: This article was not intended to be a complete report of a standard clinical trial. It is a report of the outcomes of preliminary data for validation of the CMECD procedure (Coletti Method of EMG ChemoDenervation) protocol for the treatment of chronic pain resulting from chronic muscle spasm. Methods are here detailed on how to approach the patient with chronic pain, identify the presence of chronic muscle spasm, undertake the treatment protocol and how to perform the follow up process to confirm that chronic pain secondary to chronic muscle spasm was the accurate diagnosis. Furthermore, this article presents the results of a cohort of more than 90 patients treated by the CMECD procedure regarding location and duration of prior pain, prior treatment strategies, degree of success in resolving pain and duration of relief. Outcome data consisting of patient and staff reporting of specific situations in which the chronic pain treatment was successful has been included to help establish the “believability” of outcome successes and to elucidate the potential life altering effects of successful treatment of chronic pain secondary to chronic muscle spasm. This article will hopefully increase the interest in this treatment protocol and increase the chance that a classical international clinical trial will be undertaken.

The Flack Parameter is now almost universally reported for all chiral materials characterized by X-ray crystallography. It’s elegantly simplicity was an inspired development by Flack, and although the original algorithm for its computation has been strengthened by other workers, it remains an essential outcome for any crystallographic structure determination. As with any one-parameter metric, it needs to be interpreted in the context of its standard uncertainty.

Triple-negative breast cancer (TNBC), lacking specific receptors found in other breast cancer subtypes, poses significant treatment challenges due to limited therapeutic options. Therefore, it is necessary to develop novel treatment approaches for TNBC. In the last few decades, many attempts have been reported for alternative tools for TNBC treatment: immunotherapy, radiotherapy, targeted therapy, combination therapy, and nanotechnology-based therapy. Among them, combination therapy and nanotechnology-based therapy show the most promise for TNBC treatment. This review outlines recent advancements in these areas, highlighting the efficacy of combination therapy (immunotherapy paired with chemotherapy, targeted therapy, or radiotherapy) in both preclinical and clinical stages and nanotechnology-based therapies utilizing various nanoparticles loaded with anticancer agents, nucleic acids, immunotherapeutics, or CRISPRs in preclinical stages for TNBC treatment.

Climate change-induced Sea level rise, shoreline changes, and coastal erosion are projected to drive massive population displacement and mobility in Africa. This study was conducted to examine the pattern of shoreline changes, coastal erosion, land use/Land cover dynamics their projections, and its implications on internal migration in Senegal, Kenya and Tanzania representing West and East Africa. The digitized shoreline was mapped into both erosion, accretion and trend analysis which further explains the vulnerability and physical processes that could trigger human displacement within the context of environmental/climate migration. Analysis of landuse and land cover dynamics was obtained from Landsat 5 TM of 1986, Landsat 7 ET of 2006, Landsat 8 OLI/TIRS of 2016 and Landsat 9 OLI/TIRS 2022 and computed using ArcGIS 10.7 for Land-use change and percentage change in square kilometers was conducted to examine landuse/landcover dynamics and their contributions to the risk of coastal erosion in the study regions. The outcome of the shoreline analysis reveals that 972.03sqkm of land has been lost to coastal erosion in Senegal from 1986-2022 with 2016-2022 described as the period with the highest in terms of land loss. In Kenya, -463.30sqkm of land has also been lost to coastal erosion and agents of wave processes with 1986-2006 recording the highest share of -87.74% loss of valuable land while In Tanzania, -1033.35sqkm of valuable land has been lost from 1986-2022 to coastal erosion with 2006-2016 alone recording -10.4634% of land loss. The result of the land use/land cover percentage change analysis indicates a massive loss of vegetation cover with a significant increase in settlement representing urbanization. The scenario modeling of the shoreline on 10,20 and 30ms indicates that 567 persons per sq, 25904.5 persons per sqm and 25904.5 persons per sq km for both 20 and 30ms will be displaced in Senegal while in Kenya 577.5 persons per sq km will be displaced at 10m followed by 1210.3 persons per sq km at 20m and 7737.3 sq km at 30m. In, Tanzania, 702001.9 persons per sq km are projected to be displaced at 10m shift in the shoreline. Structured Questionnaires were administered to elicit responses from coastal dwellers on their perception of coastal erosion and environmental migration as part of ground truthing and the result of the survey affirms that coastal erosion and its exposure are the major drivers of environmental migration in the study area.

This paper explores the relationships between marketing strategies, social media platforms, the adoption and diffusion of products and services, and organizational resilience to gain an understanding of the ability of organizations to cope with disruptive events (e.g., COVID-19). This can be achieved through effective marketing strategies and the efficient use of social media platforms. In fact, resilience thinking can help organizations maintain their operations by increasing the adoption and diffusion of their products and services through the use of effective marketing strategies. To achieve this article’s objectives, a literature review is conducted to help develop a conceptual framework that highlights a clear relationship between the previously discussed concepts. In addition, the novel nature of the relationship between marketing strategies and organizational resilience is dissected and its significance for organizations is demonstrated. In fact, the findings of this study suggest that effective marketing strategies that consider the "what," "who," and "how" dichotomies and the efficient use of social media to promote the adoption and diffusion of products and services can significantly enhance the resilience of organizations. These relationships can serve as a starting point for further studies examining and empirically analyzing marketing strategies and their positive effect on strengthening organizational resilience.

Microelectromechanical System (MEMS) vibrating gyroscope design considerations are always intriguing due to their microscale mechanical, electrical, and material behavior. MEMS vibrating ring gyroscopes have become important inertial sensors in inertial measurement units (IMU) for navigation and sensing applications. The design of a MEMS vibrating ring gyroscope incorporates an oscillating ring structure as a proof mass, reflecting unique design challenges and possibilities. This paper presents a comprehensive design analysis of the MEMS vibrating ring gyroscope from the mechanical, electrical, and damping perspectives. The mechanical design of the MEMS vibrating ring gyroscope investigates the various frame designs of the vibrating ring structure, as well as the various beam structures, including curved, rectangular, and semicircular beam structures, which are analyzed using mathematical models and finite element analysis (FEA) simulations that provide an in-depth analysis of the stiffness and deflection of the vibrating structures. The electrical designs of the MEMS vibrating ring gyroscope were analyzed using various electrode configurations, electrostatic actuation, and capacitive detection mechanisms, respectively. The design analysis of various forms of damping, including viscous, structural, thermoelastic, and anchor damping, has been discussed. The variety of design structures investigated for MEMS vibrating ring gyroscopes' mechanical, electrical, and damping performance.

Atmospheric propagational phase variations are the dominant source of error for InSAR timeseries analysis, generally exceeding uncertainties from poor SNR or signal correlation. The spatial properties of these errors have been well studied, but their temporal dependence and correction have received much less attention to date. We present here an evaluation of the magnitude of tropospheric artifacts in derived time series after compensation using an algorithm that requires only the InSAR data themselves. The level of artifact reduction equals or exceeds that from many weather model based methods, while avoiding the need to access fine-scale atmosphere parameters globally at all times. Our method consists of identifying all points in an InSAR stack with consistently high correlation, and computing, then removing, a fit of the phase at each of these points with respect to elevation. Comparison with GPS truth yields a reduction of 3, from an rms misfit of 5-6 cm to ~2 cm over time. This algorithm can be readily incorporated into InSAR processing flows without need for outside information.

The current paper provides a detailed review of the historical outbreaks of each of the four plague locust species found in South Africa, namely the brown locust, the African migratory locust, the red locust and the southern African desert locust. The history and dynamics of the plague infestations and the major local outbreaks are summarized. The typical patterns of the outbreaks of the different species are described and the threat of these locusts to agriculture in South Africa is defined. The brown locust produces regular outbreaks in the semi-arid Karoo, with large-scale eruptions of plague proportions occurring once or twice per decade. Patterns of outbreaks often repeat themselves, but the sheer size of the plague outbreaks are almost impossible to stop and the brown locust has the potential to threaten food security throughout southern Africa. The African migratory locust produces outbreaks in some of the main maize and wheat cropping areas where it is difficult to control. This locust has taken advantage of the man-made crop environment to produce an extra generation per year that was not previously possible in the original grasslands. The coastal area of KwaZulu Natal in South Africa was a prime reception and breeding area for plague invasions of the red locust in the past and the country therefore relies on the successful control of outbreaks in east and central Africa into prevent the recurrence of the plague invasions. The southern African desert locust occurs in the Kalahari Desert area and outbreaks requiring chemical control are rare.

During the 90 days following hospitalization for acute heart failure, ejection fraction and type of discharge medications have been shown in clinical trials to have little effect on mortality. We examined the recent literature addressing brain-related etiologies of sudden death following heart failure. Two mechanisms of sudden unexpected death have been suggested to possibly result from 4 significant influences on pathophysiology in the brain. The two causes of death are severe cardiac arrhythmia, and neurogenic pulmonary edema. They are both mediated through the brainstem autonomic nuclei generally, and executed specifically through the dorsal motor nucleus of the vagus nerve. The four significant influences on pathophysiology in the brainstem autonomic nuclei are: 1) Hyper-stimulation of neurons in the solitary tract nucleus, increasing their metabolic requirements; 2) Inadequate blood flow at a vascular watershed terminus; 3) Additionally decreased blood flow following vasoconstriction related to relative hyperventilation and decreased pCO2 levels; 4) Gravitational ischemia in the brain—caused by the weight of the brain mass sitting above the brainstem. Changes in head tilt release gravitational ischemia in the brain. There is no specific head position (relative to gravity) that is considered favorable or unfavorable for an extended period of time (i.e. more than 24 hours). Even a small degree of head elevation, used in managing pulmonary congestion, may increase gravitational ischemia in the posterior fossa and brainstem. In this paper we suggest a new and important research avenue for intervening in cardiac arrhythmias, and preventing their occurrence, through the non-invasive use of head-tilting, and other head repositioning maneuvers. This could potentially help many geriatric patients with heart failure, who have decreased mobility in bed, and who tend to stay in one position longer, thereby increasing gravitational ischemia in the brain.

Methylation in the estrogen receptor alpha (ESRα) promoter is an epigenetic abnormality in breast cancer (BCa) and hypermethylation results in the loss of ER expression. We used pyrosequencing to investigate if there is a direct link between P0/P1 promoters of ESRα aberrant methylation and risk of progression of benign tumors to BCa. Results showed a significant elevated level of DNA methylation in ESRα P1 promoter (p = 0.0001) in fibroadenoma than ER-negative BCa tissues, and a 2-fold increased ESRα expression in fibrocystic, and fibroadenoma. In addition, the methylation level of HIN-1 and RASSF1A promoters were elevated in ER-positive when compared to ER-negative BCa (p-value <0.5). ANOVA Mixed Model revealed a significant interaction between RASSF1A with fibroadenoma and ER-positive BCa (p = 0.004). Tumors with unclassified molecular subtype (ER-positive, PR-negative, HER2-negative) had elevated levels of methylation (p = 0.046) in the P0 promoter compared with luminal B (ER-positive, PR-positive, HER2-positive) tumors. Tumors with grade 3 showed a borderline association with ESRα P1 promoter methylation when compared with grade 2 tumors (p = 0.056). These results showed a highly methylated ESRα P0 promoter in the initial stages of breast carcinogenesis while the methylation in the P1 promoter occurs at later stages of BCa with poor prognosis. Therefore, methylation of ESRα promoter and tumor-related genes could serve as potential biomarker for prediction of fibroadenoma that are at elevated risk of progressing to BCa.

Children’s health, development and education cannot be handled separated; they form one process and are profoundly interrelated. This article considers how to ensure children’s physical and mental fitness for school and maintain it once they are there. Rwanda Is a case study of health and development issues which render children unreceptive to education. This is not news to Rwanda’s government, but until recently the donor community was not interested in supporting implementation. The story of Rwanda illustrates the need to think about changes of policy and practice in their context of structures and culture – how they interact and how they are facilitated or constrained by structures and by cultural understandings. To grasp what is going on and for successful implementation of policy, it is necessary to look at situations as a whole and consider human and governmental agency as real influences rather than just consequences of causal mechanisms.

Municipal Solid Waste Management (MSWM) struggles with significant policy and operational challenges, particularly concerning recyclables collection routes and fleet composition. Within the European Union, phasing out traditional fuel-based vocational vehicles, like garbage trucks, in favor of zero-emission alternatives is mandatory to achieve sustainable development objectives. Integrating electric solid waste collection vehicles into municipal fleets presents challenges due to differences in range, capacity, and noise levels. The emission is even more crucial in the systems where recyclables are collected separately, which requires a greater number of trips to be performed. This study addresses MSWM’s strategic aspect by minimizing the total cost of replacing waste collection vehicles while meeting emission constraints. The Fleet Transition Problem (FTP) was formulated and solved using a MARKAL-based approach. The objective of the FTP and a mixed integer linear program used to solve it is minimizing the overall cost of fleet modernization throughout a multi-phase planning horizon so that the sustainable transition of the fleet can be assured. Computational experiments affirmed the model’s effectiveness in strategizing fleet transition. This research outlines a multi-period model for transitioning to a zero-emission fleet and demonstrates the FTP’s potential for strategic decision-making. Notably, the study observes a consistent reduction in permissible emissions across the planning horizon.

Background: COVID-19 vaccines have been linked to myocarditis which in some circumstances can be fatal. This systematic review aims to investigate potential causal links between COVID-19 vaccines and death from myocarditis using post-mortem analysis. Methods: We performed a systematic review of all published autopsy reports involving COVID-19 vaccination-related myocarditis through July 3^rd, 2023. All autopsy studies that include COVID-19 vaccine-induced myocarditis as a possible cause of death were included, without imposing any additional restrictions. Causality in each case was determined by three independent reviewers with cardiac pathology experience and expertise. Results: We initially identified 1,691 studies and, after screening for our inclusion criteria, included 14 papers that contained 28 autopsy cases. The cardiovascular system was the only organ system affected in 26 cases. In 2 cases, myocarditis was characterized as a consequence from multisystem inflammatory syndrome (MIS). The mean and median number of days from last COVID-19 vaccination until death was 6.2 and 3 days, respectively. Most of the deaths occurred within a week from the last injection. We established that all 28 deaths were causally linked to COVID-19 vaccination by independent adjudication. Conclusions: The temporal relationship, internal and external consistency seen among cases in this review with known COVID-19 vaccine-induced myocarditis, its pathobiological mechanisms and related excess death, complemented with autopsy confirmation, independent adjudication, and application of the Bradford Hill criteria to the overall epidemiology of vaccine myocarditis, suggests there is a high likelihood of a causal link between COVID-19 vaccines and death from suspected myocarditis in cases where sudden, unexpected death has occurred in a vaccinated person. Urgent investigation is required for the purpose of risk stratification and mitigation in order to reduce the population occurrence of fatal COVID-19 vaccine-induced myocarditis.

Dirofilaria immitis infection is one of the most severe parasitic diseases of dogs. Prevention is achieved by the administration of drugs containing macrocyclic lactones (MLs). These products are very safe and highly effective, targeting the third and fourth larval stages (L3, L4) of the parasite. Until 2011, claims of ineffectiveness of MLs, reported as “Lack of Efficacy” (LOE), were generally attributed to owners’ non-compliance, or other reason for inadequate preventative coverage. There was solid argumentation that a resistance problem is not likely to occur because of i) the great extent of refugia, ii) the complexity of resistance development to MLs, and iii) the possible big number of genes involved in resistance selection. Nevertheless, today it is unequivocally proven that ML resistant D. immitis strains exist, at least in the Lower Mississippi region, USA. Accordingly, tools have been developed, to evaluate and confirm the susceptibility status of D. immitis strains. A simple, in-clinic, microfilariae suppression test, 14-28 days after ML administration, and a “decision tree” (algorithm), including compliance and preventatives’ purchase history, and testing gaps, may be applied for assessing any resistant nature of the parasite. On the molecular level, specific SNPs may be used as markers of ML resistance, offering a basis for validation of clinically suspected resistant strains. In Europe, no LOE/resistance claims have been reported so far, and the existing conditions (stray dogs, rich wildlife, majority of owned dogs not on preventive MLs treatment) do not favor selection pressure on the parasites. Considering the genetic basis of resistance and the epizootiological characteristics of D. immitis, ML resistance neither establishes easily nor spreads quickly, a fact confirmed by the current known dispersion of the problem, which is limited. Nevertheless, ML resistance may propagate from an initial geographical point, via animal and vector mobility, to other regions, while it can also emerge as an independent evolutionary process in a new area. For these reasons and considering the current chemoprophylaxis recommendations and increasing use of ML endectoparasiticides as a potential selection pressure, it is important to remain vigilant for timely detection of any ML LOE/resistance, in all continents where D. immitis is enzootic.

Abstract:Background: Foot ulcers, especially dorsal foot ulcers caused by straps in footwear, can lead to discomfort, pain, and severe complications, particularly in individuals with diabetes and leprosy. While plantar foot pressure measurements have been extensively studied, research on the impact of strap-induced pressure on the dorsal foot aspect remains limited.Research question: The main research question of this prospective study is: Does the implementation of a rolled inner seam strap design (RIS) in flip-flops result in reduced pressure at the toehold area compared to traditional strap designs (Control) in healthy volunteers?Methods: We studied healthy female volunteers, with 10 feet (5 left and 5 right) per arm of the study. Two types of flip-flops, RIS and Control, were compared in a standardized 5-step walk trial on a hardwood floor. Pressure at the toehold was measured using Pressure Sensitive Switches with portable, accurate, ultra-thin pressure sensors. Paired t-tests compared the maximum pressure at the toehold between RIS and Control flip-flops (p < 0.05).Results: The study revealed a statistically significant difference in pressure at the toehold between the RIS and Control flip-flops (p = 0.0014). The mean difference of -40.90 grams (95% CI: -61.22 to -20.58) indicated that the RIS exerted significantly lower pressure than the Control flip flops. The RIS group had a mean pressure of 29.30 grams. The Control group had a mean pressure of 70.20 grams at the toehold area.Significance: The findings of this study have significant clinical implications for individuals at risk of foot ulcers, particularly those with neuropathic conditions such as diabetes and leprosy. The implementation of the RIS design in flip-flops may offer a practical and cost-effective solution to reduce strap-induced pressure and mitigate the risk of strap-related foot ulcers, especially in resource-limited settings where comprehensive foot care is lacking.

This paper outlines the evolution of a learning technology interface from a Beta version to launch with educators and its alignment to pedagogical theory, designed to maximise collaboration between teacher and student. It explores how the “co-creation” of curricula via textual sources that underpin teaching and learning can be enhanced through interactive e-books and outlines the challenges involved in this praxis. With a number of stakeholders involved in the live use of the platform (including teachers, students, HE educators, course instructors, curriculum designers and software developers), iterative feedback loops informed real-time design improvements to both the interface and the-ory. This collaboration utilised a design-based research (DBR) approach (Wang and Hannafin, 2005), which is outlined here as explanation of how the tool developed and how iterative feedback helped to reconsider the challenges educators face in implementing pedagogical innovation across differing contexts. We propose how speculative design (Lukens and DiSalvo, 2012) and Activity Theory (Engeström, 1987) workshops can methodologically enhance the planning and evaluation phases inherent to DBR approaches, which involve students to prepare for educators’ innovation. Finally, we conclude with how educators can utilise these design principles using stratified approaches to help prepare organisational approaches for innovation.

Autism spectrum disorder (ASD) is a neurodevelopmental disease characterized by persistent deficits in social interaction and communication, repetitive movements, abnormal focusing on objects, or activity that can significantly affect the quality of life of the afflicted. Brain neuronal and glial cells have been implicated. It has a genetic component but can also be triggered by environmental factors or drugs. For example, prenatal exposure to valproic acid (VPA) or acetaminophen (APAP) or ingestion of propionic acid (PPA) can increase the risk of ASD. Recently, epigenetic influences on ASD have been brought to the forefront of investigations on the etiology, prevention, and treatment of this disorder. Epigenetics refers to DNA modifications that alter gene expression without making any changes to the DNA sequence. Although an increasing number of pharmaceuticals and environmental chemicals are being implicated in the etiology of ASD, here we specifically focus on the molecular influence of the above-mentioned drugs on epigenetic alterations in neuronal and glial cells and their potential connection to ASD. It is concluded that a better understanding of these phenomena can lead to more effective interventions in ASD.

A global existential and interlocking environmental, climate and cooperation/equity polycrisis is being faced, which increasingly impacts and is impacted by water and land systems. As a result, transformations in response are gaining increasing traction. Advances in approaches to visualising and communicating how innovations and changes in landscape features enable shifts, transformations and transitions are more crucial than ever before. Visions help focus actions, collaboration and alignment of multiple actors in working towards a common purpose, whilst also entering people’s consciousness at the deep level of values, transforming beliefs and consequently, thinking and action. They give direction on effort and pull on transformational innovation. The evidence-based ‘Water Visions Visualisation Platform’ presents an innovative and accessible way to illustrate, communicate and support future water visioning and strategizing at the landscape scale based on composite paradigms, scenarios, horizons and concepts. Plausible visions of the future are envisioned, illustrated, narratively described and qualitatively assessed, as well as connected with real-world examples and resources through the interactive Platform. This paper outlines the co-creation methodology, the architecture and the co-development of the Platform, as well as a preliminary evaluation through literature-based criteria and the sharing of the Platform with a number of audiences.

Motivated for improving the efficiency and reliability of wind turbine energy conversion, this paper presents an advanced control design that enhances the power regulation efficiency and re-liability. The constrained behaviour of the wind turbine is taken into account, by using the barrier Lyapunov function in the analysis of the Lyapunov direct method. This, consequently, guarantees that the generated power remains within the desired bounds to satisfy the grid power demand. Moreover, a Nussbaum-type function is utilized in the control scheme, to cope with the unpre-dictable wind speed. This eliminates the need for accurate wind speed measurement or estimation. Furthermore, via properly designed adaptive laws, a robust actuator fault-tolerant capability is integrated into the scheme, handling the model uncertainty. Numerical simulations are performed on a high-fidelity wind turbine benchmark model, under different fault scenarios, to verify the effectiveness of the developed design. Also, a Monte-Carlo analysis is exploited for the evaluation of the reliability and robustness characteristics against the model-reality mismatch, measurement errors and disturbance effects.

Huntington’s disease (HD) is a rare but progressive and devastating neurodegenerative disease characterized by involuntary movements, cognitive decline, executive dysfunction, and neuropsychiatric conditions such as anxiety and depression. It follows an autosomal dominant inheritance pattern. Thus, a child who has a parent with the mutated huntingtin (mHTT) gene has a 50% chance of developing the disease. Since HTT protein is involved in many critical cellular processes including neurogenesis, brain development, energy metabolism, transcriptional regulation, synaptic activity, vesicle trafficking, cell signaling, and autophagy, its aberrant aggregates lead to disruption of numerous cellular pathways and neurodegeneration. Essential heavy metals are vital at low concentrations, however, at higher concentrations, can exacerbate HD by disrupting the glial-neuronal communication, and/or causing dysbiosis (disturbance in the gut microbiota, GM), both of which can lead to neuroinflammation and further neurodegeneration. Here, we discuss in detail the interactions of iron, manganese and copper with glial-neuron communication and GM and indicate how this knowledge may pave the way for development of a new generation of disease-modifying therapies in HD.

How does the human neurophysiological system self-organize to achieve optimal phase relationships among joints and limbs, such as in the composite rhythms of butterfly and front crawl swimming, drumming, or dancing? We conducted a systematic review of literature relating to CNS control of phase among joint/limbs in continuous rhythmic activities. SCOPUS and Web of Science were searched using keywords ‘Phase AND Rhythm AND Coordination’. This yielded 998 matches from which 23 papers were extracted for inclusion based on screening criteria. The empirical evidence arising from in-vivo, fictive, in-vitro, and modelling of neural control in humans, other species, and robots indicates that the control of movement is facilitated and simplified by innervating muscle synergies by way of spinal central pattern generators (CPGs). These typically behave like oscillators enabling stable repetition across cycles of movements. This approach provides a foundation to guide the design of empirical research in human swimming and other limb independent activities. For example, future research could be conducted to explore whether the two-layer CPG model proposed by Saltiel et al [1] to explain locomotion in cats might also explain the complex relationships among the cyclical motions in human swimming.

Causation concepts for work-related musculoskeletal disorders vary among authors and academic disciplines. Major causation concepts are single-event and repetitive motion. The aim of this short communication is to share findings from a recent survey, conducted by the U.S. Bureau of Labor Statistics of United States employers about work-related musculoskeletal cases, and more specifically, about whether the employers regard the cause of their employee’s musculoskeletal problem as being from a single exposure or from multiple exposures. Recommendations are offered for using terminology consistent with employer understandings.

mRNA-lipid nanoparticle (LNP) medicinal products can be considered a platform technology because the development process is similar for different diseases and conditions, with similar noncoding mRNA sequences and lipid nanoparticles and essentially unchanged manufacturing and analytical methods utilised often for different products. It is critical not to lose the momentum built using the platform approach during the development, regulatory approval and rollout of vaccines for SARS-CoV-2 and its variants. This Review proposes a set of modifications to existing regulatory requirements for mRNA products, based on a platform perspective for quality, manufacturing, preclinical and clinical data. For the first time, we address development and potential regulatory requirements when the mRNA sequences and LNP composition vary in different products as well. In addition, we propose considerations for self-amplifying mRNA, individualised oncology mRNA products and mRNA therapeutics. Providing a predictable development pathway for academic and commercial groups, so they can know in detail what product characterisation and data are required to develop a dossier for regulatory submission, has many potential benefits. These include reduced development and regulatory costs; faster consumer/patient access and more agile development of products in the face of pandemics; and for rare diseases where alternatives may not exist or to increase survival and the quality of life in cancer patients. Therefore, achieving consensus around platform approaches is both urgent and important. This approach with mRNA can be a template for similar platform frameworks for other therapeutics and vaccines to enable more efficient development and regulatory review.

The concept of spiritual intelligence is currently at the focus of scientific debate. One of the most important problems is if it is a valid intelligence that meets the criteria developed by scholars. In this paper, I look at this idea in the context of Howard Gardner's theory of multiple intelligences and show some evidence from biology, neurology, and other scientific disciplines

The rapid advancement of technology has revolutionized language learning, introducing innovative methods that depart from traditional instructional approaches. This study employs a mixed-methods research design to examine the impact of chatbot-based language learning support, adaptive learning algorithms, and virtual reality language immersion on the language learning proficiency and self-regulated learning skills of English as a Foreign Language (EFL) learners. The research design includes quantitative analysis of language proficiency scores and qualitative exploration of learner experiences with the technological interventions. The theoretical implications of this study are rooted in constructivist and socio-cultural learning theories, which underpin the design and implementation of the technological interventions. The triangulation of qualitative and quantitative data revealed that the participants' positive perceptions of the effectiveness of chatbot-based language learning support were supported by the quantitative results, with the variable "chat-bot based support" demonstrating a substantial mean difference compared to other groups. This convergence of findings reinforces the positive influence of chatbot-based support on language learning outcomes and highlights the importance of integrating theoretical perspectives with empirical evidence to gain a comprehensive understanding of the impact of technological interventions on language learning outcomes for EFL learners. The study's findings provide insights into the potential of these technological interventions to optimize language learning outcomes for EFL learners and promote autonomous learning behaviors.

The benchmarking of hotel energy use comprehensively identifies the controllable and uncontrollable factors affecting energy performance, including building characteristics, management strategies, operations, and maintenance systems. Other factors include climatic conditions, floor areas, operating hours, occupancy rates, and guest populations. A benchmarking study on energy consumption patterns in significant hotels (each with less than 100 rooms and an average staff strength of 40 employees), situated in the university town of Nsukka (longitude 70 23' E, latitude 60 52' N), Nigeria, was performed using the data envelopment analysis (DEA) methodology. DEA, a linear programming technique that measures the relative performances of units, was chosen as a benchmarking methodology due to its ability to handle multiple inputs and outputs. Following a correlation test, energy use intensity, diesel consumption, and the number of employees were selected as the analysis inputs, while the occupancy rate was chosen as the output variable. Data on these variables spanning 12 months were collected using questionnaires, interviews, site visits, and oral conversations with hotel managers to ensure validity. Grid-supplied electricity accounted for most of the hotels' energy needs, followed by diesel used in generators. More than 70% of the electricity use was for HVAC. From the DEA, Hotel 3 (DMU H3) had a technical efficiency score of 1, whereas adjustments were recommended for improving the efficiency scores of the other hotels, which were deemed inefficient. DMU H7 had the lowest efficiency score (0.474) and the highest identified savings for electricity and diesel. The analysis also revealed that occupancy rates were generally low in the months of June and July, coinciding with the high rainfall season with its accompanying decline in outdoor activities. Consistent with this, electricity consumption was highest in the Christmas and Easter holiday months of December, January, and April following increased travel-related activities.

The present paper is aimed at presenting an updated review of prediction methods for the aerodynamic noise of ducted rotor-stator stages. Indeed, ducted rotating-blade technologies are in continuous evolution and increasingly used, for both aeronautical propulsion units, power generation and air conditioning systems. Different needs are faced, from the early design stage to the final definition of a machine. Fast-running, approximate analytical approaches and high-fidelity numerical simulations are considered as the best suited tools for each, respectively. Recent advances are discussed, with emphasis on their pros and cons.

Subjective Cognitive Decline (SCD) is a possible earliest detectable sign of dementia, but we do not know what mental processes lead to elevated concern. We summarize the previous literature on the biomarkers and functional neuroanatomy of SCD. To extend the current most-popular theory of SCD, compensatory hyperactivition, we introduce a new model: breakdown of homeostasis in the prediction error minimization system. A cognitive prediction error is a discrepancy between an implicit cognitive predictions and the corresponding outcome. Experiencing frequent prediction errors may be a primary source of elevated subjective concern. Our homeostasis breakdown model explains the progression both from normal cognition to SCD and from SCD to advanced dementia stages.

In this work we have critically reviewed the processes in high-temperature sublimation growth of graphene in Ar atmosphere using enclosed graphite crucible. Special focus is put on buffer layer formation and free charge carrier properties of monolayer graphene and quasi-freestanding monolayer garphene on 4H-SiC. We show that by introducing Ar at different temperatures, TAr one can shift to higher temperatures the formation of the buffer layer for both n-type and semi-insulating substrates. A scenario explaining the observed suppresed formation of buffer layer at higher TAr is proposed and discussed. Increased TAr is also shown to reduce the sp3 hybridization content and defect densities in the buffer layer on n-type conductive substrates. Growth on semi-insulating substrates results in ordered buffer layer with significantly improved structural properties, for which TAr plays only a minor role. The free charge density and mobility parameters of monolayer graphene and quasi-freestanding monolayer graphene with different TAr and different environmental treatment conditions are determined by contactless terahertz optical Hall effect. An efficient annealing of donors on and near the SiC surface takes place in intrinsic monolayer graphene grown at 2000∘C, and which is found to be independent of TAr. Higher TAr leads to higher free charge carrier mobility parameters in both intrinsically n-type and ambient p-type doped monolayer graphene. TAr is also found to have a profound effect on the free hole parameters of quasi-freestanding monolayer graphene. These findings are discussed in view of interface and buffer layer properties in order to construct a comprehensive picture of high-temperature sublimation growth and provide guidance for growth parameters optimization depending on the targeted graphene application.

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.

Unhealthy diet can lead to the development of metabolic disorders, and studies have shown strong associations between those conditions and biomarkers, such as c-reactive protein (CRP) and adiponectin. Recently, marine algal biomaterials have been investigated extensively due to their health benefits. We report on associations between metabolic markers and bioactive nutrients from diet and Sujiaonori algal biomaterial (SBM), a natural adiponectin modulation inducer (NAMI) containing 60% of ulvan-rich fiber, in a sample of Japanese women. The study comprised dietary survey and intervention conducted in Kochi, Japan (2016-2017), involving 31 women who completed a dietary survey and provided biospecimen for CRP and adiponectin measurement using ELISA. Sixteen women received 3g SBM daily for one month and 15 others (controls) received 3g of corn starch. In SBM group, mean age was 23.06 (2.21) years [vs. 23.06 (1.55)], BMI was 21.11 (0.59) kg/m² [vs. 21.43 (0.60) in controls], and daily intake of n3-PUFA [3.83 (0.24) vs. 2.21 (0.33) mg/day; p=0.042] and total fiber [364.12 (2.45) vs. 48.13 (1.57) mg/day in controls; p=0.000] were markedly higher. Furthermore, CRP was inversely associated with total fiber, total n3-PUFA, SBM-n3PUFA, vitamin D and vitamin B6, whereas adiponectin was strongly and positively associated with SBM-fiber and total n3-PUFA. Thus ulvan-rich SBM supplement, which contains ulvan-rich fiber and n3-PUFA, might be beneficial in reducing metabolic risk.

A study is made of the progressive ‘decoherence’ of cosmic ray extensive air shower particle detector signals in small air showers through measurements of coincidence rates for pairs of detectors versus the detector separation. Measurements are made both when only the two separated detectors themselves trigger in coincidence, and when that coincidence trigger also requires the detection of a local air shower by a small external air shower array. The addition of the explicit air shower trigger ensures that the latter data correspond to showers of a larger particle size, and triggering by very localised shower cores is then unlikely. When including a shower trigger, the decoherence results appear substantially different in form. The coincidence rate between two detectors only can be approximated by a power law variation with separation distance. When triggering involves an air shower array, the variation becomes close to an exponential form with characteristic exponent distances varying systematically with increasing detector and air shower size thresholds. A result is that one can see that small air showers will exhibit clear non-Poissonian density fluctuations near their cores out to distances of ~5m, or at shower energies below ~0.05 PeV. These ideas can be helpful in understanding the statistical properties of signals when using large detectors in air shower arrays.

Major depressive disorder (MDD) and substance use disorder (SUD) are of immense medical and social concerns. Although significant progress on neuronal involvement in mood and reward circuitries has been achieved, only relatively recently the role of glia in these disorders have attracted attention. Detail understanding of the glial function in these devastating diseases could offer novel interventions. Here, following a brief review of circuitries involved in mood regulation and reward perception, specific contribution of the neurotrophic factors, neuroinflammation and gut microbiota to these diseases are highlighted. In this context, the role of specific glial cells (e.g., microglia, astroglia, oligodendrocytes and synantocytes) on phenotypic manifestation of MDD or SUD are emphasized. In addition, potential use of this knowledge in developing novel therapeutics is touched upon.

Lunar seismology is a critical area of research, providing insights into the Moon's internal structure, composition, and thermal history, as well as informing the design of safe and resilient habitats for future human settlements. This paper presents the development of a state-of-the-art, three-axis broadband seismometer with a low frequency range of 0.001-1 Hz and a target sensitivity over an order of magnitude greater than previous Apollo-era instruments. The paper details the design, assembly, methodology and test results. We compare the acceleration noise of our prototype and commercial seismometers across all three axes. Increasing the test mass and reducing its natural frequency may further improve performance. These advancements in seismometer technology hold promise for enhancing our understanding of the Moon's and other celestial bodies' internal structures, and for informing the design of future landed missions to ocean worlds.

Unhealthy diet can lead to the development of metabolic disorders, and studies have shown strong associations between those conditions, c-reactive protein (CRP) and adiponectin. We report on associations between targeted metabolic markers and active nutrients from diet and Sujiaonori algal supplement (SBM), a natural adiponectin modulation inducer (NAMI) containing 60% of bioactive ulvan-rich fiber, in Japanese women. The study comprised dietary survey and intervention conducted in Kochi, Japan (2016-2017), involving 31 women who completed a dietary survey and provided biospecimen for CRP and adiponectin measurement using ELISA. Sixteen women received 3g SBM daily for one month and 15 others (controls) received 3g of corn starch. In SBM group, mean age was 23.06 (2.21) years [vs. 23.06 (1.55)], BMI was 21.11 (0.59) kg/m2 [vs. 21.43 (0.60) in controls], and daily intake of n3-PUFA [3.83 (0.24) vs. 2.21 (0.33) mg/day; p=0.042] and total fiber [364.12 (2.45) vs. 48.13 (1.57) mg/day in controls; p=0.000] were markedly higher. Furthermore, CRP was inversely associated with total fiber, total n3-PUFA, SBM-n3PUFA, vitamin D and vitamin B6, whereas adiponectin was strongly and positively associated with SBM-fiber and total n3-PUFA. Thus ulvan-rich SBM supplement, which contains ulvan-rich fiber and n3-PUFA, might be beneficial in reducing metabolic risk.

Lithium-ion batteries are key elements in the development of electrical energy storage solutions. However, due to cycling, environmental and operating conditions, battery capacity tends to degrade over time. Capacity fade is a common indicator of battery state of health (SOH) because it is an indication of how capacity has been degraded. However, battery capacity cannot be measured directly, so there is an urgent need to develop methods for estimating battery capacity in real time. By analyzing the historical data of a battery in detail, it is possible to predict the future state of the battery and forecast its remaining useful life. This paper develops a real-time, simple and fast method to estimate the cycle capacity of a battery during the charge cycle using only data from a short period of each charge cycle. This proposal is attractive because it does not require data from the entire charge period, since batteries are rarely charged from zero to full. The proposed method allows simultaneous and accurate real-time prediction of the health and remaining useful life of the battery over its lifetime. The accuracy of the proposed method has been tested using experimental data from several lithium-ion batteries with different cathode chemistries under various test conditions.

The topic of technology development and its disruptive effects has been the subject of much debate over the last 20 years with numerous theories at both macro and micro scale offering potential models of technology progression and disruption. This paper focuses on how the potential theories of technology progression can be integrated and considers whether suitable indicators of this progression and any subsequent disruptive effects (particularly considering these geographically) might be derived, based on the use of big data analytic techniques. Given the magnitude of the economic, social and political implications of many disruptive technologies, the ability to quantify disruptive change at the earliest possible stage could deliver major returns by reducing uncertainty, assisting public policy intervention and managing the technology transition through disruption into deployment. However, determining when this stage has been reached is problematic because small random effects in the timing, direction of development, the availability of essential supportive technologies or “platform” technologies, market response or government policy can all result in failure of a technology, its form of adoption or optimality of implementation. This paper reviews some of the key models of technology evolution and their disruptive effect including, in particular, the geographical spread of disruption. It suggests a methodology for utilising the recent explosion of open and web-discoverable data to determine a methodology to achieve this earlier determination and considers the potential exploitation of big data modelling and predictive analytical techniques to achieve this goal.

Introduction: The goals of this retrospective cohort study of 129,443 persons admitted to Calgary acute care hospitals 2013-2021 were to ascertain correlations of “potentially inappropriate medi-cations” (PIMs), “potential prescribing omissions” (PPOs) and other risk factors with readmissions and mortality. Methods: Processing and analysis codes were built in Oracle Database 19c (PL/SQL), R and Excel. Results: The percentage dying during their hospital stay rose from 3.03% during the first to 7.2% during the 6th admission. The percentage dying within 6 months of discharge rose from 9.4% after the first to 24.9 after the sixth admission. Odds ratios (adjusted for age, gender and comorbidities) for readmission were the post-admission number of medications (1.16; 1.12-1.12), STOPP PIMs (1.16; 1.15-1.16); AGS Beers PIMs (1.11; 1.11-1.11) and START omissions not corrected with a prescription (1.39 (1.35-1.42). Odds ratios for mortality were post-admission number of medications (1.04; 1.04-1.05), STOPP PIMs (0.99; 0.96-1.00); AGS Beers PIMs (1.08; 1.07-1.08) and START omissions not corrected with a prescription (1.56 (1.50-1.63). START omissions corrected with a prescription correlated with a dramatic reduction in mortality (0.51; 0.49-0.53). Odds ratios for readmissions for the second through 39th admission were consistently higher if START PPOs were not corrected for the second admission (1.41; 1.36-1.46), third (1.41;1.35-1.48); fourth 1.35;1.28-1.44); fifth 1.38; 1.28-1.49); sixth (1.47;1.34-1.62) and 7th through 39th admission (1.23; 1.14-1.34). For all admissions when a pre-scription was given to correct START PPOs ORs for mortality within six months of discharge were dramatically improved (0.51; 0.49-0.53). This was also true for the second (0.52; 0.50-0.55; fourth (0.56; 0.52-0.61; fifth (0.63; 0.57-0.68); sixth (0.68; 0.61-0.76); and 7th through 39th admissions (0.71; 0.65-0.78). Conclusions: PPOs should be corrected by prescriptions and teams of family physicians, pharmacists and nurses should focus on patients’ understanding of their illnesses, medications and ability for self-care.

Heat-treated aluminum-silicon (Al-Si)-based alloys have dominated the cast lightweight alloy industry for several decades. However, in the last decade, Al-Ce-based alloys have shown promise in replacing Al-Si alloys due to their ability to remove the need for costly heat treatments. Since the properties of Al-Ce alloys depend on the as-cast microstructure, it is important to characterize the solidification kinetics of these alloys. Therefore, this study focused on characterizing the solidification of a near eutectic Al-Ce alloy with additions of Ni and Mn. The alloy was cast in a wedge mold configuration, resulting in cooling rates between 0.18 and 14.27 °C/s. SEM coupled with EDS and DSC techniques characterized the evolution rate of solid phases. The SEM/EDS data revealed that an Al10CeMn2 phase is present at higher cooling rates. At lower cooling rates, near the center of the casting, a proeutectic Al23Ce4Ni6 phase was more present. It was observed that up to 2.6 at. % of Mn was dissolved in this proeutectic Al23Ce4Ni6 phase, thereby removing a large portion of the available Mn for forming the Al10CeMn2 phase. DSC analysis showed differences in the samples' liquidus temperatures which is indicative of compositional variations. Inductively coupled plasma atomic emission spectroscopy (ICP-OES) and Scheil solidification simulations correlated the compositional differences to phase formation, which agreed with the SEM and DSC results. This experimentation provides insight into novel Al-Ce-Ni-Mn alloys and where their potential lies in industrial applications.

Recent satellite measurements of glacier mass balance show mountain glaciers all over the world had generally negative mass balances in the first decades of the 21st century. Mean summer temperatures all over the world rose from 1961-90 to 1991-2020, implying increasingly negative mass balances. We study archived annual balances for 38 Northern Hemisphere glaciers to assess changes within in the 19612020 period. We use a modified doublemass curve to visualize mass balance changes occurring around 1990. Mean balances 196190 were already small negative for many of the studied glaciers and became even more negative in 19912020 for glaciers in the Alps, at high latitudes and in western North America. The largest mass balance changes are for some glaciers in the Alps. We are unable to explain the lack of change in mean balance for one glacier in High Mountain Asia. We find complex changes for eight glaciers in Scandinavia, even including one glacier with positive balance. We explain these changes by visualizing deviations of winter and summer balances from their respective 1961-90 mean values. High winter balances in the 1990s for Scandinavia partly obscured the emerging trend of increasingly negative summer balances, which we expect to continue in the future.

Animals are distinguished by their complex developmental programs, in which transcription factors play essential roles in coordinating the regulation of the genome. Thus, it has been hypothesized that animal origins involved the evolution of increasingly complex transcriptional regulatory mechanisms that permit greater spatiotemporal control over gene expression. Here, we revisit this hypothesis in light of new genomic and functional data from diverse phylogenetically-relevant taxa, including early branching animals (sponges, ctenophores) and close relatives of animals (choanoflagellates, filastereans, ichthyosporeans). We argue that many of the mechanisms posited to explain animal transcriptional complexity, such as large increases in transcription factor numbers, new transcription factor families, and distal enhancers, did not factor significantly into animal origins. Instead, we propose that the re-purposing of pre-existing transcriptional regulatory modules through cis-regulatory evolution and gene duplication events, combined with new protein-protein interactions among TFs, may have been fundamental to the transcriptional regulatory architecture of the first animals.

Global anaesthesia workforce limitations contribute to emigration of skilled anaesthesiologists from lower- to higher-income countries, jeopardizing workforce balance and patient outcomes in Pakistan. This study aims to explore challenges experienced by anaesthesiologists in Punjab, Pakistan’s most populous province, and necessary changes to encourage their retention. We conducted a qualitative study to examine perspectives of anaesthesiologists who chose to serve in Pakistan. We drew data from semi-structured interviews conducted with 25 purposively-sampled consultant anaesthesiologists. We analysed data thematically and distinguished the practice hurdles faced by anaesthesiologists in public and private hospitals of Punjab. The main reasons to work abroad could be broadly categorized under two inductive themes, i.e. practice hurdles in public and private sector. Both had distinct issues which compromised the number and quality of anaesthesia workforce in the country. The key outcomes were workplace security, promotion/incentive issues and gender inequalities in the government sector. The private sector had improper salaries and facilities, anaesthesiologist’s dependency on surgeons for getting work and lack of out-of-theatre practice which minimise the scope and earnings of anaesthesiologist within the country. There is a need to overcome surgeon dependency and hospital manipulation by fixing salary percentages for each surgical case and encouraging direct patient-anaesthesiologist relationships.

This paper presents a novel adaptive fault-tolerant neural-based control design for wind turbines with unknown dynamic and unknown wind speed. By utilizing the barrier Lyapunov function in the analysis of the Lyapunov direct method, the constrained behavior of the system is provided in which the rotor speed, its variation and generated power remain in the desired bounds. In addition, input saturation is also considered in terms of smooth pitch actuator bounding. Furthermore, by utilizing a Nussbaum-type function in designing the control algorithm, the unpredictable wind speed variation is captured without requiring accurate wind speed measurement, observation or estimation. Moreover, with the proposed adaptive analytic algorithms, together with the use of radial basis function neural networks, a robust adaptive and fault-tolerant control scheme is developed without the need for precise information about the wind turbine model nor the pitch actuator faults. Additionally, the computational cost of the resultant control law is reduced by utilizing a dynamic surface control technique. The effectiveness of the developed design is verified using theoretical analysis tools and illustrated by numerical simulations on a high-fidelity wind turbine benchmark model with different fault scenarios. Comparison of the achieved results to the ones that can be obtained via an available industrial controller shows the advantages of the proposed scheme.

A hand-held laser-induced breakdown spectroscopy device was used to acquire spectral emission data from laser-induced plasmas created on the surface of cerium-gallium alloy samples with Ga concentrations ranging from 0 to 3 weight percent. Ionic and neutral emission lines of the two constituent elements were then extracted and used to generate calibration curves relating the emission line intensity ratios to the gallium concentration of the alloy. The Ga I 287.4 nm emission line was determined to be superior for the purposes of Ga detection and concentration determination.A limit of detection below 0.25% was achieved using a multivariate regression model of the Ga I287.4 nm line ratio versus two separate Ce II emission lines. This LOD is considered a conservative estimation of technique’s capability given the type of the calibration samples available and low power( 5 mJ per 1 ns pulse) and resolving power (λ/∆λ= 4000) of this handheld device. Nonetheless, the utility of the technique is demonstrated via a detailed mapping analysis of the surface Ga distribution of a Ce-Ga sample which reveals significant heterogeneity resulting from the sample production process.

In this paper, we investigated transducer placement strategies for detecting crack in primary aircraft structures using ultrasonic Structural Health Monitoring (SHM). The approach developed is for an expected damage location based on fracture mechanics, for example fatigue crack growth in a high stress location. To assess the performance of the developed approach, finite-element (FE) modelling of a damage tolerant aluminum fuselage has been performed by introducing an artificial crack at a rivet hole into the structural FE model and assessing its influence on the Lamb wave propagation, compared to a baseline measurement simulation. The efficient practical sensor position was determined from the largest change in area that is covered by reflected and missing wave scatter using an additive color model. Blob detection algorithms were employed in order to determine the boundaries of this area and to calculate the blob centroid. To demonstrate that the technique can be generalized, the results from different crack lengths and from tilted crack are also presented.

Cucumber green mottle mosaic virus (CGMMV) is a re-emerging threat to greenhouse cucumber and other Cucurbitaceae crop productions worldwide. This seed-borne virus can easily spread from a contaminated seed to seedlings and to adjacent plants through mechanical contact of the foliage of diseased and healthy plants causing extensive yield losses. Additionally, infection may not be limited to the current crop but may also affect subsequent crops due to the long-term persistence of the virus on contaminated crop residues, greenhouse hard surfaces and soil or soil-less greenhouse substrates. In the present work, three greenhouse trials were conducted to develop an integrated pest management strategy towards controlling CGMMV in commercial cucumber greenhouses, by implementing an effective sanitization program and using resistant and grafted cucumber varieties. Results of sanitization trial highlighted that pressure washing and cleansing with an alkaline foam cleanser has eliminated CGMMV on some of the most heavily infested areas. However, three successive applications of cleanser and disinfectants were essential to completely eliminate CGMMV on porous and uneven surfaces, such as cement alleyway, tray gutter and floor mats. The varietal trial revealed that out of 15 cucumber varieties evaluated, two Mini (‘Katrina’ and ‘Khassib’) and three Long English (‘Sepire’, ‘Bomber’ and ‘LC13900’) had reduced or delayed CGMMV infection spread in the greenhouse but were intermediate in yield. The varieties ‘Sunniwell’ and ‘Bonbon’ were the most tolerant to CGMMV. They showed a high CGMMV infection level without compromising yield. These results proved the need for new productive cucumber varieties with CGMMV resistance. Grafting experiment showed only yield increase in case of grafted ‘Picowell’ over ‘Bonbon’ and not marked CGMMV resistance, which is a much desirable result when the grafting experiments are evaluated for their economic potential. In all, the current experimental trials unfold unique methodologies on CGMMV management in commercial greenhouses that are recommended to the growers to be followed for reducing crop losses and get benefitted on revenue compromise.

This paper describes developing and analyzing an analytical model of Microelectromechanical Systems (MEMS) internal vibrating ring gyroscope. The internal ring structure consists of eight semicircular beams attached to the externally placed anchors. The paper analyses the vibrating ring gyroscope inplane displacement behavior and the resulting elliptical vibrational modes. The elliptical vibrational modes appear as pairs with the same resonance frequency due to the symmetric nature of the design. The analysis commences by conceptualizing the ring as a geometric structure with a circular shape, possessing specific dimensions such as thickness, height, and radius. We construct a linear model that characterizes the vibrational dynamics of the internal vibrating ring. The analysis encompasses comprehensive mathematical formulations for the radial and tangential displacements in local polar coordinates, considering the inextensional displacement of the ring structure. By utilizing the derived equations, we highlight the underlying relationships driving the vibrational characteristics of the MEMS vibrating ring gyroscope. These dynamic vibrational relationships are essential in enabling the vibrating ring gyroscope's future utilization in accurate navigation and motion sensing technologies.

Globally, habitat fragmentation has increased the proximity between wildlife, humans, and emerging predators such as free-ranging dogs. In these fragmented landscapes, encounters between primates and dogs are escalating, with primates often falling victim to dog attacks while navigating patchy landscapes and fragmented forests. We aim to investigate how these primates deal with the simultaneous threats posed by humans and predators, specifically focusing on the adaptive strategies of Central Himalayan Langur (CHL) in the landscape of fear. To address this, we conducted a behavioral study on the CHL in an agro-forest landscape, studying them for a total of 3912 hours over two consecutive years. Our results indicate that, compared to their most common resting behavior, CHL allocate more time to feeding and locomotion, and less time to socializing in the presence of humans and predatory dogs. Additionally, they exhibit increased feeding and locomotion and reduced social behavior in agro-forest or open habitats. These behavioral patterns reflect adaptive responses to the landscape of fear, where the presence of predators significantly influences their behavior and resource utilization. This study suggests measures to promote coexistence between humans and wildlife through the integration of effective management strategies that incorporate both ecological and social dimensions of human-wildlife interactions.

Introduction Our aim was to determine the impact of antimicrobial stewardship tools (AST) and COVID-19 pandemic on antibiotic consumption (AC). Methods We used the national software Consores to determine AC in DDD / 1000 days of hospitalization from 2017 to 2022 in voluntary private hospitals in France. The AST considered were 1/ internal guidelines 2/ list of antibiotics with restricted access 3/ presence of an antibiotic referent or 4/ an ID specialist 5/ proof of annual meeting on antimicrobial resistance. Institutions with dedicated units for COVID-19 patients were specified. Results In 30 institutions total AC varied from (means) 390 to 405 DDD/1000 DH from 2017 to 2022. Fluoroquinolones and amoxicillin / clavulanate consumption decreased from 50 to 36 (p = 0.003) and from 112 to 77 (p = 0.025) respectively, but consumption of piperacillin / tazobactam increased from 9 to 21 (p < 0.001). Over the study period, 10 institutions with ≤ 2 AST had lower AC compared to 20 institutions with ≥ 3 AST (p < 0.01). COVID-19 units opened in 10 institutions were associated with a trend toward higher macrolide consumption from 15 to 25 from 2017 to 2020 (p = 0.065) and with an acceleration of piperacillin / tazobactam consumption from 2020 to 2022 (p ≤ 0.003). Conclusion Antibiotic consumption in 30 private hospitals in France was inversely related to the number of AST. The COVID-19 pandemic was associated with limited impact on AC but special attention should be paid on piperacillin / tazobactam consumption.

Some contaminants of emerging concern (CECs) are known to survive conventional wastewater treatment plants, which introduce them back to the environment and can potentially cycle up in drinking water supplies. This is especially concerning because of the inherent ability of some CECs to induce physiological effects in humans at very low doses. Advanced oxidation processes (AOPs) such as TiO2 based photocatalysis are of prominent interest for addressing CECs in aqueous environments. Natural water resources often contain dissolved metal cations concentrations in excess of targeted CEC concentrations. These cations may significantly, adversely impact degradation of CECs by scavenging TiO2 surface generated electrons. Consequently, simple pseudo first order or Langmuir-Hinshelwood kinetics are not sufficient for reactor design and process analysis in some scenarios. Rhodamine B dye and dissolved copper cations were studied as reaction surrogates to demonstrate that TiO₂ catalyzed degradation for very dilute solutions is very nearly completely due to homogeneous reaction with hydroxyl radicals and that in this scenario the hole trapping pathway has negligible impact. Chemical reaction kinetic studies were then carried out to develop a robust model for RB/metal reactions that is exact in the electron pathways for hydroxyl radical production and metal scavenging.

This paper proposes an approach to estimate the parameters of an AC-DC boost power factor corrector converter which includes an EMI filter. To this end, once the topology is known, measurements at the input and output terminals of the converter are done to identify the values of the passive elements. The proposed methodology is based on the trust-region nonlinear least squares algorithm to identify the parameters of the converter. The steady-state and the transient signals of the converter at the input/output terminals are acquired non-intrusively without any internal modification of the circuitry. The accuracy of the parameter identification carried out is determined by comparing the estimated values with the actual values provided by the manufacturer, and by contrasting the measured signals with the ones obtained with a simulation model with the estimated values of the parameters. The results presented in this paper prove the accuracy of the proposed approach, which can be extended to other power converters and filters.

While it is well known that 98-99% of the human genome do not encode proteins, but are nevertheless transcriptionally active and give rise to a broad spectrum of noncoding RNAs (ncRNAs) with complex regulatory and structural functions, specific functions have so far been assigned to only a tiny fraction of all known transcripts. On the other hand, the striking observation of an overwhelmingly growing fraction of ncRNAs, in contrast to an only modest increase in the number of protein-coding genes, during evolution from simple organisms to humans, strongly suggests critical but so far essentially unexplored roles of the noncoding genome for human health and disease pathogenesis. Research into the vast realm of the noncoding genome during the past decades thus lead to a profoundly enhanced appreciation of the multi-level complexity of the human genome. Here, we address a few of the many huge remaining knowledge gaps and consider some newly emerging questions and concepts of research. We attempt to provide an up-to-date assessment of recent insights obtained by molecular and cell biological methods, and by the application of systems biology approaches. Specifically, we discuss current data regarding two questions: (1) By which mechanisms could evolutionary recent ncRNAs with critical regulatory functions in a broad spectrum of cell types (neural, immune, cardiovascular) constitute novel thera-peutic targets in human diseases ? (2) Since noncoding genome evolution is causally linked to brain evolution, and given the pro-found interactions between brain and immune system, could human-specific brain-expressed ncRNAs play a direct or indirect (immune-mediated) role in human diseases? Synergistic with the remarkable recent progress regarding delivery, efficacy, and safety of nu-cleic acid-based therapies, the ongoing large-scale exploration of the noncoding genome for human-specific therapeutic targets is encouraging to proceed with the development and clinical evaluation of novel therapeutic pathways suggested by these research fields.

In a hyperconnected society, computer networks play a pivotal role in all activities that permeate our daily lives. In the context of smart cities, theses networks play a pivotal role in enhancing urban efficiency and sustainability. The continuous flow of packets in these networks poses security challenges, from personal data leakage to service unavailability. Anomaly-based methods are commonly used to detect network attacks. In this context, Software-Defined Networking (SDN) emerges as a solution for anomaly detection in network traffic, facilitating comprehensive, real-time analyses and dynamic adaptation to changes. This study aims to present a systematic review of feature selection techniques and evaluate the effectiveness of attribute selection with a multi-class classifier in network anomaly detection. The objective of this paper is to inspire future research and identify trade-offs among these techniques for detecting Denial of Service (DoS) attacks. Based on the findings, the analysis of the entire dataset yields superior results in terms of precision (99%), but using the output of OneR, although resulting in a slight loss of precision compared to the complete dataset, presents the highest precision among other studied techniques, indicating a trade-off between precision and processing time efficiency.

This paper presents the design, modelling, and comparative analysis of two internal MEMS vibrating ring gyroscopes for harsh environmental conditions. The proposed designs investigate the symmetric structure of the vibrating ring gyroscopes that operate at the identical shape of wine glass mode resonance frequencies for both driving and sensing purposes. This approach improves the gyroscope’s sensitivity and precision in rotational motion. The analysis starts with the investigation of the dynamic behaviour of the vibrating ring gyroscope with the detailed derivation of motion equations. A comprehensive evaluation of the design geometry, meshing technology, and simulation results presented on two internal vibrating ring gyroscopes. The two designs are distinguished by their support spring configurations and internal ring structures. Design I comprises eight semicircular support springs and Design II comprises with sixteen semicircular support springs. These designs were modelled and analyzed using finite element analysis (FEA) in Ansys software. The paper further evaluates static and dynamic performance, emphasizing mode matching and temperature stability. The results reveal that Design II, with additional support springs, offers better mode matching, higher resonance frequencies, and better thermal stability compared to Design I. Additionally, electrostatic, modal, and harmonic analyses highlight the gyroscope's behaviour under varying DC voltages and environmental conditions. Furthermore, the study investigates the impact of temperature fluctuations on performance, demonstrating the robustness of the designs within a temperature range of -100°C to 100°C. These research findings suggest that the internal vibrating ring gyroscopes are highly suitable for harsh conditions such as high-temperature applications and space applications.

In Rwanda, more than 90% of the population is insured for health care. Despite the comprehensiveness of health insurance coverage in Rwanda, some health services at partner institutions are not available, causing insured patients to pay unintended cost. We aimed to analyze the effect of health insurance on health care utilization and factors associated with the use of health care services in Rwanda. This is an analysis of secondary data from the Rwanda integrated living condition survey 2016-2017. The survey gathered data from 14580 households, and decision tree and multilevel logistic regression models were applied. Among 14580 households only (20%) used health services. Heads of households aged between [56-65] years (AOR=1.28, 95% CI:1.02-1.61), aged between [66-75] years (AOR=1.52, 95% CI: 1.193-1.947), aged over 76 years (AOR=1.48, 95% CI:1.137-1.947), households with health insurance (AOR=4.57, 95% CI: 3.97-5.27) displayed a significant increase in the use of health services. This study shows evidence of the effect of health insurance on health care utilization in Rwanda: a significant increase of 4.57 times greater adjusted odds of using health services compared to those not insured. The findings from our research will guide policymakers and provide useful insights within the Rwanda context as well as for other countries that are considering moving towards universal health coverage through similar models.

Studies on Medical Geology have up till recently tended to emphasise the harmful effects of geological material and processes. This is perhaps justifiable, given the realisation that many environmental diseases could have causal links with some geo-environmental variables as co-factors, making such studies extremely valuable in the improvement of diagnoses and therapy. However, this review aims to show that in addition to the high value of such research, studies conducted on the beneficial properties of Earth materials also have considerable merit, given their enormous potential for assuaging a wide range of environmental health disorders. For instance, certain geological materials including clay minerals contain active substances that show considerable promise in various applications such as pharmaceutical formulations, aesthetic medicine, and indigenous medicine. This review synthesises current knowledge of how certain geological materials can be exploited in formulating remedies for some human health problems. Reports of the therapeutic uses of clay minerals, zinc oxide (zincite), zeolite, and kaolin are appraised. The review shows that ancient and contemporary use of geological materials such as clay minerals have played crucial roles in the treatment of several human diseases, with recent and ongoing research revealing further development in these applications. Well strategised clinical trials using available resources could give impetus to further research in elucidating the potential of various geomaterials as innovative clinical remedies for some human diseases and infections as well as aid the proper scientific documentation of their natural uses.

The genus Dirphys Howard is synonymized with Encarsia Förster syn. n. and treated as a species-group of Encarsia, referred to henceforth as the Encarsia mexicana species-group. The monophyly of Encarsia is discussed in relation to Dirphys. The new synonymy is based on phylogenetic analyses of the nuclear ribosomal 28S-D2 gene region (43 taxa, 510 bp). The Encarsia mexicana species-group is recovered as strongly monophyletic within Encarsia. All species of the Encarsia mexicana species-group are revised. The group includes six previously described species, and fourteen newly described species. All species are described (or redescribed) and illustrated. Detailed distributional data, and, where available, plant associate and host records are provided for all species. Encarsia myartsevae Kresslein &amp; Polaszek nom. nov. is here proposed as a replacement name for Encarsia mexicana Myartseva, now preoccupied by Encarsia mexicana (Howard). A dichotomous identification key, supplemented by an online multiple-entry key, is provided for all species.

Since the beginning of the COVID-19 pandemic, extensive drug repurposing efforts sought to identify small molecule antivirals with various mechanisms of action. Here we aim to review research progress on small molecule viral entry and fusion inhibitors that directly bind to the SARS CoV-2 Spike protein. Early in the pandemic, numerous small molecules were identified in drug repurposing screens and reported to be effective in vitro SARS CoV-2 viral entry or fusion inhibitors. However, given minimal experimental information regarding the exact location of small molecule binding sites on Spike, it was unclear what the specific mechanism of action was, or where the exact binding sites were on Spike for some inhibitor candidates. The work of countless researchers has yielded great progress, with the identification of many viral entry inhibitors that target elements on the S1 receptor binding domain (RBD) or N-terminal domain (NTD) and disrupt S1 receptor binding function. In this review, we will also focus on highlighting fusion inhibitors that target inhibition of the S2 fusion function, either by disrupting the formation of the postfusion S2 conformation or alternatively by stabilizing structural elements of the prefusion S2 conformation to prevent conformational changes associated with S2 function. We highlight experimentally validated binding sites on the S1/S2 interface and on the S2 subunit. While most mutations to the Spike protein to date in variants of concern (VOCs) have been localized to the S1 subunit, the S2 subunit sequence is more conserved with only a few observed mutations in proximity to S2 binding sites. Several recent small molecules targeting S2 have been shown to have robust activity over numerous recent VOC mutant strains and/or greater broad spectrum antiviral activity for other more distantly related coronaviruses.

The sustainability of agricultural commodities produced in the Southern U.S. under irrigation is increasingly at risk due to erratic rainfall patterns, inadequate water supplies and compromised water quality. This study assessed the needs of crop growers in the United States Department of Agriculture (USDA) Southern Region. The purpose was to identify growers’ critical water resource management concerns to identify research priorities from the perspective of growers in this region. To obtain this information, a questionnaire was developed and distributed to growers throughout the Southern Region in 2020. The final sample included 112 crop (row and specialty) production growers from the Southern Region. Overall, respondents named the water available to irrigate as the greatest water resource management priority. Within all the water availability priorities asked, respondents’ first choice was declining water supply in the future. Declining water supply and the cost of irrigating presently were the next most frequently named water availability priorities. Growers named both increasing the efficiency of irrigation and development of farming practices to improve soil moisture retention as the first and second focus of future irrigation research, respectively. These results will aid in strengthening existing and developing new initiatives for water research and Extension in this region.

NaClO3 and NaBrO3 are believed to form a complete solid solution from RT to fusion. The unique solid phase can thus be written: NaClO3 (1-x)-NaBrO3 (x) with: 0 ≤ x ≤ 1. This study shows that at high temperature this statement might be valid. Nevertheless, up to 50°C and probably up to 160°C and even higher temperature, this is not true when the system is in thermodynamic equilibrium. A large miscibility gap exists at room temperature (RT). This gap could be reduced up to a complete disappearance by fast crystallization, for instance by spray-drying. The necessary conditions to access to equilibrium including homochirality are also discussed.

Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by resting tremor, bradykinesia, rigidity, postural instability, that also includes non-motor symptoms such as mood dysregulation. Dopamine (DA) is the primary neurotransmitter involved in this disease, but cholinergic imbalance has also been implicated. Current intervention in PD is focused on replenishing central DA, which provides remarkable temporary symptomatic relief but does not address the neuronal loss and the progression of the disease. It has been well established that neuronal nicotinic cholinergic receptors (nAChRs) can regulate DA release and that nicotine itself may have neuroprotective effects. Recent studies have identified nAChRs in nonneuronal cell types including glial cells, where they may regulate inflammatory responses. Given the crucial role of neuroinflammation in dopaminergic degeneration, and the involvement of microglia and astrocytes in this response, glial nAChRs may provide a novel therapeutic target in prevention and/or treatment of PD. In this review, following a brief discussion of PD, we focus on the role of glial cells and specifically their nAChRs in PD pathology and/or treatment.

Conservation of natural habitats in human-dominated landscapes is critical for halting biodiversity loss. Maintaining habitat quantity and connectivity requires landscape-level collective action, which results from environmental decisions made by individual land owners. We investigate how individual decision making in a rural collective translates into quantitative differences in landscape-level environmental outcomes. Behavioral science has become a critical domain of knowledge in conservation, but little attention has been paid to how multiple behavioral drivers determine the success of collective environmental action. We developed a social-ecological model for landscape-level conservation using a detailed data set of 600 land owners in New Zealand. With the model, we tested whether the effect of social influence networks on collective conservation action was altered by their interplay with land owners’ personal characteristics, connections to cross-scale actors and local environmental contexts. Interactions between multiple behavioral drivers determined the environmental outcomes of collective action in unexpected ways by modifying, muting or amplifying the effects of single drivers. Importantly, we detected a social-ecological mechanism for rapid change in the extent of protected habitats, which can explain highly successful or failed environmental outcomes of collective conservation. Further, when environmentally desirable and undesirable behaviors spread simultaneously through the social network, homophily and network cohesion hinder desirable environmental outcomes. This effect can be modified by other drivers such as social responses to local environmental change. Thus, understanding how the antagonistic and synergistic effects of behavioral drivers can be best utilized in conservation will benefit biodiversity and ensure benefits that humans obtain from biodiversity.

The etiology of ‘dual harm’ (the co-occurrence of self-harm and externalized violence in the same individual) is under-researched. Risk factors have mostly been investigated for each behavior separately. We aimed to examine adversities experienced between birth and age 15 years among adolescents and young adults with histories of self-harm and violent criminality, with a specific focus on dual harm. Three nested case-control studies were delineated using national interlinked Danish registers; 58,409 cases in total aged 15-35 were identified: 28,956 with a history of violent criminality (but not self-harm), 25,826 with a history of self-harm (but not violent criminality), and 3987 with dual harm history. Each case was matched by date of birth and gender to 20 controls who had not engaged in either behavior. We estimated exposure prevalence for cases vs. controls for each of the three behavior groups, and incidence rate ratios (IRRs). Experiencing 5 or more childhood adversities was more prevalent among individuals with dual harm history (19.3%; 95% CI 18.0, 20.8%) versus self-harm (10.9%; 10.5, 11.3%) and violence (11.4%; 11.0%, 11.8%) histories. The highest IRRs for dual harm were linked with parental unemployment (5.15; 95% CI 4.71, 5.64), parental hospitalization following self-harm (4.91; 4.40, 5.48) or assault (5.90; 5.07, 6.86), and parental violent criminality (6.11; 5.57, 6.70). Growing up in environments that are characterized by poverty, violence and substance misuse, and experiencing multiple adversities in childhood, appear to be especially strongly linked with elevated dual harm risk. These novel findings indicate potential etiologic pathways to dual harm.

This paper presents the development of an analytical model of Microelectromechanical Systems (MEMS) internal vibrating ring gyroscope. The internal ring structure consists of eight semicircular beams that are attached to the externally placed anchors. The research work analyses the vibrating ring gyroscope inplane displacement behavior and the resulting elliptical vibrational modes. The elliptical vibrational modes appear as pairs with the same resonance frequency due to the symmetric structure of the design. The analysis commences by conceptualizing the ring as a geometric structure with a circular shape, possessing specific dimensions such as thickness, height, and radius. We construct a linear model that characterizes the vibrational dynamics of the internal vibrating ring. The analysis develops a comprehensive mathematical formulation for the radial and tangential displacements in local polar coordinates, considering the inextensional displacement of the ring structure. By utilizing the derived motion equations, we highlight the underlying relationships driving the vibrational characteristics of the MEMS vibrating ring gyroscope. These dynamic vibrational relationships are essential in enabling the vibrating ring gyroscope's future utilization in accurate navigation and motion sensing technologies.

There is currently an interest in “active” implantable biomedical devices that include mechanical stimulation as an integral part of their design. This paper reports the experimental use of a porous scaffold made of interconnected networks of slender ferromagnetic fibres that can be actuated in vivo by an external magnetic field applying strains to in-growing cells. Such scaffolds have been previously characterized in terms of their mechanical and cellular responses. In this study, it is shown that the shape changes induced in the scaffolds can be used to promote osteogenesis in vitro. In particular, immunofluorescence, gene and protein analyses reveal that the actuated networks exhibit higher mineralization and extracellular matrix production, and express higher levels of osteocalcin, alkaline phosphatase, collagen type 1a1, runt-related transcription factor 2 and bone morphogenetic protein 2 than the static controls at the 3-week time point. The results suggest that the cells filling the inter-fibre spaces are able to sense and react to the magneto-mechanically induced strains facilitating osteogenic differentiation and maturation. This work provides evidence in support of using this approach to stimulate bone ingrowth around a device implanted in bone and can pave the way for further applications in bone tissue engineering.

Astroviruses (AstVs) are occurs globally and are common causes of gastroenteritis in human and animals. The genetic diversity and epidemiology of AstVs in Africa is not well known, hence, we aimed to genetically characterize astroviruses in asymptomatic smallholder piglets in East Africa. Twenty-four samples randomly selected from 446 piglets (<6 months old), initially collected for rotavirus study, was sequenced for metagenomic analysis. Thirteen (13/24) samples had contigs with high identity to genus Mamastrovirus. Analysis of 7 strains with complete (or near complete) genome revealed variable nucleotide and amino acid sequence identities with known PoAstV strains. The U083 and K321 strains had nucleotide sequence similarities ranging from 66.4 to 75.4 % to the known PoAstV2 strains, nucleotide sequence similarity of U460 strain with known PoAstV3 ranged 57.0 to 65.1 % to the, while K062, K366, K451, and K456 strains showed nucleotide sequence similarities of 63.5 to 80 % to the known PoAstV4 strains. The low sequence identities (<90 %) indicate that novel genotypes of PoAstVs are circulating in the study area. Multiple recombination events were detected in our PoAstV4 strains, indicating that the genetic diversity observed in these strains may be due to recombination. Importantly, we identified potential candidate epitopes with conserved peptides in our PoAstV strains that could aid in the design of immune diagnosis tools and subunit vaccines. Our data provide new intuitions into the genetic structure of porcine astroviruses in East African.

In the past decade, a growing demand for sustainable cosmetic ingredients has yielded numerous biodegradation protocols. While OECD (Organization for Economic Co-operation and Development) aquatic assays are suitable for water-borne chemicals, it is crucial for the personal care industry to consider the persistence of plastics in soil, compost, and municipal sludge. Adopting this cradle-to-grave holistic approach would strengthen product appeal, while increasing the accuracy and ethical integrity of green-product labeling. Our study employs quantitative CO2 detection and thermophilic composting protocols specified in ASTM D5338, along with pass level criteria outlined in ASTM D6400, to assess the mineralization of plastics commonly formulated into personal care products. The results indicate that many cellulose ethers, cationic guars, starches, and labile polyesters demonstrate satisfactory disintegration, biodegradation, and seed germination rates to secure an ASTM D6400 compostability claim. In contrast, macromolecules designed with carbon-carbon backbones resisted acceptable mineralization in composting experiments, suggesting that unadulterated municipal compost lacks the microbial diversity to enzymatically digest many synthetically derived resins. Additionally, polymers that demonstrated acceptable biodegradability in internal and published OECD aquatic studies—including chitosan and polyvinyl alcohol—exhibited limited fragmentation in local municipal compost; hence, untested correlations between aquatic, soil, and compost testing outcomes should never be assumed.

Polycystic ovary syndrome (PCOS) is a prevalent condition characterized by manifestations that can influence self-image and potentially result in psychological distress; however, data from literature on sexual function (SF) in PCOS women are contradictory. We aimed to evaluate sexual dysfunction (SD) in PCOS women by carrying out a systematic review and meta-analysis, using the gold-standard assessment tool SD-diagnosis (Female Sexual Function Index:FSFI). Seven databases were analyzed until August-2023; study quality was assessed by risk of bias and Newcastle Ottawa Scale. Our analysis encompassed 25 case-control studies (9933 women). PCOS group presented significantly lower scores in arousal (MD= -0.36 CI95%-0.60;-0.11), lubrication (MD= -0.52 CI95%-0.75;-0.28), orgasm (MD= -0.39 CI95%-0.57;-0.20), satisfaction (MD= -0.32 CI95%-0.50;-0.14) and pain subdomains (MD= -0.46 CI95%-0.75;-0.16), as in overall FSFI score (MD= -2.27 CI95%-3.23;-1.31). Overweight/obese (OW/O) patients exhibited significantly higher overall FSFI than OW/O controls (MD=1.98 CI95%0.68;3.27), particularly in lubrication (MD= -0.34), orgasm (MD= -0.26) and satisfaction (MD= -0.25) subdomains. These findings offer insights regarding SD in PCOS women and emphasize the need to incorporate SF assessment into multidisciplinary care. By this way, PCOS can be also considered a gateway diagnosis to other long-term consequences. Further research should focus on controlling variables, as ethnicity, culture, religion and economic disparities.

The GLUT members belong to a family of glucose transporter proteins that facilitate glucose transport across the cell membrane. The mammalian GLUT family consists of thirteen members (GLUTs 1-12 and HMIT). Humans have a recently duplicated GLUT member, GLUT14. Avians express the majority of GLUT members. The arrangement of multiple GLUTs across all somatic tissues signifies the important role of glucose across all organisms. Defects in glucose transport have been linked to metabolic disorders, insulin resistance and diabetes. Despite the essential importance of these transporters, our knowledge regarding GLUT members in avians is fragmented. It has been clear that there are no chicken orthologs of mammalian GLUT4 and GLUT7. Our examination of GLUT members in the chicken revealed that some chicken GLUT members do not have corresponding orthologs in mammals. We review the information regarding GLUT orthologs and their function and expression in mammals and birds, with emphasis on chickens and humans.

Lithium-ion batteries serve as the primary sources of power for electric vehicles (EVs) and hybrid electric vehicles (HEVs). For vehicle applications, battery management systems (BMSs) are nec-essary to protect lithium-ion batteries from overheating and to ensure optimum vehicle perfor-mance. Our approach to developing a BMS was based on recent advances in the application of phase field models for lithium-ion batteries. In particular, our reduced-order model (ROM) uti-lized a dataset generated from the COMSOL® Multiphysics simulation of the Cahn–Hilliard equation for a single particle of a lithium iron phosphate (LiFePO4) cathode: an example of using a reduced-order model (ROM) based on a single-particle model (SPM). The main innovation of our ROM is that the SPM is fully coupled to a heat transfer model at the battery cell level. We utilized principal component analysis to identify a lower-order model that could reproduce the battery’s voltage and temperature response for ambient temperatures ranging from 253 to 298 K and for discharge rates ranging from 1 C to 20.5 C. The reduced-order dataset was then fitted to the ex-perimental data for an A123 Systems 26650 2.3 Ah cylindrical battery using deep neural network (DNN) regression.

Photoacoustic imaging is attracting a great deal of interest owing to its distinct advantages over other imaging techniques such as fluorescence or magnetic resonance image. Availability of photoacoustic probes for reactive oxygen and nitrogen species (ROS/RNS) could shed light on a plethora of biological processes mediated by these key intermediates. Tetramethylbenzidine (TMB) is a non-toxic and non-mutagenic colorless dye that develops a distinctive blue color upon oxidation. In this work we have investigated the potential of TMB as photoacoustic probe for ROS/RNS. Our results indicate that TMB reacts with hypochlorite, hydrogen peroxide, singlet oxygen and nitrogen dioxide to produce the blue oxidation product, while ROS such as the superoxide radical anion, sodium peroxide, hydroxyl radical or peroxynitrite yield a colorless oxidation product. TMB does not penetrate Escherichia coli cytoplasm but is capable of detecting singlet oxygen generated in its outer membrane.

Most striking observations in COVID-19 patients are the hints on pulmonary edema (also seen on CT scans as ground glass opacities), dry cough, fluid restrictions to prevent more severe hypoxia, the huge PEEP that is needed while lungs are compliant, and the fact that anti-inflammatory therapies are not powerful enough to counter the severity of the disease. We propose that the severity of the disease and many deaths are due to a local vascular problem due to activation of B1 receptors on endothelial cells in the lungs. SARS-CoV-2 enters the cell via ACE2, a cell membrane bound molecule with enzymatic activity that next to its role in RAS is needed to inactivate des-Arg⁹ bradykinin, the potent ligand of the bradykinin receptor type 1 (B1). In contrast to bradykinin receptor 2 (B2), the B1 receptor on endothelial cells is upregulated by proinflammatory cytokines. Without ACE2 acting as a guardian to inactivate the ligands of B1, the lung environment is prone for local vascular leakage leading to angioedema. Angioedema is likely a feature already early in disease, and might explain the typical CT scans and the feeling of people that they drown. In some patients, this is followed by a clinical worsening of disease around day 9 due to the formation antibodies directed against the spike (S)-antigen of the corona-virus that binds to ACE2 that could contribute to disease by enhancement of local immune cell influx and proinflammatory cytokines leading to damage. In parallel, inflammation induces more B1 expression, and possibly via antibody-dependent enhancement of viral infection leading to continued ACE2 dysfunction in the lung because of persistence of the virus. In this viewpoint we propose that a bradykinin-dependent local lung angioedema via B1 and B2 receptors is an important feature of COVID-19, resulting in a very high number of ICU admissions. We propose that blocking the B1 and B2 receptors might have an ameliorating effect on disease caused by COVID-19. This kinin-dependent pulmonary edema is resistant to corticosteroids or adrenaline and should be targeted as long as the virus is present. In addition, this pathway might indirectly be responsive to anti-inflammatory agents or neutralizing strategies for the anti-S-antibody induced effects, but by itself is likely to be insufficient to reverse all the pulmonary edema. Moreover, we provide a suggestion of how to ventilate in the ICU in the context of this hypothesis.

RLF-100 (Aviptadil), a synthetic form of Vasoactive Intestinal Peptide (VIP) is shown to block replication of the SARS-CoV-2 virus and has been granted Fast Track Designation by the US FDA for the treatment of Critical COVID-19 with Respiratory Failure. We describe the clinical course of the first patient treated with this investigational medication in an open label manner -- a 54 year old patient suffering antibody-mediated rejection of his double lung transplant who contracted COVID-19 with respiratory failure refractory to all currently available therapies. He received three infusions of RLF-100 under an FDA-approved emergency use IND. Within 24 hours of the third infusion, substantial improvement in oxygen saturation and radiographic improvement in characteristic COVID-19 pneumonitis was noted. He was discharged from intensive care at that point and scheduled for discharge to home at 1 week on room air. Despite an intervening hospitalization for trauma, he remains alive and free of respiratory failure at 28 days post treatment.

In radiotherapy, accurate deposition of energy to the targeted volume is vital to ensure effective treatment. Gel dosimeters are attractive detection systems, as tissue substitutes with potential to yield three-dimensional dose distributions. Radio-fluorogenesis is creation fluorescent chemical products in response to energy deposition from high-energy radiation. This report shares studies of a radio-fluorogenic gel dosimetry system, gelatin with coumarin-3-carboxlyic acid (C3CA), for the quantification of imparted energy. Aqueous solutions exposed to ionizing radiation result in the production of hydroxyl free radicals through water radiolysis. Interactions between hydroxyl free radicals and coumarin-3-carboxylic acid produce a fluorescent product. 7-hydroxy-coumarin-3-carboxylic acid has a blue (445 nm) emission, following UV to near UV (365–405 nm) excitation. Effects of C3CA concentration and pH buffers were investigated for this system. The response of the system was explored with respect to strength, type, and exposure rate of high-energy radiation. Results show a linear dose response relationship with a dose-rate dependency and no energy or type dependencies. This report supports the utility of gelatin-C3CA for phantom studies of radio-fluorogenic processes.

Intracellular aggregates of the alpha-synuclein protein result in cell loss and dysfunction in Parkinson’s disease and atypical parkinsonism, such as multiple system atrophy and dementia with Lewy bodies. Each of these neurodegenerative conditions, known collectively as alpha-synucleinopathies, may be characterized by a different suite of molecular triggers that initiate pathogenesis. The mechanisms whereby alpha-synuclein aggregates in turn mediate cytotoxicity also remain to be fully elucidated. However, recent studies have implicated the cell-to-cell spread of alpha-synuclein as the major mode of disease propagation between brain regions during disease progression. Here, we review the current evidence for different modes of alpha-synuclein cellular release, movement and uptake, including exocytosis, exosomes, tunnelling nanotubes, glymphatic flow and endocytosis. A more detailed understanding of the major modes by which alpha-synuclein pathology spreads throughout the brain may provide new targets for therapies that halt the progression of disease.

Crimean-Congo haemorrhagic fever virus (CCHFV) is the most geographically widespread tick-borne virus. However, African strains are poorly represented in sequence databases. In addition, almost all sequence data have been obtained from cases of human disease, while information regarding circulation of the virus in tick and animal reservoirs is severely lacking. Here, we characterise the complete coding region of a novel CCHFV strain, detected in African blue ticks (Rhipicephalus (Boophilus) decoloratus) feeding on cattle in an abattoir in Kampala, Uganda. These cattle originated from a farm in Mbarara, a major cattle-trading hub for much of Uganda. Phylogenetic analysis indicates that the newly sequenced strain belongs to the African genotype II clade, which predominantly contains the sequences of strains isolated from West Africa in the 1950’s and South Africa in the 1980’s. Whilst, the viral S (nucleoprotein) and L (RNA polymerase) genome segments shared >90% nucleotide similarity with previously reported genotype II strains, the glycoprotein-coding M segment shared only 80% nucleotide similarity with the next most closely related strains, which were from India and China. This segment also displayed a large number of non-synonymous mutations previously unreported in genotype II strains. Characterisation of this novel strain adds to our limited understanding of the natural diversity of CCHFV circulating in both ticks and in Africa. Such data can be used to inform the design of vaccines and diagnostics, as well as studies exploring the epidemiology and evolution of the virus for the establishment of future CCHFV control strategies.

Background:Malignant pleural effusion (MPE),a frequent complication of advanced malignancies. This pilot study characterized and compared the immune landscapes of breast carcinoma (BC) and lung adenocarcinoma (LADC) primary tumors(PTs) and their corresponding MPEs and tested the incorporation of multiplexed image technology for the study of malignant fluids. Methods: We studied the immune contexture of 6 BC and 5 LADC PT samples and their MPEs using 3 multiplex immunofluorescence panels. We explored associations between sample characteristics and pleural effusion–free survival. Results: Although we found 3 out of 11 PTs PD-L1 positive more than 1% by malignant cells, no MPE samples reached positive expression by malignant cells. In addition, CD3+ T cells and CD3+CD8+ cytotoxic T cells predominated (median percentages for MPEs vs. PTs: 45.5% vs. 40.7% and 4.7% vs. 6.6%, respectively). In the BC samples, CD68+ macrophages predominated (median percentages for MPEs vs. PTs:61% vs. 57.1%). Generally, CD3+CD8+FOXP3+ T cells in PTs and the distances from the malignant cells to CD3+CD8+Ki67+ and CD3+PD-1+ T cells were correlated in the first event of MPE after diagnosis. Conclusions: The immune cell phenotypes in the MPEs and PTs were similar within each cancer type but were different for LADC vs. BC.MPE analysis could be used as a substitute for PT analysis, but an expanded study on this topic is essential.

Recent events concerning jet fuel contamination of drinking water have shown that we need a better understanding of the effects of ingested jet fuel. To this end, a reproductive study with in-gested jet fuel in rats was undertaken with relatively high concentrations of Jet Propellant (JP)-5 along with a human estrogen receptor activation in vitro assay using JP-5, JP-8, and an alternative jet fuel derived from the camelina plant to help evaluate potential effects of ingested jet fuel. Results of the in vivo study provided evidence that JP-5 can act as an endocrine disruptor, with specific observations including altered hormone levels with JP-5 exposure (significantly lower estradiol levels in male rats and significantly increased Dehydroepiandrosterone levels in females), indi-cations of abnormal estrous cycles, and a decreased male/female offspring ratio. The in vitro hormone receptor activation assay indicated JP-5 and JP-8 are capable of upregulating human estrogen receptor (ER) activity, while the alternative jet fuel derived from the camelina plant was not active in the ER assay. The jet fuels were not able to activate androgen or glucocorticoid re-ceptors in further in vitro assays. These results infer potential endocrine disruption associated with JP-5, with activation of the estrogen receptor as one potential mechanism of action.

Drowsiness detection is an important task in road safety and other areas that require sustained attention. In this article, an approach to detect drowsiness in drivers is presented, focusing on the eye region, since eye fatigue is one of the first symptoms of drowsiness. The method used for the extraction of the eye region is Mediapipe, chosen for its high accuracy and robustness. Three neural networks were analyzed based on: InceptionV3, VGG16 and ResNet50V2 that implement deep learning. The database used is NITYMED, which contains videos of drivers with different levels of drowsiness. The three networks were evaluated in terms of accuracy, precision and recall in detecting drowsiness in the eye region. The results of the study show that all three convolutional neural networks have high accuracy in detecting drowsiness in the eye region. In particular, the Resnet50V2 network achieved the highest accuracy, with a rate of 99.71% on average. For better visualization of the data, the Grad-CAM technique is used, with which we get a better understanding of the performance of the algorithms in the classification process.

We demonstrate a compact 4x4 wavelength selective switch with 50 % fewer electrical pads as compared with our previous generation. We report loss and crosstalk for different paths of the switch. We measure median loss of 5.32 dB and worst case crosstalk of -35 dB. The microring resonators tune by more than one free spectral range, which is an improvement over our previous generation of switches. This switch can support 8 channels at 400 GHz spacing. We conclude that it is not possible to drive both microring resonators with the same voltage and separate control is required because of fabrication variation of the current technology.

Karst aquifers show dissolution/precipitation processes of the minerals present in the carbonate rocks. The Ring of Cenotes (RC) extends along the edge of the Chicxulub crater, in the limestone platform of the Yucatan Peninsula (YP), where groundwater shows preferential flow paths toward the coast near Celestun and Dzilam Bravo towns. This study aimed to describe the regional hydrogeochemical evolution of groundwater of the RC, and its association with the dissolution/precipitation of the minerals present along its path to the ocean. To achieve this aim, we: a) characterized groundwater's hydrogeochemistry; b) determined the calcite, dolomite, and gypsum saturation indexes (reaction phases with the groundwater) in the study area; c) proposed a hydrogeochemical model developed through PHREEQC using an inverse modelling approach. The model predictions confirmed that there are two evolution pathways of the groundwater consistent with the preferential flow paths suggested in a previous regionalization of the RC. On the western path, where groundwater flows towards Celestun, an important marine intrusion influences the hydrogeochemical processes and represents a risk for the prevalence of freshwater. On the eastern path, where groundwater flows toward Dzilam Bravo, the hydrogeochemistry in the sinkholes correlates well with rainfall, suggesting a higher vulnerability during droughts than during rainy periods.

There was no significant difference in bacterial adhesion between the 3 bone graft types tested, regardless of the bacterial strain used (p &gt; 0.22). After 72 hours of culture, there was no significant difference between the Fresh and Frozen bone groups, while the number of CFU in the Decellularised group was significantly lower (p &lt; 0.01), averaging -0.72 +/- 0.08 lg, -0.20 +/- 0.01 lg and -0.78 +/- 0.48 lg with S. epidermidis, S. aureus and E. coli respectively. Absolute values differences are low, and considering fresh bone (equivalent to autograft) as the gold standard due to its low infection rates in clinical studies, we can conclude that adhesion and biolfilm development characteristics are similar between Fresh, Frozen and Decellularised bone grafts..

Risk management of electric power transmission lines requires knowledge from different areas such as environment, land, investors, regulations, and engineering. Despite the widespread availability of databases for most of those areas, integrating them into a single database or model is a challenging problem. Instead, in this paper, we use a single source, the Brazilian National Electric Energy Agency’s (ANEEL) weekly reports, which contains decisions about the electrical grid, comprising most of the areas. Since the data is unstructured (text), we employed NLP techniques such as stemming and tokenization to identify keywords related to common causes of risks provided by an expert group on energy transmission. Then, we used models to estimate the probability of each risk. Our results show that we were able to estimate the probability of 97 risks out of 233.

Direct assessments of executive function (EF) are increasingly used in research and clinical settings, with a central assumption that they assess “universal” underlying skills. Their use is spreading globally, raising questions about the cultural appropriateness of assessments devised in Western, industrialized countries. We reviewed multidisciplinary evidence and theory to identify sets of cultural preferences that may be at odds with the implicit assumptions of EF assessments. These preferences relate to motivation and compliance; cultural expectations for interpersonal engagement; contextualized vs. academic thinking; cultural notions of speed and time; the willingness to be silly, be incorrect, or do the opposite; and subject-matter familiarity. In each case, we discuss how the cultural preference may be incompatible with the assumptions of assessments, and how future research and practice can address the issue. Many of the cultural preferences discussed differ between interdependent and independent cultures and between schooled and unschooled populations. Adapting testing protocols to these cultural preferences in different contexts will be important for expanding our scientific understanding of EF from the narrow slice of the human population that has participated in the research to date.

Long-acting (LA) drug-delivery system (DDS) successes are linked to their abilities to harness biocompatible polymers and materials for sustained and predictable release of therapeutic agents over an extended period of time. For human immune deficiency virus type one (HIV-1) infections, LA DDSs hold great promise in closing the gaps of daily oral therapy for treatment and prevention. Examples are Cabenuva, Apretude and Sunlenca, which have been shown to be safe and effective. Alternative promising drug delivery technologies such as implants, prodrugs, vaginal rings, and microarray patches are being explored to further meet patients’ needs. We posit that improved physicochemical properties of the formulation payloads and material chemistry design with optimal drug release kinetics holds the potential to optimize release profiles. Furthermore, for the treatment and prevention of HIV-1 infection, the landscape of LA medicines now in clinical or preclinical development offers hope that the strategic design of polymers will further improve upon controlled delivery of drugs to simplify dosing schedules.

Co-delivery of antigens and adjuvants to the same antigen presenting cells (APCs) can significantly improve the efficacy and safety profiles of vaccines. Here, we report amine-grafted silica nanoparticles (A-SNPs) as a tunable vaccine co-delivery platform for TLR7/8 agonists along with the recombinant influenza antigen hemagglutinin H7 (H7) to APCs. A-SNPs of two different sizes (50 and 200 nm) were prepared and coated with INI-4001 at different coating densities, followed by co-adsorption of H7. Both INI-4001 and H7 showed &gt; 90% adsorption to the tested A-SNP formulations. TNF-α and IFN-α cytokine release by human peripheral blood mononuclear cells as well as TNF-α, IL-6, and IL-12 release by mouse bone marrow-derived dendritic cells revealed that the potency of the INI-4001-adsorbed A-SNPs (INI-4001/A-SNP) formulations can be improved relative to aqueous formulation control. This improved potency was dependent on particle size and ligand coating density. In addition, slow-release profiles of INI-4001 were measured from INI-4001/A-SNP formulations in plasma with 30-50% INI-4001 released after 7 days. In vivo murine immunization studies demonstrated significantly improved H7-specific humoral and Th1/Th17-polarized T cell immune responses with no observed adverse reactions. Low-density 50 nm INI-4001/A-SNP elicited significantly higher IFN-γ and IL-17 induction over that of the H7 antigen only group and INI-4001 aqueous formulation controls. In summary, this work introduces an effective and biocompatible SNP-based co-delivery platform that enhances the immunogenicity of TLR7/8 agonist-adjuvanted subunit influenza vaccines.

Different types of gold nanoparticles have been synthesized that great potential in medical applications such as medical imaging, bio-analytical sensing and photothermal therapy. However, their stability, polydispersity and biocompatibility are major issues of concern. For example, the synthesis of gold nanorods, obtained through the elongated micelle process, produce them with a high positive surface charge that is cytotoxic. While gold nanoshells are unstable and within a few weeks they decompose due to Ostwald ripening. In this work, we report the self-assembly of the capsid protein of cowpea chlorotic mottle virus (CCMV) around spherical gold nanoparticles, gold nanorods and gold nanoshells to form virus-like particles (VLPs). All gold nanoparticles were synthesized or treated to give them a negative surface charge, so they can interact with the positive N-terminus of the capsid protein leading to the formation of the VLPs. To induce the protein self-assembly around the negative gold nanoparticles, we use different pH and ionic strength conditions that were determined from the capsid protein phase diagram. The encapsidation with the viral capsid protein confers them better biocompatibility, stability, monodispersity and a new biological substrate on which one can introduce specific ligands towards particular cells, broadening the possibilities of medical application.

Bedbug (Cimex spp.) are a nuisance public-health pest that is on the rise globally, particularly in crowded cities such as Hong Kong. To investigate the health impacts of bedbug infestations among bedbug victims, online surveys were distributed in Hong Kong between June 2019 to July 2020. Data on sociodemographics, self-rated health, average hours of sleep per day, and details of bedbug infestation were collected. Bivariate and multivariable analysis were performed using logistic regression. The survey identified 422 bedbug victims; among them, 223 (52.9%) experienced ≥5 bites in the past month, most bites occurred on the arms (n=202, 47.8%) and legs (n=215, 51%), and the most common reaction to bites were itchiness (n=322, 76.3%), redness, and swelling of the skin (n=246, 58.1%), and difficulties sleeping or restlessness (n=125, 29.6%). Bites usually occurred during sleep (n=230, 54.5%). For impact on daily life in the past month, most bedbug victims reported moderate to severe impact on mental and emotional health (n=223, 52.8%) and sleeping quality (n=239, 56.6%). Lower self-rated health (aOR&lt;1) was independently associated with impact to physical appearance (p=0.008), spending money on medication or doctor consultation (p=0.04), number of bites in the past month (p=0.023), and irregular time of bites (p=0.003). Lower average hours of sleep per day (aOR&lt;1) was independently associated with impact on mental and emotional health (p=0.016). This study brings attention to the neglected issue of bedbug infestation by considering bedbugs as an infectious agent instead of a vector and providing empirical evidence describing its health impacts.

Pathogenic water-borne protozoa and helminths sometimes cause debilitating infections in children and immunocompromised people, and the poorest of the poor communities living adjacent to wildlife protected areas in sub-Saharan Africa are at risk. This study aimed to assess the existence of protozoan cysts/ trophozoites, and helminth eggs in fresh surface and piped tap water utilised by locals and tourists in the Queen Elizabeth Protected Area (QEPA) in western Uganda. Water samples were taken from natural (environmental) sources and domestic water sources (piped tap water). The samples were analysed for helminth eggs, free-living amoeba (FLA) trophozoites, Cryptosporidium oocysts, and Giardia cysts. The parasites were examined under the microscope, after which they were identified, counted, and recorded. The overall prevalence of the protozoan parasites, from highest to lowest, were: FLA (56.6%), Cryptosporidium spp. (38.2%), Giardia spp. (36.5%), Eimeria spp. (20.3%), and Paramecium spp. (2.7%). Similarly, helminth parasite prevalence was: Strongyle (38.2%), Ascaris spp. (33.3%), Trematodes (25%), Strongyloides (10.5), Toxocara spp. (8.3%), and Capillaria spp. (3.2%). Necessary steps should be taken to improve the water quality in QEPA.

The illegal wildlife trade is a significant threat to global biodiversity, often targeting already threatened species. In combating the trade, it is critical to know the provenance of the traded animal or part, to facilitate targeted conservation actions, such as education and enforcement. Here we present and compare two methods, portable X-ray fluorescence (pXRF) and stable isotope analysis (SIA), to determine both the geographic and source provenance (captive or wild) of traded animals and their parts. Using three critically endangered, frequently illegally traded Philippine species, the Palawan forest turtle (Siebenrockiella leytensis), the Philippine cockatoo (Cacatua haematuropygia), and the Philippine pangolin (Manis culionensisis) we demonstrate that using these methods we can more accurately assign provenance using pXRF data (x ̅ = 83%), than SIA data (x ̅ = 47%). Our results indicate that these methods provide a valuable forensic tool that can be used in combating the illegal wildlife trade.

An HFMD outbreak spread over the city of Hải Phòng from Summer 2011 to Autumn 2012. This epidemic was chosen because it was the very first HFMD epidemic in North Vietnam, eliminating thus interferences with previous outbreaks. This epidemic displayed 3 separate waves. A complete dataset was collected for more than 9500 patients during this period, which enabled us to analyze this epidemic at different scales. Access to the healthcare system was crucial during this period, with a reorganization of the system in February-March 2012. An analysis at commune level enables us to track the epidemic along certain communication routes. The three-waves structure reveals a wide disparity at district level. We develop a mathematical model showing high accuracy at the adjustment of data for both the total number of cases and for the number of cases per week. As a consequence, the model was able to accurately determine the dates of beginning and end of each wave and to show that they overlapped. Using mathematical functions associated with this model, it was possible to calculate the probability for a patient to belong to a specific wave.

In the present study, we compare energy transition scenarios from a new set of Integrated Assessment Models, the suite of MEDEAS models, based on a systems dynamic modelling approach, with scenarios from two already well know structurally and conceptually different Integrated Assessment Models, the Integrated MARKAL-EFOM System (TIMES) and the Long-range Energy Alternatives Planning system (LEAP). The investigation was carried out to cross-compare and benchmark the response of MEDEAS models with TIMES and LEAP in depicting the energy transition in two different countries, Austria and Bulgaria. The preliminary results show a good agreement across all the models in representing scenarios projecting historical trends, while a major discrepancy is detectable when the rate of implementation of renewable energy is forced to increase to achieve energy system decarbonization. The discrepancy is mainly traceable to the differences in the models’ conception and structures rather than in a real mismatch in representing the same scenarios. The present study is put forward as a guideline for validating new modelling approaches that link energy policy decision tools to the global biophysical and socioeconomic constraints.

Modified mRNAs (modRNAs) are an emerging delivery method for gene therapy. In particular, the modRNA-based COVID-19 vaccines have proven that modRNA is a safe and effective therapeutic tool. Moreover, modRNA has the potential to treat various human diseases including cardiac dysfunction. Acute myocardial infarction (MI) is a major cardiac disorder that currently lacks curative treatment options. MI is commonly accompanied by fibrosis and impaired cardiac function. Our group previously demonstrated that the matricellular protein CCN5 inhibits cardiac fibrosis (CF) and improves cardiac dysfunction. However, it remains elusive whether the early intervention of CF under stress conditions is beneficial or more detrimental due to potential adverse effects such as left ventricular (LV) rupture. To obtain acute CCN5 expression, we used modRNA-mediated gene transfer in a mouse MI model. To evaluate CCN5 activity, we established two independent experimental schemes: 1) preventive intervention and 2) therapeutic intervention. Cardiac function and structural changes were measured by echocardiography and magnetic resonance imaging. Finally, fibrosis and the underlying molecular pathway were analyzed by western blotting, quantitative real-time polymerase chain reaction, and immunohistochemistry. The modRNA-CCN5 gene transfer successfully ameliorated CF and enhanced cardiac function in both preventive and therapeutic interventions without LV rupture or any adverse cardiac remodeling. Conclusively, early intervention in CF by modRNA-CCN5 gene transfer is an efficient and safe therapeutic modality for treating MI-induced heart failure without adverse structural remodeling.

This paper presents an extensive performance analysis of open-ended waveguide elements for direct radiating arrays with high scan angle (± 50º/60º). The evaluated designs are based on square and hexagonal apertures loaded with ridges. Both square and triangular lattices are considered in the framework of Ka-band downlink design requirements for future LEO mega-constellations. The parameter space defined by the monomodal condition has been explored to find an optimum value for each structure. The analyses are validated with both infinite and finite full-wave models in terms of active reflection coefficient, scan loss and cross-polar discrimination.

In 2011-2012, Northern Vietnam suffered its first large scale hand foot and mouth disease (HFMD) epidemic. Two sets of official guidelines were issued during the outbreak to handle the HFMD crisis. The city of Hai Phong was therefore used as a model to analyze the impact of the guidelines release. 9621 HFMD cases were reported in Hai Phong city from April 2011 to December 2012. Three distinct waves of HFMD occurred. Enterovirus A71 and Coxackievirus A16 were successively associated to the epidemics. Two periods, before and after guidelines realease, could be distinguished which were characterized by different patient patterns Time to admission and severity changed notably. Guideline publication help the health system refocusing on the 0.5-3 years age group with highest incidence of the disease. The three waves showed different special distribution but main routes of infection were rivers and local secondary roads most likely through local trade and occupational movements of people.

Flushing tap water is often promoted as a simple and low cost approach to reducing water lead exposures. This study evaluated lead reduction when prevailing flush guidelines (30 seconds-2 minutes) are implemented in a city compliant with lead-associated water regulations (New Orleans, LA). Water samples (n=1,497) collected from a convenience sample of 376 residential sites (2015-2017) were analyzed for lead in samples collected: at 1) first draw (n=375), and after incremental flushes of 2) 30-45 seconds (n=375), 3) 2.5-3 minutes (n=373), and 4) 5.5-6 minutes (n=218). There was no significant reduction when compared to the first draw lead level, until the 6 minute flush (p<0.05); but most sites (52%) still had detectable lead (≥1 ppb) after 6 minutes. Older homes (pre-1950) and low occupancy sites had significantly higher WLLs (p<0.05).Each sample type had health-based standard exceedances at over 50% of sites sampled (max: 58 ppb). While flushing is an effective short-term approach to remediate high lead, prevailing flush recommendations are an inconsistently effective exposure prevention measure that can often inadvertently increase exposures. Public health messages should be modified to ensure appropriate application of flushing for specific cities, while acknowledging its short-comings and practical limitations.

Background: Medical comorbidities increase the risk of severe COVID-19 infection. In some studies, obstructive sleep apnea (OSA) has been identified as a comorbid condition that is associated with an increased prevalence of COVID-19 infection and hospitalization, but few have investigated this association in a general population. Research Question: In a general population, is OSA associated with increased odds of COVID-19 infection and hospitalization and are these altered with COVID-19 vaccination? Study Design: Cross-sectional survey of a diverse sample of 15,057 U.S. adults Results: COVID-19 infection and hospitalization rates were 38.9% and 2.9% respectively. OSA or OSA symptoms were reported in 19.4%. In logistic regression models adjusted for demographic, socio-economic and comorbid medical conditions, OSA was positively associated with COVID-19 infection (aOR: 1.58, 95%CI: 1.39-1.79) and COVID-19 hospitalization (aOR: 1.55, 95% CI: 1.17-2.05). In fully adjusted models, boosted vaccination status was protective against both infection and hospitalization. Boosted vaccination status attenuated the association between OSA and COVID-19 related hospitalization, but not infection. Participants with untreated or symptomatic OSA were at greater risk for COVID-19 infection; those with untreated, but not symptomatic OSA were more likely to be hospitalized. Interpretation: In a general population sample, OSA is associated with a greater likelihood of having had a COVID-19 infection and a COVID-19 hospitalization with the greatest impact observed among persons experiencing OSA symptoms or who were untreated for their OSA. Boosted vaccination status attenuated the association between OSA and COVID-19 related hospitalization.

Clofazimine and Arbidol have both been reported to be effective in vitro SARS-CoV-2 fusion inhibitors. Both are promising drugs repurposed for treatment of COVID-19 and have been used in several previous and ongoing clinical trials. Small-molecule binding to expressed constructs of the trimeric S2 segment of Spike and the full-length SARS-CoV-2 spike protein were measured using a Surface Plasmon Resonance (SPR) binding assay. We demonstrate that Clofazimine, Toremifene, Arbidol and other Arbidol derivatives bind to the S2 segment of the Spike protein. Clofazimine provided the most reliable and highest quality SPR binding data to S2 over the conditions explored. A molecular docking approach was used to identify the most favorable binding sites on the S2 segment in the prefusion conformation, highlighting two possible small-molecule binding sites for fusion inhibitors. Results from molecular docking and modeling the structure-activity-relationship (SAR) of a newly reported series of Clofazimine derivatives supports the proposed Clofazimine binding site on the S2 segment. When the proposed Clofazimine binding site is superimposed with other experimentally determined coronavirus structures in structure-sequence alignments, the changes in sequence and structure may rationalize the broad-spectrum antiviral activity of Clofazimine in closely related coronavirus such as (SARS-CoV, MERS, hCoV-229E, hCoV-OC43).

We report the first case of COVID 19 pneumonia in a preterm neonate in Mayotte, an overseas department of France. The respiratory distress with typical thoracic imaging lesions appears at 14 days of life. This case-report emphasizes the need for a cautious and close up follow-up for asymptomatic neonates born to mothers with COVID-19 infection. Vertical transmission cannot be excluded in this case.

The oncological outcomes are improving in gastrointestinal cancer with advancement in systemic therapies, and there is notable potential in combining immunotherapy and radiation therapy (RT)to allow for further improvements in outcomes. Various preclinical and early phase II studies have shown promising synergy with immunotherapy and RT in gastrointestinal cancer. Consolidative nivolumab in esophageal cancer after neoadjuvant chemoradiation (CRT) and complete resection has recently been approved as standard treatment after improved disease free survival in phase III study. Immunotherapy has shown promising results in hepatocellular carcinoma and colorectal cancer as well. We have reviewed the published and ongoing studies of the combinations of immunotherapy and RT in gastrointestinal cancers.