Dietary inclusion of trace minerals (TM), such as copper (Cu), manganese (Mn) and zinc (Zn) is of importance to cover the ever-evolving requirements for growth, production, and reproduction in ruminants. Various sources of TM are commercially available, such as inorganic (ITM), organic (OTM) or hydroxy (HTM) forms, however their bioavailability and efficiency to improve ruminant zootechnical parameters may be highly influenced by ruminal solubility and effects on the rumen environment. The objective of this review was to compile the most up-to-date information on the ruminal solubility of ITM, OTM and HTM, and their effects on fermentation parameters and rumen microbiota, aiming to support specialists from the animal feed industry when choosing TM products for ruminant supplementation. Some commonly used ITM sources, like sulfates, have a high ruminal solubility, while oxides are less soluble. The ruminal solubility of OTM is mostly found to be high, however data on these TM forms are still lacking. Regarding HTM, ruminal solubility is reported to be low, nevertheless results are inconsistent. Considering rumen fermentation, ITM show a negative effect, OTM might improve, while HTM do not affect parameters like dry matter degradability, volatile fatty acid production, pH, or microbial protein synthesis. As to rumen microbiota, ITM do not affect microbial populations; OTM could decrease abundance of some specific bacteria, like fibrolytic microorganisms, while studies with HTM are missing or inconclusive. Further research is necessary to better understand the ruminal solubility kinetics of TM sources and the different interactions with fermentation parameters and rumen microbiota to successfully apply precision TM supplementation of ruminants, tackling deficiency occurrences.

The aim of this study was to assess the effects of supplementation of inorganic sources of manganese (MnO, MnSO4), zinc (ZnO, ZnSO4) and copper (CuSO4) at different levels (0.06%DM for Mn, 0.05%DM for Zn; and 0.01 and 0.05%DM for Cu) on in vitro rumen fermentation, solubility and bioavailability. Fermentation activity was measured by total gas production (TGP) and dry matter degradability after 70hrs of fermentation (dDM%). Trace-mineral (TM) solubility was estimated by the TM concentration in the supernatant of the final fermentation medium (SOL) and TM bioavailability by the TM concentration in a bacterial enriched fraction (BACT). Mn (regardless of source) and ZnO tended (p<0.10) to decrease, while Cu showed no significant effect on TGP. The addition of inorganic Mn and of ZnO tended (p<0.10) to decrease, ZnSO4 tended to increase (p<0.10), whilst Cu showed no effect on dDM%. Concerning solubility, Mn (MnO and MnSO4), ZnSO4 and CuSO4 significantly (p<0.05, p<0.001 and p<0.01) increased, while ZnO did not affect TM content of the SOL. These results indicate that MnSO4, ZnSO4 and CuSO4 are highly soluble, MnO is quite soluble, while ZnO has a low solubility in the rumen. Based on the TM content of BACT, MnO, MnS4 and CuSO4 have a high bioavailability, while ZnO is poorly assimilated by rumen bacteria. However, the lack of clear inhibition or improvement of fermentations suggests that the rumen microbiota has low requirement for TM supplementation.

In this paper, a system of searching for optimal paths is developed and concreted on a FPGA. It is based on a memristive emulator, used as a delay element, by configuring the test graph as a memristor network. A parallel algorithm is applied to reduce computing time and increase efficiency. The operation of the algorithm in Matlab is checked beforehand and then exported to two different Intel FPGAs: a DE0-Nano board and an Arria 10 GX 220 FPGA. In both cases reliable results are obtained quickly and conveniently, even for the case of a 300x300 nodes maze.

This paper provides the solution to understanding the hitherto unknown writing system used for the manuscript listed as MS 408 at the Beinecke Library, Yale University. The writing system uses symbols, punctuation, grammar and language that are each unique. The manuscript is not encrypted, in the sense that its author made an effort to conceal the contents of the manuscript, as has been presumed by some scholars. Instead, it is code only in the sense that the modern reader needs to be versed in the calligraphic and linguistic rules to be able to translate and read the texts. Furthermore, in discovering its writing system, it became apparent that the manuscript is of invaluable importance to the study of the evolution of the Romance languages and the scheme of Italic letters and associated punctuation marks now commonplace in those and other modern languages. In short; it is revealed to be the only known document both written in Vulgar Latin, or proto-Romance, and using proto-Italic symbols. The original title for the manuscript, given by its female author, is: What one needs to be sure to acquire for the evils set in one’s fate. It is a book offering homeopathic advice and instruction to women of court on matters of the heart, of sexual congress, of reproduction, of motherhood and of the physical and emotional complications that can arise along the way through life. The manuscript has now been dated to the year 1444 and the location of its creation has been pinpointed to the court of Castello Aragonese, on the island of Ischia: as expounded in the companion paper Linguistically Dating and Locating Manuscript MS408: http://ling.auf.net/lingbuzz/003808.

Conventional greenhouse accounting inadequately describes land use/land use change and forestry (LULUCF) emissions, cooling emissions, and sequestration potential. As we enter the age of drawdown, we propose an accounting framework that offers greater consistency and transparency. By unfolding net accounting of LULUCF CO2 emissions; aggregating biosphere sinks; accounting for all emissions (heating and cooling); com-paring sectors with emissions-based Effective Radiative Forcing (ERF) rather than global warming potential; and including drawdown potential of land use carbon opportunity cost (COC), this reveals fresh insight into sector contributions and mitigation potential. Consistent gross emissions reporting of LULUCF CO2 emissions finds these to be at least 3.5 times greater than conventionally understood. Consolidating natural sequestration on ‘managed’ and ‘intact’ land, we find that since 1750 vegetation and the oceans have removed from the atmosphere an amount equivalent to 2.4 times cumulative fossil fuel CO2 emissions, demonstrating the immense drawdown potential of the biosphere. This accounting places deforestation (responsible for 77% of LULUCF emissions) as the main source of historic CO2 emissions, and attributes drawdown potential COC to sectors. The most extensive land use sector, animal agriculture, was found to have contributed the greatest warming (52% of net ERF since 1750) and to offer the greatest drawdown potential COC.

Quantum-dot cellular automata (QCA) is an emerging transistor-less field-coupled nanocomputing (FCN) approach to ultra-scale ‘nanochip’ integration. In QCA, to represent digital circuitry, electrostatic repulsion between electrons and the mechanism of electron tunnelling in quantum dots are used. QCA technology can surpass conventional complementary metal-oxide semiconductor (CMOS) technology in terms of clock speed, reduced occupied chip area, and energy efficiency. To develop QCA circuits, irreversible majority gates are typically used as the primary components. Recently, some studies have introduced reversible design techniques, using reversible majority gates as the main building block, to develop ultra-energy efficient QCA circuits. However, this approach resulted in time delays, an increase in the number of QCA cells used, and an increase in the chip area occupied. This work introduces a novel hybrid design strategy employing QCA irreversible, reversible, and partially reversible gates to establish an optimal balance between power consumption, delay time, and occupied area. The hybrid technique allows the designer to have more control over the circuit characteristics to meet different system needs. A combination of reversible, irreversible, and innovative partially reversible majority gates is used in the proposed hybrid design method. We have evaluated the hybrid design method by examining the half-adder circuit as a case study. We have developed four hybrid QCA half-adder circuits, each of which simultaneously incorporates various types of majority gates. The QCADesigner-E 2.2 simulation tool was used to simulate the performance and energy efficiency of the half-adders. This tool provides numerical results for the circuit input/output response and heat dissipation at the physical level, within a microscopic quantum mechanical model.

A new method for multi-shot reconstruction of high-energy photon distributions in the context of studying the interaction between a beam and a plasma in plasma wakefield acceleration (PWFA) experiments is presented. The study investigates the effects of beam perturbations on betatron radiation and analyzes how these perturbations can lead to hosing, a transverse instability that can degrade the quality of the beam. The potential of betatron radiation spectroscopy as a non-invasive diagnostic technique for PWFA experiments is also emphasized.

Photoplethysmography (PPG) is a simple-to-perform vascular optics measurement technique that can detect changes in blood volume in the microvascular tissue bed. Beat-to-beat analysis of the PPG waveform enables the study of the variability of pulse features such as amplitude and pulse arrival time (PAT), and when quantified in the time and frequency domains, has considerable potential to shed light on perfusion changes associated with peripheral arterial disease (PAD). In this pilot study innovative multi-site bilateral finger and toe PPG recordings from 43 healthy control subjects and 31 PAD subjects were compared (recordings each at least 5 minutes, collected in a warm temperature-controlled room). Beat-to-beat normalized amplitude and PAT variability was then quantified in the time-domain using SD and IQR measures and in the frequency-domain bilaterally using Magnitude Squared Coherence (MSC). Significantly reduced normalized amplitude variability (healthy control 0.0384 (IQR 0.0217-0.0744) vs PAD 0.0160 (0.0080-0.0338) (p<0.001) and significantly increased PAT variability (healthy control 0.0063 (0.0052-0.0086) vs PAD 0.0093 (0.0078-0.0144) (p<0.001) was demonstrated in PAD using the time-domain analysis. Frequency-domain analysis demonstrated significantly lower MSC values across a range of frequency bands for PAD patients. These changes suggest a loss of right-to-left body side coherence and cardiovascular control in PAD. This study has also demonstrated the feasibility of using these measurement and analysis methods in studies investigating multi-site PPG variability for a wide range of cardiac and vascular patient groups.

Given the accelerating scientific, clinical and consumer interest in highly-prevalent functional gastrointestinal disorders, appropriate therapeutic strategies are needed to address the many aspects of digestive dysfunction. Accumulating evidence for the crucifer-derived bioactive molecule, sulforaphane in upstream cellular defence mechanisms highlights its potential as a therapeutic candidate in targeting functional gastrointestinal conditions together with systemic disorders. This article catalogues the evolution of and rationale for a hypothesis that utilises multifunctional sulforaphane as the initial step in restoring the ecology of the gut ecosystem; it does this primarily by targeting the functions of intestinal epithelial cells. A growing body of work has identified the colonocyte as the driver of dysbiosis, so that targeting gut epithelial function could provide an alternative to targeting the microbes themselves for remediation of microbial dysbiosis. The hypothesis discussed herein has evolved over several years and is supported by case studies showing the application of sulforaphane in gastrointestinal disorders, related food intolerance and several systemic conditions. To our knowledge, this is the first time the effects of sulforaphane have been reported in a clinical environment where several of its key properties within the gut ecosystem appear to be related to its nutrigenomic effects on gene expression.

Identifying a vestibular source of pathology in patients complaining of post-traumatic brain injury (TBI) dizziness can be difficult. We describe a possible new method utilizing the reduction of post-TBI symptom (including dizziness) with the use of a noise cancellation device (NCD). This retrospective case series included patients with TBI and dizziness presenting to a binocular vision specialty clinic, who were diagnosed with a vertical heterophoria (VH). If they did not respond adequately to microprism lenses and/or if they experienced hyperacusis, they were evaluated with an NCD. If there was marked reduction of TBI symptoms (including dizziness), the patients were referred to a neuro-otologist for vestibular diagnostic evaluation and treatment. Fourteen patients were identified and found to have abnormalities on vestibular testing consistent with Third Mobile Window Disorder (TMWD). All were treated with a 6-week medical protocol (diuretics, no straining, low sodium/no caffeine diet). Five responded positively, requiring no further treatment. Nine required surgical intervention and responded positively. In conclusion, 14 patients with post-concussive dizziness and VH, a positive response to NCD was associated with abnormal vestibular testing, a diagnosis of TMWD, and symptom reduction/resolution with a medical or surgical approach. The removal of sound resulting in reduction or resolution of vestibular symptoms represents an Inverse Tullio Phenomena.

Global food security for the increasing world population not only requires increased sustainable production of food but a significant reduction in pre- and post-harvest waste. The timing of when a fruit is harvested is critical for reducing waste along the supply chain and increasing fruit quality for consumers. The early in field assessment of fruit ripeness and prediction of the harvest date and yield by non-destructive technologies have the potential to revolutionize farming practices and enable the consumer to eat the tastiest and freshest fruit possible. A variety of non-destructive techniques have been applied to estimate the ripeness or maturity but not all of them are applicable for in situ (field or glasshouse) assessment. This review focuses on the non-destructive methods which are promising, or have already been, applied to the pre-harvest in field measurement including colorimetry, visible imaging, spectroscopy and spectroscopic imaging. Machine learning and regression models used in assessing ripeness are also discussed.

Quantum-dot cellular automata (QCA) are a promising nanoscale computing technology that exploits the quantum mechanical tunneling of electrons between quantum dots in a cell and electrostatic interaction between dots, in neighboring cells. QCA can achieve higher speed, lower power, and smaller areas than conventional complementary metal–oxide–semiconductor (CMOS) technology. Developing QCA circuits in a logically and physically reversible manner can provide exceptional reductions in energy dissipation. The main challenge of reversible QCA design is to maintain reversibility down to the physical level. The arithmetic logic unit (ALU) is an essential component of the central processing unit (CPU) of a computer. It performs various arithmetic and logical operations on the data that the CPU processes. Current QCA ALU designs are either irreversible or logically reversible; however, they lack physical reversibility, a crucial requirement to increase energy efficiency. In this paper, we present a novel multilayer design for a logically and physically reversible QCA ALU based on majority gates as the key components, which can perform 16 different operations. We use QCADesigner-E software to simulate and evaluate energy dissipation. The proposed logically and physically reversible QCA ALU offers an improvement of 88.8% in energy efficiency. Compared to the next most efficient 16-operation QCA ALU, this ALU uses 51% fewer QCA cells and 47% less area.

