Review on Hydroxyurea Usage in Young Children with Sickle Cell Disease: Examining Hemoglobin Induction, Potential Benefits, Responses, Safety, and Effectiveness

Sickle cell disease (SCD) is a prevalent condition, particularly in the countries of sub-Saharan Africa, where the presence of specific genes associated with Malaria contributes to its high prevalence. Patients with sickle cell disease frequently experience painful episodes necessitating hospitalization, and their hemoglobin levels are typically lower than those of the general population. There are different treatment options available to manage complications, such as transfusing blood, hydroxyurea, and strong anti-pains. However, with all these treatments, patients still commonly experience pain crises and suffer from organ damage. Hydroxyurea, the sole approved medication for sickle cell anemia in developed and developing countries, is widely used in children despite being primarily indicated for adults. Multiple studies have demonstrated the efficacy of hydroxyurea in inducing HbF production in young children with SCD. Elevated HbF levels have been associated with improved clinical outcomes, including a reduction in vaso-occlusive crises, acute chest syndrome, and the need for blood transfusions. Furthermore, increased HbF levels have been shown to ameliorate disease-related organ damage, such as pulmonary hypertension and sickle cell retinopathy. The response to hydroxyurea treatment in young children with SCD is variable. Some patients achieve substantial increases in HbF levels and experience significant clinical benefits, while others may have a more modest response. Factors influencing the response include baseline HbF levels, genetic modifiers, treatment adherence, and dose optimization. Safety is a crucial consideration when using hydroxyurea in young children. Studies have shown that hydroxyurea is generally well-tolerated, with the most common adverse effects being myelosuppression, gastrointestinal symptoms, and dermatological manifestations. However,long-term effects and potential risks, such as renal dysfunction and reproductive impacts, require further investigation. The effectiveness of hydroxyurea in young children with SCD has been demonstrated in various clinical trials and observational studies. These studies have shown a significant reduction in disease-related complications and improved quality of life. However, optimal dosing, treatment duration, and long-term outcomes are still areas of ongoing research. This review focuses on recent studies investigating the benefits, effectiveness, responses, and safety of hydroxyurea in pediatric individuals diagnosed with sickle cell disease.

Impact of effective stress on permeability for carbonate fractured-vuggy rocks

To gain insight into the flow mechanisms and stress sensitivity for fractured-vuggy reservoirs,several core models with different structural characteristics were designed and fabricated to investigate the impact of effective stress on permeability for carbonate fractured-vuggy rocks(CFVR).It shows that the permeability performance curves under different pore and confining pressures(i.e.altered stress conditions)for the fractured core models and the vuggy core models have similar change patterns.The ranges of permeability variation are significantly wider at high pore pressures,indicating that permeability reduction is the most significant during the early stage of development for fractured-vuggy reservoirs.Since each obtained effective stress coefficient for permeability(ESCP)varies with the changes in confining pressure and pore pressure,the effective stresses for permeability of four representative CFVR show obvious nonlinear characteristics,and the variation ranges of ESCP are all between 0 and 1.Meanwhile,a comprehensive ESCP mathematical model considering triple media,including matrix pores,fractures,and dissolved vugs,was proposed.It is proved theoretically that the ESCP of CFVR generally varies between 0 and 1.Additionally,the regression results showed that the power model ranked highest among the four empirical models mainly applied in stress sensitivity characterization,followed by the logarithmic model,exponential model,and binomial model.The concept of“permeability decline rate”was introduced to better evaluate the stress sensitivity performance for CFVR,in which the one-fracture rock is the strongest,followed by the fracture-vug rock and two-horizontalfracture rock;the through-hole rock is the weakest.In general,this study provides a theoretical basis to guide the design of development and adjustment programs for carbonate fractured-vuggy reservoirs.

