Pesticide residues are monitored in many countries around the world. The main aims of the programs are to provide data for dietary exposure assessment of consumers to pesticide residues and for verifying the compliance of the residue concentrations in food with the national or international maximum residue limits. Accurate residue data are required to reach valid conclusions in both cases. The validity of the analytical results can be achieved by the implementation of suitable quality control protocols during sampling and determination of pesticide residues. To enable the evaluation of the reliability of the results, it is not sufficient to test and report the recovery, linearity of calibration, the limit of detection/quantification, and MS detection conditions. The analysts should also pay attention to and possibly report the selection of the portion of sample material extracted and the residue components according to the purpose of the work, quality of calibration, accuracy of standard solutions, and reproducibility of the entire laboratory phase of the determination of pesticide residues. The sources of errors potentially affecting the measured residue values and the methods for controlling them are considered in this article. A sufficient amount of safe food cannot be provided for the continuously growing population of the world without the use of pesticides at the current technological level. The global demand for, and the production as well as the use of pesticides have increased steadily during the past decades and are projected to continue growing ,2. PestiTo protect consumers and the environment, the national authorities authorize the use of pesticides only after the critical evaluation of their toxicity, biological efficacy and residues remaining in/on food as well as in the environment ,9,10,11.To control the safe and efficient use of pesticides, their residues are regularly monitored in food and environmental samples in many countries according to risk-based sampling plans ,28,29,30Most publications referenced above ,48,49,50Drawing realistic conclusions and making appropriate corrective actions can only be done if the monitoring results are accurate and derived from the analyses of samples taken according to the specific objectives of the program. That can only be achieved by implementing rigorous internal quality control of the whole process of the determination of pesticide residues. The basic quality requirements for the monitoring results are defined in five major guidance documents ,64,70,71R) is influenced by four main factors (Equation (1)): sampling (S), laboratory sample handling including subsampling of large crops (CVSS), comminution (CVSp), test portion selection and analyses of sample extracts (CVA)  of the measured residues (R) is equal to ‘n’. The two estimates of CVL with Equations (15) (0.1283) and (17) (0.1608) are slightly, but statistically not significantly, different. We recommend using the larger CVL to avoid underestimating the long term within-laboratory reproducibility of the residue determination process.The degree of freedom for the corresponding standard deviations [sd = CVThe gas and liquid chromatographic separation and MS detection conditions are generally well described in the publications often following the guidance given by SANTE/11312/2021, SANTE/2020/12830, USFDA documents ,63,64. HThe reported LOD values or reporting limits should always be checked at the beginning and at the end of the analytical batch of sample extracts for all targeted analytes preferably in blank sample extract, because loading the column with coextracted materials may change the resolution of the column and or shift the retention times as illustrated in The inertness and satisfactory operating conditions of gas chromatographic columns can be improved by applying the so-called analyte protectants ,113 A cr2, Log, 1/sd2). The reported results can be quite different depending on which integration options are selected. Attention is also required to assess the number of disabled points and the reported confidence limits of the slope and intercept of the regression equations. For instance, where three out of six calibration points are disabled the predicted analyte concentration should be critically considered, and possibly additional calibration injections should be made.The data analyses reports provided by the software should not be viewed as a ‘black box’ and accept it without verification of its correctness. The modern data analyzers  usually offer six different curve fit types , four possible choices for the origin , and seven for weighing  acquisition includes the whole peek(s) and their integration is correct .For multi-level calibration the standard concentrations should be equidistantly distributed over the calibrated range. Such a calibration program type is only justified where analytes potentially present at low concentrations are looked for in screening analyses.2) provides information only on the linearity of the calibration but does not characterize the quality of the calibration. It can be assessed based on confidence intervals, calculated by those of the data processing software for the slope and intercept of the regression line or from the standard deviation of the relative residuals. The latter parameters should also be reported together with ‘r’ or R2.It should be recognized that the correlation coefficient (r) or the coefficient of determination  indicating the scatter of the responses around the regression line as well as the width of the confidence and tolerance intervals are substantially different. The confidence intervals around the regression line are strongly influenced by the number of standard injections (not shown in the figure).The regression residual The standard deviation of the relative residuals is calculated as:k times, the number of degrees of freedom is (nk–2).When each reference material is measured 2 values are practically the same, the Sdrr values indicating the large difference in the confidence/tolerance intervals in 2 is not a proper indicator of the accuracy of the calibration [rr should be <0.1 (10%). The Codex quality control guidelines suggest accepting a maximum of 20% relative residuals (30% near the instrument LOQ) [Nonetheless the Ribration . Our expent LOQ) .dietary exposure assessment of consumers;evaluating the residue levels and their compliance with national or international maximum residue limits or guidance values;assessing the contamination of the environment;providing the basis for the necessary corrective actions if the residues exceed the reasonably expectable levels in the treated crops.The monitoring programs are conducted around the world including large number of samples to provide data for carrying out:Each analysis may have significant consequences. Therefore, the results should be representative and defendable even in legal proceedings. Analysts must be aware of their responsibilities and the fact that their credibility could be at stake. They should be able to verify the correctness of their measurements with documented evidence.The international standards and guidelines provide the frame and acceptable performance criteria for performing the pesticide residue analytical measurements. They would facilitate obtaining accurate, defendable results only if the laboratory operations are performed by staff members  who are aware of their own responsibility and are working in coordination with each other.It is not sufficient to validate our methods or test the performance of already validated methods once. The laboratories should establish their own internal quality control programs to be used daily for ensuring that their methods satisfy the specified performance characteristics when applied for instance to screen over several hundreds of analytes in samples of unknown origin or to test the residues in commodities before export.The provisions of guidance documents should be fulfilled bearing in mind that the priorities of internal quality control are in order: (1) good analytical practice; (2) good science; (3) minimum bureaucracy; (4) facilitating reliability and (5) efficiency. The quality assurance/quality control (QA/QC)should only be an appropriate proportion of the activities related to the analyses of samples and reporting of the results.Keeping in mind the above priorities, we emphasize that it is not sufficient to report the recoveries obtained with spiked test portions, the linearity of calibration, detection conditions, and confirmation of the identity of substances. In addition, we propose checking and preferably briefly reporting, for instance, the validity of samples considering the parameters that can be verified in the laboratory, accuracy of analytical standards, stability of analytes during the laboratory operations, quality of calibration characterized with the relative residuals or their standard deviation, and the reproducibility relative standard deviation of the measured residues.Moreover, the selection of the parts of samples and the composition of the residues to be determined should always be matched with the objectives of the work.It is advisable to take part regularly in proficiency tests that provide a means of objectively evaluating and demonstrating the accuracy and reliability of our measurements. Critical review of the Z-scores and identification of the sources of the potential errors can help to improve the technical operation standard of the laboratory. However, participating in proficiency tests does not replace the regular and rigorous internal quality control actions.Finally, reliable results on which regulatory decisions are based can be expected only from well-trained analysts whose knowledge should be regularly updated to fully utilize the advantages of the high-performance instruments and benefit from the rapidly expanding methodical experience gained by other laboratories through the analyses of a great variety of samples.