This research article presents the integration of participatory modeling and system dynamics as a novel methodology for the consolidation of social dynamic models for the subsequent evaluation and prioritization of green projects in Colombian post-conflict communities. In the first instance, through participatory work carried out along with the community, it was possible to identify, evaluate and systematize citizen factors in relation to the problems and needs of the region. Second, based on the results obtained, to calibrate a simulation model based on system dynamics that facilitates decision making with regard to the evaluation of green projects. The proposed methodology leads to the conclusion that, with the participation of the community and with a model based on the dynamics of variables such as supply and demand for natural resources of water and land, it is possible to warn decision makers about the variables that can lead to the maximization of investments and thus prioritize and select the most appropriate environmental, social or economic initiatives, that certainly meet the needs or expectations of the involved community. In the future, the model could be used to facilitate the management, administration and control of water and land resources by creating alerts called reserve margins.

Background: With a rapid rise in our older adult population globally and due to their multimorbidities, our older adults are more likely to engage in the services provided in the emergency department at a higher rate than younger adults. The current emergency service delivery model may be ineffective against such an ageing phenomenon. Research reports most older adults having one or more co-morbidities including functional decline, dementia, and frailty. Studies have shown that older adults have been undertriaged with physicians not being able to comprehend their complex needs related to their presenting complaints in the emergency department. Geriatric emergency departments have incepted worldwide to better manage this care deficiency in the rapidly ageing society around the world. Data Sources: A search of published literature from 2010-2020 using (keywords) as described below was undertaken of which, relevant literature were selected for an informed review. Implications for Nursing: Understanding geriatric emergencies can enable healthcare workers to reduce undertriaging and provide appropriate care that improves patient's health outcomes currently and in the future in the emergency department. Further education in gerontology can also be a platform for our nurses to enhance their care and thought process, likewise upskilling themselves for the future geriatric population seeking treatment. Older healthcare workers will also be able to enhance their current job scope before retirement. In-house teachings from trained gerontologists or certified programs can shed light on the special care needs of our senior citizens globally. Conclusion: With our rapidly increasing population, we can expect an influx of our older patients both from home and long-term care facilities to present to the emergency department with a wide range of geriatric emergencies. By being able to create a geriatric screening process and tailored care models, healthcare workers will be able to understand their care process and in turn, improve patients' health outcomes and provide a quicker transition of care.

Citizen participation has always been of vital importance in decision-making processes and, likewise, joint work in the formulation and execution of projects that respond to territorial needs. This in order to ensure the best impact of public or private investment, optimizing the result and community articulation. For this reason, this investigation proposes a methodology of evaluation and prioritization of projects based on an approach integrated between the modelling in dynamics systems (SDM) and the Analytical process network (ANP), in which the citizen factors are used as qualitative and quantitative variables inside the posed balance sheet model. This is how the model developed by the Stella Architect software, it offers to the decision makers approximate information about the reality of the community, especially those who were affected by the Colombian conflict and where the expectations of a comprehensive repair could disrupt the socioeconomic system and reveal more pressing interests than those of the central government. The methodology is described by the information gotten through the participatory workshops done in the California county that belongs to the Magdalena region, this is a very affected region by the conflict in Colombia. The investigation results confirm the useful of, first of all, the use of the modelling as an information-generating tool by allowing the simulation of relevant variables in the evaluation and prioritization of projects at different moments of time and, in second place, use the knowledge of the experts that expose the ANP method for establishing the importance of each variable compared with other variables and, likewise of each project compared to the rest of the alternatives in each of the different instants of time in which the evaluation is carried out, given that the results could change in any time, the official ranking is showed after an optimization process with partial results.

This study propounds a sustainable alternative to petroleum-based polyurethane (PU) foams aiming to curtail this nonrenewable resource's continued and uncontrolled use. Coconut fatty acid distillate (CFAD) and crude glycerol (CG), both wastes from vegetable oil processes, were utilized for bio-based polyol production for rigid PU foam application. The raw materials were subjected to catalyzed glycerolysis with alkaline-alcohol neutralization and bleaching. The resulting polyol possessed properties suitable for rigid foam application with an average OH number of 215 mg KOH/g, acid number of 7.2983 mg KOH/g, and Gardner color value of 18. The polyol was used to prepare rigid PU foam, and its properties were determined using FTIR, TGA/DTA, and UTM. Additionally, the cell foam morphology was investigated by scanning electron microscope (SEM) in which most of its structure revealed an open-celled network and quantified at 92.71% open cell content using pycnometric testing. The PU foam thermal and mechanical analysis results showed an average compressive strength of 70.59 kPa, thermal conductivity of 46.50 mWm-1K-1, and density of 32.79 kgm-3. These properties showed its applicability as thermal insulating foam, thus, demonstrating the potential use of CFAD and CG in commercial polyol and PU foam production.

The world is progressing towards a more advanced society where end-consumers have access to local renewable-based generation and advanced forms of information and technology. Hence, it is in a current state of transition between the traditional approach to power generation and distribution, where end-consumers of electricity have typically been inactive in their involvement with energy markets and a new approach that integrates their active participation. This new approach includes the use of distributed energy resources (DER) such as renewable-based generations and demand response (DR), which are being rapidly adopted by end-consumers, where incentives are strong. This paper presents the role of DR aggregator to effectively integrate DER technologies as a new source of energy capacity, into the electricity networks using information communication technology and industry knowledge. This framework based on DR aggregators will facilitate renewable energy integration and customer engagement in electricity market efficiently. To this aim, advantages and disadvantages of DR aggregators are discussed in this paper from political, economic, social and technological (PEST) point of views. Based on this analysis, a strengths, weaknesses, opportunities, and threats (SWOT) analysis for a typical DR aggregator is presented.

This paper describes a novel thruster fault-tolerant control system (FTC) for open-frame remotely operated vehicles (ROVs). The proposed FTC consists of two subsystems: a model-free thruster fault detection and isolation subsystem (FDI) and a fault accommodation subsystem (FA). The FDI subsystem employs fault detection units (FDUs), associated with each thruster, to monitor their state. The robust, reliable and adaptive FDUs use a model-free pattern recognition neural network (PRNN) to detect internal and external faulty states of the thrusters in real time. The FA subsystem combines information provided by the FDI subsystem with predefined, user-configurable actions to accommodate partial and total faults and to perform an appropriate control reallocation. Software-level actions include penalisation of faulty thrusters in solution of control allocation problem and reallocation of control energy among the operable thrusters. Hardware-level actions include power isolation of faulty thrusters (total faults only) such that the entire ROV power system is not compromised. The proposed FTC system is implemented as a LabVIEW virtual instrument (VI) and evaluated in virtual (simulated) and real-world environments. The proposed FTC module can be used for open frame ROVs with up to 12 thrusters: eight horizontal thrusters configured in two horizontal layers of four thrusters each, and four vertical thrusters configured in one vertical layer. Results from both environments show that the ROV control system, enhanced with the FDI and FA subsystems, is capable of maintaining full 6 DOF control of ROV in the presence of up to 6 simultaneous total faults in the thrusters. With the FDI and FA subsystems in place the control energy distribution of the healthy thrusters is optimised so that the ROV can still operate in difficult conditions under fault scenarios.

A model that predicts levels of coronavirus (CoV) respiratory/fecal-oral transmission potentials based on the outer shell hardness has been built using neural network (artificial intelligence, AI) analysis of the percentage of disorder (PID) in the nucleocapsid, N, and membrane, M, proteins of the inner and outer viral shells, respectively. Based mainly on the PID of N, SARS-CoV-2 is categorized as having intermediate levels of both respiratory and fecal oral transmission potential. Related to this, other studies have found strong positive correlations between virulence and inner shell disorder among numerous viruses, including Nipah, Ebola, and Dengue viruses. There is some evidence that this is also true for SARS-CoV-2 and SARS-CoV, which have N PIDs of 48% and 50%, and are characterized by case-fatality rates of 7.1% and 10.9%, respectively. The link between levels of respiratory transmission and virulence lies in viral load of body fluids and organ respectively. A virus can be infectious via respiratory modes only if the viral loads in saliva and mucus exceed certain minima. Likewise, a person may die, if the viral load is too high especially in viral organs. Inner shell proteins of viruses play important roles in the replication of viruses, and structural disorder enhances these roles by providing greater efficiency in protein-protein/DNA/RNA/lipid binding. This paper outlines a novel strategy in attenuating viruses involving comparison of disorder patterns of inner shells of related viruses to identify residues and regions that could be ideal for mutation. The M protein of SARS-CoV-2 has one of the lowest M PID values (6%) in its family, and therefore this virus has one of the hardest outer shells, which makes it resistant to antimicrobial enzymes in body fluid. While this is likely responsible for its contagiousness, the risks of creating an attenuated virus with a more disordered M are discussed.

Concrete is the most utilized construction material worldwide. In the marine environment, it is subject to chemical degradation through reactions with chloride (the most important ion), sulfate and magnesium ions in seawater and to biodeterioration resulting from biological (initially microbiological) activities, principally acid production. These two types of corrosion are reviewed and the failure of attempts to predict the degree of deterioration resulting from each is noted. Chemical (abiotic) corrosion is greatest in the splash zone of coastal constructions, while phenomenological evidence suggests that biodeterioration is greatest in tidal zones. There have been no comparative experiments to determine the rates and types of microbial biofilm formation in these zones. Both chemical and microbiological concrete deterioration are complex and have not been successfully modeled. The interaction between abiotic corrosion and biofilm formation is considered. EPS can maintain surface hydration, potentially reducing abiotic corrosion. The early marine biofilm contains relatively specific bacterial colonizers, including cyanobacteria and proteobacteria; these change over time, producing a generic concrete biofilm, but adhesion of microorganisms to concrete in the oceans is little investigated. The colonization of artificial reefs is briefly discussed. Concrete appears to be a relatively prescriptive substrate, with modifications necessary to increase colonization for the required goal of increasing biological diversity.

This paper discusses the mathematical modelling of exothermic explosions in a slab. This model is based on a nonlinear equation containing a nonlinear term related to Arrhenius, bimolecular, and sensitised laws of reaction kinetics. The absolute temperature can be obtained by solving the nonlinear equation using Akbari-Ganji’s method. The influence of the parameters Frank-Kamenetskii, activation energy and numerical exponent on temperature is discussed. The analytical results are compared with previous available analytical and numerical results ( Matlab). A satisfactory agreement is noted.

COVID-19 is the most severe health crisis of the 21st century. COVID-19 presents a threat to almost all countries world-wide. The restriction of human mobility is one of the strategies used to control the transmission of COVID-19. However, it has yet to be determined how effective this restriction is in controlling the rise in COVID-19 cases, particularly in major capital cities such as Jakarta, Indonesia. Using Facebook's mobility data, our study explores the impact of restricting human mobility on COVID-19 case control in Jakarta. Our main contribution is showing how the restriction of human mobility data can give important information about how COVID-19 spreads in different places. We proposed modifying a global regression model into a local regression model by accounting for the spatial and temporal interdependence of COVID-19 transmission across space and time. We applied Bayesian hierarchical Poisson spatiotemporal models with spatially varying regression coefficients. We estimated the regression parameters using an Integrated Nested Laplace Approximation. We found that the local regression model with spatially varying regression coefficients outperforms the global regression model based on DIC, WAIC, MPL, and R2 criteria for model selection. In Jakarta's 44 districts, the impact of human mobility varies significantly. The impacts of human mobility on the log relative risk of COVID-19 range from –4.445 to 2.353. The prevention strategy involving the restriction of human mobility may be beneficial in some districts but ineffective in others. Therefore, a cost-effective strategy had to be adopted.

The world is in the grips of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increase concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D [25(OH)D] concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome, and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D₃ for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40–60 ng/ml (100–150 nmol/l). For treatment of people who become infected with COVID-19, higher vitamin D₃ doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.

SARS-CoV-2 was empirically and computationally found to be of a specific but peculiar evolution. Shell disorder models found that the outer shell (M protein) of SARS-CoV-2 to be among the hardest in its CoV family. The hard outer shell (low M percentage of disorder (PID)) is likely to be related to the SARS-CoV-2 resistance to the antimicrobial enzymes in saliva and mucus, and be responsible for the high-level of viral shedding which has been observed clinically. Experimental studies have also shown that SARS-CoV-2 is more resilient in the environment than many other CoVs, including SARS-CoV-1. Another aspect of the shell disorder models predicts that SARS-CoV-1 is more virulent than SARS-CoV-2 because of higher inner shell disorder (N PID) that helps SARS-CoV-1 replicate faster in vital organs despite being of lesser viral loads in the saliva and mucus, unlike SARS-CoV-2. This has been reaffirmed experimentally, where higher levels (50 folds) of infectious particles were detected in the SARS-CoV-1 samples in comparison with those of SARS-CoV-2. The hard outer shell of SARS-CoV-2 has been found to be associated with burrowing animals, particularly pangolins, which are often in contact with buried feces. For these reasons, the M protein is highly conserved among close relatives of SARS-CoV-2. The phylogenetic tree using M, unlike the genome-wide one, shows that pangolin-CoVs are more closely related to SARS-CoV-2 than bat-RaTG13. Previous phylogenetic studies may have been confused by recombinations that are usually poorly handled. According to the shell disorder models based on the N PID, an attenuated COVID-19 strain is likely to have entered humans via pangolins in 2017 or before, which provides the virus enough time to adapt to humans. This could explain why the SARS-CoV-2 S protein is highly adapted to the human ACE-2. The specific but peculiar evolution has a wide range of clinical, immunological, and epidemiological implications.

