Functional magnetic resonance imaging (fMRI) is an indirect measure of neural activity with the hemodynamic response function (HRF) coupling it with unmeasured neural activity. The HRF, modulated by several non-neural factors, is variable across brain regions, individuals and populations. Yet, a majority of resting-state fMRI connectivity studies continue to assume a non-variable HRF. In this article, with supportive prior evidence, we argue that HRF variability cannot be ignored as it substantially confounds within-subject connectivity estimates and between-subjects connectivity group differences. We also discuss its clinical relevance with connectivity impairments confounded by HRF aberrations in several disorders. We present limited data on HRF differences between women and men, which resulted in a 15.4% median error in functional connectivity estimates in a group-level comparison. We also discuss the implications of HRF variability for fMRI studies in the spinal cord. There is a need for more dialogue within the community on the HRF confound, and we hope that our article is a catalyst in the process.

Barry Turner’s 1978 Man-made Disasters and Charles Perrow’s 1984 Normal Accidents were seminal books but a detailed comparison has yet to be undertaken. Doing so is important to establish content and priority of key ideas underpinning contemporary safety science. Turner’s research found socio-technical and systemic patterns that meant that major organisational disasters could be foreseen and were preventable. Perrow’s macro-structuralist industry focus was on technologically deterministic but unpredictable and unpreventable ‘system’ accidents, particularly rare catastrophes. Andrew Hopkins and Nick Pidgeon respectively suggested that some prominent writers who wrote after Turner may not have been aware of, or didn’t properly acknowledge, Turner’s work. Normal Accidents didn’t cite Turner in 1984 or 1999. Using a methodology involving systematic reading and historical, biographical and thematic theory analysis, a detailed review of Turner’s and Perrow’s backgrounds and publications sheds new light on Turner’s priority and accomplishment, highlighting substantial similarities as well as clear differences. In a previously unpublished letter, Perrow confirmed reading Man-made Disasters while writing Normal Accidents. Turner became better known after a 1997 second edition but under-acknowledgment issues continued. Ethical citation and potential reasons for under-acknowledgment are discussed. It is concluded that Turner’s foundational importance for safety science should be better recognised.

The cause of the systematic daily march of barometric pressure in the tropics, notably the late morning and late evening peaks seen almost every day at all locations, was a puzzle that persisted through the nineteenth and much of the twentieth centuries. The efforts to explain the physics of the prominent 12-hour solar tidal variation helped inspire some of the earliest developments in theoretical atmospheric dynamics and ultimately led in the 1960’s to a satisfactory dynamical theory for the atmospheric tides. These important theoretical developments followed the observational discoveries, which date to the late 18th and early 19th centuries, of the surprising character of the barometric daily march and of its resolution into solar and lunar period cycles. These important, if simple, discoveries emerged primarily from the efforts of European scientists to systematically study the environment in remote areas of the globe. The two key figures in initially advancing the scientific community’s understanding of the character of barometric tides were the great German polymath Alexander von Humboldt (1769-1859) and the French naturalist Robert de Lamanon (1752-1787), who each made their discoveries on their most famous and colorful scientific expeditions of their respective careers. This paper examines the history of the early observations of the barometric tide.

Artificial Intelligence is developing at a rapid place, with examples of Machine Learning already utilized in aviation to improve efficiency. In the coming decade it is likely that Intelligent Assistants (IAs) or ‘Digital Colleagues’ will be developed and deployed to assist aviation personnel in the cockpit, the air traffic control centre and airports. This will be a game-changer and may herald the way forward for single pilot operations, AI-based management of Urban Mobility including fleets of drones and sky-taxis, and more carbon-efficient transport across global commercial transport networks. Yet in aviation there is a core underlying tenet that ‘people make safety’ and keep the skies and passengers safe, based on a robust industry-wide safety culture. The introduction of IAs into aviation could potentially undermine aviation’s hard-won track record in this area. This paper applies a scientifically validated safety culture tool to explore the potential impacts of the introduction of IAs into aviation. The results suggest that there are indeed potential negative outcomes, but also possible safety ‘affordances’ wherein AI could strengthen safety culture. Safeguards and mitigations are suggested for the key ‘risk owners’ in aviation organisations, to ensure safety remains a priority in the industry.

We study the divisibility properties of the constant terms of certain meromorphic modular forms for Hecke groups. We relate those properties to those of some sequences that have already appeared in the literature. For possible use in later drafts, we show how to invert the map taking a Laurent series $f(x) = 1/x + \sum_{n=0}^{\infty}a_{n+1} x^n$ to the sequence of constant terms of its positive powers. At the end of the article, we construct from elementary arithmetic functions some meromorphic but not necessarily modular functions and study their constant terms.

We explore the class of positive integers n that admit idempotent factorizations n=pq such that lambda(n) divides (p-1)(q-1), where lambda(n) is the Carmichael lambda function. Idempotent factorizations with p and q prime have received the most attention due to their cryptographic advantages, but there are an infinite number of n with idempotent factorizations containing composite p and/or q. Idempotent factorizations are exactly those p and q that generate correctly functioning keys in the RSA 2-prime protocol with n as the modulus. While the resulting p and q have no cryptographic utility and therefore should never be employed in that capacity, idempotent factorizations warrant study in their own right as they live at the intersection of multiple hard problems in computer science and number theory. We present some analytical results here. We also demonstrate the existence of maximally idempotent integers, those n for which all bipartite factorizations are idempotent. We show how to construct them, and present preliminary results on their distribution.

Olfactory dysfunction affects often has severe consequences on patients’ quality of life. The most common complaint in these patients is their reduced enjoyment of food in both patients with olfactory loss and parosmia. How the different types of olfactory dysfunction differ in relation to food and cooking habits, sensory awareness, and food-related quality of life has not yet received much attention. By applying questionnaires on cooking, food, olfactory function, weight changes, sensory awareness, and food-related quality of life, we investigate how various aspects of eating differ between participants with olfactory loss (n=271), parosmia(n=251), and normosmic controls(n=166). Cooking habits in olfactory dysfunction revealed pronounced differences as compared with normosmic controls. Cooking with olfactory dysfunction was associated with e.g., a lack of comfort and inspiration for cooking and an inability to make new foods successfully. Significant differences in cooking were also found between olfactory loss and parosmia. Food items were less familiar in participants with olfactory loss and parosmia, while the ratings of liking food items differed between olfactory loss and parosmia, indicating the importance of adapting ingredients in meals separately for olfactory loss and parosmia. Parosmia was associated with a higher incidence of weight loss, but we found no difference in the food-related quality of life between participants with olfactory loss and parosmia. While olfactory loss and parosmia have wide-ranging consequences on patients’ cooking and food habits, adapting meals to include ‘safer food items’ and integrating multisensory stimulation may be a possible avenue for improving the enjoyment of food.

Disruption of the in utero environment can have dire consequences on fetal growth and development. Intrauterine growth restriction (IUGR) is a pathological condition by which the fetus deviates from its expected growth trajectory, resulting in low birth weight and impaired organ function. The developmental origins of health and disease (DOHaD) postulates that IUGR has lifelong consequences on offspring well-being, as human studies have established an inverse relationship between birth weight and long-term metabolic health. While these trends are apparent in epidemiological data, animal studies have been essential in defining the molecular mechanisms that contribute to this relationship. One such mechanism is cellular stress, a prominent underlying cause of the metabolic syndrome. As such, this review considers the role of oxidative stress, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and inflammation in the pathogenesis of metabolic disease in IUGR offspring. In addition, we summarize how uncontrolled cellular stress can lead to programmed cell death within the metabolic organs of IUGR offspring.

The grand antiprism A is an outlier among the uniform 4-polytopes, since it is not obtainable from Wythoff’s construction. Its symmetry group G(A) has been incorrectly described as [[10,2+,10]] or even as an `ionic diminished Coxeter group’. In fact, G(A) is another group of order 400, namely the group ±[D10×D10]·2, in the notation of Conway and Smith.

Abstract: As more and more numerical and analytical solutions to the linear neutron transport equation become available, verification of numerical results is increasingly important. This presentation concerns the development of another benchmark for the linear neutron transport equation. There are numerous ways of solving the transport equation, such as the Wiener-Hopf method based on analyticity, method of singular eigenfunctions, Laplace and Fourier transforms and analytical discrete ordinates, which is arguably one of the most straightforward, to name a few. Another potential method is the PN method, where the solution is expanded in terms of full range orthogonal Legendre polynomials and with orthogonality and truncation, the moments form a set of second order ODEs. Because of the half-range boundary conditions for incoming particles however, full range Legendre expansions are inaccurate near material discontinuities. For this reason, a double PN (DPN) expansion is more appropriate, where the incoming and exit-ing flux distributions are expanded separately to preserve the discontinuity at material interfaces. Here, a new method of solution for the DPN equations is proposed and demonstrated for an iso-tropically scattering medium.

Aedes aegypti (L.) is the primary vector of chikungunya, dengue, yellow fever and Zika viruses. The leucine-rich repeats (LRR)-containing domain is evolutionarily conserved in many proteins associated with innate immunity in invertebrates and vertebrates, as well as plants. We focused on the AaeLRIM1 and AaeAPL1 gene expressions in response to Zika virus (ZIKV) and Chikungunya virus (CHIKV) infection using a time course study, as well as the developmental expressions in the eggs, larvae, pupae, and adults. RNA-seq analysis data provided 60 leucine-rich repeat related transcriptions in Ae. aegypti in response to Zika virus (Accession number: GSE118858, https://www.ncbi.nlm.nih.gov/gds/?term=GSE118858). RNA-seq analysis data showed that AaeLRIM1 (AAEL012086-RA) and AaeAPL1 (AAEL009520-RA) were significantly upregulated 2.5 and 3-fold during infection by ZIKV 7-days post infection (dpi) of an Ae. aegypti Key West strain compared to an Orlando strain. The qPCR data showed that LRR-containing proteins AaeLRIM1, AaeAPL1 and five paralogues were expressed 100-fold lower than other nuclear genes, such as defensin, during all developmental stages examined. Together, these data provide insights into transcription profiles of LRR proteins of Ae. aegypti during its development and in response to infection with emergent arboviruses.

The conventional rolled-up model for carbon nanocones assumes that the cone is constructed from a rolled-up graphene sheet joined seamlessly, which predicts five distinct vertex angles. This model completely ignores any effects due to the changing curvature and all bond lengths and bond angles are assumed to be those for the planar graphene sheet. Clearly curvature effects will become more important closest to the cone vertex, and especially so for the cones with the smaller apex angles. Here we construct carbon nanocones which in the assembled cone are assumed to comprise bond lengths and bond angles which are, as far as possible, equal throughout the structure at the same distance from the conical apex. Predicted bond angles and bond lengths are shown to agree well with those obtained by relaxing the conventional rolled-up model using the LAMMPS software. The major objective here is not simply to model physically realisable carbon nanocones for which numerical procedures are far superior, but rather to produce an improved model that takes into account curvature effects close to the vertex, and from which we may determine an analytical formula which represents an improvement on that for the conventional rolled-up model.

Recycling information can be complex and often confusing which may subsequently reduce the participations in any waste recycling schemes. As a result, this research explored the roles as well as the importance of a holistic approach in designing recycling information using 15 expert-based in-depth interviews. The rationale was to offer a better understanding of what constitutes waste, recycling, and how recycling information should be designed and presented to make recycling more attractive/convenient. Based on the research participants’ perceptions with supports from the existing studies, this research sub-categorised recycling information into three different themes, termed the “WWW” of recycling information components. As a result, these components (or attributes) were extensively described (using findings of semi-structured interviews) to elicit pragmatic guidance for practitioners, policy-makers, and other stakeholders in designing structured communication or information strategies that may simplify and subsequently increase waste-recycling practices. The policy implications of holistic information in enhancing recycling are further discussed.

Peroxiredoxins play central roles in the detoxification of reactive oxygen species and have been modelled across multiple organisms using a variety of kinetic methods. However, the peroxiredoxin dimer-to-decamer transition has been underappreciated in these studies despite the 100-fold difference in activity between these forms. This is due to the lack of available kinetics and theoretical framework for modelling this process. Using published isothermal titration calorimetry data, we obtained association and dissociation rate constants of 93.0 µM-4·s-1 and 102 s-1, respectively, for the dimer-decamer transition of human PRDX1. We developed an approach that greatly reduces the number of reactions and species needed to model the peroxiredoxin decamer oxidation cycle. Using these data, we simulated horse radish peroxidase competition and NADPH-oxidation linked assays and found that the dimer-decamer transition had an inhibition-like effect on peroxidase activity. Further, we incorporated this dimer-decamer topology and kinetics into a published and validated in vivo model of PRDX2 in the erythrocyte and found that it almost perfectly reconciled experimental and simulated responses of PRDX2 oxidation to hydrogen peroxide insult. By accounting for the dimer-decamer transition of peroxiredoxins, we were able to resolve several discrepancies between experimental data and available kinetic models.