Understanding the Relationship Between Shrinking Cities and Land Prices:Spatial Pattern,Effectiveness,and Policy Implications

Urban shrinkage has emerged as a widespread phenomenon globally and has a significant impact on land,particularly in terms of land use and price.This study focuses on 2851 county-level cities in China in 2005–2018(excluding Hong Kong,Macao,Taiwan,and‘no data’areas in Qinhai-Tibet Plateau)as the fundamental units of analysis.By employing nighttime light(NTL)data to identify shrinking cities,the propensity score matching(PSM)model was used to quantitatively examine the impact of shrinking cities on land prices,and evaluate the magnitude of this influence.The findings demonstrate the following:1)there were 613 shrinking cities in China,with moderate shrinkage being the most prevalent and severe shrinkage being the least.2)Regional disparities are evident in the spatial distribution of shrinking cities,especially in areas with diverse terrain.3)The spatial pattern of land price exhibits a significant correlated to the economic and administrative levels.4)Shrinking cities significantly negatively impact on the overall land price(ATT=–0.1241,P<0.05).However,the extent of the effect varies significantly among different spatial regions.This study contributes novel insights into the investigation of land prices and shrinking cities,ultimately serving as a foundation for government efforts to promote the sustainable development of urban areas.

Thermal conductivity of hydrate and effective thermal conductivity of hydrate-bearing sediment

The research on the thermal property of the hydrate has recently made great progress,including the understanding of hydrate thermal conductivity and effective thermal conductivity(ETC)of hydratebearing sediment.The thermal conductivity of hydrate is of great significance for the hydrate-related field,such as the natural gas hydrate exploitation and prevention of the hydrate plugging in oil or gas pipelines.In order to obtain a comprehensive understanding of the research progress of the hydrate thermal conductivity and the ETC of hydrate-bearing sediment,the literature on the studies of the thermal conductivity of hydrate and the ETC of hydrate-bearing sediment were summarized and reviewed in this study.Firstly,experimental studies of the reported measured values and the temperature dependence of the thermal conductivity of hydrate were discussed and reviewed.Secondly,the studies of the experimental measurements of the ETC of hydrate-bearing sediment and the effects of temperature,porosity,hydrate saturation,water saturation,thermal conductivity of porous medium,phase change,and other factors on the ETC of hydrate-bearing sediment were discussed and reviewed.Thirdly,the research progress of modeling on the ETC of the hydrate-bearing sediment was reviewed.The thermal conductivity determines the heat transfer capacity of the hydrate reservoir and directly affects the hydrate exploitation efficiency.Future efforts need to be devoted to obtain experimental data of the ETC of hydrate reservoirs and establish models to accurately predict the ETC of hydrate-bearing sediment.

Effects of Initial Defects on Effective Elastic Modulus of Concrete with Mesostructure

An exquisite mesostructure model was presented to predict the effective elastic modulus of concrete,in which concrete is realized as a four-phase composite material consisting of coarse aggregates,mortar matrix,interfacial transition zone(ITZ),and initial defects.With the three-dimensional(3D)finite element(FE)simulation,the highly heterogeneous composite elastic behavior of concrete was modeled,and the predicted results were compared with theoretical estimations for validation.Monte Carlo(MC)simulations were performed with the proposed mesostructure model to investigate the various factors of initial defects influencing the elastic modulus of concrete,such as the shape and concentration(pore volume fraction or crack density)of microspores and microcracks.It is found that the effective elastic modulus of concrete decreases with the increase of initial defects concentration,while the distribution and shape characteristics also exert certain influences due to the stress concentration caused by irregular inclusion shape.

Analytical solution for the effective elastic properties of rocks with the tilted penny-shaped cracks in the transversely isotropic background

Seismic prediction of cracks is of great significance in many disciplines,for which the rock physics model is indispensable.However,up to now,multitudinous analytical models focus primarily on the cracked rock with the isotropic background,while the explicit model for the cracked rock with the anisotropic background is rarely investigated in spite of such case being often encountered in the earth.Hence,we first studied dependences of the crack opening displacement tensors on the crack dip angle in the coordinate systems formed by symmetry planes of the crack and the background anisotropy,respectively,by forty groups of numerical experiments.Based on the conclusion from the experiments,the analytical solution was derived for the effective elastic properties of the rock with the inclined penny-shaped cracks in the transversely isotropic background.Further,we comprehensively analyzed,according to the developed model,effects of the crack dip angle,background anisotropy,filling fluid and crack density on the effective elastic properties of the cracked rock.The analysis results indicate that the dip angle and background anisotropy can significantly either enhance or weaken the anisotropy degrees of the P-and SH-wave velocities,whereas they have relatively small effects on the SV-wave velocity anisotropy.Moreover,the filling fluid can increase the stiffness coefficients related to the compressional modulus by reducing crack compliance parameters,while its effects on shear coefficients depend on the crack dip angle.The increasing crack density reduces velocities of the dry rock,and decreasing rates of the velocities are affected by the crack dip angle.By comparing with exact numerical results and experimental data,it was demonstrated that the proposed model can achieve high-precision estimations of stiffness coefficients.Moreover,the assumption of the weakly anisotropic background results in the consistency between the proposed model and Hudson's published theory for the orthorhombic rock.