Energy efficiency considerations in terms of reduced power dissipation is a significant issue in the design of digital circuits for very large-scale integration (VLSI) systems. Quantum-dot cellular automata (QCA) is an emerging ultra-low power dissipation approach, distinct from the traditional complementary metal-oxide semiconductor (CMOS) technology, for building digital computing circuits. Developing fully reversible QCA circuits has the potential to significantly reduce energy dissipation. The multiplexer is a fundamental element in the construction of useful digital circuits. In this paper, a novel, multilayer, fully reversible QCA 8:1 multiplexer circuit, with ultralow energy dissipation, is introduced. The proposed multiplexer power dissipation is simulated using the QCADesigner-E version 2.2 tool, describing the microscopic physical mechanisms underlying the QCA operation. The results showed that the proposed reversible QCA 8:1 multiplexer consumes 89% less energy than the most energy-efficient 8:1 multiplexer circuit presented previously in the scientific literature.

This comprehensive study focused on the standard taxi sign used in Ireland, its impact on drag production, fuel expenses, and CO2 emissions. Experimental analysis revealed that the conventional taxi sign significantly increased drag, especially when mounted on streamlined vehicles such as saloon cars, due to flow separation issues on the rear roof and rear windshield. Longitudinal reorientation of the sign offered a 14-fold reduction in drag increase compared to the traditional placement. It was found that positioning the sign in the middle of the roof offered the greatest fuel efficiency. Furthermore, the study estimated that implementing longitudinal repositioning on all Irish taxi signs could save drivers approximately 832 per year and reduce national CO2 emissions by a substantial 22,464 tonnes annually. Comparative analyses with international taxi signs demonstrated that the Irish sign had significantly larger drag contributions, emphasizing the need for improved aerodynamics. To address the inherent drag issue, the study explored novel appendable devices and proposed alternative taxi sign designs. Among the tested solutions, a magnet-mounted front ramp proved the most effective, reducing total drag by nearly 30%. Additionally, a motorized flip-up taxi sign design demonstrated a remarkable 40% reduction in drag. Finally, a newly proposed taxi sign design, featuring longitudinal positioning and pointed triangular front and rear faces, resulted in a minimal 4.3% increase in vehicle drag compared to the baseline car.

This article presents a study on the aerodynamic drag of a generic dual-axle flatbed trailer and explores ways to reduce the drag using appendable drag-reducing devices. The primary sources of drag originated from the van and trailer’s rear, along with the trailer’s wheels. The most effective initial device for reducing drag was a full trailer underside cover which offered a 7% drag reduction. Additionally, ladder racks, dropsides, and rear gates were studied, and it was found that protruding ladder racks significantly increased drag. Rear gates added large amounts of drag and should be removed and stored when not needed. The study also explored novel mid-section devices that increased the van’s base pressure and reduced drag. An axle test revealed that drag for single, dual, and triple axle trailers was very similar in direct flow, but different in yawed flow. A drawbar length test showed a near-linear relationship between drawbar length and drag, manifesting as a 1.7% change in drag per 250mm change in drawbar length. Several novel modifications were made to the trailer, including fitting six unique appendable devices, which offered a total 7.3% drag reduction. A novel rear van device known as the Multi-Stage Converging Cavity was introduced which reduced drag by nearly 18%. When all the devices were used together, a total 25% drag reduction was observed for the van-trailer combination.

We investigate the effect of geopolitical risk on the returns of the Information Technology, Communication Services, and Consumer Staples sector firms within the S&P 500 index. We use the event study methodology and perform more than 17,000 regressions to provide empirical evidence at the sector level that geopolitical risk leads to different responses across these 3 sectors. The response of the Information Technology sector is negative for all event windows under study, except the one spanning 10 days prior to the geopolitical event and 10 days after. The Communication Services sector has positive returns as a result of geopolitical events for all event windows, except the one from the geopolitical event date and 5 days after. The Consumer Staples sector shows a negative impact on geopolitical risk for all event windows except the one from the geopolitical event date and 5 days after, demonstrating a negative correlation to the Communication Services sector.

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

As the global demand for water increases, so does the quantity of wastewater requiring treatment. Due to a relatively low carbon footprint, compared with conventional wastewater treatment technologies, anaerobic digestion (AD) was identified in the 1970s as a forerunner in the push for sustainability, when interest in sustainable technologies and renewable energy sources was first sparked. AD technology development ultimately resulted in the discovery of the ‘anaerobic granule’. It is a spontaneously-forming bio-aggregate of microbial cells capable of digesting pollutants and producing methane-rich biogas as a renewable source of bioenergy. The high settling velocity of such granules meant that AD systems could be operated as high-rate treatment processes, because the active, relatively-slow-growing, pollutant-removing biomass would be retained inside, and not washed out of, even bioreactors operated at extremely high volumetric loading rates. In the intervening years the emergence of the anaerobic ammonium oxidising (anammox) granule, aerobic granule, hydrogenic granule, oxygenic photogranule, and many other functionally-specialised granules, has opened new opportunities in wastewater treatment biotechnology. Whilst environmental engineering based around wastewater treatment is still a growing field of research and implementation, the granule (in all forms) is starting to catch the attention of microbial ecologists. It is a self-immobilised biofilm, with many of the properties of ‘conventional’ biofilms formed in Nature. However, as a single entity, a granule represents an entire community of microorganisms, competing or functioning cooperatively or in syntrophy. Together, inside a bioreactor, granules perform side-by-side arguably representing a meta-organism. Granules are gaining traction as the perfect samples for high-throughput studies on fundamental ecological concepts. Granular biofilms can be used to test hypotheses around drivers of diversity, community assembly, biofilm formation and maturation, community expansion and succession, community stress response, among others. This review outlines the history of three of the most influential types of granules: the anaerobic (methanogenic), aerobic and anammox granule. The main biochemical processes found in each type; their primary characteristics; and the typical makeup of the microbial community underpinning the processes are compared. Finally, the adoption of granules as the perfect ‘playground’ for experiments in microbial ecology is reviewed.

Preparing high school students for engineering disciplines is crucial for sustainable scientific and technological developments in the USA. This paper discusses a pre-college program, which not only exposes students to various engineering disciplines but also enables them to consider engineering as the profession. The four-week long “Engineering Innovation (EI)” course is offered every year to high school students by the center of outreach, Johns Hopkins University. EI program is designed to develop problem-solving skills through extensive hands-on engineering experiments. A team consisting of an instructor, generally a PhD in Engineering, and a teaching fellow, generally a high school science teacher, closely work with students to pedagogically inculcate basics of core engineering disciplines such as civil, mechanical, electrical, materials, and chemical engineering. EI values independent problem-solving skills and simultaneously promote the team spirit among students. A number of crucial engineering aspects such as professional ethics, communications, technical writing, and understanding of common engineering principles are inculcated among high school students via well-designed individual and group activities. This paper discusses the model of EI program and its impact on students learning and their preparation for the engineering career.

Many insights into human disease have been built on experimental results in Drosophila, and research in fruit flies is often justified on the basis of its predictive value for questions related to human health. Additionally, there is now a growing recognition of the value of Drosophila for the study of rare human genetic diseases, either as a means of validating the causative nature of a candidate genetic variant found in patients, or as a means of obtaining functional information about a novel disease-linked gene when there is little known about it. For these reasons, funders in the US, Europe, and Canada have launched targeted programs to link human geneticists working on discovering new rare disease loci with researchers who work on the counterpart genes in Drosophila and other model organisms. Several of these initiatives are described here, as are a number of output publications that validate this new approach.

Reliable and robust control of power converters is a key issue in the performance of numerous technological devices. In this paper we show a design technique for the control of a DC-DC buck converter with a switching technique that guarantees not only good performance but also global stability. We show that making use of the contraction theorem in the Jordan canonical form of the buck converter, it is possible to find a switching surface that guarantees stability but it is incapable of rejecting load perturbations. To overcome this, we expand the system to include the dynamics of the voltage error and we demonstrate that the same design procedure is not only able to stabilize the system to the desired operation point but also to reject load, input voltage and reference voltage perturbations.

Despite considerable progress in the diagnosis of various diseases, an ideal, simple tool for diagnosing patients with respiratory tract infections has not yet been invented. Many simple diagnostic tests are widely available to most doctors, provided they are aware of the prevalence of primary immunodeficiency. Other, more accurate studies are available only to immunologists. The aim of the study was to investigate the occurrence of dependence between selected physical parameters of serum such as: electrical conductivity, electrical permeability, dielectric loss factor, and selected parameters of the immune system. In addition, we have also included the ionogram (Na, K, Cl, Ca, Mg) and glucose concentration. As a result of research, the statistically significant, but very weak correlations between impedance magnitude |Z| and platelet counts (PLT), mean platelet volume (MPV) and chloride ions (Cl-) were found. The statistically significant differences according |Z| between children with and without deficiency in parameters of the immune system were noticed. Values of |Z| are higher in the case of children without deficiency in parameters of the immune system. The method of impedance measurements presented in our work is significantly easier then biosensors presented by other scientists. Taking into account our results, it can be stated that this method is promising for fast and easy detection of immunological disorders.

Temperature Cycle Induced Deracemization (TCID) offers a promising approach to obtain enantiopure solids from racemic mixtures. By combining rapid racemization in solution and temperature swings, homochirality is theoretically achieved. Despite theoretical expectations of doubled yields compared to traditional chiral separation methods, such as in Preferential Crystallization, experimental validation remains lacking. We applied TCID to (1-(4-chlorophenyl)-4,4-dimethyl-2-(1H-1,2,4-triazol-1-yl) pentan-3-one) (Cl-TAK), introducing a post-TCID cooling step to enhance yield and a washing step to augment enantiopurity. This refinement yielded an 89.8% mass yield with 99.1% enantiomeric excess in the crystal phase (c.e.e.) within 24 hours on an 8.75g scale, showcasing improved performance with insignificant process duration extension. Additionally, we explored the stochasticity of deracemization, observing the development from low initial crystal enantiomeric excesses(1-6% c.e.e0) at a 2.5 g scale. Kinetic analysis revealed that a 2% c.e.e0 effectively mitigates chiral flipping risks and induction time in our system. Our study underscores the potential for reduced initial c.e.e. to expedite deracemization and presents a straightforward method to optimize yield and purity, facilitating industrial application.

In the literature on occupational stress and recovery from work several facets of thinking about work in off-job time have been conceptualized. However, research on the focal concepts is currently rather disintegrated. In this study we take a closer look at the five most established concepts, namely (1) psychological detachment, (2) affective rumination, (3) problem-solving pondering, (4) positive work reflection, and (5) negative work reflection. More specifically, we scrutinized (1) whether the five facets of work-related rumination are empirically distinct, (2) whether they yield differential associations with different facets of employee well-being (burnout, work engagement, thriving, satisfaction with life, and flourishing), and (3) to what extent the five facets can be distinguished from and relate to conceptually similar constructs, such as irritation, worry, and neuroticism. We applied structural equation modeling techniques to cross-sectional survey data from 474 employees. Our results provide evidence that (1) the five facets of work-related rumination are highly related, yet empirically distinct, (2) that each facet contributes uniquely to explain variance in certain aspects of employee well-being, and (3) that they are distinct from related concepts, albeit there is a high overlap between (lower levels of) psychological detachment and cognitive irritation. Our study contributes to clarify the structure of work-related rumination and extends the nomological network around different types of thinking about work in off-job time and employee well-being.

Current cellular facts allow us to follow the link from chemical to biochemical metabolites, from the ancient to the modern world. In this context, the "RNA world" hypothesis proposes that early in the evolution of life, the ribozyme was responsible for the storage and transfer of genetic information and for the catalysis of biochemical reactions. Accordingly, the hammerhead ribozyme (HHR) and the hairpin ribozyme, belong to a family of endonucleolytic RNAs performing self-cleavage that might occur during replication. Furthermore, regarding the ultraconserved occurrence of HHR in several genomes of modern organisms (from mammals to small parasites and elsewhere), these small ribozymes have been regarded as living fossils of a primitive RNA world. They fold into 3D structures that generally require long-range intramolecular interactions to adopt the catalytically active conformation under specific physicochemical conditions. By studying viroids as plausible remains of ancient RNA, we recently demonstrated that they replicate in non-specific hosts, emphasizing their adaptability to different environments, which enhanced their survival probability over the ages. All these results exemplify ubiquitously features of life. Those are the versatility and efficiency of small RNAs, viroids and ribozymes, as well as their diversity and adaptability to various extreme conditions. All these traits must have originated in early life to generate novel RNA populations.

In addition to absorbing nitrogen from the soil, legumes have the ability to use atmospheric N2 through symbiotic nitrogen fixation. Therefore, legumes have developed mechanisms regulating nodulation in response to the amount of nitrate in the soil; in the presence of high nitrate concentrations, nodulation is inhibited while low nitrate concentrations stimulate nodulation and nitrogen fixation. This allows the legumes to switch from soil nitrogen acquisition to symbiotic nitrogen fixation. Recently, a particular interest has been given to the nitrate transporters, such as NPF or NRT2, having a role in the functioning of nodules. Nitrate transporters of the two model plants, Lotus japonicus and Medicago truncatula, shown to have a positive and/or a negative role in nodule functioning, depending on nitrate concentration, are presented in this review. Also, by exploiting available genomic and transcriptomic data in the literature we have identified the complete PsNPF family in Pisum sativum (69 sequences previously described and 21 new that we have annotated) and putative nitrate transporters candidate for playing a role in nodule functioning in P. sativum.