Double-sided self-pierce riveting (DSSPR) has been presenting itself as a proper alternative to self-pierce riveting (SPR) with many advantages for joining geometries of different thicknesses and cross-sections. To ensure its successful future industrial application, this paper presents a detailed comparison between different strategies to produce mechanical joints by means of the DSSPR process and discusses its performance and feasibility. Results show that the use of flat-bottom holes in both sheets provide interesting results, since they allow for a precise positioning of the tubular rivet in specific pre-defined locations, thus avoiding an incorrect joining procedure. This strategy tightens the tolerances of the process, while keeping a suitable level of destructive performance as demonstrated by the lap shear tests. Pre-riveting of the sheet has also been shown to produce suitable results in combination with or without a flat-bottom hole in the opposite sheet. This strategy comes at a cost of a slightly lower performance than that obtained with flat-bottom holes in both sheets, although the requirements of force and energy to complete the joining process are smaller. The conclusions of this research work are essential for selecting the joining strategy with DSSPR according to the requirements of the intended application. For the production of mechanical joints by means of the technology of joining by forming with auxiliary joining elements , self-piLightweight construction demands for multi-material design, which in turn demand the utilization of versatile joining processes that circumvent the metallurgical incompatibilities, provide a low heat input and can provide an adequate level of flexibility . At the The application of SPR to aluminium sheets of different alloys have been extensively investigated. From those studies, the effect of rivet and die shapes on the joint properties have been studied ,7,8. TheAn innovative self-pierce riveting process consists of double-sided self-pierce riveting (DSSPR) which makes use of a tubular rivet with chamfered ends that are capable of producing hidden joints between sheets placed over each other b. The tuThe validation of the DSSPR joining technology has been performed with tubular rivets of stainless steel AISI 304 and aluminium AA5754 sheets, to investigate the working principle and the geometric scalability of the tubular rivets. Recently, the chamfered ends of the rivets have been optimized to improve the rivet penetration and final morphology, and therefore increase the overall joint strength of the mechanical connection .Since there is no upper thickness limit in DSSPR contrary to what it is observed for SPR, sheets with a thickness of 5 mm were originally tested , and morFrom an industrial point of view or when demanded from the material combination, some strategies may need to be developed. For instance, the authors have shown that while keeping all the other parameters constant, the chamfered angle of the tubular rivet can be modified at each end of the rivet, to account for the different resistances to penetration of the materials from the two sheets . HoweverAnother possible solution is the introduction of flat bottom holes in the strongest sheet by means of machining or forming, in order to correctly position the tubular rivets before piercing. This promotes the penetration in harder materials and their subsequent assembly to softer materials by means of the opposite end of the tubular rivet . At the Therefore, the objective of this work is to combine the different previous strategies and compare their performance when subjected to static loads. To support the investigation, numerical predictions are employed to analyse the mechanics of the deformation and the stress–strain levels for the different strategies and modifications introduced. Along with the numerical analysis, different specimens are produced and subjected to lap shear strength tests to determine the performance produced by each modification. This will allow us to define the strategy to be followed in accordance with the load and energy requirements for both the joining process and the intended application, towards a closer industrial implementation of DSSPR. Different compromises are made with each joining strategy, although the introduction of flat-bottom holes in both sheets is able to provide a similar performance to conventional DSSPR joints without holes, that offers the best performance among all strategies. The utilization of pre-riveting follows the introduction of flat-bottom holes in terms of performance and its applicability regards the utilization of sheets of very different strengths or thicknesses.The materials chosen and their respective flow curves were retrieved from a previous work of the authors on conventional DSSPR  to whichThe main process parameters of the tubular rivet were retrieved from the original work on conventional DSSPR  and resuRegarding the sheets, the upper and lower sheet thicknesses tom hole b was evatom hole c, that wtom hole d or withtom hole e, was taConventional DSSPR between two plain sheets;DSSPR between sheets with each one having a flat-bottom hole with a given depth DSSPR with pre-riveting of one of the sheets in combination with a plain sheet;DSSPR with pre-riveting of one of the sheets in combination with a sheet having a flat-bottom hole with a given depth The different strategies consist of:The experimental work was carried out at ambient temperature in the same hydraulic testing machine utilized to previously obtain the material flow curves. The range of values for each parameter is presented on A minimum of five specimens were produced for each strategy with some being halved lengthwise to observe and compare the mechanical interlocking The numerical simulations of DSSPR were performed with the finite element computer program i-form  where thThe finite element equations resulting from (1) use a control volume with velocities approach . The symained in .A rotational symmetry was considered for modelling the plastic deformation, with the sheets and tubular rivets being modelled as deformable isotropic objects subjected to axisymmetric loading. Their cross-sections were discretized by means of quadrilateral elements with a larger number of elements at the locations where the riveting process takes place and larger deformations are generated refer to . The tooRegarding the friction conditions, a friction factor of −3 was employed after which the geometry was updated based on the calculated velocities. Whenever large local deformations were generated from the rivet being pushed through the sheets which distorted some mesh elements, local repairment of the finite element model was carried out several times by semi-automatic repositioning of nodal points with appropriate transfer of field variables from previous to newer locations. That procedure was in some cases complemented by intermediate global remeshings of the entire deformed objects. Along the simulations, the finite element flow formulation equilibrium is checked by means of an iterative procedure meant to minimise the residual of (1) to within a specified tolerance. A convergence criterion of the residual equal to 10Comparisons between the Different StrategiesThrough the combination of finite element modelling and experimentation, it was possible to identify the mechanics of deformation for the different strategies analysed. Generally, the thickness of the tubular rivet increases along the deformation due to compression and strain hardening of the sheet and rivet, the latter being responsible for promoting a combined piercing and flaring of the tubular rivet, which results in the formation of a mechanical interlocking . As the After the tools were removed, a very small protrusion is visible in the top of the sheet surfaces which results from the elastic recovery of the materials from those sheets  to which it follows a steep increase of the overall force as the two overlapped sheets are being pressed against each other. The required maximum force to produce the mechanical joints is in the range of 100 kN for all the strategies analysed.Conventional DSSPR demands higher levels of joining energy, as the total rivet height has to penetrate the two plain sheets. In contrast, smaller levels of joining energy are found to the other alternatives, in particular for the alternative of sheets with flat-bottom holes, since the joining energy for the pre-riveted joints is the sum of the energy in each one of the two stages.The differences in displacement for the different joining strategies in comparison with conventional DSSPR are due to the smaller free height of the rivets that is now placed inside the flat-bottom holes, whereas for the case of the pre-riveting strategy, only half of the rivet height is compressed against the sheet in each stage.Regarding the destructive performance evaluation, the lap shear tests in refer to a, as welIn contrast, the increase of the depth of the flat-bottom holes to 2 mm provided a lower performance, justified by the reduced penetration of the rivet that results from the utilization of a deeper flat-bottom hole. This facilitates the detachment of the rivet from the sheets, as seen by the photographs included in For the pre-riveted joints and despite the differences in the amount of mechanical interlocking, the performances are very similar whether a plain sheet or a sheet with a flat-bottom hole with a depth of 1 mm is employed, since the detachment is constrained by the larger strain hardening levels of the sheet material at the pre-riveted side. The photographs in Different strategies were analysed to produce joints in overlapped sheets with DSSPR, making use of the strong advantages of this joining technology while ensuring the conditions for its industrial implementation in a wide range of scenarios.The introduction of flat-bottom holes in the sheets ensures both positioning and alignment of the rivets, while eliminating any protrusions above the sheet surfaces. As a result of the gap created by the holes, the joining forces and energies are lower than for conventional DSSPR, while their performances are very similar. However, the depth of the flat-bottom holes cannot be so high because it can compromise the performance of the mechanical connection or may even not be feasible for thinner sheet thicknesses. In the latter case, pre-riveting of one of the sheets  should be employed instead to ensure a proper riveted joint.For the pre-riveting strategy, two iterations can be utilized without any relevant differences in terms of performance, other than the advantages that arise from the simplicity of placement of the opposite rivet end when a localized flat-bottom hole is already present in the opposite sheet. Nevertheless, if the opposite sheet material is much softer than the pre-riveted sheet material, a flat-bottom hole may create a weaker region in the softer sheet that can compromise the joining process. The selection of the pre-riveting strategy comes at a cost of a slightly reduced destructive performance and the need to have an additional stage other than the single stroke in which the other strategies are produced. Therefore, this strategy is more suited for different material and thickness combinations where a greater or lesser penetration of the rivets into the sheets may be desired.In conclusion, the guidelines established during this work help to create the conditions for selecting a suitable joining strategy with DSSPR depending on the material and geometry specifications.


Psychiatry is facing major challenges during times of a pandemic as illustrated by the current COVID-19 pandemic. The challenges involve its actual and perceived role within the medical system, in particular how psychiatric hospitals can maintain their core mission of attending to the mentally ill while at the same time providing relief to general medicine. Although psychiatric disorders are the top leading causes of global burden of disease, we can witness mental health care being de-emphasized in the wake of the massive onslaught of the pandemic: psychiatric wards are being downsized, clinics closed, psychiatric support systems discontinued etc. in order to make room for emergency care. While nobody can deny the need to act decisively and swiftly and ramp up intensive care readiness, we believe that there is no need to do this at the expense of psychiatric care. Using the pandemic COVID-19 contingency plan developed at the Department of Psychiatry and Psychotherapy of the University Hospital of LMU Munich as a case in point, we demonstrate how a psychiatric hospital can share in the acute care of a health care system facing an acute and highly infectious pandemic like COVID-19 and at the same time provide for the mentally ill, with or without a COVID-19 infection, and develop mid and long-term plans for coping with the aftermath of the pandemic.No significant relationships.


Risk assessment is a key component of patient care in forensic psychiatry. This audit aimed to measure the completion of different aspects of the Formulation Information Risk Management (FIRM) risk assessment for patients in the care of Low Secure Services. The FIRM incorporates formulation and a care plan into the risk assessment and should be completed for all inpatients in the trust. It was hoped that this audit would help identify any areas of improvement required in the completion of this risk assessment, and provide recommendations that would contribute to improving standards where required.Data were collected on 23rd December 2021 from the electronic patient records of 37 inpatients at a Low Secure Services Unit in Northern England. 5 audit criteria were devised following review of the trust standards regarding the completion of the FIRM assessment. These criteria included the completion of the Current / Historical Risks section, Formulation and Staying Safe / Staying Well Care Plan aspects of the assessment. It also assessed patient involvement in completion of the assessment and whether the assessment had been updated in the last Care Programme Approach (CPA) period. The findings of the audit were presented at a local academic meeting and were distributed to the relevant staff.100% of patients had the Current / Historical Risks section completed89% of the patients had the Formulation completed73% of patients had the Staying Safe / Staying Well Care Plan completedIn 16% the service user had been involved in the risk assessment completionIn 70% of cases the FIRM had been updated since the last CPA (or in the last year if not applicable)Current / Historical Risks section completion rates matched expected trust standards. Significant improvement was seen in completion of the Formulation and Care Plan compared to auditing done in October 2021. There was room for improvement regarding increasing patient involvement in the completion of the risk assessment, often due to it being completed at night leading to the patient being unavailable. It was recommended that the FIRM should be more consistently reviewed and updated as part of each patient's 6 monthly CPA review. A re-audit would prove useful to monitor the progress of these measures, and the scope of a future audit could also be widened to include the timeliness in which the FIRM is completed for new patients.


Leprosy is a neurocutaneous infectious disease with a highest prevalence in African region in the world. With the introduction of newer monitoring strategies of identifying the cases and multidrug therapy the overall global burden of leprosy has reduced. However, early detection and treatment is still important in leprosy due to the rapidly developing nerve damage by the bacteria and the associated disability. Here, presenting a case of a 65-year-old male patient of leprosy in borderline pole, with complaint of hyperpigmentation over back, chest and arm in a ring like pattern from past 4 months. Patient has been on WHO multibacillary multidrug regimen . On starting the treatment patient started noticing resolution in thickness of the lesion along with appearance of reddish-brown color of the lesion. On cutaneous examination, multiple geographic and annular patches with central clearing and shiny coppery reddish brown pigmentation in the peripheral margin of the lesion is seen. This case exemplifies the lesional hyperpigmentation, secondary to accumulation of ceroid lipofuscin pigment and Clofazimine inside the macrophage phagolysosome. Also, only marginal pigmentation with central clearing attributes to the punched-out lesion of the borderline lepromatous leprosy primarily which on histopathology typically shows presence of macrophage granuloma. Clofazimine induced pigmentation is reversible but takes months to years to clear after stopping the drug. As a dermatologist with leprosy moving towards elimination monitoring and managing the adverse effect of treatment and course of the disease is important.


To the Editor:The authors reported no conflicts of interest.Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.The Lehmann and colleaguesFirst, the authors did not present any comparative evidence to support that the Trifecta bioprosthesis is noninferior to the other valves on the market. Instead, they cited published data from elsewhere, which weakens any comparison. They reported that the rate of structural valve deterioration (SVD) in their cohort is comparable with the 10% rate of SVD in the Carpentier Edwards Perimount (CEP) (Edwards Lifesciences) valve at 10 years.,There is a growing body of evidence in the literature that suggests that Trifecta has an increased risk of early SVDAnother issue raised in the article is the success of valve-in-valve (ViV) transcatheter aortic valve implantation (TAVI) as a treatment for failed Trifecta valves. In this regard, the Trifecta is again inferior to alternative valves such as CEP because the metal stent in small sizes of Trifecta valve cannot be fractured for insertion of an adequate size of TAVI prosthesis.Overall, we believe the conclusion reached by Lehmann and colleagues


Prescribing antidepressants in the treatment of bipolar depression remains highly controversial due to the inconsistency between routine clinical practice and the results of controlled trials.To assess the validity of antidepressants use in bipolar depression from the point of view of evidence-based medicine.Database search (Scopus and MEDLINE) followed by analysis of studies concerning the efficacy and safety of antidepressants in the bipolar depression treatment.The search found 23 studies. There was a high degree of inconsistency in the results, apparently related to the methodology. Only two studies compared the effectiveness of antidepressants in monotherapy with placebo. No differences were found in the study with 740 participants but in the study with 70 participants with type 2 bipolar disorder antidepressants were found to be more effective than placebo. Nevertheless, both studies had significant methodological issues. In 6 studies comparing the effectiveness of the combination of antidepressants with mood stabilizers against the combination of mood stabilizers with placebo, only the effectiveness of fluoxetine in combination with olanzapine was confirmed, other antidepressants were ineffective. At the same time, studies where antidepressants were compared with each other in combination with mood stabilizers revealed a significant clinical response to therapy. Risk of the treatment emergency adverse events were relatively low for SSRI.Despite the contradictory literature data, the use of antidepressants in bipolar depression is justified from the point of view of evidence-based medicine for certain groups of patients with taking into account risk factors.


Both cells and the niche may stimulate and mutually signal each other to maintain functions and regulate responses during development and adulthood.The term “cellular microenvironment” is a generic expression used to describe the complex collection of stimuli that contribute to cell and tissue functions . This “nMoreover, the native cellular niche plays a critical role in dictating, for example, the fate of stem cells . TherefoMany research groups are now directing their efforts towards the design and manufacture of topographically controlled biomaterials that are capable of mimicking different aspects of the native stem cell niche . This isThe latest advancements in bioengineering have allowed for the control of individual aspects of the cellular microenvironment. Therefore, this Special Issue focuses on collecting outstanding contributions covering recent approaches used to recreate and promote the formation of tissue-like structures from cells and materials.Abdul-Al et al. begin by discussing the importance of stem cell niches in the human eye . They reTherefore, given the importance of microfabrication in the generation of artificial cellular niches, Ramos-Rodriguez et al. present microfabrication techniques used in the design and manufacture of cell microenvironments for tissue regeneration . In factIn summary, different fabrication techniques were developed for the successful generation of artificial microenvironments. Future tissue engineering scaffolds will also benefit from the identification of the critical elements of a given cell niche since this will influence the complexity and functionality of the construct. This capacity to produce dynamic 3D environments where stem cells are capable of residing and differentiating is particularly important for the recreation of bone marrow and the hematopoietic niche .Bioengineering the essential topics and exciting future innovations related to the research in this area. It is now evident that many research efforts are being directed towards the design and manufacture of topographically controlled biomaterials that can mimic different aspects of the native stem cell niche. Furthermore, this Special Issue provides outstanding insights into relevant issues related to stem cell research and regenerative medicine.In conclusion, this Special Issue, entitled “Design and Fabrication of Artificial Stem Cell Microenvironments”, offers to the readers of


Reducing health inequalities is on the agenda of many countries. Despite an increasing concern and awareness on health inequalities a wide gap exists in Europe in terms of political response. The main objective of JAHEE was to strengthen a cooperative approach among participating countries and implement concrete actions to reduce health inequalities. The partnership was composed of 24 countries including many strategically most relevant public health institutions in the European Union, which contributed with different backgrounds, skills and know-how to the achievement of the project objectives. The main results will be presented.


The presentation will focus on two main outcomes of the WHO initiative: a global research agenda to steer future evidence generation on PHSM, and a central monitoring system for PHSM research. In September 2021, a global technical consultation with over 60 global experts was organized to review the existing evidence on PHSM and identify the initiative's priorities. The consultation provided an opportunity to have an initial discussion on potential research priorities. This became the basis for an iterative online consultation process. The draft research agenda includes seven main research themes including effectiveness, unintended consequences, methodological challenges and implementation considerations affecting the uptake of and adherence to PHSM. Workshop participants will be invited to comment on the suggested themes and propose additional priority questions for the research agenda. The central research monitoring system will consist of a global repository of primary studies and reviews investigating the effectiveness and broader multisectoral impact of PHSM. Indexed studies will be mapped against the key themes of the research agenda, facilitating real-time monitoring and evaluation of its progress. An AI-based mechanism for automated updating of systematic reviews will complement the database. This one-stop shop will allow researchers and decision-makers worldwide to access the latest evidence on PHSM and keep track of the synthesized effectiveness and impact of different interventions and combinations. The platform will further provide a protected working interface. This monitoring system for PHSM research enables timely access to and utilization of evidence indecision-making processes during health emergencies and fosters international collaboration on the analysis and interpretation of data. Workshop participants will be invited to review the alpha version of the platform.


The present study is a detailed literal survey on the bond behavior of FRP (Fiber Reinforced Polymer) reinforcing bars embedded in concrete. There is an urgent need for the accurate assessment of the parameters affecting the FRP–concrete bond and quantification of these effects. A significant majority of the previous studies could not derive precise and comprehensive conclusions on the effects of each of these parameters. The present study aimed at listing all of the physical parameters affecting the concrete-FRP bond, presenting the effects of each of these parameters based on the common opinions of the previous researchers and giving reasonable justifications on these effects. The studies on each of the parameters are presented in detailed tables. Among all listed parameters, the surface texture was established to have the most pronounced effect on the FRP–concrete bond strength. The bond strength values of the bars with coarse sand-coating exceeded the respective values of the fine sand-coated ones. However, increasing the concrete strength was found to result in a greater improvement in bond behavior of fine sand-coated bars due to the penetration of concrete particles into the fine sand-coating layer. The effects of fiber type, bar diameter and concrete compressive strength on the bar bond strength was shown to primarily originate from the relative slip of fibers inside the resin of the bar, also known as the shear lag effect. Fiber-reinforced polymer (FRP) bars have been increasingly used in the field of structural engineering due to their significant advantages, such as high tensile and fatigue strengths, high corrosion resistance, lightweight, ease of transportation and handling, thermal and electrical insulating (GFRP only) properties and being unresponsive to magnetic fields ,2,3. On The previous research studies and field applications concentrated on four different types of FRP  that can be used in the form of concrete reinforcement. BFRP and GFRP bars are the most preferred types as internal reinforcement in concrete members owing to their lower prices and ease of supply than the CFRP and AFRP bars. BFRP bars have slightly higher modulus of elasticity and tensile strength values than GFRP bars, yet the respective values of both BFRP and GFRP are considerably lower than those of CFRP and AFRP ,7. GFRP CFRP has various superiorities over the other three types, including the highest tensile and fatigue strengths and being the least vulnerable FRP type to environmental effects , fatigue and creep rupture. Nevertheless, CFRP also has some major disadvantages, including the electric conductivity, high price, vulnerability to electrochemical corrosion when in contact with metal materials in a humid environment and the highly brittle nature ,4. RecenThe bond between an FRP bar and the surrounding concrete is the governing factor that determines the efficiency and suitability of the utilization of FRP bars as concrete reinforcement. In flexural RC members (slabs and beams), the compression forces in concrete are counterbalanced by the tension forces in the reinforcement and the development of these tension forces entails the adequacy of the reinforcement–concrete bond in the tension zone. The types of bond mechanism of FRP bars in concrete are similar to those of steel bars, which are the mutual adhesion, surface friction and shear interlock. Nevertheless, the mechanical properties of FRP bars are completely different from those of steel bars  14,15].,15.14,15In the literature, numerous experimental, analytical and numerical studies were conducted on identifying the prominent factors affecting the concrete-FRP bond; nevertheless, a great majority of these studies concentrated on monitoring the influence of only one or a few of all parameters. In the current study, on the contrary, all main parameters affecting the bond strength of FRP bars in concrete were investigated by conducting an extended literature survey. This survey indicated that there is consensus among the researchers on the effects of certain parameters on the FRP–concrete bond, while the effects of the other parameters have not been clearly unveiled yet. There is a variety of opinions on the effects of these parameters. The present literature review introduces the parameters one by one together with the findings of the previous researchers on this parameter. Besides, the related provisions from the structural FRP RC codes are also discussed throughout the manuscript. Accordingly, the main goal of the present study is to present the recent developments and challenges related to the utilization of FRP bars in concrete by underscoring the most influential factors affecting the FRP–concrete bond based on the previous works on this topic.d);Bar Diameter  and bar spacing (cs);Concrete cover (dl) or embedment length (el);Development ;Compressive strength  the inherent properties of FRP rebars; (ii) the arrangement and configuration of reinforcement; (iii) the inherent properties of concrete; and (iv) the method of testing. The complete list of parameters is as follows:A detailed section is devoted to each one of these parameters in the following discussion. A detailed table, which compiles the tests and studies used in that section, is given in each section to avoid any confusion and to clearly reveal the effects of each parameter on the FRP–concrete bond. The entire table of each section was discussed and debated in its entirety with additional comments of the authors.The previous researchers did not reach an agreement on the denominations of the surface textures of FRP bars. In other words, the same surface type was termed differently by different researchers. This discrepancy caused significant confusion among researchers. To avoid confusion in the present review, each table contains two columns for the bar surface notations. The first column corresponds to the original notations in the source papers, while the second one refers to the notations suggested and used in the present text. The bar surface notations of the present review are given in The graphs and test results in the majority of the previous studies cannot provide credential comments on the effects of a certain test parameter on bond strength. The previous experimental studies do not possess the merit of focusing on a single parameter by isolating the related experiments from the remaining test parameters. Consequently, the experiments, which are intended to unfold the effects of a certain parameter on bond strength, include the coupled effects of numerous parameters. Moreover, the average values of the test results were adopted in the previous works when explicating the scatter plots. However, the values in these plots are scattered in a broad range and reliable and precise results may not be inferred by using the average values. Unlike the other review studies, the coupling of effects of different parameters were taken into account in the present text and the findings were elaborated by avoiding controversial arguments.The effect of a single parameter (dependent variable) on the independent variable (the FRP–concrete bond strength in this case) can only be unfolded if all other dependent variables are kept fixed in the related experiments. Otherwise, the coupling between the effects of several parameters will not allow the researchers to isolate of the effect of a single parameter and set a relationship between the examined dependent variable and the independent variable. In the context of investigating the effects of the FRP material type on the FRP–concrete bond strength, for instance, the surface texture, diameter, clear cover and distance from the adjacent bar of the tested bars need to be kept identical in the related experiments as well as the concrete grade, concrete type and fiber content of the concrete mixture. In that respect, the existing experiments in the literature do not suffice for the development of specific relations between each test parameter and the FRP–concrete bond strength.The test data on FRP–concrete bond strength is extremely scattered. The wide dispersion of this data mainly stems from the coupling between the effects of several parameters in the previous experimental studies, which were designed without paying attention to all parameters affecting the FRP–concrete bond. The mathematical analyses on the data with such a dispersion do not generate meaningful and accurate expressions, since the deviation of the actual data from the mathematical curve remains high, meaning that the mathematical curve does not accurately represent the experimental data.The surface texture types of FRP bars have not been standardized with regulations, standards and previous experimental studies. For instance, the rib dimensions of the ribbed FRP bars and the grain sizes of the coating layer in the sand-coated bars are rather different in different studies. Hence, the surface type with the same notation can be excessively different in the related tests, which exacerbates the broad scatter of the test data and even results in opposing test data in different experimental studies.In this study, as much data as possible was compiled from the literature to prepare tables from which clear and accurate conclusions on the effects of a single parameter could be reached. In this way, the effects of the remaining parameters on the FRP–concrete bond were minimized, if not completely eliminated. Furthermore, each finding or conclusion was justified with sufficient reasoning. The authors did not utilize scatter graphs or curves. Furthermore, the authors avoided using precise statements on certain parameters due to significant discrepancies between the related experiments in the literature. The ambiguous and even sometimes opposing findings in different studies complicates to draw definitive conclusions on these parameters. These discrepancies have been completely ignored in the previous statistical review studies. The present paper leaves it to the readers on these parameters instead of deriving conclusions from the controversial data. Only obvious and well-explained conclusions were drawn according to the existing test results, presented in tables in each section. In the present study, the dependent and independent (bond strength) variables needed to be presented in the table format rather than conducting an analysis and presenting them in a mathematical form for three main reasons:The authors could not make separate analyses on each type of FRP bars  in each section due to the absence of an adequate number of studies in the literature. For instance, the number of studies on CFRP and AFRP reinforcing bars is so limited that conducting separate analysis and reaching specific conclusions on these two types is not possible at all. Strictly speaking, the majority of the studies in the literature pertain to the bond behavior of GFRP and BFRP reinforcing bars in concrete. Consequently, the authors tried to reach general conclusions on the effects of each parameter on the FRP–concrete bond without diving into special comments on different FRP types. The findings from a single type of FRP were not generalized to all types, but only the common conclusions on all FRP types were given in the manuscript.The present pertains solely to the short-term bonding performances of FRP reinforcing bars in concrete. The FRP–concrete interfacial bond strength is subject to degradation due to environmental factors, including but not limited to the temperature, corrosive environments and humidity. Furthermore, long-term effects, including creep and fatigue, are also responsible for the changes in the adherence of FRP bars to concrete. The long-term bonding performances of FRP bars and the durability issues are planned to be covered in a companion paper.Significant effort has been spent in the literature to determine the effects of FRP bar diameter on bond strength. There are three basic opinions on the influence of bar diameter on bond strength. The first of these opinions relies on the concept of the relative slip between the core and the fibers on the outer surface (shear lag effect) resulting from the low slip resistance within the epoxy resin and at the epoxy–fiber interface under the action of axial tension forces ,19,20,21In this respect, the main reason for the differences between the findings of different researchers are expected to be a result of the shear lag effect. Several inherent properties of an FRP bar, including the fiber density, resin type, resin density and the mechanical properties of the constituents, were found to impinge on the shear lag effect. The degree of this effect also changes with the manufacturing conditions of the bar and the persistence of these conditions. Hence, the effects of bar diameter on bond strength can only be identified by considering all these variables.The literature contains a lot of studies on the influence of fiber type  on FRP–concrete bond strength. The statistical, review and research studies on this very topic are presented in In order to determine the effect of fiber properties on bond strength, The only clear outcome from this comparison is that the GFRP bars is the least favorable polymer bars in terms of adherence with concrete among the four types of FRP. However, reaching a crystal-clear conclusion about the contribution of AFRP, BFRP and CFRP fibers to the adherence with concrete is impossible to reach based on the available test results. The improved bonding properties of CFRP, BFRP and AFRP bars originate from two main reasons. The first reason is the shear lag effect, just like the related discussion on the effect of bar diameter. The shear lag effect is lower in FRP bars with resin and fibers strong in tension as compared to those with resin and fibers weak in tension. Considering that AFRP, BFRP and CFRP bars generally possess higher tensile stiffness values in comparison to the GFRP rebars ,43, the In the literature, a limited number of studies have been conducted on the effect of the modulus of elasticity of FRP on the concrete–FRP bond. Although various views on the effect of the change in the modulus of elasticity on adherence are presented in the literature ,52,53,54A good number of research studies in the literature are devoted to the influence of surface texture on concrete–FRP bar bond strength. Statistical, review and research studies on this topic are summarized in Accordingly,R1 and R2 is the fine sand-coating (SCf).R3 and R4 shows the coarse sand-coating (SCr).R5 is the standard sand-coating (SC).R6 illustrates the helically wrapped (HW) surface.R7, R8 and R9 are the helically wrapped and sand-coated surface (HWSC).R10 shows the indented (In) surface.R11, R12 and R13 correspond to the ribbed (Rb) surface.As shown in Hence, the adherence behavior alters into the mechanical interlocking with increasing concrete strength in bars with fine coating. Moreover, the surface areas of the fine sand-coated bars are larger due to the presence of indentations on the surface, and therefore, the contribution of improving the concrete quality to the bond strength becomes more considerable in these bars, having greater contact surface with concrete.The other surface types, which have deeper surface deformations, convey the internal forces to the surrounding concrete through both friction and mechanical interlocking. The two-component transfer mechanism is the main reason for the higher bond strengths of these bars. The mechanical interlocking capacity changes with the rib height, rib spacing and rib thickness. From this point of view, with some exceptions, as the rib height increases and the rib spacing decreases, the bond strength increases. This increase stems from the increased surface area for the mechanical interlocking forces to develop. On the other side, significantly narrow and deep ribs might also lead to considerable reductions in the rigidity of ribs, and hence, lower limits for the spacing and upper limits for the rib height need to be established with the help of more detailed studies. In general, the bars with “In” surface type have larger rib spacings due to the increased rib thickness values and these bars possess lower bond strengths as compared to the bars with “Rb” surface texture. The lower bond strength values are caused by the fact that the force transfer in the indented bars rely mostly on the surface friction rather than mechanical interlocking. As in the case of indented bars, the bond strength values of the ribbed bars remain below the respective values of the helically wound bars.In HW bars, the proportion of the forces transferred by the surface friction and mechanical interlocking varies with the height of the ribs. The contribution of mechanical interlocking increases with increasing rib depth, resulting in the increased adherence. Additionally, the bar starts to behave similar to a wedge with increasing rib height. Consequently, the shear forces are transmitted to the HW bars gradually, dissimilar to the sudden transfer of the shear forces in the FRP bars with In and Rb surface types. At around the peaks of the ribs, the mechanical interlocking forces turn completely into friction forces. This gradual transfer might also delay the shear failure of the beam by providing the transmission of shear forces along numerous interlaminar shear surfaces on the FRP bar instead of a single surface. The bars with “Rb” type of surface have superior bonding strength values when compared to the bars with “HW” type of surface.The effects of concrete cover and bar spacing on FRP–concrete bond strength have also been subject to a variety of studies in the literature. The researchers have sought to identify the changes in the failure modes of FRP bars with changing bar spacing and concrete cover. Albeit an adequate number of studies were devoted to the effect of concrete cover, the bar spacing has caught the attention of only few researchers. d (bar diameter) in all concrete types, i.e., NSC , HSC (high-strength concrete), UHSC (ultra-high-strength concrete) .,63.60,63oncrete) ,65. Whenplitting , while ampletely . ACI 440The previous studies adopted a variety of surface textures and FRP mechanical properties. Furthermore, significant variations in concrete strength and embedment length makes it almost impossible to reach precise conclusions on the need for concrete cover for the complete prevention of concrete splitting. The concrete splitting failure is a result of the transfer of splitting forces to concrete , which iIn summary, the FRP–concrete bond strength generally increases with increasing concrete cover since the confinement around the bar is improved with increasing cover thickness. The general tendency of the change in the FRP–concrete bond strength with increasing cover is complicated to specify as the failure mode also changes with increasing thickness of the concrete layer around the bar. Strictly speaking, the bond strength undergoes sudden changes while increasing the concrete cover, particularly at the transition of the failure mode from concrete splitting to debonding or rupture. Furthermore, concrete cover cannot be considered alone in the evaluation of test results, since this parameter governs the failure mode of a rebar together with the bar embedment length. Hence, the previous studies refrained from focusing on the simultaneous effects of concrete cover and embedment length on the FRP–concrete cover. Instead, only one of these two parameters changed in the related tests while keeping the other parameter fixed.d, the bond strength was found to be unaffected by further increasing the bar spacing [The number of studies on the influence of bar spacing on the FRP–concrete bond is rather limited and these studies showed that increasing the spacing between bars can contribute to the bond strength up to 50% ,50. If t spacing .There has been a great deal of research undertaken in the literature on the effects of embedment or development length on the FRP–concrete bond strength ,76,77,78The studies on the effects of reinforcement location concentrated on two positions, namely the lower and upper portions of the member, according to the direction of concrete cast. These studies generally concluded that the bond strengths of the upper bars are smaller than their lower counterparts since the water, air and fine aggregates in the mixture move upwards and accumulate underneath the rebars  65,81,8,881,82.In two of these studies ,81, the A great majority of the previous studies in the literature consisted of pull-out tests for determining the FRP–concrete bond strength, and hence, the number of studies on the effects of transverse reinforcement on the FRP–concrete bond is rather limited. The confining effect of transverse reinforcement on the longitudinal bars can only be reflected with the help of beam tests. There are two common opinions on this confining effect. The first one is the contribution of transverse reinforcement to bond strength through limitation of the crack widths in the member . AccordiThe effect of concrete compressive strength on bond behavior may differ in steel and FRP reinforcing bars. Since steel rebars are homogeneous and isotropic as well as have a wholistic structure, bond failure patterns and stresses are governed by the shear strength of concrete . HoweverThe effects of fiber addition to concrete mixture, which aims at controlling the crack widths by increasing the tensile strength of concrete, on the FRP–concrete bond has been subject to various studies in the literature. Some of these studies are given in This cracking might also be affected by the fibers inside the mixture by improving the tensile strength of concrete and this effect will primarily depend on the density and length of fibers in the vicinity of the rebars . NonetheVarious types of concrete were employed in the previous studies on the FRP–concrete bond . HoweverThe present paper is a detailed literature review on all parameters affecting the bond behavior of FRP reinforcing bars embedded in concrete. The influence of each parameter is discussed in the light of the findings of previous researchers. Precise and clear comments are given throughout the manuscript. The controversial and opposing comments of the previous researchers are not mentioned in the manuscript, since most of these comments originate from the differences between the testing conditions and test methods in different studies and negligence of certain parameters affecting the FRP–concrete bond. With the aim of not listing the inconsistent and ambiguous findings, only the following unquestionable conclusions are given in the present text together with the justifications behind each finding.The bond strength of an FRP bar decreases with increasing bar diameter. This decrease is associated with three possible reasons. First, the slip of fiber layers within the resin, also known as the shear lag effect, is aggravated with increasing bar size and this effect has a negative impact on the FRP–concrete bond. Secondly, the amount of air voids and mixing water, accumulating underneath the bar, increases with increasing bar size and the weakness of the concrete around the bar results in the reduction of the bond strength. Finally, the mechanical interlocking and surface friction forces of a bar decrease as a result of the greater degree of Poisson’s effect on the bar with increasing bar diameter.The bond strength values of GFRP bars are lower than the respective values of their CFRP, AFRP and BFRP counterparts, embedded in a similar concrete mixture. The lower adherence of GFRP to concrete stems from the more considerable shear lag effect in the GFRP bars due to the lower axial stiffness than the other three types of FRP. The greater slip of fibers from the core in GFRP results in the reduced bond strength values of these bars. Furthermore, the increase in the radial thermal expansion of the BFRP, AFRP and CFRP bars due to the friction at the bar–concrete interface improves the mechanical interlocking and surface friction of these bars in concrete, as compared to the GFRP bars, which are known to have smaller thermal expansion coefficient.FRP bars with coarse sand-coating layer have higher bond strength values in normal-strength concrete than the bars with fine sand-coating layer. However, the bonding behavior of the fine sand-coated bars is improved to a greater extent with increasing concrete strength as compared to the coarse sand-coated bars. The better compaction and the lower amounts of air voids in high-strength concrete mixtures enable the fine particles of concrete to penetrate into the fine sand-coating layer and improve the bond behavior.The mechanical interlocking mechanism is improved in ribbed bars with increasing rib height and decreasing rib spacing. The increase in the surface area for the development of mechanical interlocking forces results in the FRP–concrete bond strength to increase when using deeper ribs. However, further studies on the topic are needed to determine the minimum spacing and maximum height limits of the ribs since too closely-spaced and/or too deep ribs might reduce the rib rigidity and have adverse effects on the bond strength.The thicker and more widely-spaced ribs in the bars with indented surface enables them to transmit greater surface friction forces as compared to the ribbed bars. Therefore, the bond strength values of the indented bars remain below the respective values of the ribbed and helically wrapped bars.The concrete cast depth underneath an FRP bar influences the bond strength to a significant extent. With increasing cast depths, the amount of air voids and water underneath a bar increases, resulting in the compressive strength of concrete surrounding the bar and the FRP–concrete bond strength to decrease.According to the existing studies in the literature, a clear concrete cover of at least three times the bar diameter is compulsory to avoid concrete splitting failure and to allow the debonding or tensile rupture failures to govern the specimen behavior. Increasing this spacing beyond seven times the bar diameter does not have a considerable effect on the FRP–concrete bond strength.The contribution of increasing the compressive strength of concrete to FRP–concrete bond strength is bounded by upper limits. Increasing this strength contributes to the shear strength of the concrete layers around the bar, yet beyond certain limits of concrete strength, the peeling of the outer bar surface from the core and/or slip of the fibers inside the resin can trigger the bond failure of the bar rather than the shear failure of the surrounding concrete.The bond strength tends to decrease with increasing embedment length of an FRP bar in concrete. The non-uniform stress distributions along the bar length and the reductions in the ability of a bar to convey the internal forces through surface friction are the primary reasons for the reduction in bond strength with increasing embedment length. This decrease follows a uniform path with increasing embedment length.The transverse reinforcement definitely affects the FRP-concrete bond strength. However, further studies are needed to unfold the degree of this effect due to wide range of variation of the other test variables in the existing studies.The maximum aggregate size and fiber length controls the initiation and spread of cracks in concrete based on the surface texture. Further studies are needed to uncover the effects of maximum aggregate size on the bond strengths of FRP bars embedded in the concrete mixtures with fibers.The existing studies are not sufficient to specify the concrete cover boundaries for the change in the type of failure of FRP bars in concrete due to wide variations in the surface types and mechanical properties of the tested bars as well as the wide ranges of concrete strength and bar embedment length in the related tests. The concrete splitting failure necessitates the transfer of adequate splitting forces in concrete , which i


Extending well beyond the energy conversion function, transition metals are also essential for mitochondrial biosynthetic and proteolytic machinery, and antioxidant defenses. Moreover, mitochondria are the sites of synthesis of vital metal-containing cofactors such as heme and iron-sulfur clusters that support a variety of cellular functions inside and outside of mitochondria. Last but not least, metal homeostasis in mitochondria influences the management of transition metals at the cellular level. Therefore, unraveling the mechanisms behind the function, formation, and regulation of mitochondrial metalloproteome is crucial to understanding the involvement of transition metals in the life of eukaryotic cells.Mitochondria are essential metabolic and redox hubs of eukaryotic cells, which apart from their best-known role in energy generation, participate in a plethora of biochemical processes. Many of the critical mitochondrial functions depend on transition metals as cofactors of enzymes that are housed within the organelle. One canonical example is the mitochondrial respiratory chain, which utilizes the redox chemistry of iron-sulfur clusters, copper ions, and heme to transport electrons from reducing equivalents such as NADH and FADHc oxidase. Nonetheless, a number of outstanding questions in the area of mitochondrial transition metal homeostasis remain to be addressed. For example, the regulation of metal homeostasis in mitochondria and coordination of cofactor biosynthesis with other functions of these organelles remains to be elucidated.In recent years, various aspects of the role and regulation of transition metals homeostasis in mitochondria were explored. An important research hotspot was the assembly of metal cofactors into mitochondrial metalloproteins and the machinery that chaperones and secures safe handling of immature cofactors. Another vital development includes the identification of key enzymes that catalyze the synthesis of metal cofactors such as iron-sulfur clusters and heme and proteins involved in the delivery of copper to the respiratory complex IV, also known as cytochrome This Research Topic of Frontiers in Cellular and Developmental Biology features three reviews and one original research report that provide state-of-the-art perspectives on the biogenesis of mitochondrial metalloproteome, its functions, and regulation.Medlock et al. for the first time summarizes and discusses an intriguing connection between homeostasis of mitochondrial transition metals and mitochondria contact site and cristae organizing complex that emerged over the last few years. The unique (and still largely uncharted) spatial organization of mitochondrial membranes is inherently intertwined with metabolic and energy transitions in mitochondria. Could it also serve as a coupling mechanism that efficiently distributes organellar resources to secure an adequate supply of metal cofactors? The review by Yien and Perfetto provides an updated overview of mitochondrial heme synthesis with particular emphasis on mechanisms that regulate this pathway. The authors focus equally on the enzymes directly involved in successive steps of heme synthesis as well as on much less explored mitochondrial transporters that control the movement of heme and critical intermediates across the mitochondrial membranes. In their perspective, the authors underscore the importance of tissue-specific mechanisms that tailor heme synthesis to the requirements of a particular cell type. The authors also stress the significance of protein-protein interactions and complex formation in crucial nodes of this vital pathway. An emerging concept of spatiotemporal regulation of mitochondrial processes is also relevant and applicable to metal homeostasis in the organelle. In the era of cryo-EM technology-powered structural studies that are proven to be so effective in deepening our understanding of the dynamic nature of the other mitochondrial supramolecular machinery, the fact that enzymes involved in heme synthesis form such assemblies is particularly intriguing. Related to that note, the article by Obi et al. presents a comprehensive review of the structure of the key heme biosynthetic enzyme ferrochelatase. Based on the structures of substrate-bound and free ferrochelatase from humans and other species, the authors propose an unifying model of the catalytic cycle of this enzyme that describes mechanisms of entry of protoporphyrin IX and iron into the active site as well as the release of the heme molecule. Obi et al. further discuss regulation and posttranslational modifications of ferrochelatases. Interestingly, the authors review the inhibition of human ferrochelatase as a side effect of certain approved drugs, additionally touching upon the curative potential of the evoked photosensitivity in photodynamic therapies. Finally, the original research paper by Brischigliaro et al. investigates the effects of cytochrome c oxidase deficiency in flies and reports on the discovery of new intriguing connections between the fitness of mitochondrial respiratory chain and cellular homeostasis of transition metals such as copper.The review by Altogether, this Research Topic offers a selection of articles providing comprehensive summaries or conveying new findings pertaining to a complex topic of the biogenesis and maintenance of mitochondrial metalloproteome. Both established and new lines of evidence link these processes to diseases in humans for which no effective treatments currently exist. It is therefore important to understand these facets of mitochondrial biology in order to develop potential new avenues for therapies targeting relevant pathways. We anticipate that this Research Topic will be of equal interest to both the experts in the field and researchers looking to learn more about metals in mitochondria.


If we were to look back at the history of orthopedics only two generations ago, the intertrochanteric osteotomy was a well-established procedure for the treatment of osteoarthritis of the hip . The proProximal femur osteotomies were mainly reserved for selected pediatric orthopedic indications, leaving the majority of modern adult reconstructive surgeons unfamiliar with the technique and its pitfalls. THA thus became the “bread & butter” procedure for the adult reconstruction surgeon.With total hip arthroplasty on the rise and the corresponding huge focus on refining implants and surgical techniques, there was still enough space for the birth of the niche of hip preservation surgery. This field emerged after a publication by Reinhold Ganz and his colleagues in 2003 , describWith the current improved understanding of morphology and pathology, a revival of the periacetabular osteotomy (PAO) and proximal femur osteotomies is on the rise and in demand, more than any time before .The fact that reduced femoral antetorsion causes an early anterior conflict upon internal rotation of the hip has raised the significance of appreciating torsional correction in cases where cam and pincer correction alone would result in an inadequate restoration of internal rotation . On the The robust method of tackling such pathologies is by working on correcting the underlying morphological abnormality. This mandates sweeping the dust off the stored instrument sets of angled blade plates that are likely to still be found in the cellars of most orthopedic departments. The coming generation of young adult hip surgeons will have to revive the techniques of osteotomy and possibly initiate implant innovation and precision surgery in the field.On the acetabular side, anterosuperior undercoverage is no longer the only indication for reorientation. The understanding of three-dimensional anatomy underlines the problem of posterolateral undercoverage in a truly retroverted acetabulum as well as focal anterior undercoverage in an anteverted acetabulum with sufficient posterolateral coverage. This allows a wide range of possible variants of pathomorphology that require individualized treatment. With the improvement in safety and efficacy of reorientation procedures, such as the PAO, the threshold for performing surgery is also lowering, allowing many more patients to benefit from the power of its success. Digital technology will aid in this development by driving improvement in the simulation of pathology, surgical planning, and accuracy of concept implementation.The ideal future hip surgeon will encompass a diverse set of surgical skills that are utilized on an individual patient-specific basis after meticulous analysis of individual pathomorphology based on evidence and digital assistance. That said, the future of hip surgery is certainly exciting and bright!


The racial riots of 2020 in the US, beginning in Minneapolis, had a global impact inciting protests internationally. We look at the impact of COVID, the social isolation and frustration that therefore existed and how this effected the instigation of the riots.--To review the history of racism in the United States and the abolition theories, comparing US and UK. --To consider the impact of international immigration on the cultural tension in the US; Minnesota accepted a large population of Somalis in 1992 as refugees. --To explore how this progress toward racial equality has stagnated under the leadership of President Donald Trump. --To look at how COVID in the context of the above historical factors has served as a unwitting catalyst to racial riots and global protests.Literature research including historical accounts of principles of abolition, post-civil war reconstructive political manuevers, 1950’s segregation protests and political supports (US and UK), refugee relief efforts made by the US [specifically related to Somalia], and reports regarding the impact of COVID on the 2020 reaction to racial injustice.Evidence suggests that across time periods, recourses of politicians [US and global] resulted in negative relations internationally with respect to immigration. The unique situation created by COVID resulted in a crucible effect following the death of George Floyd.Previous attempts at creating equality have proven unsuccessful and apathetic on the part of those in power. This has lead to a situation where COVID created a perfect storm in order to ignite racial tensions in the US.


Knowledge on the anatomy of the sphenopalatine artery (SPA) and its branches is fundamental for the success of the endoscopic treatment of posterior epistaxis. However, the complex anatomical variations seen in the irrigation of the nasal cavity poses a significant surgical challenge.Objective: This paper aims to describe the endoscopic anatomy of the SPA in human cadavers.Materials and Methods: This is a contemporary cross-sectional cohort study carried out between April 2010 and August 2011. The presence of the ethmoidal crest on the lamina perpendicular to the palatine bone and the location of the principal sphenopalatine foramen (PSF) and the accessory sphenopalatine foramen (ASF) were analyzed in 28 cadavers, and the branches emerging from the foramens were counted.Results: Fifty-six nasal fossae were analyzed. The ethmoidal crest was present in 96% of the cases and was located anteriorly to the PSF in most cases. The PSF was located in the transition area between the middle and the superior meatus in all cases. The ASF was seen in 12 cases. Most nasal fossae (n = 12) presented a single bilateral arterial trunk emerging from the PSF. In other cases, three (n = 8) or two (n = 5) arterial trunks emerged bilaterally from the PSF. In most cases, the SPA emerged as a single trunk from the ASP.Conclusions: The anatomy of the SPA is highly variable. The success of the treatment for severe epistaxis relies heavily on adequate knowledge of the possible anatomical variations of the sphenopalatine artery. The main source of blood in the nasal cavity is the sphenopalatine artery (SPA), a branch of the external carotid system. The SPA is situated in the posterior region of the nasal cavity, and is involved in most severe epistaxis episodesThe sphenopalatine foramen is a notch on the upper margin of the palatine bone between the orbit and the sphenopalatine process. It turns into a foramen as the palatine bone joins the sphenoid bone on the lateral nasal wall. Variations in size, shape, location, and number of branches emerging from its orifice have been described scarcely in the literatureCurrent trends dictate that posterior packing should be replaced by the endoscopic ligation of the sphenopalatine artery in cases of posterior bleeding to reduce morbidity and patient discomfort levelsThis study aims to describe the endoscopic anatomy of the sphenopalatine artery in cadavers and the possible anatomic variations, and assess the bone landmarks used to identify the sphenopalatine foramen.A descriptive anatomic study on the sphenopalatine artery was performed at the Pathology Service of a tertiary care hospital between April of 2010 and August of 2011. Twenty-eight cadavers were included in the study. Specimen collection took place between three and 12 hours as of the time of death of the subjects. The data collected on the cadavers included race, gender, age, time of death, time of autopsy, and cause of death as per the autopsy protocol of the hospital's pathology service. Cadavers with nose trauma, previous nose surgery, or nasal diseases preventing dissection were excluded.The analysis of the endoscopic anatomy of the sphenopalatine artery was carried out using a nasal endoscope with a 30-degree rigid scope, 4.0 mm (Karl Storz), fiber optics, and a Komlux light source (250 watts), a Toshiba monitor (model CRT 1030), and a video endoscopy device (model Toshiba IK-CU44A). Images were recorded and stored using a video capturing software .All dissections were done bilaterally, in accordance with the following steps of nose endoscopic surgery: (1) The middle concha was shifted medially to expose, with the aid of an endonasal probe, the transition between the posterior medial maxillary wall and the perpendicular portion of the palatine bone; one vertical incision was made on the mucosa of the lateral nasal wall of 1.5 cm from the beginning of the perpendicular portion of the palatine bone to the upper portion of the inferior concha; (2) A mucoperiosteal flap was made along the posterior area of the nose, from the transition between the middle and posterior meatus, until the sphenopalatine foramen and its vessels were identified; (3) Dissection was done until the anterior wall of the sphenoid sinus to identify other possible arterial branches. Samples of one centimeter starting from the point of emergence of the foramen were collected from the best segments bilaterally. These samples were taken to histopathology for testing to validate the arterial origin of the visualized structure.The anatomic structures were identified and categorized for: (1) Presence of anterior ethmoidal spine on the perpendicular plate of the palatine bone; (2) Location and presence of the sphenopalatine foramen (SPF) and the accessory SPF (ASPF). The SPF was considered as the largest bony orifice on the lateral nasal wall from which the arterial trunks adjacent to the ethmoid crest of the lamina perpendicular to the palatine bone. The ASPF was described as a smaller bony orifice beyond the SPF; (3) Number of arterial branches stemming from the identified foramens; and (4) Prevalence and analysis of symmetry .The locations of the sphenopalatine foramen and the accessory sphenopalatine foramen were defined in relation to the insertion point of the middle concha: a) on the superior meatus (SM): the opening of the SPF appears above the middle concha insertion point; b) on the transition between the superior and middle meatus (SM/MM): the opening of the SPF occurs under the ethmoidal spine; c) on the middle meatus (MM): the opening of the SPF is below the line of insertion of the middle concha.This study was approved by the local Ethics Committee and given permitFifty-six nasal fossae of 28 cadavers were analyzed, 13 of which males and 15 females. Mean age was 58.32 ± 17.17 years, and ages ranged between 11 and 91. Fifteen were Caucasians and 13 were of African descent. .Table 1SThe ethmoidal spine was present in 96.4% of the cases . Only onMost nasal fossae had a single bilateral arterial trunk (n = 12) emerging from the SPF. Others had three (n = 8) or two arterial trunks (n = 5) bilaterally . On onlyHistology analysis confirmed that all specimens collected were of arterial origin.DISCUSSIONKnowledge on the anatomy of the sphenopalatine artery and its branches is fundamental in the endoscopic treatment of severe posterior epistaxis. Success rates can be greater than 95% in the hands of experienced surgeons. This procedure is associated with low complication ratesThe methods employed in nasal anatomy studies vary depending on the specimens and approaches used. Herrera Tolosana et al.Age ranges are rarely cited in studies on nasal anatomy. Cranial facial development from childhood to adult age alters the ratio between the surgical landmarks of the skullThe ethmoidal spine is present and close to the sphenopalatine foramen in most human beings. Many authors consider the ethmoidal spine as the main anatomic landmark when facing difficulties ligating the sphenopalatine artery during an episode of epistaxisHerrera Tolosana et al.Simmen et al.The presence of an accessory foramen on the lateral nasal wall has been well established in the literature. However, its occurrence varies significantly. The presence of an accessory foramen may be related to failure of the endoscopic treatment of severe epistaxis•ANTERIOR: the anterior border of the perpendicular portion of the palatine bone is the best landmark to start dissecting the mucoperiosteal flap. The easiest way to find this landmark is by palpating the posterior medial maxillary wall at the level of the hrizontal portion of the middle concha. The posterior medial maxillary wall is a moving soft structure. As you palpate it from the anterior to the posterior nasal fossa, you will soon find a stiff hard structure, the anterior plate of the palatine bone, where the mucoperiosteal detachment is initiated .Figure 4•SUPERIOR: the highest point of the anterior plate of the palatine bone ends where it meets the fat tissue of the pterygopalatine fossa. The dissection of the mucoperiosteal flap up to this level will reveal all possible accessory foramens of the superior portion of the sphenopalatine artery complex .•INFERIOR: the insertion point of the inferior concha is the most inferior point in the extension of the mucoperiosteal flap. From this line the accessory branches of the sphenopalatine artery cannot be identified .Figure 5•POSTERIOR: as the anterior wall of the sphenoid sinus and the Eustachian tube are identified, the dissection of the mucoperiosteal flap is completed with the certainty that all branches and foramens of the sphenopalatine artery have been identified .In order to ensure the identification of all branches of the sphenopalatine artery, we propose the delimitation of the endoscopic “Sphenopalatine Quadrangle”  for the The anatomy of the sphenopalatine artery is highly variable. The ethmoidal spine is an important anatomic landmark, as it is present in almost all cases in a position anterior to the sphenopalatine foramen. The most frequent location of the sphenopalatine foramen was in the transition between the middle and superior meatus.


The presence of acquired speech disorders of varying evidence can cause maladjustment and job loss. Often there is no adequate psychological and psychotherapeutic assistance for these patients, which hinders the process of recovery and reintegration into the social environment.To study the level of anxiety and depression in patients with dysarthria who have undergone various types of cerebrovascular accidents. To give practical recommendations regarding the correction of these conditions.To assess the level of anxiety and depression, the Hospital Anxiety and Depression Scale (HADS) was used as the most convenient for application in clinical practice.The study involved 42 people in the age group 45-60 years old with the consequences of cerebrovascular accident in the form of various types of dysarthria and without severe movement disorders. All participants had a university degree and a confirmed stroke of anamnesis. According to the data obtained, 45% of patients had symptoms of depression, 52% – anxiety. It should be clarified that specific weight of men with manifestations of depression and anxiety was higher . The beginning of active antidepressant therapy in a hospital setting showed a positive subjective effect from such influences – in 38% of patients.The use of modern methods for assessing the level of anxiety and depression in patients with speech disorders should become an obligatory stage of diagnostic measures. Psychological assistance and pharmacological correction not only helps patients to adapt to new social conditions, but also promotes prevention the progression of depressive manifestations.No significant relationships.