Models to Simulate Effective Coverage of Fire Station Based on Real-Time Travel Times

In recent years,frequent fire disasters have led to enormous damage in China.Effective firefighting rescues can minimize the losses caused by fires.During the rescue processes,the travel time of fire trucks can be severely affected by traffic conditions,changing the effective coverage of fire stations.However,it is still challenging to determine the effective coverage of fire stations considering dynamic traffic conditions.This paper addresses this issue by combining the traveling time calculationmodelwith the effective coverage simulationmodel.In addition,it proposes a new index of total effective coverage area(TECA)based on the time-weighted average of the effective coverage area(ECA)to evaluate the urban fire services.It also selects China as the case study to validate the feasibility of the models,a fire station(FS-JX)in Changsha.FS-JX station and its surrounding 9,117 fire risk points are selected as the fire service supply and demand points,respectively.A total of 196 simulation scenarios throughout a consecutiveweek are analyzed.Eventually,1,933,815 sets of valid sample data are obtained.The results showed that the TECA of FS-JX is 3.27 km^(2),which is far below the standard requirement of 7.00 km^(2) due to the traffic conditions.The visualization results showed that three rivers around FS-JX interrupt the continuity of its effective coverage.The proposed method can provide data support to optimize the locations of fire stations by accurately and dynamically determining the effective coverage of fire stations.

Source localization in signed networks with effective distance

While progress has been made in information source localization,it has overlooked the prevalent friend and adversarial relationships in social networks.This paper addresses this gap by focusing on source localization in signed network models.Leveraging the topological characteristics of signed networks and transforming the propagation probability into effective distance,we propose an optimization method for observer selection.Additionally,by using the reverse propagation algorithm we present a method for information source localization in signed networks.Extensive experimental results demonstrate that a higher proportion of positive edges within signed networks contributes to more favorable source localization,and the higher the ratio of propagation rates between positive and negative edges,the more accurate the source localization becomes.Interestingly,this aligns with our observation that,in reality,the number of friends tends to be greater than the number of adversaries,and the likelihood of information propagation among friends is often higher than among adversaries.In addition,the source located at the periphery of the network is not easy to identify.Furthermore,our proposed observer selection method based on effective distance achieves higher operational efficiency and exhibits higher accuracy in information source localization,compared with three strategies for observer selection based on the classical full-order neighbor coverage.

Leading directions and effective distance of larch offspring dispersal at the upper treeline in the Northern and Polar Urals, Russia

Climate has changed sufficiently over the last 150 years and forced out upper treeline advance at the most studied sites around the world.The rate of advance has been extremely variable–from tens to hundreds meters in altitude.This is because the degree at which tree frontal populations respond to climate change depends on the complex interaction of biological and physical factors.The resulting stand pattern is the consequence of the interaction between dispersal and survival functions.A few publications have addressed the question of how this pattern is generated.In order to understand how the spatial structure of tree stands was formed at the upper limit of their distribution in the Ural Mountains,we assessed the distance and direction of dispersal of offspring from maternal individuals.We found that in frontal Larix sibirica Ledeb.populations,‘effective’dispersal of offspring ranges from 3 to 758 m(with a median of 20–33 m in open forest and 219 m in single-tree tundra in the Polar Urals and 107 m in open forest in the Northern Urals).We revealed that most of the offspring effectively dispersed not only in the direction of the prevailing winds,but also in the opposite direction up the slope,and the distance can reach 500–760 m.The data obtained can be used to develop an individual-based model which is capable of simulating in detail the dynamics of tree stands at the upper limit of their growth and reliably predicting the future position and pattern of treeline ecotone as growth conditions continue to improve in the face of observed climate change.

