Remote video imagery using shoreline edge detection is widely used in coastal monitoring in order to acquire measurements of nearshore and swash processes. Some of these systems have very limited flexibility due to their rigid structures and require considerable investment in hardware. As such, there is a need for an autonomous low-cost system (~€500) that can be rapidly deployed in the field, while still producing the outcomes required for coastal monitoring. This research presents a sensitivity analysis of time-lapse intervals for two low-cost cameras located in a remote coastal area, overlooking a dissipative beach-dune system. The analysis shows that RMSD in the detected shoreline is similar to other studies for intervals ranging between 1 second and 30 seconds (i.e., RMSDmax for Camera 1 = 2.8 m and Camera 2 = 1.3 m). The increase of the sampling interval from 1 s to 30 s is shown to have no significant adverse effect on the precision of shoreline detection. The research found that the limitations of battery life and memory storage substantially decrease when sampling intervals increase without an effect on the data quality. This also has a positive effect for low-cost systems and removes the requirement for external battery and memory storage. On the systems used, the battery life increased from ~10 days to ~100 days when the sampling interval was increased from 1 to 5 s., As such, the current standard of producing Timex images from 1 s sampling intervals over 10 minutes can be changed depending on the application and requirements needed for analysis.

Before COVID-19, post-secondary learning was dominated by in-person, institution-organized meetings. With the March 12, 2020 lockdown, learning became virtual, largely dependent on commercial online platforms. Already more likely to experience anxiety and depression in re-lation to their research work, perhaps no students have endured more regarding the limitations imposed by COVID-19 on their mentorship and supervision than graduate students. The in-crease in mental health issues facing graduate students has come to the attention of their post-secondary institutions. Programs have been devised with the aim of reducing these chal-lenges. However, the additional attention and funds to combat depression and anxiety have not shown anticipated results. A new approach to mitigate anxiety and depression in graduate students through mentorship and supervision is warranted. Offered here is an award-winning model featuring self-directed learning in a community based on consensus decision-making where consensus represents the adding together of different points of view rather than agreement. The approach is non-hierarchical in structure, based in narrative research. The proposed model and approach are presented and limitations considered. This model and approach are offered as a likely solution to ebb the increase in anxiety and depression in graduate stu-dents—particularly in response to COVID-19.

Scholarly publication in international journals depends on qualified, unbiased and available referees: (1) qualified in their ability to assume each role inherent to being a peer reviewer and in willingly and competently accepting the responsibilities that coincide with these roles; (2) unbiased in focusing on the submitted research content irrespective of their own research programs in judging the submission’s merit; and (3) available to devote time to read and understand the paper, check the accuracy and relevance of references, and write a comprehensive review commenting on the strengths and weaknesses of the manuscript, the ability of the research to be replicated, and the contribution of the work to the discipline. This study investigates the range of reviewer’s roles and responsibilities in relation to author’s own assessment as a frequent reviewer for fourteen journals representing five publishing houses—and as an active researcher—in comparison with a 2019 comprehensive study of the views of 224 authors on peer review. Based on this investigation, advice will be provided to potential reviewers regarding what is expected of them in undertaking their work. Recommendations will be offered for peer review to mitigate weaknesses in the process and increase the pool of qualified peer reviewers.

The COVID-19 virus is spread to the respiratory system by minute airborne particles in contrast to large particle fomite transmission. Yet, an often-repeated health directive during the COVID-19 pandemic was to improve handwashing to limit the spread of the virus. Persistent handwashing can aggravate obsessive-compulsive disorder (OCD), diminishing mental health. Given that handwashing is unlikely to control the spread of COVID-19, it is pertinent to determine if the directive for handwashing to eradicate the COVID-19 virus increased the incidence of OCD and, as such, promoted negative mental health. This scoping review of the parameter, “handwashing, mental health, COVID-19, OCD”, conducted during July 2023, searched six relevant databases. The result was that negative mental health related to increased handwashing was evident both for those already diagnosed with OCD and regarding new cases of OCD throughout the duration of the pandemic. The conclusion is that health officials should update details of their health directives as information becomes available during a pandemic and, concerning COVID-19, the directive to concentrate on handwashing should have been relaxed once it was known that spread of the virus by fomite transmission was improbable. This likely would have reduced the incidence of OCD and improved mental health.

As distinct human societies, three unique intentional communities are investigated regarding their preferred consensus decision-making practices. It is Identified that each has adopted a different form of consensus decision-making to solve potential group-wide interpersonal conflict. The individual attributes of these three consensus decision-making practices are considered, both from the perspective of maintaining group stability and in relation to individual member's mental health. The communities are a Canadian self-directed public senior elementary and secondary school, an annual English conference for those self-identifying as on the autistic spectrum, and a self-producing Korean popular music (K-pop) group. It is found that the intentional community and participants’ mental health are sustained regarding each of the three consensus decision-making practices. Nevertheless, the resulting decisions generate various stresses within the communities, both as a whole and concerning the individual members. To retain group cohesion and maintain individual mental health, these stresses must be recognized and understood by participants. The novel finding of this research is that, dependent on the time available for decision-making, and the members’ perspective adopted, intentional communities might practice more than one form of consensus decision-making and still support both group cohesion and individual mental health, maintaining the democracy of these distinct societies.

In European thought, the relationship among the fields of psychology, education, and health is both complex and obscured. Foucault’s acclaimed work, The Order of Things, offers a framework to evaluate their interconnection by identifying three distinct periods of European thought since the 16th century with respect to the ordering of phenomena—Renaissance, Classical and Modern. Theoretically dense and often difficult to decipher, the book’s categorization of language, value and being has been understandably underused, yet it provides deep insights into what have come to be known as psychology, education and health and remains invaluable in understanding the origin, limits and consequences of these fields. How Foucault’s analysis can be interpreted concerning the development of these areas as to each of the three periods of European thought is investigated. An approach based on narrative research appraises the analysis offered in the book. The results, presented for the first time in table form, compare these three periods, demonstrating a continuing practical value to Foucault’s insights. With the aid of the framework revealed by these tables, the boundaries and relationship of psychology, education and health become clear and their limitations—plus potential solutions to them—can be identified to mitigate anticipated negative consequences.

Informal dementia home caregiving is viewed negatively and can result in caregiver depression and anxiety from burnout, potentially compromising caregiving. Solutions are unclear, as caregiving relationships are unique—caregiver creation of a graphic memoir may help to mitigate the negative dementia narrative and reduce experienced burnout. This investigation examines the writing of a graphic memoir by one informal dementia home caregiver, created with the help of a cartoon illustrator and a publisher who edited, printed, and made the graphic memoir available at the psychiatric bookstore considered the largest in North America. Mother of the illustrator and the editor and publisher of this graphic memoir, this author provides the perspective taken in this investigation. The analysis, developed by this author, represents psychoanalytic narrative research, serving as the historical method. Aided by email threads between the publisher/caregiver, publisher/printer, and publisher/bookseller, and a published interview with the dementia caregiver are answers to how writing, illustrating, and publishing the graphic memoir affected the caregiver’s narrative reconstruction and burnout. Providing an example for other informal dementia home caregivers similarly to write and illustrate a publishable graphic memoir for their positive narrative reconstruction and to help decrease their depression and anxiety from burnout is the aim.

Depression and anxiety are prevalent, persistent and difficult to treat industrialized world mental health problems. These disorders negatively modify an individual’s life perspective through brain function imbalances, notably in the amygdala and hippocampus, and are primarily treated with pharmaceuticals and psychotherapy. Nevertheless, these mental health issues have only increased in the number of individuals affected and the intensity of their suffering—especially as a result of COVID-19 restrictions and fears. An approach to alleviating depression and anxiety in relation to researchers self-identifying as experiencing burnout is promising. Enhancing resilience, the approach considers depression and anxiety as consequences of the particular method people adopt in ordering their memories, and focuses on narrative development. The method encourages accepting of different perspectives as unique and necessary in creating safe protection from research burnout. Moving from an identification of personal character to prompting plot development of memory, the method promotes resilience by encouraging thoughtful reconsideration of the negative assessments by participants of their circumstances that can lead to depression and anxiety. The method of ordering and group members’ feedback are inspected, including during the period of COVID-19 restrictions, and conclusions are offered regarding further research to encourage burnout resilience to diminish depression and anxiety.

Concerning the hippocampal mechanisms that simultaneously function to map environmental position and to generate episodic memories, a developing consensus emerged by the early 21st century. The hippocampus was recognized as embodying the primary location of personal narrative development, with the ability to create stable and coherent narrative largely representing the mental health of individuals. Determining recent advances regarding the relationship among the hippocampus, narrative, and mental health, a limited, six-database review was conducted for peer reviewed articles published since 2019. Of the 127 records located, 14 reports were included for study. The results support the necessity of creating and maintaining a stable and coherent narrative as fundamental to human mental health such that facts will be distorted in personal accounts, sleep will be disrupted, and DNA altered to retain one’s personal narratives. With narrative development fundamental to human mental health, a goal of interventions concerning hippocampal function and positive health outcomes is enhancing personal narratives in providing individuals with the ability to construct and recall those that are robust and effective. One such intervention that has proven successful in this regard, the Health Narratives Research Process, is outlined with its most recent results presented, offering opportunity for further such research.

Cultural tourism in Tanzania presents a diverse tapestry of traditions, varied ethnic groups, and historical accounts. This article aims to pinpoint areas for further exploration in the cultural tourism sector of Tanzania and analyze their potential impacts. The study conducted a systematic review of the literature following established inclusion criteria as well as the Preferred Reporting Items for Systematic Reviews and meta-analysis guidelines. A total of 21 articles focused on Tanzania Cultural Heritage Tourism from sources such as Google Scholar and web databases were examined, revealing several research gaps, including theoretical, contextual and methodological aspects. Furthermore, the research offers insights into theoretical implications and recommends avenues for future studies that could advance the field by addressing these knowledge gaps providing valuable direction to new researchers interested in exploring these specific areas as well as practitioners seeking a comprehensive understanding of various aspects related to Tanzania's cultural heritage tourism

Human resources management (HRM) development aims at career sustainability. Work-related flow, as originated and defined by Csikszentmihalyi, is a process experienced by those optimally challenged by their work, considered the optimal work-related experience. Happiness is a judgment-dependent state of a pleased satisfaction with one’s current experience that one hopes will continue. PERMA (Positive Emotions, Engagement, Relationships, Meaning, and Accomplishment) represents five measurable factors of positive psychology that constitute well-being. As the optimal work-related experience, flow determines career sustainability compared with either happiness or PERMA factors. HRM development programs focused on happiness or PERMA factors thus represents risk factors regarding an inability to develop career sustainability. Established from this publisher’s founding ongoing concern with sustainability, articles published in MDPI journals with the keywords “flow, Csikszentmihalyi, work” were searched, excluding those pertaining to education, health, leisure, marketing, non-workers, and spirituality. Of 628 results returned, 28 reports were included for potential assessment. Although current studies on flow represented only three, the results regarding flow position it as the best indicator of career sustainability, contrasted to either happiness or PERMA. Consequently, HRM is advised to concentrate on developing practices for assessing and encouraging employees’ engagement with work-related flow in its aim of career sustainability.

Emily Howard Jennings Stowe is acclaimed as Canada’s first female school principal, physician to practice medicine, and a founding Canadian suffragette. Yet, relatively little has been investi-gated regarding the life-changing events permitting her to pioneer in these chosen fields. To reveal relationships among the life-changing events in Emily Stowe’s life, a unique narrative research process is engaged to take Stowe’s story and develop it into a particular point of view based on responses to questions posed regarding her life, ranging from those most objective and specific to those that are subjective and more general. This is accomplished by following a prescribed order of question-asking: when, where, who, what, how, and why. The aim is to facilitate a comparison and interpretation of the connections regarding twenty-two of her life-changing events. Four dis-tinct aspects of her life are noted: personal, teacher, physician, and suffragette. It is found that much of Stowe’s success originated from her family’s Establishment connections, her studious intellectual ability, and her decision to obtain her medical education in the United States. There were notable periods in her life that might have ended her career. However, the aforementioned protective features of her status permitted the successful withstanding of these difficulties.

Negative mental health in students currently is classified as a global crisis with the highest and lowest student achievers recognized at greatest risk. Public schooling, in reproducing accepted psychosocial beliefs through standardized learning, developed separately from necessitating student mental health, in contrast to self-directed learning. Differing from standardized learning, the objective of self-directed learning in public schools is the creation of relevant support structures for student mental health, promoting positive psychosocial outcomes. The designed separation of public schooling from both mental health and self-directed learning was first acknowledged—and lamented—by John Dewey, over 100 years ago, in anticipating today’s mental health crisis. Yet, in responding effectively to the limitations of COVID-19, self-directed learning became an acknowledged learning method in public schools, potentially able to be accommodated by them regularly in support of mental health through the use of online technology. This study investigates the COVID-19 results of self-directed online learning in public schools through a Google Scholar search of peer reviewed research regarding self-directed learning, online learning, and mental health during COVID-19, recommending support for self-initiated self-directed online learning so that self-directed learning can continue, post COVID-19, improving student mental health in public schools, leading to positive psychosocial outcomes.

