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This chapter explores the psychopathological signs associated with catatonia, aiming to clarify their definitions and support these with clinical studies. We focus on the complex nature of catatonic signs by: (1) describing the wide range of signs, (2) explaining catatonia subtypes, (3) discussing the diagnostic challenges, (4) listing the possible differential diagnoses of catatonia, and finally (5) addressing serious health risks, including circulatory collapse, respiratory failure, and renal failure with their implications for clinical diagnosis and therapy. This comprehensive overview serves as a vital resource for clinicians, providing tools to accurately diagnose and effectively treat catatonia. By understanding the subtypes, differential diagnoses, and severe complications such as circulatory collapse and respiratory failure, clinicians can better identify life-threatening conditions and implement timely appropriate therapeutic interventions.
Visceral larva migrans syndrome (VLM) is caused by L2 Toxocara canis. This parasitic disease is difficult to diagnose in humans, but specific antigen identification could allow for parasite detection. The aim of this study was to analyse antigens of different parasite developmental stages and observe their cross-reactions with antigens from other parasites to determine their importance in the diagnosis of VLM caused by T. canis. Sera from 14 children with cryptogenic epilepsy previously positive for T. canis were analysed via Western blot (WB) using T. canis excretion-secretion antigens (TESs) from distinct morphological parasite stages; cross-reactivity of these antigens with antigens from other parasites were evaluated. Children sera recognized antigens from L2 T. canis TES, mainly a protein of 24 kDa. Proteins in the medium- and high-molecular-weight ranges were also detected in the egg phase. In the adult phase, only 42.9% of analysed sera recognized a protein of high-molecular weight. Cross-reaction tests identified medium and high-molecular weight proteins, mainly from L2 of Ascaris lumbricoides and Gnathostoma binucleatum and adults of Ancylostoma caninum, but none of the proteins found had crossover with low-molecular weight proteins from Toxocara canis. Antigens in the larval morphological stage of T. canis TES were recognized in the highest percentage of the analysed sera; these antigens could be used to diagnose VLM.
Political scientists regularly rely on a selection-on-observables assumption to identify causal effects of interest. Once a causal effect has been identified in this way, a wide variety of estimators can, in principle, be used to consistently estimate the effect of interest. While these estimators are all justified by appeals to the same causal identification assumptions, they often differ greatly in how they make use of the data at hand. For instance, methods based on regression rely on an explicit model of the outcome variable but do not explicitly model the treatment assignment process, whereas methods based on propensity scores explicitly model the treatment assignment process but do not explicitly model the outcome variable. Understanding the tradeoffs between estimation methods is complicated by these seemingly fundamental differences. In this paper we seek to rectify this problem. We do so by clarifying how most estimators of causal effects that are justified by an appeal to a selection-on-observables assumption are all special cases of a general weighting estimator. We then explain how this commonality provides for diagnostics that allow for meaningful comparisons across estimation methods—even when the methods are seemingly very different. We illustrate these ideas with two applied examples.
Male genital schistosomiasis (MGS), a gender-specific manifestation of urogenital schistosomiasis and neglected tropical disease, typically results from the entrapment of Schistosoma haematobium eggs within the male genital tract. Across the world, there are no current and accurate estimates of the burden of MGS, due to disease underreporting primarily from diagnostic challenges and a lack of general awareness within the health system. Diagnostic methods for MGS are extremely limited. Conventionally, semen microscopy for Schistosoma ova is used though this technique suffers from low sensitivity and lacks protocol standardization. The introduction of molecular diagnostics, such as polymerase chain reaction (PCR), has partly helped overcome this challenge of low sensitivity, though may not be suitable for use in resource-constrained settings. To address these challenges, in this review, we propose a two-step diagnostic algorithm for MGS in accordance with recent WHO guidelines, consisting of a high sensitivity serological test followed by a high specificity test (microscopy or molecular assay, dependent on setting). Further investigation is required into standardization of sample collection, processing, storage, and analysis in order to identify an evidence-based optimal diagnostic pipeline. New diagnostic tools are needed such as isothermal molecular assays, alongside optimization for semen analysis, which may alleviate barriers to diagnosis and present opportunities for integration with other sexual and reproductive health screening. These areas of future investigation underpin the development of a suitable diagnostic pipeline, as the continued neglect of MGS and its underdiagnosis presents a threat to the goal of elimination of schistosomiasis as a public health problem.
Epilepsy is a relatively common condition that affects approximately 4–5 per 1000 individuals in Ontario, Canada. While genetic testing is now prevalent in diagnostic and therapeutic care plans, optimal test selection and interpretation of results in a patient-specific context can be inconsistent and provider dependent.
Methods:
The first of its kind, the Ontario Epilepsy Genetic Testing Program (OEGTP) was launched in 2020 to develop clinical testing criteria, curate gene content, standardize the technical testing criteria through a centralized testing laboratory, assess diagnostic yield and clinical utility and increase genetics literacy among providers.
Results:
Here we present the results of the first two years of the program, demonstrating the overall 20.8% diagnostic yield including pathogenic sequence and copy number variation detected by next-generation sequencing panels. Routine follow-up testing of family members enabled the resolution of ambiguous findings. Post-test outcomes were collected as reported by the ordering clinicians, highlighting the clinical benefits of genetic testing.
Conclusion:
This programmatic approach to genetic testing in epilepsy by OEGTP, together with engagement of clinical and laboratory stakeholders, provided a unique opportunity to gather insight into province-wide implementation of a genetic testing program.
Different agencies have emphasized the need to evaluate current serological methods for screening patients with suspected urogenital schistosomiasis. However, there is still a lack of evidence regarding the most appropriate methods for this purpose. Here we assessed the diagnostic efficacy of a newly developed serological technique that utilizes the recombinant protein Sh-TSP-2, applied to the urine and serum of migrants suspected of having urogenital schistosomiasis. The sensitivity, specificity, positive and negative predictive values of an in-house enzyme-linked immunosorbent assay (ELISA) using the recombinant protein Sh-TSP-2 were analysed and compared with other commercial serological methods. Due to the limitations of microscopy as a perfect reference method, a latent class analysis (LCA) and composite reference standard (CRS) approach was used to determine the sensitivity and specificity of each test. According to the LCA model, the commercial tests NovaLisa® and immunochromatography test (ICT) immunoglobulin G–immunoglobulin M (IgG–IgM) presented the highest sensitivity (100%), whereas the Sh-TSP-2 serum ELISA test had 79.2%. The Sh-TSP-2 urine and serum ELISA tests had the highest specificities among the serological methods (87.5 and 75%, respectively). CRS modelling showed that the ICT IgG–IgM, NovaLisa® and Sh-TSP-2 serum tests led in sensitivity at 97.1, 88.6 and 71.4%, respectively, with all tests except that the ICT IgG–IgM test having a specificity >90%. Sh-TSP-2 has been validated as a screening tool for patients suspected of having urogenital schistosomiasis. Although commercial serological tests have shown higher sensitivities, Sh-TSP-2 could be valuable for confirming results from tests with lower specificity. Nevertheless, further studies with larger patient cohorts are necessary to fully verify its potential.
Buildings employ an ensemble of technical systems like those for heating and ventilation. Ontologies such as Brick, IFC, SSN/SOSA, and SAREF have been created to describe such technical systems in a machine-understandable manner. However, these focus on describing system topology, whereas several relevant use cases (e.g., automated fault detection and diagnostics (AFDD)) also need knowledge about the physical processes. While mathematical simulation can be used to model physical processes, these are practically expensive to run and are not integrated with mainstream technical systems ontologies today. We propose to describe the effect of component actuation on underlying physical mechanisms within component stereotypes. These stereotypes are linked to actual component instances in the technical system description, thereby accomplishing an integration of knowledge about system structure and physical processes. We contribute an ontology for such stereotypes and show that it covers 100% of Brick heating, ventilation, and air-conditioning (HVAC) components. We further show that the ontology enables automatically inferring relationships between components in a real-world building in most cases, except in two situations where component dependencies are underreported. This is due to missing component models for passive parts like splits and join in ducts, and hence points at concrete future extensions of the Brick ontology. Finally, we demonstrate how AFDD applications can utilize the resulting knowledge graph to find expected consequences of an action, or conversely, to identify components that may be responsible for an observed state of the process.
Next generation high-power laser facilities are expected to generate hundreds-of-MeV proton beams and operate at multi-Hz repetition rates, presenting opportunities for medical, industrial and scientific applications requiring bright pulses of energetic ions. Characterizing the spectro-spatial profile of these ions at high repetition rates in the harsh radiation environments created by laser–plasma interactions remains challenging but is paramount for further source development. To address this, we present a compact scintillating fiber imaging spectrometer based on the tomographic reconstruction of proton energy deposition in a layered fiber array. Modeling indicates that spatial resolution of approximately 1 mm and energy resolution of less than 10% at proton energies of more than 20 MeV are readily achievable with existing 100 μm diameter fibers. Measurements with a prototype beam-profile monitor using 500 μm fibers demonstrate active readouts with invulnerability to electromagnetic pulses, and less than 100 Gy sensitivity. The performance of the full instrument concept is explored with Monte Carlo simulations, accurately reconstructing a proton beam with a multiple-component spectro-spatial profile.
In this introductory chapter, we provide a brief overview of some of the main topics related to dementia communication research that are addressed by the different chapters in this edited volume: Dementia and Diagnostics, Dementia and Conversational Strategies, Dementia and Epistemics, and Communicative Challenges in Everyday Social Life. One of the central aims of this volume is to shed more light on how persons with dementia accomplish relevant goals in interaction and also how changes in an individual’s discursive abilities may impact how conversationalists negotiate a world in common and continue to build their social relationships. All contributions for this edited volume draw on the methods of Conversation Analysis (CA), an approach to social interaction that provides a detailed view of the moment-by-moment accomplishment of social life. By exploring interactional practices through the lens of CA, this volume seeks to explore interactions involving people with dementia in a variety of contexts (everyday and institutional), pointing to both the interactional difficulties that often arise, but also the creativity and collaboration within these interactional encounters. A summary of each of the volume’s chapters is also provided.
Multiple linear regression generalizes straight line regression to allow multiple explanatory (or predictor) variables, in this chapter under the normal errors assumption. The focus may be on accurate prediction. Or it may, alternatively or additionally, be on the regression coefficients themselves. Simplistic interpretations of coefficients can be grossly misleading. Later chapters elaborate on the ideas and methods developed in this chapter, applying them in new contexts. The attaching of causal interpretations to model coefficients must be justified both by reference to subject area knowledge and by careful checks to ensure that they are not artefacts of the correlation structure. There is attention to regression diagnostics, to assessment, and comparison of models. Variable selection strategies can readily over-fit. Hence the importance of training/test approaches and cross-validation. The potential is demonstrated for errors in x to seriously bias regression coefficients. Strong multicollinearity leads to large variance inflation factors.
A colliding microjet liquid sheet target system was developed and tested for pairs of round nozzles of 10, 11 and 18 μm in diameter. The sheet’s position stability was found to be better than a few micrometers. Upon interaction with 50 mJ laser pulses, the 18 μm jet has a resonance amplitude of 16 μm at a repetition rate of 33 Hz, while towards 100 Hz it converges to 10 μm for all nozzles. A white-light interferometric system was developed to measure the liquid sheet thickness in the target chamber both in air and in vacuum, with a measurement range of 182 nm–1 μm and an accuracy of ±3%. The overall shape and 3D shape of the sheet follow the Hasson–Peck model in air. In vacuum versus air, the sheet gradually loses 10% of its thickness, so the thinnest sheet achieved was below 200 nm at a vacuum level of 10–4 mbar, and remained stable for several hours of operation.
The COVID-19 pandemic caused unprecedented loss as it swept through humanity wiping out 6.69 million human lives. It is now estimated that 660 million of the world’s population was infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus that emerged in Wuhan, China, and then rapidly spread across continents. This is our story of how we came together during an incredibly challenging time to fight a common enemy. Times of crisis can often serve as strong drivers of creativity and innovation. It was during the crisis of the pandemic that the National Institutes of Health (NIH) launched the Rapid Acceleration of Diagnostics (RADx®) initiative to accelerate the translation of innovation into high-performing diagnostic tests. This book chronicles the power of innovating during a crisis, the compression of product launch timelines from over five years to under a year, the birth of creative financing ventures, the commitment of entrepreneurs, and the agility and resourcefulness of government institutions as they adapted to meet the imminent needs of the pandemic and serve the community. It is our sincere hope that the lessons learned from the trenches will improve our nation’s ability to fight the next pandemic.
To meet the demands of laser-ion acceleration at a high repetition rate, we have developed a comprehensive diagnostic system for real-time and in situ monitoring of liquid sheet targets (LSTs). The spatially resolved rapid characterizations of an LST’s thickness, flatness, tilt angle and position are fulfilled by different subsystems with high accuracy. With the help of the diagnostic system, we reveal the dependence of thickness distribution on collision parameters and report the 238-nm liquid sheet generated by the collision of two liquid jets. Control methods for the flatness and tilt angle of LSTs have also been provided, which are essential for applications of laser-driven ion acceleration and others.
The European grapevine moth Lobesia botrana (Denis & Shiffermüller 1776) is an economically important pest of the vine-growing areas worldwide. Chemical insecticides have been used for its control; however, its resistance status is largely unknown in many regions. We monitored the susceptibility of several L. botrana populations from Greece and Turkey. In addition, based on RNAseq transcriptome analysis, we identified and phylogenetically classify the cytochrome P450 genes of L. botrana, as well as analysed target site sequences and looked for the presence of known resistance mutations. Resistance against chlorantraniliprole, alpha-cypermethrin, spinetoram, etofenprox, and acetamiprid was very low (below 2.5-fold in all cases, compared to a reference strain from Greece) in all populations from Greece that were included in the study. However, resistance against indoxacarb (4–30-fold), spinosad (5–59-fold), and deltamethrin (18–30 fold) was detected in the L. botrana populations from Turkey, compared to a reference population from Turkey. De novo transcriptome assembly and manual annotation, and subsequent PCR-based analysis of insecticide target sequences (i.e. voltage-gated sodium channel – VGSC: target of pyrethroids and oxadiazines; nicotinic acetylcholine receptor subunit a6 – nAChR_α6: target of spinosad; ryanodine receptor – RyR: target of diamides; glutamate-gated chloride channel – GluCl: target of avermectins and; acetylcholinesterase – AChE: target of organophosphates) showed the absence of known resistance mutations in all specimens from both countries. Finally, the L. botrana CYPome (116 genes) was manually analysed and phylogenetically characterised, to provide resources for future studies that will aim the analysis of metabolic resistance.
Those who responded to the COVID-19 pandemic have now had the opportunity to reflect on lessons learned, and in this science and data-rich book, those reflections are presented as a behind-the-scenes chronology of events and discoveries that occurred in COVID-19's wake. Offering a rubric for a future pandemic response, each chapter is written by experts, with their unique perspectives, experience, and learnings woven into visual roadmaps throughout the book. These roadmaps serve as a scaffolding upon which future healthcare leaders can build when creating, implementing and executing operational strategies in the face of future infectious disease outbreaks. Written for both lay and scientific audiences and featuring case studies which give clinical insight into the unique bond between COVID patients, their loved ones and their healthcare providers, this important book allows readers to leverage the knowledge of experts to improve the outcomes of future pandemics.
Over the past several decades, clay minerals have been applied in various bio-fields such as drug and drug additives, animal medicine and feed additives, cosmetics, biosensors, etc. Among various research areas, however, the medical application of clay minerals is an emerging field not only in academia but also in industry. In particular, cationic and anionic clays have long been considered as drug delivery vehicles for developing advanced drug delivery systems (DDSs), which is the most important of the various research fields including new drugs and medicines, in vitro and in vivo diagnostics, implants, biocompatible materials, etc., in nanomedicine. These applications are obviously related to global issues such as improvements in welfare and quality of life with life expectancy increasing. Many scientists, therefore, in various disciplines, such as clay mineralogy, material chemistry, molecular biology, pharmacology, and medical science, have been endeavoring to find solutions to such global issues. One of the strategic approaches is probably to explore new drugs possessing intrinsic therapeutic effects or to develop advanced materials with theranostic functions. With this is mind, discussions of examples of cationic and anionic clays with bio- and medical applications based on nanomedicine are relevant. In this tutorial review, nanomedicine based on clay minerals are described in terms of synthetic strategies of clay nanohybrids, in vitro and in vivo toxicity, biocompatibility, oral and injectable medications, diagnostics, theranosis, etc.
Chapter 7 takes a closer look at some of the Sea Around Us fish-landings data that we assessed for Benford agreement in Chapter 5. We chose these data because of the mixed agreement findings among them: while the full dataset and several sets of subgroups indicated that the data exhibited Benford validity, when we analyzed West African countries individually, a number of them were found to have unacceptable Benford agreement and therefore problematic Benford validity. We present ways in which researchers can assess the impact of unacceptable Benford agreement on their analyses.
New product development processes need to be compliant to regulatory requirements, and this chapter highlights the salient processes and quality systems to put into place to achieve success. Project management is made simple with specific tools provided here. Customer feedback is channeled into specific product characteristics, and the right tools are shown in this chapter. The biopharma industry has statistics showing less than 10% of starting compounds succeed in reaching market approval, and this chapter explains what causes these failures. The key issues that have repeatedly caused failure during device and diagnostic product development are also pointed out. Ethical decisions have to be made during product development as shown in this chapter. Outsourcing is a real option due to the availability of many contract research and manufacturing organizations, and judicious use of this option is discussed in this chapter. Key milestones that reduce risk and show transition from early stage to preclinical prototype stages are reviewed here. Does the popular concept of minimum viable product in software development apply in biomedicine prototyping? Other similar questions that help the reader understand pitfalls and best practices are answered here.
How do you read a patent and what subject matter is patentable? What is the purpose of a patent? Who is an inventor on the patent if work is done by many people on the project? What is the process of obtaining a patent in my country and globally? Read this chapter to see how you could lose commercialization rights to your own invention. When exactly does an invention or idea become patentable? Once you own a patent, how can you make money from it? What is the process of licensing and the key terms that should be negotiated in such a license agreement? What is the use of a copyright or a trade secret in biotech? What exactly constitutes patent infringement ? These questions and many others are addressed in this chapter on intellectual property.
From the long path through preclinical development, entering the regulatory field of interactions for human clinical trials can sometimes feel like you are walking into the lion’s den. This chapter guides you through an understanding of how to interact and how to prepare for FDA meetings so that they are on your side rather than fighting you. The common goals of companies and the FDA are highlighted here. Specific issues with identifying the appropriate regulatory approval pathway are discussed here with cautionary case studies. Complex new technologies which combine diagnostics and drugs, or devices and software, or AI-based dynamic software are reviewed here. The best approach to the appropriate regulatory pathway will be clear after reading this chapter. Case studies are used to show successful pathways taken by cutting-edge developments, such as cell-based therapy.