Artificial reefs improve the yield of artisanal fishing grounds by creating habitats with enhanced productivity, similar to those of natural reefs. For an adequate definition of an artificial reef, all its pathways of interaction with the ecosystem must be quantitatively assessed. In this way, the final design will lead to an increase in the production of services. Therefore, this study presents the MEEM tool as well as the AREIT index. Through the former, it is possible to obtain different reef solutions, while the index allows the user to select the best alternative by taking into account the specific situation of the ecosystem to be enhanced. The AREIT index facilitates the decision-making process by means of a three-dimensional graphical representation, based on the three aspects of greatest relevance for the ecosystem: energy, nutrient circulation and the presence of cavities for the shelter of species, in particular those of fishing interest. The definition process ends with the application of a procedure for calculating the stability of the final design under the action of waves and currents.Overfishing and pollution have led to marine habitat degradation, and as a result, marine fisheries are now in decline. Consequently, there is a real need to enhance marine ecosystems while halting the decline of fish stocks and boosting artisanal fishing. Under these circumstances, artificial reefs (ARs) have emerged as a promising option. Nevertheless, their performance is traditionally assessed years after installation, through experimental and field observations. It is now necessary to adopt an alternative approach, adapting the design of artificial reefs to the specific characteristics of the ecosystem to be enhanced. In this way, it will be possible to determine the potential positive impacts of ARs before their installation. This paper presents a general and integrated conceptual framework to assist in the design of AR units by adopting an ecosystem ecology (EE) perspective. It consists of three main parts. In the first one, starting from an initial geometry, EE principles are used to include modifications with the aim of improving autotrophic resource pathways  and leading to a habitat enhancement . The second part of the framework is a new dimensionless index that allows the user to select the best AR unit design from different alternatives. The potential impacts on the ecosystem in terms of energy, nutrient cycling and shelter are considered for such a purpose. Finally, a general hydrodynamic methodology to study the stability of the selected AR unit design, considering the effect of high waves under severe storms, is proposed. The framework is applied through a case study for Galician estuaries. Research on artificial reefs (ARs) is a multidisciplinary activity that has attracted the attention of a great number of researchers all over the world ,2. In faOverfishing and pollution have led to a marine habitat degradation, endangering the exploitation of its resources . On the As pointed out by Carral et al.  new measOn the other hand, according to Daza-Cordero et al. , hard suThe performance of artificial reefs was traditionally assessed through population and community ecology through approaches based on experimental and field observations to quantify fish density, biomass or composition, among other indicators linked to the species of interest. Nevertheless, some authors  to propose a conceptual framework to assist in the design of artificial reefs according to the specific characteristics of the ecosystem to be enhanced, (ii) to propose a comparative index (AR-Ecosystem Index Transformation or AREIT) and (iii) to develop a hydrodynamic methodology to evaluate the stability of AR units considering high waves and surfaces.The conceptual framework will be based on EE principles; therefore, the relationship between the design of an artificial reef and the secondary production of the ecosystem  through The framework proposed in this study consists of three main parts as can be seen in Together with the input information , MEEM usAs will be explained later in When the desired AR unit design is obtained, the third part of the framework comes into play, that is, the stability study. This analysis may lead to the inclusion of a concrete slab with a certain height H in .It is important to remark an alternative use of the proposed framework that affects the nomenclature of The remainder of Food web dynamics are an important part of ecosystems. An artificial reef can create, on a nearly deserted area, a system with its entire food web, functioning as an “energy trap”. Consequently, nutrients are recycled and incorporated into the food web, instead of being deposited in the ocean floor for thousands of years .In other words, a submerged structure interacts with the aquatic environment, creating new attachment locations. Therefore, sessile organisms in a planktonic larval stage circulating through sea currents find new attachment surfaces. In this way, artificial reefs are first colonized by algae and sessile invertebrates, and their energy is consumed by vagile organisms such as crustaceans and herbivorous rockfish. These and other organisms will spawn at the artificial reefs and, predators and top predators will also find a place to shelter, feed and reproduce. As a result, artificial reefs increase both the energy and nutrient availability, boosting the food web of a specific ecosystem .Plants exercise control over the energy of the ecosystem, since they delimit the amount that is received. Consequently, the productivity of marine ecosystems may be limited even if there is high nutrient availability, particularly in cases where there is not enough substrate for benthic organisms to settle . Under tOn the other hand, artificial reefs cause changes in the velocity field of the water , favouriOne of the reasons fish aggregate around ARs is local upwelling and back eddy effects ,38,39. MIn describing the foundations of the MEEM model, it is necessary to consider a baseline design for the AR unit. In this case, taking into account the logistical processes of the management and enhancement of an estuary in Galicia by installing AR units , a cube As previously indicated, MEEM is aimed at guiding the design of an AR by improving the two autotrophic resource pathways that an ecosystem has  and increased nutrient circulation (phytoplankton)), and also by leading to habitat enhancement.According to Bohnsack  artificiFrom Vertical surfaces increase the available substrata, while at the same time collect less sunlight than horizontal planes. Including an interior cavity  with an opening at the top can serve to increase the sunlight collection. Furthermore, lateral holes (connecting the interior of the AR unit with the exterior) in vertical surfaces reduce the substrate availability but favour nutrient circulation inside the AR. Lemoine et al.  state thEM (energy modification index), NM (nutrient modification index), and HM (habitat modification index), Equation (1).The index proposed in this section measures the potential transformation that the ecosystem may experience after the installation of one AR unit in comparison with a basic or reference design. It consists of three partial indices: AREIT index is a comparative, dimensionless parameter and a higher value is associated with a higher positive impact on the ecosystem in comparison with a reference design. The same is also applicable to the three partial indices. More information on how to interpret these parameters will be provided later in this section.In Equation (1), it has been assumed that the three dimensions or partial indices present the same weight or relative importance. Nevertheless, this may vary from one ecosystem to another, depending on the particular needs. Consequently, Equation (1) can be easily modified to consider this possibility, by including the weight of each partial index. On the other hand, it is important to remember that the application of this index is limited to those cases in which the reference design contributes to the improvement of the ecosystem in terms of energy, nutrient availability and habitat. The EM is estimated through Equation (2):vS is the total area of the external and internal vertical surfaces of the AR unit exposed to sunlight, measured in cm2. Similarly, hS is the total area of the external and internal horizontal surfaces of a specific AR design, expressed in the same units. vrS and hrS are analogous to vS and hS for the basic or reference AR design. Moreover, evf and ehf are the dimensionless exposure factors for vertical and horizontal surfaces and they adopt the values 0.5 and 1, respectively. It is important to note that EM takes a value of 1 for the reference AR design. Accordingly, EM values below 1 are not desirable. On the contrary, the higher this partial index is compared to the reference case (EM = 1), the better the AR design is in terms of its contribution to the ecosystem energy increase. The same is also true for NM and HM indices in terms of nutrient and habitat enhancement. On the other hand, Equation (2) was designed for ARs that do not present slope surfaces. Nevertheless, it can be easily adapted to designs with inclined planes by including new exposure factors varying between 0.5 and 1, depending on the inclination angle.The impact on the energy of the ecosystem depends on the primary producers and, consequently, on the AR attachment surfaces exposed to sunlight. Therefore, NM index. The reader should bear in mind these both effects are correlated, since upwelling always leads to back eddy formation. Therefore, by taking into account the upwelling effect, the back eddy phenomenon is also implicitly considered. Equation (3) is used for estimating NM:The positive impact on the nutrient transfer among the organisms of the ecosystem depends on the modification that the AR unit introduces in terms of nutrient cycling. In other words, both the upwelling and back eddy effects come into play at the time of defining the upwellingS is the total area in cm2 of the AR surfaces that contribute to the upwelling and back eddy effects, that is, vertical ones, from which the area of the lateral holes is subtracted. Lateral holes communicate the interior of the AR unit with the exterior, generating a permeability effect that reduces upwelling and back eddying. Consequently, Equation (4) is used for calculating upwellingS:rvf is the roughness factor for the vertical surfaces. This factor, as its name suggests, measures the roughness of the material and depends on its type and finishing. The same roughness factor is assumed for all the vertical surfaces, since all of them are usually made of the same material with the same finish. Nevertheless, Equation (4) can be easily modified for other different cases. Furthermore, n is the total number of lateral holes. There can be holes with different dimensions. Consequently, lh,iS is the surface in cm2 of each one of the holes “i” with r,if its corresponding roughness factor. As was the case with Equation (2), Equation (4) is valid for AR designs in which all surfaces are vertical or horizontal. For those cases with sloping surfaces, this equation must be modified, by taking into account the sloping surface areas with their corresponding roughness factors. In this sense, the closer a specific surface approaches verticality, the higher its contribution to upwelling and back eddy effects. Therefore, it will be necessary to consider and additional dimensionless factor to reflect this fact, varying between 0  and 1 . The computation of upwelling_rS is analogous but, this time, for the reference design.In previous equation, HM) is estimated by applying the following equation:Finally, the habitat modification index (nest_cavitiesS (cm2) is calculated from Equation (6), where nc is the number of nest cavities and n,jS is the surface area of nest cavity j. nest_cavities_rS is estimated by applying Equation (6) but, this time, for the reference AR design.As can be deduced, it depends on the number of nest cavities and their