A presently ubiquitous idea, how gender is defined remains deeply indebted to modern thought, depending on the concept of sex as its reference point. Originating with practices arising with capitalism, modern thought’s concept of sex was enhanced with the search for the norm regarding standardization, then further refined through the research program of eugenics. Gender, in contrast to sex, has its roots in sexual practice changes from the second half of the twentieth century onward, developed in association with 1980s postmodern thought. The presuppositions of the two concepts differ radically. Understanding the difference between sex and gender matters because gender is now more than a critique of sex—it’s an idea accepted and understood in popular culture and affects how people interpret their sexuality. This review examines the foundations of modern and postmodern thought then focuses on sex and gender with respect to their history within these modes of thought. The conclusion, pointing to future research, is that a further reformulation of sexuality will be required for gender, as a postmodern idea, to truly separate itself from the presumptions of sex as a modern concept, permitting individuals to express their sexuality as they choose without negative social and psychological repercussions.

Extraversion, a Big Five personality trait, has been identified as a significant factor in COVID-19 positive coping—yet, relevant research is conflicting. Studies have not situated the influence of extraversion within a geographical and historical context. Thus, a sound base is lacking for assessing when opposing results regarding extraversion and COVID-19 positive coping are likely to result. Furthermore, extraversion with respect to COVID-19 coping has not been considered concerning other-directed learning in contrast to self-directed learning. To establish a sufficiently sound base, an examination of the range of high-ranking Google Scholar results on extraversion and COVID-19 coping from different countries during the pandemic’s various waves—pre and post vaccine introduction—is undertaken. The same are then considered for insights into public opinion. Following, extraversion is compared with other-directed learning and differentiated from self-directed learning. An understanding is thus presented for assessing when extraversion will necessarily be an effective personality trait for COVID-19 positive coping and when it will not. Extraversion’s effect will be found inherently inconsistent for identifying COVID-19 positive coping as a result, because of its dependence on other-directed learning. The conclusion: COVID-19 positive coping stability is contingent on personal values that guide self-directed learning, rather than other-directed extraversion.

Burnout, a negative job-related psychological state particularly associated with the health professions, equates to a loss of valuable research in healthcare researchers. Team mindfulness, recognized to enhance personal fulfilment through work engagement, represents one important aspect found effective in reducing burnout. In a specific series of diverse membership academic meetings intended to reduce research burnout—employing writing prompts, doodling and continuous developmental feedback to do so—team mindfulness was demonstrated when conducted in person. Therefore, determining if team mindfulness is evident when holding such academic meetings online is relevant. When COVID-19 limitations required moving these academic meetings online, it was previously noted and reported that team mindfulness was affected in no longer being present during the first eighteen months of restrictions. To discover if this result persisted, question asking, doodles submitted and feedback responses were analyzed of the following year’s academic meetings for the same group, both quantitively and qualitatively. In finding the team mindfulness of these meetings additionally compromised the second full year, online practices actually found successful at creating and supporting team mindfulness—online games—are identified and considered. Concluding implications are noted and recommendations made regarding team mindfulness in reducing burnout for future online academic meetings.

The ability to self-direct a research program determines graduate degree completion. Yet, research on incompletion of graduate physics programs assume students’ present level of self-direction adequate and neglects to recognize a lack of self-directed learning as key. One theoretical mathematical physicist focused on changing this challenge of physics graduate education by promoting self-directed learning through the type research flow that has been found to bring the greatest satisfaction to researchers with respect to their insights. This he provided through his space, time, open mindedness and theoretical contributions with his students and in collaboration with his colleagues. A self-directed learner himself, David J. Rowe developed methods of mentoring for encouraging physics graduate students to recognize symmetry as valuable in identifying solutions to problems quickly—helping these students take the lead in finding insightful resolutions to complex, multidimensional, mathematical physics uncertainties. How Rowe set about supporting self-directed learning in his graduate physics education interactions will be examined with the use of narrative research to interpret the texts and conversations with the author he made available. His techniques will be presented and recommendations made regarding how Rowe’s work in this regard can be modeled to improve self-direction in STEM graduate education.

Pre-COVID-19, doodling was identified as a measure of burnout in researchers attending a weekly, in-person health narratives research group manifesting team mindfulness. Under the group’s supportive conditions, variations in doodling served to measure change in participants’ reported depression and anxiety—internal states directly associated with burnout, adversely affecting healthcare researchers, their employment, and their research. COVID-19 demanded social distancing during the group’s 2020/21 academic meetings. Conducted online, the group’s participants who chose to doodle did so alone during the pandemic. Whether the sequestering of group participants during COVID-19 altered the ability of doodling to act as a measure of depression and anxiety was investigated. Participants considered doodling during the group’s online meetings increased their enjoyment and attention level—some expressed it helped them to relax. However, unlike face-to-face meetings during previous non-COVID-19 years, solitary doodling during online meetings was unable to reflect researchers’ depression or anxiety. COVID-19 limitations necessitating doodling alone maintained the benefits group members saw in doodling but hampered the ability of doodling to act as a measure of burnout in contrast to previous in-person doodling. This result is seen to correspond to one aspect of the group’s change in team mindfulness resulting from COVID-19 constraints.

The online learning necessitated by COVID-19 social distancing limitations has resulted in the utilization of hybrid online formats focused on maintaining visual contact among learners and teachers. The preferred option of video conferencing for academic meetings has become that of Zoom. The needs of one voluntary, democratic, self-reflective university research group—grounded in responses to writing prompts—differed in learning focus. Demanding a safe space to encourage and record both self-reflection and creative questioning of other participants, the private Facebook group was chosen over video conferencing to maintain the concentration on group members’ written responses rather than how they saw themselves (and thought others saw them) on screen. A narrative research model initiated in 2015, the 2020/21 interaction of the group in the year’s worth of Facebook entries, and the yearend feedback received from group participants, will be compared with previous years when the weekly group met in-person. The results in relation to COVID-19 limitations indicate that an important aspect of self-directed learning related to trust that comes from team mindfulness is lost when face-to-face interaction is eliminated regarding the democratic nature of these meetings. With online meetings the new standard, maintaining trust requires improvements to online virtual meeting spaces.

Late January 2020, COVID-19 unexpectedly imposed world-wide limitations on daily life. Deemed a pandemic mid-March 2020, lockdowns were imposed for an indefinite period, including at academic institutions. Consequently, interest in digital literacy—an on-going and increasing concern of academic institutions in the 21^st century—exponentially heightened. Continuing meetings of academic groups now necessitated online communication. In the almost overnight closure of all non-essential services, academic units at one post-secondary institution expeditiously selected Zoom—a popular video conferencing application—as the preferred platform for meetings until social distancing was lifted. In contrast to this widely accepted use of Zoom for scheduled meetings, one unique health-related group at the institution, tailored to the 4Cs of 21^st century learning of critical thought, communication, cooperation and creativity, found social networking through a private Facebook group a more appropriate and satisfying group experience than likely possible with the Zoom app. Pros and cons of both online platforms are presented along with when each choice is warranted. In promoting digital literacy as the primary goal in online communication for academic meetings, private Facebook groups hold promise for collaborative online academic meetings with similar features to this health-related group.

In this study, I will present some documentary evidence that Carlos Drummond de Andrade’s poem “A Máquina do Mundo” [The Machine of the World] (1949) was based on prior reflections contained in a forgotten newspaper article entitled “Poesia e Pesadelo” [Poetry and Nightmare] (1949). In that article, Drummond critically analyzed some of the theses of Stephen Spender's essay “What Is Modern in Modern Poetry” (1948), which had just been published in The Tiger's Eye magazine. As soon as he read Spender's text, Drummond wrote “Poetry and Nightmare” and began to elaborate a narrative poem whose protagonist would be a machine. All the documentary evidence indicates that Drummond took Spender's lessons as touchstones for the elaboration of the narrative and allegorical structure of “The Machine of the World.” According to the interpretation I am proposing here, Drummond, in writing the machine poem, put into practice at least six lessons drawn from Spender’s essay, namely: 1) the modern poet must represent the tension between the external machinelike landscape and the landscape of the inner world of the creative imagination; 2) he must also represent the machinelike, ugly, and urban world around him in a beautiful and poetic way; 3) he must avoid the misconceptions of excessive utopian visionarism, as well as creeping realism; 4) he must reject the imperative of political engagement, whose principle of action states that poetry has a transformative mission in society; 5) he must free himself from the obsession with free verse as the only form of modern poetry and start using the traditional fixed forms; 6) he must understand machines as poetic symbols of human passions, and not just as exotic objects foreign to human reality. My conclusion is that, after reading Spender’s essay, Drummond changed his aesthetic and philosophical understanding of what defines the essence of modern poetry, both in terms of form and content.

We present a normative methodology, for value-pricing B2B services, using a Nash Equilibrium mechanism. Value is fundamental to any service, yet it has defied a definition. The literature is conspicuously silent on how to define value, but abounds in richly descriptive characterizations. To overcome this deficit, we focus on the financial economics of service-value. We formulate an axiomatic definition and a differential equation that embodies the idea of service-value. We specify a set of value axioms and multidisciplinary postulates that coherently form our service-value constructs. Value-pricing is challenging. It is natural that providers desire a high price and customers want a low price. Realistically, both will agree on a win-win price. To uncover this price, we specify an algorithm to reveal the Nash Equilibrium. Once agreed, it validates providers’ and customers’ commitments, and payment obligations. Service value is cocreated by both provider and customer. For a reciprocal process, its treatment is remarkably asymmetric favoring the customer. We argue that one-sided descriptions of value-in-use and value-proposition are limiting mental models. We propose the additional ideas of value-from-use and value-supposition to strengthen the conceptual symmetry of cocreation. Our work reveals a critical gap in service science, metrology. Metrology, the science of measurements, is absent from service-science. Service-value is silent on the questions of quantities, units, scales, measurement principles and instruments. We argue for a call to action for Service Metrology. We sketch a roadmap of actionable suggestions to get started.

Liver related diseases are the 3rd leading causes (9.3%) of mortality in type 2 diabetes mellitus (T2DM) in Japan. T2DM is closely associated with nonalcoholic fatty liver disease (NAFLD) which is the most prevalent chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can lead to hepatocellular carcinoma (HCC) and hepatic failure. There are no established pharmacotherapies for NASH patients with T2DM. Though vitamin E is established as a 1st line agent in NASH without T2DM, its efficacy was recently denied in NASH with T2DM. The effects of pioglitazone on NASH histology with T2DM have extensively been established, but several concerns exist such as body weight gain, fluid retention, cancer incidence, and bone fracture. Glucagon-like peptide 1 (GLP-1) receptor agonists and sodium/glucose cotransporter 2 (SGLT2) inhibitors are expected to ameliorate NASH　(LEAN study, LEAD trial, and E-LIFT study). Among a variety of SGLT2 inhibitors, dapagliflozin have already entered phase 3 trials (DEAN study). A key clinical question is what kinds of anti-diabetic drugs are the most appropriate for the treatment of NASH to prevent progression of hepatic fibrosis resulting in HCC/liver-related mortality without increasing risk at cardiovascular or renal events. The combination therapies such as glucagon receptor agonist/GLP-1 or gastrointestinal peptide /GLP-1 will be under development. This review focuses on antidiabetic agents and future perspectives on the view of the treatment of NAFLD with T2DM.

In this work, we investigate the embedding of a four-dimensional spherically symmetric metric in a six dimensional bulk. By using the Nash-Greene theorem, the additional $SO(2)$ symmetry of the two space-like extra-dimensions induces the appearance of horizons of a lukewarm charged black hole. Accordingly, an emerged mass-dependent cosmological constant is obtained with a prediction with a bound for the mass and minimal charge.

BACKGROUND Relaxin (RLX), a hormone-like molecule with pleiotropic effects, has been found to reduce matrix deposition and mediate collagen degradation in animal models of chronic liver injuries and might be considered as an adjuvant therapeutic agent for progressive liver diseases. AIMS In the present study, we evaluated whether RLX affects the development of liver fibrosis in an experimental mouse model of NASH in C57BL6 male mice fed with a methionine-choline deficient diet (MCD). Methods Mice were treated per os as we intended to assess the enteric absorption and bioavailability of orally administered RLX (RLX purified from pig ovaries, IBSA SA, Lugano, Switzerland). Mice were fed the MCD diet for 6 weeks. After the initial 3 weeks, one group received drinking water supplemented with RLX (25 mcg/ml) whereas the other continued to receive regular water. A third group of mice fed a regular diet served as control. After 3 additional weeks mice were anesthetized and sacrificed. Results A significant, reduced expression of the pro-inflammatory cytokines TNF-α and of relevant markers of active fibrogenesis and extracellular matrix deposition, Col1A1 and α-SMA, was observed in mice treated with RLX vs controls. RLX also induced a significant decrease of TIMP1 and an increase of both MMP 2 and 9 when evaluated by zymographic analysis in liver extracts. Conclusions Although preliminary pharmacokinetics experiments showed barely detectable amounts of RLX in the blood of mice treated per os, these data support the absorption of orally administered RLX and confirm its potential therapeutic use in the management of liver fibrosis.