Fog, haze, or smoke are usual atmospheric phenomena that dramatically compromise the overall visibility of any scene, critically affecting features such as illumination, contrast, and contour detection of objects. The decrease in visibility compromises the performance of computer vision algorithms such as pattern recognition and segmentation, some of them very relevant for decision-making for the security or autonomous vehicle industries. Several dehazing methods have been proposed, however, to the best of our knowledge, all proposed metrics compare the defogged image to its ground truth for evaluation of the defogging algorithms, or need to estimate parameters through physical models. This fact hinders progress in the field as obtaining proper ground truth images is costly and time-consuming, and physical parameters greatly depend on the scene conditions. This paper aims to tackle this issue by proposing a contour-based metric for image defogging evaluation that does not need a ground truth image. The proposed metric only requires the original hazy RGB image and the RGB image after the defogging procedure. A comparison of the proposed metric with metrics currently used in the NTIRE 2018 defogging challenge is performed to prove its effectiveness in a general situation, showing comparable results to conventional metrics.

The global trend towards increased demand for organic food, greener environments, and the integration of biological control agents into pest management strategies has greatly enhanced the need for biological pesticides (biopesticides). Biopesticides are generally environmentally friendly and are made from micro-organisms or other natural substances. Despite their great potential, relatively few have been registered and commercialised in Nigeria compared to other African countries such as South Africa and Kenya. Biological active agents are so diverse such that ap-plying the same safety standards or environmental conditions to all of them is almost impossible. A review of risk assessment processes and comparative assessments of Nigeria's biopesticide regulations with other developing African countries and developed regions was conducted. Prolonged field testing, lack of bridged risk assessments and technical checklists have been identified as key factors hampering the timely development and commercialisation of biopesti-cides in Nigeria. Recommendations on necessary changes to the existing Nigeria biopesticide regulations have been made. Risk assessment matrices for microbial and biochemical biopesti-cides and a scientific/technical checklist have also been developed. Harmonisation and data ex-change among other countries in the region will also enhance the advancement of scientific and technical knowledge for sustainable regulation and cross-border trade.

The combination of interstitial hyperthermia treatment (IHT) with high dose rate brachytherapy (HDR-BT) for prostate cancer treatment and has the potential to improve clinical outcome, since it highly enhances the efficiency of cell kill, especially when applied simultaneously. Therefore, we have developed the ThermoBrachy applicators. To effectively apply optimal targeted IHT, treatment planning is considered essential. However, treatment planning in IHT is rarely applied since it is regarded difficult to accurately calculate the deposited energy in the tissue in a short enough time for clinical practice. In this study, we investigated various time-efficient methods for fast computation of the electromagnetic (EM) energy deposition resulting from the ThermoBrachy applicators. Initially, we investigated the use of an electro-quasistatic solver. Next, we extended our investigation to the application of geometric simplifications. Furthermore, we investigated the validity of the superpositioning principle, which can enable adaptive treatment plan optimization without the need for continuous recomputation of the EM field. Finally, we evaluated the accuracy of the methods by comparing them to the golden standard Finite-Difference Time-Domain calculation method using gamma-index analysis. The simplifications considerably reduced the computation time needed, improving from &gt;12 h to a few seconds. All investigated methods showed excellent agreement with the golden standard by showing a &gt;99% passing rate with 1%/0.5 mm Dose Difference and Distance-to-Agreement criteria. These results allow the proposed electromagnetic simulation method to be used for fast and accurate adaptive treatment planning.

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

A model to predict the relative levels of respiratory and fecal-oral transmission potentials of coronaviruses (CoVs) by measuring the percentage of protein intrinsic disorder (PID) of the M (Membrane) and N (nucleoprotein) proteins in their outer and inner shells, respectively, was built before the MERS-CoV outbreak. Application of this model to the 2003 SARS-CoV indicated that this virus with M_PID = 8.6% and N_PID = 50.2% falls into group B, which consists of CoVs with intermediate levels of both fecal-oral and respiratory transmission potentials. Further validation of the model came with MERS-CoV (M_PID = 9%, N_PID = 44%) and SARS-CoV-2 (M_PID = 5.5%, N_PID = 48%) falling into the groups C and B, respectively. Group C contains CoVs with higher fecal-oral but lower respiratory transmission potentials. Unlike SARS-CoV, SARS-CoV-2 with M_PID = 5.5% has one of the hardest outer shells among CoVs. This shell hardness is believed to be responsible for high viral loads in the mucus and saliva making it more contagious than SARS-CoV. The hard shell is able to resist the anti-microbial enzymes in body fluids. Further searches have found that high rigidity of outer shell is characteristic for the CoVs of burrowing animals, such as rabbits (M_PID = 5.6%) and pangolins (M_PID = 5-6%), which are in contact with the buried feces. A closer inspection of pangolin-CoVs from 2017-19 reveals that these animals provided a unique window of opportunity for the entry of an attenuated SARS-CoV-2 precursor into the human population in 2017 or earlier, with the subsequent slow and silent spread as a mild cold that followed by its mutations into the current more virulent form. Evidence of this lies in the similarity of shell disorder and genetic proximity of the pangolin-CoVs to SARS-CoV-2 (~90%). A 2017 pangolin-CoV strain shows evidence of higher levels of attenuation and higher fecal-oral transmission associated with lower human infectivity via having lower N_PID (44.8%). Our shell disorder analysis also revealed that lower inner shell disorder is associated with the lesser virulence in a variety of viruses.

Several studies have suggested that pre and/or postdiagnosis physical activity can reduce the risk of recurrence in breast cancer patients, however its effect according to follow-up time has not yet been investigated. We analyzed recurrence and mortality dynamics in randomized clinical trials (RCTs) from Australia and Canada. The combined Australian RCTs evaluated, at median follow-up of 8.3 years, an 8-month pragmatic exercise intervention in 337 women with newly diagnosed breast cancer, while the Canadian RCT evaluated, at median follow-up of 7.4 years, supervised aerobic or resistance exercise during chemotherapy in 242 patients. For each RCT, the control arm consisted of patients undergoing usual care. We estimated the event dynamics by the discrete hazard function, through flexible regression of yearly conditional event probabilities with generalized additive models. In the considered RCTs, the recurrence and mortality risk of patients enrolled in the physical activity arm was stably reduced at medium/long term after five year of follow-up. In the Australian RCTs where patients were recruited by urban versus rural area, the latter group did not display benefit from physical activity. Estimated Odds Ratios (95% Confidence Intervals) for Disease Free Survival (DFS) in urban women were 0.63 (0.22-1.85); 0.27 (0.079-0.90); 0.11 (0.013-0.96) at the 3rd, 5th and 7th year of follow-up, respectively. For rural women, DFS patterns were overlapping with ORs approximating 1 at the different years of follow-up. Although not reaching statistical evidence, the estimates in the Canadian trial were in line with the results from the Australian urban women with ORs (95% CI) forDFS of 0.70 (0.33-1.50); 0.47 (0.19-1.18); 0.32 (0.077-1.29) at 3rd, 5th, 7th follow-up year, respectively. While we acknowledge that the analyzed RCTs were not designed for investigating disease recurrence over time, these results support the evidence that physical activity reduces the risk of developing medium/long-term metastases. Additional translational research is needed to clarify the mechanisms underlying these observations.

Scientific studies had shown that mixed forests of silver fir (Abies alba Mill.) and European beech (Fagus sylvatica L.) provide higher ecosystem services than monospecific forests. Mixed forests are known for their high resilience to climate change impacts and superior biodiversity compared to monospecific forests. In many countries, promotion of mixed forests in forest management is becoming a government policy since they can contribute to fulfill the Sustainable Development Goals set by the United Nation, respectively Goal 13 and 15. However, not much is known about public perceptions on mixed forests compared to monoculture forests. Our study on ecosystem services provided by mixed and monospecific forests in southwest Germany fill this gap. Based on a survey with 520 valid responses we analyzed people’s perception on 18 different supporting, cultural, regulating and provisioning ecosystem services measured by Likert scale. Stepwise regression analyses show relations between social profiles (gender, age, education, profession) and preferences on respondents’ perceptions. Our findings show that people perceive that mixed forests provide better cultural, regulating and supporting ecosystem services than monospecific forests of fir and beech whereas provisioning services were perceived as being equally or better provided by monospecific forests. Significant effects towards a positive perception on ecosystem services provided by mixed forests were mainly influenced by the perceived abundance of old trees, feeling of pleasantness in mixed forests, age, profession, and education. Our findings indicate that there is a high public support for the promotion of silver fir and beech mixed forests in Southwest Germany.

Although work events can be regarded as pivotal elements of organizational life, only a few studies have examined how positive and negative events relate to and combine to affect work engagement over time. Theory suggests that to better understand how current events affect work engagement (WE), we have to account for recent events that have preceded these current events. We present competing theoretical views on how recent and current work events may affect employees (e.g., getting used to a high frequency of negative events or becoming more sensitive to negative events). Although the occurrence of events implies discrete changes in the experience of work, prior research has not considered whether work events actually accumulate to sustained mid-term changes in WE. To address these gaps in the literature, we conducted a week-level longitudinal study across a period of 15 consecutive weeks among 135 employees, which yielded 849 weekly observations. While positive events were associated with higher levels of WE within the same week, negative events were not. Our results support neither satiation nor sensitization processes. However, high frequencies of negative events in the preceding week amplified the beneficial effects of positive events on WE in the current week. Growth curve analyses show that the benefits of positive events accumulate to sustain high levels of WE. WE dissipates in the absence of continuous experience of positive events. Our study adds a temporal component and informs research that has taken a feature-oriented perspective on the dynamic interplay of job demands and resources.

Numerous cities in our modern world are unfortunately encountering the negative effects of urban sprawl: this includes unrestricted settlement, degradation in the quality of their environment, traffic congestion, sub-standard buildings, and air pollution as well as flooding, swampy areas, landslides, and settlement zones with dilapidated utilities and infrastructures that are not safe for living. The Ulaanbaatar City land management master plan defined the settlement zone area suitable for living as 33,698 hectares. However, due to unrestricted urban sprawl caused by exponential growth of the city’s population, the settlement zone area reached 39,235 hectares, which exceeds the limit by 5,537 hectares. In order to tackle this issue, several urban planning concepts were developed to be implemented within the Ulaanbaatar City urban planning framework. It is, in any case, problematic to choose a single planning concept due to the fact that neither measurements nor analyses are being made of the respective spatial quantitative indicators in urban planning assumptions that are taking the current situation into consideration. One of the prerequisites for identifying an optimal concept in urban planning is an assessment of the current situation, and measuring the impacts against its quantitative data. In the current research, when defining Ulaanbaatar city sprawl, the base year was selected as 1990, the time when the city started to sprawl. Research analyses were made using geographic information systems based on the satellite data 1990, 1995, 2000, 2005 Landsat ТМ-5, 2010 Quickbird, 2015 World View and 2020 Sentinel2, respectively. Based on the results of determining the city sprawl using spatial indicators, the urban planning concepts applied thus far have been analyzed in relation to land use efficiency and land use structural changes. This research paper addresses the issue of reducing unrestricted urban sprawl by increasing the internal density of the city. The research results show that, by applying the concept of a compact city in urban redevelopment planning for 4,604 hectares, and by allocating the settlements in 12,479 hectares, it is possible to reduce the urban expansion threefold and increase land use efficiency accordingly.

Gas and power networks are tightly coupled and interact with each other due to physically interconnected facilities. In an integrated gas and power network, a contingency observed in one system may cause iterative cascading failures, resulting in network wide disruptions. Therefore, understanding the impacts of the interactions in both systems is crucial for governments, system operators, regulators and operational planners, particularly, to ensure security of supply for the overall energy system. Although simulation has been widely used in the assessment of gas systems as well as power systems, there is a significant gap in simulation models that are able to address the coupling of both systems. In this paper, a simulation framework that models and simulates the gas and power network in an integrated manner is proposed. The framework consist of a transient model for the gas system and a steady state model for the power system based on AC-Optimal Power Flow. The gas and power system model are coupled through an interface which uses the coupling equations to establish the data exchange and coordination between the individual models. The bidirectional interlink between both systems considered in this studies are the fuel gas offtake of gas fired power plants for power generation and the power supply to LNG terminals and electric drivers installed in gas compressor stations and underground gas storage facilities. The simulation framework is implemented into an innovative simulation tool named SAInt (Scenario Analysis Interface for Energy Systems) and the capabilities of the tool are demonstrated by performing a contingency analysis for a real world example. Results indicate how a disruption triggered in one system propagates to the other system and affects the operation of critical facilities. In addition, the studies show the importance of using transient gas models for security of supply studies instead of successions of steady state models, where the time evolution of the line pack is not captured correctly.

Agricultural productivity is expected to decrease under changing climate conditions that correspond to the stability of West African food systems. Although numerous studies evaluated food production gaps or impacts of climate variability on crop yields, many uncertainties are associated with climate extremes, but also rapid population growth and the corresponding dietary lifestyle determine farming activities. Here, we present a food supply and demand analysis based on the relationship between climate change, crop production, as well as population growth in three experimental sites from southwestern Burkina Faso to southwestern Ghana. The method consists of a tiered approach that encompassed a statistical analysis of historical climate as well as agricultural time series using boxplots and a trend test by Mann-Kendall. Food balance sheets were calculated by estimating the demand using a population growth model linked to food supply with local consumption patterns. Results of the boxplot analysis revealed for the majority of climate time series light to strong right-skewed distributions with either a few heavy rainfall or hot temperature events. We found almost insignificant rainfall and temperature trends for both sites in the Sudano-Guinean savannah. The rainfall regime of southwestern Ghana indicated an insignificant upward or downward trend while the temperature significantly increased over time. Crop yield boxplots demonstrated mainly right-skewed distributions for cereals, legumes and tubers as well as cash crops such as cotton. Backed by the Mann-Kendall test, maize and sorghum significantly enhanced in both study areas of the Sudano-Guinean savannah. Southwestern Ghana depicted a different crop pattern where cassava and plantain showed a strong upward trend at a confidence level of 1%. The grouped food balances sheets across the regions illustrated a surplus for the Sudano-Guinean savannah ranging from 221.2 megatons (Mt) to 4,846.77 Mt while southwestern Ghana exhibited a deficit between -193.33 Mt and -16,188.82 Mt. Despite a growing yield of various crops, food demand outpaces the regional production. Hence, it is recommended to focus on a larger array of commodities, imports and marketing of farm products.

Reactive oxygen species (ROS), which were originally classified as exclusively deleterious compounds, have gained increasing interest in the recent years given their action as bona fide signalling molecules. The main target of ROS action is the reversible oxidation of cysteines, leading to the formation of disulfide bonds, which modulate protein conformation and activity. ROS endowed with signalling properties are mainly produced by NADPH oxidases at the plasma membrane, but their action also involves a complex machinery of multiple redox-sensitive protein families that differs in their subcellular localization and their activity. Given that the levels and distribution of ROS are highly dynamic in part due to their limited stability, the development of various fluorescent ROS sensors, some of which are quantitative (ratiometric), represents a clear breakthrough in the field and have been adapted to both ex vivo and in vivo applications. The physiological implication of ROS signalling will be presented mainly in the frame of morphogenetics processes, embryogenesis, regeneration, and stem cell differentiation. Gain and loss of function as well as pharmacological strategies have demonstrated the wide but specific requirement of ROS signalling at multiple stages of these processes and its intricate relationship with other well-known signalling pathways.

Hidradenitis suppurativa and Langerhans cell histiocytosis are rare disorders that can reveal similar clinical manifestations, making differential diagnosis difficult. A definitive diagnosis requires biopsy and histological confirmation in suspicious cases. The complex pathophysiology of these diseases has still not been understood, therefore the treatment is still a challenge for physicians. It is seen with predilection in the intertriginous areas of the body, predominantly in the axillary region, rarely requiring a surgical procedure. However perineal, perianal, and gluteal HS usually necessitates some form of surgical treatment. Langerhans cell histiocytosis (histiocytosis X) is a very rare systemic disease manifested by clonal cell proliferation of histiocytic-dendritic nature, with pseudonodular manifestation that deeply infiltrates the hypodermis and ulcerates the epidermis on the surface. Langerhans cells are dendritic, antigen-presenting cells localized in the suprabasal regions of the squamous epithelium of the skin and mucous membranes, which help regulate the immune system. In this report, we present our experience with extensive gluteal, perineal, and perianal hidradenitis suppurativa and Langerhans cell histiocytosis cases, including our treatment methods and outcomes.

Aronia berries contain antioxidants that may have health promoting properties e.g., demonstrated positive effects on hypertension and dyslipidemia. There is a close link between cardiovascular diseases and hypertension and dyslipidemia, and cardiovascular events are the leading cause of death among subjects with T2D. Thus, we investigated the effect of 8 weeks supplementation with fermented aronia extract (FAE), non-fermented aronia extract (AE) and placebo on cardiovascular risk factors. The extracts were incorporated into snack bars containing 34 g (37%) aronia extract, or 17 g (21%) wheat bran for placebo, as well as raisins and coconut oil. The study was randomized and blinded with a triple-cross-over design. We examined the effects of aronia extracts on blood pressure, adiponectin and high-sensitive C-reactive protein and found no effects. After supplementation with placebo, there were significantly higher total-cholesterol, LDL-cholesterol, and HDL-cholesterol, with the placebo group showing significantly higher increases in total-cholesterol and LDL-cholesterol than the FAE group. Furthermore, we observed an increase in HDL-cholesterol in the AE group and an increase in triglyceride in the FAE group. Thus, we assume that raisins may have increased the participants’ cholesterol levels, however, with both AE and FAE having the potential to prevent this increase.

This study aims to understand Filipino rice farmers’ aspirations, both farming and non-farming-related. Understanding aspirations can help the government and interested third-party entities to provide impactful initiatives to farmers. The Role Identity Theory guided our analysis in this study. This study is predominantly qualitative, with focus group discussion as the main method of collecting data. The research sites were in Kalinga, Nueva Ecija, Laguna, Quezon, Northern Samar, Zamboanga del Sur, Sultan Kudarat, and Agusan del Norte. Among the farming-related aspirations noted in this study relate to property, fair price, infrastructure, government support, and good governance. The non-farming related aspirations relate to infrastructure development; progress; government support and governance; love, passion, peace, and unity; wellness and long life.

In this paper, Akbari-Ganji's and Taylor series methods are applied to find analytical solutions to nonlinear differential equations that arise in an immobilized-cell photobioreactor. Approximate analytical expressions for substrate and product concentrations and both liquid and gas phases for various parameter values are derived using both methods. Efficiency, accuracy, and convergence of the two methods relative to highly accurate numerical methods are investigated to establish reliable profiles of these two methods for solving general nonlinear equations that model various physical phenomena. Numerical simulations are presented to validate the theoretical investigations.

Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus, for which there is no vaccine or cure. This viral infection, once acquired, is life-long, residing latently in hematopoietic cells. However, latently infected individuals with weakened immune systems often undergo HCMV reactivation, which can cause serious complications in immunosuppressed and immunocompromised patients. Current anti-viral therapies target late stages of viral replication, and are often met with therapeutic resistance, necessitating the development of novel therapeutics. In this current study, we identified a naturally occurring flavonoid compound, deguelin, which inhibits HCMV lytic replication. Our findings reveal that nanomolar concentrations of deguelin significantly suppress the production of infectious virus. Further, we show that deguelin inhibits the lytic cycle during the phase of the replication cycle consistent with early (E) gene and protein expression. Importantly, our data reveal that deguelin inhibits replication of a ganciclovir-resistant strain of HCMV. Together, our findings identify a novel, naturally occurring compound that may prove useful in the treatment of HCMV replication.

This paper describes the optimal design of a miniature fiber-optic linear displacement sensor. It is characterized by its ability to measure displacements along a millimetric range with sub-micrometric resolution. The sensor consists of a triangular reflective grating and two fiber-optic probes. The measurement principle of the sensor is presented. The design of the sensor's triangular grating has been geometrically optimized by considering the step angle of the grating to enhance the sensor's resolution. The optimization method revealed a global optimum at which the highest resolution is obtained

Phytoplasma diseases pose a substantial threat to diverse crops of agricultural importance. Management measures are usually implemented only after the disease has already occurred. Early detection of such phytopathogens, prior to disease outbreak, has rarely been attempted but would be highly beneficial for phytosanitary risk assessment, disease prevention and mitigation. In this study we present the implementation of a recently proposed proactive disease management protocol (DAMA: Document, Assess, Monitor, Act) for a group of vector-borne phytopathogens. We used insect samples collected during a recent biomonitoring program in southern Germany to screen for the presence of phytoplasmas. Insects were collected with Malaise traps in different agricultural settings. DNA was extracted from these mass trap samples and subjected to PCR-based phytoplasma detection and COI sequence metabarcoding. In about 1% of the analyzed samples, phytoplasma DNA was detected. Phytoplasma group identification was performed by 16S rRNA gene sequence analysis and the detected phytoplasmas could be assigned to the 16SrI subgroups B and L. Insect species in the sample were identified by DNA metabarcoding. By using established databases, checklists, and archives, we documented historical associations and records of phytoplasmas and its hosts in the study region. For the assessment in the DAMA protocol, phylogenetic triage was performed in order to determine the risk for tri-trophic interactions (plant-insect-phytoplasma) and associated disease outbreaks in the study region. A phylogenetic heat map constitutes the basis for risk assessment and was used here to identify a minimum number of seven leafhopper species suggested to be monitored by stakeholders in this region. A proactive stance in monitoring changing patterns of association between hosts and pathogens can be a cornerstone in capabilities to prevent future phytoplasma disease outbreaks. To our knowledge, this is the first time that the DAMA protocol has been applied in the field of phytopathology and vector-borne plant diseases.

Self-employed individuals comprise around 15% of Canada’s workforce. For those with cancer, frequent functional loss and diminished work ability due to side effects of the disease and its treatment significantly impact their well-being and business vitality. Compared to salaried can-cer survivors, the self-employed experience greater reductions in work hours and up to 48% greater income loss, yet most research addresses the former population. To describe self-employed Canadian cancer survivors’ experiences continuing and returning to work, our quali-tative study examines their strategic efforts to continue working throughout the disease trajecto-ry or return to work post-recovery. Employing an interpretive description approach and an in-terview guide based on a vocational rehabilitation model for cancer survivors, we analyze data from 23 participants—both French- and English-speaking—from six Canadian provinces, with eight different job types and nine different cancer diagnoses. Our constant comparative analysis of the transcribed interviews reveals four major themes and twelve sub-themes: Impact of can-cer on the self-employed function (physical, cognitive, and psychological), on their ability to maintain their business, and financial well-being, and facilitating factors for working with can-cer. Cancer disclosure and non-disclosure were both deemed viable strategies, but ceasing work was not. We thus recommend professional support for self-employed cancer survivors in plan-ning any necessary business modifications to accommodate their condition and cancer treatment to lessen the negative impact of cancer on self and on their business well-being.

Traceability is the ability to determine the path of a product from purchase to consumption to determine when and where it originated. This paper aimed to determine the factors that influence fishers’ decision-making to participate in tuna traceability program, it also explores the determinants of fish catch for small-scale fishers and the feasibility of implementing tuna traceability in the Davao Gulf, Philippines. The result of the interview showed that the significant factors that highly affected the decision-making of fishers in implementating tuna traceability program: boat capacity, fishing hours and communication of fishers (P≤0.05). Household size, years in community, fishing hours, volume of fish sold, and the fishers' communication in the fishing ground (P≤0.05) were other factors that determined the daily catch of the fishers. The results of this study showed that fishers from the Davao Gulf were willing to be part of traceability program that would sustain and increase the value of their fish catch. Moreover, communication was shown to be critically needed in such programs adjusting it for the fish catch to remain fresh or of good quality. Our study will help in deterring and mitigating illegal, unregulated and unreported fishing (IUU) through fish catch traceability.

Coronaviruses (CoVs) are enveloped positive-sense single-stranded RNA viruses with a genome 27-31kbases in length. Critical genes include the spike (S), envelope (E), membrane (M), nucleocapsid (N) and 9 accessory open reading frames encoding for non-structural proteins (NSPs) that have multiple roles in the replication cycle and immune evasion (1). There are 7 known human CoVs that most likely appeared after zoonotic transfer, the most recent being SARS-CoV-2 responsible for the Covid-19 pandemic. Antivirals that have been approved by the FDA for use against Covid-19 such as Paxlovid can potentially target and successfully inhibit the main protease (MPro) activity of multiple human CoVs, however alternative proteomes encoded by CoV genomes have a closer genetic similarity to each other, suggesting that antivirals could be developed now that target future CoVs. New zoonotic introductions of CoVs to humans are inevitable and unpredictable. Therefore, new antivirals are required to control not only the next human CoV outbreak, but also the 4 common human CoVs (229E, OC43, NL63, HKU1) that circulate frequently and to contain sporadic outbreaks of the severe human CoVs (SARS-CoV, MERS and SARS-CoV-2). The current study found that emerging antiviral drugs, such as Paxlovid, have only been proven to target SARS-CoV-2. Other drugs which have the potential to target other human CoVs, are still within clinical trial and are not yet available for public use. Monoclonal antibody (mAb) treatment and vaccines for SARS-CoV-2 can reduce mortality and hospitalisation rates, however they target the Spike protein whose sequence mutates frequently and drifts. Spike also is not applicable for targeting other HCoVs as these are not well conserved sequences among human CoVs. Thus, there is a need for readily available treatments globally that target all 7 human CoVs and improve the preparedness for inevitable future outbreaks. Here we discuss antiviral research contributing to the control of common and severe CoV replication and transmission, including the current SARS-CoV-2 outbreak. The aim was to identify common features of CoVs for antivirals, biologics and vaccines that could reduce the scientific, political, economic and public health strain caused by CoV outbreaks now and in the future.

A modified free-wake vortex ring model is proposed to compute the dynamics of a floating horizontal-axis wind turbine. The model is divided into two parts. The near wake model uses a blade bound vortex model and trailed vortex model, which is developed based on vortex filament method. By contrast, the far wake model is based on the vortex ring method. The proposed model is a good compromise between accuracy and computational cost, for example when compared with more complex vortex methods. The present model is used to assess the influence of floating platform motions on the performance of a horizontal-axis wind turbine rotor. The results are validated on the 5MW NREL rotor and compared with other aerodynamic models for the same rotor subjected to different platform motions. It was found that the results from the proposed method are more reliable than the results from BEM theory especially at small angles of attack in the region of low wind speeds, on the one hand, and high wind speeds with blade pitch motions, on the other hand. And also the proposed method is less time consuming and has similar accuracy when comparing with more advanced vortex based methods.

