Formalized breeding schemes are a key component of breeding program design and a gateway to conducting plant breeding as a quantitative process. Unfortunately, breeding schemes are rarely defined, expressed in a quantifiable format, or stored in a database. Furthermore, the continuous review and improvement of breeding schemes is not routinely conducted in many breeding programs. Given the rapid development of novel breeding methodologies, it is important to adopt a philosophy of continuous improvement regarding breeding scheme design. Here, we discuss terms and definitions that are relevant to formalizing breeding pipelines, market segments and breeding schemes, and we present a software tool, Breeding Pipeline Manager, that can be used to formalize and continuously improve breeding schemes. In addition, we detail the use of continuous improvement methods and tools such as genetic simulation through a case study in the International Institute of Tropical Agriculture (IITA) Cassava east-Africa pipeline. We successfully deploy these tools and methods to optimize the program size as well as allocation of resources to the number of parents used, number of crosses made, and number of progeny produced. We propose a structured approach to improve breeding schemes which will help to sustain the rates of response to selection and help to deliver better products to farmers and consumers. Any pipeline should have a clear deliverable/product to be handed at the end of the pipeline and a clear customer . A market segment is defined by the target population of environments in which the final product is grown, as well as descriptions of the target clients and product traits that are valued for production and consumption by farmers and end-users. Products to be placed in a market segment are described through product profiles/concepts; detailed descriptions of the traits and their thresholds  to be found in the desired product or variety (sometimes based on current variety in the market) that aims to increase the likelihood of acceptance in the market. A breeding pipeline within a program may target one or more market segments and the associated product profiles using one or more breeding schemes. Breeding schemes are a collection of crossing, evaluation, and selection (CES) tasks and decisions which vary across breeding stages  and ultimately define a breeding strategy , the selection method , and the selection unit, etc.Another layer of complexity in communicating breeding schemes is that the number of stages in a scheme depends on the biology of the species, the multiplication ratio, the evaluation steps required to identify new parents, and the complexity of the market segment and product profile(s) for the desired final product . Most brDespite the inherent complexity of CES decisions, in some organizations breeding schemes are rarely shared formally or presented in writing. It is common for breeding leads to inherit a breeding program and its scheme from their predecessor. Usually, the predecessor transfers the breeding scheme verbally and practically rather than providing a quantitative description of the scheme in a formal document or software. This requires overlap between breeders and on-site presence of the predecessor, potentially for years at a time. Information about the breeding scheme may also be spread among several staff members within the program, interspersed in various publications, or buried in personal notes or presentations. Unfortunately, this method of transferring breeding schemes has led to the total loss of information (and even germplasm) of many breeding programs that have disappeared in the last century . Improve2). As suggested by In addition, codified, systematic documentation of breeding schemes could spur continuous improvement and lead to increased genetic gain and varietal turnover  and how varying these decisions affect the outcome. Given the cost and time associated with piloting new methods or ways to run this complex process, the use of simulations has a particular relevance to the design of breeding schemes . StochasHere, we propose a process to formalize and improve the breeding schemes. In addition, we introduce a publicly available software tool, Breeding Pipeline Manager (BPM), which has capabilities to quantitatively document and record breeding schemes as well as the market segments and product profiles they target in a standardized yet customizable way. The BPM module can be added to any compatible enterprise breeding system (database) to link the phenotypic data to clear targets, pipelines and breeding schemes . In addidefine, measure, analyze, improve, and control . The steps are undertaken iteratively to create a cyclical method for continuous improvements. Six-sigma was originally proposed by Bill Smith at Motorola in 1986 to improve industrial processes, in which 99.99966% of all opportunities to produce some features of a part are statistically expected to be free of defects  and the CES tasks and decisions in columns. BPM provides a graphical user interface for capturing breeding schemes in a standard format. BPM also allows users to create visualizations (flowcharts) of their breeding scheme. In addition, the BPM allows market segment and product profile definition and users can link breeding schemes to market segments.We applied the continuous improvement methodology known as six-sigma to approach breeding as a process and enable breeding scheme improvements. Six-sigma is a five-step method:  defects . In the