There has been a rising interest in compliant legged locomotion to improve the adaptability and energy efficiency of robots. However, few approaches can be generalized to soft ground due to the lack of consideration of the ground surface. When a robot locomotes on soft ground, the elastic robot legs and compressible ground surface are connected in series. The combined compliance of the leg and surface determines the natural dynamics of the whole system and affects the stability and efficiency of the robot. This paper proposes a bio-inspired leg compliance planning and implementation method with consideration of the ground surface. The ground stiffness is estimated based on analysis of ground reaction forces in the frequency domain, and the leg compliance is actively regulated during locomotion, adapting them to achieve harmonic oscillation. The leg compliance is planned on the condition of resonant movement which agrees with natural dynamics and facilitates rhythmicity and efficiency. The proposed method has been implemented on a hydraulic quadruped robot. The simulations and experimental results verified the effectiveness of our method. Legged robots have superior mobility and maneuverability in complex unstructured environments, benefitting from the ability afforded by their morphology and varied gaits . Recent An essential property of animal locomotion is the alternative foot-ground contact in the swing and support phases of a locomotor cycle based on their inherent dynamics, roughly defining the locomotion’s rhythmicity ,17. ElasAn emerging amount of research in biomechanics and kinesiology has revealed that elastic structures, including tendons, ligaments, muscles, and foot pads , play anTo approach the performance and efficiency of the biological archetype, researchers have expended plenty of endeavors in realizing legged locomotion in theory and engineering practice and made numerous profound achievements ,31. RaibTo achieve tunable compliance of the robot leg, it is crucial to employ physical or virtual elasticity in drive units. Physical elasticity means that the drive unit consists of some physical elastic components, and may be actively controlled to adjust the stiffness. Virtual elasticity means that the elasticity is achieved by an active compliance control algorithm. One approach to the implementation of physical elasticity is to add elastic components to the leg ,46,47, aThis paper proposes a systematic compliance planning and implementation method for a quadrupedal robot on various terrains. The stiffness of the ground surface is estimated during locomotion based on the analysis of ground reaction forces in the frequency domain. The compliance of the robot leg is actively controlled to offer virtual elasticity and is regulated as changes of locomotion parameters and the environment to achieve harmonic oscillation of the elastic leg-ground system in the stance phase.In developing the bio-inspired compliance planning and implementation method, we mainly offer two contributions: (a) A novel surface stiffness estimation method is proposed for legged robots. Through analysis of ground reaction forces in the frequency domain, the estimation can be completed within one step period. (b) The principle of harmonic locomotion is exploited for the leg compliance planning to improve rhythmicity and efficiency. The leg compliance is actively regulated on the condition of resonant movement which agrees with the natural dynamics of the leg-ground system.The paper is organized into six sections: As stated before, legged animals exploit elastic properties and adjust leg compliance to maintain longitudinal harmonic oscillation. Inspired by biological research, this paper takes harmonic locomotion as a basic principle for the motion planning and control of a quadruped robot. The leg compliance is planned on the condition of resonance to exploit the natural dynamics of elastic leg and to match the desired motion in terms of locomotion rhythmicity on various ground surfaces.The dynamics of legged locomotion can be revealed by the SLIP model, and various locomotion gaits of quadruped robots such as trotting, pacing, and bounding are expressed as elastic oscillations of the sample mass-spring bouncing system in SLIP, as illustrated in However, the natural dynamics of robots are actively controlled and the motion is arbitrarily generated, respectively; thus, the harmonic motion can hardly be achieved directly. In pursuit of efficient harmonic motion, the dynamics determined by the actively controlled joints should agree with the rhythmicity of motion, and foot reaction forces should match the oscillation of the CoM during each stance phase.k is the stiffness of the spring, m is the center mass, and f is the natural bouncing frequency. The natural dynamics described by k and m determine the passive harmonic motion parameterized by f.For a simple spring-mass bouncing system, the natural dynamics are governed byFor quadruped robots locomoting on various ground surfaces, the compressible ground surface and compliant leg are connected in series to form an elastic combination, and the combined effective stiffness regulates the legged motion on ground surfaces. To achieve harmonic locomotion for the quadruped robot, the estimation of the surface compliance under the current robot statuses and the prediction of the leg compliance for the next step based on the estimation are the main issues for the compliance planning.M1 and M2 represent the mass of the foot and body mass of the robot and, In the practical quadruped robot, the contact force can be directly and precisely measured while the deformation value estimated from the robot state is usually not reliable. Thus, the surface stiffness estimation should mainly be based on the foot reaction forces. The robotground contact model is shown in x1 and the height of the robot mass x2 as the generalized coordinates, the Lagrangian Equation for the system is given byT, V, D and Q denote the kinetic energy, potential energy, dissipated energy, and general forces of the system, respectively, and the details are given asThe simplified robot–ground model possesses two degrees of freedom. Selecting the height of the foot Assuming that the damping of the spring leg and ground surface is negligible, the dynamics Equation (2) can be converted intoTo solve the Equation (4), the variable transformationConsidering the analytical solutions of the ordinary differential Equation system (6) have the same frequency and different amplitudes, then the solutions can be assumed to beThe solutions for Equation (8) generally have the following formEquation (9) can be substituted into (6) to generateTo ensure the existence of the solution, the determinant of Equation (10) should be zero, that isEquation (11) can be converted into an algebraic equationThe analytical solutions of Equation (12) can be derived asThus, the two modes of vibration for the robot-ground system are fully developed and can be expressed by Equations (5) and (13). On the assumption of the negligible damping of the ground surface, the foot reaction force is directly proportional to the displacement. Therefore, the vibration mode of the foot reaction force and that of the displacement, and the current spring leg stiffness and surface stiffness can be calculated by solving the vibration mode of the foot reaction force with Equation (13).T consists of the aerial phase period Ta and stance phase period Ts; that isAccording to the SLIP model of legged locomotion, the whole gait cycle period The stance phase period can also be expressed as c is used to relate the stance phase period Ts and harmonic vibration period Th, and we can thus obtainThe longitudinal oscillations of the stance leg during the stance phase approximately operate as a part of the simple harmonic vibration. The coefficient fs and gait step frequency fstep can be expressed asThe relation between vibration frequency K of the combined robot–ground system determines the resonant frequency fs:The synthetical stiffness K can be calculated from Equations (16) and (17):The preferred synthetical stiffness K and surface stiffness K1, leg stiffness K2 is governed byThrough the relationship between the synthetical stiffness The preferred leg stiffness can be derived from Equations (18) and (19) and can be expressed bylegK based on the gait characteristics of legged locomotion.Equation (20) can be used to estimate the preferred leg stiffness The implementation of the active compliance control and planning for the quadruped robot is depicted in This section presents our implementation of the bio-inspired compliance planning for a hydraulically actuated quadruped robot. In contrast to electric motors, the main superiority of hydraulic actuation is its high power density, which is critical for heavy-duty legged robots. On the other hand, the control of hydraulic actuation is more challenging because of the wide variety of nonlinearities in the system. This section presents the detailed implementation of the compliance planning methods for the hydraulically actuated quadruped robot based on the framework in ® based controller.The hydraulic actuator of the quadruped robot under consideration is depicted in The pressure dynamics of the cylinder considering the compressibility of the oil can be modeled asThe considered servo valve is developed for high dynamic response applications. The dynamics of the servo valve are neglected; thus the control input The net fluid force can be described byThe time derivative of Equation (24) is given bySubstituting Equations (21) and (22) into (26) yieldsz is presented in Equation (28). We see that Equation (27) maps the control voltage to the fluid force. Through the inverse of Equation (27), the hydraulic force controller can be obtained asThe exponential force stabilization is guaranteed byEquation (31) indicates that Active compliance control plays an important role in the period of contact of the actuator and the load. It indicates the synchronous control of force and position during the contact by tuning the stiffness, damping and inertia, and can be described asReferring to Equation (32), position and velocity tracking errors are used to compute the desired force. The measured acceleration is usually unreliable since it is calculated through the second-order difference of the position signals. The desired acceleration is used to replace the acceleration feedback. Thus, the ideal desired force is derived asIn practice, the friction force of the hydraulic cylinder also affects the character of the contact. In hydraulic systems, notable friction force exists in hydraulic cylinders for leak tightness requirements. A dynamic friction force identification method is used based on our previous work . For furEquations (29) and (34) reveal the main framework of the active compliance controller for the hydraulic quadruped robot. The velocity gain It should be noted that the active compliance parameters in the Equation (34) are expressed in the actuation space. Based on the virtual work principle, the relation between the stiffness in each actuation and joint space can be derived asAs is known, the Jacobian relates the joint torques and the forces applied on the foot byFrom the definition of stiffness, we differentiate Equation (38) and we haveThe systematic method of compliance planning and implementation proposed in this paper consists of two major steps: the compliance planning and the compliance implementation. For the compliance implementation, the position and force tracking experiments were conducted to verify the inner force controller and the outer position controller of the active compliance controller, as illustrated in In the control framework of this paper, the inner-loop torque control is the basis of the compliance control algorithm, while, ideally, the compliance control will not reduce the position tracking performance. To verify the force and position tracking performance of the compliance controller, the experiment was conducted on the left front leg of the quadruped robot hanging in the air. The robot was controlled to perform a 50 mm range of squatting motion when a 25 kg load was mounted on the foot. The pressure sensors on the hydraulic cylinder allow for the calculation of the measured force of the hydraulic cylinder. The encoder on the joint allows for the indirect measurement of the joint position, which is represented by the cylinder length.We expect the robot leg to behave as an actual spring under the active compliance controller to cope with the impact disturbances exerted on the robot feet. We designed the corresponding experiment on our quadruped robot. The impact disturbance force was exerted to the foot when the robot was lifted in the air and the position response was measured. Without loss of generality, the actuation stiffness of 500 N/mm was set for the hydraulic cylinder. The impact disturbance force was also sensed by the three-axis force sensor. We took the compression of an ideal virtual spring with the same stiffness as the desired position response and measured the actual position response of the hydraulic cylinder. The comparison is shown in The experimental setup of a single robot leg is built for the study of robot–ground contact behaviors. The internal components, including the spring of the robot leg, substrate surface, sliding rail and sensors are illustrated in The proposed surface compliance estimation method was verified on the experimental setup of a single robot leg. The leg was released after being lifted to a certain height to excite the contact of the robot foot and ground surface. The contact force and surface deformation were measured as shown in As can be seen from ® and Simscape®. The mass and geometric dimensions were set according to the robot experimental setup. The robot walked with different step frequencies and leg stiffness using a trotting gait at a speed of 2 m/s. The energy consumption of the robot locomotion was normalized by the displacement on the ground surface. The preferred leg stiffness to obtain minimum energy consumption at a given gait frequency was investigated and compared with the calculated leg stiffness using the Equation (20). The simulation result in To observe the influence of leg stiffness on legged locomotion performance, a quadrupedal robot simulation model was constructed based on MatlabCompliant legged locomotion has recently become an emerging area of interest in the field of robotics. Few studies, however, have been carried out on the planning and implementation of leg compliance with the consideration of ground stiffness. As mentioned in the introduction section, the main challenge is the lack of rapid and affordable ground compliance estimation methods and of reasonable principles for leg compliance planning. In this paper, a systematic compliance planning and implementation method for the quadrupedal robot is proposed to plan and control the leg compliance continuously with the consideration of the ground through surface stiffness estimation. In this way, the compliant robot leg behaves naturally following bio-inspired principles, and the performance is improved in terms of locomotion efficiency and rhythmicity. The effectiveness of the proposed control method has been shown through simulations and experimental results on a hydraulic quadruped robot. The proposed method can also be extended to other legged robots actuated by hydraulic systems or motors where both the torque and compliance are controllable.Future work will include the development of the proposed control architecture for a practical hydraulic quadruped robot, walking and running in a more challenging ground environment.


