them. The largest part of the secreted proteins could not be annotated, indicating they are either novel or severely altered during recent coevolution to function in host manipulation. We found not only secreted proteins, but also shifts in the host proteome, in particular an overabundance of vitellogenin-like A in infected ants, a protein that regulates division of labour in Temnothorax ants, which ﬁts the observed behavioural changes. Our results thus point at two different strategies that are likely employed by this parasite to manipulate its host – by secretion of proteins with immediate inﬂuence on the host’s phenotype and by altering the host’s translational activity. Our results reveal the intricate molecular interplay required to inﬂuence host phenotype and shed light on potential signalling pathways and genes.
Structural analysis of wild-type and Val120Thr mutant Candida boidinii formate dehydrogenase by X-ray crystallography

Candida boidinii NAD+-dependent formate dehydrogenase (CbFDH) has gained significant attention for its potential applications in the production of biofuels and various industrial chemicals from inorganic carbon dioxide. The present study reports the atomic X-ray crystal structures of the wild-type CbFDH at cryogenic and ambient temperatures as well as Val120Thr mutant at cryogenic temperature determined at the Turkish Light Source “Turkish DeLight”. The structures reveal new hydrogen bonds between Thr120 and water molecules in the mutant CbFDH’s active site, suggesting increased stability of the active site and more efficient electron transfer during the reaction. Further experimental data is needed to test these hypotheses. Collectively, our findings provide invaluable insights into future protein engineering efforts that could potentially enhance the efficiency and effectiveness of CbFDH.
Digital Competences for Improving Digital Inclusion in E-Government Services: A Mixed-Methods Systematic Review Protocol

The e-government requires citizens that have a certain level of digital skills. Contact restrictions caused by the COVID-19 pandemic has accelerated the digital transformation of Public Administration in most countries and has increased the social digital divide. Therefore, the training of citizens in digital competences is one of the main challenges of the knowledge society. This mixed-methods systematic review protocol aims to synthesize quantitative and qualitative findings about conditioning factors of digital inclusion, in a multidimensional perspective, related with the education, healthcare and welfare sectors and the political actions involved to improve the digital competences of citizenship for allowing and enhancing their interactions with these online public services. The protocol has been written following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines. Nine databases including Web of Science, Scopus, Educational Resources Information Center Library and Information Science Abstracts (LISA), ProQuest, MEDLINE, PubMed, SocINDEX and Cairn.info will be searched for peer-reviewed empirical studies published from 2011 or later. Grey literature and citation chaining will be undertaken. Quantitative, qualitative and mixed-methods studies will be included. Data items will be extracted and coded in a standardized format. A convergent segregated approach to synthesis and integration will be used. The results will be of interest to educational policymakers who want to take into account citizens’ digital skills in the design of online services and lifelong learning programs.
Theoretical Substruction of Resilience Theory: Dementia Caregivers’ Burden and Their Care Recipients’ Behavior

Theoretical substruction is vital in clarifying models and guiding research. In this article, the process of theoretical substruction was examined through resilience theory to provide an example of the congruence between theoretical and operational definitions in nursing research. The author examines the significance of resilience theory in the context of dementia caregivers’ burden and their care recipients’ behavioral problems. The steps of theoretical substruction are included, and a model of resilience is presented that includes middle-range concepts, relational statements, and propositions derived from the research literature. The rigorous process of theoretical substruction provides an example of a theoretically sound basis for exploring the role of positive thinking in the lives of dementia caregivers and their care recipients. Geropsychiatric nurses working with dementia patients and their caregivers should consider the role of positive thinking in decreasing caregivers’ burden.
The 360 Diary Method: A New Approach to Student Assessment and Intervention

STUDENT AFFAIRS PRACTITIONERS, faculty, and researchers rely heavily on surveys to assess elements of students’ college experience such as student satisfaction and cocurricular participation. The ubiquitous student survey has serious drawbacks for informing institutional improvement, however, given typically low response rates and systematic underrepresentation of students from marginalized campus groups among those who do respond (Fosnacht, Sarraf, Howe, & Peck, 2017; Lin, Hewitt, & Videras, 2017; Porter, 2004; Standish & Umbach, 2019). Surveys are ill-equipped to capture in-the-moment, unfiltered responses of students’ lived experiences in the arenas students themselves consider important. Moreover, surveys that ask for self-reported retrospective accounts make recall bias another roadblock to understanding what is currently going on in students’ lives (Zirkel, Garcia, & Murphy, 2015). It is therefore imperative that higher education professionals adopt innovative student assessment strategies that elicit deeper and more representative accounts of student perceptions to inform student affairs policies and interventions. New affordances in technology and the increased use of digital communication among college students (Pew, 2019) offer unprecedented opportunities for creative, longitudinal, and formative student assessment methods that center student perspectives and occur in real time. The 360 Diary Method (360DM) provides a promising new approach to student assessment and intervention where current methods fall short.
A nonorthogonal finite-difference time-domain method for computing the band structure of a two-dimensional photonic crystal with dielectric and metallic inclusions

