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We develop the scale transformed power prior for settings where historical and current data involve different data types, such as binary and continuous data. This situation arises often in clinical trials, for example, when historical data involve binary responses and the current data involve some other type of continuous or discrete outcome. The power prior, proposed by Ibrahim and Chen, does not address the issue of different data types. Herein, we develop a new type of power prior, which we call the scale transformed power prior (straPP). The straPP is constructed by transforming the power prior for the historical data by rescaling the parameter using a function of the Fisher information matrices for the historical and current data models, thereby shifting the scale of the parameter vector from that of the historical to that of the current data. Examples are presented to motivate the need for such a transformation, and simulation studies are presented to illustrate the performance advantages of the straPP over the power prior and other informative and noninformative priors. A real dataset from a clinical trial undertaken to study a novel transitional care model for stroke survivors is used to illustrate the methodology.

Summary There has been increased interest in using prior information in statistical analyses. For example, in rare diseases, it can be difficult to establish treatment efficacy based solely on data from a prospective study due to low sample sizes. To overcome this issue, an informative prior to the treatment effect may be elicited. We develop a novel extension of the conjugate prior of Chen and Ibrahim (2003) that enables practitioners to elicit a prior prediction for the mean response for generalized linear models, treating the prediction as random. We refer to the hierarchical prior as the hierarchical prediction prior (HPP). For independent and identically distributed settings and the normal linear model, we derive cases for which the hyperprior is a conjugate prior. We also develop an extension of the HPP in situations where summary statistics from a previous study are available. The HPP allows for discounting based on the quality of individual level predictions, and simulation results suggest that, compared to the conjugate prior and the power prior, the HPP efficiency gains (e.g., lower mean squared error) where predictions are incompatible with the data. An efficient Monte Carlo Markov chain algorithm is developed. Applications illustrate that inferences under the HPP are more robust to prior-data conflict compared to selected nonhierarchical priors.

Summary In clinical trials, it is common to have multiple clinical outcomes (e.g., coprimary endpoints or a primary and multiple secondary endpoints). It is often desirable to establish efficacy in at least one of multiple clinical outcomes, which leads to a multiplicity problem. In the frequentist paradigm, the most popular methods to correct for multiplicity are typically conservative. Moreover, despite guidance from regulators, it is difficult to determine the sample size of a future study with multiple clinical outcomes. In this article, we introduce a Bayesian methodology for multiple testing that asymptotically guarantees type I error control. Using a seemingly unrelated regression model, correlations between outcomes are specifically modeled, which enables inference on the joint posterior distribution of the treatment effects. Simulation results suggest that the proposed Bayesian approach is more powerful than the method of Holm (1979), which is commonly utilized in practice as a more powerful alternative to the ubiquitous Bonferroni correction. We further develop multivariate probability of success, a Bayesian method to robustly determine sample size in the presence of multiple outcomes.

A gas chromatography with flame ionization detection (GC-FID) method was developed to quantify reductive catalytic fractionation (RCF) monomers.

Positron emission tomography is the imaging modality of choice when it comes to the high sensitivity detection of key markers of thrombosis and inflammation, such as activated platelets. We, previously, generated a fluorine-18 labelled single-chain antibody (scFv) against ligand-induced binding sites (LIBS) on activated platelets, binding it to the highly abundant platelet glycoprotein integrin receptor IIb/IIIa. We used a non-site-specific bio conjugation approach with N-succinimidyl-4-[18F]fluorobenzoate (S[18F]FB), leading to a mixture of products with reduced antigen binding. In the present study, we have developed and characterised a novel fluorine-18 PET radiotracer, based on this antibody, using site-specific bio conjugation to engineer cysteine residues with N-[2-(4-[18F]fluorobenzamido)ethyl]maleimide ([18F]FBEM). ScFvanti-LIBS and control antibody mut-scFv, with engineered C-terminal cysteine, were reduced, and then, they reacted with N-[2-(4-[18F]fluorobenzamido)ethyl]maleimide ([18F]FBEM). Radiolabelled scFv was injected into mice with FeCl3-induced thrombus in the left carotid artery. Clots were imaged in a PET MR imaging system, and the amount of radioactivity in major organs was measured using an ionisation chamber and image analysis. Assessment of vessel injury, as well as the biodistribution of the radiolabelled scFv, was studied. In the in vivo experiments, we found uptake of the targeted tracer in the injured vessel, compared with the non-injured vessel, as well as a high uptake of both tracers in the kidney, lung, and muscle. As expected, both tracers cleared rapidly via the kidney. Surprisingly, a large quantity of both tracers was taken up by organs with a high glutathione content, such as the muscle and lung, due to the instability of the maleimide cysteine bond in vivo, which warrants further investigations. This limits the ability of the novel antibody radiotracer 18F-scFvanti-LIBS to bind to the target in vivo and, therefore, as a useful agent for the sensitive detection of activated platelets. We describe the first fluorine-18 variant of the scFvanti-LIBS against activated platelets using site-specific bio conjugation.