corresponding areas. There can be nest cavities with different dimensions. As a result, AREIT index under 3  implies that the AR design presents an overall worse performance than the reference one. By contrast, values higher than 3 mean that the AR design generates a higher positive impact on the ecosystem (EE perspective) than the reference case. It is important to note the AREIT index is a comparative parameter. In other words, it measures how good a specific design is compared to a reference one with the same volume. Comparing two designs with very different sizes and volumes using this indicator can lead to wrong conclusions. Furthermore, the ultimate objective of this index is to help the decision maker identify the design with the greatest positive impact on the ecosystem per unit of volume (occupying the same space).In light of the above, an AREIT. Therefore, by estimating the partial indices on an individual basis, it will be possible to identify the design that most improves the specific weakness of the ecosystem. As a result, the graphical representation in a three-dimensional space with three axes  is proposed  considered in proposed .EM and NM axes allows the user to quickly identify the improvements achieved according to the two autotrophic resource pathways that delimit the primary productivity. The remaining axis provides information on the new habitat possibilities for sheltering, feeding and reproducing. The position of the plane defined by the three partial indices of a specific AR design in comparison with the plane of the base case serves the same purpose.The AREIT. However, as previously stated, the conceptual framework presented in this study is a starting point for the design of AR units according to EE principles. On a practical level, a compromise solution between the design provided by the framework and other potential factors will need to be found. Despite the advantage of being able to predict the potential impact of an AR unit design on the ecosystem through AREIT, experimental and field observations are still valuable, and they can serve to validate and, if necessary, to modify the index proposed.The reader should bear in mind that there are other ecological factors and processes as well as other social, economic and environmental issues that can affect the design of AR units and that are not considered in sH, in the Ría de Ares-Betanzos  under deep-water wave conditions for a return period rT = 20 years and NW direction is plotted. It can be observed that under these conditions, extensive areas of the outer and middle estuary present sH values greater than 5–6 m, which in turn would correspond to maximum wave heights, maxH, of about 10 m.The study of the stability of ARs should be based on a thorough analysis of their interaction with the hydrodynamics at the site where they are planned to be installed, with special consideration of extreme conditions with large wave heights, which are usually regarded as the major forcing agent in the design of coastal structures, and in particular of aquaculture farms . This isAs a result, the analysis of the stability of an AR configuration considering wave action should be divided in two phases of the same process: (a) a hydrodynamic characterization where the hydrodynamics generated by the most relevant forcing agents under extreme conditions are assessed, amongst which the estimation of the so-called design wave  at the AR site is usually of paramount importance; and (b) a force analysis in which the behaviour of the AR under the action of the design conditions defined in (a) is addressed. In the following paragraphs, key aspects and a possible procedure for developing an accurate AR stability analysis are described. For the sake of clarity, in As previously stated, waves are usually the most relevant hydrodynamic agent under extreme conditions in most areas of interest for AR operation. Reliable estimation of the wave field, and on its basis, of the design sea state or wave for a specific coastal structure, requires analysis of a large dataset of sea states. Field data can be used to develop a thorough study at specific locations where a buoy has been in operation over extensive periods of time. Unfortunately, instrumental data is not usually available at the locations of interest for AR installation. In this context, once the most suited locations for AR operation are identified, a buoy or ADCP (acoustic doppler current profiler) could be installed at these sites; however, the resulting dataset would cover a limited period of time, which would not be adequate to determine the design wave conditions. In order to overcome this, meteorological agencies run global wind–wave models, which consider wind field estimations for numerically generating long-term wave data over large areas, leading to an accurate description of the wave field at sites where instrumental data is not available. Unfortunately, these models usually do not consider the interaction of the wave field with the bathymetry , and undIn this regard, as previously stated, a large proportion of ARs are intended to be located in coastal areas with large biological production, such as estuaries, generally sheltered to a certain extent from wave action; however, during severe storms, as stated, wave action is usually the most relevant hydrodynamic forcing agent in these areas. This results in the need to consider two additional major aspects when defining the downscaling procedure to be implemented.N is the density of wave action, t stands for the time, C represents the propagation velocity in the geographical space, θC and σC the propagation velocities in the wave direction, θ, and relative frequency, σ, and S stands for the source or sink term.First, resulting from the usual coastal configuration of estuaries and the depth-limited areas of interest for AR installation, the highest nearshore waves at the AR site may not correspond to the highest offshore waves, thereby requiring the analysis and selection of many conditions to be propagated towards the area of interest, for which the implementation of wave spectral numerical models is the common valid procedure. Spectral models compute the wave spectrum evolution by solving the action balance equation, Equation (7):L×10−1, where L is the wavelength) is required [Selection of the wave conditions to be analysed should be conducted using methodologies developed ad hoc, such as those provided by IHCantabria ,54, or arequired . AnotherFinally, it is important to note that the forces exerted over the AR configuration by nearshore currents either generated by the tide, river discharges, wind or baroclinic flows are expected in most cases to be virtually negligible compared to those caused by the action of an extreme wave. However, certain areas of interest for AR operation could be subject to strong currents—usually tidal currents—which should also be considered in the stability analysis, both for the definition of the design hydrodynamic conditions to be analysed in part (b), and for the analysis of the complex wave–current interaction process, which could also affect the definition of the design conditions. To this end, the implementation of shallow water numerical models  has been shown to provide accurate results of the flow field in coastal regions, and more specifically in estuaries.Once the design conditions are determined at the site selected for the installation of an AR, its stability should be analysed (part (b)), and on this basis, actions defined  if necessary, to ensure that the reef does not overturn or slide. To this end, several approaches of different complexity ―and therefore of computational effort― are available, whose selection depends on the level of accuracy required. In this document we identify three procedures : (i), (ii) and (iii) (from higher to lower complexity and accuracy).An accurate analysis of the stability (i) requires the implementation of CFD modelling, in which the selected AR configuration is considered, subject to the action of the design conditions previously defined. In addition, in the case of possible significant modifications in the wave field in the surroundings of the AR resulting from the presence of a complex bathymetric configuration and reduced depths, which may not be accurately captured by the spectral propagation model, the bottom configuration in the proximity of the AR can be easily represented in CFD models in the form of a bottom slope. This type of model demands a high computational cost resulting from the different orders of grid size that are necessary to implement . Furthermore, analysis of the behaviour of an AR ideally requires the generation of many waves (200 or more) in order to decrease the sampling variation of the wave statistics  and to iThe previously described methodology has emerged as the most accurate approach; however, it consists of a complex procedure which can be significantly simplified when conducting preliminary studies. First, in procedure (ii) a CFD model can be used to accurately compute the characteristics of the design wave conditions at the location of interest instead for the analysis of the hydrodynamics–AR interaction. In this case, once the hydrodynamic characteristics are computed at the AR location, the stability analysis can be carried out through empirical or analytical formulations traditionally used in coastal engineering for submerged structures, or designed ad-hoc for an AR configuration . Among tIt is important to highlight that in the case of areas subject to strong currents, as previously explained, they should be incorporated in the definition of the design conditions and considered in the force analysis following the aforementioned procedures.AREIT index.This section is divided into two subsections. In The cubic shape was used since this provides a proper upwelling, as will be shown below. This cube has several cylindrical holes. The cylindrical shape of the holes was adopted for constructive reasons, since the concrete manufacturing of a cylindrical hole is easier than other shapes . A 600 mComing back to the design of A CFD model was developed, validated with experimental measurements in a previous work . This isAs can be seen in Regarding the communication along the AR, the velocity field illustrated in The proposed design favours the exposure to sunlight as well as current and sedimentation processes. These factors strongly influence both the settlement of individuals and the evolution of the community . Rouse eNew habitat is provided by the inclusion of nest cavities (20 or 30 cm diameter) in the lateral faces of the cube. They serve as nests for cephalopods and crustaceans. Furthermore, these cavities imply that a greater proportion of the AR unit serves as habitat for benthic species, which can result in higher productivity . In factAREIT index. As previously explained, a reference design must be considered for such purpose. The starting design presented in HM partial index . Therefore, another alternative design was considered as reference for this section. It is also a cube with an edge of 1.5 m but, in this case, with a reduced number of nest cavities (HM contribution), as can be seen in The final AR design presented in AREIT index as well as the corresponding partial indices for the final design. As explained in EM = 1, NM = 1 and HM = 1). Consequently, its AREIT index is equal to 3. The results for the final design in terms of EM, NM and HM should be higher than 1 in all cases. This would mean that it is better than the reference in the three dimensions considered in this study. In this case, this is true as can be seen in From the information included in NM value of 1.2, which is 20% higher than the reference index. In other words, the proposed design considerably improves nutrient circulation in comparison with the base case. Furthermore, this is achieved by maintaining (even slightly increasing) its capacity as a support for vegetal substrate (EM = 1.02). At the same time, the positive impact in terms of habitat modification that the proposed design produces is