Genetically modified pigs:Emerging animal models for hereditary hearing loss

Hereditary hearing loss(HHL),a genetic disorder that impairs auditory function,significantly affects quality of life and incurs substantial economic losses for society.To investigate the underlying causes of HHL and evaluate therapeutic outcomes,appropriate animal models are necessary.Pigs have been extensively used as valuable large animal models in biomedical research.In this review,we highlight the advantages of pig models in terms of ear anatomy,inner ear morphology,and electrophysiological characteristics,as well as recent advancements in the development of distinct genetically modified porcine models of hearing loss.Additionally,we discuss the prospects,challenges,and recommendations regarding the use pig models in HHL research.Overall,this review provides insights and perspectives for future studies on HHL using porcine models.

High-speed penetration of ogive-nose projectiles into thick concrete targets:Tests and a projectile nose evolution model

The majority of the projectiles used in the hypersonic penetration study are solid flat-nosed cylindrical projectiles with a diameter of less than 20 mm.This study aims to fill the gap in the experimental and analytical study of the evolution of the nose shape of larger hollow projectiles under hypersonic penetration.In the hypersonic penetration test,eight ogive-nose AerMet100 steel projectiles with a diameter of 40 mm were launched to hit concrete targets with impact velocities that ranged from 1351 to 1877 m/s.Severe erosion of the projectiles was observed during high-speed penetration of heterogeneous targets,and apparent localized mushrooming occurred in the front nose of recovered projectiles.By examining the damage to projectiles,a linear relationship was found between the relative length reduction rate and the initial kinetic energy of projectiles in different penetration tests.Furthermore,microscopic analysis revealed the forming mechanism of the localized mushrooming phenomenon for eroding penetration,i.e.,material spall erosion abrasion mechanism,material flow and redistribution abrasion mechanism and localized radial upsetting deformation mechanism.Finally,a model of highspeed penetration that included erosion was established on the basis of a model of the evolution of the projectile nose that considers radial upsetting;the model was validated by test data from the literature and the present study.Depending upon the impact velocity,v0,the projectile nose may behave as undistorted,radially distorted or hemispherical.Due to the effects of abrasion of the projectile and enhancement of radial upsetting on the duration and amplitude of the secondary rising segment in the pulse shape of projectile deceleration,the predicted DOP had an upper limit.

Quantitative prediction model for the depth limit of oil accumulation in the deep carbonate rocks:A case study of Lower Ordovician in Tazhong area of Tarim Basin

With continuous hydrocarbon exploration extending to deeper basins,the deepest industrial oil accumulation was discovered below 8,200 m,revealing a new exploration field.Hence,the extent to which oil exploration can be extended,and the prediction of the depth limit of oil accumulation(DLOA),are issues that have attracted significant attention in petroleum geology.Since it is difficult to characterize the evolution of the physical properties of the marine carbonate reservoir with burial depth,and the deepest drilling still cannot reach the DLOA.Hence,the DLOA cannot be predicted by directly establishing the relationship between the ratio of drilling to the dry layer and the depth.In this study,by establishing the relationships between the porosity and the depth and dry layer ratio of the carbonate reservoir,the relationships between the depth and dry layer ratio were obtained collectively.The depth corresponding to a dry layer ratio of 100%is the DLOA.Based on this,a quantitative prediction model for the DLOA was finally built.The results indicate that the porosity of the carbonate reservoir,Lower Ordovician in Tazhong area of Tarim Basin,tends to decrease with burial depth,and manifests as an overall low porosity reservoir in deep layer.The critical porosity of the DLOA was 1.8%,which is the critical geological condition corresponding to a 100%dry layer ratio encountered in the reservoir.The depth of the DLOA was 9,000 m.This study provides a new method for DLOA prediction that is beneficial for a deeper understanding of oil accumulation,and is of great importance for scientific guidance on deep oil drilling.