Most of the educational interventions proposed so far in the field of mental well-being in education ‎usually address just students. In this study, we focused on teachers as the Covid-19 pandemic reiterated ‎the importance of their mental well-being during demanding times. We investigated whether ‎neurofeedback (NF) training can increase optimism, self-esteem, life satisfaction, and the ability to ‎cope with stressful events, reflecting on the research literature that emphasizes these four factors, ‎which affect the ability to be confident in dealing with uncertainty and distress. ‎ Forty teachers aged 35-55 participated in the study. The test group took part in 12 NF training sessions, ‎and the control group was not treated. Our findings indicate that compared to the control group, ‎measures of optimism, self-esteem, life satisfaction, and coping with stressful events improved ‎significantly in the test group.‎ To the best of our knowledge, this is the first attempt to test a mental welfare intervention program for ‎teachers through NF. This study responded to a call to develop teacher intervention programs using ‎physiological measurement and technological innovations to improve their mental health and allow ‎them to cope better with stressful teaching conditions.

Aerosol optical depth (AOT) was measured at Xavier University of Louisiana (29.96ᵒ N, 90.11ᵒ W and about 3m above sea level) using a hand-held sun photometer. AOT was measured at two different wavelengths (green at 505nm and red at 625nm) during the period from Sept-2017 to Feb-2018. In this study, we investigate the relationship between AOT and temperature, precipitation, barometric pressure and relative humidity. The maximum monthly average value for green AOT was 0.176 (measured in September) and the minimum monthly value is 0.040 (measured in January). For the red AOT the maximum monthly average value was 0.123 (measured in September) and the minimum is 0.034 (measured in December). The AOT–temperature relationship was predominantly positive, meaning that high AOT values correspond to high temperatures and low AOT values correspond to low temperatures. Relationship between AOT and rainfall is negative, meaning high rainfall averages are associated with low AOT values. AOT and atmospheric pressure have a predominantly negative relationship. The relationship between relative humidity and AOT is a complicated one and is hard to qualify as relative humidity varies very little during the study period.

The market for autonomous vehicles (AV) is expected to experience significant growth over the coming decades and to revolutionize the future of transportation and mobility. The AV is a vehicle that is capable of perceiving its environment and perform driving tasks safely and efficiently with little or no human intervention and is anticipated to eventually replace conventional vehicles. Self-driving vehicles employ various sensors to sense and perceive their surroundings and, also rely on advances in 5G communication technology to achieve this objective. Sensors are fundamental to the perception of surroundings and the development of sensor technologies associated with AVs has advanced at a significant pace in recent years. Despite remarkable advancements, sensors can still fail to operate as required, due to for example, hardware defects, noise and environment conditions. Hence, it is not desirable to rely on a single sensor for any autonomous driving task. The practical approaches shown in recent research is to incorporate multiple, complementary sensors to overcome the shortcomings of individual sensors operating independently. This article reviews the technical performance and capabilities of sensors applicable to autonomous vehicles, mainly focusing on vision cameras, LiDAR and Radar sensors. The review also considers the compatibility of sensors with various software systems enabling the multi-sensor fusion approach for obstacle detection. This review article concludes by highlighting some of the challenges and possible future research directions.

Since its initial development in the 1970’s by Phil Burke and his collaborators, the R-matrix theory and associated computer codes have become the de facto approach for the calculation of accurate data for general electron-atom/ion/molecule collision and photoionization processes. The use of a non-orthonormal set of orbitals based on B-splines, now called the B-spline R-matrix (BSR) approach, was pioneered by Zatsarinny. It has considerably extended the flexibility of the approach and improved particularly the treatment of complex many-electron atomic and ionic targets, for which accurate data are needed in many modelling applications for processes involving low-temperature plasmas. Both the original R-matrix approach and the BSR method have been extended to the interaction of short, intense electromagnetic (EM) radiation with atoms and molecules. Here we provide an overview of the theoretical tools that were required to facilitate the extension of the theory to the time domain. As an example of a practical application, we show results for two-photon ionization of argon by intense short-pulse extreme ultraviolet radiation

The construction of optimized biological fuel cells requires a cathode which combines the longevity of a microbial catalyst with the power density of an enzymatic catalyst. Laccase secreting fungi were grown directly on the cathode of a biological fuel cell to facilitate the exchange of inactive enzymes with active enzymes with the goal of extending the lifetime of laccase cathodes. Additionally, a functionally graded coating was developed to increase enzyme loading at the cathode. Directly incorporating the laccase producing fungus at the cathode extends the operational lifetime of laccase cathodes while eliminating the need for frequent replenishment of the electrolyte. Additionally, the hybrid microbial-enzymatic cathode addresses the issue of enzyme inactivation by using the natural ability of fungi to exchange inactive laccases at the cathode with active laccases. Finally, enzyme adsorption was increased through the use of a functionally graded coating containing an optimized ratio of titanium dioxide nanoparticles and single walled carbon nanotubes. The hybrid microbial-enzymatic fuel cell combines the higher power density of enzymatic fuel cells with the longevity of microbial fuel cells and demonstrates the feasibility of a self-regenerating fuel cell in which inactive laccases are continuously exchanged with active laccases.

Abstract. Background: This paper investigates the propagation of behaviorally transmitted traits with negative effect on host fitness. Methods: We analyze equilibrium between genetically transmitted and behaviorally transmitted competing propagators and consider whether a behavioral propagator is linked to reproduction (e.g. vertical culture transmission), or not. We employ combined genetic and behavior-induced fitness components for hosts, while behavioral propagators have replication factors to distinguish from what’s good for the host (fitness). Results: A trait which spreads faster than its marginal host fitness contribution reduces population will establish itself. The often transient nature of laterally transmitted traits may be a defense against accumulation of deleterious traits. Laterally transmitted traits with high spreading rate often do not equalize with genetic traits, spreading outside natural selection of the hosts. Vertical transmission reduces replication rate and allows group selection against deleterious behaviorally transmitted traits. Competing mutually exclusive propagators contribute to inequality and altruism, but compete through adverse fitness since exclusivity assumes low conversion. Conclusion: Behaviorally transmitted traits, in some cases a tremendous advantage, may also be a significant problem in the development of societies.

One of the oldest problems in physics is that of calculating the motion of N particles under a specified mutual force: the N-body problem. Much is known about this problem if the specified force is non-relativistic gravity, and considerable progress has been made by considering the problem in one spatial dimension. Here I review what is known about the relativistic gravitational N-body problem. Reduction to one spatial dimension has the feature that gravitational radiation is absent, thereby allowing for a clear comparison between the physics of one-dimensional relativistic and non-relativistic self-gravitating systems. After describing how to obtain a relativistic theory of gravity coupled to N point particles, I discuss in turn the 2-body, 3-body, 4-body, and N-body problems. Quite general exact solutions can be obtained for the 2-body problem, unlike the situation in general relativity in 3 spatial dimensions for which only highly specified solutions exist. The 3-body problem exhibits mild forms of chaos, and provides one of the first theoretical settings in which relativistic chaos can be studied. For N4 other interesting features emerge. Relativistic self-gravitating systems have a number of interesting problems awaiting further investigation, providing us with a new frontier for exploring relativistic many-body systems.

Currently the bimatoprost implant (DURYSTA) is approved for a single administration secondary to concern for progressive corneal endothelial cell (CEC) loss with intracameral administration. In order to better understand the cause of CEC loss and other adverse events (AEs) with intracameral administration, multimodal imaging of the implant utilizing optical coherence topography (OCT), robotic ultrasound and bio microscopy video recording was utilized. Inherently the anterior chamber is a non-confined space. In certain examples the implant assumed a round and spotted structure as it picked up iris pigment as it migrated around the anterior chamber. Accordingly, we explored delivery of the implant in the middle segment behind the iris and in front of the pseudophakic lens. We then evaluated the suitability of various imaging modalities to assess the implant in this location. For middle segment administration, the ArcScan Insight 100 robotic ultrasound provided resolution and repeatability sufficient to monitor the implant behind the iris. This preliminary study hypothesizes that DURYSTA migration in the anterior chamber is the main source of AEs. Through use of a confined location, the middle segment, the implant is unlikely to migrate and cause CEC loss while also delivering drug closer to its site of action, the ciliary body. Further efforts are underway to understand the suitability of the middle segment for serial DURYSTA administration to maximize intraocular pressure lowering while minimizing AEs.

Construction Design Management (DM) involves the coordination of design process and activity to ensure quality project design, yet it involves many challenges. This work reports on a collaborative Knowledge Transfer Project (KTP) that tackled several challenges faced by construction design management practitioners. Employing a design science research methodology (DSRM), qualitative analysis of semi-structured interviews with purposively identified design managers first uncovered real world concerns around design coordination, and designer performance monitoring. Then to address these concerns, a web-based design management prototype dashboard was developed which uses typical project data to aid the management of design coordination activity and facilitate design management task prioritization and reporting functionalities. By digitalizing selected design management processes to improve efficiency, and productivity, the visual reporting capability of the dashboard enables design production to be monitored at project and portfolio levels; trends in designer performance to be assessed and focus to be retained on technical queries (TQs) and requests for information (RFIs). By reporting on the development of this web-based Design Management prototype dashboard and illustrating how it can enhance design management productivity in construction firms, this work also provides further evidence of how employing a design science research methodology in construction can produce practical solutions that address real world construction concerns.

The characteristic lesion of primary tuberculosis is the granuloma as is widely studied in human tissues and animal models. Post-primary tuberculosis is different. It develops only in human lungs and begins as a prolonged subclinical obstructive lobular pneumonia that slowly accumulates mycobacterial antigens and host lipids in alveolar macrophages with nearby highly sensitized T cells. After several months, the lesions under necrosis to produce a mass of caseous pneumonia large enough to fragment and be coughed out to produce a cavity or be retained as the focus of a post-primary granuloma. Here we extend these findings with the demonstration of mycobacterial antigen, but not AFB, of M. tuberculosis in the cytoplasm of ciliated bronchiolar epithelium and alveolar pneumocytes in association with elements of the programmed death ligand 1 (PD-L1), cyclo-oxygenase (COX)-2, and fatty acid synthase (FAS) pathways in the early lesion. This suggests that M. tuberculosis use its secreted antigens to coordinate prolonged subclinical development of the early lesions in preparation for a necrotizing reaction sufficient to produce a cavity, post-primary granulomas and fibrocaseous disease

The inherited ‘EIA’ process at Brexit is based on a ‘Project’ period from Inception tothe start of construction works. The ‘Incompleteness’ of the process covers andidentifies stages that will impact on the environmental cycle: construction period,operational life, de-commissioning and a return to acceptable environmental footprint.A master environment structure-plan framework is required to commence with theupgrading of the complete ‘EIA’ process, embracing separate limbs for the UK’spriority environmental targets for climate change, and other major adverse effectswhich result in serious ‘harm’ to the UK environment. The identification of the processfor ‘incompleteness’ requires effective sustainability, and inclusion of effectivemanagement tools, for the essential ‘monitoring/control/recording’ proceduresthroughout the project life and the natural environmental cycle. This will allow theopportunity for a new approach to a structured ‘Suite of EIAR Directives’, to enable a‘EIAR’ regime that ‘will remain fit and proper for UK purpose’.

The characteristic lesion of primary tuberculosis is the granuloma as is widely studied in human tissues and animal models. Post-primary tuberculosis is different. It develops only in human lungs and begins as a prolonged subclinical obstructive lobular pneumonia that slowly accumulates mycobacterial antigens and host lipids in alveolar macrophages with nearby highly sensitized T cells. After several months, the lesions undergo necrosis to produce a mass of caseous pneumonia large enough to fragment and be coughed out to produce a cavity or be retained as the focus of a post-primary granuloma. Here we extend these findings with the demonstration of mycobacterial antigen, but not AFB, of M. tuberculosis in the cytoplasm of ciliated bronchiolar epithelium and alveolar pneumocytes in association with elements of the programmed death ligand 1 (PD-L1), cyclo-oxygenase (COX)-2, and fatty acid synthase (FAS) pathways in the early lesion. This suggests that M. tuberculosis uses its secreted antigens to coordinate prolonged subclinical development of the early le-sions in preparation for a necrotizing reaction sufficient to produce a cavity, post-primary granulomas and fibrocaseous disease.