considerably higher than that of the reference case (HM = 1.67). The AREIT index for the proposed AR unit takes a value of 3.89. This figure, in comparison with the reference value of 3, gives the decision maker a quantitative idea of the extent to which the proposed design better enhances the ecosystem. Consequently, it can be concluded that the proposed index is suitable for comparative purposes with the considerations made in In fact, the upper central hole together with the lateral ones generated a AREIT) that allows the user to select among different alternatives by comparing their contribution to energy, nutrient cycling and shelter. Finally, once the desired design is obtained, the third part of the framework comes into play. This is a general hydrodynamic methodology to study the stability of AR units, considering the effect of extreme waves on their surfaces. As a way of validating the methodology proposed, a simple example for the particular case of Galician (in the northwest of Spain) estuaries was considered. The main conclusions from this study are:This study proposed a new general and integrated conceptual framework intended to guide the design of artificial reef (AR) units by adopting an ecosystem ecology (EE) perspective, that is, by taking into account the particular characteristics of the ecosystem to be enhanced. The framework consists of three main parts. In the first one, the designer or decision maker starts from a basic initial geometry that is site-dependent and employs the Marine Ecosystem Ecology Model (MEEM) to include modifications. Logistical and structural constraints are considered during this step. As a result of following the EE principles, several AR unit designs may arise. Consequently, the second part of the framework is a new comparative and dimensionless index  proved to be a promising metric for predicting the positive impacts that different AR unit designs can have on a specific marine ecosystem. However, experimental and field observations, after the installation of AR units, are still necessary for several reasons. On one hand, AREIT provides comparative and relative results, but it does not give and idea about absolute impacts, although there is a connection between them. On the other, field observations may serve to improve the proposed AREIT index, in case of being necessary.The The application of the MEEM tool to the starting AR unit design for Galician estuaries led to the incorporation of an interior cavity  that improves the reception of sunlight. It also led to the inclusion of lateral holes that, together with the central one, favour nutrient circulation. Nest cavities were another result of applying the MEEM tool. Although these modifications provided good results for the particular case of Galician estuaries, they are likely also to be valid for other marine ecosystems. Obviously, the number and dimensions of the holes and nest cavities, as well as the initial geometry, will depend on the specific characteristics of the ecosystem to be enhanced.The analysis of the AR’s stability under wave action is a key aspect in most areas with interest for AR operation. To this end, an accurate estimation of the wave conditions at the AR site and analysis of the wave–AR interaction by considering complex procedures are necessary. In the case of areas subject to strong currents, they should also be considered in the AR stability analysis.The proposed AR unit design for Galician estuaries is only one of the several options that can be obtained by using the proposed framework. This solution is suitable for those ecosystems in which a balance among energy uptake, nutrient circulation and habitat enhancement is needed.


Without doubt, the High Luminosity Large Hadron Collider (HL-LHC) is one of the major projects in particle physics at the high energy frontier in the upcoming decades. Planned to come into operation mid-2027 it will substantially increase the amount of proton-proton collisions at 14 TeV delivered to the LHC experiments with a planned integrated luminosity of 3000  It became soon obvious to the particle physics community that an HL-LHC would offer a unique chance to significantly advance our current understanding of particle physics and a large variety of measurements will get into reach for the first time , 2. ExamThe European Strategy for Particle Physics which was approved by the CERN Council in June 2020  prioritiWhilst the intention here is not to decrease the engagement with the HL-LHC (quite the opposite), it is still inevitable: Now is the time to start engaging with the new proposed projects and become a leader in one of these new activity areas. Similar tendencies were observed during the last years of running of the LEP, HERA and the Tevatron colliders where collaboration sizes dwindled whilst large data sets were still being recorded which subsequently were analyzed in smaller groups; some analyses were not carried out at all due to the missing person power. The long time scales of the HL-LHC will presumably pose a problem for PhD students who generally need to publish on a timeline of a few years in order to have a chance for a career in particle physics. The less opportunities for publications, the less students will join the experiments and the less person power will be available to sustain the experiment and conduct world-leading measurements. Often this is compensated by recruiting new collaborators into the collaborations which are geographically more dispersed with less means to travel regularly to the experiments. At the same time, travel might become more sparsely available, given immense effort to reduce carbon emissions to limit climate change , 5.To address these challenges we – as a community – need to find and document new ideas for LHC physics during Run-4 and beyond. In particular we need to ask ourselves, which physics measurements can be done beside a handful of flagship analyses? What can be done to maximize the physics output? How can we improve detector performance and optimize the use of resources? What are our long term goals for the collaborations and their culture?With the Covid-19 pandemic and the related travel restrictions an explosion of experiments with virtual conference formats happened – either forced by the pandemic (as e.g. the International conference of High energy physics - ICHEP2020 in “Prague-on-the-net” or the Large Hadron Collider Physics Conference for which both the The new ideas presented ranged from new searches and measurements during the HL-LHC phase, over innovative analysis methods and tools to new experimental setups at the LHC. In addition, overview talks on the challenges and opportunities from the experimental and theoretical communities have been given and discussed.The schedule was arranged in two live time slots containing the same contributions with presentations given by authors residing in that particular time zone.


Cranial base tactics comprise the regulation of tiny and complicated structures in the domains of otology, rhinology, neurosurgery, and maxillofacial medical procedure. Basic nerves and veins are in the nearness of these buildings. Increased the truth is a coming innovation that may reform the cerebral basis approach by supplying vital physical and navigational facts brought together in a solitary presentation. In any case, the awareness and acknowledgment of prospective results of expanding reality frameworks in the cerebral base region are really poor. This article targets examining the handiness of expanded reality frameworks in cranial foundation medical procedures and emphasizes the obstacles that present innovation encounters and their prospective adjustments. A specialized perspective on distinct strategies used being produced of an improved realty framework is furthermore offered. The newest item offers an expansion in interest in expanded reality frameworks that may motivate more secure and practical procedures. In any case, a couple of concerns have to be cared to before that can be for the vast part fused into normal practice. Augmented reality (AR) has gained tremendous adoption over the past two decades, but its use in the workplace is still being developed and evaluated. AR is a natural environment in which certified products are augmented with PC-generated virtual information. These partner markers are available in a variety of designs including sight, hearing, touch, smell, and taste. Augmented reality systems can be divided into two types, considering the level of sensation present in a given environment. That is, visible (momentary) and semi-determined (hidden) (hidden). Spectacular augmented reality hints at a structure in which the client articulates a real-world environment and additional data are projected onto it. However, translucent AR suggests a system in which the client is somewhat limited by the authenticated climate and cannot receive proprioceptive information about the body directly. In the workplace, AR can essentially be transmitted through glasses, shows, loudspeakers, gloves, joysticks, or jointly controlled robots. AR was first introduced in the 1960s under the name of “Theatre of Engagement” and takes the form of overlapping a real room with modern items .All image steering coordinate systems adhere to three basic principles: obstacles, bearings, and orientations . (i) ConExperts have approved imaging intercession procedure to remove visceral perversion that weakens the impact of standard imaging schemes such as endoscopes and microscopes. Image-based moderators have been shown to outperform standard strategies for both dominant outcomes and less disturbance . CriticaThe most important benefit of AR in clinical interactions is the ability to view plans and recover hidden data without changing the mindfulness cycle. AR has been used for mindful organization, internal visualization, and deliberate pathway and target structure control , 6, 7. IThis article constitutes several review articles on the level of explicit termination that gives interesting fact on the use of augmented reality in neurosurgery, otolaryngology, and maxillofacial surgery –24. HoweClinical management of the base of the skull is one of the areas that have benefited most from improved imaging capabilities . This arThe base of the main skull is sometimes accessed through the nasal cavity using an inflexible endoscope inserted through the nostrils. A watchful view is displayed on the screen in front of the wizard. Research in this field includes accurate information on actual resting places according to 2D images and endoscopy headers and major limitations of 3D courses. In case of doubt, actual service stations will be changed or deleted due to previously used clinical drugs, contamination, or unnecessary waste . TherefoThe flat bottom of the skull is often pulled closer through the stony bone containing the ear and important veins . This constituency requires extremely high-contrast tools and careful interaction. Sensory specialists break through the rock walls under meticulous reinforcement mechanisms, revealing actual development layer by layer and their progress into the cerebellar point and intracranial space of the pyramidal space . HoweverA more accurate analysis and proactive planning have made management strategies in this area less cumbersome. Mortality and severity of interventions were significantly reduced . Until tThis article analyzes several strategies presented using AR methodologies in specific real-world areas  and describes the different cycles used to treat interesting difficulties in this area. This seemed to be a smarter strategy than a strategy based on prudent qualities. Typically, these outlines are not provided in writing.In this computed review, we will describe the efforts of AR on modern neurocurrent structures and the application of AR to clinical treatment in noncritical compulsive cranial settings. Then, around this point, let us take a concrete view of essential augmented reality. Finally, we will explore and test various methods of AR management and future contact with AR progression