Effective Capacity of URLLC over Parallel Fading Channels with Imperfect Channel State Information

This paper investigates the effective capacity of a point-to-point ultra-reliable low latency communication(URLLC)transmission over multiple parallel sub-channels at finite blocklength(FBL)with imperfect channel state information(CSI).Based on reasonable assumptions and approximations,we derive the effective capacity as a function of the pilot length,decoding error probability,transmit power and the sub-channel number.Then we reveal significant impact of the above parameters on the effective capacity.A closed-form lower bound of the effective capacity is derived and an alternating optimization based algorithm is proposed to find the optimal pilot length and decoding error probability.Simulation results validate our theoretical analysis and show that the closedform lower bound is very tight.In addition,through the simulations of the optimized effective capacity,insights for pilot length and decoding error probability optimization are provided to evaluate the optimal parameters in realistic systems.

Prediction and quantification of effective gas source rocks in a lacustrine basin:Western Depression in the Liaohe Subbasin,China

Due to limited data on the geochemical properties of natural gas,estimations are needed for the effective gas source rock in evaluating gas potential.However,the pronounced heterogeneity of mudstones in lacustrine successions complicates the prediction of the presence and geochemical characteristics of gas source rocks.In this paper,the Liaohe Subbasin of Northeast China is used as an example to construct a practical methodology for locating effective gas source rocks in typical lacustrine basins.Three types of gas source rocks,microbial,oil-type,and coal-type,were distinguished according to the different genetic types of their natural gas.A practical three-dimensional geological model was developed,refined,and applied to determine the spatial distribution of the mudstones in the Western Depression of the Liaohe Subbasin and to describe the geochemical characteristics(the abundance,type,and maturation levels of the organic matter).Application of the model in the subbasin indicates that the sedimentary facies have led to heterogeneity in the mudstones,particularly with respect to organic matter types.The effective gas source rock model constructed for the Western Depression shows that the upper sequence(SQ2)of the Fourth member(Mbr 4)of the Eocene Shahejie Formation(Fm)and the lower and middle sequences(SQ3 and SQ4)of the Third member(Mbr 3)form the principal gas-generating interval.The total volume of effective gas source rocks is estimated to be 586 km^(3).The effective microbial,oil-type,and coal-type gas source rocks are primarily found in the shallow western slope,the central sags,and the eastern slope of the Western Depression,respectively.This study provides a practical approach for more accurately identifying the occurrence and geochemical characteristics of effective natural gas source rocks,enabling a precise quantitative estimation of natural gas reserves.

Effective dynamics for a spin-1/2 particle constrained to a curved layer with inhomogeneous thickness

We derive an effective Hamiltonian for a spin-1/2 particle confined within a curved thin layer with non-uniform thickness using the confining potential approach.Our analysis reveals the presence of a pseudo-magnetic field and effective spin–orbit interaction(SOI)arising from the curvature,as well as an effective scalar potential resulting from variations in thickness.Importantly,we demonstrate that the physical effect of additional SOI from thickness fluctuations vanishes in low-dimensional systems,thus guaranteeing the robustness of spin interference measurements to thickness imperfection.Furthermore,we establish the applicability of the effective Hamiltonian in both symmetric and asymmetric confinement scenarios,which is crucial for its utilization in one-side etching systems.

A novel Effective Panicle Number per Plant 4 haplotype enhances grain yield by coordinating panicle number and grain number in rice

Increasing effective panicle number per plant(EPN)is one approach to increase yield potential in rice.However,molecular mechanisms underlying EPN remain unclear.In this study,we integrated mapbased cloning and genome-wide association analysis to identify the EPN4 gene,which is allelic to NARROW LEAF1(NAL1).Overexpression lines containing the Teqing allele(TQ)of EPN4 had significantly increased EPN.NIL-EPN4^(TQ) in japonica(geng)cultivar Lemont(LT)exhibited significantly improved EPN but decreased grain number and flag leaf size relative to LT.Haplotype analysis indicated that accessions with EPN4-1 had medium EPN,medium grain number,and medium grain weight,but had the highest grain yield among seven haplotypes,indicating that EPN4-1 is an elite haplotype of EPN4 for positive coordination of the three components of grain yield.Furthermore,accessions carrying the combination of EPN4-1 and haplotype GNP1-6 of GNP1 for grain number per panicle showed higher grain yield than those with other allele combinations.Therefore,pyramiding of EPN4-1 and GNP1-6 could be a preferred approach to obtain high yield potential in breeding.

Theoretical study on the effective thermal conductivity of silica aerogels based on a cross-aligned and cubic pore model

Aerogel nanoporous materials possess high porosity, high specific surface area, and extremely low density due to their unique nanoscale network structure. Moreover, their effective thermal conductivity is very low, making them a new type of lightweight and highly efficient nanoscale super-insulating material. However, prediction of their effective thermal conductivity is challenging due to their uneven pore size distribution. To investigate the internal heat transfer mechanism of aerogel nanoporous materials, this study constructed a cross-aligned and cubic pore model(CACPM) based on the actual pore arrangement of SiO_(2) aerogel. Based on the established CACPM, the effective thermal conductivity expression for the aerogel was derived by simultaneously considering gas-phase heat conduction, solid-phase heat conduction, and radiative heat transfer. The derived expression was then compared with available experimental data and the Wei structure model. The results indicate that, according to the model established in this study for the derived thermal conductivity formula of silica aerogel, for powdery silica aerogel under the conditions of T = 298 K, a_(2)= 0.85, D_(1)= 90 μm, ρ = 128 kg/m^(3), within the pressure range of 0–10^(5)Pa, the average deviation between the calculated values and experimental values is 10.51%. In the pressure range of 10^(3)–10^(4)Pa, the deviation between calculated values and experimental values is within 4%. Under these conditions, the model has certain reference value in engineering verification. This study also makes a certain contribution to the research of aerogel thermal conductivity heat transfer models and calculation formulae.

Electronic structure and effective mass of pristine and Cl-doped CsPbBr_(3)

Organic–inorganic lead halide perovskites(LHPs) have attracted great interest owing to their outstanding optoelectronic properties.Typically,the underlying electronic structure would determinate the physical properties of materials.But as for now,limited studies have been done to reveal the underlying electronic structure of this material system,comparing to the huge amount of investigations on the material synthesis.The effective mass of the valance band is one of the most important physical parameters which plays a dominant role in charge transport and photovoltaic phenomena.In pristine CsPbBr_(3),the Fr?hlich polarons associated with the Pb–Br stretching modes are proposed to be responsible for the effective mass renormalization.In this regard,it would be very interesting to explore the electronic structure in doped LHPs.Here,we report high-resolution angle-resolved photoemission spectroscopy(ARPES) studies on both pristine and Cl-doped CsPbBr_(3).The experimental band dispersions are extracted from ARPES spectra along both ■ and ■ high symmetry directions.DFT calculations are performed and directly compared with the ARPES data.Our results have revealed the band structure of Cl-doped CsPbBr_(3) for the first time,which have also unveiled the effective mass renormalization in the Cl-doped CsPbBr_(3) compound.Doping dependent measurements indicate that the chlorine doping could moderately tune the renormalization strength.These results will help understand the physical properties of LHPs as a function of doping.

Seismic effectiveness evaluation and optimized design of tie up method for securing museum collections

To quantify the seismic effectiveness of the most commonly used fishing line tie up method for securing museum collections and optimize fixed strategies for exhibitions,shaking table tests of the seismic systems used for typical museum collection replicas have been carried out.The influence of body shape and fixed measure parameters on the seismic responses of replicas and the interaction behavior between replicas and fixed measures have been explored.Based on the results,seismic effectiveness evaluation indexes of the tie up method are proposed.Reasonable suggestions for fixed strategies are given,which provide a basis for the exhibition of delicate museum collections considering the principle of minimizing seismic responses and intervention.The analysis results show that a larger ratio of height of mass center to bottom diameter led to more intense rocking responses.Increasing the initial pretension of fishing lines was conducive to reducing the seismic responses and stress variation of the lines.Through comprehensive consideration of the interaction forces and effective securement,it is recommended to apply 20%of breaking stress as the initial pretension.For specific museum collections that cannot be effectively protected by the independent tie up method,an optimized strategy of a combination of fishing lines and fasteners is recommended.