Multiple model PHD filter for tracking sharply maneuvering targets using recursive RANSAC based adaptive birth estimation

An algorithm to track multiple sharply maneuvering targets without prior knowledge about new target birth is proposed. These targets are capable of achieving sharp maneuvers within a short period of time, such as drones and agile missiles.The probability hypothesis density (PHD) filter, which propagates only the first-order statistical moment of the full target posterior, has been shown to be a computationally efficient solution to multitarget tracking problems. However, the standard PHD filter operates on the single dynamic model and requires prior information about target birth distribution, which leads to many limitations in terms of practical applications. In this paper,we introduce a nonzero mean, white noise turn rate dynamic model and generalize jump Markov systems to multitarget case to accommodate sharply maneuvering dynamics. Moreover, to adaptively estimate newborn targets’information, a measurement-driven method based on the recursive random sampling consensus (RANSAC) algorithm is proposed. Simulation results demonstrate that the proposed method achieves significant improvement in tracking multiple sharply maneuvering targets with adaptive birth estimation.

A Triple Nexus Water-Energy-Housing (WEH) Framework Modelling towards Improved Decision-Making in Humanitarian Operations

Given the challenges facing most humanitarian operations worldwide, a change of approach is needed to ensure greater sustainability of humanitarian settlements right from the planning stage. Some studies attribute unsustainability to inadequate provision of basic resources and highlight the apparent bottlenecks that prevent access to the meaningful data needed to plan and remedy problems. Most operations have relied on an “ad hoc ism” approach, employing parallel and disconnected data processing methods, resulting in a wide range of data being collected without subsequent prioritization to optimize interconnections that could enhance performance. There have been little efforts to study the trade-offs potentially at stake. This work proposes a new framework enabling all subsystems to operate in a single system and focusing on data processing perspective. To achieve this, this paper proposes a Triple Nexus Framework as an attempt to integrate water, energy, and housing sector data derived from a specific sub-system within the overall system in the application of Model-Based Systems Engineering. Understanding the synergies between water, energy, and housing, Systems Engineering characterizes the triple nexus framework and identifies opportunities for improved decision-making in processing operational data from these sectors. Two scenarios illustrate how an integrated platform could be a gateway to access meaningful operational data in the system and a starting point for modeling integrated human settlement systems. Upon execution, the model is tested for nexus megadata processing, and the optimization simulation yielded 67% satisfactory results, demonstrating that an integrated system could improve sustainability, and that capacity building in service delivery is more than beneficial.

Study of The Technical Index of Online Learning Behavior Analysis of Nursing Majors on The Superstar Platform Based on The Kirkpatrick Evaluation Model

Objective:To analyze the technical indexes of students’online learning behavior analysis based on Kirkman’s evaluation model,sort out the basic indexes of online learning behavior,and extract scientific and efficient evaluation indexes of online learning effect through statistical analysis.Methods:The online learning behavior data of Physiology of nursing students from 2021-2023 and the first semester of 22 nursing classes(3 and 4)were collected and analyzed.The preset learning behavior indexes were analyzed by multi-dimensional analysis and a correlation analysis was conducted between the indexes and the final examination scores to screen for the dominant important indexes for online learning effect evaluation.Results:The study found that the demand for online learning of nursing students from 2021-2023 increased and the effect was statistically significant.Compared with the stage assessment results,the online learning effect was statistically significant.Conclusion:The main indicators for evaluating and classifying online learning behaviors were summarized.These two indicators can help teachers predict which part of students need learning intervention,optimize the teaching process,and help students improve their learning behavior and academic performance.

基于24Model-D-ISM的地铁站火灾疏散影响因素研究

为预防地铁站火灾事故,深入了解地铁站火灾人员疏散影响因素间的内在联系与层次结构,基于第6版“2-4”模型(24Model)分析63起地铁站火灾疏散事故,充分考虑各个因素之间的交互作用,提取19个影响地铁站人员疏散的关键因素,建立地铁站火灾人员疏散影响因素指标体系;采用算子客观赋权法(C-OWA)改进决策试验与评价实验法(DEMATEL),确定地铁站火灾人员疏散的重要影响因素;在此基础上,采用解释结构模型(ISM)分析各个因素间的层次结构及相互作用路径,构建地铁站火灾人员疏散影响因素的多级递阶结构模型。研究结果表明:疏散引导、恐慌从众行为、人员拥挤为地铁站火灾人员疏散的关键影响因素;地铁站火灾人员疏散受表层因素、中间层因素、深层因素共同作用的影响,其中,疏散教育与培训、设施维护与检查、疏散预案等因素是根源影响因素,重视根源影响因素的改善有利于从本质上预防和控制事故的发生。

MicroRNAs in mouse and rat models of experimental epilepsy and potential therapeutic targets