A finite-difference time-domain scheme in a nonorthogonal coordinate system is presented to calculate the band structure of a two-dimensional photonic crystal consisting of a skew lattice. The method can be used for a photonic crystal of complicated configuration, such as a photonic crystal with both dielectric and metallic inclusions. The method is verified by comparing with the results obtained by other methods for some special cases. The band structure of a photonic crystal with a dielectric layer coated on a metallic cylinder as an inclusion is studied. For such a case, it is noticed that both the dielectric and metallic characteristics of the band structure are inherited.
Population-Based Studies in Dementia and Ageing Research: A Local and National Experience in Cambridgeshire and the UK

Dementia has been recognised as a key challenge in many ageing societies across the world. Several population-based studies have been developed to investigate dementia and cognitive ageing from perspectives of biology, health, psychology and social sciences. However, there is a need to provide a better understanding of ‘contexts’, the circumstance where these ageing populations existed, and heterogeneity within and across the populations in different time and places. In this article, we summarise some examples of earlier population-based studies undertaken by our research groups in England and Wales and their contribution to the epidemiology of dementia, neuropathology, cognitive and mental health in older age. We also describe how these studies illustrated variation among ageing populations and changes in their health conditions across time and place. These findings highlight the contribution that population-based studies can make, along with the vital to incorporate contexts in ageing research. A lifecourse approach within social context is needed to integrate life experiences, social circumstances, and multiple dimensions of cognition, functioning, physical health and wellbeing over the ageing process. We also discuss how evidence from population-based studies can support various international initiatives on dementia, healthy ageing and Sustainable Development Goals and facilitate tailored approaches for diverse populations across global societies.
Variable Structure Control of a Pneumatic Actuator

In an effort to overcome the nonlinearities associated with a pneumatic system the variable structure control (VSC) technique has been employed to control the position of a pneumatic actuator. To accomplish this a model of a pneumatic actuator was developed to allow the control systems to be studied via simulations. The results from the simulations indicated that the VSC technique can position the actuator rapidly, via a first-order trajectory, in response to a step input. An experimental study of the VSC control system was then performed. These experiments verified the simulation work, and demonstrated that inherent system delays and the quantisation of the control signals can cause an uncontrollable oscillatory behaviour; stability limits were established for three of the system parameters. It was also found, that the actuator could be placed within ± 5 mm of the desired position
SOCIOECONOMIC AND ENVIRONMENTAL PERFORMANCE: A COMPOSITE INDEX APPROACH AND COMPARATIVE APPLICATION TO THE USA AND CHINA IN THE NEW MILLENNIUM*

This paper deals with an analytical framework to provide a measure of overall performance which involves both socioeconomic activities and environmental sustainability using a recent Index of well-being. The composite indicator, created by Medrano-B & Teixeira (2013), is associated with the so called “Magic Square”, a diagram stimulated by the work of Kaldor (1971). From this starting point, we introduce a robust set of four variables to measure their total impact on the sustainable development of each economy or region. They are: human development index, per capita carbon dioxide, drinkable water and sanitation, and intensity of renewable energy measured as a fraction of the total generated. This formal approach is applied to the comparative performance of the USA and China from 2002 to 2012. As expected, environmental, socioeconomic and institutional indicators affect the level of welfare. This being the case, an important lesson is that careful regulation and policy actions, not just proposals, are required to implement a sustainable and acceptable quality of life. In this article we completed the argument by suggesting that a new paradigm is required to fulfill our desirable objectives, and thus get more out of our intellectual effort, capabilities and political influence. This proposal may well be indigestible or simply ignored by many. On the other hand, now that disillusionment with the current state of affairs is setting in, perhaps this new vision will get a strong hearing at last.
Knowledge, Attitude, and Practice of Obstetrics Trainees in Sudan Medical Specialisation Board (SMSB), Sudan, Towards Postpartum Depression

Introduction: Postpartum Depression (PPD) refers to non-dysphoric changes in a woman’s physical, mental and behavioral states that occur in the postpartum period. Approximately one in seven women can suffer from postpartum depression (PPD). Obstetrics trainees have a major role in diagnosing and managing PPD patients, specially in developing countries such as Sudan. Methods: A descriptive cross-sectional hospital-based study design to evaluate obstetrics trainees’ knowledge, attitude and practice in the Sudan Medical Specialisations Board (SMSB), towards postpartum depression in Sudan, performed between April 2020 to October 2020. Data Collection was done using an Online structured self-filled questionnaire distributed to the Obstetrics registrars in training in Sudan Medical Specialisations Board (SMSB). Data analysis was performed using SPSS. Result & Conclusion: The knowledge of PPD among the obstetrics trainees is relatively below average, with moderate attitude and poor practice. Obstetric trainees should have formal training in psychiatry to identify Postpartum Depression. The Edinburgh Postnatal DepressionScale should be used in screening women for postpartum depression.