The Fugl-Meyer assessment (FMA) is the most widely used and recommended clinical assessment scale for evaluating sensorimotor impairments in stroke patients, but an official Danish version has not been available. This study aimed to perform a standardized translation and cross-cultural adaptation (TCCA) of the FMA into Danish.First, a comprehensive eight-step TCCA procedure including forward and backward translation and step-wise reviewing by proof-reader and bilingual physiotherapists, to ensure conceptual and semantic equivalence was applied to develop a Danish version of the FMA. Second, inter-rater reliability of the Danish FMA was assessed in 10 subacute stroke patients. Svensson's statistical method designed for rank-based paired ordinal data to identify items showing non-systematic or systematic disagreements in relative position or concentration was used to make further improvements on translation.A Danish FMA version was successfully made by the step-wise TCCA procedure. The clinical validation revealed satisfactory to excellent inter-tester reliability across all items (70-100%). Significant systematic disagreement either in position or concentration or both were observed in about 20% of the items.The Danish version of the FMA was translated and adapted allowing for a wider standardized use of the FMA in stroke rehabilitation in Denmark.Implications for rehabilitationThe Fugl-Meyer assessment (FMA) is the most used and recommended clinical assessment scale for evaluating sensorimotor impairments in stroke patients.The translated and adapted Danish version of the FMA is now available for use in research and clinical practice in Denmark.This allows for a standardized and unified description of stroke motor recovery and severity in neurorehabilitation nationwide as well as the possibility to compare and conduct trials using FMA internationally.

Background Cryptosporidium sp. are common intracellular parasites responsible of severe diarrhea in T-cell-immunocompromised patients. We report the first case of a woman who contracted cryptosporidiosis after treatment with fingolimod, a drug labeled for multiple sclerosis and responsible for marked lymphopenia. Case presentation A 60-year-old woman was admitted for abdominal pain diarrhea and fever. The patient suffered from multiple sclerosis and had been treated with fingolimod from august 2017 to september 2018 time of occurrence of the first digestive symptoms. Stool culture was negative but parasitological examination was positive for Cryptosporidium sp. Blood biological examination profound lymphopenia of 240/mm3 [17 CD4/mm3 (7%) and 32 CD8/mm3 (14%)]. Fingolimod was stopped, and the patient was put on nitazoxanide 500 mg bid for 7 days. The diarrhea resolved and no relapse was observed. Six other cases were found in the Pharmacovigilance database. Conclusion Physicians should be aware of this association and screen for Cryptosporidium in cases of diarrhea in patients treated with fingolimod. Patients should be aware of this risk and advise to take appropriate measures to avoid such contamination.

In this paper, we present our investigations on the Emerald Avenue, a potential Mississippian period (a.d. 1050–1400) roadway in southwestern Illinois. It is hypothesized that this road connected t...

Archaeological and isotopic evidence from Greater Cahokia and several prominent outlier sites argues against simple diaspora models either for the rise or fall of this pre-Columbian urban phenomenon. Besides indications that a culturally diverse population was associated with the city throughout its history, we argue that a spiritual vitality undergirded its origins such that many movements of people would have been two-way affairs. Some Cahokians who ultimately left the city may have been members of foreign lineages in the beginning.