Epilepsy is a common and serious neurological disease that causes recurrent seizures. The brain damage caused by seizures can lead to depression, anxiety, cognitive impairment, or disability. In almost all cases chronic seizures are difficult to cure. MicroRNAs are widely expressed in the central nervous system and play important roles in the pathogenesis of several neurological disorders, including epilepsy. A variety of animals(mostly mice and rats) have been used to induce experimental epilepsy using different protocols and miRNA profiling performed. Most of the recent studies reviewed had performed miRNA profiling in hippocampal tissues and a large number of microRNAs were dysregulated when compared to controls. Most notably, miR-132-3p,-146a-5p,-10a-5p,-21a-3p,-27a-3p,-142a-5p,-212-3p,-431-5p, and-155 were upregulated in both the mouse and rat studies. Overexpression of miR-137 and miR-219 decreased seizure severity in a mouse epileptic model, and suppression of miR-451,-10a-5p,-21a-5p,-27a-5p,-142a-5p,-431-5p,-155, and-134 had a positive influence on seizure behavior. In the rat studies, overexpression of miR-139-5p decreased neuronal damage in drug-resistant rats and inhibition of miR-129-2-3p,-27a-3p,-155,-134,-181a, and-146a had a positive effect on seizure behavior and/or reduced the loss of neuronal cells. Further studies are warranted using adult female and immature male and female animals. It would also be helpful to test the ability of specific agomirs and antagomirs to control seizure activity in a subhuman primate model of epilepsy such as adult marmosets injected intraperitoneally with pilocarpine or cynomolgus monkeys given intrahippocampal injections of kainic acid.

耦合优化蚁群算法与P-Median model的选址模型设计

为节省城建部门对于公共体育设施的投入成本以及提高城市人民生活质量,以运动场所优化选址为例,提出一种新型设施选址模型。该模型主要基于P-Median model(最小化阻抗模型)根据需求点数量从全部候选设施选址中选择设施空间位置,让用户达到离自己最近设施距离成本总和最小的目的,对选址的基本原则和实际情况提出要求,构造目标函数用于优化后蚁群算法求解进行选址工作。优化蚁群算法实现基于Python语言模块,通过改进蚁群原始信息素,提升原有算法的收敛速度,求出目标函数最优解,可以很好地模拟对于运动场所的选址。用二者耦合进行优势互补所设计的选址模型来搜寻研究区蚁群信息素浓度残留最大的栅格像元,从而确定未被已有设施点服务半径覆盖的最佳设施点建立位置。实验结果表明,该新型选址模型相较于最小化阻抗模型与最大化覆盖模型,新增优化设施点使整体服务半径覆盖率分别高出10.42%和6.95%,适合求解较为精确且小规模空间下的选址问题。

Prediction of Sedimentary Microfacies Distribution by Coupling Stochastic Modeling Method in Oil and Gas Energy Resource Exploitation

In view of the problem that a single modeling method cannot predict the distribution of microfacies, a new idea of coupling modeling method to comprehensively predict the distribution of sedimentary microfacies was proposed, breaking the tradition that different sedimentary microfacies used the same modeling method in the past. Because different sedimentary microfacies have different distribution characteristics and geometric shapes, it is more accurate to select different simulation methods for prediction. In this paper, the coupling modeling method was to establish the distribution of sedimentary microfacies with simple geometry through the point indicating process simulation, and then predict the microfacies with complex spatial distribution through the sequential indicator simulation method. Taking the DC block of Bohai basin as an example, a high-precision reservoir sedimentary microfacies model was established by the above coupling modeling method, and the model verification results showed that the sedimentary microfacies model had a high consistency with the underground. The coupling microfacies modeling method had higher accuracy and reliability than the traditional modeling method, which provided a new idea for the prediction of sedimentary microfacies.