Nonalcoholic steatohepatitis (NASH), which is characterized by liver steatosis, inflammation and fibrosis, is the most severe variation of nonalcoholic fatty liver disease (NAFLD). This disease is a consequence of several metabolic alterations such as type 2 diabetes and dyslipidemia that trigger different pathways of cell dysfunction and systemic inflammation which ultimately affect the liver. Furthermore, those mechanisms activate a complex cascade of immune response after repeated cell aggression. In the liver cytokines and interleukins interact with network of innate immune cells, including Kupffer cells (KCs), dendritic cells (DCs), lymphocytes and hepatic stellate cells (HSC). These cells translate those signals into immune responses and pathologic hepatic changes during the development of NASH. In this scenario the development of fibrosis is the most important change since it is an adaptive mechanism that in the short time has the objective of repair the damaged tissue but after prolonged injury it progresses to parenchymal scarring, cellular dysfunction and finally to organ failure. Finally, since NASH is an important cause of liver cirrhosis; this review addresses the cellular pathways of fibrosis in the setting of NASH explained by the interaction between immune and hepatic cells.

Non-alcoholic steatohepatitis (NASH) is a clinically serious stage of non-alcoholic fatty liver disease (NAFLD). Histologically characterized by hepatocyte ballooning, immune cell infiltration and fibrosis, NASH at a molecular level involves lipid induced hepatocyte death and cytokine production. Currently, there are very few diagnostic biomarkers available to screen NASH, and no pharmacological intervention is available for its treatment. In this study, we show that hepatocyte damage by lipotoxicity results in the release of extracellular RNAs (eRNAs) which serve as damage-associated molecular patterns (DAMPs) that stimulate the expression of pro-apoptotic and pro-inflammatory cytokines, aggravating inflammation, and cell death in HepG2 cells. Furthermore, the inhibition of eRNA activity by RNase 1 significantly increased cellular viability and reduced NF-kB mediated cytokine production. Similarly, RNase 1 administration significantly improved hepatic steatosis, inflammatory and injury markers in a murine NASH model. This study, therefore, for the first time, underscores the therapeutic potential of inhibiting eRNA action as a novel strategy for NASH treatment.

Children—Dependents in Social Construction Theory—are assessed within democracies regarding their ability to self-direct their behavior concerning their associated society. In this regard, childhood represents a lack of self-direction, a life period when people require the guidance and protection of adults. The assumed necessity of adults supervising children in democracies requires substantial social resources, reducing the self-direction of those charged with overseeing children. Given that self-direction defines the optimal experience of people within democratic society, finding ways to increase the self-direction of children is an individual and a social benefit. In this regard, smartphones have improved self-direction in children. How children have become empowered to self-direct their lives with smartphone use considering Social Construction Theory—as Advantaged, Contenders, or Deviants—is the focus of a scoping review conducted on “children, empowerment, smartphones” of the following databases: OVID, JSTOR, ProQuest, PubMed, Scopus, and Web of Science. The result is that children permitted to self-direct their activities aided by smartphone technology have comparable social behavior to adults positioned as Advantaged, Contenders, or Deviants and, as such they should be encouraged to utilize smartphone technology to improve their self-direction, as doing so will augment individual and caregiver self-direction, providing increased social benefit.

The Rev. Martin Luther King Jr. and Nelson Mandela were two of the world's most iconic civil (political) (human) rights advocates and leaders of all time. Both advocated for, and to varying degrees, applied elements of peaceful protests to the achievement of their goals. Both spent time in jail, often concurrently, but eventually forced their respective countries to extend the same rights that white populations had denied Africans and African Americans. For the US, civil rights, voting rights, right to education, housing and housing loans suggested that equality had been achieved, capped in South Africa by the election of Nelson Mandela as the first majority-rule president, and in the US, by Barack Obama’s election to the presidency. Yet the historical over-policing, police mistreatment and more generally, the judicial system’s inordinate ‘targeting’ of African Americans, with egregious cases running from Emmett Till to Rodney King to Walter Scott to Breonna Taylor to George Floyd to Rayshard Brooks and thousands of others shows the danger of such magical thinking. The now-persistent global wave pursuing human rights, civil rights and the right to be treated equally, primarily driven by the loosely-organized Black Lives Matter (BLM) movement, has become the leading voice in pursuit of equality. Riots such as those in LA, protests in Ferguson and everywhere in summer 2020 has ushered new civil rights campaign. In the US and elsewhere, it has morphed to include historical issues such as monuments to colonialism, the US civil war, slavery and slave owners and traders, institutions, companies and people whose wealth and existence has links to slavery. Instructively, the protests persisted even as COVID-19, the hundred-year plague, continues to ravage the world. Lost in the moment is the absence of central leadership and leaders such as MLK or Mandela. Their charisma and effectiveness has been lacking for 50 years. This paper evaluates whether this has led to inconsistent civil and human rights pursuit for equality, or whether perchance, Mandela and MLK were extraordinary, once-in-a-lifetime transformative leaders uniquely selected by history for their time.

1. Background: The global COVID-19 lockdowns are unique psychological factors, requiring adjustment and coping. This illustrative, South African case study investigated the influence the COVID-19 lockdown context would have on meditation and physical activity. As these were lifestyle patterns the null hypothesis was of no change. 2. Method: The methodology consisted of quantitative and qualitative phases. The quantitative phase was an empirical, case study review of data from the author’s HeartMath and Fitbit electronic devices, as from 9 November 2019 to 31 July 2021. This consisted of coherence and achievement data from the HeartMath Inner Balance application (app), as well as distance and activity data from the Fitbit app. The qualitative phase consisted of the selection and illustration of meditation sessions documented over lockdown. 3. Results: The highly significant increases in physical activity and meditation coherence and achievement collectively indicated significant health promotion over the COVID-19 Lockdown period. Subtle energetic, experiential descriptions of meditation apprehensions resonated and supported these quantitative findings. 4. Conclusions: COVID-19 lockdown has meant transformation, humility, and reordering of priorities. The meditation descriptions amplified information from the HeartMath and Fitbit electronic devices, together co-creating conscious, embodied, relationship science for discussion, instruction, and further research.

Based upon a radically new approach, this paper describes a 2-box absolute flow model that calculates the CO₂ transfer between the atmosphere and a terrestrial / ocean mixing reservoir. Given the inputs of anthropogenic fossil fuel emissions (CO2ff), atmospheric CO₂ mixing-ratio and nuclear weapons bomb yields, the model calculates atmospheric d¹³C and Δ¹⁴C time-series, with the level of agreement for d¹³C being to within ± 0.05 ‰, for Δ¹⁴C to within ± 3‰, spanning 200 years. The model contains only seven internal parameters which are varied to optimize the fit. Yet according to conventional wisdom, this model should not work. It is commonly held that the ¹³C and ¹⁴C isotopic forms of carbon bypass seawater carbonate chemistry, resulting in very different absorption properties (Revelle factor) as compared to ¹²C. This study rejects this assumption, and uses the same residence time and reservoir mixing properties for all isotopes. The paper includes an analysis justifying why the isotopic bypass of the Revelle factor is not significant. The study describes the use of the model to track CO2ff takeup using two separate measures, a) the amount of molecular CO2ff remaining in the atmosphere and b) the amount of atmospheric growth attributable to CO2ff, thereby resolving discrepancies in published values.

The increased adoption of information and communication technology for smart grid applications will require innovative cyber-physical system (CPS) testbeds to support research and education in the field. The groundbreaking CPS testbeds with realistic and scalable platforms have progressively gained interest in recent years, with electric power flowing in the physical layer and information flowing in the network layer. However, CPSs are critical infrastructures and not designed for testing or direct training, as any misbehaving in an actual system operation could cause a catastrophic impact on its operation. Based on that, it is not easy to efficiently train professionals in CPSs. Aiming to support the advancement and encourage the training of industry professionals, this paper proposes and develops a complete testbed with commercial tools. The testbed can reliably replicate the performance of smart grid systems and the main potential cyber threats that electric grids may face. The complex interdependencies between the cyber and physical domains are discussed in detail, and different case scenarios are presented, providing insightful guidelines for key features and design decisions for future smart grid testbeds.

Although total nett CO₂ atmospheric flow can be estimated with reasonable accuracy, the contributing gross fluxes between the atmosphere and the earth's surface are poorly understood. This paper presents a method, driven by the objective of simplicity, by which the global outflow and inflow of CO₂ between atmosphere and a globally equivalent "mixing reservoir" can be estimated, using the isotopes ¹⁴C and ¹³C as tracers. It has been asserted that the isotopic carbon in CO₂ cannot be directly used as a tracer in flow studies because it is not subject to the Revelle factor. Evidence is provided showing that this view is mistaken. The model contains 7 key parameters which are used to create synthetic records of Δ¹⁴C and d¹³C spanning 200 years or more, including during the period of atmospheric weapons testing and its decay known as the "bomb pulse". By optimising the fit between these computed values and the historical records of d¹³C and Δ¹⁴C, all seven key parameters are determined. The effective "mixing reservoir" is thereby determined to have a size around six times that of the atmosphere, with global outflux rising from 39.7 GTC yr-1 in 1750 to 58.9 GTC/yr in 2020, this figure probably not including annually cycled carbon.

Floods and droughts are driven, in part, by spatial patterns of extreme rainfall. Heat waves are driven by spatial patterns of extreme temperature. It is therefore of interest to design statistical methodologies that allow the identification of likely patterns of extreme rain or temperature from observed historical data. The standard work-horse for identifying patterns of climate variability in historical data is Principal Component Analysis (PCA) and its variants. But PCA optimizes for variance not spatial extremes, and so there is no particular reason why the first PCA spatial pattern should identify, or even approximate, the types of patterns that may drive these phenomena, even if the linear assumptions underlying PCA are correct. We present an alternative pattern identification algorithm that makes the same linear assumptions as PCA, but which can be used to explicitly optimize for spatial extremes. We call the method Directional Component Analysis (DCA), since it involves introducing a preferred direction, or metric, such as `sum of all points in the spatial field'. We compare the first PCA and DCA spatial patterns for US rainfall anomalies on a 6 month timescale, using the sum metric for the definition of DCA in order to focus on total rainfall anomaly over the domain, and find that they are somewhat different. The definitions of PCA and DCA result in the first PCA spatial pattern having the larger explained variance of the two patterns, while the first DCA spatial pattern, when scaled appropriately, has a higher likelihood and greater total rainfall anomaly, and indeed is the pattern with the highest total rainfall anomaly for any given likelihood. In combination these two patterns yield more insight into rainfall variability and extremes than either pattern on its own.

This work presents significant results obtained by the application of global optimization techniques to the design of finite, normal form games with mixed strategies. To that end, the Fuzzy ASA global optimization method is applied to several design examples of strategic games, demonstrating its effectiveness in obtaining payoff functions whose corresponding games present a previously established Nash equilibrium. In other words, the game designer becomes able to choose a convenient Nash equilibrium for a generic finite state strategic game and the proposed method computes payoff functions that will realize the desired equilibrium, making it possible for the players to reach the favorable conditions represented by the chosen equilibrium. Considering that game theory is a very significant approach for modeling interactions between competing agents, and Nash equilibrium represents a powerful solution concept, portraying situations in which joint strategies are optimal in the sense that players cannot benefit from individually modifying their current strategies provided that other players do not change their strategies as well, it is natural to infer that the proposed method may be very useful for strategists in general. In summary, it is a genuine instance of artificial inference of payoff functions after a process of global machine learning, applied to their numerical components.

This paper presents a new implementation of a 2-box absolute flow model, enabling the calculation of CO₂ transfer between the atmosphere and a mixing reservoir representing the combined effect of the terrestrial and ocean regions. The model uses published values of anthropogenic CO₂ fossil fuel emissions (CO2ff), atmospheric CO₂ mixing ratio and nuclear weapons bomb yields, to compute atmospheric d¹³C and Δ¹⁴C time-series. The level of agreement between the calculated values and the accepted values for d¹³C is within ± 0.05 ‰, and for Δ¹⁴C is within ± 3‰, spanning 200 years. The model contains only seven internal parameters; these are varied to optimize the fit, leading to reasonable parameter values, indicating the validity of the method. In addition, the model shows how a rising CO₂ exchange influx fluctuating with surface temperature is compatible with a nett atmospheric CO₂ sink. The study demonstrates that a single CO₂ residence time applies to both the ¹⁴C bomb pulse and the anthropogenic flux, contrary to the conventional view that "bomb radiocarbon and anthropogenic CO₂ do not behave identically." [Joos 1994 Nature 370, 181–182]. It is shown that the difference in behaviour, claimed to be due to seawater chemistry, is not significant in practice since fluctuating bulk carbon dominates fluctuating isotopic ratio. A new analysis of the airborne fraction indicates that the assumption of a time-dependent exchange influx results in a similar residence time for bulk CO₂ as for ¹⁴C in the nuclear bomb pulse, reinforcing the view that the ¹²C, ¹³C and ¹⁴C carbon isotopic forms of CO₂ behave similarly in the carbon cycle.

Accurate and timely testing has become an essential measure in combatting the COVID-19 global pandemic. Currently, polymerase chain reaction (PCR) based assays are the most relied on methods for SARS-CoV-2 detection. This traditional workflow involves a viral RNA extraction from the viral transport media storing nasopharyngeal swabs collected from patients, followed by PCR based detection. While accurate, this methodology is time consuming and resource heavy, causing for delays in receiving results or limited access to testing. Herein, we demonstrate a validated method for SARS-CoV-2 detection from viral transport media using a two-step, direct-to-PCR workflow revolving around shaker-mill homogenization. This method completely bypasses the extraction steps of the traditional workflow, replacing it with 30 seconds of mechanical disruption sufficient to allow for COVID-19 detection with a 96.43% sensitivity and 100% specificity when compared to traditional extraction to PCR based methods.