before AR is widely accepted as clinical therapy at our headquarters.In this review, we used a combination of the terms such as augmented reality, coordinated imaging, search, and medical procedures using the base of the skull, ears, and nose to fake a computerized study of public review dated October 2021 in “PubMed” in terms of otolaryngology, nasal, cranio-maxillofacial, sinus, base cranial, nasal cavity, otolaryngology, transitional bone, head and neck, and practical neurosurgery. The Fundamental Mission generated 250 tests. It eliminated duplicates and moderated the legitimacy of the review. We linked 45 tests to reviews to review and cross-reference 4 valuable articles.Neuronavigation constructs are primarily aimed at directional developmental resection in neurosurgery. The incredible unpredictability of neuroanatomy has made it imperative to create incredibly accurate connections between patients and various devices and devices. Modern neuronavigation structures show central, coronal, and sagittal perspectives on a patient's preoperative CT or MRI, regardless of the screen. In addition to preoperative photographs, the application areas of various instruments are traced and clearly marked on the real plane . This prObviously, the impact of augmented reality systems was far more exclusive to less experienced professionals. Such kind of systems can also be useful for teaching and preparing for causes. AR could replace neural navigation technology. Unambiguous AR constructs have been developed that either provide exploratory information about underlying cognitive sources or provide direct patient/possible perspectives  6, 7, 4, 47. In A variety of prudent options are available for your skull crafting strategy. The open clinical strategy is the most common option for incisions of the face and skull to obtain target structures. Although this structure is best suited for objective planning, it creates more tissue damage around the methodology and may include organ dissemination, frustration, pain, anxiety, and prolonged postoperative stay in the center . SimilarDifferent mechanistic approaches to AR are available by region name, but these mechanisms must match and apply to the base of the cranial region, keeping ergonomics in mind and carefully addressing the need for accuracy, consistency, and well-being of that particular region. In the image-oriented procedure, it is very important to build a general three-dimensional device inside the studio as a reference method. This usually ends with monitoring equipment changing patients, devices, and various devices . These dCoordination is one of the most essential systems in this kind of equipment. A strategy for combining all the great vehicles is to deliver results within reasonable limits. The basic rule is to use as a reference a generic verifiable item with a predefined scope. The various subsystems that combine image capture and display devices, navigation ideas, surveillance designs, and sophisticated fixtures must first be coordinated before they can be used.Each supported computer requires a careful tuning strategy to ensure accuracy. For certain projects, coordination must be cultivated before each rigorous task , while Previous AR structures have used ISG point size indicators or observation to adjust aspect ratio devices , 58, 64.A key step in a prudent AR machine is registration. Registration creates associations between interesting gadgets and special effects and solidly homogenizes them into a single mechanism. Recruitment is usually described as a structure of change that includes variables of rotation, interpretation, and deviation. Inclusion can be described as device , order , or degree  . The kind of registration your AR platform requires depends on the gadget you use. Getting started is the most basic methodology in a carefully crafted augmented reality framework because any issues that occur within an hour of this procedure will propagate for the rest of the journey. The most commonly used recruitment techniques are based on point-and-shape-based approaches Figures  and 6. POnce recorded, listening to music on the patient's movements or holding the device is a great way to keep a great device connected. Like the registration process, it creates a transformation to show the entitlements between the old and newer stages. A huge part of the design is electromagnetic and optical design –65, 74. Albeit new designs had been set up that give specific sorts of benefits yet, inferable from high precision, optical age stays to be one of the most extreme regularly utilized constructions inside the cranial base area. Electromagnetic and optical global positioning frameworks need strong reference outlines that fuse novel markers. To forestall this issue, different types of CV-based techniques have been introduced to tune any general movements among patients and picture catch gear , 71, 73.With maximum AR structure, the result is a two-dimensional image that ends up lacking persuasiveness. Similarly, when using a MIS strategy, the actual site is not immediately clear. This increases the need for augmented reality devices to access all the sensitive equipment and deliver data to healthcare professionals with interpretable technology.The image on the left is an endoscopic view of the tympanic layer, and the image on the right is an AR exit showing the segmented central ear structure. Potential targets of the central ear, discernible only through magnified truth, have been indicated by (a) hammers, (b) anvils, (c) oval spears, and (d) circular spears. A discriminative model has been proposed to distinguish gadgets to enable technicians to gather the specific responsibilities of a device in a three-dimensional global realm. As with subsequent developments, advanced designs used electromagnetic and mechanical verification devices corresponding to devices , 75, 76.Replacement units by design have also been favorably presented , 9, whicz directions. However, the introduction of improved data is impossible due to the helpless execution of the gadget. A head-snared show (HMD) is an always-on device that includes a tiny show in front of one (monocular) or each (binocular) eye. Some HMDs also capture pictures for viewing by clients. With care, the helmet cap can overlay PC-generated virtual objects throughout the movie. This can be done both electrically and partially through intelligent radiation. Tablet-like HMDs are primarily used in a limited number of cranial-based projects and are now primarily used within cranio-maxillofacial areas that do not include very sensitive areas. In a rather vivid environment, it is possible to impose secret physical frames and route information on the patient. Binocular HMDs are not fixed to have better performance than single HMDs. Considering the effect of three-dimensional effect while maintaining good shape with careful handling of the head base, it was concluded that the use of binocular HMD resulted in a normal 35% improvement in accuracy and time of each conditioner compared with the monoscopic inventive reasonable [We analyzed different strategies for recognizing the consequences of augmented reality, including traditional screens, the age of wearables, and viewing and projection gadgets created for clinical exercise. A few examples of augmented reality shows are shown in asonable . The devasonable . Inattenasonable . StylishThe base of the skull contains the smallest and most fragile anatomy in the human body, and for image-oriented frames to function, their accuracy must be less than 1–2 mm within the elements of the workspace environment , 8, 80. All the above factors are key characteristics of AR machines and require evaluation. For AR innovations to be effective in skull-based methodologies, analysts must focus on 1 mm sub-defects for each of the standards. Figures In the form of the project, the experts used a photo-centric scheme. From rigorous symptom-based interventions to intraoperative imaging, routes, and easy-to-use assessments, image-based innovations have a fundamental role in expanding the impact of treatment. The clinical goal is to overcome the shortcomings of outdated strategies that can complicate intraoperative appraisement and lead to inadequate execution. AR time has brought an additional perspective to such a framework. The combination of augmented reality with clinical imaging and atomic therapy (for cancer readers) provides specific physical local finding and integration of pre- and intraoperative data in an ergonomic and environmentally friendly methodology. The basis of the AR machine at the base of the skull is the precise reality of a very dangerous scaffold with veins and major nerves to prevent unwanted situations from occurring. In AR devices, virtual tricks can be superimposed on the real world as an approach. (a) Annotated or advanced models assembled in a pre-planned strategy are projected onto the sophisticated film. (b) The real world of the discreet film is combined with the virtual image. Previous versions of augmented reality used standard sensors such as optical and electromagnetic devices to communicate with interesting devices and customize every movement. The first bundles in the late 90s used electromagnetic observation methods that relied entirely on sensors in the lobby to set up tasks and tools , 64. TheEase of implementation and preparation before useMinimum calibration procedureA general interest in virtual objects and photographs in the real worldQualitative (sub-millimetric for science)Minimum registration periodSingle fusion of surgical equipmentReduced burdenDepth indication of both virtual objects and devicesOverlay virtual objects only when neededHD resolution and high frame rateMinimum latencyAdaptable appropriate contrast of the target image throughout the projectionAt this stage, it has been found that AR is not best at providing meticulous accuracy and guidance, but further limits the duration of activity . HoweverA new investigation of endoscopic-based skull treatment therapy has been demonstrated that the impact of augmented reality structures on the result depends on the working revel of the specialist : AlthougNatural outlines may be proposed to students giving an all the more full and far-reaching clarification of the life structures and running statute of each organ. As per a new survey, 81% of undergrads energized the consolidation of any such device into their residency programming albeit 93% allowed its usage inside the activity room .Artificial intelligence-based augmented reality has been applied for providing support to investigation and ID in other important disciplines. The most exactness got is 84% that is superior to uninformed specialists (45%) all things considered more awful than master specialists (95%) related to a new glance at , 86. ProAugmented reality is a solid device, which has a possibility to change the cranial-based careful treatment through expanding the careful experience and giving additional data in a protected, easy-to-use, and instinctive strategy. Late examinations show that route structures fusing AR convey comparable outcomes to standard route structures as far as exactness with better ergonomics and AR has been utilized in a few parts of the functional control such as forecast, medical procedure preplanning, navigational, intraoperative imaging, and MIS strategies. AR furthermore might be powerful for instructing capacities. In any case, extra exertion actually must be led to expand the state-of-the-art country, gain the most extreme insurance and trustworthiness, and diminish machine cost. Recent fads in advanced mechanics, representation, area sensors, haptics, engineered insight, and PC innovative and farsighted methods may all help the AR age in its large acknowledgment among specialists. Even though AR provides an efficient way to visualize the cranial base surgery, it is not possible to interact with visualize objects so in future integration of both augmented reality and virtual reality (VR) can be used to interact with visualize objects of cranial base surgery.