Mshpy23:a user-friendly,parameterized model of magnetosheath conditions

Lunar Environment heliospheric X-ray Imager(LEXI)and Solar wind−Magnetosphere−Ionosphere Link Explorer(SMILE)will observe magnetosheath and its boundary motion in soft X-rays for understanding magnetopause reconnection modes under various solar wind conditions after their respective launches in 2024 and 2025.Magnetosheath conditions,namely,plasma density,velocity,and temperature,are key parameters for predicting and analyzing soft X-ray images from the LEXI and SMILE missions.We developed a userfriendly model of magnetosheath that parameterizes number density,velocity,temperature,and magnetic field by utilizing the global Magnetohydrodynamics(MHD)model as well as the pre-existing gas-dynamic and analytic models.Using this parameterized magnetosheath model,scientists can easily reconstruct expected soft X-ray images and utilize them for analysis of observed images of LEXI and SMILE without simulating the complicated global magnetosphere models.First,we created an MHD-based magnetosheath model by running a total of 14 OpenGGCM global MHD simulations under 7 solar wind densities(1,5,10,15,20,25,and 30 cm)and 2 interplanetary magnetic field Bz components(±4 nT),and then parameterizing the results in new magnetosheath conditions.We compared the magnetosheath model result with THEMIS statistical data and it showed good agreement with a weighted Pearson correlation coefficient greater than 0.77,especially for plasma density and plasma velocity.Second,we compiled a suite of magnetosheath models incorporating previous magnetosheath models(gas-dynamic,analytic),and did two case studies to test the performance.The MHD-based model was comparable to or better than the previous models while providing self-consistency among the magnetosheath parameters.Third,we constructed a tool to calculate a soft X-ray image from any given vantage point,which can support the planning and data analysis of the aforementioned LEXI and SMILE missions.A release of the code has been uploaded to a Github repository.

24Model与LCM原因因素定义对比研究

为探究损失致因模型(LCM)原因因素定义与事故致因“2-4”模型(24Model)存在的异同和优缺点,梳理2个模型各层面原因和结果的定义,对比定义内容及其对事故原因分析等安全实务的指导作用,并以一起瓦斯爆炸事故为例加以实证分析,获得二者分析结果之间的差异。研究结果表明:LCM是首个将管理因素纳入事故致因分析的一维事件序列模型,可明确各层面原因因素的定义和因素间的逻辑关系,但部分定义存在交叉重复的问题,并没有揭示安全工作指导思想等深层次事故致因因素;24Model作为系统性事故致因模型,对各类因素的定义均以组织为主体,描述事件、事故、安全的概念内涵,划分个体安全动作、安全能力和组织安全管理体系的类别并给出含义解析,探究组织安全文化层面的问题并以32个元素体现;2个模型的事故原因分析方法均建立在对各层级原因因素定义的基础上,并适用于模型理论体系本身。

Multi-Objective Adaptive Optimization Model Predictive Control:Decreasing Carbon Emissions from a Zinc Oxide Rotary Kiln

The zinc oxide rotary kiln,as an essential piece of equipment in the zinc smelting industrial process,is presenting new challenges in process control.China’s strategy of achieving a carbon peak and carbon neutrality is putting new demands on the industry,including green production and the use of fewer resources;thus,traditional stability control is no longer suitable for multi-objective control tasks.Although researchers have revealed the principle of the rotary kiln and set up computational fluid dynamics(CFD)simulation models to study its dynamics,these models cannot be directly applied to process control due to their high computational complexity.To address these issues,this paper proposes a multi-objective adaptive optimization model predictive control(MAO-MPC)method based on sparse identification.More specifically,with a large amount of data collected from a CFD model,a sparse regression problem is first formulated and solved to obtain a reduction model.Then,a two-layered control framework including real-time optimization(RTO)and model predictive control(MPC)is designed.In the RTO layer,an optimization problem with the goal of achieving optimal operation performance and the lowest possible resource consumption is set up.By solving the optimization problem in real time,a suitable setting value is sent to the MPC layer to ensure that the zinc oxide rotary kiln always functions in an optimal state.Our experiments show the strength and reliability of the proposed method,which reduces the usage of coal while maintaining high profits.