This contribution has two key objectives. First, inspired by earlier studies in comparative welfare state and in  gerontology, we develop a conceptualization of autonomy that is rooted in its social dimensions. This concept is then deployed to assess its policy considerations within the field of home care, both with regards to access and generosity in 21 industrialized countries. Second, this contribution performs a comparative assessment of the key factors resulting in a prioritization of the social dimensions of home care and social services in long term care. This study involves an-depth analysis of policy instruments deployed by public authorities to enhance the  autonomy of older adults, complemented with interviews with policy makers in diverse home care policy settings . As such, this study features an evaluation of the presence of social elements in the definition and supply of care needs across 21 countries. It leads to the construct of a social dimensions of autonomy index based upon these instruments and the budgetary prioritization of home care within long term care policies. Among core findings, one discovers broader access and more generous funding when home care responsibilities are firmly embedded at the local level.


The Mental Heath Commission (MHC) is an independent body in Ireland, set up in 2002, to promote, encourage and foster high standards and good practices in the delivery of mental health services and to protect the interests of patients who are involuntarily admitted. Guidelines on the rules governing the use of seclusion are published by the MHC. These guidelines must be followed and recorded in the patient's clinical file during each seclusion episode. A Seclusion Integrated Care Pathway (ICP) was devised in 2012 for use in the Approved Centre in Tallaght University Hospital. This ICP was developed in conjunction with the MHC guidelines to assist in the recording and monitoring of each seclusion episode. Since its introduction in 2012, this ICP has become an established tool used in the Approved Centre in Tallaght University Hospital.The aim of this audit was to assess adherence to MHC guidelines on the use of seclusion in the Approved Centre in Tallaght University Hospital 8 years after the introduction of an ICP and compare it to adherence prior to its introduction and immediately after its introduction.Thirteen rules governing the use of seclusion have been published by the MHC. These include the responsibility of registered medical practitioners (RMP), nursing staff and the levels of observations and frequency of reviews that must take place during each seclusion episode. Using the seclusion register we identified a total of 50 seclusion episodes between August 2019 and July 2020. A retrospective chart review was conducted to assess documentation of each seclusion episode.There was an overall improvement in adherence with MHC guidelines compared to adherence prior to the introduction of the ICP and immediately after its introduction. Areas of improvement included medical reviews, nursing reviews, informing patient of reasons for, likely duration of and circumstances that could end seclusion, and informing next of kin. The range of compliance levels across the thirteen MHC guidelines improved from 3–100% to 69–100%. Post intervention there was 100% compliance with five of the thirteen guidelines.The introduction of an ICP led to an overall improvement in compliance with MHC guidelines. The ICP has ensured that many of the rules governing seclusion are explicitly stated; however adjustments and revisions to the document and ongoing staff training are needed to ensure full adherence to MHC guidelines.