Parts I and II of this 3-part series indicated how a global review of both English-language and non-English language papers plus a focus on a lipidosterolic extract of Serenoa repens (LSESr) having a standardized fatty acid profile have together engendered new insights about the biological activity of LSESr vs. LUTS. In this last of a 3-part series, data from the world literature is presented that confirms that LSESr efficacy is the predominant finding in clinical trials. Despite two placebo-controlled clinical trials performed in the U.S. that failed to confirm a benefit of LSESr vs. placebo in LUTS, the global body of the peer-reviewed literature attests not only to efficacy but also to safety. Results will be presented of important trials that compare LSESr to alpha-blockers such as tamsulosin (Flomax®) as well as to 5α-reductase inhibitors such as finasteride (Proscar®) that demonstrate consistent findings of near equivalency between LSESr and these pharmacologic agents. Studies relating data indicative of an additive effect or synergy between LSESr and tamsulosin will be presented as well. The heightened effectiveness of LSESr in men with severe LUTS vs. moderate LUTS expands the importance of our scrutinization of the global literature concerning LSESr. Of great consequence are the contributions of non-English language peer-reviewed publications that have consistently provided evidence of LSESr efficacy in treating LUTS/BPH. These peer-reviewed articles have shown that the effect of LSESr is not that of a placebo. Finally, a comparison of the LSESr extraction products used in the treatment of LUTS, and a discussion of the milieu factors that affect the natural history of LUTS and influence the outcome of clinical trials complete this sedulous analysis of LSESr vs. LUTS.

Given the extent of this global analysis, this report will be presented in three sections. Part I will introduce LUTS. What are the demographics of LUTS? What symptoms are assessed by LUTS and how do we quantify LUTS? Why would a non-prescription item be a valuable consideration in LUTS treatment versus other treatment options? What is basic information about Serenoa repens and what defines a standardized LSESr product? What are the published trials that have affected the acceptability of Serenoa repens in the treatment of LUTS? Finally, a major portion of Part I will discuss the four major reviews of Serenoa repens versus LUTS that have influenced how it is accepted in the USA, in Europe, and other parts of the world. Part I, therefore, lays the groundwork and is foundational for the important findings relating to LUTS and Serenoa repens that will be presented in Parts II and III.

Part I of this 3-part series provided the groundwork for understanding the role of a standardized lipidosterolic extract of Serenoa repens (LSESr) in the treatment of LUTS. It documented that a treatment having a high therapeutic index (i.e., a ratio of benefit to adverse reactions) is a critical need in the demographic context of a rapidly growing elder population. Part I described the clinical symptomatology of LUTS and how it is quantified. A critique of the reports from four authoritative bodies: the European Scientific Cooperative on Phytotherapy (ESCOP), Cochrane 2012, the European Medicines Agency (EMA), and the AUA (American Urological Association) was presented. The foundation above then fine-tuned our search to require (a) consistent evaluability criteria, (b) the quantification of clinical findings, (c) the need to focus on studies employing a standardized LSESr product meeting the fatty acid profile set forth by the European Medicines Agency (EMA) and the US Pharmacopeia and (d) a global assessment of scientific investigations published in all languages and not limited to only English. Part II details the following “new” findings when LSESr vs. LUTS is examined with the above constraints.

In an $m$-person symmetric game, all players are identical and indistinguishable. In this paper, we find that the payoff tensor of the player $k$ in an $m$-person symmetric game is $k$-mode symmetric, and the payoff tensors of two different individuals are the transpose of each other. Furthermore, we reformulate the $m$-person symmetric game as a tensor complementary problem and demonstrate that locating a symmetric Nash equilibrium is equivalent to finding a solution to the resulting tensor complementary problem. Finally, we use the hyperplane projection algorithm to solve the resulting tensor complementary problem, and we present some numerical results to find the symmetric Nash equilibrium.

Burnout represents a concern for all healthcare providers, particularly those specializing in emergency medical care for whom burnout outcomes have been well-documented. What remains unknown is the effect of burnout on redeployed medical specialists during the COVID-19 pandemic from an appointment-centered practice to emergency care directed by public health considerations. This research aims to identify and assess the burnout responses of fourteen medical specialties noted in searched returns of the four most cited articles published since 2020 about non-emergency physicians regarding their burnout brought on by the unanticipated need for them to provide emergency care during the recent pandemic. The hypothesis is that medical specialists accustomed to planning for emergency possibilities in their appointment-centered practice would demonstrate the least burnout regarding COVID-19-related emergencies. Considering coping as a process based on Lazarus's research, comparing and ranking the COVID-19 emergency responses across the various normally appointment-centered medical specialties in their employed coping strategies determines the outcome. With the hypothesis supported, suggested interventions for future pandemics—when these specialists are, again, redeployed to emergency care directed by public health considerations—are those coping strategies identified as most effective in reducing burnout while maintaining the viability of the medical specialty and excellent patient care.

(1) Background: Although multiple studies have reported on the therapeutic effects of Atezo+Bev for the treatment of NASH-related liver cancer, few studies have focused on its effect on liver reserve. Here, we aimed to compare the changes in hepatic reserve during the Atezo+Bev treatment of NAFLD/NASH-related HCC and of non-NAFLD/non-NASH-related HCC. (2) Methods: We retrospectively compared the changes in ALBI score in 109 patients with NAFLD/NASH or non-NAFLD/non-NASH during 12 weeks of treatment with Atezo+Bev for advanced HCC between September 2019 and January 2022. PSM was performed, and the OS, PFS, and PPS of the two groups were compared. (3)Results: The ALBI after 12 weeks of Atezo+Bev treatment was significantly worse in the NAFLD/NASH group than in the non-NAFLD/non-NASH group. Analysis of the 24 propensity score-matched pairs of cases with NAFLD/NASH or non-NAFLD non-NASH yielded similar results. The prognoses of the two groups were similar with respect to OS and PFS, but the NAFLD/NASH group had a significantly shorter PPS. The 24 matched pairs had similar OS and PFS, but the PPS of the NAFLD/NASH group was shorter. (4)Conclusion: Atezo+Bev treatment may worsen hepatic reserve, and there-fore life expectancy, in patients with NAFLD/NASH-related liver cancer.

Non-alcoholic steatohepatitis (NASH), which is the most severe manifestation of non-alcoholic fatty liver disease (NAFLD), has been recognized as a major hepatocellular carcinoma (HCC) catalyst. However, the molecular mechanism of NAFLD-NASH-HCC sequence remains unclear and a specific and effective treatment for NASH has not yet been established. The progress in this field depends on the availability of reliable preclinical models which show the steady progress to NASH, liver cirrhosis, and HCC. However, most of NASH mouse models that have been described to date develop NASH generally for more than 24 weeks and there is an uncertainty of HCC development. To overcome such shortcomings of experimental NASH studies, we established a novel NASH-HCC mouse model with very high reproducibility, generality, and convenience. We treated male C57BL/6J mice with a newly developed choline-deficient and methionine-restricted high-fat diet (CDMRHFD) for 60 weeks. Treatment of CDMRHFD for 3 weeks revealed marked steatosis, lobular inflammation, and fibrosis, histologically diagnosed as NASH. Liver cirrhosis was observed in all mice with 36-week treatment. Liver nodule emerged at 12 weeks of the treatment, and diameter >2 mm liver tumors developed in all mice at 24 weeks of the treatment. In conclusion, our rapidly progressive and highly reproducible NASH-liver cirrhosis-HCC model is helpful for preclinical development and research on the pathogenesis of human NAFLD-NASH-HCC. Our mouse model would be useful for the development of novel chemistry for NASH-HCC-targeted therapies or HCC prevention strategies.

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and the third-leading cause of cancer-related mortality. Currently, the global burden of nonalcoholic fatty liver disease (NAFLD) has dramatically overcome both viral and alcohol hepatitis thus becoming the main cause of HCC incidence. NAFLD pathogenesis is severely influenced by lifestyle and genetic predisposition. Mitochondria are highly dynamic organelles which may adapt in response to environment, genetics and epigenetics in the liver (“mitochondrial plasticity”). Mounting evidence highlighted that mitochondrial dysfunction due to loss of mitochondrial flexibility, may arise before overt NAFLD and since the early stages of liver injury. Mitochondrial failure not only promotes hepatocellular damage, but also release signals (mito-DAMPs) which trigger inflammation and fibrosis, generating an adverse microenvironment in which several hepatocytes select anti-apoptotic programs and mutations that may allow survival and proliferation. Furthermore, one of the key events in malignant hepatocytes is represented by remodeling of glucidic-lipidic metabolism combined to reprogramming of mitochondrial functions, optimized to deal with energy demand. In sum, this review will discuss how mitochondrial defects may be translated into causative explanations of NAFLD-driven HCC, emphasizing future directions for research purposes and for development of potential preventive or curative strategies.

Using a joint statistical analysis, we test a four-dimensional FLWR model embedded in a five-dimensional bulk based on the Nash-Greene embedding theorem. Performing a Markov Chain Monte Carlo (MCMC) modelling, we combine observational data sets as those of the recent ``Gold 2018'' growth data, the best-fit Planck2018/$\Lambda$CDM parameters on the Cosmic Microwave Background (CMB), the Baryon Acoustic Oscillations (BAO) measurements, the Pantheon Supernovae type Ia and the Hubble parameter data with redshift ranging from $0.01 < z < 2.3$ to impose restrictions on the model. From linear Nash-Green fluctuations of the metric, we obtain the related perturbed equations in longitudinal Newtonian gauge to obtain the evolution of growth matter. We show that a mild alleviation is obtained from the $\sigma$ tension between the growth amplitude factor and the matter content $(\sigma_8$-$\Omega_m)$ of the observations from CMB and Large Scale Structure (LSS) probes with degeneracies on the parameters. We also apply the Om(z) diagnosis to distinguish the model from $\Lambda$CDM. The Akaike Information Criterion (AIC) is used and we find a relative statistical consistence of the present model with both $\Lambda$CDM and $w$CDM models up to 1$\%$ of percentage difference at early times.

This paper presents an extension of the results obtained in previous work concerning the application of global optimization techniques to the design of finite strategic games with mixed strategies. In that publication the Fuzzy ASA global optimization method was applied to many examples of synthesis of strategic games with one previously specified Nash equilibrium, evidencing its ability in finding payoff functions whose respective games present those equilibria, possibly among others. That is to say, it was shown it is possible to establish in advance a Nash equilibrium for a generic finite state strategic game and to compute payoff functions that will make it feasible to reach the chosen equilibrium, allowing players to converge to the desired profile, con- sidering that it is an equilibrium of the game as well. Going beyond this state of affairs, the present article shows that it is possible to ”impose” multiple Nash equilibria to finite strategic games by following the same reasoning as before, but with a fundamental change: using the same fundamental theorem of Richard McKelvey, modifying the originally prescribed objective function and globally minimizing it. The proposed method, in principle, is able to find payoff functions that result in games featuring an arbitrary number of Nash equilibria, paving the way to a substantial number of potential applications.

We employ the solution concept of ex post Nash equilibrium to predict the interaction of a finite number of agents competing in a finite number of basic games simultaneously. The competition is called a multi-game. For each agent, a specific weight, considered as private information, is allocated to each basic game representing its investment in that game and the utility of each agent for any strategy profile is the weighted sum, i.e., convex combination, of its utilities in the basic games. Multi-games can model decision making in multi-environments in a variety of circumstances, including decision making in multi-markets and decision making when there are both material and social utilities for agents as, we propose, in the Prisoner's Dilemma and the Trust Game. Given a set of pure Nash equilibria, one for each basic game in a multi-game, we construct a pure Bayesian Nash equilibrium for the multi-game. We then focus on the class of so-called uniform multi-games in which each agent is constrained to play in all games the same strategy from an action set consisting of a best response per game. Uniform multi-games are equivalent to multi-dimensional Bayesian games where the type of each agent is a finite dimensional vector with non-negative components. A notion of pure type-regularity for uniform multi-games is developed and it is shown that a multi-game that is pure type-regular on the boundary of its type space has a pure ex post Nash equilibrium which is computed in constant time with respect to the number of the types and is independent of prior probability distributions. We then develop an algorithm, linear in the number of types of the agents, which tests if a multi-game is pure type-regular on the boundary of its type space in which case it returns a pure ex post Nash equilibrium for the multi-game.

A series of (benzoimidazol-2-ylmethyl)amine palladium(II) complexes have been employed as catalysts in the homogenous hydrogenation of alkenes and alkynes under mild conditions. A correlation between the catalytic activity and the nature of the ligand was established. Kinetic studies of the hydrogenation reactions of styrene established pseudo-first-order dependence on styrene substrate. On the other hand, partial orders with respect to H2 and catalyst concentrations were obtained consistent with the formation of palladium(II) monohydride species as the active species. The nature of the solvent used influenced the hydrogenation reactions, where coordinating solvents resulted in lower catalytic activities. Density functional theory investigations provided valuable insights into the reactivity trends and influence of complex structure on the hydrogenation reactions.