Assessing the Performance of CMIP6 Models in Simulating Droughts across Global Drylands

Both the attribution of historical change and future projections of droughts rely heavily on climate modeling. However,reasonable drought simulations have remained a challenge, and the related performances of the current state-of-the-art Coupled Model Intercomparison Project phase 6(CMIP6) models remain unknown. Here, both the strengths and weaknesses of CMIP6 models in simulating droughts and corresponding hydrothermal conditions in drylands are assessed.While the general patterns of simulated meteorological elements in drylands resemble the observations, the annual precipitation is overestimated by ~33%(with a model spread of 2.3%–77.2%), along with an underestimation of potential evapotranspiration(PET) by ~32%(17.5%–47.2%). The water deficit condition, measured by the difference between precipitation and PET, is 50%(29.1%–71.7%) weaker than observations. The CMIP6 models show weaknesses in capturing the climate mean drought characteristics in drylands, particularly with the occurrence and duration largely underestimated in the hyperarid Afro-Asian areas. Nonetheless, the drought-associated meteorological anomalies, including reduced precipitation, warmer temperatures, higher evaporative demand, and increased water deficit conditions, are reasonably reproduced. The simulated magnitude of precipitation(water deficit) associated with dryland droughts is overestimated by 28%(24%) compared to observations. The observed increasing trends in drought fractional area,occurrence, and corresponding meteorological anomalies during 1980–2014 are reasonably reproduced. Still, the increase in drought characteristics, associated precipitation and water deficit are obviously underestimated after the late 1990s,especially for mild and moderate droughts, indicative of a weaker response of dryland drought changes to global warming in CMIP6 models. Our results suggest that it is imperative to employ bias correction approaches in drought-related studies over drylands by using CMIP6 outputs.

Genetically modified non-human primate models for research on neurodegenerative diseases

Neurodegenerative diseases(NDs)are a group of debilitating neurological disorders that primarily affect elderly populations and include Alzheimer's disease(AD),Parkinson's disease(PD),Huntington's disease(HD),and amyotrophic lateral sclerosis(ALS).Currently,there are no therapies available that can delay,stop,or reverse the pathological progression of NDs in clinical settings.As the population ages,NDs are imposing a huge burden on public health systems and affected families.Animal models are important tools for preclinical investigations to understand disease pathogenesis and test potential treatments.While numerous rodent models of NDs have been developed to enhance our understanding of disease mechanisms,the limited success of translating findings from animal models to clinical practice suggests that there is still a need to bridge this translation gap.Old World nonhuman primates(NHPs),such as rhesus,cynomolgus,and vervet monkeys,are phylogenetically,physiologically,biochemically,and behaviorally most relevant to humans.This is particularly evident in the similarity of the structure and function of their central nervous systems,rendering such species uniquely valuable for neuroscience research.Recently,the development of several genetically modified NHP models of NDs has successfully recapitulated key pathologies and revealed novel mechanisms.This review focuses on the efficacy of NHPs in modeling NDs and the novel pathological insights gained,as well as the challenges associated with the generation of such models and the complexities involved in their subsequent analysis.

The impact of Internet access on household dietary quality:Evidence from rural China

Over the past few decades,the Internet has rapidly diffused across China.The spread of the Internet has had a profound economic and social impact on Chinese rural areas.Existing research shows that Internet access significantly impacts agricultural production and improves smallholder farmers’income.Beyond these,the Internet can affect other dimensions of social welfare.However,research about the impact of Internet access on dietary quality in rural China remains scarce.This study utilizes multi-period panel data from Fixed Observation Point in rural China from 2009 to 2015 to estimate the impact of Internet access on dietary quality and food consumption of rural households and conducts a causal analysis.Regression models with time and household fixed effects allow robust estimation while reducing potential issues of unobserved heterogeneity.The estimates show that Internet access has significantly increased rural household dietary quality(measured by the Chinese Diet Balance Index).Further research finds that Internet access has increased the consumption of animal products,such as aquatic and dairy products.We also examine the underlying mechanisms.Internet access improves dietary quality and food consumption mainly through increasing household income and food expenditure.These results encourage the promotion of Internet access as a valuable tool for nutritional improvements,especially in rural areas.