Endo-reticular stress induces the unfolded protein response including a highly conserved set of genes crucial for cell survival against a variety of onslaughts. Among the activated stress response genes is Ire1, which undergoes auto-phosphorylation and acquires a regulated Ire1-dependent mRNA decay activity. Ire1P non-canonically splices the mRNA for Xbp1 in the cytoplasm. This spliced Xbp1 serves as mRNA encoding a transcription factor for unfolded protein response genes. Meanwhile the mRNA decay function of Ire1P degrades other cellular mRNAs and can cause changes to the translation machinery by altering regulators in a cell specific manner. Naïve splenic B cells differentiate into Antibody Secreting Cells and activate Ire1 phosphorylation early on after LPS stimulation, within 18 hrs. When Ire1 is activated in B cells, in addition to Xbp1 splicing, there are large-scale changes in mRNA; inhibition of the mRNA degradation function of Ire1 both reduces the number and changes the type of genes involved in altered splicing patterns, including factors for snRNA transcription. Some of the splicing changes seen at 18 hrs after LPS persist into the late stages of antibody secretion, up to 72 hrs, while others are supplanted by new splicing changes introduced by the induction of ELL2, a transcription elongation factor. ELL2 changes mRNA processing patterns and is necessary for Immunoglobulin secretion. RNA splicing patterns in antibody secreting cells are thus shaped by endo-reticular stress, ELL2 induction, and are associated with changes in the levels of snRNAs.

This study examines demographic factors which may influence opinions concerning medical students’ self-care and substance use behaviors as a means of providing insights into how future doctors view these issues compared to Australian doctors and members of the public. We conducted national, multicenter, prospective, on-line cross-sectional surveys using hypothetical scenarios to three cohorts- Australian medical students, medical doctors, and the public. Participants’ responses were compared for the different contextual variables within the scenarios and the participants’ demographic characteristics. In total 2,602 medical students, 809 doctors and 503 members of the public participated. Compared with doctors and the public, medical students were least tolerant of alcohol intoxication, and most tolerant of using stimulants to assist with study, and cannabis for anxiety. Doctor respondents more often aligned with the public’s opinions on the acceptability of the medical students’ behaviors. Although opinions are not equivalent to behaviour, Australian students’ views on the acceptability for cannabis to help manage anxiety, and inappropriate use of prescription-only drugs are concerning; these future doctors will be responsible for prescribing drugs and managing patients with substance abuse problems. However, if current Australian medical student’s opinions on alcohol misuse persist, one of the commonest substance addictions amongst doctors may decrease in future.

Immune Checkpoint Inhibitors are monoclonal antibodies that are used to treat over one in three cancer patients. While they have changed the natural history of disease, prolonging life and preserving quality of life, they are highly active in less than 40% of patients, even in the most responsive malignancies such as melanoma, and cause significant autoimmune side effects. Licenced biomarkers include tumour Programmed Death Ligand 1 expression by immunohistochemistry, microsatellite instability, and Tumour Mutational Burden, none of which are particularly sensitive or specific. Emerging tumour and immune tissue biomarkers such as novel immunohistochemistry scores, tumour, stromal and immune cell gene expression profiling, and liquid biomarkers such as systemic inflammatory markers, kynurenine/tryptophan ratio, circulating immune cells, cytokines and DNA are discussed in this review. We also examine the influence of the faecal microbiome on treatment outcome and its use as a biomarker of response and toxicity.

We aimed at analyzing Chlorophyll-a and CDOM dynamics from field measurements and at assessing the potential of multispectral satellite data for retrieving water-quality parameters in three small surface reservoirs in the Brazilian semiarid region. More specifically, this work comprises i) analysis of Chl-a and trophic dynamics; ii) characterization of CDOM; iii) estimation of Chl-a and CDOM from OLI/Landsat-8 and RapidEye imagery. The monitoring lasted 20 months within a multi-year drought, which contributed to water-quality deterioration. Chl-a and trophic state analysis showed a highly eutrophic status for the perennial reservoir during the entire study period, while the non-perennial reservoirs ranged from oligotrophic to eutrophic, with changes associated with the first events of the rainy season. CDOM characterization suggests that the perennial reservoir is mostly influenced by autochthonous sources, while allochthonous sources dominate the non-perennial ones. Spectral-group classification assigned the perennial as CDOM-moderate and highly eutrophic reservoir, whereas the non-perennial ones were assigned as CDOM-rich and oligotrophic-dystrophic reservoirs. The remote sensing initiative was partially successful: the Chl-a was best modelled using RapidEye for the perennial; whereas CDOM performed best with Landsat-8 for non-perennial reservoirs. This investigation showed high potential for retrieving water quality parameters in dry areas with small reservoirs.

A high proportion of dogs and cats are fearful during veterinary visits, which in some cases may escalate into aggression. Here, we discuss factors that contribute to negative emotions in a veterinary setting and how these can be addressed. The set-up of the waiting area (e.g. spatial dividers; elevated places for cat carriers), tailoring the examination and the treatment to the individual, considerate handling (minimal restraint when possible, avoiding leaning over or cornering animals) and offering high-value food or toys throughout the visit can promote security and, ideally, positive associations. Desensitisation and counterconditioning are highly recommended both to prevent and address existing negative emotions. Some negative experiences such as short-term pain from injections can be minimised by using tactile and cognitive distractions. Preemptive analgesia is recommended for known painful procedures. Recommendations for handling fearful animals to minimise aggressive responses are discussed. However, anxiolytics or sedation should be used whenever there is a risk of traumatising an animal or for safety reasons. Stress-reducing measures can decrease stress and fear in patients and consequently their owners – thus strengthening the relationship with the clients as well as increasing the professional satisfaction of veterinary staff.

TGF-β signaling transduces immunosuppressive biochemical and mechanical signals in the tumor microenvironment. In addition to canonical SMAD signaling, TGF-β can promote tumor growth and survival by inhibiting proinflammatory signaling and extracellular matrix remodeling. In this article, we will review how TAK1 activation lies at the intersection of proinflammatory signaling by immune receptors and anti-inflammatory signaling by TGF-β receptors. Additionally, we will discuss the role of TGF-β in the mechanobiology of cancer. Understanding how TGF-β dampens proinflammatory responses and induces pro-survival mechanical signals throughout cancer development will be critical in designing therapeutics which inhibit tumor progression while bolstering the immune response.

Inert gas asphyxiation is a rarely observed form of suffocation in which the decedent breathes in an inert chemical, such as helium or nitrogen, in the absence of oxygen. The ultimate cause of death is not a result of the chemical itself, but rather from the oxygen starvation as the inert gas displaces vital oxygen. In this case report, a 66-year-old Caucasian female with a history of gastroparesis, degenerative disc disease, and chronic pain was found deceased with a plastic bag secured around her head. Plastic tubing terminated inside the bag and connected to a nearby canister of nitrogen gas. This case study discusses the challenges in determining inert gas asphyxiation as the cause of death in a postmortem setting and emphasizes the importance of understanding the decedent’s history and context of the environment in which they were found.

It is important to be familiar with the presentation of Turner syndrome and to understand the common causes of death associated with the disease. Using the autopsy case as an example, this case report will outline the classic presentation of Turner syndrome, go over its physiology, epidemiology, pathogenesis and explain the cause of death in this particular case while also highlighting other common causes of death/risk factors within Turner syndrome. Differential diagnosis and mimicking disease processes will also be discussed. This report will also highlight the molecular tests used for the diagnosis of Turner syndrome, discuss developments using in situ hybridization, and discuss why this method is best for the determination of Turner syndrome over conventional karyotyping.

Objective: To explore the effect of rural-urban residence on self-reported health status with UK cancer survivors. Design: A cross-sectional postal questionnaire that collected data on demographics, post-code and self-reported health status. Methods: Independent Samples t test was used to detect differences in health status between rural and urban respondents. Pearson’s χ2 was used to control for confounding variables and multivariate analysis was conducted using Stepwise linear regression. Setting: East Midlands of England. Participants: Adult cancer survivors who had undergone primary treatment in the last five years. Participants were excluded if they had recurrence or metastatic spread, started active oncology treatment in the last twelve months and were in receipt of palliative or end of life care. Main Outcome: Residence was measured using the UK ONS RUC2011 Rural-Urban Classifications and Health Status via the UK ONS self-reported health status measure. Results: 227 respondents returned a questionnaire. Forty-five per cent (N=103) were resident in a rural area and fifty-three per cent (N=120) in an urban area. Rural (4.11±0.85) respondents had significantly (p<0.001) higher self-reported health status compared to urban (3.65±0.93) respondents (MD 0.47; 95% CI 0.23, 0.70). Conclusion: Rural respondents had significantly higher self-reported health status compared to their urban counterparts. It is hoped that the results will stimulate further work in this area and that researchers will be encouraged to collect data on rural-urban residency where appropriate.

The incorporation of unmanned aircraft terminal operations into the scope of Detect and Avoid systems necessitates analysis of the safety performance of those systems—principally, an assessment of how well those systems prevent loss of well clear from and collision with other aircraft. This type of analysis has typically been conducted by Monte Carlo simulation with synthetic, statistically representative encounters between aircraft drawn from an appropriate encounter model. While existing encounter models include terminal airspace classes, none explicitly represents the structure expected while engaged in terminal operations, e.g., aircraft in a traffic pattern. The work described herein is an initial model of such operations, scoped at this time specifically for assessment of unmanned aircraft landings and encounters with other aircraft either landing or taking off. The model shares the Bayesian network foundation of other MIT Lincoln Laboratory encounter models but tailors those networks to address structured terminal operations, i.e., correlations between trajectories and the airfield and each other. This initial model release is intended to elicit feedback from the standards-writing community.

Local air quality is a major concern for the population regularly exposed to high levels of air pollution. The airport, mainly due to its aircraft engines activities during taxiing and take off, is often submitted to heterogeneous but important concentrations of NOx and PM. The study suggests an innovative approach to determine the air traffic impact on air quality at the scale of the airport, its runways and terminals, in order to be able to locate the persistent high concentrations spots. The pollutants concentrations at 10 m resolution and 1 s time step are calculated in order to identify the most affected areas of an airport platform. A real day of air traffic on a regional airport is simulated, using real data as aircraft trajectories (from radar streams). In order to estimate the aircraft emissions, the Air Transport Systems Evaluation Infrastructure (IESTA) is used. Regarding local air quality, IESTA relies on the non-hydrostatic meso-scale atmospheric model Meso-NH using grid-nesting capabilities with 3 domains, for this study. The detailed cartography of the airport distinguishes between grassland, parking and terminals, allowing to compute exchanges of heat, water and momentum between the different types of surfaces and the atmosphere as well as the interactions with the building using a drag force. The dynamic parameters like wind, temperature, turbulent kinetic energy and pollutants concentration are computed at 10 m resolution over the 2 × 4 km airport domain. The pollutants are considered in this preliminary study as passive tracers, without chemical reactions. This preliminary study aims at proving the feasibility of high scale modelling over an airport with state of the art physical models.

This study examines the effect of a hyaluronic acid (HyAc) containing tricalcium phosphate putty scaffold material (TCP-P) and of a particulate tricalcium phosphate (TCP-G) graft on bone formation, volume stability and osteogenic marker expression in biopsies sampled 6 months after bilateral sinus floor augmentation (SFA) in 7 patients applying a split-mouth design. Biopsies were processed for immunohistochemical analysis of resin embedded sections. Sections were stained for collagen type I (Col I), alkaline phosphatase (ALP), osteocalcin (OC) and bone sialoprotein (BSP). Furthermore, the bone area and particle area fraction were determined histomorphometrically. Cone-beam CT data recorded after SFA and 6 month later were used for calculating the graft volume at these two time points. TCP-P displayed more advantageous surgical handling properties and a significantly greater bone area fraction and smaller particle area fraction. This was accompanied by significantly greater expression of Col I and BSP and in osteoblasts and osteoid and a less pronounced reduction in grafting volume with TCP-P. SFA using both types of materials resulted in formation of sufficient bone volume for facilitating stable dental implant placement with all dental implants having been in function without any complications for 6 years. Since TCP-P displayed superior surgical handling properties and greater bone formation than TCP-G, without the Hyac hydrogel matrix having any adverse effect on bone formation or graft volume stability, TCP-P can be regarded as excellent grafting material for SFA in a clinical setting.

Infectious as well as most non-infectious diseases share certain common molecular mechanisms. Among them, oxidative stress and the subsequent inflammatory reaction are of particular note. Metabolic disorders induced by external agents, be they bacterial or viral pathogens, excessive calorie intake, poor-quality nutrients, or environmental factors, produce an imbalance between the production of free radicals and endogenous antioxidant systems; the consequence being the oxidation of lipids, proteins and nucleic acids. Oxidation and inflammation are closely related, and whether oxidative stress and inflammation represent the causes or consequences of cellular pathology, they produce metabolic alterations that influence the pathogenesis of the disease. In this review we highlight two key molecules in the regulation of these processes: Paraoxonase-1 (PON1) and chemokine (C-C motif) ligand 2 (CCL2). PON1 is an enzyme bound to high-density lipoproteins. It breaks down lipid peroxides in lipoproteins and cells, participates in the protection conferred by HDL against different infectious agents, and is considered part of the innate immune system. With PON1 deficiency, CCL2 production increases, which induces migration and infiltration of immune cells in target tissues, and is involved in disturbing normal metabolic function. This disruption involves pathways controlling cellular homeostasis as well as metabolically-driven chronic inflammatory states. Hence, an understanding of these relationships would help improve treatments and, as well, identify new therapeutic targets.

Human papillomavirus (HPV) can potentially compromise both unassisted conception and success rates with assisted reproductive technology (ART). We aimed to evaluate the rates of HPV vaccination among women presenting for fertility care. This was a prospective study analyzing a self-reported intake form completed by all new patients presenting to a fertility clinic. The primary outcome was HPV vaccination status. Among the 523 new patients included in this study 172 (32.9%) were fully vaccinated, 237 (45.3%) were unvaccinated, and 95 (18.2%) patients didn’t respond. There was a significant age difference between fully vaccinated patients (33.1 years) compared to unvaccinated patients (37.4 years) p&lt;0.001 and a significant difference in gravidity between fully vaccinated patients (average 0.65) and unvaccinated patients (average 1.11) p=0.0005. No significant association was found between HPV vaccination status and history of abnormal Pap smears or relationship status (single vs. married). Less than half of patients presenting to our fertility center were vaccinated against HPV, despite being eligible to receive the vaccine. Younger patients with lower gravidity were more likely to be vaccinated against HPV than older patients with higher gravidity. Reproductive Endocrinologists have the opportunity to recommend HPV vaccination for eligible patients presenting for fertility care.