A cloud model target damage effectiveness assessment algorithm based on spatio-temporal sequence finite multilayer fragments dispersion

To solve the problem of target damage assessment when fragments attack target under uncertain projectile and target intersection in an air defense intercept,this paper proposes a method for calculating target damage probability leveraging spatio-temporal finite multilayer fragments distribution and the target damage assessment algorithm based on cloud model theory.Drawing on the spatial dispersion characteristics of fragments of projectile proximity explosion,we divide into a finite number of fragments distribution planes based on the time series in space,set up a fragment layer dispersion model grounded in the time series and intersection criterion for determining the effective penetration of each layer of fragments into the target.Building on the precondition that the multilayer fragments of the time series effectively assail the target,we also establish the damage criterion of the perforation and penetration damage and deduce the damage probability calculation model.Taking the damage probability of the fragment layer in the spatio-temporal sequence to the target as the input state variable,we introduce cloud model theory to research the target damage assessment method.Combining the equivalent simulation experiment,the scientific and rational nature of the proposed method were validated through quantitative calculations and comparative analysis.

Simple and effective method for treating severe adult skeletal class II malocclusion: A case report

BACKGROUND Severe skeletal class II malocclusion is the indication for combined orthodontic and orthognathic treatment.CASE SUMMARY A woman with a chief complaint of a protruding chin and an inability to close her lips requested orthodontic camouflage.The treatment plan consisted of extracting the right upper third molar,right lower third molar,left lower second molar,and left upper third molar and moving the maxillary dentition distally using a convenient method involving microimplant nail anchors,push springs,long arm traction hooks,and elastic traction chains.After 52 months of treatment,her overbite and overjet were normal,and her facial profile was favorable.CONCLUSION This method can be used for distal movement of the maxillary dentition and to correct severe skeletal class II malocclusion in adults.

Research on the path of effective management of participation in joint-venture railway companies by China railway group

Purpose-Following the regional restructuring,the number of joint-venture railway companies in which the Group participates has significantly increased.This paper aims to explore the challenges faced by China Railway Group in managing participation in joint-venture railway companies.The study seeks to propose specific approaches to ensure the effective management of these companies,thereby maximizing the benefits of the regional restructuring and supporting the development of a strong transportation country and a modern infrastructure system.Design/methodology/approach-Based on the change in the shareholding relationship between China Railway Group and the joint-venture railway companies,and considering the current situation of the regional restructuring of these companies,as well as the insights from existing literature and typical case studies,this paper proposes some specific paths for effective management of joint-stock railway companies which China Railway Group participated in.Findings-The problems in participation management are the unclear dual leadership role of the party committee,the lack of discourse power,the lack of synergy between shareholders,the increasing risk of sustainable operation of the loss-making companies and the role of dispatched personnel is not fully played.Based on the theories,combined with the existing research and practical cases,the paper proposed specific approaches,such as perfecting top-level system design,maintaining the discourse power,carrying out differentiated management,arranging personnel rationally,arranging shareholders synergy,and innovating methods to provide references for China Railway Group’s subsequent management of joint venture railway companies.Originality/value-This paper contributes to the existing literature by providing a comprehensive analysis of the challenges faced by China Railway Group in managing participation in joint-venture railway companies following the regional restructuring.The study offers novel insights and practical recommendations for addressing these challenges.The findings can serve as valuable references for China Railway Group’s subsequent management of joint-venture railway companies which participated in,as well as for other stateowned enterprises facing similar challenges in managing their joint ventures.

Dermal thickness,rather than drug concentration and injection speed,influences the effective area of botulinum toxin type A in the dermis

Background:Recently,microbotulinum,a new technique that involves injecting botulinum toxin type A(BoNTA)microdroplets into superficial cutaneous tissue,has gained popularity.The precise distribution of BoNTA in the targeted area profoundly affects outcomes.Many factors may influence the effective area of BoNTA in the dermis.This study aimed to determine the dermal distribution properties of BoNTA to guide microbotulinum injection.Methods:Ten healthy males aged 18–65 years without BoNTA treatment in the previous year were recruited to receive intradermal injections in the chest and back.Ultrasound was used to ensure the intradermal delivery of injections and measure the dermal thickness.The minor iodine starch test was performed at baseline and 3 days,7 days,21 days,1 month,and 2 months after treatment.Results:All participants received intradermal injections.The dermis was thinner on the chest(thickness,0.20±0.03 cm)than on the back(thickness,0.39±0.07 cm)(P<0.05).An injection in the thicker dermis had a significantly smaller effective area at every follow-up visit.The drug concentration did not affect the effective area except at 3 days after treatment.Injection speed did not influence the effective area at any follow-up visits.Conclusion:An injection in a thicker dermis leads to a smaller effective area for intradermal injections.When the BoNTA dose is the same,the drug concentration and injection speed do not matter.