AbstractLocal estimates of coastal flood risk are required for coastal planning and development, including the location and design of sea-defences and coastal buildings, such as harbours and associated infrastructure. This paper discusses the use of three parameters associated with estimating such risks; the flood return period, the instantaneous flood probability and the flood design risk, and it describes the mathematical background for their derivation. The discussion is extended to include the effects of sea level rise and how it can be incorporated into the calculations. Flood height can vary quite rapidly with distance along the coast, being affected by coastal topology, which may magnify or diminish the tidal and surge effects. Similarly land heave influences the local effects of sea level rise and can be influenced by water extraction, tectonic movements and melting ice. Tide gauge measurements provide a local historical record from which the various parameters can be retrieved. This paper discusses the algorithms used to derive these measures from tide-gauge records. The figures have been derived for four tide gauges located on the UK east coast.

Detecting cracks in teeth is a clinical challenge. Patients may complain of diffuse pain on chewing, pain, at times, on temperature change and pain that occurs episodically. Common diagnostic tools such as radiographs and visual examination may not detect cracks. This case report shows how PTR-LUM in The Canary System can detect cracks in teeth not seen with other devices. In this clinical situation, the crack involved a portion of the mesial and distal surfaces of a mandibular second molar.

The objective was to conduct a scoping review and produce a publicly available database characterizing the design and reporting elements of the literature on dietary added sugars and select health outcomes. Relevant studies published from 1990 – 2021 were identified to create a database containing information on study and population characteristics, reported added sugars source and concentrations, diet energy balance, total energy intake, and outcome measures related to body composition, obesity, cardiovascular disease, and diabetes mellitus. There were 245 publications identified, 22% of which describe interventions and 78% describe observational studies. Publications pertaining to added sugars have risen dramatically since 2010, led by studies primarily assessing body composition (36%) or cardiovascular health (32%), including adults (65%), measuring liquid-only sources of added sugars (56%). Over 65% of studies reported total energy intake, 61% controlled for total energy intake in the design and analysis, and fewer than 5% of studies reported the energy balance of subjects. There has been a significant increase in research on added sugars since 2010, with substantial heterogeneity across all facets of methodology – study designs, exposures and outcomes of interest, terminology, and reporting of dietary intake data – thus limiting the ability to synthesize evidence in this scope of literature. This evidence map highlights gaps and important areas for improvement to strengthen the state of research to better inform future policies and dietary recommendations on added sugars.

What is the ideal soil-grass combination for maximum photosynthesis? In this study, we investigated how soil and grassland types affect photosynthesis in the grasslands of Gannan, China. We divided the grasslands of Gannan into 166 study sites, each with a unique soil-grass combination by intersecting the soil and ecoregion maps using ArcGIS. We obtained 19 years of data on the Net Photosynthesis (PsnNet) of grasslands in the area from 2000 to 2018 and then divided them into “growing season” (June to September) and “non-growing season” (October top May). Between 2000 and 2018, PsnNet of grasslands showed a gradually increasing trend. The effect of soil type on PsnNet was not significant during the growing season. However, it was highly significant during the non-growing season. Among the soil types, grasses that grew in Mollic, Gelic, and Haplic soils had the highest rate of photosynthesis. The difference in PsnNet among the various grass types was highly significant during both seasons. However, Tropical and Subtropical succulent evergreen broad-leaf shrubs and Temperate meadows had the highest rate of photosynthesis. Additionally, there was a highly significant difference in PsnNet among the various soil-grass interactions. In the growing season, TStEgBLS growing Eutric soils had the highest PsnNet. However, SaDBLS growing in Gelic soils had the the highest.

Asphaltene precipitation and deposition pose significant operational challenges in both reservoirs and surface facilities by inducing formation damage. To understand the kinetics involved in asphaltene particle nucleation, growth, and aggregation, this study employed confocal microscopy and centrifuge-based methods under a unified set of experimental parameters. The acquired time-resolved particle size images were analyzed using MIPAR image processing software, while asphaltene mass yield was quantitatively evaluated through centrifugation. Experimental conditions were varied to study the effects of heptane concentration, asphaltene concentration, and shear rate. Notably, this investigation introduces, for the first time, the parameter of particle count as an additional variable influencing asphaltene mass production. This study aims to discern how particle count correlates with asphaltene mass yield over time. Results indicate that the minimum mean particle diameter was observed to be 2 microns, which progressively grew up to 80 microns. The mean particle diameter exhibited a positive correlation with both asphaltene concentration and shear rate, whereas an inverse correlation was seen with heptane concentration. Furthermore, the asphaltene mass yield was found to increase with greater asphaltene and heptane concentrations, as well as with higher shear rates. The relationship between mean particle diameter and mass yield was found to be nonlinear. In the early stages, a higher prevalence of small particles contributed to a greater total particle count, while at later stages, particle aggregation led to the formation of larger particles that influenced the overall asphaltene mass. The insights gained from understanding the relationship between particle diameter, count, and mass yield are crucial for advancing the fundamental science of asphaltene precipitation and deposition. These findings may also guide future research that relies solely on particle counts for assessing asphaltene deposition.

Non-alcoholic fatty liver disease (NAFLD) affects up to a quarter of the adult population in many developed and developing countries. This spectrum of liver disease ranges from simple steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. The incidence of NASH is projected to increase by up to 56% over the next 10 years. There is growing epidemiological evidence that NAFLD has become the fastest growing cause of hepatocellular carcinoma (HCC) in industrialized countries. The annual incidence of HCC varies between patients with NASH cirrhosis and patients with noncirrhotic NAFLD. In this review, NAFLD/NASH-associated HCC will be described, including its epidemiology, risk factors promoting hepatocarcinogenesis, and management of HCC in patients with obesity and associated metabolic comorbidities, including preventive strategies and therapeutic approaches to address this growing problem.

The species composition of vultures and their interactions on carcasses of various stages of decomposition is not well understood yet it potentially affects their food acquisition and survival. We collected data from six carcasses between June and December 2021 using camera traps that were set on carcasses undergoing various decomposition states in Sinamatella Camp of Hwange National Park, Zimbabwe. Of interest were the cases in which each vulture species was dominating in interactions which gave it an advantage in terms of food acquisition. Four vulture species were observed (White-backed, White-headed, Lappet-faced and Hooded Vultures). Vulture abundances were greatest on fresh carcasses and least on dry ones. Although dominance behaviors by the White-backed and White-headed Vultures were recorded over all other vulture species, there were no records of the Lappet-faced dominating other vultures. In addition, the Hooded Vultures were mostly dominating non-vulture avian species on advanced decay carcasses. Our results demonstrate how various species may be prone to intense competition that may further place them at disadvantageous positions if food sources decline, more so under climatic shifts and various anthropogenic pressures.

From the linear Nash-Green fluctuations of background metric, we present the perturbation equations in an embedded four space-time. In the context of a five-dimensional bulk, we show that the perturbations are only propagated by the gravitational tensorial field equation. In a Newtonian conformal gauge, we study the matter density evolution in sub-horizon regime and on how such scale may be affected by the extrinsic curvature. We use the "extended Gold 2018'' growth dataset with 25 datapoints and the best fit Planck2018/LambdaCDM parameters. Hence, we determine the evolution equation for the density growth delta(a) as a result from the embedded equations of the background geometry. By using solar constraints, we analyse the evolution of the effective Newtonian constant G_eff and showing that applying Taylor expansion to G_eff (a) under the constraint of time-derivative of G_eff(0)=G at a= 1 in matter domination era, we get an agreement with Big Bang Nucleosynthesis (BBN) and also an alleviation of the 3-sigma tension to 1-sigma contour between (sigma8-Omega_m) of the observations from Cosmic Microwave Background (CMB) and Large Scale Structure (LSS) probes.

A novel means of applying radiotherapy in cancer treatment is the application of the radiation dose at a very high intensity for a very short time, FLASH radiotherapy (FLASH-RT). This technique involves exposure of tumors to >40 Gy/s, usually for less than one second. Studies conducted in cell and preclinical models suggest that FLASH-RT seems less damaging to normal tissues from adverse effects, relative to the same overall dose of radiation administered in conventional therapy (CONV-RT) which involves administration of lower levels of radiation repeated intermittently over a protracted period. In contrast, the susceptibility of tumor tissues to FLASH-RT is not diminished relative to CONV-RT. Within solid tumors both modes of dispensation of radiation produce an equivalent degree of cell damage. This differential between normal and malignant material has been found in isolated tissues, animal studies, and more recently in clinical trials. However, the classical radiation concept is that high energy linear transfer radiation (LET) is more damaging than the equivalent total dose of low LET. Thus, the susceptibility of cells should be greater to short-term exposure to high LET. This article discusses the potential reasons that may account for this discrepancy. While the relative protection given to untransformed tissues by FLASH-RT relative to tumor tissue is a major step forward in radiation therapy of cancer, the processes that lie behind this phenomenon are incompletely understood and are considered here.

Perovskite Solar Cell (PSC) is a third-generation photovoltaic device known for its rapid improvement in efficiency levels over the past decade. Moreover, the added benefits of abundant sourcing of raw materials, uncomplicated fabrication process, organic and inorganic device materials, and tuneable bandgaps make this technology a sustainable energy alternative. However, the efficiency values of these devices are subjected to variation depending on factors such as material compatibility, environmental conditions, energy band alignment of device components and stability characteristics to extrinsic and intrinsic factors. One such vital intrinsic factor is film morphology, homogenous and superior film quality formation and pinhole and trap-free films. In this study, we have investigated the formation of perovskite films on a qualitative basis using metal chloride washing of salts such as Erbium, Antimony, Cadmium and Chromium Chloride. The study aims to analyse the difference in film formation with various metal chloride washing and how this could potentially impact or contribute to photovoltaic performance if the devices are fabricated.

In developing countries today, population growth and the penetration of higher standard of living appliances in homes has resulted in a rapidly increasing residential load. In South Africa, the recent rolling blackouts and electricity price increase only highlighted this reality calling for sustainable measures to reduce the overall consumption and peak load. The dawn of the smart grid concept, embedded systems and ICTs have paved the way to novel HEMS design. In this regard, the Internet of Things (IoT), an enabler for smart and efficient energy management systems is seeing increasing attention for optimizing HEMS design and mitigate its deployment cost constraints. In this work, we propose an IoT platform for residential energy management applications focusing on interoperability, low-cost, technology availability and scalability. We focus on the backend complexities of IoT Home Area Networks (HAN) using the OCF IoTivity-Lite middleware. To augment the quality, servicing and reduce cost and complexities, this work leverages open-source Cloud technologies from Back4App as BaaS to provide consumer and Utilities with a data communication platform within an experimental study illustrating time and space agnostic “mind-changing” energy feedback, Demand Response Management (DRM) and appliance operation control via a HEM App via an Android smartphone.

This review describes how resonance in amides is greatly affected upon substitution at nitrogen by two electronegative atoms. Nitrogen becomes strongly pyramidal and resonance stabilisation, evaluated computationally, can be reduced to as little as 50% that of N,N-dimethylacetamide. However, this occurs without significant twisting about the amide bond, which is borne out both experimentally and theoretically. In certain configurations, reduced resonance and pronounced anomeric effects between heteroatom substituents are instrumental in driving the HERON (Heteroatom Rearrangement On Nitrogen)^† reaction, in which the more electronegative atom migrates from nitrogen to the carbonyl carbon in concert with heterolysis of the amide bond, to generate acyl derivatives and heteroatom-substituted nitrenes. In other cases the anomeric effect facilitates S­_N1 and S_N2 reactivity at the amide nitrogen.

Broflanilide is a novel active ingredient from a unique insecticide class (IRAC Group 30) and was investigated as a control option against modern insecticide resistant strains of the common bed bug, Cimex lectularius. The susceptibility of technical grade broflanilide and efficacy of a broflanilide-based aerosol formulation (Earth Corp., Japan) were evaluated against five C. lectularius strains (MONH, SYD, DARL, PARRA, RIPPO). Results demonstrated that bed bugs had high susceptibility to broflanilide (RR50: SYD=1.22-fold, DARL=1.03-fold, PARRA=3.65-fold, RIPPO=2.77-fold), compared to the susceptible MONH strain. The aerosol showed high efficacy to adult bed bugs (97.5–100 % mortality to five strains after 24 hrs post-spray) and produced a notable decrease in egg hatch rates (MONH=9.7–23.4 %, PARRA=14.9–22.6 %). The aerosol also demonstrated high residual activity with 97.5–100% mortality in all five bed bug strains within 7 days exposure. The impact of different surface types upon aerosol residual efficacy was limited, although residues on a non-porous surface (tile) killed bed bugs slightly quicker than that on a porous surface (filter paper). The aerosol provided long residual activity to bed bugs, as 6-month-old residues were as equally efficacious to that of fresh residues. Bed bugs did not avoid surfaces treated with the aerosol. The high efficacy (including ovicidal efficacy), long residual activity, and non-avoidance of bed bugs on treated surfaces, demonstrated that broflanilide is highly suitable for modern bed bug management.

This review examines the categorization of Essentially Derived Varieties (EDV) introduced in the 1991 revision of the Convention of the Union internationale pour la protection des obtentions végétales (UPOV). Challenges in the implementation of the concept and progress made on a crop-by-crop basis to provide greater clarity and more efficient implementation are reviewed. The current approach to EDV remains valid provided i) clarity on thresholds can be achieved including through resource intensive research on an individual crop species basis and ii) that threshold clarity does not lead to perverse incentives to avoid detection of essential derivation. However, technological advances leading to new varieties resulting from the simultaneous introduction or change in expression of more than “a few” genes will so challenge the concept to require a new Convention. Revision could include deletion of the concept of essential derivation and revision on a crop-by-crop basis of the breeder exception. Countries that allow utility patents for individual plant varieties per se should consider removing that possibility unless plant breeders utilize those encouragements for risk taking and investment to broaden the germplasm base upon which the long-term sustainability of plant breeding resides.