The working environment of rotating machines is complex, and their key components are prone to failure. The early fault diagnosis of rolling bearings is of great significance; however, extracting the single scale fault feature of the early weak fault of rolling bearings is not enough to fully characterize the fault feature information of a weak signal. Therefore, aiming at the problem that the early fault feature information of rolling bearings in a complex environment is weak and the important parameters of Variational Modal Decomposition (VMD) depend on engineering experience, a fault feature extraction method based on the combination of Adaptive Variational Modal Decomposition (AVMD) and optimized Multiscale Fuzzy Entropy (MFE) is proposed in this study. Firstly, the correlation coefficient is used to calculate the correlation between the modal components decomposed by VMD and the original signal, and the threshold of the correlation coefficient is set to optimize the selection of the modal number  As the rotating support components of most machinery, the fault detection and diagnosis of rotating machinery such as rolling bearings is essential to prevent mechanical failures ,2. A varThe key to fault diagnosis lies in analyzing the original signals from the time-frequency domain and constructing feature sets from different aspects to describe the running state of the rotating machinery. At present, one of the most commonly used time-frequency analysis methods is Empirical Mode Decomposition (EMD) . Bustos Fuzzy Entropy (FE) is a measure of the probability that a time series will generate new patterns when its dimensionality changes . MoreoveMost of the above methods only consider the fault diagnosis in the case of a single feature, which creates a problem of insufficient fault feature representation. In order to describe the weak fault features from multiple perspectives better, this study proposes an early fault feature extraction method that combines AVMD and MFE. The parameters of the MFE are optimized by the Particle Swarm Optimization (PSO)  algorithThe second part of the article introduces the principles of AVMD and PSO to optimize MFE. The third part introduces the specific process of constructing a fault feature set based on AVMD combined with optimized MFE. The fourth part uses the DDS test bench for experimental analysis. It is proved that the combination of AVMD and optimized MFE can describe the MFE characteristics of fault signals in multiple frequency bands, which can better characterize more weak fault information, and is more sensitive to the early weak faults of rotating machinery. Additionally, compared with the traditional decomposition method, the method proposed in this study has higher fault diagnosis accuracy.The overall framework of VMD is to solve the variational problem in order to minimize the sum of the estimated bandwidths of each eigenmodal function, where each eigenmodal function is assumed to be a finite bandwidth with different center frequencies. To solve this variational problem, the alternating direction multiplier method is used to continuously update each eigenmode function and its center frequency, which can demodulate each eigenmode function to the corresponding fundamental frequency band and, finally, extract each eigenmode function and its corresponding center frequency.The decomposition steps of the variational modal decomposition are as follows:(1)Initialize (2)(3)update according to the update formula for (4)update (5)Given the precision ω, if the stopping condition Where Compared with EEMD and other adaptive decomposition algorithms, the VMD algorithm has better sparse modal components, but the decomposition result of the VMD algorithm is affected by multiple parameters, among which the modal number This article chooses the method of combining the correlation coefficient with VMD to optimize the value of parameter In the formula, Therefore, due to the smaller The penalty factor is one of the parameters that must be adjusted manually in VMD. Too small a penalty factor VMD and the correlation coefficient are combined to optimize the selection of the modal number. The initial modal number ,In order to check the effectiveness of the algorithm, this section takes the simulated signal as an example, and uses the AVMD algorithm proposed in this article to verify the decomposition effect. For periodic simulation signal: It can be seen from the correlation coefficient between each modal component and the original signal that when As shown in According to the sampling frequency of the periodic simulation signal, From the spectrogram of each modal component after VMD under different Therefore, from the above analysis of the simulated signal, it can be seen that the default penalty factor Multiscale Fuzzy Entropy (MFE) is improved on the basis of fuzzy entropy and combined with multiscale entropy to measure the complexity and similarity of time series under different scale factors. MFE can be calculated as follows:(1)Coarse-grained original time series (2)Calculate the fuzzy entropy of coarse-grained sequence under each scale factor, and its calculation formula is:The parameter selection of the MFE has a great influence on the extracted MFE features of the vibration signal. Selecting the default parameter settings cannot adequately characterize the weak fault characteristics of rotating machinery. It will have a greater impact on the diagnostic results.The Particle Swarm Optimization (PSO) algorithm is one of the evolutionary algorithms. It starts from a random solution, finds the optimal solution through iteration, and evaluates the quality of the solution through fitness. However, it is simpler than the genetic algorithm rule, and finds the global optimum by following the currently searched optimal solution. This algorithm has the advantages of easy implementation, high precision and fast convergence. Additionally, it has demonstrated its superiority in solving practical problems. Therefore, this study chooses to optimize the parameters of MFE with a PSO algorithm.The PSO is initialized to a group of random particles (random solutions), and then the optimal solution is found through iteration. At each iteration, the particle updates itself by tracking two “extreme values” Obtain the original signal, initialize the modal number (2)Perform VMD on the vibration signal and calculate the correlation coefficient between each mode and the original signal. When the correlation coefficient satisfies the termination condition, the correlation coefficient threshold less than (3)The optimized VMD is performed on the vibration signal to generate (4)In order to minimize the Ske of the original signal, the optimal MFE parameters are obtained by adaptive optimization using the PSO algorithm.(5)Calculate the MFE of (6)Input the fuzzy entropy feature set obtained in the previous step into the classifier for fault identification.In order to further verify the effectiveness of the method proposed in this article, five different types of bearing and gear faults on the DDS test bench were collected, and the cube method proposed in this article was used for fault diagnosis to prove the effectiveness of the method. Five different categories of bearing and gear failure are: (1) inner ring fault; (2) outer ring fault; (3) rolling body fault; (4) inner ring + gear wear fault; (5) inner ring + broken tooth fault. The DDS fault diagnosis comprehensive test bench and test gear are shown in Using the method proposed in this study, the initial AVMD cross-correlation coefficient threshold was set to After that, taking Ske as the objective function, the parameters of MFE embedding dimension M, scale factor S and time delay T are optimized by PSO algorithm. Set the population size to 15 and the maximum iteration times to 30. Set the value range of optimization parameters according to fault signal characteristics: M is , S is  and T is . The MFE parameters of the five types of fault vibration signals are shown in A total of 500 samples was extracted from five different fault vibration signals collected by the DDS test bench, with each sample having 1024 sampling points. It can be seen from In order to further analyze the feature vector set constructed by the method in this study, the T-SNE method was introduced to visualize the eigenvector set, and the distribution of five types of faults in the low-dimensional space was observed. As shown in As shown in the The MFE feature set constructed by the five methods were put into the SVM, and the accuracy of the five methods is shown in As shown in It can be seen from In this study, a method combining AVMD and optimized MFE is proposed to construct a fault feature set, and this method is verified by DDS test bench data. Compared with other decomposition methods and feature extraction methods, the fault diagnosis accuracy rate in the proposed method reaches the highest 98%. The superiority of the method proposed in this study is proved.(1)By analyzing the simulation and experimental results, AVMD optimizes the mode number (2)The early fault feature extraction method based on AVMD and optimized MFE mainly decomposes the fault signal through AVMD. Taking Ske as the objective function, PSO searches for the optimal parameters of MFE and extracts the MFE features in multiple frequency bands. Through this method, the MFE of the modes in different frequency bands is calculated by decomposing the adaptive variational modes, and the MFE in different frequency bands is used to form a feature vector set. In this way, the weak fault information of rotating machinery can be more fully characterized, and it is more conducive to the early weak fault identification. Simultaneously, it can achieve higher fault diagnosis accuracy.(3)The MFE feature extraction method based on AVMD can effectively extract the weak fault information of the fault signal, but the calculation amount of MFE is large. The next work will improve this problem to improve the computational efficiency.


Ireland previously had widespread voluntary fortification but there has been a major decline in the number of food staples fortified with folic acid in Irish supermarkets in the past 15 years. In this research we set out to examine the level of folic acid in food staples in supermarkets with the leading market share in the Republic of Ireland.The food labels of food staples  were photographed in supermarkets with the leading market share in the Republic of Ireland  between 2017 and 2021.The data was extracted and collated in an excel spreadsheet. The data was analysed to examine the level of folic acid in each product. We compared the levels captured at the current times with the levels previously captured in 2017.Preliminary analysis suggests that folic acid level in food staples in Ireland continues to decline. Folic acid was not found in any breads (except a number of gluten free breads), milks, spreads but was found in several cereals marketed mainly at children.This study reports on the declining levels of folic acid in the food chain in Ireland. The number of food staples fortified with folic acid continues to decline demonstrating that voluntary fortification in Ireland is no longer an effective measure for passively augmenting the folic acid levels of consumers. This is of concern due to the incidence of neural tube defects in Ireland largely preventable by folic acid.This study reports on the declining levels of folic acid in the food chain in Ireland.The number of food staples fortified with folic acid continues to decline.