Allergic rhinitis (AR) represents a global health concern where it affects approximately 400 million people worldwide. The prevalence of AR has increased over the years along with increased urbanization and environmental pollutants thought to be some of the leading causes of the disease. Understanding the pathophysiology of AR is crucial in the development of novel therapies to treat this incurable disease that often comorbids with other airway diseases. Hence in this mini review, we summarize the well-established yet vital aspects of AR. These include the epidemiology, clinical and laboratory diagnostic criteria, AR in pediatrics, pathophysiology of AR, Th2 responses in the disease, as well as pharmacological and immunomodulating therapies for AR patients. Atopic allergic sensitization is defined by the production of immunoglobulin E (IgE)-mediated immune response toward allergens. Allergic rhinitis (AR) is a common disorder that afflicts 400 million people worldwide and it represents a global concern as its prevalence has increased over the years . AR usuaAllergic rhinitis prevalence has increased significantly since the 1990s . It is rPrevalence of AR has increased with years due to several risk factors including global urbanization as shown by several studies comparing AR prevalence in urban settings with rural areas , 18. ThiSmoking, however, did not show a significant association with the severity of nasal symptoms in AR but usually impacted patients with chronic rhinitis , 24. ConThe economic impact of AR is significant where the total annual cost of self-reported AR in Sweden is estimated at €1.3 billion  and up tAR is characterized by the presence of nasal and non-nasal symptoms. Nasal symptoms include anterior or posterior rhinorrhea, sneezing, nasal blockage and/or itching of the nose . These sHypersensitivity reactions can be observed in AR, bronchial asthma, allergic conjunctivitis, allergic dermatitis, food allergy and anaphylactic shock . Over 30In terms of AR severity, it can be classified as mild and moderate/severe based on the AR and its Impact on Asthma (ARIA) guidelines . It is min vivo skin tests including skin prick test  and intradermal (intracutaneous) skin tests (IDST), and in vitro serum allergen-specific IgE (ssIgE) immunoassay. SPT and ssIgE immunoassay are the most common laboratory tests to determine the causative allergen(s)  , 31. Howergen(s) , 32. SPTergen(s) .ssIgE immunoassay utilizes commercially available test panels which are more costly . It is aAnother uncommon diagnostic test for AR includes intradermal skin testing (IDST) in which tiny quantity of allergen is injected into the dermis with a hypodermic needle for the diagnosis of IgE-mediated allergic conditions . Other aDiagnostic criteria are generally broad and must reflect the different features of a disease , with a view to accurately identify as many patients with the condition as possible . Due to However, for patients to be diagnosed with AR, they must have clinical symptoms and possess laboratory characteristics as discussed in the previous section. AR patients must encounter two or more of the following clinical symptoms for more than 1 h on most days: (1) Watery rhinorrhea; (2) Sneezing, especially paroxysmal; (3) Nasal obstruction; (4) Nasal pruritis; (5) With or without conjunctivitis. When individuals present with clinical symptoms of AR, allergy laboratory tests are conducted for confirmation.Dermatophagoides pteronyssinus, Dermatophagoides farinae and Blomia tropicalis) tested on an AR patient who attended the ORL-HNS clinic of Hospital Universiti Sains Malaysia, and each wheal size was greater than 4 mm. The SPT protocols were approved by the Human Research Ethics Committee of Universiti Sains Malaysia .In skin tests, positive result is considered when the wheal-and-flare reaction occurs on the skin test site after 20 min of exposure to allergens. For SPT, positive result must demonstrate wheal  size in diameter of ≥4 mm , 47. FigThe performance of any diagnostic criteria is dependent on the prevalence of the disease in a given geographical area or clinical setting . AR diagnostic criteria are summarized in 2010) have shown higher prevalence of AR, asthma and aeroallergen sensitization in children exposed to urban environment in their early age compared with those exposed to rural environment  as well as differential diagnosis based on the clinical symptoms suggestive of AR but not evidence of systemic atopy . A very Type I hypersensitivity is an allergic reaction mediated by IgE antibody in response to allergens . Type I + T cells, resulting in differentiation of naïve CD4+ T cells into allergen-specific Th2 cell. Cytokines such as IL-4 and IL-13 released from the activated Th2 cells interact with B cells to produce allergen-specific IgE. This allergen-specific IgE binds to high-affinity Fc receptor for IgE (FcεR) present on mast cells, leading to mast cell activation  class II molecule. The antigen complex and the MHC class II molecule serve as a ligand for T cell receptors on naïve CD4tivation , 59, 60.Cross-linking of the FcεR on mast cells causes release of allergic mediators consisting of histamine, proteases and lipid mediators such as leukotriene (LT) C4, and prostaglandin D2 (PGD2) that cause vascular leak, bronchoconstriction, inflammation, and intestinal hypermotility , 61–63. After 4–6 h of allergens exposure, the late phase of allergic response is initiated. In this phase, nasal mucosal inflammation occurs with the influx and activation of a variety of inflammatory cells such as T cells, eosinophils, basophils, neutrophils, and monocytes into the nasal mucosa . RecruitAllergens are typically proteins with molecular weight ranging from 10 to 40 kDa that induce type I hypersensitivity by reacting with specific IgE antibodies , 67. ComMajor indoor allergens  have been consistently demonstrated to be the strongest risk factor for AR . LifestyIn terms of HDM, one of the most common causes of AR, the protease activity of HDM leads to excessive IgE production. In normal physiological state, the level of IgE production by B cells is controlled by a negative feedback mechanism that involves IgE binding to CD23 . Upon binding of IgE/allergen-complexes to CD23, IgE production by B cell is then downregulated . HoweverApart from HDMs, previous reports have demonstrated that pollen allergens also impair tight junction (TJ) barrier function of epithelial cells. Pollens conferred proteolytic activities by degrading the TJ occludin in monolayers of Calu-3 cells , resulted in increased paracellular permeability of the cells . Reduced+ T cells (T Helper 2 (Th2) cells activate type 2 responses by stimulating B cells to proliferate and differentiate into plasma cells through the production of Th2 cytokines including IL-4, IL-5, IL-6, and IL-13 . Th2 cel T cells . The mecTh2 cytokines not only enhance inflammatory cell activation but also may deregulate epithelial cell barrier integrity in allergic disease  , 84–87. Pharmaceutical management of AR rests on symptomatic treatments with antihistamines, nasal or oral glucocorticoids, nasal decongestants and leukotriene receptor antagonists that act as symptoms reliever in AR. Antihistamines is the most utilized first line medication to treat mild AR, however, first generation of antihistamines  are no longer recommended due to various adverse side effects impacting the central nervous system, anticholinergic side effects and cardiac toxicity –93. NeweBesides, intranasal corticosteroid that acts as first-line pharmacotherapy by suppressing immune cells infiltration in AR is effective for both mild and moderate-severe AR in both children and adults . CurrentNext, leukotriene receptor antagonists  block the activity of cysteinyl leukotrienes, an important potent allergic mediator that causes allergic inflammation and various allergic symptoms such as nasal congestion and mucus production , 99. A mTreatment using nasal decongestants reduces nasal congestion symptoms through their agonistic action at α1 and α2-adrenergic receptors on endothelial cells of nasal mucosa, leading to reduced mucosa swelling . AvailabTreatment of AR targeting immune modulation aims to modify the natural courses of AR rather than to cause a shift to an immunologically naive or unresponsive state. In this section, we focused on allergen immunotherapy (AIT) in AR. A fraction of AR patients do not respond toward treatment with conventional pharmacotherapy, thus disease-modifying therapeutic agents are adopted such as AIT. Administration of AIT can be delivered either through subcutaneous (SCIT) or sublingual (SLIT) route. AIT of HDM-SCIT can induce temporary increase in FcεRI expression on DCs, but not on basophils, demonstrating potential tolerogenic roles of IgE/FcεRI signaling in DCs in the setting of AIT .Basophils are important mediators in initiating early phase responses in AR, thus targeting these biomarkers through AIT is promising. One year therapy with SLIT for Parietaria can reduce the threshold of basophil activation which highlights the importance of AIT in treating disease and halting the disease progression . High seAnother independent study measuring SNOT-20 score after SLIT treatment in AR reported a reduction in AR symptoms and improvement in QOL of AR patients . AIT is Increased prevalence of AR and that it is an incurable disease pose major unmet needs to alleviate these issues. AR comorbidities also confer increased health and socioeconomic burden on AR patients. Moreover, diagnosing AR is more challenging in patients with dual AR (DAR), a recently defined AR phenotype in which the DAR patients display perennial and seasonal allergies-related nasal symptoms, and only allergic to seasonal allergies. This indicates the importance of measuring inflammation at local allergic sites which might be different from peripheral inflammation in DAR patients –116. ThuSMNH, HTT, NSMA, and KKW conceived the manuscript. SMNH and KKW designed the manuscript, performed literature search, wrote and revised the manuscript. SMNH prepared the figures and table. HTT, NSMA, and NMS revised the manuscript. All authors have read and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