Smartwatches provide technology-based assessments in Parkinson’s disease (PD). We present results for sensor validation and disease classification via Machine Learning (ML). A comparison setup was designed with two different series of Apple smartwatches, one Nanometrics seismometer and a high-precision shaker to measure tremor-like amplitudes and frequencies. Clinical smartwatch measurements were acquired from a prospective study including 450 participants with PD, differential diagnoses (DD) and healthy participants. All participants wore two smartwatches and within a 15-min examination. Symptoms and medical history were captured on the paired smartphone. A broad range of different ML classifiers were cross-validated. Amplitude and frequency differences between smartwatches and the seismometer were under the level of clinical significance. The most advanced task of distinguishing PD vs DD was evaluated with 74,1% balanced accuracy, 86,5% precision and 90,5% recall by Multilayer Perceptrons. Deep Learning architectures significantly underperformed in all classification tasks. Smartwatches are capable of capturing subtle-tremor signs with low noise. This study provided the largest PD sample size of two-hand smartwatch measurements and our preliminary ML-evaluation shows that such a system provides powerful means for diagnosis classification and new digital biomarkers but it remains challenging for distinguishing similar disorders.

The incorporation of nanomaterials on (bio)sensors based on composite materials has led to important advances in analytical chemistry field due to the extraordinary properties that these materials offer. Nanodiamonds (NDs) are a novel type of material that has raised much attention, as they have the possibility of being produced on large scale by using relatively inexpensive synthetic methodologies. Moreover, NDs present some other interesting features as suitability for fluorescence due to surface functionalization and a proved biocompatibility, which makes them well suited for biomedical applications. In addition, NDs can be modified with metallic nanoparticles (NP), such as silver or gold, in order to combine the special features of both. The aim of this research work is the nanostructuration of novel sensing devices using NDs combined with silver (Ag@NDs) and gold (Au@NDs) nanoparticles. A complete morphological and electrochemical characterization as function of the prepared nanocomposite composition have been performed in order to improve the electroanalytical properties of the developed (bio)sensors.

Metabarcoding of prokaryotic and fungal ribosomal DNA was used to describe the microbial communities in soils of remnant equatorial rainforest, maize-bean intercrop, and sugarcane in western Kenya. Cropping systems influenced the microbial community composition and functional traits (energy source and nutrient cycling) of bulk soil in each crop. Microbial richness and diversity tended to increase with cultivation intensity. Soil of maize-bean intercrop had lower percentages and sugarcane had higher percentages of unique amplicon sequence variants of both bacteria and fungi compared to the remnant forest. Functional traits were altered by cultivation intensity. Compared to remnant forest soils, maize-bean intercrop soil had lower percentages of aerobic chemoheterotrophic bacteria and higher percentages of N-cycling bacteria, while sugarcane had higher percentages of aerobic chemoheterotrophic bacteria and lower percentages of N-cycling bacteria. In the face of increasing forest loss and pressures for agricultural productivity, this landscape provides a rich site for studying the impacts of cropping systems on soil health.

The constant increase in current density in electrical wires leads to increasingly significant heat losses due to Joule effect. Therefore, reducing the electrical resistivity of copper wires becomes necessary. To achieve this goal, the development of a composite material incorporating a more conductive reinforcement, the graphene, is a promising way. The design of a copper/graphene composite using a powder metallurgy-based method is presented. This synthesis method allows for interface control through the growth of CuO(Cu) nanoparticles tightly bonded to the reinforcement. It also involves the dispersion of graphene through ultrasonic treatment and its alignment within the matrix using a uniaxial pressing densification method. The increase in the hardness (+12 HV) demonstrates the effective dispersion and separation of graphene layers. The impact on the electrical properties of dendritic copper (ρe = 2.30 µΩ.cm) remains limited, with a decrease in electrical resistance of approximately 1.4%. However, for copper with higher electrical resistivity, flake copper (at 2.71 µΩ.cm) and brass at (7.66 µΩ.cm), reductions of 2.7% and 10% have been achieved, respectively. With the improvement of graphene quality, there is more room to improve the electrical properties. This work paves the way for the development of composites with improved electrical resistivity.

The number of children diagnosed with autism spectrum disorder (ASD) has increased substantially over the past two decades with current research unable to fully account for this dramatic increase in prevalence. One explanation proposes that both intrinsic (e.g., genetic) and extrinsic (e.g., environmental) risk factors may be involved in the etiology of ASD. The goal of this review paper is to explore modifiable pathways for intervention in children at risk for ASD, specifically examining how early social experience may be correlated with epigenetic change in genes associated with autism. We present an innovative model which proposes that polygenic risk and social experience (via epigenetic mechanisms) may both contribute to the observed ASD phenotype. Previous research on genetic, environmental, and epigenetic mechanisms implicated in the etiology of ASD will be reviewed, with an emphasis on the oxytocin receptor gene, which is epigenetically altered by early social experience, plays a crucial role in mammalian social and cognitive development, and is associated with both genetic and epigenetic risk for ASD. Identifying intrinsic (e.g., genetic) and extrinsic (e.g., social experience) risk markers for ASD, a combination of which has not previously been examined, would transform our understanding of this condition, facilitate earlier identification of ASD risk, and guide early intervention efforts. This may have a far-reaching impact on individuals with ASD, their families, and society.

The study purpose was to train and validate a deep-learning approach to detect micro-scale streetscape features related to pedestrian physical activity. This work innovates by combining computer vision techniques with Google Street View (GSV) images to overcome impediments to conducting audits (e.g., time, safety, and expert labor cost). The EfficientNETB5 architecture was used to build deep-learning models for eight micro-scale features guided by the Microscale Audit of Pedestrian Streetscapes-Mini tool: sidewalks, sidewalk buffers, curb cuts, zebra and line crosswalks, walk signals, bike symbols, and streetlights. We used a train--correct loop, whereby images were trained on a training dataset, evaluated using a separate validation dataset, and trained further until acceptable performance metrics were achieved. Further, we used trained models to audit participant (N=512) neighborhoods in the WalkIT Arizona trial. Correlations were explored between micro-scale features and GIS-measured- and participant reported-macro-scale walkability. Classifier precision, recall, and overall accuracy were all >84%. Total micro-scale was associated with overall macro-scale walkability (r=0.300,p<.001). Positive associations were found between model-detected and self-reported sidewalks (r=0.41,p<.001) and sidewalk buffers (r=0.26,p<.001). Computer vision model results suggest an alternative to trained human raters, allowing for audits of hundreds or thousands of neighborhoods for population surveillance or hypothesis testing.

Barley straw was used to reinforce PHB in a discontinuous semi-industrial process. Four different fibres were used as reinforcing material : sawdust (SW), defibred (DFBF), delignified (DBF) and bleached (BBF) fibres. Looking at the mechanical properties, onlythe elastic moduli (Et) revealed an improvement. Oppositely, the strengths at break, under both tensile and bending assays, tended to decrease, evidencing a poor affinity between both components. Thanks to the mechani-cal treatment applied on the fibre, DFBF appeared as the most promising filler with the mechani-cal properties of the composites closest to those of neat PHB. DFBF-based composites were then produced by means of a process intensification using a twin-screw extruder, and then moulded into flowerpots. Mechanical results showed almost the same properties between the discontinuous and intensification processes. The suitability of the material to be used on agriculture flowerpots was demonstrated by simulation. . PHB-DFBF composite material can be considered an alterna-tive to replace petrol-based products for applications in agriculture and horticulture.

Background: Protein CCDC186 is involved in the maturation of dense core vesicles in the trans-Golgi network in neurons and endocrine cells. To date, only one patient, within a large sequencing study of 1000 cases, and a single case report with variants in CCDC186 had previously been described. However, no functional studies in any of these two cases had been performed. Methods: Exome sequencing from one affected individual of each family was performed. In addition, Sanger sequencing of the parents and one of the affected siblings was also performed. CCDC186 protein was assessed in cultured fibroblasts or muscle tissue by western blot. Transcriptomic analysis was done by means of RNA sequencing. Results. We identified three patients from two gypsy families, unrelated to each other, with the same homozygous mutations in CCDC186 gene. Clinically, all patients presented with seizures, frontotemporal atrophy, hypomyelination, recurrent infections, and endocrine disturbances such as severe non ketotic hypoglycemia. Low levels of cortisol, insulin or growth hormone could only be verified in one patient. All of them had a neonatal onset and died between 7 months and 4 years of age. WES identified a homozygous variant in CCDC186 gene (c.2215C>T, p.Arg739Ter) in the index patients of both families. Protein expression studies demonstrated that the CCDC186 was practically undetectable in fibroblasts and muscle tissue. These observations correlated perfectly with the transcriptomic analysis performed in fibroblasts in one of the patients, which showed a significant reduction of CCDC186 mRNA levels. Conclusion. Our study provides functional evidence that mutations in this gene have a pathogenic effect on the protein and reinforces CCDC186 as a new disease-associated gene. In addition, mutations in CCDC186 could explain the combined endocrine and neurologic alterations detected in our patients

Molecularly imprinted polymers (MIPs) have been widely used in nanomedicine during the last few years. However, their potential is limited by their intrinsic properties resulting, for instance, in lack of control in drug release processes or complex detection for in vivo imaging. Recent attempts in creating hybrid nanomaterials combining MIPs with inorganic nanomaterials succeeded in providing a wide range of new interesting properties suitable for nanomedicine. Through this review, we aim to illustrate how hybrids molecularly imprinted polymers may improve patient care with enhanced imaging, treatments and combination of both.

Despite the strong links between sleep, circadian rhythms, and mental health, sleep education has been neglected in mental healthcare provider training programs. The current pilot study examined the potential efficacy and acceptability of a sleep education workshop for trainee psychologists, called the Sleep Psychology Workshop. Eleven students completing their Master of Psychology degrees (90% female, 24.4 ± 1.6 years old) attended the Sleep Psychology Workshop as part of their Health Psychology course, delivered as three, two-hour lectures (total six hours). Trainees’ sleep psychology knowledge quiz scores (% correct) demonstrated significant improvement from pre- (M = 60%, SD = .09) to post-workshop (M = 79%, SD = .08), t (6) = -5.18, p = .002. Trainees also reported increased self-efficacy to use common sleep-related assessment instruments and empirically supported interventions to manage sleep and circadian rhythm disturbances, along with increased confidence to manage insomnia disorder in clinical practice (all p<.02). Trainees also endorsed the workshop as an acceptable sleep education program for trainee psychologists via a post-workshop feedback survey, focus group, and six-month follow-up survey. This pilot study provides preliminary evidence for the Sleep Psychology Workshop as an effective and acceptable sleep education program for trainee psychologists.

The global increase of recreational escape rooms has inspired teachers around the world to implement escape rooms in educational settings. As escape rooms are increasingly popular in education, there is a need to evaluate their use, and a need for guidelines in order to develop and implement escape rooms in the classroom. This systematic review synthesizes current practices and experiences, focussing on important educational and game design aspects. Subsequently, relations between the game design aspects and the educational aspects are studied. Finally, student outcomes are related to the intended goals. In different disciplines, educators appear to have different motives to use aspects such as time constraints or teamwork. These educators make different choices for related game aspects such as the structuring of the puzzles. Other educators base their choices on common practices in recreational escape rooms. However, in educational escape rooms players need to reach the game goal by achieving the educational goals. More alignment in game mechanics and pedagogical approaches are recommended. These and more results lead to recommendations for developing and implementing escape rooms in education, and will help educators creating these new learning environments, and eventually help students’ foster knowledge and skills more effectively.

Viral infections cause metabolic dysregulation in the infected organism. The present study used metabolomics techniques and machine learning algorithms to retrospectively analyze the alter-ations of a broad panel of metabolites in the serum and urine of a cohort of 126 patients hospi-talized with COVID-19. Results were compared with those of 50 healthy subjects and 45 COVID-19 negative patients but with bacterial infectious diseases. Metabolites were analyzed by gas chro-matography coupled to quadrupole time-of-flight mass spectrometry. The main metabolites al-tered in the sera of COVID-19 patients were those of pentose glucuronate interconversion, ascorbate and fructose metabolism, nucleotide sugars, and nucleotide and amino acid metabolism. Alterations in serum maltose, mannonic acid, xylitol, or glyceric acid metabolites segregated positive patients from the control group with high diagnostic accuracy, while succinic acid seg-regated positive patients from those with other disparate infectious diseases. Increased lauric acid concentrations were associated with severity of infection and death. Urine analyses could not discriminate between groups. Targeted metabolomics and machine learning algorithms facilitated the exploration of the metabolic alterations underlying COVID-19 infection, and to identify po-tential biomarkers for the diagnosis and prognosis of the disease.

There is a general lack of research involving older lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ) people. This systematic review aimed to synthesize Japanese and Swedish qualitative research on LGBTQ people aged 60 years or older. PRISMA guidelines were followed. Japanese and Swedish articles, published in English-language journals, were searched across PsychINFO, Medline, CINAHL, and Sociological Abstracts databases. Additional searches were carried out to include studies written in Japanese or Swedish. There were no papers from Japan, and five from Sweden were reviewed. Four articles were included, including 48 participants aged 60–94 years. We summarized the findings using a deductive thematic synthesis. Two major themes emerged: (a) quality of life, minority joy, and resilience (positive aspects), and (b) experiences of discrimination, stigmatization, and minority stress (negative aspects). The participants described a wish to be acknowledged for their own assets and unique life histories, and to be treated as everyone else. They emphasized the importance of knowledge of LGBTQ issues among nursing staff, so that older LGBTQ people are treated in a competent and affirmative way. The study revealed several important topics for understanding older LGBTQ people’s life circumstances and the severe lack of qualitative studies in Japan and Sweden.

The relationship between pangolin-CoV and SARS-CoV-2 has been a subject of debate. Further evidence of a special relationship between the two viruses can be found by the fact that all known COVID-19 viruses have abnormally hard outer shell (low M disorder; i.e., low content of intrinsically disordered residues in the membrane (M) protein) that so far was found in CoVs associated with burrowing animals, such as rabbits and pangolins, in which transmission involves virus remaining in buried feces for a long time. While a hard outer shell is necessary for viral survival, a harder inner shell could also help. For this reason, the N disorder range of pangolin-CoVs, not bat-CoVs, more closely matches that of SARS-CoV-2 especially when Omicron is included. The low N disorder (i.e., low content of intrinsically disordered residues in the nucleocapsid (N) protein), first observed in pangolin-CoV-2017 amd later in Omicron, is associated with attenuation according to the Shell-Disorder-Model. Our experimental study revealed that pangolin-CoV-2017 and SARS-CoV-2 Omicron (XBB.1.16 subvariant) show similar attenuations with respect to viral growth and plaque formation. Subtle differences have been observed that are consistent with disorder-centric computational analysis.

Red beetroot, is a well-recognized and established source of bioactives (e.g., betalains and polyphenols) with anti-inflammatory and antimicrobial properties. It is proposed as a potential alternative to zinc oxide, with a focus on gut microbiota modulation and metabolite production. In this study, weaned pigs aged 28-days were fed either a control diet, diet supplemented with zinc oxide (3,000 mg/kg), or 2% and 4% pulverized whole red beetroot (CON, ZNO, RB2 and RB4; respectively) for 14 days. After the pigs were euthanized, blood and digesta samples were collected for microbial composition and metabolite analyses. Results showed, red beetroot supplemented diet at 2% improved the gut microbial richness relative to other diets, but marginally influenced the caecal microbial diversity compared to zinc oxide supplemented diet. Further increase in red beetroot levels (4% -RB4) lead to loss of caecal diversity, decreased short chain fatty acids and secondary bile acid concentrations. An increased Proteobacteria abundance, presumably due to increased lactate/lactic acid producing bacteria was also observed. Summarily, red beetroot contains several components conceived to improve the gut microbiota and metabolite output of weaned pigs. Future studies investigating individual components in red beetroot will better elucidate their contributions to gut microbiota modulation and pig health.

Pentadecanoic acid (C15:0) and heptadecanoic acid (C17:0) have been described as dietary biomarkers of dairy-fat consumption with varying degrees of reliability between studies. It remains unclear how the total amount of dietary fat; one of the main confounding factors in these biomarker investigations, affects C15:0 and C17:0 circulating compositions independently to their relative intake. Additionally, it is unknown how changes in the dietary total-fat affects other fatty acids in circulation. Through two dietary studies with different total-fat levels but maintaining individual fatty acid compositions we were able to see how the dietary total-fat affects the fatty acids in circulation. We saw that there was a significant, proportionate, and robust decrease in the endogenous C15:0 levels with an increase in dietary total-fat. However, there was an increase in the circulating C17:0 compositions as the total-fat increased. To conclude, the dietary total-fat content and fat-type have a very complex influence on the relative compositions of circulating fatty acids, which are independent to the actual dietary fatty acid composition. Knowing how to manipulate circulating C15:0 and C17:0 composition is far-reaching in nutritional/pathological research as they highlight a dietary route to attenuate the development of metabolic disease (both by reducing risk and improving prognosis).

This study aims to quantify carotenoids and tocopherols in human milk from healthy Chinese women, and to explore their associations with region, lactation stage, and maternal socio-economic and obstetric factors. Human milk was obtained from 509 healthy mothers and the compounds of carotenoids and tocopherols were analyzed by high-performance liquid chromatography after mild saponification and solvent extraction. Socio-economic and obstetric characteristics of the mothers and their dietary intakes through a single 24-hour dietary recall were evaluated. The median content of each component [μg/100mL, median (interquartile range)] in colostrum and mature milk was, respectively, β-carotene 8.0 (4.7-15.2) and 1.8 (1.4-2.7), β-cryptoxanthin 6.2 (2.4-12.9) and 1.8 (1.1-3.4), lutein 5.7 (2.9-10.2) and 3.4 (1.5-6.0), lycopene 6.3 (4.0-9.9) and 1.4 (1.1-2.0), zeaxanthin 1.0 (0.6-1.5) and 1.0 (0.6-1.4), α-tocopherol 645 (388-1176) and 211 (131-321), γ-tocopherol 68 (48-121) and 77 (45-120). The levels of all those vitamins presented regional differences, and decreased as lactation stage increased except for zeaxanthin and γ-tocopherol. Associations of carotenoid contents with maternal education, delivery mode, and present body mass index were found in multivariate analyses. These results suggest that some region, lactation stage, obstetric and socio-economic factors are associated with human milk concentrations of carotenoids and tocopherols in healthy Chinese mothers.

Monitoring glycosylation changes within cells upon response to stimuli remains challenging because of the complexity of this large family of post-translational modifications (PTMs). We have developed an original tool enabling labeling and visualization of the cell cycle key-regulator b-catenin in its O-GlcNAcylated form based on intramolecular Förster resonance energy transfer (FRET) technology in cells. We opted for a bioorthogonal chemical reporter strategy based on the dual-labeling of b-catenin with a green fluorescent protein (GFP) for protein sequence combined with a chemically-clicked imaging probe for PTM resulting in a fast and easy to monitor qualitative FRET assay. We validated this technology by imaging the O-GlcNAcylation status of b-catenin in HeLa cells. Moreover, the changes in O-GlcNAcylation of b-catenin were varied by perturbing global cellular O-GlcNAc levels with inhibitors of O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Finally, we provided a flowchart demonstrating how this technology is transposable to any kind of glycosylation.

SARS-CoV-2 infection produces a response of the innate immune system causing oxidative stress and a strong inflammatory reaction termed ‘cytokine storm’ that is one of the leading causes of death. Paraoxonase-1 (PON1) protects against oxidative stress by hydrolyzing lipoperoxides. Alterations in PON1 activity have been associated with pro-inflammatory mediators such as the chemokine (C-C motif) ligand 2 (CCL2) and the glycoprotein galectin-3. We aimed to investigate the alterations in the circulating levels of PON1, CCL2 and galectin-3 in 126 patients with COVID-19 and their interactions with clinical variables and analytical parameters. A machine learning approach was used to identify predictive markers of the disease. For comparisons, we recruited 45 COVID-19 negative patients and 50 healthy individuals. Our approach identified a synergy between oxidative stress, inflammation and fibrogenesis in positive patients that is not observed in negative patients. PON1 activity was the parameter with the greatest power to discriminate between patients who were either positive or negative for COVID-19, while their levels of CCL2 and galectin-3 were similar. We suggest that the measurement of serum PON1 activity may be a useful marker for the diagnosis of COVID-19.

Autoimmune hemolytic anemias (AIHAs) are conditions whereby a person produces an antibody to their own red blood cells (RBCs). These conditions can be primary with unknown cause or secondary, associated with diseases or infections. There are seven different categories of AIHA, warm-antibody AIHA (wAIHA); cold-antibody AIHA that includes cold agglutinin syndrome (CAS) and cold agglutin disease (CAD); mixed AIHA, also called combined cold and warm AIHA; paroxysmal cold hemoglobinuria (PCH) also termed Donath-Lansteiner test-positive AIHA; direct antiglobulin test-negative AIHA (DAT-neg AIHA); drug-induced immune hemolytic anemia (DIIHA); and passenger lymphocyte syndrome. This review will discuss each of these AIHAs and provide information on diagnosis and treatment.

Background: There is a lack of knowledge about how nurses and general practitioners (GPs) collaborated during the COVID-19 pandemicin primary care settings. Our study examined the roles of primary care nurses during the pandemic’s first wave, between March and June 2020, in Switzerland. Methods: The study involved all eight general practices implementing of a nursing role to the practice’s team. Primary care practice staff members (nurses, GPs and medical assistants) have been involved on the development of a new organizational model. A mixed-methods design study collected quantitative data using daily activity monitoring and an electronic survey. Additionally, eight nurses and nine GPs participated in a focus group discussion and individual interviews. Results: GPs recognized the substantial contributions, versatility, and autonomy of the primary care nurses in their practices during the pandemic. Those nurses experienced their involvement positively, mainly thanks to their perceived autonomy. The distribution of activities between primary care practice professionals was heterogenous due to extrinsic and intrinsic factors. Conclusion: Both nurses and GPs agreed that there was added value in having primary care nurses ingeneral practices in time of crisis, and this agreement will bolster plans to integrate this workforce across the canton. The development of nurses’ roles in primary care during the pandemic was reliant on many factors, including practice organization and Switzerland’s healthcare reimbursement and payment system

Fermented foods have long been known to have immunomodulatory capabilities and fermentates derived from the lactic acid bacteria of dairy products can modulate the immune system. We have used skimmed milk powder to generate novel fermentates using Lb. helveticus strains SC234 and SC232 and we demonstrate here that these fermentates can enhance key immune mechanisms that are critical to the immune response to viruses. We show that our novel fermentates SC234 and SC232 can positively impact on cytokine and chemokine secretion, nitric oxide (NO) production, cell surface marker expression, and phagocytosis in macrophage models. We demonstrate that fermentates SC234 and SC232 increase the secretion of cytokines IL-1β, IL-6, TNF-α, IL-27, and IL-10, promote an M1 proinflammatory phenotype for viral immunity via NO induction, decreases chemokine expression of Monocyte Chemoattractant Protein (MCP), increasing cell surface marker expression, and enhance phagocytosis in comparison to their starting material. These data suggest that these novel fermentates have potential as novel functional food ingredients for the treatment, management and control of viral infection.

Objective: Design and validate a wireless, low-cost, easy-to-use, mobile, dry-electrode headset for scalp electroencephalography (EEG) recordings for closed-loop brain-computer (BCI) interface and internet-of-things (IoT) applications. Approach: The EEG-based BCI headset was designed from commercial off-the-shelf (COTS) components using a multi-pronged approach that balanced interoperability, cost, portability, usability, form factor, reliability, and closed-loop operation. Main Results: The adjustable headset was designed to accommodate 90\% of the population. A patent-pending self-positioning dry electrode bracket allowed for vertical self-positioning while parting the user's hair to ensure contact of the electrode with the scalp. In the current prototype, five EEG electrodes were incorporated in the electrode bracket spanning the sensorimotor cortices bilaterally, and three skin sensors were included to measure eye movement and blinks. An accelerometer provides monitoring of head movements. The EEG amplifier operates with 24 bits resolution up to 500 Hz sampling frequency, and can communicate with other devices using 802.11 {b/g/n/WiFi}. It has high SNR and CMRR (121 dB and 110 dB, respectively), and low input noise. In closed-loop BCI mode, the system can operate at 40 Hz, including real-time adaptive noise cancellation and 512 MB of processor memory. It supports LabVIEW as backend coding language and JS, CSS, HTML as front-end coding languages, and includes training and optimization of Support Vector Machine (SVM) neural classifiers. Extensive bench testing supports the technical specifications and human subject pilot testing of a closed-loop BCI application to support upper-limb rehabilitation provides proof-of-concept validation for device use at both the clinic and at home. Significance: The low-cost, accessibility, usability, interoperability, and programmability of the proposed closed-loop BCI system provides a low-cost solution for BCI and neurorehabilitation research and IoT applications.

Lactic acid bacteria are traditionally applied in a variety of fermented food products and have the capability to produce a wide range of bioactive ingredients during fermentation including vitamins, bacteriocins, bioactive peptides and bioactive compounds. The bioactivity and health benefits associated with these ingredients have gained interest in applications in the functional dairy market and have relevance both as components produced in situ and as functional additives. This review provides a brief description of the regulations regarding the functional food market in the European Union as well as an overview of some of the functional dairy products currently available in the Irish and European markets. A better understanding of the production of these ingredients excreted by lactic acid bacteria can further drive the development and innovation of the continuously growing functional food market.

The bivalve mollusk, Anadara tuberculosa (Black Shell, in Spanish Concha prieta, "CP"), is found on America's Pacific coast, where it is harvested for subsistence and commercial markets. This paper aims to diagnose the performance of the black shell's value chain. We also identify several challenges that must be addressed to improve the sustainability of the black shell fishery in Ecuador. The descriptive methodology was quantitative, with a non-experimental, field, cross-sectional, and ex post facto design. Similar questionnaires were designed, validated, and applied to each link in the production chain to collect information. The performance of the value chain was diagnosed in the dimensions of productivity, competitiveness, and quality of life, reaching a 75.1% index, a result that indicates that the value chain has a moderate to good performance level. However, the value chain can be improved if the following challenges are met: 1) Restoration of the mangrove ecosystem, 2) Promotion of low-intensity shellfish aquaculture, 3) Good sanitary management and purification, 4) Promotion of value-focused ventures, 5) Strengthening of organizations and agreements for the use and custody of mangroves, and 6) Strengthening of institutions that contribute to the advancement of these challenges.