One of the main challenges of cultured meat is reducing the costs of production, often described as scaling. The main components of the cultivation process include: cells, media, scaffolds and bioreactors. This work presents an alternative to current stainless steel or glass bioreactors and uses food-grade plant-based scaffolds. Bioreactors must be sterile and leak-free to maintain a proper environment for cell growth. Thermoplastic films are a popular material for constructing these fluidic systems, but traditional methods of welding these film are expensive and do not allow rapid prototyping resulting in high research and development costs for companies. In this study, a laser welding method was developed to join thermoplastic films in a way that prevents contamination and leaks, affording effective macro-fluidics fabrication. This technique was tested using polyethylene (PET) films and a laser cutter operating with settings calibrated for the material to be welded or cut. The laser welding method was found to produce strong, leak-free seals in PET films with minimal heat-induced damage to the films. The ability to design fluidics, chambers and ports of various size. Using this method afforded the incorporation of plant-based scaffolds from food-grade plants (Rice). The laser welding method developed in this study provides a reliable, contamination-free method for the rapid fabrication of fluidic systems for cell cultivation. This technique has the potential to be compatible with a vast range of cell types and scaffolds and to be widely adopted in tissue engineering for regenerative medicine and food applications such as cultured meat.

Three-dimensional (3D) printing technology, also known as additive manufacturing (AM), has emerged as an attractive state-of-the-art tool for precisely fabricating functional materials with complex geometries, championing several advancements in tissue engineering, regenerative medicine, and therapeutics. However, this technology has an untapped potential for biotechnological applications, such as sensor and biosensor development. By exploring these avenues, the scope of 3D printing technology can be expanded and pave the way for groundbreaking innovations in the biotechnology field. Indeed, new printing materials and printers would offer new possibilities for seamlessly incorporating biological functionalities within the growing 3D scaffolds. Herein, we review the extrusion-based 3D printing modalities emphasizing biosensor applications. We highlighted the application of natural, synthetic, and composite biomaterials as 3D-printed soft hydrogels. Emphasis was placed on the approach by which the sensing molecules were introduced during the fabrication process. Finally, the future perspective was provided.

This review focuses on the emerging evidence for the association between estimated cardiorespiratory fitness (eCRF) and metabolic risk factors. Given the challenges associated with directly measuring cardiorespiratory fitness (CRF) in large populations, eCRF presents a practical alternative for predicting metabolic health risks. A literature search identified six relevant cohort studies from 2021 to 2024 that investigated the association of eCRF with hypertension, hyperglycemia, dyslipidemia, and obesity. The review findings highlight a consistent inverse relationship between higher eCRF and lower incidence of metabolic risks in line with CRF cohort studies. This review highlights the importance of low eCRF as a primordial indicator for metabolic risks and underscores the need for broader application. Future research directions should include exploring eCRF's predictive accuracy across diverse populations and health outcomes and testing its real-world applicability in healthcare and public health settings.

The optimization of photovoltaic (PV) systems is vital for enhancing efficiency and economic viability, especially under Partial Shading Conditions (PSCs). This study focuses on the development and comparison of traditional and advanced algorithms, including Perturb and Observe (P&O), Incremental Conductance (IC), Fuzzy Logic Control (FLC), Grey Wolf Optimization (GWO), Particle Swarm Optimization (PSO), and Artificial Neural Networks (ANN), for efficient Maximum Power Point Tracking (MPPT). Simulations conducted in MATLAB/SIMULINK evaluated these algorithms’ performance under various shading scenarios. The results indicate that while traditional methods like P&O and IC are effective under uniform conditions, advanced techniques, particularly ANN-based MPPT, exhibit superior efficiency and faster convergence under PSCs. The study concludes that integrating AI and ML into MPPT algorithms significantly enhances the reliability and efficiency of PV systems, paving the way for broader adoption of solar energy technologies in diverse environmental conditions. These findings contribute to advancing renewable energy technology and support the green energy transition.

Pervasive purifying selection on non-synonymous substitutions is a hallmark of papillomavirus genome history. Whereas the role of selection on, and drift of, non-coding DNA elements on HPV diversification is poorly understood. More than a thousand complete genomes representing Alphapapillomavirus types, lineages and SNP variants were examined phylogenetically and interrogated for the number and position of non-coding DNA sequence motifs using Principal Components Analyses, Ancestral State Reconstructions and Phylogenetic Independent Contrasts. For anciently diverged Alphapapillomavirus types, composition of the 4 nucleotides (A,C,G,T), codon usage, trimer usage and 13 established non-coding DNA sequence motifs revealed phylogenetic clusters consistent with genetic drift. Ancestral state reconstruction and Phylogenetic Independent Contrasts revealed ancient genome alterations, particularly for CpG and APOBEC3 motifs. Each evolutionary analytical method we performed supports the unanticipated conclusion that genetic drift and different evolutionary drivers have structured Alphapapillomavirus genomes in distinct ways during successive epochs, even extending to differences in more recently formed variant lineages

: Arboviruses transmitted by Aedes aegypti and Ae. albopictus have been introduced to Florida on many occasions. Infrequently, these introductions lead to sporadic local transmission and, more rarely, sustained local transmission. Both mosquito species are present in Florida, with spatio-temporal variation in population composition. We developed a 2-vector compartmental, deterministic model to investigate factors influencing Chikungunya virus (CHIKV) establishment. The model includes a non-linear, temperature-dependent mosquito mortality function based on minimum mortality in a central temperature region. Latin Hypercube sampling was used to generate parameter sets used to simulate transmission dynamics, following the introduction of one infected human. The analysis was repeated for 3 values of the mortality function central temperature. Mean annual temperature was consistently important in the likelihood of epidemics, and epidemics increased as the central temperature increased. Ae. albopictus recruitment was influential at the lowest central temperature while Ae. aegypti recruitment was influential at higher central temperatures. Our results indicate that the likelihood of CHIKV establishment may vary, but overall Florida is permissive for introductions. Model outcomes were sensitive to the specifics of mosquito mortality. Mosquito biology parameters are variable, and improved understanding of this variation will improve our ability to predict the outcome of introductions.

The goal of this paper is to contribute the perspective of a systems engineer to the effort to fight pandemics. The availability of low latency case data and effectiveness of social distancing suggest there is sufficient control for successful smoothing and targeting almost any desired level of low or high cases and immunity. This control proceeds from spontaneous public reaction to caseloads and news as well as government mediated recommendations and orders. We simulate multi-step and intermittent-with-feedback partial unlock of social distancing for rapidly-spreading moderate-mortality epidemics and pandemics similar to COVID-19. Optimized scenarios reduce total cases and therefore deaths typically 8% and up to 30% by controlling overshoot as groups cross the herd immunity threshold, or lower thresholds to manage medical resources and provide economic relief. We analyze overshoot and provide guidance on how to damp it. However, we find overshoot damping, whether from expert planning or natural public self-isolation, increases the likelihood of transition to an endemic disease. An SIR model is used to evaluate scenarios that are intended to function over a wide variety of parameters. The end result is not a case trajectory prediction, but a prediction of which strategies produce near-optimal results over a wide range of epidemiological and social parameters. Overshoot damping perversely increases the chance a pathogen will transition to an endemic disease, so we briefly describe the undershoot conditions that promote transition to endemic status.

Background: Recently some photon models of a Wigner's friend experiment have led investigators to suggest objective reality does not exist, and to publish non-academic articles with such claims. The public is not equipped to evaluate the severe limitations of these experiments. The separation of Wigner from the experiment and use of only reversible coherent processes for the friend allow operations that are not possible in ordinary reality according to the latest quantum research. Methods: We suggest directly testing the implied claim that objective reality, including incoherent objects with irreversible non-destructive memory, can be held in superposition. We suspect it will fail, but provide for a graduated approach that may discover something about the conditions for superposition collapse. To this end we design a thought experiment to model the objective world, investigating under what conditions experimenters in the same world (ensemble member) will be able to record a result and find it does not appear to change. An observer has a viewing apparatus and a memory apparatus. A second uncorrelated viewer of the same recorded result is employed to obtain objectivity. By hypothesis the uncorrelated second viewer obtains the same view of the measurement record as the first observer. There are not two measurements. This is not an investigation of hidden variables. Results: To model the objective world, incoherent and irreversible processes must be included. To test for superposition, coherence has to be established. These seem to present a contradiction. Conclusions: The thought experiment has suggested new places to look other than size for the origin of objective reality from the quantum world, casts doubt on the Many-Worlds interpretation, and provides a method of testing it.

Methylation is a biochemical process involving the addition of a methyl group (-CH3) to various chemical compounds. It plays a crucial role in maintaining the homeostasis of the endothelium, which lines the interior surface of blood vessels and has been linked, among other conditions, to coronary artery disease (CAD). Despite significant progress in CAD diagnosis and treatment, intensive research continues into genotypic and phenotypic CAD biomarkers. This review explores the significance of the methylation pathway and folate metabolism in CAD pathogenesis, with a focus on endothelial dysfunction resulting from deficiency in the active form of folate (5-MTHF). We discuss emerging areas of research into CAD biomarkers and factors influencing the methylation process. By highlighting genetically determined methylation disorders, particularly the MTHFR polymorphism, we propose the potential use of the active form of folic acid (5-MTHF) as a novel CAD biomarker and personalized pharmaceutical for selected patient groups. Our aim is to improve the identification of individuals at high risk of CAD and enhance their prognosis.

Policies to require front-of-package labels (FOPLs) on foods may help Indian consumers better identify foods high in nutrients of concern including sugar, saturated fat, and sodium, and discourage their consumption, outcomes critical for preventing rises in diet-related non-communicable disease. The objective was to test whether FOPLs helped Indian consumers identify ‘high-in’ foods and reduce intentions to purchase them. We conducted an in-person randomized experiment (n=2,869 adults between ages 18 and 60 years old) in six states of India in 2022. Participants were randomized to one of five FOPLs: a control label (barcode), warning label (octagon with “High in [nutrient]”), Health Star Warning (HSR), Guideline Daily Amount (GDA), or traffic light label. Participants then viewed a series of foods high in sugar, saturated fat, or sodium with the assigned FOPL, and rated product perceptions and label reactions. Fewer than half of participants in the control group (39.1%) correctly identified all products high in nutrient(s) of concern. All FOPLs led to an increase in this outcome, with the biggest differences observed for the warning label (60.8%, p<0.001) followed by the traffic light label (54.8%, p<0.001), GDA (55.0%, p<0.001), and HSR (45.0%, p<0.01). Relative to the control, only the warning label led to a reduction in intentions to purchase the products. The results suggest that warning labels are the most effective FOPL to help Indian consumers identify and avoid unhealthy foods.

Abstract: The biological process of photosynthesis was critical in catalyzing the oxygenation of Earth’s atmosphere 2.5 billion years ago, changing the course of development of life on Earth. Recently, the fields of applied and synthetic photosynthesis have utilized the light-driven protein-pigment supercomplexes central to photosynthesis for the photocatalytic production of fuel and other various valuable products. The reaction center Photosystem I is of particular interest in applied photosynthesis due to its high stability post-purification, non-geopolitical limitation, and its ability to generate the greatest reducing power found in Nature. These remarkable properties have been harnessed for the photocatalytic production of a number of valuable products in the applied photosynthesis research field. These primarily include photocurrents and molecular hydrogen as fuels. The use of artificial reaction centers to generate substrates and reducing equivalents to drive non-photoactive enzymes for valuable product generation has been a long-standing area of interest of the synthetic photosynthesis research field. In this review, we cover advances in these areas and further speculate synthetic and applied photosynthesis as photocatalysts for the generation of valuable products.

First, we examine how spin is treated in special relativity and the necessity of introducing spin supplementary conditions (SSC) and how they are related to the choice of a center-of-mass of a spinning particle. Next, we discuss quantum electrodynamics and the Foldy-Wouthuysen transformation which we note is a position operator identical to the Pryce-Newton-Wigner position operator. The classical version of the operators are shown to be essential for the treatment of classical relativistic particles in general relativity, of special interest being the case of binary systems (black holes/neutron stars) which emit gravitational radiation.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. The interferons (IFNs) were discovered in 1957, and recombinant IFN-β-1b was approved by the US Food and Drug Administration as the first disease-modifying therapy (DMT) for MS in 1993. Since that time, clinical trials and real-world observational studies have demonstrated the effectiveness of IFN therapies. The pivotal intramuscular IFN-β-1a phase 3 trial was the first to demonstrate that a DMT could reduce accumulation of sustained disability in MS. Patient adherence to treatment is higher with intramuscular IFN-β-1a, given once weekly, than with subcutaneous formulations requiring multiple injections per week. Moreover, subcutaneous IFN-β-1a is associated with an increased incidence of injection site reactions and neutralizing antibodies compared with intramuscular administration. In recent years, revisions to MS diagnostic criteria have improved clinicians’ ability to identify patients with MS and have promoted the use of magnetic resonance imaging (MRI) for diagnosis and monitoring. MRI studies show that treatment with IFN-β-1a, relative to placebo, reduces T2 and gadolinium-enhancing lesions and gray matter atrophy. Since the approval of intramuscular IFN-β-1a, several high-efficacy therapies have been approved for MS, though the benefit of these high-efficacy therapies should be balanced against the increased risk of serious adverse events. For some subpopulations of patients, including pregnant women, the safety profile of IFN-β formulations may provide a particular benefit. In addition, the antiviral properties of IFNs may indicate therapeutic opportunities for IFN-β in the treatment of viral infections such as COVID-19.