For some types of cancers, bone marrow transplant (BMT) represents a valid therapeutic support, especially in the case of the necessity of high-dose chemotherapy and radiotherapy. For a successful BMT, it is necessary that a donor’s hematopoietic stem cells (HSCs) correctly reach the staminal niche in the recipient’s bone marrow (BM) and contribute to restore normal hematopoiesis in order to rapidly repopulate BM and provide all the healthy blood cells of which the patient needs. Generally, it takes a long time. Control and accelerate homing and engraftment of HSCs could represent a helpful approach to avoid the complications and undesirable effects of BMT. The evidence that the β-adrenergic system has a role in the BM can be found in different studies, and this leads us to hypothesize that studying this field could be interesting to meliorate the most critical aspects of a BMT. Here, we collected the data present in literature about the role of β3-AR in the BM with the purpose of discovering a possible utility of β3-AR modulation in regulating HSC trafficking and hematopoiesis. G proteins are classified into four families according to the α subunit, inhibitory G-protein (Gi), stimulatory G protein (Gs), G12/13, and Gq with different activities , activation of guanylate cyclase (GC), and formation of cGMP. Therefore, the type of the downstream effectors is determined by the subtype of β-AR that is activated (Adrenergic receptors (ARs) are a class of membrane proteins that mediates the multiple metabolic and neuroendocrine effects of epinephrine and norepinephrine, the two neurotransmitters responsible for sympathetic nervous system (SNS)–induced “fight-or-flight” stress responses. Through the application of different functional and molecular techniques for studying ARs, it was possible to identify three major categories that differ for function and localization: α1-adrenoceptors, α2-adrenoceptors, and β-adrenoceptors  was successfully experimented from 1950 to 1970 by a team under the leadership of Edward Donnall Thomas, whose work was later recognized with the Nobel Prize in Physiology and Medicine .Starting from Thomas’s studies up to the present day, BMT has become the optimal therapy for a wide variety of hematological and nonhematological diseases, including leukemias , lymphomToday, BMT is often helpful in oncological patients who need high-dose chemotherapy and/or radiation therapy. Chemotherapy and radiotherapy can target the tumors because cancer cells divide rapidly, more often than healthy cells. However, BM cells also divide frequently, so high-dose treatments can severely damage or destroy the patient’s BM. BMT represents a valid support to restore BM function that would otherwise be irreversibly altered; in this way, the patient can retrieve the blood cells they need to carry oxygen, fight infections, and prevent bleeding. The main objective of BMT is to substitute a defective system for a healthy one. Particularly, for the treatment of malignancies, it is important to eliminate malignant cells through the administration of cytotoxic drugs and/or radiation and the ability of donor cells to mediate the immunologic effect termed “graft-versus-tumor” against the malignant host cells; instead, for the treatment of immune deficiency or genetic diseases, it is necessary to replace defective host hematopoietic cells with normal hematopoietic stem cells (HSCs) capable of re-establishing hematopoiesis.The main stages of a BMT are essentially two: the first is a recipient preparative treatment called “conditioning” regimens that usually lasts 1 week; the second consists of the transfusion of healthy BM.The conditioning regimens are usually based on the administration of supralethal doses of total body irradiation and chemotherapeutic agents to the recipient with the goal of providing sufficient immunoablation to prevent graft rejection and reduce the tumor burden, increasing the chance of engraftment and decreasing the chance of relapse. However, as it was recognized that the graft-versus-tumor effects substantially contributed to the effectiveness of the transplant, reduced-intensity and nonmyeloablative conditioning regimens have been developed, making the transplant applicable to older and medically infirm patients .via intravenous infusion , β3-AR can contribute to the degradation of Sp1-decreasing cAMP levels in the pathway that triggers after coupling to Gi proteins. All these data demonstrate how the Sp1 function is relevant for an efficient Cxcl12 expression and consequently how the β3-AR can affect the circulation of HSCs just acting on these elements , 51.Based on ample evidence, the inhibition of β3-AR could be used to support a crucial step for a successful BMT or the BM repopulation, through increasing the Cxcl12 release to stimulate the homing of HSCs  and graft failure (GF). PGF is characterized by the presence of an initial full donor engraftment. In the primary form, bone marrow cellularity remains low, and patients present persistent cytopenia. In the secondary form, a prompt recovery is followed by a progressive decrease in blood counts. Instead, GF occurs as the result of a classical alloreactive immune response mediated by residual host immunity persisting after the conditioning regimen , 50. AccMoreover, we decided to perform a CFU assay on total mouse BM cells because it is the most widely used assay to get information about the frequency and types of progenitor cells present in the original cell population and their ability to proliferate and differentiate. As shown in To verify if our data truly proved an increased hematopoietic differentiation process in BM, rather than a redistribution of hematopoietic cells between BM, PB, and secondary lymphoid organs, we also analyzed the number of common myeloid progenitors (CMPs) and common lymphoid progenitors (CLPs) in the mouse BM, PB, and spleen. Cytofluorimetric analysis showed a higher number of CMPs in the BM of SR59230A-treated mice compared to control mice and no significative variation on the CLP number (Here, we have described a brief overview of the basic information regarding β3-AR and BMT, and we have speculated that targeting β3-AR could represent a new strategy to overcome complications related to BMT. Collectively, the studies reported here proved that the HSC release is not random or steady but rather follows a circadian rhythm regulated by “the molecular clock” of the SNS that exerts this function through the rhythmic secretion of catecholamines from the nerves in the BM, activation of the β3-AR, degradation of Sp1, and downregulation of Cxcl12. We focused on the possibility of a β3-AR inhibition to support the homing of HSCs in the BM, the step of a BMT in which the donor’s HSCs infused in the recipient patient must reach the staminal niche. In addition, with pilot experiments, we have put forward the hypothesis that β3-AR may also be involved in the HSC differentiation, an essential goal for a sustained long-term and effective engraftment phase of BMT (The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The animal study was reviewed and approved by University of Florence and Italian Health Minister research permit no. 796/2021-PR.NN wrote the review. NN and GB performed experiments. CF and MC supervised the project. All authors have read and agreed to the published version of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


We reviewed the published literature on rehabilitation outcomes in patients with cortical blindness (CB) and highlighted the characteristic features and prognosis of CB due to cardiac arrest. The studies excluded were those involving the pediatric population (<age 16), written in a language other than English, and studies with no mention of outcomes. The literature search was done by PubMed and EBSCOhost databases from the oldest available literature through November 2019. Due to the scarcity of published literature and a qualitative description of outcomes, a narrative review of the literature was deemed appropriate. Seven case reports and one retrospective cohort study met the inclusion criteria. Cognitive and visual impairments were significant barriers to rehabilitation in CB. Improvement of visual deficits occurred within one to two months. Those with complete blindness, cognitive impairments, and a delay in resuscitation were more likely to have poorer functional outcomes in the performance of activities of daily living and were less likely to be discharged home. This is the most comprehensive review of published literature to focus on the function of patients with cortical blindness. The limitations include the small number of published literature and the qualitative approach utilized. Despite the limitations, the findings of this review can inform future studies that would investigate the most efficient and comprehensive methods of CB rehabilitation. Cortical blindness (CB) is a type of vision loss resulting from bilateral occlusion or flow reduction within the posterior cerebral arteries (PCAs). Specifically, the blood supply to the geniculocalcarine visual pathways of the occipital lobes is compromised, leading to bilateral vision loss . PCA terWhile numerous studies focus on vision rehabilitation methods in patients with visual field deficits and cortical blindness -17, studThe purpose of this paper is to review the published literature on rehabilitation outcomes in patients with cortical blindness. Ischemia secondary to cardiac arrest is more likely to cause cortical blindness due to bilateral deficits because of hypoperfusion. Given this unique pathophysiology, we decided to look at the characteristics and prognosis of cortical blindness due to cardiac arrest. The authors hope that this will enhance understanding of the current knowledge of CB secondary to cardiac arrest and stroke and aid in the counseling of patients and their families on the impact that CB has on their functional outcomes.This article was previously presented as a meeting abstract at the 2022 Association of Academic Physiatrists Annual Meeting on May 27, 2022.MethodsA literature search was performed using the PubMed MeSH  and EBSCOhost databases. The following terms were used in the search: "cortical blindness [MeSH]," "rehabilitation [MeSH]" or "function," "cortical blindness [MeSH]" and "heart arrest [MeSH]," and "outcome" or "prognosis." The references to the papers were then reviewed to find additional literature on the topics of interest. The search timeframe was from the oldest available literature on PubMed through November 2019. The studies excluded were those involving the pediatric population (<age 16), those written in a language other than English, and studies with no mention of outcomes. Functional rehabilitation outcome was determined by performance on activities of daily