Systemic inflammation plays a central role in many diseases and is, therefore, an important therapeutic target. In a scoping review, we assessed the evidence base for anti-inflammatory effects of pre-, pro- and synbiotics in children. Of 1254 clinical trials published in English in Ovid Medline and Cochrane Library PubMed from January 2003 through September 2022, 29 were included in the review. In 6 studies of healthy children (n=1552), one reported that fructo-oligosaccharides added to infant formula significantly reduced pro-inflammatory biomarkers and one study of a single strain probiotic reported both anti- and pro-inflammatory effects. No effects were seen in the remaining two single-strain and one multi-strain probiotic and one synbiotic study. In 23 studies of children with diseases (n=1550), prebiotics were tested in 3, single-strain in 16 and multi-strain probiotics in 6 and synbiotics in 2 studies. Significantly reduced inflammatory biomarkers were reported in 7/10 studies of atopic/allergic conditions, 3/5 studies of auto-immune diseases, 1/2 studies of preterm infants, 1 study of overweight/obesity, 2/2 studies of severe illness and 2/3 studies of other diseases. However, often only one or two of several biomarkers were improved, increased pro-inflammatory biomarkers occurred in 5 of these studies and a probiotic increased inflammatory biomarkers in a study of newborns with congenital heart disease. The evidence base for the effects of pre-, pro- and synbiotics on systemic inflammation in children is weak. Further research is needed to determine if anti-inflammatory effects depend on the specific pre-, pro- and synbiotic preparations, health status and biomarkers studied.

Multi-morbidity and polypharmacy are common in older people and pose a challenge for health and social care systems especially in context of global population ageing. They are complex and interrelated concepts in the care of older people that require early detection and patient centred decision making that are underpinned by the principles of multidisciplinary led comprehensive geriatric assessment (CGA). Personalised care plans need to remain responsive and adaptable to the needs of a patient, enabling an individual to maintain their independence.

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are fast becoming the most common chronic liver disease and are often preventable with healthy dietary habits and weight management. Sugar-sweetened beverage (SSB) consumption is associated with obesity and NAFLD. However, the impact of different types of SSB, including artificially sweetened beverages (ASB), is not clear after controlling for total sugar intake and total caloric intake. In this study, we examined the association between different SSB consumption and the risk of NAFLD and NASH. A total of 3,739 US adults aged ≥20 years old who had completed 24-hour dietary recall interviews and measurements, including dietary, SSB, smoking, physical activity, and liver stiffness measurement, using the National Health and Nutrition Examination Survey 2017-2020 surveys were included in this study. Chi-square tests, t-tests, and weighted logistic regression models were utilized for analyses. The prevalence of NASH was 20.5%, and NAFLD (defined without NASH) was 32.7% of .S.U.S. adults. We observed a higher prevalence of NASH/NAFLD in men, Mexican-Americans, sugar intake from SSB, light-moderate alcohol use, individuals with lower physical activity levels, higher energy intake, obesity, and medical comorbidities. Heavy sugar consumption through SSB was significantly associated with NAFLD (aOR=1.60, 95% CI=1.05-2.45). In addition, intake of ASB only (compared to non-SSB category) was significantly associated with NAFLD (aOR=1.78, 95% CI=1.04-3.05), after adjusting for demographic, risk behaviors, and body mass index. Higher sugar intake from SSB and exclusive ASB intake are both associated with the risk of NAFLD.

Inflammatory processes play major roles in carcinogenesis and progression of hepatocellular carcinoma (HCC) derived from non-alcoholic steatohepatitis (NASH). But there are no therapies for NASH related HCC, especially focusing on these critical steps. Previous studies reported that farnesyltransferase inhibitors (FTIs) have anti-inflammatory and anti-tumor effects. However, the influence of FTIs on NASH-related HCC has not been elucidated. In HCC cell lines, HepG2, Hep3B, and Huh-7, we confirmed expression of hypoxia-inducible factor (HIF)-1α, an accelerator of tumor aggressiveness and the inflammatory response. We established NASH-related HCC models under inflammation and free fatty acid burden and confirmed that HIF-1α expression was increased under both conditions. Tipifarnib, which is an FTI, strongly suppressed increased HIF-1α, inhibited cell proliferation, and induced apoptosis. Simultaneously, intracellular interleukin-6 as an inflammation marker was increased under both conditions and significantly suppressed by tipifarnib. Additionally, tipifarnib suppressed expression of phosphorylated nuclear factor-κB and transforming growth factor-β. Finally, in a NASH-related HCC mouse model burdened with diethylnitrosamine and a high fat diet, tipifarnib significantly reduced tumor nodule formation in association with decreased serum interleukin-6. In conclusion, tipifarnib has anti-tumor and anti-inflammatory effects in a NASH-related HCC model and may be a promising new agent to treat this disease.

We present a modified version of the Szilard Engine, demonstrating that an explicit measurement procedure is entirely unnecessary for its operation. By considering our modified engine, we are able to provide a new interpretation of Landauer’s original argument for the cost of erasure. From this view, we demonstrate that a reset operation is strictly impossible in a dynamical system with only conservative forces. Then, we prove that to approach a reset yields an unavoidable instability at the reset point. Finally, we present an original proof of Landauer’s principle that is completely independent from the Second Law of Thermodynamics.

Hydrogels have gained significant attention as vehicles for transdermal delivery systems. These polymeric-structured substances have been implemented in pharmaceutical and cosmetic applications. Many factors are employed in their preparation. Light, pH, temperature and specific molecules ligands are commonly used in the production of hydrogels. The Transdermal delivery system (TDD) is a widely used route, used to deliver actives/drugs via the skin. Hydrogels as a TDD have been shown to be efficient in enhancing the efficacy in delivering the actives and drugs. The aim of this review is to discuss the hydrogels application in both dermatological therapeutic and cosmetic applications, covering the types, and properties of hydrogel polymer networks. Furthermore, this review presents one of the most extensively used polymers (Hyaluronic acid HA) in this field and discusses the properties, preparation methods and applications of HA hydrogel patches as a delivery system, including methods of loading the actives and the releasing of these actives from them.

The changes in the properties of three biological events, that occur with cerebral aging, are discussed. These adverse changes already begin to develop early in mid-life and gradually become more pronounced with senescence. Essentially, they are reflections of the progressive decline in effectiveness of key processes, resulting in the deviation of essential biochemical trajectories to ineffective and ultimately harmful variants of these programs. The emphasis of this review is the major role played by mitochondria in such transition of these three important processes toward more deleterious variants as brain aging proceeds. 1. The immune system. The shift away from an efficient immune response to a more unfocused, continuing inflammatory condition. Such a state is both ineffective and harmful. 2. Reactive oxygen species are important intracellular signaling systems. Also, microglial phagocytic activity utilizing short lived reactive oxygen species contribute to the removal of aberrant or dead cells and bacteria. These processes are transformed into an excessive, untargeted and persistent generation of pro-oxidant free radicals (oxidative stress). 3. The normal efficient neural transmission is modified to a state of undirected, chronic low-level excitatory activity. Each of these changes is characterized by the occurrence of continuous activity that is inefficient and diffuse. The signal/noise ratio of several critical biological events is thus reduced as beneficial responses are gradually replaced by their impaired and deleterious variants.

School-aged children may benefit from education interventions focused on healthy eating and physical activity to improve their quality of life. This article aims to review scientific evidence on food and nutrition education (FNE) in Spanish-speaking countries for the prevention of overweight and obesity in school-aged children (6-12 y). Articles were searched between April and August 2021. The searches were conducted using MEDLINE, Google Scholar, and SciELO. The primary search for articles focused on the experience of FNE interventions in Spanish-speaking countries. Overall, 518 articles were found and 33 studies were eligible for data extraction. Forty-two percent of the studies had a focus on FNE and 64% were focused on describing the eating habits of schoolchildren. Nutritional assessments (anthropometric) were found frequently with 91% and 30% of the studies focused on physical activity. All interventions focused on preventing or reducing overweight and obesity in school-age children. Educational, cognitive, dietary, and physical activity practices were described, whit being educational the most frequent intervention. Interventions reported positive effects of FNE interventions to improve knowledge and practices of healthy lifestyles in school-age children.

BACKGROUND. Two sequelae of non-alcoholic steatohepatitis (NASH), ESLD and HCC, have become the leading causes for liver transplantation in the Western. The present study aims to approach the cellular metabolic disturbances involved in NASH progression that are associated with microbiota community changes. METHODS. Metabolic effects and microbiota community changes were explored in the murine with NASH progression by blocking the Na/K-ATPase/Src/reactive oxygen amplification loop using the synthetic targeting peptide pNaKtide. DNA from the terminal ileum microbiota habitat was obtained and amplified by PCR to develop DNA bacterial phylogenic sequence analysis of wild type and treated animals at 12, 24 and 48 weeks. Induced changes by pSrc normalization at 24 weeks were correlated with liver morphological changes, intestinal CD4+/CD8+ ratio, and liver macrophage CD14+ expression. Differences among groups were evaluated by ANOVA/t-test and Principal Component Analysis (PCA). RESULTS. Microbiota communities varied significantly at all time points (12, 24 and 48 weeks), with an increase of Verrucomicrobia and a decrease of Bacteroidetes and Firmicutes in the HFD group. Microbiota community changes regressed to their wild-type state at 24 weeks on treated animals, and those changes were associated with a decrease in liver inflammation and senescence, lower ileum CD4+/CD8+ T cells and higher liver CD14+ cells (p<0.05). Concomitantly, the metabolic disturbances in our diet-induced NASH model were normalized by NKA/Src signaling blockage and exercise with a paucity of apoptotic activity, mitigation of cell senescence, and regression of liver fibrosis (p<0.01). CONCLUSIONS. pSrc inhibition at caveolar α1-Na/K-ATPase rescinded NASH-related metabolic disturbances establishing resident physiological microbiota communities with concomitant paucity on apoptotic activity and regression of liver fibrosis; effects that were associated with both gut and liver T-lymphocyte responses.

Real-time multi-axis distributed tactile sensing is a critical capability if robots are to perform stable gripping and dexterous manipulation, as it provides crucial information about the sensor-object interface. In this paper, we present an optical-based 6-axis tactile sensor designed in a fingertip shape for robotic dexterous manipulation. The distributed sensor can precisely estimate local XYZ force and displacement at ten distinct locations, and provide global XYZ force and torque measurements. Its compact size, comparable to that of a human thumb, and minimal thickness allow seamless integration onto existing robotic fingers, eliminating the need for complex modifications to the gripper. The proposed sensor design uses a simple, low-cost fabrication method. Moreover, the optical transduction approach uses light angle and intensity sensing to infer force and displacement from deformations of individual sensing units that form the overall sensor, providing distributed 6-axis sensing. The local force precision at each sensing unit in the X, Y, and Z axes is 20.89 mN, 19.19 mN, and 43.22 mN, respectively, over an local force range of approximately ±1.5 N in X and Y and 0 to -2 N in Z. The local displacement precision in the X, Y and Z axes is 56.70 μm, 50.18 μm and 13.83 μm, respectively, over a local displacement range of ±2 mm in the XY directions and 0 to -1.5mm in Z (i.e., compression). Additionally, the sensor can measure global torques, Tx, Ty and Tz, with a precision of of 1.90 N-mm, 1.54 N-mm and 1.26 N-mm, respectively. The fabricated design is showcased by integrating it with an OnRobot RG2 gripper and illustrating real-time measurements during in simple demonstration task which generate changing global forces and torques.

Recently, there have been revolutions in the development of both gene therapy and genome surgical treatments for inherited diseases. Much of this progress has been centered around hereditary retinal dystrophies, because the eye is an immune-privileged and anatomically ideal target. Gene therapy treatments, already demonstrated to be safe and efficacious in numerous clinical trials, are benefitting from the development of new viral vectors, such as dual and triple AAVs. CRISPR/Ca9, which revolutionized the field of gene editing, is being adapted into more precise “high fidelity” and catalytically dead variants. New CRISPR endonucleases, such as CjCas9 and Cas12a, are generating excitement in the field as well. Stem cell therapy has emerged as a promising alternative, allowing human embryo derived stem cells and induced pluripotent stem cells to be edited precisely in vitro and then reintroduced into the body. This article highlights recent progress made in gene therapy and genome surgery for retinal disorders, and it provides an update on precision medicine FDA treatment trials.

Cellular senescence has recently been recognized as a hallmark of cancer, reflecting its association with aging and inflammation, its role as a response to deregulated proliferation and oncogenic stress, and its induction by cancer therapies such as radiation, chemotherapy, and targeted agents. While such therapy-induced senescence (TIS) has been linked to resistance, recurrence, metastasis and normal tissue toxicity, TIS has the potential to enhance therapy response and stimulate anti-tumor immunity. In this review, we examine the Jekyll and Hyde nature of senescent cells (SnCs), with a particular focus on how their persistence while expressing the senescence-associated secretory phenotype (SASP) modulates the tumor microenvironment through autocrine and paracrine mechanisms. Via the SASP, the formation of SnCs may alternately mediate resistance or response to conventional therapy. Further, toward fulfilling the unmet potential of cancer immunotherapy, we consider how SnCs may influence tumor inflammation and serve as a source of antigen to potentiate anti-tumor immunity. This new view suggests treatment strategies based on inducing TIS to enhance immune checkpoint blockade. Finally, we describe strategies for mitigating the detrimental effects of senescence, such as modulating the SASP or targeting SnC persistence, toward enhancing the benefits of cancer treatment.

Abstract: Herbicide flashback is an undesirable response that results in damage or mortality of non-target plants near chemically treated plants. In severe instances, crop trees can be injured resulting in financial loss or inability to capture management objectives. Land managers need to know the potential limitations of using triclopyr acid (50% solution in water) and what quantity can cause damage to non-target trees (trees not aimed to control via herbicide). Three naturally regenerated (previous clearcut) bottomland hardwood sites, ranging from 14–20 years of age, received partial overstory deadening using Trycera® herbicide. Residual “leave” trees experienced indirect herbicide uptake resulting in some trees either experiencing mortality or partial mortality with top die-back/epicormic branching. An increased probability of damage occurred as tree diameter decreased and the number of treated stems around non-target stems increased. American sycamore, green ash, and sweetgum were most susceptible to flashback. This study examines the unanticipated chemical effect of deadening adjacent stems surrounding residual leave trees in poorly drained soils.

The efficient recognition and classification of personal protective equipment are essential for en-suring the safety of personnel in complex industrial settings. Using the existing methods, manually performing macro-level classification and identification of personnel in intricate spheres is tedious, time-consuming, and inefficient. The availability of several artificial intelligence models in recent times presents a new paradigm shift in object classification and tracking in complex settings. In this study, several compact and efficient deep learning model architectures are explored, and a new efficient model is constructed by fusing the learning capabilities of the individual, efficient models for better object feature learning and optimal inferencing. The new model construct follows the contributory learning theory whereby each fussed model brings its learned features, which are then combined to obtain a more accurate and rapid model using normalized quantization-aware learning. During the investigation, a separable convolutional driven model was constructed as a base model, and then the various efficient architectures combined for the rapid identification and classification of the various hardhat classes used in complex industrial settings. A remarkable rapid classification and accuracy were recorded with the new resultant model.

Accurate pose estimation is a fundamental ability that all mobile robots must posses in order to navigate a given environment. Much like a human, this ability is dependent on the robot's understanding of a given scene. For Autonomous Vehicles (AV's), detailed 3D maps created beforehand are widely used to augment the perceptive abilities and estimate pose based on current sensor measurements. This approach however is less suited for rural communities that are sparsely connected and cover large areas. Topological maps such as OpenStreetMaps have proven to be a useful alternative in these situations. However, vehicle localization using these maps is non-trivial, particularly for the global localization task, where the map spans large areas. To deal with this challenge, we propose road descriptors along with an initialization technique for localization that allows for fast global pose estimation. We test our algorithms on (real world) maps and benchmark them against other map based localization as well as SLAM algorithms. Our results show that the proposed method can narrow down the pose to within 50 centimeters of the ground truth significantly faster than the state of the art methods.

We assessed how close human perceptions of landscape modification matched a multivariate index based on remotely sensed data of the same locations. Using a Human Footprint (HF) map of the continental U.S. (scaled 0-100), we created three series of aerial images, each with ten images distributed evenly across the 10 deciles of HF score. Using a web-based survey, 290 members of the global public ranked the images in one series based on their perception of the degree of human modification. Respondents also reported age, sex, and country. The degree of correspondence between rankings by respondents and by HF score was high, an average of 1.29 units of difference out of a maximum possible of 5.0. Differences among respondents were not explained by age, sex, or general geographic location. These results suggest that human perception of relative landscape modification conforms closely with the relative ranking made by a multivariate, analytical index.

We firstly discuss classical stability for a dynamical system of two ions levitated in a 3D Radio-Frequency (RF) trap, assimilated with two coupled oscillators. We obtain the solutions of the coupled system of equations that characterizes the associated dynamics. In addition, we supply the modes of oscillation and demonstrate the weak coupling condition is inappropriate in practice, while for collective modes of motion (and strong coupling) only a peak of the mass can be detected. Phase portraits and power spectra are employed to illustrate how the trajectory executes quasiperiodic motion on the surface of torus, namely a Kolmogorov-Arnold-Moser (KAM) torus. In an attempt to better describe dynamical stability of the system, we introduce a model that characterizes dynamical stability and the critical points based on the Hessian matrix approach. The model is then applied to investigate quantum dynamics for many-body systems consisting of identical ions, levitated in 2D and 3D ion traps. Finally, the same model is applied to the case of a combined 3D Quadrupole Ion Trap (QIT) with axial symmetry, for which we obtain the associated Hamilton function. The ion distribution can be described by means of numerical modeling, based on the Hamilton function we assign to the system. The approach we introduce is effective to infer the parameters of distinct types of traps by applying a unitary and coherent method, and especially for identifying equilibrium configurations, of large interest for ion crystals or quantum logic.

This year marks the 20th anniversary of the discovery that proteins with various cellular functions can be temporarily immobilized in the nucleolus, a process known as nucleolar sequestration. This review reflects on the progress made to understand the physiological roles of nucleolar sequestration and the mechanisms involved in protein immobilization. We discuss how nucleolar sequestration consists of a highly choreographed amyloidogenic liquid-to-solid phase transition that converts the nucleolus into Amyloid bodies (A-bodies). The study of solid condensates A-bodies will offer unique perspectives on cellular assembly of membrane-less compartments and provide alternative insights on pathological amyloidogenesis involved in neurological disorders.

Keywords: conservation; cultural pluralism; environmental regulation; community-based natural resource management; Indigenous law

Coronary angiography, long considered the gold standard for coronary imaging, faces limitations in assessing coronary vessel wall anatomy and guiding percutaneous coronary intervention (PCI). Despite its prevalence, studies have demonstrated that it is suboptimal in estimating the severity of coronary disease and physiologic significance of stenosis. Intracoronary imaging techniques, such as intravascular ultrasound (IVUS) and optical coherence tomography (OCT), offer promising alternatives to overcome these limitations. This review delves into the nuances of IVUS and OCT, highlighting their strengths and limitations as adjuncts to PCI. IVUS, utilizing ultrasound technology, and OCT, based on near-infrared light, each provide unique insights into coronary pathology. They differ in terms of temporal and spatial resolution, influencing their capabilities in plaque characterization and vessel assessment. The discussion navigates their historical evolution, technical specifications, and clinical utility. Meta-analyses and adjusted observational studies suggest that both IVUS and OCT-guided PCI correlate with reduced cardiovascular risks compared to angiographic guidance alone. While IVUS has demonstrated consistent benefits in terms of clinical outcomes, the evidence supporting OCT is less robust. However, the utilization of these imaging modalities remains variable across regions, with increasing adoption in recent years, particularly in IVUS-guided PCIs. Intravascular ultrasound's journey from early motion detection to current high-resolution mechanical systems is traced, including improvements in catheter size and compatibility. On the other hand, optical coherence tomography has advanced significantly, utilizing near infrared light to achieve unparalleled resolutions, albeit requiring temporary blood clearance for optimal imaging. In conclusion, IVUS and OCT offer valuable insights into coronary pathophysiology and guide interventions with improved precision compared to traditional angiography. While IVUS remains more extensively utilized, OCT's growing potential is underscored by advancements in technology, culminating in enhanced imaging capabilities. Both modalities demonstrate comparable clinical outcomes, emphasizing the need for tailored imaging choices based on individual clinical scenarios. The continued refinement and broader integration of intravascular imaging are expected to play a pivotal role in optimizing coronary interventions and patient outcomes.

Liver is structurally organized into zonation where LSECs endothelial cells play a crucial role during chronic liver injury and early stages of fibrosis. Fibrosis can be reversed if diagnosed early at molecular level in zonation before progressing to advanced stages like bridging fibrosis. This study identified zonation marker genes using scRNA-seq and spatial transcriptomics molecular profiling technologies in normal and diseased fibrotic human liver. DGE analysis is performed over LSECs and identified the top 20 expressed genes in periportal, perivenous, and intermediate acinar zones. Multi-omics and scRNA-seq analysis over Visium images and ECs liver cells figured out OIT3, DNASE1L3, CLEC4G, LYVE1, FCN2, CRHBP as commonly expressed mid-lobular zonation-specific genes. Also, this study detected STAB2, F8, AQP1, TEK, TIMP3, TIE1, CTSL genes as expressed in DILI and NASH ECs populations. The connection between LSECs marker genes in zone 2 and liver fibrosis holds significant promise for advancing our understanding in developing new therapeutic strategies for fibrosis reversal and designing computational molecular biomarkers in NASH and DILI fibrotic liver diseases.

We proposed a novel concept of flight time matrix (FTM). In this work, the proposed FTM was verified first numerically. The numerical simulation revealed perfect results which showed that FTM can be used to assist the nondestructive evaluation of ballistic armor plates using acousto-ultrasonics. Two donated commercial ballistic armor plates were sought for a case study where artificial defects were prepared. The results of FTM were reasonably well. The artificial defects were clearly identifiable in one directional location array and FTM contour graphs. More comprehensive superimpositions of flight time vs location and FTM contour plots can be advanced to a better visualization of the defect presence. The resolution of FTM method is in the range of submillimeter or less. This study demonstrated that AU (acousto-ultrasonics) technique is a field applicable and yet reliable tool for inspection of the hidden defects in body armors. A broader merit of the proposed FTM algorithm is that it may promote the development of specific tools/device for nondestructive evaluations field.

Non-destructive testing is an emerging need in manufacturing processes and in service of ballis-tic armor plates. It has been shown that acoustic emission and ultrasonics are among the most applicable techniques. However, these techniques often require relative sophisticated processing and strong tech background for the evaluators. The purpose of the present work is to develop a flight time based algorithm and to demonstrate this algorithm using commercial multilayered armor plates. We proposed a novel concept of flight time matrix (FTM). In this work, the proposed FTM was verified first numerically. The numerical simulation revealed perfect results which showed that FTM can be used to assist the nondestructive evaluation of ballistic armor plates using acous-to-ultrasonics. Two donated commercial ballistic armor plates were sought for a case study where artificial defects were prepared. The results of FTM were reasonably well. The artificial defects were clearly identifiable in one directional location array and FTM contour graphs. More com-prehensive superimpositions of flight time vs location and FTM contour plots can be advanced to a better visualization of the defect presence. The resolution of FTM method is in the range of submillimeter or less. This study demonstrated that AU (acousto-ultrasonics) technique is a field applicable and yet reliable tool for inspection of the hidden defects in body armors. A broader merit of the proposed FTM algorithm is that it may promote the development of specific tools/device for nondestructive evaluations field.

Abstract: A two-year study of pearl millet-groundnut cropping systems across two fertilizer levels was conducted at the INRAN/TARNA research station in Maradi, Niger in the Sahelian zone of West Africa. The objective of this study was to identify the best cropping system with and without fertilizer application to optimize pearl millet and groundnut yields, land use efficiency, and economics as measured by value-to-cost ratio. The experiment was conducted with three replications, and ten treatments combination of five pearl millet and groundnut cropping systems (pearl millet and groundnut sole crops, and three pearl millet – groundnut intercrops), and two fertilizer levels. Sole cropping produced the highest pearl millet grain by over 300 kg ha-1 and groundnut pod yields by over 500 kg ha-1, but all the intercropping systems had a LER above 1.0 with land use efficiency increased by 19 to 41%, also intercropping increased diversity, and reduced risk. Fertilizer application increased yields in all cropping systems by 200 to 600 kg ha-1. Government subsidy increased the value-to-cost ratio by 0.5 to 2, 5 units, and was required for economic response for pearl millet sole and intercrops in 2022. The groundnut sole cropping system had the greatest economic response to fertilizer application. Based on the risky environment and multiple end uses needed by producers, the intercrop system M-G: 1:3:1 with fertilizer application is usually the best option to optimize pearl millet and groundnut production.

An introductory course of Arka Dhyana, also known as Intuitive Meditation (IM), consisting of five sessions, was offered to an international audience via Zoom technology. Participants were shown how to connect to their deeper self, essence or soul by bringing their I-ego-awareness from the thinking mind, often associated with the frontal part of the brain, to 19 energetic stations in the body including the heart centre. In this limited study, evaluation was both process and outcome orientated and included HeartMath (HM) Inner Balance or emWave2 electronic technology to measure mean coherence and achievement before and after each session. A highly significant increase in both coherence and achievement in six participants was found, which was also reflected in a reported increase in wellbeing related to feelings in qualitative statements indicating changes in levels of consciousness and individual transformative experiences as predicted by the Theory of the Six Main Levels of Consciousness.

In Yaoundé, Cameroon, excessive and inappropriate speeding remains a major public health concern. Part of the problem are the unsafe speed limits, lack of evidence, and effective evaluation of speeding safety performance indicators (SSPIs), and the absence of speed management, hindering the city's ability to mitigate the risks associated with speeding. This study aimed to address this knowledge gap by assessing SSPIs using a well-defined methodology and suggesting speed management strategies. Data on speed, traffic volumes and road attributes were collected from a random selection of 16 representative road sections in Yaoundé. Seven SSPIs were calculated, and weights were assigned to evaluate city-level SSPIs. The findings showed that 66.8% of drivers drive within the speed limit, generally operating at speeds of 54 km/h with a speed variation of 26 km/h. Based on the speed analysis, evidence-based strategies are proposed, and implementing these strategies could potentially reduce fatalities and serious injuries by 16% to 84% across study locations, as indicated by Elvik's model. These findings have significant policy implications for reducing speeding in Yaoundé, and the methodological approach can be replicated in other urban settings. Future research should extend SSPI evaluation to the national level and test the effectiveness of the recommended strategies.