Bottom-up systems biology entails the construction of kinetic models of cellular pathways by collecting kinetic information on the pathway components (e.g. enzymes) and collating this into a kinetic model, based for example on ordinary differential equations. This requires integration and data transfer between a variety of tools, ranging from data acquisition in kinetics experiments, to fitting and parameter estimation, to model construction, evaluation and validation. Here, we present a workflow that uses the Python programming language, specifically the modules from the SciPy stack, to facilitate this task. Starting from raw kinetics data, acquired either from spectrophotometric assays with microtitre plates or from NMR spectroscopy time courses, we demonstrate the fitting and construction of a kinetic model using scientific Python tools. The analysis takes place in a Jupyter notebook, which keeps all information related to a particular experiment together in one place and thus serves as an e-labbook, enhancing reproducibility and traceability. The Python programming language serves as an ideal foundation for this framework because it is powerful yet relatively easy to learn for the non-programmer, has a large library of scientific routines and active user community, is open-source and extensible, and many computational systems biology software tools are written in Python or have a Python API. Our workflow thus enables investigators to focus on the scientific problem at hand rather than worrying about data integration between disparate platforms.

Current theories of autoimmunity are diverse, sometimes contradictory, and suffer from incompleteness. Although substantial evidence exists that adaptive and innate immunity, sex, genetic predisposition, and the microbiome all play essential roles in autoimmune disease etiologies and pathogenesis, and that antigen processing is altered during disease induction, no existing theory integrates all of these factors through a single, coherent mechanism. In an attempt to focus the field on the need to elucidate such an integrative mechanism, I propose one possibility here that, if nothing else, helps to identify the nature of the problems that need to be addressed. My theory is that autoimmune diseases are induced by normal immunological responses to unique pairs of complementary antigens, at least one of which is a molecular mimic of a host target. Each antigen in the complementary pair induces a complementary immune response (T or B cell); although each immune response is idiotypic in origin, the antigenic complementarity results in what appears to be an idiotype-anti-idiotype relationship between the responses. Additionally, because of the antigenic complementarity, each immune response mimics one of antigens, abrogating the distinction between self and non-self. If at least one of the antigens mimics a host antigen, then the resulting immunological civil war spreads to a host tissue. Complementary antigens also alter antigen processing so that antigens that would normally be proteolytically digested are presented by the major histocompatibility complex (MHC) to T and B cell receptors inducing a cross-reactive immune response. The resulting civil war is supported by the innate immune system due to the complementarity of the initiating antigens.. Complementary antigens stimulate synergistic toll-like receptors (TLR) and/or nucleotide-binding oligomerization receptors (NOD) resulting in up-regulation of cytokine production and further stimulation of the adaptive immune response. Because the immune responses (e.g., antibodies) mimic the initiating antigens, this synergistic activation of innate immunity becomes chronic. Additionally, TLR and NOD function are highly sensitive to sex hormones, some becoming up-regulated and some down-regulated in the presence of either testosterone or estrogens. This sensitivity explains how sex modifies susceptibility to autoimmune diseases. Genetic mutations in TLR, NOD and MHC further alter antigen presentation and the degree to which antigens stimulate an immune response explaining how genetics also modifies susceptibility. Finally, sex hormones also alter the host microbiome, which in turn modulates autoimmune disease risk by shaping the immunological nature of self and by mediating susceptibility to microbial infection. Moreover, it appears that the microbiome camouflages itself from the immune system by mimicking the host antigenic repertoire; the mimicry between the antigens of the microbiome and the host results in selective attacks on microbiome constituents concomitant with any autoimmune attack on host tissues. This antigenic complementarity theory thereby integrates all major elements known to affect, or be affected by, autoimmune diseases and provides a set of testable implications.

SARS-CoV-2 continues to widely circulate in populations globally. Underdetection is acknowledged and is problematic when attempting to capture the true prevalence. Seroprevalence studies, where blood samples from a population sample are tested for SARS-CoV-2 antibodies that react to the SARS-CoV-2 virus, are a common method for estimating the proportion of people previously infected with the virus in a given population. However, obtaining reliable estimates from seroprevalence studies is challenging for a number of reasons, and the uncertainty in the results is often overlooked by scientists, policy makers and the media. This paper reviews the methodological issues that arise in designing these studies, and the main sources of uncertainty that affect the results. We discuss the choice of study population, recruitment of subjects, uncertainty surrounding the accuracy of antibody tests themselves, and the relationship between antibodies and infection over time. Understanding these issues can help the reader to interpret and critically evaluate the results of seroprevalence studies.

New information suggests female autistic spectrum disorder (ASD) is much more common than previously thought, with a likely prevalence of 6% and with 80% undiagnosed at the age of 18. ASD then becomes a common comorbidity of female mental illness with nearly one in five women who develop a mental illness being autistic. ASD has heretofore been regarded as a pediatric condition and though now thought to be life long it is still not well recognized by adult health services. Most mental illness first presents in the teens and early twenties. Comorbid ASD is more difficult to diagnose due to diagnostic overshadowing, and ASD comorbidity maks the mental illness more severe and mor difficult to treat. Recognized ASD is readily treatable with an approach sympathetic to neurodiversity. Improving the pathway from adolescence to adulthood by increasing knowledge of autism in adult health services would dramatically improve female mental health at surprisingly little extra cost. It is low hanging fruit in a very fraught area of healthcare. This paper will examine the extent of the problem. It will explore solutions and quantify the gains of appropriate therapy.

This new study revised interlinked issues of global soil organic carbon (SOC), annual net primary productivity (NPP) and atmospheric CO₂ turnover time (τ). Soil is confirmed as both the greatest sink and source for excess atmospheric CO₂. Most terrestrial NPP (~218 Gt C/yr) is ultimately processed in topsoil and SOC stocks now total >10,000–12,000 Gt. More excess carbon is released into the air and water from SOC loss (>20 Gt C/yr) due to land clearance for pasture/crops, fires, agrichemical poisoning and erosion, than from fossil fuels (~10 Gt C/yr). NOAA’s Barrow bounce and isotopic analyses support high terrestrial flux up to ~800 Gt C/yr and CO₂ turnover time of ~1–4 years. Earth’s re-humification via compost offers the best and only practical/time-critical fix for climate, strategy for species extinction plus remedy for human health.

Shutdown for just six days enables land plants to entirely fix CO₂ excess of +4 Gt C per yr. Rebuilding soil organic carbon (SOC) in worm-worked humus is the only practical carbon capture and storage (CCS) capable of freely offsetting annual anthropogenic emissions. A case is made to redirect all available resources towards proven, earthworm-based, organic husbandry. Priority is to safely combat mounting global threats due to irreversible species extinction, perilous climate change and deteriorating human wellbeing (mental/physical health). All three interlinked risks are underpinned by a relentless, yet largely ignored, critical loss of precious topsoil. A first step to topsoil recovery is vermi-composting all vegetable and animal ‘wastes’ for return to the field.

Two conundrums have puzzled COVID-19 investigators: 1) morbidity and mortality is rare among Infants and young children and 2) rates of morbidity and mortality exhibit very large variances across nations, locals and even within cities. These differences correlate with rates of Haemophilus influenzae type B (Hib) and pneumococcal vaccination, which are almost universal among infants and vary widely by geography among adults and the elderly. The higher the rate of vaccination, the lower the COVID-19 morbidity and mortality. Vaccination rates with other vaccines, including BCG and poliovirus, do not correlate with COVID-19 risks. Notably, both Hib and pneumoccoci are common co-infections with influenza and coronaviruses and are associated with more severe disease and risk of death. Whether the vaccines simply protect against COVID-19 complications, directly protect against COVID-19 infection by inducing cross-reactive immunity, or are markers for some other types of protection such as availability of better healthcare, is not yet known. What is known is that improving coverage rates of Hib and pneumococcal vaccination has significantly lowered severe morbidity and mortality in influenza epidemics and might have similar efficacy for mitigating coronavirus outbreaks. If infants and children are valid indicators, the beneficial effects might be very significant. The possibility that anti-viral proteins in milk (e.g., lactoferrin) protect against COVID-19 is also explored.

The ratio of males to females with ASD is generally quoted as 4:1 though it is believed that there are biases preventing females being diagnosed and that the true ratio is lower. These biases have not been clearly identified or quantified. Starting with a clinical dataset of 1711 children <18 years old four different methods were employed in an inductive study to identify and quantify the biases and calculate the proportion of females missed. A mathematical model was constructed to compare the findings with current published data. The true male to female ratio appears to be 3:4. Eighty per cent of females remain undiagnosed at age 18 which has serious consequences for the mental health of young women.

Electromagnetic interference (EMI) generated by switching operations within high voltage DC (HVDC) converter stations is an issue that has been addressed by CIGRE and methods to manage EMI should be considered in the design phase using electromagnetic modeling techniques. It is shown that method of moments-based techniques that have been used in many previous studies may not be sufficient. Here, the finite-difference time-domain method is used to study the properties of single switching events using a realistic model of an HVDC converter station with special emphasis on determining the impact of the valve hall on shielding EMI. It is shown that the valve hall does not confine high frequency electromagnetic fields to the valve hall; rather it delays them from exiting through bushings in the wall. Further, it is shown that incorporating electromagnetic absorbing material into the valve hall design can significantly reduce EMI outside the converter station.

The growing concerns about floods have highlighted the need for accurate and detailed precipitation data as extreme precipitation occurrences can lead to catastrophic floods, resulting in significant economic losses and casualties. Integrated Multi-satellitE Retrievals for the Global Precipitation Measurement (GPM-IMERG) is a commonly used high-resolution gridded precipitation dataset and is recognized as trustworthy alternative sources of precipitation data. The aim of this study is to comprehensively evaluate the performance of GPM IMERG Early (IMERG-E), Late (IMERG-L), and Run Final (IMERG-F) in precipitation estimation and their capability in detecting extreme rainfall indices over southwestern Iran during 2001-2020. The Asfezari gridded precipitation data which are developed using a dense of ground-based observation were utilized as the reference dataset. The findings indicate that the IMERG-F performs reasonably well in capturing many extreme precipitation events (defined by various indices). All the three products showed a better performance in capturing fixed and non-threshold precipitation indices across the study region. The findings also revealed that both IMERG-E and IMERG-L have problems in rainfall estimation over elevated areas showing values of overestimations. Examining the effect of land cover type on the accuracy of the precipitation products suggest that both IMERG-E and IMERG-L show large and highly unrealistic overestimations over inland water bodies and permanent wetlands. The results of the current study highlight the potential of IMERG-F as a valuable source of data for precipitation monitoring in the region.

Our study aimed to identify predictors for the effectiveness of tumor regression in lung cancer patients undergoing neoadjuvant treatment and cancer resections. Patients admitted between 2016 and 2022 were included in the study. Based on the histology of the tumor, patients were categorized into lung adenocarcinoma group (LUAD), and squamous cell carcinoma group (SQCA). Ninety-five patients with non-small cell lung cancer were included in the study. Fifty-eight (61.1%) and 37 (38.9%) patients were included in the LUAD and SQCA groups, respectively. Nine (9.5%), 56 (58.9%), and 30 (31.6%) patients were categorized with a tumor regression score of I, II, and III respectively. In multivariable analyses, histology of the primary tumor (SQCA), lymph node size in the preoperative CT scan (>1.7cm) and absolute tumor size reduction after neoadjuvant treatment (>2.6 cm) independently predict effectiveness of tumor regression (OR, [95% Confidence interval, p-value] of 6.88 [2.40-19.77, p70 years, extended resection >one lobe, and tumor recurrence or metastasis were identified as significant independent predictors of reduced overall survival. Assessment of tumor size before and after neoadjuvant treatment might help to identify high-risk patients with decreased survival and to improve patient management and care.

This study introduces an innovative seeding method for cells on large scaffolds (1-100 sqcm) with an accuracy of 0.1mm, comparing the conventional drop-wise seeding technique with an automated seeding approach using an open sourced robotic liquid handling system (OpenLH). This automated system employs an algorithm in which the user inputs the desired droplet volume and seeding pattern dimensions such in number of rows, columns and distance between droplets, thus optimizing the distribution of cells on the scaffold. By adjusting these parameters, the method achieves greater accuracy and consistency over manual seeding and requires less operation space volume than dynamic seeding. Additionally, the system’s tip replacement feature can support the precise seeding of multiple cell types on a single scaffold and the dispensing of growth factors to foster patterns of cell differentiation and proliferation on the large 3D scaffold. This seeding method not only enhances the precision and efficiency of cell distribution on scaffolds but also shows significant potential for scalability in the cultured meat industry, where large scaffolds are essential. The adoption of such automated systems could promote efficient scaffold-based tissue engineering by promoting uniform cell distribution and enabling the creation of complex tissue constructs, thereby advancing both biomedical research and cultured meat production.

Stellar NGC 6853, also known as the Dumbbell Nebula, is a remarkable example of an elliptical morphological type 1 multiple shell planetary nebula, which is now in one of its last evolutionary stages. This project focuses on examining the distinct varieties of the nebula temperatures and densities using observation data from the Issac Newton Group of Telescopes and comparing them with the observation data from Observatoire de Haute Provence from 14th to 18th of October 2019, with a primary focus on the data from the Issac Newton Telescope (INT). The densities ranged from diffused regions of 376.63 ± 228.97 atoms per cm³ to dense regions of 6441.11 ± 228.90 atoms per cm³; these values are slightly lower approximately by 2000 than the values from the Observatoire de Haute Provence. The radial velocity and the expansion velocity were also calculated using the spectroscopic data and were found to be 29.50 ± 0.38 km⁻¹ and 37.40 ± 0.38 km⁻¹ respectively. This result is expected from a multi-shell nebula that consists of the main body and surrounding halo

Subsurface drainage systems remove excess water from the soil profile thereby improving crop yields in poorly drained farmland. Knowledge of the position of the buried drain lines is important: 1) to improve understanding of leaching and offsite release of nutrients and pesticides, and 2) for the installation of a new set of drain lines between the old ones for enhanced soil water removal efficiency. Traditional methods of drainage mapping involve the use of tile probes and trenching equipment. While these can be effective, they are also time-consuming, labor-intensive, and invasive, thereby entailing an inherent risk of damaging the drainpipes. Non-invasive geophysical soil sensors provide a potential alternative solution. Previous research has focused on the use of time-domain ground penetrating radar (GPR), with variable success depending on local soil and hydrological conditions and the central frequency of the specific equipment employed. The objectives of this study were 1) to test the use of a stepped-frequency continuous wave (SFCW) 3D-GPR (GeoScope Mk IV 3D-Radar with DXG1820 antenna array) for subsurface drainage mapping, and 2) to evaluate the performance of a 3D-GPR with the use of a single-frequency multi-receiver electromagnetic induction (EMI) sensor (DUALEM) in-combination. The 3D-GPR system offers more flexibility for application to different (sub)surface conditions due to the coverage of wide frequency bandwidth. The EMI sensor simultaneously provides information about the apparent electrical conductivity (EC_a) for different soil volumes, corresponding to different depths. This sensor combination was evaluated on twelve different study sites with various soil types with textures ranging from sand to clay till. While the 3-D GPR showed a high success rate in finding the drainpipes at five sites (sandy, sandy loam, loamy sand, and organic topsoils), the results at the other seven sites were less successful due to limited penetration depth (PD) of the 3D-GPR signal. The results suggest that the electrical conductivity estimates produced by the inversion of EC_a data measured by the DUALEM sensor could be a useful proxy to explain the success achieved by the 3D-GPR in finding the drain lines. The high attenuation of electromagnetic waves in highly conductive media limiting the PD of the 3D-GPR can explain the findings obtained in this research.

Background: A large percentage of deaths in an epidemic or pandemic can be due to overshoot of population (herd) immunity, either from the initial peak or from planned or unplanned exit from lockdown or social distancing conditions. Objectives: We study partial unlock or reopening interaction with seasonal effects in a managed epidemic to quantify overshoot effects on small and large unlock steps and discover robust strategies for reducing overshoot. Methods: We simulate partial unlock of social distancing for epidemics over a range of replication factor, immunity duration and seasonality factor for strategies targeting immunity thresholds using overshoot optimization. Results: Seasonality change must be taken into account as one of the steps in an easing sequence, and a two step unlock, including seasonal effects, minimizes overshoot and deaths. It may cause undershoot, which causes rebounds and assists survival of the pathogen. Conclusions: Partial easing levels, even low levels for economic relief while waiting on a vaccine, have population immunity thresholds based on the reduced replication rates and may experience overshoot as well. We further find a two step strategy remains highly sensitive to variations in case ratio, replication factor, seasonality and timing. We demonstrate a three or more step strategy is more robust, and conclude that the best possible approach minimizes deaths under a range of likely actual conditions which include public response.

(1) Background: TNF inhibitors (TNFi) have revolutionized the treatment of rheumatoid arthritis (RA). However, 30-40 % of RA patients do not respond adequately to those biologics. In addition to neutralizing soluble TNF, TNFi have the ability to bind the transmembrane form of TNF, tmTNF. Importantly, tmTNF can act itself as a receptor that induces a “Reverse Signaling” (RS) in cells. We previously showed that certolizumab, a Fab’ TNFi, activates RS in human primary monocytes, at least in part through the transcription factor NRF2 that is known to regulate the expression of genes involved in anti-inflammatory response and oxidative stress. (2) Methods: Here, we have developed an assay for the prediction of clinical response of RA patients to TNF inhibitors. This assay is based on mRNA quantitation of CD36 activation and of 6 genes induced by NRF2 following tmTNF RS in fresh monocytes. (3) Results: We could predict the response to anti-TNF monoclonal antibodies (mAbs) with 93.3 % accuracy. However, our method was not suitable for the prediction of the response to TNF soluble receptor etanercept. (4) Conclusions: We have developed a rather simple, short-term, test that can be standardized. Predicting the response to TNF mAbs will help physicians offer the best available treatment and provide patients with personalized medicine.

Past public health crises (e.g. tobacco, alcohol, opioids, cholera, HIV, lead, pollution, venereal disease, even COVID-19) have been met with interventions targeted both at the individual and all of society. While the healthcare community is very aware that the global pandemic of non-communicable diseases (NCD’s) has its origins in our Western ultraprocessed food diet, society has been slow to initiate any interventions other than public education, which has been ineffective, in part due to food industry interference. This article provides the rationale for such public health interventions, by compiling the evidence that added sugar, and by proxy the ultraprocessed food category, meets the four criteria set by the public health community as necessary and sufficient for regulation — addiction, toxicity, ubiquity, and externalities (how does your consumption affect me?). To its credit, some countries have recently heeded this science and have instituted sugar taxation policies to help ameliorate NCD’s within their borders. This article also supplies scientific counters to food industry talking points, in order to guide both scientists and policy makers in instituting further appropriate public health measures to quell this pandemic.

Various studies indicate that vaccination, especially with pneumococcal vaccines, protects against symptomatic cases of SARS-CoV-2 infection and death. This paper explores the possibility that pneumococcal vaccines in particular, but perhaps other vaccines as well, contain antigens that might be cross-reactive with SARS-CoV-2 antigens. Comparison of the glycosylation structures of SARS-CoV-2 with the polysaccharide structures of pneumococcal vaccines yielded no obvious similarities. However, while pneumococcal vaccines are primarily composed of capsular polysaccharides, some are conjugated to CRM197, a modified diphtheria toxin, and all contain about three percent protein contaminants, including the pneumococcal surface proteins PsaA, PspA and probably PspC. All of these proteins have very high degrees of similarity, using very stringent criteria, with several SARS-CoV-2 proteins including the spike protein, membrane protein and replicase 1a. CRM197 is also present in Hib and meningitis vaccines. Equivalent similarities were found at lower rates, or were completely absent, among the proteins in diphtheria, tetanus, pertussis, measles, mumps, rubella, and poliovirus vaccines. Notably, PspA and PspC are highly antigenic and new pneumococcal vaccines based on them are currently in human clinical trials so that their effectiveness against SARS-CoV-2 disease is easily testable.

Rainfall, or more generally the precipitation process (flux), is a clear example of chaotic variables resulting from a highly nonlinear dynamical system, the atmosphere, represented by a set of physical equations such as the Navier-Stokes equations, energy balances and hydrological cycle among others. As a generalization of the Euclidean (ordinary) measurements, chaotic solutions of these equations are characterized by fractal dimensions, which are non-integer values that represent the complexity of variables like the precipitation. However, observed precipitation is measured as an aggregate variable over time, thus physical analysis of the observed fluxes is very limited. Therefore, this review aims to go through the different approaches used in the identification and analysis of the complexity of the observed precipitation, taking advantage of its geometry footprint. To address the review, it ranges from classical perspectives of fractal-based techniques to new perspectives at temporal and spatial scales as well as for classification of climatic features, including monofractal dimension, multifractal approaches, Hurst exponent, Shannon entropy and time scaling in intensity-duration-frequency curves.

Cowpea yield improvement is done by adding agricultural inputs. The use of natural substances as pesticides is being encouraged to fight against cowpea field pests. The pesticidal potentials of aqueous extracts of Azadirachta indica and Boswellia dalzielii, Metarhizium anisopliae, alone and in combination with plant extracts, as well as the commercial insecticide Decis were tested on two Vigna unguiculata varieties in field in two agroecological zones (Guinean Savanah and Sahelian Savanah) of Cameroon. The field trials were arranged in a completely randomized block design with nine treatments including control. Each treatment was replicated four times. Vigna unguiculata plants were sprayed at flowering stage thrice with insecticidal products at 5 days interval. Data assessment consisted of counting ramifications per plant, the number of pods per block, and seed yield. All the tested insecticides significantly (p&lt;0.0001) improved the cowpea yield in the two agro-ecological zones. The productions parameters were highly influenced by variety and agroecological zone. The extracts and their combinations were as effective as synthetic pesticide (Decis). Bafia variety recorded the highest ramification rate (37.03±1.59) when treated with the combination of M. anisopliae and A. indica in Maroua (Sahelian Savanah). The same variety also produced most important pods number (90.50±16.66) in Ngaoundere (Guinean Savanah) with the combination of A. indica and B. dalzielii. The highest seed yield (44.23±2.31) was recorded in Ngaoundere with B125 variety treated with the combination of the three treatments (A. indica, B. dalzielii, M. anisopliae). A. indica, B. dalzielii, M. anisopliae and their combinations could be considered as potential natural input in the improvement of V. Unguiculata yield. This would not only increase V. unguiculata yield but also preserves environment from the pollution due to the use of synthetic residual chemicals.

Earth’s land surface area is raised from conventionally flat 15 to 64 Gha to account for hilly undulation and soil relief detail. Three main aspects are: topography, rugosity/tortuosity and micro-relief/porosity of vegetation-free ground. Recalibration is arrived at from four approaches: first, direct empirical estimates from the few compiled satellite or LiDAR data with means of +2.5–26% progressively overlain by +94% at cm² scale for soil ruggedness then +108% for mm² micro-relief; second, from digital elevation models with 1.6–2.0 times flat areas; third, by ‘reverse engineering’ global soil bulk densities and carbon reserves requiring x 2–6 land. Finally, a Fermi estimation conveniently sets the World’s new surface area – that exposed to Sun, air and rain – at 100 Gha (with 36 Gha flat ocean). Soil organic carbon (SOC) is thence raised to 8,580 Gt mainly in SOM/humus with its biotic complexity plus roots, VAM-fungi and leaf-litter, that itself = 17,800 Gt. Although four to six times IPCC’s or NASA/NOAA’s calculations of just 1,500–2,300 Gt SOC, this is likely an underestimation. Global biomass and biodiversity are at least doubled (x 2–3.5) and net primary productivity (NPP) similarly increased on land to >270 Gt C yr^-1 due to terrain.