living (ADLs), mobility or ambulation, or the Functional Independent Measure (FIM), a validated rehabilitation outcome tool used in assessing 13 motor and five cognitive tasks that is reliable in measuring functional ability . Due to ResultsOnly three studies were found on the functional outcome of rehabilitation in patients with cortical blindness: two case reports , 18 and In two of the four patients with cognitive and behavioral signs, occupational therapy was discontinued because of worsened confusion. Confusion interfered with learning compensatory mechanisms. Melatonin was used to control disturbed sleep patterns, and antiepileptics were used to control episodic aggression, with inadequate control achieved in some cases. In comparison, patients with partial blindness and fewer cognitive or behavioral signs showed excellent responses to rehabilitation . They were more likely to be discharged to their homes and families. One patient with complete blindness from bilateral occipital ischemic infarction gained 15 points in the Functional Independence Measure  showed no improvement for up to one year. However, they had the worse vision at the onset. Case three could only recognize light, and case four could not perceive light or motion, which suggests an inverse relationship between the severity of the visual deficit at onset and the pace of recovery.DiscussionThe results from the review of published literature on the functional outcomes of rehabilitation of patients with CB suggest that patients with complete cortical blindness were more likely to have neurocognitive and behavioral symptoms, as well as poorer functional outcomes, compared to those with only partial blindness. In this study, 55% of the cases with bilateral infarcts or hemorrhages of the occipital lobes experienced neurocognitive and behavioral symptoms. We theorize that the poorer functional outcome of complete blindness results from the severity of the insult combined with the anatomical distribution of the PCA, as previously argued by Brandt et al. .The PCA supplies the thalamic nuclei, limbic system, posterior limb of the internal capsule, cerebral peduncles, mesencephalon, and parts of the parietal, temporal, and occipital cortices . While t. This suggests that, in addition to neurocognitive and behavioral symptoms, the inability to navigate their environment could contribute to poorer functional outcomes.Interestingly, unlike the patients in Gaber who experienced confusion and agitation associated with CB, the cognitive impairments experienced by Case 4 were related to visual perception and imagery There is a linkage between CB and the need for high assistance with ADLs, low levels of satisfaction, and difficulty navigating environments , 23. TheTo further highlight the interplay between visual abilities and functional outcomes of rehabilitation, De Patre et al. reported on the trial of the Cognitive Therapeutic Exercises (CTEs) rehabilitation approach on a cardiac arrest patient  the small number of published literature found and included due to the scarcity of literature on the subjects of interest; (2) the qualitative approach utilized was necessary due to the inconsistency of outcome measures used; (3) the lack of additional pieces of data in some studies that would help determine relationships, such as the duration of cardiac arrest; and (4) the inconsistent reporting of long-term follow-up of the patients. Despite the limitations, the findings of this review can inform future studies that would aim to investigate the most efficient and comprehensive methods of CB rehabilitation. Future studies may want to consider the simultaneous assessment of visual impairment and neurocognitive and behavioral symptoms and their impact on functional outcomes.Patients with severe CB are more likely to have neurocognitive and behavioral impairments, which we suggest is directly proportional to the severity of the anatomical insult . These patients were also more likely to have a poor response to rehabilitation efforts and, thus, poor functional outcomes from rehabilitation and disposition. We believe that these findings emphasize the role of multidisciplinary rehabilitation involving occupational therapists trained in vision therapy. Collaboration between physiatrists and neuropsychologists is essential to selecting evidence-based pharmacologic agents to manage neurocognitive and behavioral symptoms and facilitate patient participation during acute rehabilitation.


When M was increasing, the high L/S ratio mixtures exhibited fluctuations in strengths, especially beyond a 10 M NaOH molarity. Maximum strengths of mixtures at equivalent molarity of 10 were achieved when the Na2SiO3:NaOH ratio reached 30:70, regardless of the ambient conditions and the presence of CEM I. The curing conditions, the ratio of Na2SO3:NaOH, and the presence of CEM I in the DM-based mixtures did not appear to significantly affect the mixture when NaOH concentration was between 2 M and 4 M; at higher molarities, however, these enhanced the strengths of the geopolymerized DM.Diabase mud (DM) is a silica-rich residue yielding from aggregate crushing and washing operations in quarries. This work focuses on identifying the geopolymerization potential of a diabase mud through characterization of its mineralogical composition, investigation of its reactivity, and assessment of the early compressive strengths of alkali activated mixtures formulated based on the mud’s dissolution results. The findings suggest that considerably low amounts of Al and Si metals were dissolved following the dissolution tests conducted on DM, however, the incorporation of small quantities of CEM I, gypsum, and metakaolin (MK) moderately at a Na Backed by the desire to deliver sustainable and cost-effective solutions in construction, the conversion of waste into secondary raw materials is an imperative initiative within the framework of the Circular Economy agenda for the European Union [2 emitted per tonne of fly ash produced; 52 kg of CO2 emitted per tonne of slag produced [The exponential demand for cement production–which currently reaches over 4.3 billion tonnes per annum worldwide –imposes produced ,15,16,17produced ,20,21,22In Cyprus, while slag and fly ash are in little to non-existent amounts due to the non-presence of steel industries or coal on the island. There is, however, an equally challenging issue to be addressed, and this is the large amounts of deposits of diabase mud (DM) accumulated as a sludge waste from the quarries. DM is a form of sludge waste that derives from solid fractions following aggregate crushing and/or aggregate washing operations. It is a residue yielded with a humidity content ranging between 25–30% and with a mineralogical composition consisting mainly of Al and Si oxides. This essentially makes it a promising candidate for potential alkali activation. At the same time, the accumulation rate of DM in quarries in Cyprus is indeed high, as certain plants were reported to exhibit an annual production of nearly 25,000 tonnes. Further, disposing of the mud in landfills within the production facilities is considerably limiting their storage capabilities. Considering the abovementioned issues, if a possible activation of the DM occurs to a sufficient degree so as to yield a durable, low carbon hydraulic binder, then there would be a leeway for the current issues of mud storage/accumulation/disposal in Cyprus to be controlled. At the same time, the possibility of sustainable solutions will be developed and offered to the market. Moreover, it would cater to the EU legislation related to recycling requirements of waste materials in Cyprus (which were introduced in 2012 ), thus uThe degree of the reactivity of the DM that is yielded from quarry operations for potential use in geopolymerization has not been researched to a considerable extent. Previous work ,25,26 suIn light of the above, this work seeks to define the geopolymerization potential of a diabase mud received from a Cyprus quarry through a comprehensive experimental program, which consisted of characterizing, initially, the DM, followed by quantification of its reactivity potential through dissolution tests, and finally investigating of early mechanical properties of formulations developed based on the reactivity of the material.-Characterization of the DM material as received from quarry;-Examining the DM material’s reactivity through dissolution tests  as a basis for then establishing properly proportioned inorganic polymer formulations; and-Development of the above selected inorganic polymer formulations incorporating a combination of solids and alkaline solutions and investigating their stability through early age compressive strength tests at varying curing conditions and varying mixing parameters.The experimental program consisted of three distinct stages, as described below:The first stage of the experimental program, as received DM from Pharmakas Quarries in Cyprus, was initially characterized through X-Ray Diffraction Analysis (XRD), Thermogravimetric Analysis (TGA), Energy Dispersive X-Ray Fluorescence (ED-XRF), and density tests. For these tests, the DM was oven-dried at 110 °C until constant mass, followed by being crushed into fine particles using a Los Angeles abrasion machine at 2000 cycles and then sieved through a 0.063 mm sieve.2), albite (NaAlSi3O8 or Na1.0–0.9Ca0.0–0.1Al1.0–1.1Si3.0–2.9O8), labradorite 4O8, as well as minor traces of calcite (CaCO3).X-ray diffraction analysis was conducted using a BRUKER D8 X-Ray Diffractometer  with Cu Kα1 (Ni filtered) radiation in the 2-theta range of 2° to 60° and on a 0.02°/s step. X-ray diffractogram of the material is shown in The differential thermal/thermogravimetric (DT/TGA) analysis , which w2 content, which, in combination with 11% of Al2O3, indirectly provided a good degree of reactivity potential and indicated a promising precursor for geopolymerization, even though its amorphousness profile may have seemed less favorable.For obtaining the oxide contents of the DM, ED-XRF analysis was conducted using a SPECTRO XEPOS elemental spectrometer, the results of which are shown in 3 (standard deviation = 25.2 kg/m3). This value was slightly lower than the average reported density of the aggregates crushed and processed in the particular local quarry in Cyprus.Density measurements were obtained by oven-drying the as-received sample at 105 °C until constant mass, followed by grinding the material using pestle and mortar in sizes less than 63 microns