Radiological imaging is an essential component of a swallowing assessment. Artificial intelligence (AI), and especially deep learning (DL) models, have enhanced the efficiency and efficacy through which imaging is interpreted, and subsequently have important implications for swallow diagnostics and intervention planning. However, the application of AI for the interpretation of videofluoroscopic swallowing studies (VFSS) is still emerging. This review showcases recent literature in the use of AI to interpret VFSS and highlights clinical implications for speech pathologists (SPs). With a surge in AI research, there have been advances made in dysphagia assessment. Several studies have demonstrated successful implementation of DL algorithms to analyze VFSS. Notably, convolutional neural networks (CNNs) have been used to detect pertinent aspects of the swallowing process with high levels of precision. DL algorithms have the potential to streamline VFSS interpretation, improve efficiency and accuracy, and enable precise interpretation of instrumental dysphagia evaluation, which is especially advantageous when access to skilled clinicians is not ubiquitous. By enhancing precision, speed, and depth of VFSS interpretation, SPs can obtain a more comprehensive understanding of swallow physiology and deliver targeted and timely intervention that is tailored towards the individual. This has practical applications for both clinical practice and dysphagia research. As this research area grows and AI technologies progress, the application of DL in the field of VFSS interpretation is clinically beneficial and has the potential to transform dysphagia assessment and management. With broader validation and inter-disciplinary collaborations, AI-augmented VFSS interpretation is likely to transform swallow evaluation and ultimately improve outcomes for individuals with dysphagia.

This study investigated the efficiency of scale-propellers, typically used on small drones. A scale-propeller is accepted as having a diameter of 7 to 21 inches. The Ukraine War has demonstrated the utility of relatively small, low-cost first-person view (FPV) drones, which are attritable. This investigation outlines the development of a MATLAB optimisation code, based on minimum induced loss propeller theory, which calculates the optimal chord and twist distribution for a chosen propeller operating in known flight conditions. The MATLAB code includes a minimum Reynolds number functionality, which provides the option to alter the chord distribution to ensure the entire propeller is operating above a set threshold value of Reynolds (&gt;100,000), as this has been found to be a transition point between low and high section lift-to-drag ratios. Additional functions allow plotting of torque and thrust distributions along the blade. The results have been validated on experimental data taken from an APC ‘Thin Electric’ 10” x 7” propeller, where it was found that both the chord and twist distributions were accurately modelled. The MATLAB code resulted in a 16% increase in the maximum propulsive efficiency. Further work will investigate a direct interface to SolidWorks to aid rapid propeller manufacturing capability.

Influenza A (IAV) is a major human respiratory pathogen, causing illness, hospitalizations, and mortality annually worldwide. IAV is also a zoonotic pathogen with a multitude of hosts, allowing for interspecies transmission, reassortment events, and the emergence of novel pandemics, as was seen in 2009 with the emergence of a swine origin H1N1 (pdmH1N1) virus into humans, causing the first influenza pandemic of the 21st century. While the 2009 pandemic was considered to have high morbidity and low mortality, studies have linked the pdmH1N1 virus and its gene segments to increased disease in humans and animal models. Genetic components of the pdmH1N1 virus currently circulate in the swine population, reassorting with endemic swine viruses that co-circulate and occasionally spillover into humans. This is evidenced by the regular detection of variant swine IAVs in humans associated with state fairs and other intersections of humans and swine. Defining genetic changes that support species adaptation, virulence, and cross-species transmission, as well as mutations that enhance or attenuate these features will improve our understanding of influenza biology, aid in surveillance and virus risk assessment, and guide the establishment of counter measures for emerging viruses. Here, we review current understanding of determinants of specific IAV phenotypes, focusing on the fitness, transmission, and virulence determinants that have been identified in swine IAVs and/or in relation to the 2009 pdmH1N1 virus.

Balance requires constant adjustments in muscle activation to attain force steadiness. Creating appropriate training can be challenging. The purpose of this study was to examine the effects of two weeks front squat instability training using a water-filled training tube on force steadiness during an instability challenge. Control (CON, n= 13) and experimental (EXP, n=17) subjects completed pre and post testing for EMG variability by completing one set of 10 repetitions with a stable and unstable training tube. Electrodes were placed bilaterally on the anterior deltoid, paraspinal and vastus lateralis muscles. CON subjects completed 2 weeks of training using a stable training tube, while EXP subjects trained with a water-filled instability tube. EMG data were integrated for each contraction and force steadiness computed using the natural log of coefficient of variation. CON results showed no changes in force steadiness for any condition. EXP showed significant reductions in EMG activation variability across all muscles. These results indicate a significant training effect in reducing muscle activation variability in subjects training with a water-filled instability training device. Improvements seen in these healthy subjects supports development of training implements for a more clinical population to help improve force steadiness.

This review critically examines the various ways in which the mechanical properties of wood have been understood. Despite the immense global importance of wood in construction, most understanding of its elastic and inelastic properties is based on models developed for other materials. Such models neglect wood’s cellular and fibrous nature. This review thus questions how well models that were originally developed for homogeneous and effectively continuous materials can describe wood’s mechanical properties. For example, the elastic moduli of wood have been found by many authors to depend on the size of the test specimen. Such observations are incompatible with classical elasticity theory. There is also much uncertainty about how well elastic moduli can be defined for wood. An analysis of different models for size effects of various inelastic properties of wood shows that these models only approximate the observed behaviour, and do not predict or explain the scatter in the results. A more complete understanding of wood’s mechanical properties must take account of it being in some sense intermediate between a material and a structure.

Liver is structurally organized into zonation where LSECs endothelial cells play a crucial role during chronic liver injury and early stages of fibrosis. Fibrosis can be reversed if diagnosed early at molecular level in zonation before progressing to advanced stages like bridging fibrosis. This study identified zonation marker genes using scRNA-seq and spatial transcriptomics molecular profiling technologies in normal and diseased fibrotic human liver. DEG analysis is performed over LSECs and identified the top 20 expressed genes in periportal, perivenous, and intermediate acinar zones. Multi-omics and scRNA-seq analysis over Visium images and ECs liver cells figured out OIT3, DNASE1L3, CLEC4G, LYVE1, FCN2, CRHBP as commonly expressed mid-lobular zonation-specific genes. Also, this study detected STAB2, F8, AQP1, TEK, TIMP3, TIE1, CTSL genes as expressed in DILI and NASH ECs populations. The connection between LSECs marker genes in zone 2 and liver fibrosis holds significant promise for advancing our understanding in developing new therapeutic strategies for fibrosis reversal and designing computational molecular biomarkers in NASH and DILI fibrotic liver diseases.

The Hubble parameter H(z), as a function of redshift, is modified by the presence of a new term originated from the extrinsic curvature in an embedded space-time. Assuming an asymptotic expansion factor $a\sim 0$ or, equivalently $z\rightarrow \infty$, it is obtained a nearly resemblance of the present model ($\beta$-model) with quintessence $w$CDM model with $H(z)\sim H_{wCDM}(z)$ at background level. In conjunction with $\Lambda$CDM, we test the models using a pack of recent datasets like that of the ``Gold 2018'' growth data, the best-fit Planck2018/$\Lambda$CDM parameters on the Cosmic Microwave Background (CMB), the Baryon Acoustic Oscillations (BAO) measurements, the Pantheon Supernovae type Ia and the Hubble parameter data with redshift ranging from $0.01 < z < 2.3$. Performing the Akaike Information Criterion (AIC) to ascertain the statistical viability of the model from Jeffreys' scale, we apply a joint likelihood analysis to the data with the Markov Chain Monte Carlo (MCMC) method. We find that the present model is in very good agreement with observations with a close statistical equivalence with the $\Lambda$CDM and $w$CDM cosmologies at 1-$\sigma$ level. We also show that a mild alleviation of the $\sigma$ tension between the growth amplitude factor and the matter content $(\sigma_8$-$\Omega_m)$ of the observations from CMB and Large Scale Structure (LSS) probes. A comparison of the aforementioned full pack of data in MCMC chains is made with the resulting MCMC from Pantheon SNIa+$H(z)$ in order to analyse the sensitivity of the models and how they respond to a cosmography analysis on the evolution of $H(z)$ and the deceleration parameter $q(z)$. In this sense, we find that only the $\beta$-model can be unaffected to the variations of the previous datasets due to its several minima in the likelihood (degeneracies) of the related parameters with an overall percentage relative difference only up to 4$\%$.

Despite the Hebrides and Cleveland basins being geographically close, research has not previously been carried out to determine faunal similarities and assess the possibility of links between the dinosaur populations. The palaeogeography of both areas during the Middle Jurassic shows that there were no elevated landmasses being eroded to produce conglomeratic material in the basins at that time. The low-lying landscape and connected shorelines may have provided connectivity between the two dinosaur populations. The dinosaur fauna of the Hebrides and Cleveland basins has been assessed based primarily on the abundant ichnites found in both areas as well as their skeletal remains. In the two basins the dinosaur faunas are very similar, consisting of non-neosauropod eusauropods, a possible basal titanosauriform, large and small theropods and ornithopods and europodan thyreophorans. The main difference in the faunas is in the sizes. In the Cleveland Basin the ichnites suggest that there were medium and large theropods alongside small to medium sized ornithopods whereas in the Hebrides Basin the theropods were from small to large and the ornithopods were medium to large. It is suggested that migrations could have taken place between the two areas during the Middle Jurassic. A tentative food chain from the herbivorous dinosaurs to the top predators can be inferred from the footprints.

Typhoid fever is an infectious disease that affects humanity worldwide particularly in the lower socio-economic communities where many individuals are exposed to a dirty environment and unclean food. A mathematical model is formulated to analyze the impact of control measures such as vaccination of susceptible humans, treatment of infected humans and sanitation in the different socio-economic communities. The model assumed that the population comprises of two socio-economic classes. The essential dynamical system analysis of our model was appropriately carried out. The impact of the control measures was analyzed, and the optimal control theory was applied on the control model to explore the impact of the different control measures. Numerical simulation of the models and the optimal controls were carried out and results obtained indicates that the overall combination of the control measures eradicates Typhoid fever in the population but the controls are more optimal in the higher socio-economic communities.

Background: COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global pandemic affecting approximately 490,000 people and accounting for more than 22,000 deaths and has no generally acceptable cure. Here, the recently resolved 3D structure of SARS-CoV-2 receptor binding domain (RBD) in complex with its receptor-the angiotensin converting enzyme-2 (ACE-2) have provided the basis for screening chemical database for novel entry inhibitors. Methods: Molecular docking protocols have been used to rapidly screen FDA database for high affinity interaction at the SARS-CoV-2-RBD/ACE-2 interface. One of the top candidates, ubrogepant has been selected and further studied using atomistic molecular dynamics simulation method. Results: Molecular docking result showed that ubrogepant (UBR) and darunavir have binding energies of -10.4 kcal/mol. MMPBSA free energy analyses of UBR bound to RBD, ACE-2 and RBD/ACE-2 revealed RBD/ACE-2 > ACE-2 > RBD preference. Network analysis showed that interaction captured in the crystal structure were disrupted in UBR-bound state, hydration of the interface and increased atomic fluctuation within the RBD oligomerization interface and ACE-2 zinc binding site. Conclusions: The ability of ubrogepant to rupture the interaction at the RBD/ACE-2 interface residues of SARS-CoV-2 RBD/ACE-2 complex may result in loss of protein function with direct implication on oligomerization formation in RBD and loss of function in ACE-2 thus, making binding, cellular receptor recognition impossible. General Significance: Ubrogepant represents a new therapeutic candidate in the fight against COVID-19, as it binds with relatively high affinity with free RBD, ACE-2 receptor and SARS-CoV-2 RBD/ACE-2 complex based on binding affinity calculations.

Tracking the kinematics of human movement usually requires the use of equipment that constrains the user within a room (e.g., optical motion capture systems), or requires the use of a conspicuous body-worn measurement system (e.g., inertial measurement units (IMUs) attached to each body segment). This paper presents a novel Lie group constrained extended Kalman filter to estimate lower limb kinematics using IMU and inter-IMU distance measurements in a reduced sensor count configuration. The algorithm iterates through the prediction (kinematic equations), measurement (pelvis height assumption/inter-IMU distance measurements, zero velocity update for feet/ankles, flat-floor assumption for feet/ankles, and covariance limiter), and constraint update (formulation of hinged knee joints and ball-and-socket hip joints). The knee and hip joint angle root-mean-square errors in the sagittal plane for straight walking were 7.6±2.6∘ and 6.6±2.7∘, respectively, while the correlation coefficients were 0.95±0.03 and 0.87±0.16, respectively. Furthermore, experiments using simulated inter-IMU distance measurements show that performance improved substantially for dynamic movements, even at large noise levels (σ=0.2 m). However, further validation is recommended with actual distance measurement sensors, such as ultra-wideband ranging sensors.