Introduction. Strontium-82/Rubidium-82 (⁸²Sr/⁸²Rb) generators are used widely for positron emission tomography (PET) imaging of myocardial perfusion. In this study, the ⁸²Rb isotope yield and production efficiency of two FDA-approved ⁸²Sr/⁸²Rb generators were compared.Methods. N=515 sequential daily quality assurance (QA) reports from 9 CardioGen-82® and 9 RUBY-FILL® generators were reviewed over a period of 2 years. A series of test elutions was performed at different flow-rates on the RUBY-FILL® system to determine an empirical correction-factor used to convert CardioGen-82® daily QA values of ⁸²Rb activity (dose-calibrator ‘maximum’ of 50 mL elution at 50 mL/min) to RUBY-FILL® equivalent values (integrated ‘total’ of 35 mL elution at 20 mL/min). The generator yield (⁸²Rb) and production efficiency (⁸²Rb yield / ⁸²Sr parent activity) were measured and compared after this conversion to a common scale. Results. At the start of clinical use, the system reported ⁸²Rb activity from daily QA was lower for CardioGen-82® vs RUBY-FILL® (2.3 ± 0.2 vs 3.0 ± 0.2 GBq, p<0.001) despite having similar ⁸²Sr activity. Dose-calibrator ‘maximum’ (CardioGen-82®) values were found to under-estimate the integrated ‘total’ (RUBY-FILL®) activity by ~24% at 50 mL/min. When these data were used to convert the CardioGen-82 values to a common measurement scale (integrated total activity) the CardioGen-82® efficiency remained slightly lower than the RUBY-FILL® system on average (88 ± 4% vs 95 ± 4%, p<0.001). The efficiency of ⁸²Rb production improved for both systems over the respective periods of clinical use.Conclusions. ⁸²Rb generator yield was significantly under-estimated using the CardioGen-82® vs RUBY-FILL® daily QA procedure. When generator yield was expressed as the integrated total activity for both systems, the estimated ⁸²Rb production efficiency of the CardioGen-82® system was ~7% lower than RUBY-FILL® over the full period of clinical use.

Some of the key features of inclusive and equitable teaching approaches encourage prompt feedback, student cooperation in communities of learning, active learning, and promotes diverse ways of knowing in the classroom. In my article, I present step-bystep tips to help instructors create guided microlearning inquiry questions within an inclusive and equitable general biology classroom setting. Microlearning is a special approach that helps students complete a specific task linked to a specific learning objective that would be completed in a short time window around five minutes. The step-by-step tips presented in my article helps instructors to develop questions aligned to specific learning objective to help clarify unclear or confusing topics in general biology using the Kahoot e-Learning platform. This guided microlearning inquiry toolkit provides a blueprint for helping instructors to infuse student-centered approaches to help clarify difficult concepts in general biology and further develop avenues refine students’ critical thinking and experimental design in biology research.

Damaged connective tissues between the bone and tendons or ligaments are common among adults regardless of activity level. Achilles tendinosis is one of the most common tissue defects and enthesopathies. The patient in this study is a 54-year-old female with chronic Achilles tendinosis from chronic enthesopathy at the Achilles tendon insertion with a retrocalcaneal exostosis for three years who has failed standard-of-care practices for over two years. The patient received extracorporeal pulsed-activated therapy (EPAT) before applying 2ml of CryoText, a Wharton’s jelly tissue allograft. The patient then received class IV laser therapy treatments twice weekly for three weeks. The patient started with a 10/10 VAS at the initial visit. At five weeks post-application, the patient’s score had improved by 80% at 2/10 VAS. By week 13, the patient rated her pain as 0/10 VAS. The improvement in patient-reported pain and functionality reported in this study after the application of Wharton’s Jelly, EPAT, and class IV laser therapy warrants future research studying the safety and efficacy of these patient care modalities together.

Transfer factor is the name given to material derived from activated lymphocytes that is probably composed of a complex of a peptide and a short segment of RNA and which has the reported ability to transfer specific T cell immunity to uncommitted lymphocytes. Many independent groups around the world reported isolating transfer factors between 1955 and 1990 and demonstrating their ability to transfer passive immunity from one animal or individual to another, often within 24 hours of inoculation. Such activity is potentially revolutionary both in making T cell vaccines readily manufacturable and also because the existence of transfer factors would undermine the basic assumptions of the clonal selection theory, which currently dominates immunological theory. Unfortunately, lack of the microanalytical and synthetic techniques required to properly identify transfer factors, combined with safety factors associated with it derivation from blood sources susceptible to HIV and prion infections, put an end to transfer factor research after 1990. This paper reviews the evidence supporting transfer factor activity and suggests that this potentially revolutionary concept be resurrected and subjected to renewed scrutiny in light of CRISPR-Cas mechanisms and because of its potential to make possible T cell vaccination and provide a novel basis for understanding immunological function.

Heart Rate Monitors (HRMs) are an indispensable tool for controlling training parameters of healthy athletes. They became a source of information about stress heart rhythm disturbances, recognized as unexpected increases in heart rate (HR), which can be life-threatening for athletes. Most HRMs do not recognize the type of arrhythmia, confusing them with artifacts. The aim of the study was to assess the usefulness of ECG recording functions by sports HRMs among endurance athletes, coaches, and physicians in comparison with other basic and hypothetical functions. We conducted 3 surveys among endurance athletes (76 runners, 14 cyclists, and 10 triathletes), as well as 10 coaches and 10 sports doctors to obtain information on how important ECG recording is, and what functions of HRMs should be improved to meet their expectations in the future. The respondents were asked questions regarding use and hypothetical functions, as well as preference for HRM type (optical/strap). For athletes, the 4 most important functions were distance traveled, pace, instant heart rate, and information about reaching the oxygen threshold. ECG recording was the 8th and 9th most important for momentary and continuous, respectively. Coaches opined more importance to ECG recording. Doctors placed ECG recording as most important. All participants preferred optical HRMs to strap HRMs. Research on the improvement and implementation of HRM functions shows slightly different preferences of athletes compared to coaches and doctors. Suspected arrhythmia increases the value of the HRM’s ability to record ECGs during training by athletes and coaches. For doctors, this is the most desirable feature in any situation. Considering the expectations of all groups continuous ECG recording during training will significantly improve the safety of athletes.

The motivations for the move to electrified vehicles are discussed with reference to their improved energy efficiency, their potential for lower CO2 emissions (if the electricity system is decarbonized), their lower (or zero) NOx/particulate matter (PM) tailpipe emissions, and the lower overall costs for owners. Some of the assumptions made in life-cycle CO2 emissions calculations are discussed and the effect of these assumptions on the CO2 benefits of electric vehicles are made clear. A number of new tribological challenges have emerged, particularly for hybrid vehicles that have both a conventional internal combustion engine and a battery, such as the need to protect against the much greater number of stop-starts that the engine will have during its lifetime. In addition, new lubricants are required for electric vehicle transmissions systems. Although full battery electric vehicles (BEVs) will not require engine oils (as there is no engine) they will require a system to cool the batteries – alternative cooling systems are discussed, and where these are fluid based, the specific fluid requirements are outlined.

In this review we aim to address the current status of phage therapy in the management of multidrug-resistant infections, from compassionate use cases to ongoing clinical trials, as well as the challenges this approach presents in the particular context of CF patients.

ABSTRACT: The idea of a Common Mucosal Immune system (CMS) is 50 years old. Its relevance to immune protection at mucosal sites and its potential to modulate the impact of vaccination-induced protection against infection of the airway, has been poorly understood. The consequent failure of current SARS-CoV-2 vaccination to satisfy expectations with respect to prevention of infection, viral transmission, duration of protection and pattern of clinical protection, led to public health and medical decisions now under review. This review summarises knowledge of the CMS in man, including the powerful role it plays in immune protection and lessons with respect to what can and can not be achieved by systemic and mucosal vaccination for prevention of airway infection. The powerful impact in both health and disease of optimising delivery of immune protection using selected isolates from the respiratory microbiome, is demonstrated through review of randomised controlled trials (RCT’s) in subjects with chronic airway disease, and in otherwise healthy individuals with risk factors, in whom the idea of mucosal immune resilience is introduced.

It appears that up to 80% of females with autistic spectrum disorder (ASD) have not been diagnosed by 18 years of age. This translates to a prevalence of about 5-6%, and if true has serious implications for female mental health. One way of finding the true value is to use Bayes’ Theorem with a comorbid condition as a more easily recognizable flag. An obvious choice is anorexia nervosa (AN), but it transpires that the proportion of women with ASD who develop AN is unknown. This study uses published data in novel ways to provide two methods of estimating a range for this variable, and gives a median value of 8.3% for AN in ASD and with four other methods a median prevalence of 6% for female ASD. The clinical implications for diagnosis and management of ASD and comorbidities are discussed and a solution is provided for the rate of ASD in generalized joint hypermobility.

Functional osseoconductive coatings based on hydroxylapatite (HAp) and applied preferentially by atmospheric plasma spraying to medical implant surfaces are a mainstay of modern implantology. During contact with the hot plasma jet, HAp particles melt incongruently and undergo complex dehydration and decomposition reactions that alter their phase composition and crystallographic symmetry, and thus, the physical and biological properties of the coatings. Surface analytical methods such as laser-Raman and nuclear magnetic resonance (NMR) spectroscopies are useful tools to assess the structural changes of HAp imposed by heat treatment during their flight along the hot plasma jet. In this contribution, the controversial information on the existence or non-existence of oxyapatite, i.e. fully dehydrated HAp as a thermodynamically stable compound is highlighted.

Transportation of goods is as old as human civilizations : past networks and their evolution shed light on long term trends. Transportation impact on climate change is measured as major, as well as the impact on spreading a pandemic. These two reasons motivate the importance of providing relevant and reliable historical geographic datasets of these networks. This paper focuses on reconstructing the railway network in France at its maximal extent, a century ago. The active stations and lines are well documented by the French SNCF, in open public data. However, that information ignores past stations (ante 1980), which represent probably more than what is recorded in public data. Additional open data, individual or collaborative (eg. Wikipedia) are particularly valuable, but they are not always geo-coded, and two more sources are necessary to completing that geo-coding: ancient maps and aerial photography. Therefore, remote sensing and volunteer geographic information are the two pillars of past railway reconstruction. The methods developed are adapted to the extraction of information from these sources: automated parsing of Wikipedia Infoboxes, data extraction from simple tables, even from simple text. That series of sparse procedures can be merged into a comprehensive computer-assisted process. Beyond this, a huge effort in quality control is necessary when merging these data: automated wherever possible, or finally visually controlled by observation of remote sensing information. The main output is a reliable dataset, under ODbl, of more than 9100 stations, which can be combined with the information about the 35000 communes of France, for a large variety of studies. This work demonstrates two thesis: (a) it is possible to reconstruct transport network data from the past, and generic computer assisted methods can be developed; (b) the value of remote sensing and volunteered geo info is considerable (what archeologists already know).

This article evaluates the reliability and consistency of nutrition- and supplementation-related advice for pregnant women provided by ten selected health-related Internet portals. The portals were chosen based on their perceived reliability and prominence in Google searches, with representation from both English and Polish language sources. The evaluation criteria included the adherence of the presented information to official recommendations and its evidence-based character based on specific items representing dietary aspects important in pregnancy. While the overall reliability was deemed acceptable, significant variations existed both among the portals and specific evaluated items. Notably, HealthLine, Medline Plus, and NCEZ emerged as the most evidence-based, while WebMD and Medycyna Praktyczna were identified as less reliable. Despite a number of issues, the analysed portals remain valuable sources of nutritional information for pregnant women, offering user-friendly accessibility superior to alternatives such as social media, on the one hand, and scientific articles, on the other. Improved consistency and attention to detail, especially in relation to vitamin intake and supplementation, would improve the overall quality of health portals.

Abstract: Doppler renal resistive index (RRI) has been used for several decades as a potential indi-cator for renal disease and progression. In recent years, RRI has emerged as a useful prognostic indicator for a range of co-morbidities in patients who are acutely unwell and as a potential marker for sub-clinical acute kidney injury (AKI) and post procedural AKI risk. Despite this, the clinical and theoretical determinants of RRI are poorly understood and remain contentious. Method: A narrative review of studies exploring the theoretical, experimental, and clinical evidence for factors affecting RRI. No date restrictions were set. Findings: Both experimental and clinical data confirm that RRI is markedly affected by a range of systemic and renal determinants and is influenced closely by the underlying risk factors and sys-temic vascular changes that lead to progressive renal damage. Discussion: This paper provides an overview of the key haemodynamic determinants of renal re-sistive index and aims to clarify their relative importance. With reference to a simplified theoretical model, evidence from experimental and clinical studies is reviewed. Pathophysiological factors and patient characteristics that influence RRI are explored to provide a better understanding of why RRI values change in the presence of common or complex pathologies. Conclusion: By gaining a better understanding of the complex systemic and renal factors that influ-ence RRI, ultrasound users will be better prepared to understand and interpret changes in RRI across a range of patient presentations.

In South Sudan, three case-control studies found a positive association between Nodding Syn-drome (NS) and a Mansonella perstans infection. To investigate whether M. perstans could play the primary and sole causal role in the development of NS, we examined blood films of persons with and without epilepsy in rural villages affected by NS in Mahenge, Tanzania, to identify M. perstans infections. Study participants were also examined for onchocercal nodules and skin lesions and tested for the presence of anti-O. volvulus antibodies (Ov16 ELISA). One hundred and thirteen epilepsy cases and 132 controls were enrolled, with a mean age of 28.3 years (interquartile range 22 – 34 years); 125 (51%) were females. Of the persons with epilepsy, 43 (38.1%) met the probable NS criteria. M. perstans infection was absent in all participants, but Ov16 prevalence and oncho-cerciasis-associated skin manifestations were positively associated with epilepsy, including probable NS. Onchocercal nodules in the mothers of cases were also positively associated with epilepsy. In conclusion, in contrast with O. volvulus, M. perstans is likely not endemic in Mahenge and therefore cannot be a co-factor for NS in the area. Hence, this filaria cannot be the primary and sole causal factor in the development of NS.

There has been a recent revival of interest in the notion of a `trajectory' of a quantum particle. In this paper we detail the relationship between Dirac's ideas, Feynman paths and the Bohm approach. The key to the relationship is the weak value of the momentum which Feynman calls a transition probability amplitude. With this identification we are able to conclude that a Bohm `trajectory' is the average of an ensemble of actual individual stochastic Feynman paths. This implies that they can be interpreted as the mean momentum flow of a set of individual quantum processes and not the path of an individual particle. This enables us to give a clearer account of the experimental two-slit results of Kocsis {\em et al.}}

Transgender youth experience elevated levels of victimization and may therefore report greater drug use than their cisgender peers, yet little is known about protective factors like school belonging that may mediate this relationship. Further, scant research has explored the experiences of youth at the intersection of transgender identity and youth of color status or low socioeconomic status, especially with respect to these multiple minority statuses’ associations with peer victimization, drug use, and school belonging. Using data from the California Healthy Kids Survey, the current study employs structural equation modeling to explore the relationships among school belonging, peer victimization, and drug use for transgender youth. Findings indicate that school belonging does mediate the pathway between peer victimization and drug use for transgender youth and that although youth of color experience greater victimization, they do not engage in greater drug use than their white transgender peers. Based on these results, those concerned with the healthy futures of transgender youth should advocate for more open and affirming school climates that engender a sense of belonging and treat transgender youth with dignity and fairness.

Glioblastoma is the most common and malignant primary brain tumor. Despite a century of research efforts, the survival of patients has not significantly improved. Currently, diagnosis is based on neuroimaging techniques followed by histopathological and molecular analysis of resected or biopsied tissue. A recent paradigm shift in diagnostics ranks the molecular analysis of tissue samples as the new gold standard over classical histopathology, thus correlating better with the biological behavior of glioblastoma and clinical prediction, especially when a tumor lacks the typical hallmarks for glioblastoma. Liquid biopsy aims to detect and quantify tumor-derived content, such as nucleic acids (DNA/RNA), circulating tumor cells (CTC), or extracellular vesicles (EV) in biofluids, mainly blood, cerebrospinal fluid (CSF), or urine. Liquid biopsy has the potential to overcome the limitations of both neuroimaging and tissue-based methods to identify early recurrence and to differentiate tumor progression from pseudoprogression, without the risks of repeated surgical biopsies. This review highlights the origins and time-frame of liquid biopsy in glioblastoma and points to recent developments, limitations and challenges of adding liquid biopsy to support the clinical management of glioblastoma patients.

Glycosidic linkage analysis was conducted on the unfractionated polysaccharides in the alcohol-insoluble residues (AIRs) prepared from six red seaweeds (Gracilariopsis sp., Prionitis sp., Mastocarpus papillatus, Callophyllis sp., Mazzaella splendens, and Palmaria palmata) using GC-MS/FID analysis of partially methylated alditol acetates (PMAAs). The cell walls of P. palmata primarily contained mixed-linkage xylans and small amounts of sulfated galactans and cellulose. In contrast, the unfractionated polysaccharides of the other five species were rich in galactans displaying diverse 3,6-anhydro-galactose and galactose linkages with varied sulfation patterns. Different levels of cellulose were also observed. This glycosidic linkage method offers advantages for cellulose analysis over traditional monosaccharide analysis that is known for underrepresenting glucose in crystalline cellulose. Relative linkage compositions calculated from GC-MS and GC-FID measurements showed that anhydro sugar linkages generated more response in the latter detection method. This improved linkage workflow presents a useful tool for studying polysaccharide structural variations across red seaweed species. Furthermore, for the first time, relative linkage compositions from GC-MS and GC-FID measurements, along with normalized FID and total ion current (TIC) chromatograms without peak assignments, were analyzed using principal component analysis (PCA) as a proof-of-concept demonstration of the technique's potential to differentiate various red seaweed species.

Background: The potential of Artificial intelligent (AI) models to process and interpret large health datasets at scale could revolutionize public health and epidemiology, providing a foundation for public health. Ethics has been recognized as a priority concern in the development and deployment of AI. Because AI technology can jeopardize patient safety, privacy, and posing a new set of ethical problems that must be addressed. Objectives: We aim to provide a holistic view on what are the different ethical and legal principles that was addressed in the included studies regarding the use of AI in public health and what are the ethical challenges that can arise.Methods: Following PRISMA guideline, five bibliographic databases were used in our search: PubMed, Scopus, JSTOR, IEEE Xplore, and Google Scholar from 2015 to February 2022. Four reviewers carried out study selection and data extraction, and the data extracted was synthesized by a narrative approach. Results: This review included 23 unique publications out of a total of 1123 items that were initially identified. Different ethical principles regarding the uses of AI in public health and community health were identified and discussed distinctly in the current review. The common ethical and legal themes that this review focused on are equity, bias, privacy and security, safety, transparency, confidentiality, accountability, social justice, and autonomy. In addition, five ethical challenges were mentioned. Conclusion: Research regarding ethical and legal principles and challenges about using AI in public health specifically consider a new filed, because all previous themes are concerning the physical and patients’ area where it focuses only on the clinical settings.

Pancreatic cancer is one of the most aggressive and lethal forms of cancer, with a five-year survival rate of less than 10%. Despite advances in treatment modalities, the prognosis for pancreatic cancer patients remains poor, highlighting the urgent need for innovative approaches for early diagnosis and targeted therapies. In recent years, there has been significant progress in understanding the molecular mechanisms underlying pancreatic cancer development and progression. This paper reviews the current knowledge of molecular targets for the diagnosis and treatment of pancreatic cancer.

MnSi has played a major role since the late 1970s in developing the theory of helical magnets in non-centro symmetric materials showing Dzyaloshinsky-Moriya interaction (DMI). With a long helimagnetic pitch of 175 \AA~as compared to the lattice d-spacing of 4.55\AA, it was ideal for performing neutron studies especially as large single crystals could be grown. In these studies under the application of a field of 180 mT perpendicular to Q, a so-called A-phase in the B-T phase diagram was found and interpreted as a rotation of the alignment of the magnetic helix away from the pinning axis. After the surprising discovery of the skyrmion lattice in the A-phase in 2009 much interest arose as it could be shown that the magnetic skyrmion lattice is topologically protected. Due to the rigidity of the skyrmionic lattice it is only loosely bound to the crystal lattice and therefore only relatively small current densities can already induce a motion of this lattice. Another very interesting aspect are the excitations in the spin system of MnSi. As the helimagnetic state is characterized by a long pitch of about 175 \AA, the associated characteristic excitations form a band structure due to Umklapp scattering and can only be observed at very small q with energies below 1 meV. We have investigated the the magnons in MnSi in the whole (B,T)-phase diagram starting in the single-k helimagnetic state by applying a small magnetic field B = 100 mT. This way, the complexity of the magnon spectrum is significantly reduced allowing a detailed comparison of the data with theory resulting in a full theoretical understanding of the spin system of MnSi in all its different magnetic phases.

The destruction of natural habitat for cropland and pastures represents a major threat to global biodiversity. Despite widespread societal concern about biodiversity loss associated with food production, consumers access to quantitative estimates of the impact of crop production on the world’s species has been very limited compared to assessments of other environmental variables such as greenhouse gas emissions or water use. Here, we present a consistent dataset of the biodiversity footprints of pastures and 175 individual crops at country level. The data were generated by combining maps of the global distribution of agricultural areas in the year 2000 with spatially explicit estimates of the biodiversity loss associated with the conversion of natural habitat to farmland. Estimates were derived for three common alternative measures of biodiversity – species richness, threatened species richness, and range rarity – of the world’s mammals, birds, and amphibians. Our dataset provides important quantitative information for food consumers and policy makers, allowing them to take evidence-based decisions to reduce the biodiversity footprint of global food production.

Developmental, clinical, and epidemiological research have demonstrated the salience of perceived racial discrimination (PRD) as a contributor to negative mental health outcomes in adolescence. This article summarizes secondary analyses of cross-sectional data from a large-scale youth survey within a predominantly rural state to estimate the prevalence and strength of association between PRD and serious psychological distress, suicidal ideation, and prior suicidal attempts. Data from 93,812 students enrolled in Grades 6, 8, 10, and 12 within 129 school districts across Kentucky were examined to determine prevalence rates for subgroups within the cohort. Logistic regression analyses assessed differences and established comparative strength of association among these variables for racial/ethnic subgroups. PRD was self-reported at high rates across several demographic subgroups and was most evident among Black (24.5%) and Asian (22.1%) students. Multiracial students experienced the highest rates of both SPD and suicidality. Both for the entire cohort and for each racial/ethnic subgroup, PRD was significantly associated with increased likelihood of negative mental health outcomes, although the strength of these associations varied across subgroups and developmental levels. Implications for early intervention and prevention are discussed.

Displacement mapping is a computer graphics technique that enables the design of components with regularly or randomly textured surfaces that can be quickly materialized on a three-dimensional (3D) printer when needed. This approach is in principle more flexible, faster and more economical compared to conventional texturing methods, but the accuracy of the texture depends heavily on the parameters used. The purpose of this study is to demonstrate how to produce a surface-textured part using polygonal (mesh) modeling software and a photopolymerizable resin, and to develop a universal methodology to predict the dimensional accuracy of the model file log combined with a resin 3D printer. The printed components were characterized on a scanning confocal microscope. In the setup used in this study, the mesh size had to be reduced to 10% of the smallest feature size and the textured layer had to be heavily (x4) overexposed to achieve the desired accuracy. As a practical application, two functional stamps with a regular (honeycomb) and a random texture, respectively, were successfully manufactured. The insights gained will be of great benefit in quickly and cost-effectively producing components with innovative patterns and textures for a variety of hobby, industrial and biomedical applications.

This contribution attempts to provide a state-of-the-art account on the physicochemical and biomedical properties of plasma-sprayed hydroxylapatite (HAp) coatings that are routinely applied to the surfaces of metallic endoprosthetic and dental root implants, designed to replace or restore lost functions of diseased or damaged tissues of the human body. Even though the residence time of powder particles of HAp in the plasma jet is extremely short, the high temperature applied introduces compositional and structural changes of the precursor hydroxylapatite that severely affect its chemical and physical properties and in turn, its biomedical performance. These changes are based on the incongruent melting behaviour of HAp and can be traced, among many other analytical techniques, by high-resolution synchrotron X-ray diffraction, vibrational (Raman), and nuclear magnetic resonance (NMR) spectroscopies. In vivo reactions of the plasma-sprayed coatings with extracellular fluid (ECF) can be assessed and predicted by in vitro testing using simulated body fluids as proxy agents. Ways are being discussed to safeguard appropriate biological performance of hydroxylapatite coatings in long-term service by controlling their phase content, porosity, surface roughness, residual stress distribution, and adhesion to the implant surface.

We propose the traditional goal of cancer therapists to develop a single drug or drug combination that can, by itself, eliminate all cancer cells within a host has neglected potential treatments that may achieve curative outcomes by strategically combining agents that are individually effective but non-curative. We derive basic principles for such an approach from the eco-evolutionary dynamics of background extinctions in which a “first strike” reduces the size and heterogeneity of the initial population and is followed immediately by demographic and ecological “second strikes” that push the population below an extinction threshold. This proposed strategy appears identical to the empirically-derived curative therapy in childhood Acute Lymphocytic Leukemia.

The study presents an updated overview of the 14 non-endemic threatened Crop Wild Relatives (CWR) in Italy: Aegilops biuncialis, Ae. uniaristata, Ae. ventricosa, Asparagus pastorianus, Beta macrocarpa, Brassica insularis, B. montana, Crambe hispanica subsp. hispanica, C. tataria subsp. tataria, Ipomoea sagittata, Lathyrus amphicarpos, L. palustris, Vicia cusnae and V. serinica. Geographical distribution, ecology (with plant communities and habitat 92/43/EEC aspects), genetics (focused on gene pools), property, and in situ and ex situ conservation were analyzed. In addition, with the aim of their protection and valorization, specific actions are recommended.

The aim of the research results presented in the article is to strengthen a better understanding of the processes related to the transformation of hard coal mining in Poland, in particular the preparation of employees and their representatives, as well as employers from transformed areas for the upcoming changes. In this perspective, anticipating future skills against the internal potential of entrepreneurs becomes more and more important. It is a key element that enables entrepreneurs to adapt to changes, create innovative solutions and remain competitive on the market.

We present a method using contour integration to derive definite integrals and their associated infinite sums which can be expressed as a special function. We give a proof of the basic equation and some examples of the method. The advantage of using special functions is their analytic continuation which widens the range of the parameters of the definite integral over which the formula is valid. We give as examples definite integrals of logarithmic functions times a trigonometric function. In various cases these generalizations evaluate to known mathematical constants such as Catalan’s constant and π

This study evaluates spatial analyses of groundwater quality and environmental changes to obtain information on the groundwater contamination in the Permian Basin, Texas. Coupled with the U.S. government’s open data, these analyses can identify regions where environmental change could have potentially effected groundwater quality. A total of thirty-six wells were selected within the six counties: Andrews, Martin, Ector, Midland, Crane, and Upton. Spatial distribution maps were created for six different parameters: pH, total dissolved solids (TDS), chloride, fluoride, nitrate, and arsenic. Total groundwater quality maps incorporate all the contaminants and denote regions of poor, medium, and optimum conditions. To identify spatial changes in groundwater quality, maps were separated into two different time intervals, 1992-2005 and 2006-2019. We found that groundwater contamination resulted primarily from the mobilization of the contaminant from natural sources or anthropogenic activities such as chemical fertilizers. Overall, groundwater quality decreased during the study period from 1992 to 2019 as population and urban growth began to develop in the Permian Basin. This study contributes on understanding of the response of groundwater quality associated with environmental change in the Permian Basin. Therefore, this research provides important information for groundwater managements in developing plans for the use of water resource in the future for Texas.

The development of CRISPR associated proteins, such as Cas9, has led to increased accessibility and ease of use in genome editing. However, additional tools are needed to quantify and identify successful genome editing events in living animals. We developed a method to rapidly and quantitatively monitor gene editing activity non-invasively in living animals that also facilitates confocal microscopy and nucleotide level analyses at the end of study. Here we report a new CRISPR “footprinting” approach to activate luciferase and fluorescent proteins in mice as a function of gene editing. This system is based on experience with our prior Cre-detector system and is designed for Cas editors able to target LoxP including gRNAs including SaCas9 and ErCas12a [1, 2]. These CRISPRs cut specifically within LoxP, an approach that is a departure from previous gene editing in vivo activity detection techniques that targeted adjacent stop sequences. In this sensor paradigm, CRISPR activity was monitored non-invasively in living Cre reporter mice (FVB.129S6(B6)-Gt(ROSA)26Sortm1(Luc)Kael/J and Gt(ROSA)26Sortm4(ACTB-tdTomato,-EGFP)Luo/J, which will be referred to as LSL and mT/mG throughout the paper) after intramuscular or intravenous hydrodynamic plasmid injections, demonstrating utility in two diverse organ systems. The same genome-editing event was examined at the cellular level in specific tissues by confocal microscopy to determine the identity and frequency of successfully genome-edited cells. Further, SaCas9 induced targeted editing at efficiencies that were comparable to Cre recombinase demonstrating high effective delivery and activity in a whole animal. This work establishes genome editing tools and models to track CRISPR editing in vivo non-invasively and to fingerprint the identity of targeted cells. This approach also enables similar utility for any of the thousands of previously generated LoxP animal models.

The rabbit is a popular animal model for human biomechanical research involving surgery at the hind limb. General anesthesia in rabbits is associated with significantly higher mortality rates than in dogs and cats. In addition, as prey animals, rabbits tend to mask signs of pain, making early detection particularly difficult. Regional anaesthesia, as an adjunct to general anaesthesia, may markedly reduce the need for systemic anaesthetic and analgesic drugs, limiting their associated side effects. In other species, a block of the sciatic (ScN) and the femoral nerves (FN) is usually applied in patients undergoing hind limb surgery. In phase 1 of this study, the ScN and the FN have been localized and an appropriate approach under sonographic guidance has been evaluated. In phase 2, a mixture of methylene blue and lidocaine have been administered to the ScN and the FN in 10 cadavers (20 hind limbs). Staining of the nerves was evaluated by dissection. Ultrasonographically, the ScN appeared as a binocular structure surrounded by a hyperechoic rim. The FN appeared as a hypoechoic structure in the dorsal part of the IPM, becoming hyperechoic/honey-comb-like in the ventral part. Both nerves could be successfully stained in all animals over a median length of 2.3 cm which was considered effective. This technique allows a feasible and accurate access to block of the ScN and the FN and may lead to successful analgesia in rabbits undergoing hind limb surgery.

Aim: To evaluate the panmacular subthreshold micropulse laser treatment results among patients with central serous chorioretinopathy (CSC) and their correlation with functional and morphological parameters. Material and methods: The examined group included 10 non-treated and 41 treated patients with acute, recurrent, and chronic CSC (13 F, 38 M, mean age 44.11±6.5) and 14 healthy controls (6 F, 8 M, mean age 45±9.3). The BCVA examination, ophthalmoscopy, microp-erimetry, angio-OCT and OCT were performed. The medical history regarding chronic general disorders and known risk factors were recorded. Results: Complete resorption of SRF was obtained in 100% aCSC, 86.66% cCSC, and 63.63% r CSC. BCVA and RetSens significantly improved most of the patients treated in aCSC. The lowest BCVA and RetSens, but the largest pachyvessel and disease duration, were found in rCSC. A strong negative correlation between final BCVA and disease duration was found. No patient demonstrated laser lesions following treatment. Conclusions: The panmacular MPLT therapy leads to long-term enhancement of functional and morphological parameters in all CSC patients. The acute CSC patients showed the most significant improvement. The procedure is safe and could be considered a preferred treatment option for all active CSC cases. Timely treatment is crucial for beneficial outcomes.

Despite the remarkable success of Carnot’s heat engine cycle in founding the discipline of thermodynamics two centuries ago, false viewpoints of his use of the caloric theory in the cycle still linger, limiting his legacy. An action revision of the Carnot cycle can correct this, showing that the heat flow powering external mechanical work is compensated internally with configurational changes in the thermodynamic or Gibbs potential of the working fluid, differing in each stage of the cycle quantified by Carnot as caloric. Action (@) is a property of state having the same physical dimensions as angular momentum (mrv=mr2ω). However, this property is scalar rather than vectorial, including a dimensionless phase angle (@=mr2ωδφ). We have recently confirmed with atmospheric gases that their entropy is a logarithmic function of the relative vibrational, rotational and translational action ratios with Planck’s quantum of action ħ. The Carnot principle shows that the maximum rate of work (puissance motrice) possible from the reversible cycle is controlled by the difference in temperature of the hot source and the cold sink, the colder the better. This temperature difference between the source and the sink also controls the isothermal variations of the Gibbs potential of the working fluid, that Carnot identified as reversible temperature-dependent but unequal exchanges in caloric. Importantly, the engine’s inertia ensures that heat from work performed adiabatically in the expansion phase is all restored to the working fluid during the adiabatic recompression, less the net work performed. This allows both the energy and the thermodynamic potential to return to the same values at the beginning of each cycle, a point strongly emphasized by Carnot. Our action revision equates Carnot’s calorique, or the non-sensible heat later described by Clausius as ‘work-heat’ exclusively to negative Gibbs energy (-G) or quantum field energy. This action field complements the sensible energy or vis-viva heat as molecular kinetic motion and its recognition should have significance for designing more efficient heat engines or better understanding of the heat engine powering the Earth’s climates.

Installations of decentralised Renewable Energy Systems (RES) are becoming increasing popular as governments introduce ambitious energy policies to curb emissions and slow surging energy costs. This work presents a novel model for optimal sizing for decentralised renewable generation and hybrid storage system to create a Renewable Energy Community (REC), developed in Python. The model implements PV Solar and Wind Turbines combined with a hybrid battery and Regenerative Hydrogen Fuel Cell (RHFC). The electrical service demand is derived using real usage data from a rural island case study location. Cost remuneration is managed with an REC virtual trading layer, ensuring fair distribution among actors in accordance with the European RED(III) policy. A multi-objective Genetic Algorithm (GA) stochastically determines the system capacities such that the inherent trade-off relationship between project cost and decarbonisation can be observed. The optimal design results in an LCOE of 0.15€/kWh, reducing costs by over 50% compared with typical EU grid power, with a project IRR of 10.8%, simple return of 9.6%/year, and ROI of 9 years. Emissions output from grid only use is reduced by 72% to 69 gCO2e/kWh. Further research of lifetime economics and additional revenue streams in combination with this work could provide a useful tool for users to quickly design and prototype future decentralised REC systems.

A recent paradigm shift in diagnostics of medulloblastoma allows the distinction of four major groups defined by genetic data rather than histology. This new molecular classification correlates better with prognosis and will allow better clinical management for therapies targeting druggable mutations, but also offers a new combination of monitoring tumor development in real-time and treatment response by sequential liquid biopsy. This review highlights recent developments after a century of milestones in neurosurgery, radio- and chemotherapy, but also controversial theories on the cell of origin, animal models and the use of liquid biopsy.

Mangroves offer vital ecological advantages including air and water filtration, coastal and estuarine habitat provision, sediment stabilization, and wave energy absorption. Their intricate root systems play a key role in safeguarding shorelines from tsunamis and erosive storms by dissipating wave energy. Moreover, mangroves shield against boat wakes and wind-waves, bolstering shoreline defense. Wave dissipation is a function of forest width, tree diameter, and forest density. Restoration efforts of juvenile mangroves in Florida’s Indian River Lagoon (IRL) aim to reduce wave energy in areas vulnerable to erosion. Physical model testing of wave dissipation through mangroves is limited due to the complexity in representing the mangrove structure, where prop roots are non-uniform in both diameter and location. Previous studies have quantified wave dissipating effects through use of scaled and parameterized mangrove structures. This study measures the dissipation effects of live mangroves in a wave flume, forced by conditions representative of the IRL. These measurements are used to validate a parameterized dowel model. Error between wave attenuation factors for the live mangrove and dowel system was on average 2.5%. Validation of the modularized dowel system allowed for further parameterized testing to understand forest structure effects, such as sediment stabilization and wave attenuation.

Dimethylformamide (DMF), a polar solvent, is commonly used for preparing graphene/epoxy nanocomposites. While commonly previous research has predominantly highlighted the improvement in physio-mechanical properties of these nanocomposites, the effect of DMF on processing and its direct influence on the final characteristics of MXene/epoxy nanocomposites have not been investigated.This unexplored link between DMF dosage, MXene concentrations, and the final composite properties presents an exciting direction for future research. In this study, a fixed dosage of DMF was used with varying MXene concentrations to fabricate the nanocomposites. To assess the reliability of DMF dosage on the characteristics of the fabricated nanocomposites, various evaluation techniques were employed, including dispersion evaluation, mechanical tests, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), electromagnetic interference (EMI) shielding, and surface roughness measurements. The research outcomes revealed that as MXene concentration increased, the characteristics of the MXene/epoxy nanocomposites, improved across the board, indicating their potential for use in energy storage applications.

This review discusses a broad range of recent advances (2013-2017) of chemical imaging using electrochemical methods, with a particular focus on techniques that have been applied to study cellular processes, or techniques that show promise for use in this field in the future. Non-scanning techniques such as microelectrode arrays (MEAs) offer high time-resolution (< 10 ms) imaging, however at reduced spatial resolution. In contrast, scanning electrochemical probe microscopies (SEPMs) offer higher spatial resolution (as low as a few nm per pixel) imaging, with images collected typically over many minutes. Recent significant research efforts to improve the spatial resolution of SEPMs using nanoscale probes, and to improve the temporal resolution using fast scanning have resulted in movie (multiple frame) imaging with frame rates as low as a few seconds per image. Many SEPM techniques lack chemical specificity or have poor selectivity (defined by the choice of applied potential for redox-active species). This can be improved using multifunctional probes, ion-selective electrodes and tip-integrated biosensors, although additional effort may be required to preserve sensor performance after miniaturization of these probes. We discuss advances to the field of electrochemical imaging, and technological developments which are anticipated to extend the range of processes that can be studied. This includes imaging cellular processes with increased sensor selectivity and at much improved spatiotemporal resolution than has been previously customary.

Recent advances in microscopy imaging and image analysis motivate more and more institutes world-wide to establish dedicated core-facilities for bio-image analysis. To maximize the benefits research groups at these institutes gain from their core-facilities, they should be established to fit well into their respective environment. In this article, we introduce common collaborator requests and corresponding potential services core-facilities can offer. We also discuss potential conflicts of interests between the targeted missions and implementations of services to guide decision makers and core-facility founders to circumvent common pitfalls.