Large animal models for Huntington's disease research

Huntington'sdisease(HD)isahereditary neurodegenerative disorder for which there is currently no effectivetreatmentavailable.Consequently,the development of appropriate disease models is critical to thoroughly investigate disease progression.The genetic basis of HD involves the abnormal expansion of CAG repeats in the huntingtin(HTT)gene,leading to the expansion of a polyglutamine repeat in the HTT protein.Mutant HTT carrying the expanded polyglutamine repeat undergoes misfolding and forms aggregates in the brain,which precipitate selective neuronal loss in specific brain regions.Animal models play an important role in elucidating the pathogenesis of neurodegenerative disorders such as HD and in identifying potential therapeutic targets.Due to the marked species differences between rodents and larger animals,substantial efforts have been directed toward establishing large animal models for HD research.These models are pivotal for advancing the discovery of novel therapeutic targets,enhancing effective drug delivery methods,and improving treatment outcomes.We have explored the advantages of utilizing large animal models,particularly pigs,in previous reviews.Since then,however,significant progress has been made in developing more sophisticated animal models that faithfully replicate the typical pathology of HD.In the current review,we provide a comprehensive overview of large animal models of HD,incorporating recent findings regarding the establishment of HD knock-in(KI)pigs and their genetic therapy.We also explore the utilization of large animal models in HD research,with a focus on sheep,non-human primates(NHPs),and pigs.Our objective is to provide valuable insights into the application of these large animal models for the investigation and treatment of neurodegenerative disorders.

Direct measurement and theoretical prediction model of interparticle adhesion force between irregular planetary regolith particles

Interparticle adhesion force has a controlling effect on the physical and mechanical properties of planetary regolith and rocks.The current research on the adhesion force of planetary regolith and rock particles has been primarily based on the assumption of smooth spherical particles to calculate the intergranular adhesion force;this approach lacks consideration for the adhesion force between irregular shaped particles.In our study,an innovative approach was established to directly measure the adhesion force between the arbitrary irregular shaped particles;the probe was modified using simulated lunar soil particles that were a typical representation of planetary regolith.The experimental results showed that for irregular shaped mineral particles,the particle size and mineral composition had no significant influence on the interparticle adhesion force;however,the complex morphology of the contact surface predominantly controlled the adhesion force.As the contact surface roughness increased,the adhesion force gradually decreased,and the rate of decrease gradually slowed;these results were consistent with the change trend predicted via the theoretical models of quantum electrodynamics.Moreover,a theoretical model to predict the adhesion force between the irregular shaped particles was constructed based on Rabinovich’s theory,and the prediction results were correlated with the experimental measurements.

Genome-edited rabbits:Unleashing the potential of a promising experimental animal model across diverse diseases

Animal models are extensively used in all aspects of biomedical research,with substantial contributions to our understanding of diseases,the development of pharmaceuticals,and the exploration of gene functions.The field of genome modification in rabbits has progressed slowly.However,recent advancements,particularly in CRISPR/Cas9-related technologies,have catalyzed the successful development of various genome-edited rabbit models to mimic diverse diseases,including cardiovascular disorders,immunodeficiencies,agingrelated ailments,neurological diseases,and ophthalmic pathologies.These models hold great promise in advancing biomedical research due to their closer physiological and biochemical resemblance to humans compared to mice.This review aims to summarize the novel gene-editing approaches currently available for rabbits and present the applications and prospects of such models in biomedicine,underscoring their impact and future potential in translational medicine.

An Artificial Neural Network Model Combined with Dietary Retinol Intake from Different Sources to Predict the Risk of Nonalcoholic Fatty Liver Disease

Objective This study aimed to develop an artificial neural network(ANN) model combined with dietary retinol intake from different sources to predict the risk of non-alcoholic fatty liver disease(NAFLD) in American adults.Methods Data from the 2007 to 2014 National Health and Nutrition Examination Survey(NHANES)2007–2014 were analyzed. Eligible subjects(n = 6,613) were randomly divided into a training set(n1 =4,609) and a validation set(n2 = 2,004) at a ratio of 7:3. The training set was used to identify predictors of NAFLD risk using logistic regression analysis. An ANN was established to predict the NAFLD risk using a training set. Receiver operating characteristic(ROC) curve analysis was performed to evaluate the accuracy of the model using the training and validation sets.Results Our study found that the odds ratios(ORs) and 95% confidence intervals(CIs) of NAFLD for the highest quartile of plant-derived dietary retinol intake(i.e., provitamin A carotenoids, such as β-carotene)(OR = 0.75, 95% CI: 0.57 to 0.99) were inversely associated with NAFLD risk, compared to the lowest quartile of intake, after adjusting for potential confounders. The areas under the ROC curves were 0.874 and 0.883 for the training and validation sets, respectively. NAFLD occurs when its incidence probability is greater than 0.388.Conclusion The ANN model combined with plant-derived dietary retinol intake showed a significant effect on NAFLD. This could be applied to predict NAFLD risk in the American adult population when government departments formulate future health plans.