The development of the nervous system is a time-ordered and multi-stepped process that includes neurogenesis and neuronal specification, axonal navigation, and circuits assembly. During axonal navigation, the growth cone, a dynamic structure located at the tip of the axon, senses environmental signals that guide axons towards their final targets. The expression of a specific repertoire of receptors on the cell surface of the growth cone together with the activation of a set of intracellular transducing molecules, outlines the response of each axon to specific guidance cues. This collection of axon guidance molecules is defined by the transcriptome of the cell which, in turn, depends on transcriptional and epigenetic regulators that modify the structure and DNA accessibility to determine what genes will be expressed to elicit specific axonal behaviors. Studies focused on understanding how axons navigate intermediate targets, such as the floor plate of vertebrates or the mammalian optic chiasm, have largely contributed to our knowledge of how neurons wire together during development. In fact, investigations on axon navigation at these midline structures led to the identification of many of the currently known families of proteins that act as guidance cues and their corresponding receptors. Although the transcription factors and the regulatory mechanisms that control the expression of these molecules are not well understood, important advances have been made in recent years in this regard. Here we provide an updated overview on the current knowledge about the transcriptional control of axon guidance and the selection of trajectories at midline structures. The survival of organisms relies on their ability to detect stimuli, process sensory information and generate adequate motor responses. These functions depend on the precise organization of neural networks that enable communication between cells in an efficient and accurate manner. These networks emerge during embryonic development when newly born neurons extend axons away from the cell body to navigate through the developing embryo in order to reach their final targets. The growth cone at the tip of the travelling axon is a specialized structure armed with a plethora of receptors that defines the response of the growing axon to the environmental cues and determines its direction. The existence of both commissural neurons that project to the opposite side of the brain and ipsilateral neurons that connect with targets in the same hemisphere, is essential for the distribution and integration of sensory information and the subsequent generation of coordinated motor responses in species with bilateral symmetry . IntenseDrosophila initially identified a number of TFs involved in controlling the trajectories of motoneurons (MNs) axons towards their corresponding muscles and, subsequent work in vertebrates, revealed some of the transcriptional regulators that define specific limb muscles innervation  was described as essential for the targeting of olfactory projection neurons in osophila , and Pouosophila . Also inosophila . In the osophila  and Ctiposophila . In bothe lamina  and altee lamina .In addition to the abovementioned examples, two neuronal populations have been particularly useful to study the molecular mechanisms underlying axon pathfinding: spinal neurons at the time their axons navigate the floor plate, and retinal ganglion cells when their axons traverse the optic chiasm. In the following sections we review recent findings on the transcriptional regulation of neuronal trajectories using these two classic midline axon guidance models.The population of early born interneurons located in the most dorsal part of the spinal cord is known as dI1. As soon as dI1 neurons differentiate, they migrate ventrally to finally occupy the deep dorsal horns . A largeIn vitro, Barhl2 binds to the regulatory sequences of Lhx2 and represses its expression  specifying a commissural versus ipsilateral choice in dI1 neurons given the complexity of the regulatory mechanisms linking Atoh1, Barhl1/2, Lhx2/9 and downstream targets. Together with a more precise definition of the GRN controlling the specification of dl1 subtypes, other questions such as whether Lhx TFs activate other guidance receptors such as DCC, Robo2 or members of the Wnt pathway, or whether Robo3 expression is regulated by other homeodomain TFs in different types of commissural interneurons remain to be answered.In the mouse visual system, the majority of retinal ganglion cell axons cross the ventral diencephalon at the optic chiasm level (cRGCs) while a minority of these axons project to the ipsilateral hemisphere (iRGCs). In this model, also largely used to study axon guidance mechanisms, another member of the LIM homeodomain TF family, Islet2 (Isl2), is differentially expressed in the ipsi and the contralateral RGCs subpopulations . Isl2 muUnc5c locus and represses its expression in order to facilitate their growth into the diencephalic region  located in the dorsal horns of the spinal cord. dILB neurons are born very close to the dorsal midline . These cAll together, these observations point to the existence of several gene programs that control axonal laterality in ipsilateral spinal neuron populations with dispar ontogeny. Early born dl1 neurons locate far away from the midline because the ventricle and the subventricular zone (SVZ), which is rich in progenitor cells, occupy the medial region of the dorsal tube. As progenitors exit the cell cycle, the SVZ shrinks and the somas of the late born dILB neurons locate close to the midline. In contrast to the dl1i population whose axons never approach the midline and their projection patterns rely on Lhx factors, dILB neurons are born in close contact with the midline and their axons need to be repelled as soon as they start growing in order to project ipsilaterally. Thus, it is not surprising that although both populations, dI1i and dILB neurons project ipsilaterally, they developed alternative strategies to control the guidance of their respective axons  Figure .Despite the increasing number of rapidly emerging innovative techniques that largely facilitates research on the transcriptional mechanisms regulating gene expression, only a handful of TFs have been convincingly shown to control genetic programs involved in the regulation of axonal behaviors. In the last decade, the interest to understand how neural circuits function has exponentially increased and the development and application of genetically encoded, magnetic and thermal tools to manipulate neuronal circuits is helping us to disentangle brain connectivity and circuits function. However, it is surprising that in the era of next generation sequencing and single cell transcriptomic approaches  there ar


In this review, we outline the differentclasses of oocyte transcripts that may be involved in activation of the embryonic genome aswell as those associated with epigenetic reprogramming, imprinting maintenance or the controlof transposon mobilisation during preimplantation development. We also report the influenceof cumulus-oocyte crosstalk during the maturation process on the oocyte transcriptome andhow  The notion of embryo quality refers to the capacity of an embryo to develop and support successfulpregnancy to full term. In cattle, most failed pregnancies result from embryonic mortalitythat occurs before implantation, during the first two weeks after fertilisation . The emMammalian embryos are transcriptionally quiescent at the start of development. Early embryogenesisis mainly governed by post-transcriptional and post-translational events. The stockpileof maternal RNAs and proteins, which are stored within the oocyte during oogenesis, sustainsthe first stages of development until embryonic genome activation  during the early developmentof bovine embryos is a paradigm. JMJD3 belongs to the Jumonji family of genes that are epigeneticregulators. JMJD3 is a lysine demethylase associated with histone demethylation. Its activityis required for the removal of trimethylated histone 3 lysine 27 (H3K27me3) marks during thereprogramming process . The leWhile tight temporal activation of the translation of dormant maternal mRNAs is required forsuccessful progress through the first cleavages, destabilisation and degradation of the maternalRNA pool is a major determinant for the start of EGA . DecreaPiwi-interacting RNAs (piRNAs), another class of small non coding RNAs, are potentially involvedin the control of maternal mRNA translation and decay as well as in that of transposon activityduring early embryogenesis (Long non-coding RNAs (lncRNAs) are increasingly being recognised as modulators of gene expression.These lncRNAs are a class of transcripts longer than 200 nucleotides that do not usually codefor a protein . RecentThe capacity of the fertilised egg to support successful embryonic development is reliant uponthe content of the oocyte at the time of fertilisation. The phenotype of a mature oocyte is theculmination of continuous and highly coordinated interactions between the germinal and somaticcompartments of the ovarian follicle that occur throughout folliculogenesis, and particularlyduring terminal differentiation of the cumulus-oocyte complex (COC) . The LHin vitro study using bovine model shown that modulation of miRNA-130bexpression in maturing oocyte affects the meiosis progression as well as the proliferationrate and the glucose metabolism activity of surrounding CCs  and fertilisation (IVF). The resultingzygotes undergo a 7-day culture period that permits them to reach the blastocyst stage. Embryoquality is assessed morphologically at the end of this culture period in order to select embryosthat are compatible with the transfer procedure (in vitromatured COCs with those obtained from in vivo counterparts highlightedcritical deficiencies affecting several cumulus molecular pathways known to support developmentalpotential of the oocyte in mice, humans and cattle (in vitro procedure.The alteration of terminal molecular events in CCs before fertilisation could compromise cumulus-oocytedialogue and hence the full development of oocyte competence. Studies using a bovine model haveshown that the rise in PTGS2-related PGE2 production that occurs in CCs concomitantly with theresumption of meiosis is affected by IVM conditions and the presence of exogenous EGF (in vivo maturation (in vitro procedure (In cattle, ocedure . We prein vitro produced embryos is to optimise the in vitro maturationconditions in order to preserve the integrity of cumulus-oocyte coupling, which will contributeto achieving the full developmental competence of the oocyte.Disruption or deregulation of the interactions between a maturing oocyte and surrounding CCscan affect the final stages of the storage of maternal factors and consequently of subsequentembryonic development. One of the most promising options to improve the viability of


This article explores this topic in a succinct and systematic manner for the purpose of future documentation and referencing. This history is documented and updated up to January 2021. Nigeria, also known as the Federal Republic of Nigeria, is located in the West African sub-region bordered by the Republic of Benin in the West, Chad and Cameroon in the East and the Niger Republic in the North. The Nigerian coast in the South lies on the Gulf of Guinea in the Atlantic Ocean. Nigeria has more than 250 ethnic groups, but the three major traditional groups are the Hausa-Fulani, the Yoruba and the Igbo. Geopolitically, the country consists of six regions or zones, 36 states and a Federal Capital Territory located in Abuja. It consists of about 20% of the sub-Saharan African population.2 This course spanned the period 1932–1952, after which it was phased out for a more preferable course at the Faculty of Medicine, University of Ibadan, a programme that has a special relationship with the University of London where students who completed the pre-clinical training often proceed for the clinical aspect of their training.2Early western medical training in Nigeria prior to 1932 was mostly acquired in the United Kingdom (UK), few other European countries and the United States of America. Some Nigerians also obtained scholarship to study medicine in Eastern Europe and Russia up to 1960.Indigenous Western medical training commenced in Nigeria in 1932 when the Yaba Higher College provided a 7-year basic medical education course for candidates with Senior Cambridge School Certificate and produced assistant medical officers whose certificates were only recognised in Nigeria. The assistant medical officers were like physician assistants as observed today in the United States of America.2 Notable amongst them are late Prof. Thomas Adeoye Lambo, the first Nigerian psychiatrist who later rose in his carrier to become a deputy director at the World Health Organization (WHO).3 Others include the likes of late Prof. Tolani Asuni, who is the second indigenous psychiatrist in Nigeria.4 Closely followed these two are Prof. Ayo Binitie and Prof. Betta Johnson, amongst others.5Most of these foreign trained doctors remained in the UK to acquire postgraduate training in different specialties of medicine. Those who specialised in psychiatry then came back with Diploma in Psychological Medicine. These groups of doctors became the ‘founding fathers’ as they are fondly referred to forming the foundation of indigenous postgraduate psychiatry training in Nigeria and they went ahead to train other psychiatrists in Nigeria.Medical and Dental Practitioners Act of 1963.2 The Nigerian Medical Council later became Medical and Dental Council of Nigeria (MDCN) in 1990 through the promulgation of the Medical and Dental Practitioners Act, Cap 221 Laws of the Federal Republic of Nigeria, 1990.6Medical and Dental Act of 1963 was the law regulating medical graduate registration and practice. An amendment to it led to Decree number 44 of 1969 to enable the Nigerian Medical Council to be also responsible for postgraduate medical training and registration/practice of postgraduate medicine as opposed to only undergraduate medical training.Military Decree number 44 of 1969 gave a take-off wing to indigenous postgraduate medical training in Nigeria after due approval by the then Nigerian Medical Council . This de2 The decree establishing the NMC was promulgated into law in September 1979 by former military Head of State, General Olusegun Obasanjo.2 Simultaneously, the West African Health Society established in 1976 the West African College of Physicians (WACP) that was to superintend postgraduate medical training in West African sub-region.7 It consists of the following faculties: Internal Medicine, Laboratory Medicine, Community Health, Family Medicine, Paediatrics and Psychiatry.7Postgraduate medical training including psychiatry was superintended by the then Nigerian Medical Council (Postgraduate Examinations), the section of Nigerian Medical Council that assumed the responsibility of postgraduate medical education with the support of external examiners from the UK and neighbouring West African countries from 1970 up to 1979, when postgraduate training was separated under an independent body named the National Medical College (NMC) that later metamorphosed into the National Postgraduate Medical College of Nigeria (NPMCN).Both the NPMCN under the Faculty of Psychiatry (FMCPsych) and the WACP have been responsible for producing specialists in psychiatry since their inception in 1979 and 1976, respectively, leading to the award of Fellowship of NPMCN under the Faculty of Psychiatry (FMCPsych) and Fellowship of West African College of Physicians (FWACP) Psychiatry, respectively.Under the control of the Nigerian Medical Council (Postgraduate Examinations), today’s Faculty of Psychiatry of NPMCN was founded under the administrative leadership of the first board that was chaired by late Prof. Tolani Asuni and Dr A. Anumonye as the secretary in 1974 well before the promulgation of the NPMCN into existence in 1979 by Decree number 67.Between the inception of the NPMCN and WACP and now, about 250 indigenous specialist psychiatrists have been produced till date and about 200 psychiatric trainees are presently undergoing specialist training as supervised by both colleges. Specialists are appointed into the position of Consultant Psychiatrist in Nigeria with either Fellowship of NPMCN under the Faculty of Psychiatry (FMCPsych) or with the Fellowship of West African College of Physicians under the Faculty of Psychiatry (FWACP) or their equivalent which could be the Member of the Royal College of Psychiatry (MRCPsych) with a number of years of practicing experience.To obtain the fellowship of the two colleges, one would need to undergo three stages of the examinations – the primary examination that examined related basic medical sciences, Part 1 examination that tests the core clinical expertise of the specialty and Part 2 fellowship examination that is usually made up of oral examination and defence of a dissertation or thesis before award of the fellowship of either colleges. Both colleges collaborate in the designing of training and development of curriculum. The West African College serves the countries in the West African sub-region and the NPMCN is strictly for Nigeria. The fellowships of the two colleges are equivalent in Nigeria for the purpose of employment and practising as a specialist.8The NPMCN in the Faculty of Psychiatry in recent years approved Post-Fellowship sub-specialty trainings in Child and Adolescent Psychiatry and Old Age Psychiatry in Nigeria.9 This association consists of full-fledged psychiatrist and associate members, who are usually psychiatric trainees and some allied professionals.9 The Association of Child and Adolescent Psychiatry and Allied Professionals in Nigeria (ACAPAN) was registered recently under the umbrella of APN.All the psychiatrists practising in Nigeria are bound together under the umbrella of the Association of Psychiatrists in Nigeria (APN) inaugurated in 1970.10 Since then, this controversy has continued raging and lately making the NPMCN bow under pressure to include alongside her award of Fellowship a Doctor of Medicine (MD) degree that could be deemed equivalent to PhD in other academic settings. Prior to the introduction of MD degree as a postgraduate medical degree, the degree being awarded to individuals who completed undergraduate medical training in Nigeria is Bachelor of Medicine or Bachelor of Surgery (MBBS or MBChB) depending on the particular university.Around 2008, the Nigerian University Commission (NUC), a body that regulates university education in Nigeria, issued a directive that possession of PhD degree would now be a prerequisite for promotion to a professorial level in a university setting as against just the fellowships of either colleges that are acceptable for postgraduate medical teachers in university settings in Nigeria. This directive was vehemently rejected by officials of both the NPMCN and the WACP and surgeons who argued that medical training, and more so postgraduate medical training, is a hands-on bedside training that must be combined with didactic lectures along with research competence unlike PhD that is mostly classroom taught courses and research. And there is no way a PhD degree can replace the standard offered by the level of training competence afforded by fellowships of either colleges for the purpose of postgraduate medical training in Nigeria11 The fact whether this step would improve the quality of postgraduate medical teachers in the university environment remains to be seen. It is the opinion of many specialist medical professionals that the change being accommodated by the NPMCN is just a cosmetic way of bowing to political pressure because Decree number 67 of 1979 has specified and defined the role of NPMCN as a body that would regulate the training and practice of postgraduate medical education in Nigeria. Whilst it is argued that undergraduate medical training may be under the supervision of or housed by a college in the university, postgraduate medical training, on the other hand, can actually be set up in any accredited health service institution across the country and not necessarily under the supervision of a university regulatory authority (NUC).The curriculum for the MD degree and training design which would be incorporated into the structure of normal Residency Training Programme leading to the award of Fellowship is presently going through finishing touches.This historical perspective is important at this present time in view of the current controversies arising in the university environment in Nigeria based on the new directive by the NUC, requiring every postgraduate medical teacher in a university environment to have a doctorate degree (PhD or MD) before being qualified for promotion to a professorial level in a Nigerian university setting. A moratorium was recently given by the NUC to postgraduate medical teachers in the university environment to obtain a PhD or MD degree by 2025 to be able to qualify for the promotion to the level of a university professor.


I read with great interest the article entitled “The Long-Term Effects of 12-Week Intranasal Steroid Therapy on Adenoid Size, Its Mucus Coverage and Otitis Media with Effusion: A Cohort Study in Preschool Children” by Zwierz et al. [In this study, the authors used examination adenoid hypertrophy according to Boleslavska et al. ,3. This Grade I: adenoid tissue that fills less than one third of the vertical portion of the choanae;Grade II: filling of the adenoid tissue from one third to two thirds of the choanae;Grade III: adenoid tissue that fills more than two thirds of the choanae.In this regard and according to choanal obstruction, adenoids are differentiated into three grades:Grade A: adenoid tissue not in contact with the torus tubarius;Grade B: adenoid tissue in contact with the torus tubarius without complete covering;Grade C: adenoid tissue that completely covers the torus tubarius.The condition of the nasopharyngeal orifice of the Eustachian tube was also differentiated into three grades related to the condition of adenoid tissue:I do not understand how they performed the classification of the size of the adenoids for the patients in the study. Why did the authors not classify the conditions of adenoid tissue into the nasopharyngeal orifice of the Eustachian tube? In otitis media with effusion, the relation between adenoids and torus tubarius is more important than the volume of the adenoids .


Needling interventions consist of the use of filiform needles for the management of different conditions of the neuromusculoskeletal system. The most commonly used needling therapies are trigger point dry needling, an intervention showing an increasing interest in both clinical and research setting , and acuTwo studies focused on the use of ultrasound imaging: the first one for improving the safety of some potential dangerous dry needling treatments when applied on the thorax  and the In addition, two meta-analyses support the effectiveness of trigger point dry needling for conditions that cause neck  and knee


In this Special Issue, a wide variety of original and review articles provide a timely overview of how viruses are recognized by and evade from cellular innate immunity, which represents the first line of defense against viruses. The success of the immediate response relies on the recognition of invariant features encoded by viruses termed pathogen-associated molecular patterns (PAMPs) and by specialized sensors called pattern recognition receptors (PRRs). In the review by Singh et al., the reader is provided with a broad overview of the innate sensing of viruses by diverse PRRs. The authors discuss recent progress in the understanding of the consequences of innate sensing on the central nervous system (CNS), a tissue that can be severely damaged by infections of diverse viruses .The consequence of this surveillance network and the downstream pathway activation is the secretion of cytokines and type I interferons (IFNs). Schwanke et al. provide an in-depth review on the master regulator of the type I interferon response, IRF3, and the IFNβ enhanceosome . They prBased on the nature of their nucleic acid and entry pathways, viruses are, in general, either sensed by RNA or DNA sensors. Retroviruses, including the Human Immunodeficiency virus, are RNA viruses that reverse transcribe their RNA genome into DNA. Different aspects of RNA or DNA sensing in retroviral infections are highlighted in one review  and one


Various relationships are important for the well-being of older adults. This session focuses on the vertical and horizontal relations of Korean and Korean American older adults and their well-being. The purpose of this session is to highlight the importance of intergenerational relations and social involvement of Korean and Korean American older adults. For vertical relations, two studies focus on intergenerational relationships and solidarity. The first study investigated whether intergenerational relationships and social support mediate the distressing consequences of life events, and how this improved the psychological well-being of Korean older adults. The second study developed a standardized measurement tool for intergenerational solidarity because intergenerational conflicts caused by rapid socioeconomic changes have highlighted the importance of strengthening intergenerational solidarity. The third and fourth studies focus on horizontal relations involving social isolation and social involvement. Guided by the double jeopardy hypothesis, the third study examined the health risks posed by the coexistence of social and linguistic isolation in older Korean Americans. As the opposite of social isolation, social involvement was an important factor of social integration of older adults. The fourth study examined volunteering as an example of social involvement by focusing on older adults’ volunteering on the social integration and role identity. Implications of this study suggest not only the importance of social involvement but also the intergenerational relationships on older adults’ well-being.


The pulmonary vasculature consists of a large arterial and venous tree with a vast alveolar capillary network (ACN) in between. Both conducting blood vessels and the gas-exchanging capillaries are part of important human lung diseases, including bronchopulmonary dysplasia, pulmonary hypertension and chronic obstructive pulmonary disease. Morphological tools to investigate the different parts of the pulmonary vasculature quantitatively and in three dimensions are crucial for a better understanding of the contribution of the blood vessels to the pathophysiology and effects of lung diseases. In recent years, new stereological methods and imaging techniques have expanded the analytical tool box and therefore the conclusive power of morphological analyses of the pulmonary vasculature. Three of these developments are presented and discussed in this review article, namely (1) stereological quantification of the number of capillary loops, (2) serial block-face scanning electron microscopy of the ACN and (3) labeling of branching generations in light microscopic sections based on arterial tree segmentations of micro-computed tomography data sets of whole lungs. The implementation of these approaches in research work requires expertise in lung preparation, multimodal imaging at different scales, an advanced IT infrastructure and expertise in image analysis. However, they are expected to provide important data that cannot be obtained by previously existing methodology. The gas-exchange function of the mammalian lung is closely linked to its structural composition Weibel . At the The blood reaches the lungs via the pulmonary arteries more or less in parallel with the airways. The veins draining the blood from the capillary bed run within interlobular septa and do not follow the arterial and airway paths. Like the airways and like arteries of the systemic circulation, the wall composition of the pulmonary arterial branches changes along the vascular tree. The pulmonary arteries are involved in important physiological processes such as hypoxic vasoconstriction  are essential for the physiological function of the lung and are critically involved in human diseases. Due to the close link between structure and function of the lung, (quantitative) morphological methods to analyze the different vascular compartments of the lung contribute to understanding the healthy and diseased lung Weibel . DespiteDesign-based stereology is the gold standard of morphometric studies on the lung  or rely on a group of vessels that seem to be easy to identify. Within a homogeneous cohort  the grouping of arteries according to their diameter or wall thickness may lead to consistent results. However, when these data are used to draw a comparison with an experimental group with altered vascular characteristics, it may well be that different types of arteries are compared with one another. The difficulty in defining a coherent vascular compartment can also lead to biased observations  and light microscopic stereology  generation of arterial branches. However, when looking at a human lung, such a design would not make sense: it certainly requires a lot more generations from the hilus of the lung until the subpleural parenchyma at the base of the lung than to the perihilar gas-exchange region. According to the dichotomous branching, an average number of 23–28 generations of arteries is widely accepted (Ochs and Weibel Morphological analyses of the pulmonary vascular trees as well as the alveolar capillary network are essential to improve our functional understanding of the lung vasculature in health and disease. New microscopic and X-ray imaging techniques, digital image processing and stereological estimators increase the potential of microscopic investigations of the pulmonary vasculature. Future studies will benefit from using and combining the techniques to enhance their conclusive potential.


The growing cost of healthcare services has been a concern for many countries in the world. In China, medical expenditures can account for as much as 65% of per capita income in some low-GDP counties in 2011. One of the primary goals of the New Rural Cooperative Medical Insurance (NRCMI) is to provide financial protection and alleviate the financial burdens of rural residents in China. This paper examined whether NRCMI participation impacted the incidence of catastrophic health expenditure (CHE) among middle-aged and older adults (45 years old and above) using the China Household Income Project 2007 rural data and an instrumental variable estimation method in two provinces where there was heterogeneity in NRCMI implementation schedule. The results show that NRCMI enrollment could not impact the likelihood of experiencing CHE among middle-aged and older adults. However, NRCMI participation increased the actual amount of medical expenses in one province but not in the other. Although none of the prior studies have used instruments and village fixed effects or take endogeneity issues into account to investigate the impact of NRCMI on relative financial burden among recipients, the results found in this study are generally aligned with the prior findings, especially with those using quasi-experimental studies. Findings from this study provide empirical evidence to the policymakers that the effect of NRCMI participation on financial protections is limited despite its broad population coverage. The limited effects are probably due to the low reimbursement rate and more utilization of expensive healthcare services.


In the last two decades, a change in paradigm has taken place in the management of salivary gland diseases. Hardly any type of pathological entity in this anatomical area has remained unaffected by the philosophy of individualised medicine, the general need for reducing therapeutic “invasiveness” and the necessity of achieving a satisfactory postinterventional quality of life. The need for reducing surgical invasiveness and achieving a better quality of life for patients has led to using minimal invasive surgical modalities in benign parotid gland lesions, focussing away from the dissection of the facial nerve and concentrating on the capsular features of the tumour itself. With respect to pleomorphic adenomas of the parotid gland, understanding the histological characteristics of the tumour capsule and the potential clinical relevance of their biological behaviour is fundamental for the management of these entities. Undoubtedly, the different histological subtypes, the various degrees of capsular intactness and the formation of pseudopodia, as well as satellite nodules, constitute a demanding profile with apparent clinical-surgical implications . HistoriA thorough search of the salivary-gland-relevant literature reveals that research concerning the refinement of the surgical management of parotid tumours is undoubtedly advancing further. In this context, several reports refer to the value of facial nerve monitoring in both the intraoperative and the postoperative setting of parotidectomy. In everyday surgical routine, it is of major importance to investigate the correlation between a decrease in the electromyographic signal of the facial nerve and postoperative facial nerve function . InteresThe paradigm shift in the treatment of salivary gland pathologies does not only refer to the management of parotid tumours. Expanding the use of sonography with a variety of ultrasound-assisted techniques and also new sialendoscopic-controlled modalities have led to the development of a significant number of treatment forms in obstructive sialopathy, aiming at preserving the anatomy and function of major salivary glands and reducing postinterventional morbidity . It is iWhile surgery remains the first-line treatment for salivary gland cancer, a multitude of systemic therapies including chemotherapy, targeted therapy and immunotherapy are available for inoperable and distant metastatic disease. However, there are a significant number of different studies dealing with the most common histological subtypes of salivary gland cancer that have not yet been reviewed and evaluated. A thorough search of the relevant literature reveals that systemic treatment can achieve prolonged progression-free and overall survival with a satisfactory quality of life, while the overall prognosis remains rather poor. In the future, further studies with a larger patient cohort and ideally only one histological subtype are needed in order to improve the outcome for salivary gland cancer patients. Given that clinical research on salivary glands is undoubtedly in progress and definitively advancing, the present Special Issue entitled “Treatment of salivary gland diseases: established knowledge, current challenges and new insights” is intended to provide an overview of recent advances in the management of salivary gland diseases in an effort to provide new evidence regarding several surgical and non-surgical aspects of this topic.


Automatic crankshaft production lines require high reliability and accuracy stability for the oscillating grinding machine. Crankshaft contour error represent the most intuitive data in production field selective inspection. If the mapping relation between the contour error components of the crankshaft pin journal and the axis position control error of the oscillating grinding machine can be found, it would be great significance for the reliability maintenance of the oscillating grinding machine. Firstly, a contour error decomposition method based on ensemble empirical mode decomposition (EEMD) is proposed. Secondly, according to the contour generating principle of the pin journal by oscillating grinding, a calculation method to obtain the effect of the axis position control error of the oscillating grinder on the contour error of the pin journal is proposed. Finally, through the grinding experiments, the error data are acquired and measured to calculate and decompose the contour error by using the proposed methods for obtaining the mapping relation between the crankshaft pin journal contour error and the axis position control error. The conclusions show that the proposed calculation and decomposition methods can obtain the mapping relation between the contour error components of the crankshaft pin journal and the axis position control error of the oscillating grinding machine, which can be used to predict the key functional component performance of the machine tool from the oscillating grinding workpiece contour error. The crankshaft is a critical component of the automobile engine, and its machining quality directly affects engine performance and reliability. Therefore, crankshaft manufacturing plays a very significant role in the automotive industry. In the mass production of engine crankshafts, the pin chasing grinding technology based on the oscillating grinding machines has been widely implemented to meet machining accuracy and efficiency requirements ,2. DurinEngineering surface texture is considered as the “fingerprint” of the manufacturing process , where tThe schematic of an oscillating grinder and the error sources are illustrated in jth IMF component is indicated as jC, then the original signal X(t) can be described as,r is the residue of the signal and it is a monotonic function. In essence, EMD is an adaptive dyadic filter bank [The EMD, proposed by Huang et al. in 1998 , can decter bank  which cater bank . In termC1 of the pin journal contour error is composed of the previous order component, the components with frequency less than 2 UPR, and the residual component. If the contour error is decomposed into M components, To overcome the mode mixing problem in EMD, EEMD was proposed by Wu and Huang . The decG is in the connecting line between the center of the pin journal C and the pin journals rotate around the center O of the main journal. The grinding wheel implements reciprocating chasing motion along the X axis and realizes the grinding of crankshaft pin journals.In the oscillating grinding process, the grinding wheel is always tangent with a crankshaft pin journal. The contour of crankshaft pin journal is produced by reciprocating motion of grinding wheel following rotational motion of crankshaft. Under ideal conditions, the contour of the crankshaft pin journal is a standard circle. The principle diagram of the crankshaft oscillating grinding motion is illustrated in The contour control point  can be transformed as,According to the geometric relationship, Equation (4) can be achieved as,From Equations (3) and (4), Equation (5) can be obtained as follows,When a workpiece is ground, the theoretical grinding motion control equations can be derived from Equation (2),According to Equations (6) and (7), the CNC system of the machine tool controls the motion of C axis and X axis to machine the pin journals. Only if the practical motion positions of C axis and X axis accurately meet the requirements of the equations, the grinding result is an ideal circle. However, in the practical machining, the motion control of the C axis and X axis both have errors. Therefore, the contour of the ground pin journal is not a standard circle.To accurately obtain the grinding contour generation mechanism of the crankshaft pin journal and the relation between the machine tool position control information and the crankshaft pin journal contour information, the coordinate system is created in the pin journal, where the grinding process can be considered as the grinding wheel rotation around the pin journal. If the elastic deformation of the grinding wheel and the workpiece is neglected, the inner envelope of the grinding wheel trajectory is the grinding contour of the pin journal, as illustrated in According to the above principle and neglecting elastic deformation of the mechanical system, the grinding wheel and workpiece utilize the practical contour control point  and (9), Equations (10) and (11) can be obtained,Let O, the practical pin journal center pO and the phase reference positive x axis direction can be inferred.From Equations (12) and (13), the contour information The mapping relation between the contour error components of the crankshaft pin journal and the axis position control error of the oscillating grinder is obtained. Because there are other error sources that affect the contour error of the crankshaft pin journal, there are some minor differences in the magnitude of the contour error. However, the position control error of the C axis and X axis represent the main influencing factors.(2)A contour error decomposition method based on EEMD is proposed. Boundary periodic extension is applied to avoid the boundary effect and the low frequency component discrimination method is set up to effectively extract the low frequency components.(3)The mapping relation between the contour error components of the crankshaft pin journal and axis position control error of the oscillating grinder can be applied in predicting the key functional component performance of machine tools from oscillating grinding workpiece contour error.


The second paragraph of the Methods section detailing methodology for skeletochronology was included by mistake; the authors clarify that skeletochronology to infer age by related snout-vent length (SVL) was not used in this study. Specimen age was deduced using SVL measurement only.The erroneously included description of the skeletochronology is adapted from reference [24], which is cited in support of the snout-vent length methodology used to select adult lizards .Accurate ageing beyond selection of adults is not essential for the study design in .For mitogenome analyses, tissue samples from the terminal end of the tail were collected from live specimens. To minimize demographic impact, transcriptome analyses of brain tissue were carried out only on specimens that accidentally died during capture or manipulation .Specific sanitary protocols were employed to guarantee isolation of individuals of one population from the others to avoid the potential spread of pathologies and parasitosis. The research program for capture, manipulation, tissue sampling, temporary housing, and release of individuals at the site of capture was assessed by the Istituto Superiore per la Protezione e la Ricerca Ambientale (ISPRA) and by the Societas Herpetologica Italica and subsequently approved by the Ministry of the Environment and Protection of Land and Sea.


Engineers, scientists and mathematicians are greatly concerned about the thermal stability/instability of any physical system. Current contemplation discusses the role of the Soret and Dufour effects in hydro-magnetized Carreau–Yasuda liquid passed over a permeable stretched surface. Several important effects were considered while modelling the thermal transport, including Joule heating, viscous dissipation, and heat generation/absorption. Mass transportation is presented in the presence of a chemical reaction. Different nanoparticle types were mixed in the Carreau–Yasuda liquid in order to study thermal performance. Initially, governing laws were modelled in the form of PDEs. Suitable transformation was engaged for conversion into ODEs and then the resulting ODEs were handled via FEM (Finite Element Method). Grid independent analysis was performed to determine the effectiveness of the chosen methodology. Several important physical effects were explored by augmenting the values of the influential parameters. Heat and mass transfer rates were computed against different parameters and discussed in detail. The mechanism of transport phenomenon in different materials has received reasonable attention recently due to its wider applications in industry and different medical processes. Several important materials exist for the support of these mechanisms. Due to their different characteristics, these materials cannot be explained through one constitutive relation. Carreau–Yasuda is one such important material which has the following constitute relation.For e et al.  reportede et al. . In theie et al.  presentee et al.  via the e et al.  through The involvement of nanoparticles enhanced the thermal performance and heat transportation rate. Several models of the nanomaterials are available and frequently used to study the thermal performance of different materials. Several researchers have paid attention to these materials due to their wider applications and usage. For instance, Gorla and Gireesha  developeIn the above cited literature, no study deals with the combined behavior of the following: mass, heat transport in hydro-magnetized Carreau–Yasuda material using Joule heating, viscous dissipation, heat generation, chemical reaction and the Soret and Dufour influences in the Darcy–Forchheimer porous stretching sheet. This report fills the gap in this discussion and should be used as a foundation for researchers to work further on this model. The inclusion of nanoparticles in the Carreau–Yasuda material is attractive to researchers. Organization of this research is divided in the following way: the literature survey is reported in An enhancement in the thermal and solute performance of Carreau–Yasuda rheology, inserting the impact of nanoparticles and hybrid nanoparticles, is considered as shown in The non-linear PDEs are developed according to the physical happenings and the boundary layer approximations.The no-slip theory provides the required boundary conditions of the current model:Change in variables is constructed as:Transformations are used in Equations (1)–(5) and the system of non-linear PDEs are converted to following ODEsHere, The temperature gradient because of the nano and hybrid nanoparticles isConcentration gradient at the surface of the melting sheet isThe local Reynolds number is ➢FEM has the ability to handle various complex geometries;➢This numerical method is thought to be most significant in solving physical problems with wide ranges;➢FEM requires less investment in the view of time and resources;➢A main advantage of FEM is its handling of various types of boundary conditions and➢It has a good ability with regards to the discretization (of derivative) problems into small elements;➢The Working scheme of finite element method has been shown with the help of The finite element method is an effective method in the view of accuracy and the convergence of a problem compared with other numerical approaches. There are many advantages to FEM but some are discussed here:The numerical approach called finite element scheme is used to simulate the numerical results of highly non-linear PDEs and numerous applications of FEM are found in CFD  problems. The FEM approach is explained in the following steps:Step I: The division of a problem domain into a finite number of elements and residuals. The weak form is captured from the strong form due to residuals. The approximation result is simulated using shape functions and the approximation simulations of the variables are:Here Step II: In this step, the matrices are stiffness, vector and boundary . The global stiffness (matrix) is obtained whereas the Picard (linearization approach) is utilized to obtain a linear system of equations that are defined as:Here Step III: The algebraic equations (non-linear) resulting from the assembly process are:Step IV: The computational domain is considered as Comparative analysis: The numerical result of the current problem is verified with published results [ results  by the dhed work  are presMechanisms of velocity, thermal energy and diffusion of mass influenced by chemical reaction are addressed over a stretched melting surface. Correlations between silicon dioxide and Molybdenum dioxide in EG (ethylene glycol) are used in the presence of the Carreau–Yasuda liquid. Various kinds of influences  are also addressed. As such, the complex transport phenomenon is simulated with the help of a numerical approach (FEM). The graphical computational investigations are captured in graphs and tables. The detailed outcomes are discussed below:Graphical investigations of velocity against distribution in various parameters: The change in Weissenberg, power law index, Forchheimer numbers and Carreau–Yasuda variables are addressed in the motion of fluid particles considered in cles see . It is dGraphical investigations of heat energy against distribution in various parameters:f Df see . FurtherGraphical investigations of mass diffusion against distribution in various parameters:Mechanisms of gradient temperature, surface force and mass diffusion rate versus the distribution of various parameters: The computational analysis of surface force (skin friction coefficient), gradient temperature (Nusselt number) and rate of mass diffusion versus the variation of Convergence of the problem is ensured at 270 elements;The motion of nanoparticles and hybrid nanoparticles in ethylene glycol is boosted versus the enhancement in fluid variable, power law index number, Weissenberg number and Forchheimer porous number;Significant production of heat energy versus higher values of heat generation, Eckert, Dufour and Forchheimer porous numbers;The transportation of solute particles declines versus the large values of Schmidt and chemical reaction numbers, but solute particles accelerate against higher values of Soret number;Surface force is increased via large values of Weissenberg and Forchheimer porous numbers but surface force is decreased versus the large values of heat generation number andThe transport features in the rheology of Carreau–Yasuda liquid and involvement of nanostructures and hybrid nanoparticles over a heated surface have been visualized. The Dufour and Soret effects under the action of a magnetic field have been addressed. Forchheimer porous media was also considered. The simulations of the current model were computed by finite element approach. The prime findings are captured below:The role of the Schmidt number is significant in the development of temperature and concentration gradient.


Specialized biological processes occur in different regions and organelles of the cell. Additionally, the function of proteins correlate greatly with their interactions and subcellular localization. Understanding the mechanism underlying the specialized functions of cellular structures therefore requires a detailed identification of proteins within spatially defined domains of the cell. Furthermore, the identification of interacting proteins is also crucial for the elucidation of the underlying mechanism of complex cellular processes. Mass spectrometry methods have been utilized systematically for the characterization of the proteome of isolated organelles and protein interactors purified through affinity pull-down or following crosslinking. However, the available methods of purification have limited these approaches, as it is difficult to derive intact organelles of high purity in many circumstances. Furthermore, contamination that leads to the identification of false positive is widespread even when purification is possible. Here, we present a highlight of the BioID proximity labeling approach which has been used to effectively characterize the proteomic composition of several cellular compartments. In addition, an observed limitation of this method based on proteomic spatiotemporal dynamics, was also discussed. Dear editor,We have read with great interest the recent publication by Go et al. ; a studyThe proximity labeling method has been developed to study the spatial compartmentalization of protein networks and their assembling pattern into functionally integrated complexes. This method involves the selective and covalent biotin tagging of neighbouring proteins in a living cell with the use of engineered enzymes. Isolation of the biotinylated proteins can then be carried out after cell lysis and mass spectrometry characterization. Proximity labeling has previously been applied in the mapping of different cell organelle components as well as in the identification of novel interactions with increased spatial specificity. These studies have shown that the proximity labeling approach is an efficient method for the dissection of molecular localization and interaction patterns with nanometer spatial resolution .There are two major categories of the proximity labeling methods, both of which are linked to the type of enzyme used for catalysis. The peroxidase-based proximity labeling depends on the expression of an engineered HRP (horseradish peroxidase) or APEX (ascorbate peroxidase) in the tissues or cells of interest. HRP can alternatively be targeted to specific antigens on the cell surface through antibody conjugation. To start labeling, hydrogen peroxide is always added to tissues or cells for 1 min. The cells are then to be pre-loaded with biotin-phenol or its variants, such as desthiobiotin phenol, alkyne-phenol and BxxP. Biotin-phenol is oxidized by the peroxidase into phenoxyl radical which in turn reacts with neighboring proteins at their electron-rich side chains. Because the half-life of the phenoxyl radical is less than 1 ms, the intensity of labeling falls dramatically within few nanometers from the active site of the peroxidase. This generates a biotinylation contour map which can be analyzed by quantitative proteomics to produce a list of proteins that are ranked on the basis of proximity to the enzyme .E. coli) is attached to a polypeptide of interest (regarded as bait) and this combination is expressed in organisms or cultured cells. The BirA* releases biotinoyl-AMP into its immediate environment and the released compound labels lysine residues between the range of 5–10 nm to the bait protein. The biotinylation permits the use of harsh lysis conditions to enhance the solubility of proteins from intracellular compartments that are normally poorly soluble, such as the nuclear lamina, membranes or the chromatin. The biotinylated proteins are then trapped with streptavidin affinity, followed by mass spectrometry identification. Because the diameter of an average globular protein is 5–10 nm, the radius of labeling for the BioID technique benefits the biotinylation of proteins that are localized to the immediate intracellular environment of the bait and its direct binding partners [In the biotin ligase-based (BioID) proximity labeling approach, BirA*  which permits data viewing and searching regarding all profiled organelles, baits and prey proteins. Major features of the database includes its usage for the identification of queried bait-specific preys, the localization of a query bait to particular compartments of the cell based on similarity with the interactomes of other baits, and the identification of previously queried baits that have similar interactomes. Included among these features also is the ability to make comparison between the human cell map database and user BioID data. Although the BioID-predicted proteome compartmentalization appears to share high similarity with predictions made by fractionation and large-scale microscopy studies, the inability of the method to factor in the spatiotemporal dynamics of the human proteome in its predictions remains a limitation. To illustrate this, we compared the single-cell proteogenomic-based spatiotemporal prediction of the APPL1 localization from the human protein atlas (https://www.proteinatlas.org/) (Fig. In an attempt to enhance their dataset exploration, the authors have designed the human cell map (In conclusion, the mass spectrometry in conjunction with biochemical fractionation and microscopy has been popularly applied in defining the proteomes of different cellular organelles, but most intracellular compartments of the cell have remained obstinate to such methods. Although, the specificity of the described BioID-based proximity labeling prediction for proteome compartmentalization exceeded those from previously reported approaches, limitations as a result of the spatiotemporal dynamics of the human proteome remains a factor to be considered in order to increase the specificity of predictions.