Objective To describe spasticity from the onset of acquired brain injury, time course over the first year and factors associated with prediction of the development of spasticity. Methods Recent relevant literature known to the authors, along with a complementary search yielding a total of 9 articles, represented the base for this scoping review. Results Spasticity can be seen in the first week after brain injury and is more common in the upper than lower extremity. The severity of upper-limb impairment is a major factor in the development of spasticity during the first year after stroke. The prevalence of severe spasticity seems to increase during the first year. The combination of reduced arm motor function and spasticity in an early phase (4 weeks post-stroke) is an important predictor of the development of severe spasticity after 12 months. Spontaneous reduction in spasticity was seldom reported but may occur, especially in mild forms of spasticity. Conclusion Signs of spasticity can often be noted within the first 4 weeks after brain injury and is more common in the upper than lower extremity. Impaired sensorimotor function is a predictor. These findings highlight the importance to follow up patients with increased risk of developing severe spasticity to be able to start adequate spasticity treatment and prevent the negative consequences of spasticity. Understanding spasticity onset and progression also provides a basis for the development of effective therapies.

The use of antibiotics in animal agriculture has exacerbated the presence of both antibiotic resistance genes (ARGs) and residual antibiotics excreted in animal manure. Field application of this manure is a common practice because its nutrient rich material can benefit crop growth. However, this practice can also introduce antibiotics and ARGs into nonagricultural settings. The integration of prairie buffer strips within and at the edge of crop fields is a potential management solution to reduce concentrations of ARGs commonly transported via water runoff and infiltration. An incubation experiment was conducted to investigate the fate of ARGs in directly manured crop field soils and the surrounding affected prairie strip soils. Row crop and prairie strip soils sampled from three sites received either an antibiotic spike and swine manure addition or a control water addition. The concentrations of select ARGs were then monitored over a 72-d period. Although soil vegetation and site location were not observed to influence ARG dissipation, the select genes did display different half-lives from one another. For example, tetM demonstrated the fastest dissipation of the genes quantified (average half-life, 5.18 d). Conversely, sul1 did not conform to the first-order linear regression kinetics used to describe the other investigated genes and was highly abundant in control prairie strip soils. The quantified half-lives of these select ARGs are comparable to previous studies and can inform monitoring and mitigative efforts aimed at reducing the spread of ARGs in the environment.

The Deep Underground Neutrino Experiment (DUNE) is an international, world-class experiment aimed at exploring fundamental questions about the universe that are at the forefront of astrophysics and particle physics research. DUNE will study questions pertaining to the preponderance of matter over antimatter in the early universe, the dynamics of supernovae, the subtleties of neutrino interaction physics, and a number of beyond the Standard Model topics accessible in a powerful neutrino beam. A critical component of the DUNE physics program involves the study of changes in a powerful beam of neutrinos, i.e., neutrino oscillations, as the neutrinos propagate a long distance. The experiment consists of a near detector, sited close to the source of the beam, and a far detector, sited along the beam at a large distance. This document, the DUNE Near Detector Conceptual Design Report (CDR), describes the design of the DUNE near detector and the science program that drives the design and technology choices. The goals and requirements underlying the design, along with projected performance are given. It serves as a starting point for a more detailed design that will be described in future documents. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

This article emerged as the human species collectively have been experiencing the worst global pandemic in a century. With a long view of the ecological, economic, social, and political factors that promote the emergence and spread of infectious disease, archaeologists are well positioned to examine the antecedents of the present crisis. In this article, we bring together a variety of perspectives on the issues surrounding the emergence, spread, and effects of disease in both the Americas and Afro-Eurasian contexts. Recognizing that human populations most severely impacted by COVID-19 are typically descendants of marginalized groups, we investigate pre- and postcontact disease vectors among Indigenous and Black communities in North America, outlining the systemic impacts of diseases and the conditions that exacerbate their spread. We look at how material culture both reflects and changes as a result of social transformations brought about by disease, the insights that paleopathology provides about the ancient human condition, and the impacts of ancient globalization on the spread of disease worldwide. By understanding the differential effects of past epidemics on diverse communities and contributing to more equitable sociopolitical agendas, archaeology can play a key role in helping to pursue a more just future.

Uncovering ancient Native American histories requires more than considering people, places, and events. It entails recognizing the full assemblage of human and nonhuman agents, forces, powers, affects and atmospheres—and how such were entangled with each other. Uncovering these histories requires considering the processes that drove them, but more, it requires recognizing places and things that particularly resonated because of special powers and vibrancies, that evoked powerful human responses. This requires paying attention to what the people we study believed and recognized, information accessible through material assemblages and oral histories. Alt considers Cahokian assemblages—mounds, caves, water, fire, stone, clay, human and nonhuman persons—to explore how history can be enriched and altered by historicizing an expanded assemblage.

Obesity is associated with dyslipidemia and subclinical inflammation that promotes metabolic disturbances including insulin resistance and pancreatic β-cell dysfunction. The nuclear protein, transcriptional regulator 1 (NUPR1) responds to cellular stresses and features tissue protective properties. To characterize the role of NUPR1 in endocrine pancreatic islets during inflammatory stress, we generated transgenic mice with β-cell-specific Nupr1 overexpression (βNUPR1). Under normal conditions, βNUPR1 mice did not differ from wild type (WT) littermates and display normal glucose homeostasis and β-cell mass. For induction of inflammatory conditions, mice were treated with multiple low-dose streptozotocin (mld-STZ) and/or fed a high-fat diet (HFD). All treatments significantly worsened glycaemia in WT mice, while βNUPR1 mice substantially preserved insulin secretion and glucose tolerance. HFD increased β-cell mass in all animals, with βNUPR1 mice tending to show higher values. The improved outcome of βNUPR1 mice was accompanied by decreased NF-κB activation and lymphocyte infiltration in response to mld-STZ. In vitro, isolated βNUPR1 islets preserved insulin secretion and content with insignificantly low apoptosis during culture stress and IL-1β exposure. These findings suggest that NUPR1 plays a vital role in the protection of β-cells from apoptosis, related degradation of insulin storages and subsequent secretion during inflammatory and obesity-related tissue stress.

Purpose: The Fugl-Meyer Assessment is the most used and highly recommended clinical assessment of sensorimotor function after stroke. A standardized use of the scale in different countries requires translation and cultural validation to the target language. The objective of the study was to develop an official Italian version of the scale by transcultural translation and validation.Methods: A standardized multistep translation protocol was adopted to achieve optimal conceptual and semantic equivalence. The developed Italian version was validated in 10 post-stroke hemiparetic patients. Items with low intra- and interrater agreement, quantified as percentage of agreement

Objectives Wearable sensors that measure movement and physiological variables are attractive for clinical evaluation of neurological diseases such as epilepsy and Parkinson's disease (PD). The aim of this study was to explore perceptions regarding the use of wearable technology in disease monitoring and management as reported by individuals with epilepsy and Parkinson's disease as well as health professionals working with these patient groups. Materials and Methods Six patient groups (n=25) and two groups with health professionals (n=15) participated in this qualitative, descriptive study with focus group interviews. A manifest qualitative content analysis was used. Results Four categories and nine subcategories emerged from the analysis. Participants saw possible benefits for improved treatment effect and valued this benefit more than possible inconvenience of wearing the sensors. Discrete design and simplicity were considered as facilitators for improved usability. They emphasized the importance of interactive information between patients and health professionals. However, they were concerned about unclear information and inconclusive recordings and some fears about personal integrity were at odds with the expectations on interactivity. Conclusions Patients need to feel well informed and find an added value in using wearables. Wearables need to be user-friendly, have an attractive design, and show clinical efficacy in improving disease management. Variations in perceptions regarding integrity, benefits, and effectiveness of monitoring indicate possible conflicts of expectations among participants. The engagement of end users, patients, and health professionals, in the design and implementation process, is crucial for the development of wearable devices that enhance and facilitate neurological rehabilitation practice.

In the mid eleventh century AD, Cahokia emerged as a substantial Mississippian urban centre. To the east, a shrine-complex known as the Emerald Acropolis, marking the beginning of a processional route to the city, also flourished. Excavations and geophysical survey of the monumental landscape around this site suggest that lunar cycles were important in the orientation of structures and settlement layout. They further indicate that water played a significant role in the ritual activities associated with the closure and abandonment of individual structures. The contemporary development of these sites suggests an intrinsic connection between them, and provides early evidence of the importance that the moon and water came to assume in Mississippian culture.

Supplemental Material for Standardized measurement of quality of upper limb movement after stroke: Consensus-based core recommendations from the Second Stroke Recovery and Rehabilitation Roundtable by G Kwakkel, EEH Van Wegen, JH Burridge, CJ Winstein, LEH van Dokkum, M Alt Murphy, MF Levin, JW Krakauer and on behalf of the ADVISORY group in International Journal of Stroke