and using a Quantachrome pycnometer to determine the density of the powdered sample. Four measurements were obtained, and the average density was reported as 2362 kg/mDissolution tests were conducted on the basis of assessing the reactivity of DM. Reactivity is defined as the concentration of leached-out soluble elements  following a specific time frame. The test, therefore, provided the basis for establishing and developing inorganic polymer formulations incorporating solids with alkaline solutions for the subsequent experimental phase. The leaching reagents used were either NaOH or KOH at molarities of 2 M, 4 M, 6 M, 8 M, 10 M, 12 M, and 16 M, and at a liquid to solid ratio (L/S ratio) of 250. The test involved adding 0.2 g of the DM sample in 50 g leaching reagent in a tube which was shaken for 24 h, and then centrifuging the mixture for 15 min at 3000 rpm, followed by filtrating the supernatant at 0.45 micron membrane-filter and analyzing the residue through inductively coupled plasma atomic emission spectroscopy (ICP-AES). Results of the dissolution tests are shown in 4·2H2O to EN 13279-1:2008), as well as commercially available metakaolin (MK), were all strategically incorporated in the mixtures at defined percentages . The solids were added on the basis of promoting amorphicity in the matrix and thus enhancing the geopolymerization of the DM.For achieving stability of the geopolymerized formulations, commercially available materials of portland cement (CEM I to EN 197-1:2020), gypsum ,–the amount of which was determined based on NaOH molar mass for producing the required concentrations–and then stirring the mixture for 5 min using a magnetic stirrer. The solution was insulated for 24 h in ambient conditions and mixed with a commercially available Na2SiO3 solution in the abovementioned percentages to develop the alkaline activator (thereon referred to as ‘liquid’). Properties of all solids and alkaline solutions used are shown in For preparing the alkaline activator solution, a combination of NaOH and Na-2SiO3 ratios for a liquid to solid (L/S) ratio of 0.69, incorporating DM, CEM I and gypsum and oven-cured for 48 h at 70 °C;Case 1 included the development of 12 mixtures of varying molarities  and varying NaOH/Na-2SiO3 ratios, air-cured at 20 °C and 65% RH for 72 h prior to testing;In Case 2, a total of nine mixtures were developed using DM, CEM I and MK at a low L/S ratio of 0.38, again with varying molarities  and varying NaOH/Na-2SiO3 ratios and being conditioned in the oven at 50 °C for 72 h prior to testing.And lastly, a Case 3 was considered where a total of eight mixtures were developed using DM and MK at a low L/S ratio (0.38), again with varying molarities  and varying NaOH/NaThree different cases of inorganic polymer mixtures were investigated:The nature of the DM , in combination with the very limited previous references on the characterization and valorization of the material, demanded the investigation of a wide spectrum of factors potentially influencing its activation. Therefore, the three Cases mentioned above were selected after a considerable number of small-scale preliminary trial mixtures and combinations, based on the evaluation of the results related to the characterization of the DM and either previous experiences of the research team, or some similar cases reported in the literature . It is iThe paper aims to present, discuss and evaluate the results obtained from each of the three Cases under study, and reveal the factors that could enhance the alkali activation of the three hybrid mixtures. It should be noted that due to the nature and origin of the DM, as well as due to the lack of any previous knowledge related to the potential of the material to be valorized through geopolymerisation, a variety of experimental investigations were necessary to draw conclusions on this aspect. In a subsequent paper, the most promising mixtures developed based on the information summarised in this paper will be presented, along with the obtained physical and mechanical properties, durability characteristics, and optimized curing regimes.3) in accordance to ASTM C109–20, and was vibrated using a vibrating table for 1 min. The early age uniaxial compressive strengths of the samples were then determined using a 2000 kN CONTROLS hydraulic compression machine at either 24 and 48 h (for Case 1), or 72 h (for Cases 2 and 3), and at a loading rate of 0.2 MPa/s in accordance to ASTM C109–20 [The inorganic polymers were prepared by carefully mixing the liquids and solids described in the previous section at the selected proportions shown in 2SiO3:NaOH ratios of 50:50 and 40:60 for mixtures in Case 1 are shown in Average compressive strength developments and NaOH concentrations of all investigated formulations are shown in 2SiO3:NaOH tested ratios  and at both ages , was overall inversely proportional, i.e., showcasing a declining rate, although however, changing the molarities caused fluctuations on the compressive strengths, especially in the mixtures having a Na2SiO3:NaOH ratio of 50:50. In these particular mixtures, when the highest molarity NaOH was incorporated in the liquids , a significant strength loss (66% reduction) was recorded compared to its highest strength value, which was observed at a molarity of 4 M. Another interesting point obtained was that the mixtures with Na2SiO3:NaOH ratios of 50:50 exhibited approximately 10–20% higher 48 h compressive strengths than those of the 40:60 ratio, however, this occurred only up to molarity of 8 M; beyond which, the mixtures of 50:50 ratio suffered a drastic 48 h strength loss of 66% when molarity was increased from 8 M to 10 M, and these eventually became weaker than the mixtures of 40:60 ratio, with nearly 10% lower 48 h strengths.The results obtained from Case 1 showed that the relationship between compressive strengths and molarities at both Na2SiO3:NaOH ratio of 50:50 and with a molarity of NaOH solution of 4 M exhibited the highest strengths from all compared formulations. However, the particular mixtures appeared to be highly sensitive to variations in the molarity, leading to significant fluctuations in strengths when molarities were progressively increased, and eventually suffering drastic strength losses beyond 10 M NaOH concentrations. In mixtures of a ratio of 40:60, the fluctuations in strengths were less significant when molarities were progressively increasing, although strengths were still declining across the tested molarities.The results in In Case 1 and according to Results of investigations carried on mixtures of Cases 2 and 3 are shown in 2SiO3:NaOH ratio, although this effect was ceased at concentrations beyond 8 M and towards 10 M. This difference can be also observed in 2SiO3 ratios and regardless of the presence of CEM I in the formulation. Beyond a concentration of 4 M, and at least until the 8 M, there is a significant increase in strengths, which appears to be considerably sharper in the Case 2 mixtures. However, such an increase was less significant beyond 8 M in Case 2, in contrast to Case 3 mixtures. An additional observation for Case 3 made in Cases 2 and 3 are summarized in 2SiO3:NaOH ratio, regardless of the presence of CEM I and regardless of the ambient conditions. It can be also seen, on the same figure, that the absence of CEM I in Case 3 appeared to have enhanced the strengths more significantly when the ratio was tending from 10:90 towards 30:70 when compared to Case 2 .When both Cases were compared at equivalent molarity of 10 M , the max4 monomer promotes the formation of more -Si-O-Si- bonds, thus forming a more stable bond structure.Fundamentally, the increase in compressive strengths in both Cases may be attributed to the increase of the alkalinity, which is mainly attributed to the presence of metakaolin in the mixtures, which predominantly reacts with the alkaline activator. Moreover, in Cases 2 and 3, the addition of the sodium silicate solution seems to have a positive effect on the evolution of the compressive strength. The continuous increase of Si content enhanced the content of dissolved elemental silicon, and the increase of Si(OH)Generally, the higher the Si content, the more stable it is, since the chemical bond strength of -Si-O-Si- is higher than the corresponding of -Si-O-Al- and -Al-O-Al-, and therefore higher energy is required to break the particular bond.4 will form a dimer after condensation reaction and then react with Al(OH)4 to form a stable long chain (-Si-O-Al-O-Si-O-) PSS polymer (Si/Al = 2) or more stable long chain (-Si-O-Al-O-Si-O-Si-O-) PSDS polymer (Si/Al = 3). This phenomenon is not presented in Case 2, since the presence of cement creates C-S-H phases in parallel that are not enhanced with the presence of additional Si, while it in contrast intercepts the geopolymerisation process, and thus the compressive strength decreases , the content of elemental silicon dissolved in the system is much higher than that of aluminum. Meanwhile, a part of Si(OH)ecreases .Considerably low amounts of Al and Si metals were dissolved following the dissolution tests conducted on DM, which essentially suggests that the material alone did not possess sufficient reactivity potential so as to give chemically stable alkali activated binders.2SiO3:NaOH ratio of 50:50 and with a molarity of NaOH of 4 M enhanced the geopolymerization of the DM, but appeared to be highly sensitive when M was increasing, leading to significant fluctuations in strengths and eventually suffering drastic strength losses beyond a 10 M NaOH molarity.Based on the above, mixtures of high L/S ratio incorporating CEM I, gypsum and MK at a Na2SO3:NaOH, and the presence of CEM I in the DM-based mixtures did not appear to significantly affect the compressive strengths when the NaOH concentration was between 2 M and 4 M ; at higher molarities, however, these enhanced the strengths of the geopolymerized DM.The curing conditions, the ratio of Na2SiO3:NaOH ratio reached 30:70, regardless of the ambient conditions and regardless of the presence of CEM I.Maximum strengths of mixtures at equivalent molarity of 10 were achieved when the NaA low L/S ratio DM-Metakaolin mixture with a 20:80 alkaline solution with its NaOH molarity at 10M yields almost identical 72 h strength to that of a mixture at 30:70 alkaline solution with a NaOH molarity of 6 M.The potential for geopolymerization of a diabase mud received from a Cyprus quarry was investigated in this paper and the following conclusions were drawn, based on the results: