Background Adolescents living with obesity (AlwO) can have limited exercise capacity. Exercise capacity can be predicted by a 2-factor model comprising lung function and leg muscle function, but no study has looked at cycling leg muscle function and its contribution to cycling exercise capacity in AlwO. Methods 22 nonobese adolescents and 22 AlwO (BMI>95 percentile) were studied. Anthropometry, body composition (DEXA), spirometry, 30-sec isokinetic work capacity, and maximal exercise (cycle ergometry) were measured. Results AlwO had greater lean leg mass (LLM) (14.8±4.1 vs 21.0±4.3 kg, Con vs AlwO p<0.001). Lung function did not differ, although FEV 1 trended higher in AlwO (101.0±13.1 vs 107.9±12.7 percent predicted, p=0.08). Leg 30-second work output did not differ in absolute terms or per allometrically scaled LLM. Peak oxygen consumption did not differ between the groups in absolute terms or as percent predicted values (78.5±15.4 vs 82.1±16.5 percent predicted), but was lower in AlwO when expressed per scaled kg of LLM. Peak oxygen consumption related to both lung function and 30-second work capacity, with no observed group effect. 30-second leg work capacity related to the scaled muscle mass, with a small group effect. There was some correlation between leg work capacity and time spent in moderate to vigorous physical activity in AlwO (r s=0.39, p=0.07). Conclusion AlwO have larger LLM and preserved exercise capacity, when expressed as percentage of predicted, but not per allometrically scaled LLM. Increasing time spent in moderate to vigorous activity may benefit AlwO.

The characteristic protection villages (CPVs) are the basic types of rural revitalization, and one of the essential carriers of rural cultural heritage. Identifying its spatial structure characteristics contributes to the inheritance and continuation of rural civilization. Based on the CPVs data in Hubei Province, this paper identified spatial structure and evolution characteristic of CPVs in the perspective of spatial distribution types, direction, density, and equilibrium, respectively. At the same time, the Geodetector was used to analyze the influence mechanism of CPVs from 2009 to 2020. The main results showed that: (1) The spatial distribution of CPVs was an agglomeration structure type, which showed an increasing agglomeration trend of evolution characteristics in Hubei Province. And among them, the traditional villages (TVs) had the highest degree of agglomeration. (2) The CPVs showed the pattern of “east (slightly south) – west (slightly north)” with strong centripetal force and obvious directional, and they also showed a trend of gradual diffusion to east and west. (3) The high–density areas of CPVs presented an evolution trend from scattered independent structure to massive cluster structure, and generally presented a horizontal V shape kernel density structure. Meanwhile, the high–density areas of different types of CPVs had significant differences. (4) The CPVs were distributed in an unequal probability, and there were agglomerations in Yichang, Jingzhou, Shiyan, Xiangyang, and Enshi where it showed a gradually balanced development trend. The natural environment is the background and cornerstone of the site selection and layout of CPVs in Hubei Province. The influence of resource endowment, social economy and policy environment on the spatial distribution of CPVs are increasing gradually, and there are significant differences between different types of CPVs affected by various factors. We try to fill the gap in quantitative identification on the structure of CPVs to enrich the research regarding the special type features mechanism, which has significance for the protection and revitalization development of CPVs.

Our knowledge of biodiversity hinges on sufficient data, reliable methods, and realistic models. Without an accurate assessment of species distributions, we cannot effectively target and stem biodiversity loss. Species range maps are the foundation of such efforts, but countless studies have failed to account for the most basic assumptions of reliable species mapping practices, undermining the credibility of their results and potentially misleading and hindering conservation and management efforts. Here, we use examples from the recent literature and broader conservation community to highlight the substantial shortfalls in current practices and their consequences for both analyses and conservation management. We detail how different decisions on data filtering impact the outcomes of analysis and provide practical recommendations and steps for more reliable analysis, whilst understanding the limits of what available data will reliably allow and what methods are most appropriate. Whilst “perfect” analyses are not possible for many taxa given limited data, and biases, ensuring we use data within reasonable limits and understanding inherent assumptions is crucial to ensure appropriate use. By embracing and enacting such best practices, we can ensure both the accuracy and improved comparability of biodiversity analyses going forward, ultimately enhancing our ability to use data to facilitate our protection of the natural world.

Introduction: The oral cavity is an important site for the entry and multiplication of respiratory viruses, and the immune system and oral microbiome act as antiviral barriers. Data regarding oral microbiome and COVID-19 is scarce. Therefore, a prospective cohort was conducted at the Hospital das Clínicas of FMUSP to evaluate the frequency of oral lesions associated with COVID-19 and the diversity of the oral microbiome on disease severity. Methods: Oral samples from SARS-CoV-2 positive patients were collected. After DNA extraction from the whole saliva samples, sequencing of the 16S rRNA gene using the Ion Torrent PGM platform was performed. Alpha and beta diversity analyses were conducted using the R program. Clinical data from electronic medical records were collected and multiple logistic regression model was constructed to assess the association between oral microbiome diversity and COVID-19 severity (oxygen therapy, mechanical ventilation). Results: The study included a total of 115 samples from 125 patients, 14 had oral lesions, the majority were female (54.8%), with a mean age of 55.4 years old. Around 59.1% of patients were in intensive care units(ICUs), 87.2% were using antibiotics, and 18.3% died. The most frequently antibiotics used were third-generation cephalosporins(35.7%), piperacillin/tazobactam(27%), and glycopeptides(21.7%). In general, the most abundant phyla were Firmicutes, Proteobacteria, and Bacteroidetes, representing 86.3% of the oral microbiome. Oral microbiome diversity analysis revealed statistical differences in COVID-19 severity (Shannon p=0.05), presence of oral lesions Shannon p=0.05), antibiotic use(Shannon p=0.04), and oxygen therapy Observed p=0.04). Differential abundance analysis identified specific taxa related to each variable, such as Prevotella in severe patients and Staphylococcus in individuals with oral lesions. Multivariable logistic regression pointed out that the SARS-CoV-2 PCR positive on the oral cavity and the age (above 60 years) were risk factors for disease severity. Conclusion: Despite the small number of participants with oral cavity lesions, we found significant differences in the microbial communities, particularly in the genus Staphylococcusd associated with oral lesions. Although the abundance of Prevotella was associated with severity of COVID-19 on the microbiome analysis, the multivariate model showed that only age and RT-PCR positive for SARS-CoV-2 on the oral cavity were independent risk factors for severity.

This study investigates the impact of cyberterrorism on the global food supply chain, specifically focusing on the security of grain storage facilities. Drawing from recent geopolitical events that have disrupted grain supply, the paper underscores the potential global consequences of targeted cyber attacks. The research involves a thorough review of grain storage technologies and their associated security vulnerabilities, supported by existing literature and case studies. Findings reveal significant security gaps in grain storage systems, such as centralized control systems and inadequate security protocols. The study not only offers actionable recommendations for enhancing supply chain resilience but also informs policy development aimed at safeguarding critical infrastructure. The research is pivotal for academics, industry stakeholders, and policy makers concerned with food security in the digital age.

SARS-CoV-2, the virus behind the COVID-19 pandemic, affects multiple organs, including the male reproductive system. The male reproductive tract expresses ACE-2, the primary viral entry receptor, in spermatogonia, Leydig, and Sertoli cells. While viral infections can harm male fertility through cytokine storms, the effects of SARS-CoV-2 on fertility are still unclear. Thus, this study aimed to examine the impact of COVID-19 on the male reproductive tract. Semen samples from 20 patients, collected 3 months post-SARS-CoV-2 infection, revealed the presence of ACE2 and TMPRSS2 receptors in both plasmatic and spermatozoa fractions. Five patients showed viral RNA-dependent RNA polymerase (RdRp), indicating potential viral persistence. Elevated levels of inflammatory cytokines and chemokines were observed in the plasmatic fraction, suggesting a persistent inflammatory condition affecting sperm vitality. Immune cell populations associated with viral clearance were identified in the semen fraction, correlating with receptor expression and inflammatory cytokines. To address SARS-CoV-2 uncertainties in reproductive medicine, we assessed the virus’s presence in seminal fluid before and after cryopreservation using slow freezing and vitrification. Our study confirms the safety of both techniques in preserving male fertility for assisted reproductive technology programs. In conclusion, our study highlights the impact of SARS-CoV-2 on male reproductive health, emphasizing the persistence of viral entry receptors, potential viral RNA presence, the inflammatory environment, and the involvement of immune populations in the male reproductive tract post-infection. Importantly, we confirm the safety of conventional freezing and vitrification techniques for preserving male fertility in assisted reproductive technology programs amidst the COVID-19 pandemic.

Title: Interstitial Lung Diseases and COVID19 Pneumonia

In the unique landscape of immunology research in New Zealand, this article explores the collaborative networks spanning the two main islands, through a conversation with Associate Professor Joanna Kirman and Dr. Robert Weinkove. The discussions delve into their dynamic collaborations with countries like Asia, Australia, and the United States from their labs at the University of Otago and the Malaghan Institute respectively, provides insight into the translational research landscape of New Zealand, and the integration of Māori culture into all aspects of scientific research and clinical practise. Kirman’s work in understanding immunological memory in tuberculosis and Weinkove’s research in cancer immunotherapies, particularly CAR-T cells, are highlighted. The natural beauty and accessibility of New Zealand supports it’s research diversity.

The emergence of compulsive drug seeking habits, a hallmark feature of substance use disorder, has been shown to be predicated on the engagement of dorsolateral striatum (DLS) control over behaviour, which is underpinned by a dopamine-dependent functional coupling of the nucleus accumbens and the DLS. However, the mechanisms by which this coupling occurs have not been fully elucidated. The striatum is tiled by a syncytium of astrocytes that express the dopamine transporter (DAT), whose expression is altered in individuals with a heroin use disorder. Thus, astrocytes are uniquely placed functionally to bridge dopamine-dependent mechanisms across the striatum. Thus, here we tested the hypothesis that exposure to heroin, which does not interact with DAT, influences its expression in astrocytes across the striatum before the development of DLS-dependent incentive heroin seeking habits. Using Western-blot, qPCR and RNAscope we measured DAT protein and mRNA levels in whole tissue, cultured or in situ astrocytes from striatal territories of rats with a well-established cue-controlled heroin seeking habit and rats trained to respond for heroin or food under continuous reinforcement. Incentive heroin seeking habits were associated with a reduction in DAT protein levels in the anterior DLS (aDLS) that was preceded by a heroin-induced reduction in DAT mRNA and protein content in astrocytes across the striatum. aDLS astrocytes were also shown to be uniquely susceptible to direct dopamine- and opioid-induced downregulation of DAT expression. These results suggest that astrocytes may critically regulate the striatal dopaminergic adaptations that lead to the development of incentive habits for heroin.

African science has substantial potential, yet it grapples with significant challenges. Here we describe the establishment of the Biomedical Science Research Centre (BioRTC) in Yobe State, Northeast Nigeria, as a case study of a hub fostering on-continent research and describe strategies to surmount some of these barriers. We detail the steps taken to establish BioRTC, emphasising the critical importance of stakeholder engagement, community involvement, resource optimisation, and collaborations. Although we are in the early stages of our journey, our experience can nonetheless serve as a guide to others embarking on similar endeavours in resource-limited settings. We invite the support and collaboration of those who share our vision and believe in our potential.

Due to recent advances in computational power and sophisticated software, modeling many complex systems has come within reach for the first time, promising understanding these systems better than ever before. A prime example of the impact of these advances is on the use computational models to construct performance landscapes. As interpretive tools, performance landscapes are incredibly powerful for interrogating evolutionary trends, competitive dynamics in an ecosystem, and even niche partitioning. If carefully crafted, these landscapes can lead to important insights in the evolutionary systems that they model. In this synthesis, we cover best practices for constructing performance landscapes, including: selecting parameter inputs and outputs, building morphospaces, constructing physical models, parameter spaces and surrogates, and performance space analysis. We conclude with a call for additional work linking biology and mathematics around the unique challenges presented by performance-space construction and validation.

All interactions between multiple species invading together (coinvasion) must be accounted for to predict species coexistence patterns across space. Mutualisms, particularly, are known to influence species’ population dynamics and their invasive ability (e.g. mycorrhizal fungi with partner plants). Yet, while modelling coinvasion, their role in mediating coexistence is overlooked. We build a spatial model of coinvasion of two competing plant species with a shared fungal mutualist to study how mutualism and competition shape the spatial coexistence of competitors. We find that mutualist presence engenders regional (spatial) coexistence between competitors even when local coexistence between them is impossible. Further, increasing mutualist dispersal results in sharp transitions in competitor coexistence outcomes. Finally, differences in mutualist partner dependence and competitive ability interact to produce a variety of local and regional coexistence outcomes. Thus, incorporating mutualism dependence and dispersal behaviour into coinvasion models offers new insights into spatial coexistence and invasive species distributions.

A premature newborn born to an adolescent girl with acute Ebola virus disease and malaria survives in a resource-limited setting in an Ebola Treatment Unit in DR Congo. “ A Case Report”.

Acute thrombus formation on the delivery sheath is rare condition during percutaneous left atrial appendage occlusion. We presented two cases that TEE showed a floating thrombus attached to the tip of delivery sheath during the procedure. Cerebral embolic protection devices were used to prevent neurological events after thrombus was detected. The

Background and Purpose: Our previous study reported that erythroferrone (ERFE), a newly identified hormone produced by erythroblasts, responded to recombinant human erythropoietin (rHuEPO) sensitively but its dynamics was complicated by double peaks and circadian rhythm. This study intends to elucidate the underlying mechanisms for the double peaks of ERFE dynamics, and further determine whether early ERFE measurements can predict hemoglobin (HGB) responses to rHuEPO. Experimental Approach: By expressing recombinant rat ERFE protein and investigating its deposition in rats, the production of ERFE was deconvoluted. To explore the role of iron in ERFE production, we monitored short-term changes of iron status after injection of rHuEPO or deferiprone (DFP). Pharmacokinetic/pharmacodynamic (PK/PD) modelling was used to confirm the mechanisms and examine the predictive ability of ERFE for long-term HGB responses. Key Results: The rRatERFE protein was successfully expressed and purified. The production of ERFE was deconvoluted and showed two independent peaks (2 h and 8 h). Transient iron decrease was observed at 4h after rHuEPO injection and DFP induced significant increases of ERFE. Based on this mechanism, the PK/PD model could characterize the complex dynamics of ERFE. In addition, the model predictions further revealed a stronger correlation between ERFE and HGB peak values than that for observed values. Conclusions and Implications: The complex dynamics of ERFE should be composited by an immediate release and transient iron deficiency-mediated secondary production of ERFE. The early peak values of ERFE, which occur within a few hours, can predict HGB responses several weeks after ESA treatment.

Accurate flow prediction is a primary goal of hydrological modeling studies, which can be affected by the use of varying rainfall datasets, autocalibration methods, and performance indices. The combined effect of three rainfall datasets — Fifth generation of European ReAnalysis (ERA-5), Gridded meteorological data (gridMET), Global Precipitation Measurement Integrated Multi-satellitE Retrievals (GPM IMERG) — and three autocalibration techniques — Dynamically Dimensioned Search (DDS), Generalized Likelihood Uncertainty Estimation (GLUE), Latin Hypercube Sampling (LHS) — on SWAT+ river flow prediction was measured using three evaluation metrics — Nash Sutcliffe Efficiency (NSE), Kling Gupta Efficiency (KGE) and coefficient of determination (R 2) — for two watersheds in North Carolina (Cape Fear, Tar Pamlico) using the Soil Water Assessment Tool Plus (SWAT+) model. Five parameters in the SWAT+ model, cn2, revap_co, flo_min, revap_min, and awc, were found to be significantly sensitive under all combinations for both watersheds. Simulated flow varied more with the change in rainfall than the calibration technique used. We discovered that GPM IMERG gave the best results of the rainfall datasets, followed by ERA-5 and gridMET. We observed that the NSE score is more sensitive to different combinations of rainfall datasets and calibration techniques than the KGE scores. SWAT+ underperformed in the prediction of base flow for the groundwater-driven watershed. Overall, we recommend using the GPM IMERG rainfall dataset with the GLUE optimization technique and KGE performance index for optimal flow simulations. The results from this study will help hydrological modelers choose an optimal combination of rainfall dataset, autocalibration technique, and performance index depending on watershed characteristics.

Reservoir is a vital tool for human utilization of water resources, and the deterioration of its water quality can seriously threaten the water cycle and sustainable urban development. However, there are relatively few studies in academia that analyze and evaluate the water quality of multiple reservoirs at the same time. To address this knowledge deficit, we collected 108 water samples from three different reservoirs in Chuzhou City for 36 months (from 2019 to 2021), explored the drivers of changes in water quality parameters over time and the extent of eutrophication. Our results indicated that the water quality of the reservoirs was deteriorating during the study period, among which Huanglishu Reservoir and Shahe Reservoir reached mild eutrophic status, and both had higher eutrophication levels than Chengxi Reservoir. Secchi Depth (SD), Total Nitrogen (TN), and Total Phosphorus (TP) were the principal factors inducing eutrophication. The biased utilization of reservoir functions was the major contributor to the discrepancy in the degree of eutrophication. Furthermore, Pearson Correlation Analysis revealed that there are significant correlations between many water quality parameters. Cluster Analysis (CA) grouped the 12 months of each year into three clusters (stable water level period, rainy season high flow period, and winter low flow period). Based on this, Analysis of Variance (ANOVA) showed that most water quality parameters varied considerably between the clusters. Collectively, this study identified the actual water quality conditions of three reservoirs in Chuzhou City and provided guidance for local water quality management and environmental protection.

The inherent limitation of threshold voltage drift in silicon carbide metal-oxide-semiconductor field-effect transistors has restricted their broader applicability. This paper proposes a driving method that introduces an additional gate drive level, effectively reducing the threshold voltage drift in silicon carbide metal-oxide-semiconductor field-effect transistors while preserving the advantages of a negative gate turn-off voltage. The practical effectiveness of this method is validated through experiments.

It is important to solve the problem of metal particle pollution inside the DC GIL. Using numerical simulation to calculate the trajectory of metal particles is an important method of designing particle traps and drive electrodes. In this paper, a 3D simulation method of dynamic particle motion randomly based on quadratic Rodrigues’ rotation is proposed to solve the trajectory of metal particles inside the DC GIL, considering the random reflection. Based on this model, the influence characteristics of random reflection angle, gravity inclination, particle size and other factors on particle motion are analyzed. From the results, the trapping efficiency of particle traps becomes weaker under the effect of gravity, and particles with larger sizes are more likely to escape. The drive electrodes set at the high voltage conductor can prevent particles from crossing the drive electrode. It can effectively improve the capture efficiency of the particle trap and increase the capture-escape ratio more than 45.9%.

Electricity network across the globe has witnessed an increase in penetration of distributed energy resources (DER) to the grid. A maiden attempt to integrate 50% loaded Combined Cycle Gas Turbine (CCGT) plant and doubly fed Induction Generator (DFIG) plant with DER is carried out for investigations to study frequency excursions in the hybrid system along with temperature excursions in the CCGT plant. A novel attempt is done to introduce modified beluga whale optimizer for tuning the controller gains and system parameters of the hybrid isolated system. This article emphasizes on the system behaviour of an isolated power system consisting of a CCGT plant and a DFIG plant integrated with distributed energy resources comprising of Diesel engine generator, wind turbine generator and battery energy storage system. Among the classical secondary controllers, comparison of system responses is carried out to select the best among proportional, proportional-integral, and proportional-integral-derivative controllers. A modified beluga whale optimization algorithm is utilized to tune the controllers. Various investigations conducted with different turbo generators confirm the control strategy to the frequency of excursions. The hybrid CCGT – DFIG - DER system is also evaluated under random load demand, change in generation rate constraints and DFIG power output.

The global signal (GS) in the brain potentially carries information that related with neural activities. However, the impacts of the GS on the interpretation of the consciousness-related measures during different types of anesthetics-induced unconsciousness remain unknown. Thirteen glioma patients underwent propofol and sevoflurane induced general anesthesia were enrolled for analysis. Blood oxygenation level dependent (BOLD) signals were recorded for all patients in awake state (i.e., baseline) and general anesthesia (i.e., unconscious state) by using functional magnetic resonance imaging (fMRI). Under the scenario of with GS and without GS, we examined the temporal variability and amplitude of low-frequency fluctuation (ALFF) to analyze the BLOD changes. The functional connectivity and brain networks were analyzed to investigate the alteration in different brain regions. In time domain and frequency domain analysis, both anesthetics significantly decreased in standard deviation (SD) (BF10 > 3) under both scenarios. While comparing baseline to the unconscious state, only propofol exhibited a significant normalized ALFF reduction under with GS scenario (BF10 > 3). In functional connectivity analysis, removing GS changed the significance of functional connectivity especially in Limbic network and Default network for propofol. For sevoflurane, most of functional connectivity (FC) significances were remarkably altered. In brain network analysis, removing GS changed the nodal indices, with different effects on different networks. In summary, for both anesthetics, the effects of GS had noticeable impacts on in functional connectivity and brain networks analysis-based measures. GS has a significant impact on explaining the changes of anesthetics induced functional connectivity and brain networks.

ADHD and anxiety frequently occur together; however, the cognitive outcomes of co-morbid anxiety and ADHD are not straightforward. A potential explanation for conflicting results in the literature may be that different core ADHD symptoms show different interactions with anxiety depending on the task processing demands. To address this question, we investigated whether different ADHD traits are related to different inhibitory outcomes, contingent upon the level of trait anxiety. The sample consists of 60 non-clinical university students (X ̅age= 20.5, 53% male). Conners’ Adult ADHD Rating Scale (CAARS-SL) and State Trait Anxiety Inventory (STAI) were used to measure ADHD-traits and anxiety, respectively. The participants completed a visual Go/NoGo task with and without distractor conditions while continuous EEG was recorded. Inhibitory control was operationalized as the frontocentral N2 maximum peak amplitude elicited in response inhibition (NoGo/No Distractor), cognitive inhibition (Go/Distractor), dual inhibition (NoGo/Distractor), and control (Go/No Distractor) conditions. We analyzed the moderating effect of trait anxiety on the prediction of inhibitory control by ADHD scores for each Go/NoGo condition with the varying inhibition demands. Results showed that trait anxiety moderated the effects of total ADHD and hyperactivity-impulsivity scores, but only in the response inhibition condition (NoGo/No Distractor). Additionally, inattentiveness was related to attenuated N2 amplitudes in the cognitive inhibition condition (Go/Distractor). These findings suggest that depending on the inhibitory demands of the task, unique cognitive outcomes may occur when different ADHD traits coexist with anxiety.

Multi module isolated converters (MMICs) find extensive application in various DC-DC applications due to their remarkable features of galvanic isolation, bi-directional power flow, high power density and enhanced efficiency. However, voltage and current sharing among the converter modules are the most significant issues in MMICs. This paper proposes Multi-port Integrated-Magnetics Transformers (MpIMTs) which address the input-output DC-link voltage imbalances within an ISOS converter. The proposed transformers ensure the input voltage sharing (IVS) and output voltage sharing (OVS) through balancing windings within their structures, thus substitutes the complicated active control scheme with the balancing winding. Besides, the input side and output side modules are decoupled from each other, thus the impact of parameters variation and inter-module energy transfer during a transient of one side does not reflect to the other side. These properties are achieved by proposing a custom-designed core and an off the shelf available U core assembled MpIMTs. The magnetic and electrical equivalent along with the design criteria of the balancing winding are also presented. Furthermore, the paper includes the comparative analysis of the proposed transformers which reveals that while the U-core MpIMT offers simplified construction, it comes at the expense of slightly reduced efficiency compared to the custom-designed MpIMT. Finally, the proposed U core MpIMT is validated through a laboratory prototype.

Aim The reference nutrient intake for vitamin D in people aged ≥4 years is 10 μg/day (400 IU/day) in the UK, but the recommended daily allowance is 15 μg/day (600 IU/day) for people aged 1-70 years in the US. Here, we aim to compare the 25-hydroxyvitamin D3 (25(OH)D3) serum concentration profiles between the two doses. Methods With adult trial data, we constructed a physiologically based pharmacokinetics (PBPK) model of serum concentrations of vitamin D3 and 25(OH)D3 using nonlinear mixed effects (NLME) modelling. We used this model to forecast the mean, 5% and 95% percentiles for serum 25(OH)D3 concentrations. Results Our final model uses bodyweight to adjust volume of each compartment and maximum clearance of 25(OH)D. No other covariate was identified. The model accurately predicted data from trials of a broad range of dose regimens. We simulated subjects of the average UK male and female weights with baseline 25(OH)D < 25 nmol/L. Simulation suggests circulating 25(OH)D concentrations in >5% of men and women taking 10 μg/day for a year might fail to reach 50 nmol/L, while those on 15 μg/day were predicted to attain this threshold. Conclusion The two doses generate significant difference in serum 25(OH)D3 concentrations. This needs to be considered for choosing the right dose for the public health guideline.