Iron is an element whose content in the human organism remains under strict control not only due to its involvement in many life processes but also because of its potential toxicity. The latest studies in iron metabolism, especially the involvement of hepcidin, which is the main regulator of iron homeostasis, broadened our knowledge in many medico/ fields . The present paper is a review of the literature devoted to the importance of hepcidin under selected conditions. Those discoveries opened the way for new diagnostic and therapeutic opportunities. Hence, studies on iron metabolism have become the focus of interest for scientists and doctors specializing in many fields.Only a few years ago the only tests for evaluating iron metabolism were blood iron, transferrin and ferritin levels and the iron binding capacity. Since 2001 iron homeostasis investigations have been expanded by new markers: hepcidin, ferroportin, hemojuvelin, erythroferrone. The genetic bases of iron metabolism have been determined Recent discoveries in the field of iron metabolism and the mechanisms of iron absorption and use demonstrated that hepcidin was the pivoting element of iron homeostasis . HepcidiThe association between the susceptibility to infections and the organisms iron resources is a subject of numerous studies. It is particularly important in those populations where the rate of iron deficient individuals reaches several dozen percent, and the danger of mass epidemic outbreaks  is high . The WorThe level of hepcidin as an acute phase protein is increased in the course of pneumonia. The increase leads to the so-called anaemia of inflammation through the inhibition of erythropoiesis (reduced iron availability as a result of inhibiting absorption and liberation of the element). On the other hand, anaemia and tissue hypoxia activates erythropoiesis by the inhibition of hepcidin. The transient anaemia accompanying pneumonia seems to have a beneficial effect on the limitation of bacterial development. Michels et al.  demonstrRespiratory infections are an important health problem in the paediatric population. Some reports regarding studies in disorders of iron metabolism in the course of infections of the respiratory system, particularly the lower respiratory tract, are available in the literature . The lowEscherichia coli compared to individuals reacting to bacterial infection with increased expression of hepcidin. The authors also demonstrated that bacteria were able to restrict the synthesis of hepcidin in the renal cells of infected animals. That was their protection mechanism [There are reports of attempts to use the assessment of iron metabolism parameters in the course of severe systemic infections in order to predict the course of the disease. It was observed that there is an unfavourable prognosis regarding survival in patients with sepsis whose blood iron levels were high. A possible application of iron chelating drugs was suggested in the therapy of critically ill patients . Houamelechanism .There are numerous reports regarding iron metabolism in chronic inflammations of various aetiology . The autOne of the inflammatory disorders for which the use of iron parameters for prognostic purposes is considered is Kawasaki disease. Particularly patients with a prolonged course of this disease are at a risk of anaemia. The hepcidin level was significantly higher in patients demonstrating resistance to immunoglobulin therapy, who were at a higher risk of developing lesions in coronary arteries  . The auThe role of chronic inflammation associated with the synthesis of cytokines, chemokines and growth factors secreted by adipose tissue has been underlined in the pathogenesis of obesity for several years. Problems of iron metabolism in obese people, in the context of the variability of hepcidin concentration, are of interest due to the tendency to anaemia and an inferior efficacy of treatment with iron oral preparations in obese children  . MorenoType 2 diabetes is currently regarded as a disease associated with iron overload. Increased hepcidin levels contribute to the development of insulin resistance and type 2 diabetes . HoweverDiscoveries of factors involved in iron metabolism, including hepcidin, opened the way to progress in developing knowledge about the diseases whose aetiology is primarily associated with the disruption of this metabolism. Patients with β-thalassemia of pathogenetic origin, and also patients requiring frequent blood transfusions for therapeutic reasons, demonstrate an excessive tissue storage of iron from decomposed RBCs. Increased iron absorption from the alimentary system is observed in such cases. In this group, hepcidin levels are lower compared to healthy individuals . SimilarThe liver is the principal place of hepcidin synthesis. Dysfunction of that organ in the course of chronic conditions, regardless the aetiology, leads to disturbed regulation of expression and subsequent reduced production of hepcidin . That, iKidneys are organs playing a significant role in iron metabolism. Plasma hepcidin is eliminated mostly through the kidneys – the compound is almost totally filtered in the renal glomeruli, but then re-uptaken and disrupted in the proximal tubules. As a result, only a low percent of hepcidin is eliminated in a non-altered form . In patiThe results of scientific research on the complex process of iron metabolism constitute the basis for pharmacological tests of their practical application. Attempts have been made to synthesize drugs that may be used in therapy by influencing iron metabolism. Studies on antagonists and agonists of hepcidin are underway. One of them is lexaptepid , an antaIron plays a principal role in the physiological function of the human organism. It has been known for a long time that its disturbed metabolism leads to such diseases as β-thalassemia and hemochromatosis. The current state of knowledge indicates that the complex mechanism of iron metabolism, with hepcidin playing the key role, is significantly correlated with the development of anaemia in the course of many diseases (inflammation-associated anaemia or anaemia of chronic diseases). The present review of the literature shows that not only is the pathogenesis of these disorders more fully understood, but some possibilities of targeted therapy are also emerging.


Genetic testing is associated with many ethical challenges on the individual, organizational and macro level of health care systems. The provision of genetic testing for rare diseases in particular requires a full understanding of the complexity and multiplicity of related ethical aspects. This systematic review presents a detailed overview of ethical aspects relevant to genetic testing for rare diseases as discussed in the literature. The electronic databases Pubmed, Science Direct and Web of Science were searched, resulting in 55 relevant publications. From the latter, a total of 93 different ethical aspects were identified. These ethical aspects were structured into three main categories  and 20 subcategories highlighting the diversity and complexity of ethical aspects relevant to genetic testing for rare diseases. This review can serve as a starting point for the further in-depth investigation of particular ethical issues, the education of healthcare professionals regarding this matter and for informing international policy development on genetic testing for rare diseases. Geneticividuals . This noividuals .A precise molecular diagnosis is essential for the efficient handling of rare diseases in order to provide disease management and treatment options. In addition, it enables informed future family planning decisions and the formation of supportive networks of individuals and families affected by rare diseases . Early aAdvances in genetic testing, especially next generation sequencing technologies (NGS), have positively impacted the likelihood of obtaining a genetic diagnosis in a timely manner . HoweverThe rapid technological advancements in genetics and the lack of education in this field limit the ability of many nonspecialized physicians to partake in the much needed professional discussion of ethical issues in genetic testing . The widThis review is the first, to the best of the authors’ knowledge, to present a profound overview of all ethical aspects of genetic testing for rare diseases as published in the literature. In systematizing ethical problems related to this field this review can assist researches in the field of genetics as well as clinicians and counsellors in enhancing the moral sensibility for issues pertinent to their professional practice. For example, this review systematically gives a list of ethical issues occurring at the micro-level of patient-provider-contact and enables a further in-depth literature analysis of moral problems relevant for the individual reader. It furthermore provides a systematic basis for the ethical education of not only healthcare professionals but also patients, their families and other relevant stakeholders. This review provides a systematic background for further empirical and normative investigations of ethical aspects and is meant as a comprehensive aid to health policy making.This article provides an overview of the full spectrum of ethical aspects in genetic testing for rare diseases based on a systematic review of the literature closely following the methodology used by Strech et al. . The repThe electronic databases Pubmed, Science Direct and Web of Science were searched  . Publica“Ethical aspects” were identified on the basis of the ethical theory of principlism, according to Beauchamp and Childress . This ap“Genetic testing” is defined as an laboratory examination aimed at detecting or ruling out the presence of hereditary illnesses or predisposition to such conditions in a person by directly or indirectly analyzing their genetic heritage  .Up until the completion of this article, no definite set of criteria had been established on how to conduct a quality appraisal for reviews of ethical literature . ConsequNo restriction was applied to the type of publications included in this review. Therefore, not only original articles but also comments, editorials and book chapters were included. In order to display the full spectrum of ethical aspects relevant to the review question, not only argument-based but also empirical literature  was included  Process of testing: Ethical aspects concerning the procedure of genetic testing for rare diseases, the analysis of these tests and the delivery of the results to the patient and/or the family.2) Consequences of the test outcome: Ethical aspects that result from the knowledge of the test result or the decisions made following the disclosure and patient reactions to the test result.3) Contextual challenges: Ethical aspects that are associated with the circumstances and background of the tests, the diseases tested for and the test results.The following three main categories were established: process of testing encompasses 36 ethical aspects in nine subcategories  which they did not consent to but if not disclosed might have an interest to know. This ambiguous situation needs to be extensively addressed and prepared for during counselling:“Ethical challenges are generated when information produced by the results may affect third parties, including family members not directly involved in the process.” ontextual challenges includes 21 ethical aspects in four subcategories . Prior to the final search, an exploratory search of several databases was conducted and the three databases subsequently accessed were identified as delivering the highest number of relevant results. Additionally, the neglect of literature written in languages other than English or German limits this review.No quality appraisal for the included literature was performed due to the lack of quality assessment tools for systematic reviews of ethical literature . TherefoA lack of knowledge and comprehension of the fast-paced developments of genetic testing among professionals poses an obstacle to accessing comprehensive testing . Many phThis review found that not many physicians find themselves in a position where they feel knowledgeable enough to order and conduct genetic testing, especially for rare diseases . An effeHowever, this should, on the other hand, not deviate from the much needed extension of the education of physicians and other healthcare professionals to deliberately cover the advantages and disadvantages of genetic testing in the context of rare diseases, including not only medical subjects but also the ethical and legal issues presented in this review .