https://gitlab.com/excellenceinbreeding/module2. The platform leverages NodeJS asynchronous technology to perform intensive calculations without affecting the performance of other functionalities of the system. In addition, the platform uses Docker containerization technology for continuous development and integration  by capturing all CES decisions across all stages using the BPM tool (as described in the next section) through several interactions with the breeders. The analysis of the measured decisions and the genetic gain indicators revealed many possible improvements. We first chose to analyze the crossing decisions in the breeding scheme to identify possible improvements. The number of parents (nParents), number of crosses (nCrosses), number of progeny per cross (nProgeny), and recycling strategy were prioritized for evaluation via stochastic simulation in AlphaSimR  common in project management  stated in the improvement plan changed as the improvements proceeded.We selected the CGIAR IITA-Cassava program to showcase the importance of using enabling tools and simulations to continuously optimize breeding programs. The IITA cassava program is situated in different parts of sub-Saharan Africa to serve region-specific challenges and market segments. The IITA-Cassava east-Africa pipeline, situated in Uganda, was chosen to showcase the use of SixSigma and the BPM tool to improve their breeding scheme. The five six-sigma steps were applied as follows in the cassava program. The lphaSimR . We propnagement . We thenAs a clonally propagated crop, cassava breeders currently have adopted a four-stage evaluation strategy in addition to the crossing block stage and the seedling nursery stage where planting material is multiplied. These evaluation stages include stage 1 , stage 2 , stage 3 , and stage 4  at the F1 stage to 1,632 in all experimental simulation treatments. We then developed a grid to evaluate different numbers of parents in the crossing block using the following possible numbers of parents (nParents): 4, 8, 16, 32, and 64. The number of possible crosses for each level of number of parents was constrained to a maximum of nParents * (nParents − 1)/2, which is equivalent to all possible combinations of parents or a half-diallel, while considering the initial restriction that the number of individual progeny  must be equal to 1,632. This resulted in the following possible numbers of crosses: 6, 12, 24, 48, 96, 204, 408, or 816. To keep the number of individual progeny constant at 1,632, the number of progeny per cross was set to 272, 136, 68, 34, 17, 8, 4, 2 for numbers of crosses equal to 6, 12, 24, 48, 96, 204, 408, and 816 respectively. The number of individual progeny is always equal to the number of crosses multiplied by the number of progeny per cross.As such, a total of 24 simulation treatments were defined . To iden8 base pairs. Sequences for each chromosome were generated using the Markovian coalescent simulator , and mutation rate was set to 2 × 10–9 per base pair. Effective population size was set to 30 to mimic an evolution history of natural and artificial selection.For each replicate, a genome consisting of 18 chromosome pairs was simulated for the hypothetical plant species similar to cassava. These chromosomes were assigned a genetic length of 1.43 Morgans and a physical length of 8 × 10or MaCS;  implemenSimulated genome sequences were used to produce 4 founder non-inbred individuals. These founder individuals served as the initial parents in the burn-in phase. Sites segregating in the founders’ sequences were randomly selected to serve as 100 quantitative trait nucleotides (QTN) per chromosome .A single highly complex trait representing an index of tuber yield, dry matter, cassava mosaic disease, total carotenoids and sprouting was simulated for all founders. The genetic value of this trait was determined by summing its QTN allelic effects. To model genotype-by-environment (GxE) interaction, allele effects depends on the value of an environmental effect which changes over years. For a given year, the allele effects followed this formula:ai is the allele effect for QTN i, wj is the environmental effect for year j, bi is the QTN intercept and mi is the QTN slope on the environmental effect. The slope, intercept, and environmental effects were sampled from the following normal distributions. This equation is equivalent to Finlay–Wilkinson regression. Details on the full formulation of genotype by environment interaction simulation features enabled in AlphaSimR can be found in where p-value argument (years in rows and locations in columns). The values were sampled depending on the year and number of locations used for a given stage to approximate the GxE. A summary of simulation features for the genome and phenotypes can be found in In order to simulate the multi-environment testing common in breeding programs, the variance components for genotype by year and genotype by locations were used to simulate a matrix of possible slopes for the environmental covariate used by the setPheno function in the Population means and standard errors at Stage 1 of yield evaluation across the 20–60 years of breeding for the treatments described previously were computed using the dplyr library in R , and ploFollowing the paradigm of approaching breeding as an industrial process , we adapdefining the problem was adapted to breeding scheme improvement by defining the problem as a suboptimal rate of response to selection (genetic gain) but pointing to one of the many crossing-evaluation-selection (CES) tasks and decisions at a given stage as the possible root of the problem. We found tools such as Project charter useful to define the problem  applies . The exiblueprint should specify all the crossing, evaluation and selection tasks and decisions occurring at the different stages  for the purposes of population improvement and product development. Most breeding programs have these two purposes coupled in a way that advancement decisions influence the recycling decisions. Others have proposed and shown that decoupling the population improvement from product development by moving the recycling decision to very early stages  will increase the rates of genetic gain. Better products can be expected when the product development process is regarded as separate from a rapid cycling population improvement strategy  decisions comprising the breeding scheme can and should be recorded at the highest level of detail and safeguarded for the benefit of the breeding organization in case of any adverse circumstances. In measuring step of the six-sigma process was adapted by recording numerically and categorically all the different CES decisions across the various stages directly impacting genetic gain . The lack of available tools to measure/record breeding schemes was the motivation to develop the BPM tool presented above, although the BPM tool is inspired by the Value Stream Mapping approaches commonly used in process management  to another variable in the production process to understand relationships that could indicate the part of the process that needs to be refined. We instead conducted an analysis based on known quantitative genetic relationships between the various CES decisions and genetic gain . Additional tools like Fishbone (diagram to articulate the root causes of the problem) are not discouraged but we limited this exercise to one-to-one meetings with the breeding team to discuss the possible gaps while analyzing the current scheme together in the light of quantitative genetic principles  and long (60-year) terms. At the 20-year timepoint, schemes with fewer crosses and more progeny per cross tended to have higher gain across numbers of parents, but at the 60-year timepoint schemes with relatively more crosses and fewer progeny had higher gain. However, even at the 60-year timepoint, the optimal number of crosses was much less than the possible half-diallel of unique crosses.Given the genetic parameters specified for the cassava program, the use of ∼8–16 parents, ∼24 crosses and ∼68 progeny per cross in each crossing block per year was the optimal distribution to maximize genetic gain at the 20-year time horizon . At the improvement step in the six-sigma method was adapted to breeding scheme improvement by using management tools like the A3 format to reflect the current and future state of the CES decision (subprocess) together with an action plan laying with detail the actions required to achieve the future state , deadlines, and risks, as it does in other industrial processes. To monitor or control the progress of the improvement plan in the IITA-cassava, deadlines and key performance indicators for the different actions were defined and monitored to ensure that changes occur. Once the new process was adopted, we moved to the next possible crossing evaluation or selection decision that could be causing low rates of genetic gain. This process is still undergoing together with other improvements identified.The There is tremendous potential of systematizing breeding as an industrial process and enabling continuous improvement methodologies  to the different crossing, evaluation, selection decisions and other parts of the breeding process. Successful implementation of these methodologies has potential to increase the rate of genetic gain and delivery of better products in breeding programs. To guarantee such improvements in genetic gain, the recommended changes must be near-optimal or at least better than the current strategy. We propose the use of genetic simulation to identify these solutions to guide the continuous improvement steps. The work with the IITA-cassava program resulted in improved resource allocations and adjustments to the proper number of parents to sustain gains for the breeding time horizon of interest. These and other improvements achieved through the same approach in other CES decisions are ongoing. We expect that this generalized framework will assist plant breeding professionals in transitioning toward conducting breeding as an industrial process, help prevent discontinuity and inconsistency in breeding pipelines and their schemes and implement a culture of continuous improvement in all areas of their breeding programs.The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/GC-P, PC, JD, and MQ conceived the study. GC-P, ZG, and SS developed the software. DG, CW, and ML performed the simulations and applied the continuous improvement methodologies. IR, SK, EP, EK, EM, AA, and PK produced the data and ran the programs used for the study. All authors contributed to writing the manuscript and agreed to be accountable for the content of the work.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Excessive daytime sleepiness (EDS) is a significant public health concern, with obstructive sleep apnea (OSA) being a common cause, and a particular relationship exists with the severity of depression. A literature search on OSA, depression, and EDS was performed in PubMed. The chosen evidence was limited to human studies. Available evidence was systematically reviewed to ascertain the association of EDS with depression and OSA according to the general population and some specific population subgroups. In addition, effectiveness of continuous positive airway pressure (CPAP) was analyzed as a standard therapy for improving EDS and depression in patients with OSA. In the general population, patients with OSA, and some other subpopulations, the review contributed to: (1) delineating the prevalence of EDS; (2) substantiating the relationship of EDS and depression; (3) presenting the relationship between EDS and OSA; and (4) revealing that the duration of CPAP is crucial for its therapeutic effects in improving EDS and depressive symptoms in patients with OSA. Excessive daytime sleepiness (EDS) is an important public health concern and an independent predictor of increased health care use for outpatient physician visits and all-cause hospitalization . EDS hasDepression is one of the most common psychiatric illnesses in teenagers and adults and is a major public health problem, which is common in many different medical illnesses, including OSA with EDS . High deOur goal was to carry out a systematic review for exploring the prevalence of EDS and ascertaining the possible links between OSA, EDS and depression. At the same time, we want to analyze if continuous positive airway pressure (CPAP) is effective for improving the symptoms of EDS and depression in patients with OSA.We searched PubMed to identify papers published in English. We combined keywords and medical subject indices referring to terms related to EDS syndrome (Excessive daytime sleepiness OR daytime sleepiness), terms associated with sleep apnea syndrome , and terms related to depression . Additionally, the selected papers had to meet these criteria for inclusion: (1) accessible in English; (2) human studies; (3) published between January 1990 to January 2021 unless related to some basic concept; and (4) abstracts were available. The criteria for exclusion were: (1) abstracts from conferences; (2) commentaries; (3) subjects aged <18 years; (4) reviews.The original search returned 518 articles. According to the inclusion and exclusion criteria, the abstracts were reviewed by a panel of three reviewers, and 176 full-text articles were retained for further analysis after removing duplicates and review articles. After a complete inspection of the full texts, 114 papers were excluded for different reasons. The current review focused on the remaining 62 articles .Because of the narrative character of this review, we did not assess the risk of bias of the individual studies, nevertheless, all studies were scrutinized by three reviewers, who discussed the methodology and selected only studies according to the inclusion and exclusion criteria.There is a lack of a standard definition of EDS, however, most studies use the Epworth Sleepiness Score (ESS) to assess sleepiness, which was quantified and dichotomized into presence (score >10) or absence (score ≤10) of EDS based on evidence indicating that individuals with scores >10 had an increased propensity to OSA syndrome, narcolepsy, or idiopathic hypersomnia.EDS is common worldwide, and affects an estimated 9% of 16–84-year-old adults in New Zealand . In AustSleep apnoea results from partial or total occlusion of the upper airway during sleep, causing hypopnea or apnea that leads to intermittent hypoxia, arousal from sleep, with resulting sleep fragmentation and disturbed sleep architecture. The most commonly encountered cause of EDS in a clinical setting is OSA. OSA can be reliably diagnosed using overnight polysomnography to assess the number of apneas–hypopneas per hour of sleep: the apnea hypopnea index (AHI).Compared with the general population, the prevalence of EDS in patients with OSA is even higher, and has been noted in 39.5  or 36.69The prevalence of EDS in patients with depressive symptoms and insomnia is also greater than that reported in the general population. Data from 703 individuals with MDD were retrospectively collected from the sleep laboratory research database. The prevalence of EDS was 50.8% . Among 1In other specific population subgroups, EDS has been reported in 19.1%  of commeIn summary, EDS, is reported to be common in patients with physical disease and even more common in those with OSA and depressive symptoms. EDS is highly prevalent and has a significant impact on patients' general health and quality of life. Most of the clinical and research studies have used one single subjective self-completion questionnaire (ESS) to assess EDS. Findings were robust to the ESS cut point to define sleepiness, while it is well-known that EDS has multiple dimensions and can be quantified objectively by physiological measures, such as the multiple sleep latency test (MSLT) . NeverthThere is a growing number of population-based strong and consistent relationships between depression and EDS, and vice versa –12. AlcáPrevalence studies have shown high rates of depression among patients with OSA in both community and clinical populations, and patients with OSA experience EDS and are more likely to have depressive symptoms , which aStudies have shown conflicting results on the relationship of EDS and depressive symptoms with the severity of sleep apnea, respectively. Cumulative effects of undiagnosed and diagnosed sleep apnea, such as chronic sleep deprivation, cognitive/affective dysfunction, sleep disruption, and hypoxemia, likely contribute to psychological impairment . UnexpecDepression scores are positively correlated and significantly associated with sleepiness as measured by ESS in patients with mild , mild anIt is, however, possible that ESS does not allow differentiation of depressive symptoms from real daytime sleepiness, and that objective sleepiness measurement, which was not performed in many studies, could provide different results. It may be that the different approaches and inappropriate psychological instruments, such as rating scale for depressive symptoms, with the absence of appropriate diagnosis based on DSM-IV or ICD-10 taxonomies in the diagnostic process that have led to confusion over the occurrence and nature of mental health difficulties in OSA.EDS is a common symptom in individuals with MDD or severe depression and interventions (such as antidepressants or benzodiazepines) are possible for most risk factors of EDS . Few stuEDS is considered to be the dominant sign of OSA. Around 3% of 1,011 Australian adults reported diagnosis of OSA and elevated ESS, and EDS (ESS ≥11) was associated with diagnosed and undiagnosed OSA, which was estimated using self-reported frequent loud snoring and witness apnea . More stThe association of EDS and OSA severity is inconsistent. Some studies have shown that OSA severity (AHI) is associated with the frequency of sleepiness, and higher AHI is associated with more daytime sleepiness , 43, 44.Lee et al. developed the Subjective Apnea Severity Questionnaire to measure subjective OSA symptoms during the night and on waking in the morning, which were associated with daytime sleepiness in adults with moderate and severe OSA. However, they found that there was no significant relationship between all classes of OSA as defined by the AHI and EDS . The subThe rate of unsuspected and undetected OSA in 125 suicidal adults with MDD  and moodVarious conservative behavioral therapies are also used for OSA and CPAP is commonly chosen to treat OSA. Numerous studies have been conducted to evaluate the efficacy and/or effectiveness of CPAP in treating a wide range of OSA symptoms. Baseline sleepiness is the only factor predictive of compliance , and a hA beneficial effect of short-term (2–3 months) treatment following CPAP on EDS , 52–58 aThe reasons for these differences are not clear. First, there are large placebo effects for sleepiness and mood. Second, patients in these studies may have been more neurobehaviorally impaired for the similar levels of AHI severity. Third, CPAP use, the overall mild degree of neurobehavioral impairment in these patients, or morbidity not associated with OSA may be responsible for the failure to detect positive treatment effects of CPAP . Lastly,The results of most studies were based on a 12-week follow-up, which might limit the ability to generalize from these results to long-term effects of adherence on symptoms of depression and EDS. In a long-term prospective cohort study of CPAP treatment, adherence for 6 months  or 2 yeaThese findings emphasize the importance of close follow-up of EDS and depressive symptoms once CPAP treatment is initiated in patients with OSA. It is regrettable that most of the current studies were related to OSA with depressive symptoms, and there is a lack of studies on CPAP for treatment of OSA comorbid depression. Skepticism has been expressed concerning the effectiveness of CPAP because of a lack of randomized controlled trials.The non-specific effect of OSA on performance, mood, interest, sexual desire, and somatic state  should be noted, which can be similar in other somatic conditions with pain, discomfort, and so on. Depressive symptoms can really improve if the underlying somatic condition does. It is an additional question if there is a biological link between OSA and mood disorder, probably as a confounding factor to the effectiveness of CPAP, but not possible to clarify by the present means.EDS is a widespread problem in the community with medical, societal and economic consequences, and is considered to be the major and most distinctive symptom of OSA. Similarly, MDD and many other diseases are comorbid with EDS. High prevalence rates of sleepiness in OSA patients have been reported; nevertheless, the association between EDS and AHI has been shown to be inconsistent. The relationship between depression and EDS is bidirectional, which supports the need to evaluate mental health whenever individuals in the general population present with EDS and OSA as a consequence, and comprehensive screening and testing for EDS should be considered in depression. More studies are needed to justify improved management of EDS and OSA to avoid negative consequences in patients with depression.The underlying mechanism for EDS in patients with depression and OSA needs to be investigated further to make more specific therapeutic recommendations. It is pivotal to explore specific strategies targeting such factors and it will be interesting to reproduce these studies using an objective measure of EDS (such as MSLT) since few studies have used these methods and targeted patients with OSA and comorbid depression.Effective therapies for patients with OSA not only improve OSA itself but also are likely to contribute to management of the comorbid conditions and their clinical consequences. The gold standard treatment is CPAP, which is effective in reducing AHI and improving objective and subjective measures of sleepiness and depressive symptoms . A minimThe original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors.DZ contributed to conception and design of the paper, searched PubMed to identify studies and wrote the first draft of the manuscript. ZZ, HL, and KD scrutinized all studies and wrote sections of the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Cervical radiculopathy is defined as a disorder involving dysfunction of the cervical nerve roots characterised by pain radiating and/or loss of motor and sensory function towards the root affected. There is no consensus on a good definition of the term. In addition, the evidence regarding the effectiveness of manual therapy in radiculopathy is contradictory.  To assess the effectiveness of manual therapy in improving pain, functional capacity, and range of motion in treating cervical radiculopathy with and without confirmation of altered nerve conduction.  Systematic review of randomised clinical trials on cervical radiculopathy and manual therapy, in PubMed, Web of Science, Scopus, PEDro, and Cochrane Library Plus databases. The PRISMA checklist was followed. Methodological quality was evaluated using the PEDro scale and RoB 2.0. tool.  17 clinical trials published in the past 10 years were selected. Manual therapy was effective in the treatment of symptoms related to cervical radiculopathy in all studies, regardless of the type of technique and dose applied.  This systematic review did not establish which manual therapy techniques are the most effective for cervical radiculopathy with electrophysiological confirmation of altered nerve conduction. Without this confirmation, the application of manual therapy, regardless of the protocol applied and the manual therapy technique selected, appears to be effective in reducing chronic cervical pain and decreasing the index of cervical disability in cervical radiculopathy in the short term. However, it would be necessary to agree on a definition and diagnostic criteria of radiculopathy, as well as the definition and standardisation of manual techniques, to analyse the effectiveness of manual therapy in cervical radiculopathy in depth. Cervical radiculopathy (CR) can be defined as a disorder involving dysfunction of the cervical nerve roots, commonly presenting with pain radiating from the neck towards the root affected . CommonlThe incidence of CR has been established to be between 63.5 and 107.3 per 100.000 people per year . If thisPrevious systematic reviews have provided indications that exercise is effective in treating CR, whether associated or not to manual therapy , 15, manBesides, without uniform CR diagnosis criteria, one might compare treatments with samples possibly having motor and/or sensory disorders to others in which the individuals have pain without altered nerve conduction velocity, with prognoses that are probably different. Despite conflicting evidence at the use of nerve conduction as a diagnostic criterion , 19, it The objective of our systematic review is thus to verify the effectiveness of manual therapy in CR cases with and without confirmation of altered nerve conduction—using electromyography or electroneurography—in pain, disability, function, and range of movement, in comparison to other physiotherapy techniques used in the approach to CR.https://osf.io/zgdym/.Our review was carried out in agreement with the PRISMA statement checklist  and the Search strategy was developed following advice of an information specialist (MHS) from the research group, with two-year experience in conducting systematic reviews. The following reference sources were searched: PubMed, Web of Science, Scopus, PEDro, and Cochrane Library Plus. The search terms were divided into 4 categories, as recommended by the Cochrane Back and Neck Group . The firThe inclusion criteria were as follows: (1) randomised controlled clinical trials on humans; (2) patients with CR, identified and diagnosed by clinical criteria   or by usWe excluded articles that (1) used another approach, except if they used a comparison to the manual therapy technique or were accompanied by it, and (2) with patients with neck and arm symptoms without a CR diagnosis.Two researchers (IMG and SBA) selected the studies independently. If they disagreed on the study selection, the final decision was made by a third researcher (CHG).Data on sample size, criteria for radiculopathy diagnosis, type of intervention, treatment protocol, follow-up, variables studied, and main results were included. With regard to the variables, the primary results, secondary results, and adverse effects were recorded.Two independent researchers assessed methodological quality of the studies using the PEDro scale; there was a third researcher to settle cases of doubt or disagreement. The PEDro scale  evaluateAlso, the RoB2 tool was performed. It is the second version of the Cochrane tool to assess the risk of bias in clinical trials. The biases are evaluated in 5 domains: (1) randomization process, (2) effect of being assigned to intervention, (3) missing outcome data, (4) measurement of the outcome, and (5) reported results. Within each domain, 1 or more questions must be answered. These answers lead to the judgements of “low risk of bias,” “some concerns,” or “high risk of bias” .The initial literature search yielded a total of 365 studies. After eliminating the duplicates, there were 211 articles left. Filtering on title and abstract yielded 22 articles for complete text reading, of which 5 were eliminated, because they did not meet any of the inclusion criteria. Seventeen studies were selected for final inclusion. The PRISMA flow diagram  illustraThe methodological quality of the trials included in the revision is summarised in Three studies , 40, 41 The RoB2 tools showed that the aspects with the worst methodological quality in all the studies are related to deviations from the intended intervention. Reported data and variable measurements seem to have the best methodological quality in all the studies, with 75% of the studies meeting these criteria Figures , even thCharacteristics of the studies are presented in Nerve conduction velocity was analysed in just one study, using evoked potentials . This teThe tools used to measure the study outcomes were similar in all the studies. The intensity of perceived pain was measured using a Visual Analogue Scale (VAS) in 8 studies , 43, 44,All the studies analysed reported a statistically significant improvement in the variables of pain and cervical disability index in the manual therapy intervention group, regardless of the protocol and the manual therapy technique applied. The manual therapy techniques of choice were divided among cervical manipulations, thoracic manipulations, cervical mobilisation towards the intervertebral foramen opening, cervical traction, and neural mobilisations. The techniques with the best results were those whose objective was to increase the intervertebral foramen area by transverse mobilisations in the indicated segments. These techniques had been applied with positive results in 4 of the studies , 41, 43.In contrast, manual traction and neural mobilisation were the least satisfactory techniques. Traction obtained worse results with respect to the intervertebral foramen “openings” and mobilisations , 40, butThe duration of the intervention and the guidelines for establishing the duration were reported in all the articles, except for the study of Waqas et al. . Times aThe number of sessions applied was established as 8 and 12 in most of the articles. Young et al.'s study  was the The results of this review should be taken as short-term results, given that the follow-ups were generally performed half-way through the study and/or when the intervention period ended. Just a single article  had a meNone of the studies revealed mild or serious adverse effects in the application of the techniques chosen.The objective of this review has been to ascertain the effectiveness of manual therapy in handling CR cases with and without confirmation of altered nerve conduction. In previous studies, the effectiveness of exercise in CR  and the There is a lack of scientific research on applying manual therapy techniques (such as manipulations and mobilisations) in this pathology , as wellDegenerative signs in imaging tests need to be correlated with the clinical findings of the pathology for accurate CR diagnosis . TherefoAll the studies analysed reported a statistically significant improvement in the variables pain and cervical disability index. Such improvements did not depend on the manual therapy protocol and the technique applied.This review reveals the need to establish reference criteria for diagnosing “CR” cases, attempting to avoid a catch-all approach. None of the studies included performed electromyography or electroneurography to determine nerve conduction alteration, and only 2 of the studies carried out magnetic resonance imaging to demonstrate possible structural nerve root compromise , 31. It The studies include patients with symptomology similar to radicular conditions but not objectively cases of radiculopathy, due to the used diagnostic criteria. Myofascial trigger points, faceted radiated pain, and distal neural compressions might simulate similar symptomology.δ and C nerve fibers within the evaluation. A new standard definition of radiculopathy is needed, along with relevant diagnostic criteria.Wainner et al.  formulatDifferentiation should be established between radiculalgia and radicular pain without altered nerve conduction velocity and radiculopathy involving loss of nerve conduction velocity . Similarly, Shacklock  defined A combination of diagnostic criteria based on clinical findings compatible with radiculopathy, the prediction rule of Wainner et al. , clinicaGiven that there is symptomology presumably caused by radiculopathy, the techniques that offered the best results were those searching for the intervertebral foramen opening by using pressure or transverse oscillations. The neurodynamic techniques yielded the worst results; the parameters applied were a bit unclear, categorising the neurodynamic technique used as neural gliding exercises , mobilisThis fact has led us to analyse the importance of establishing exact parameters for the technique applied and the technical development of its application. Because manual techniques are involved, the variables to control may depend on performance. Reflecting the performance parameters appropriately in the studies is recommended so that the results can be reproduced and extrapolated to the clinical setting. This is something at which the majority of studies has failed, naming the technique applied but not explaining it in detail. Our recommendation would be to avoid describing manual techniques in general, based only on the name of the used methodologies  but without identifying precisely the technique. Our recommendation is to describe the procedures precisely using the TIDieR checklist to make sure they can be reproduced .Treatment times and doses varied from some studies to others, within similar techniques. The mean was 2-3 sessions a week, applying approximately 8-12 sessions. There are no previous studies dealing with the number of sessions needed for conservative treatment of CR cases. These first guidelines in treatment times are considered interesting; in future studies, the mean treatment times with other approaches can be analysed to compare the time indication of each of the techniques.As for the number of sessions proposed, thoracic manipulation might be one of the first techniques to apply because it has demonstrated beneficial results from a single session  and can The results presented in this review should be considered at short term, as the studies involve only short-term follow-up. Manual therapy can be proposed as a way to provide relief when the symptoms might be related to radiculopathy, but its long-term effectiveness has been impossible to establish.The 3 indicators recommended by clinical guidelines for CR  have beeOur systematic review is strongly limited by the variability of the inclusion criteria of patients with CR and of the manual therapy techniques used, given that these have been very different or poorly explained in the majority of the studies. This means that it has been impossible to analyse the results specifically in the application of each of the techniques. Another limitation is that there may be references available besides the ones in Spanish, English, and French that have not been considered due to the language requirements established in our inclusion criteria. Finally, in the absence of a Cochrane Information Specialist, an information specialist of the group with a two-year experience was available that might not be able to fulfil all the functions.We cannot state that manual therapy is effective in treating CR cases confirmed by EMG or ENG tests, due to a deficit in the diagnostic criteria used in the scientific literature. Without an EMG and ENG confirmation, a multimodal approach that includes manual therapy seems to be the most effective short-term approach. The methodological deficiencies and the lack of follow-ups in the studies have to be treated cautiously. It is therefore necessary to establish greater scientific evidence with high quality with larger sample sizes and longer follow-up times, in which initial treatment parameters are established for each of the manual therapy techniques. There is currently a lack of standardisation of diagnostic processes and of treatment in this pathology, even though manual therapy has been shown to be effective in dealing with CR cases having a diagnosis based on clinical criteria.


The inclusion of spontaneously reported adverse drug reactions (ADRs) in hospital discharge reports was examined, in addition to the factors associated with their inclusion, the resulting therapeutic decisions, and any recommendations made upon patient discharge regarding the suspected offending drugs. ADRs that were spontaneously reported during 2017 and 2018 to the pharmacovigilance program were retrospectively analyzed. Information regarding patient characteristics, drug treatments, and ADRs was collected from the ADR notifications and from patient electronic medical records. The dependent variable was the mentioning of ADRs in the discharge reports, while characteristics of the ADRs, pharmacovigilance causality algorithms, and some of the suspected drugs themselves were the independent variables during bivariant analysis. A total of 286 reports of suspected ADRs from 271 patients  were included. Information regarding the ADRs was present in the discharge reports for 238 reports (83.2%); the ADR seriousness and the lack of potential alternative causes were the only associated factors. Withdrawal or withdrawal and substitution by an alternative drug were the most common therapeutic decisions, although often no recommendation was made. Overall, there is still room for improvement in terms of including information related to ADRs in hospital discharge reports. In some recent studies, the reported prevalence of adverse drug reactions (ADRs) during hospitalization varies between 10.1 and 19% , while tGiven the significant burden that ADRs carry for patients in hospitals, pharmacovigilance systems should ideally play a key role in their detection, evaluation, and quantification. However, only a small proportion of ADRs  are currently notified through the spontaneous reporting of suspected ADRs ,8.To stimulate the notification of suspected ADRs, several strategies have been implemented in our hospital ) over recent years. The VHUH is a tertiary hospital in Barcelona covering the majority of clinical and surgical specialties, with more than 1000 beds and approximately 48,000 discharges per year. As one example strategy, from 2003 to 2005, the reporting of spontaneous ADRs was included as one of the key objectives for physicians within the context of management agreements between clinical services and hospital managers. Continuous interventions related to these management agreements, including periodic educational meetings and economic incentives, were implemented during this period. As a consequence, the median number of reported ADRs per year increased from 40 (range 23–55) in the first evaluation period 1998–2002) to 224 (98–248) during the second evaluation period (2003–2005), which was attributed to such interventions [98–2002 tPatient discharge reports tend to contain the most relevant clinical information recorded for the patient during hospitalization. The accuracy of the included information is vital for health professionals who will take clinical and therapeutic responsibility for patients after discharge. It is therefore important to include information regarding any ADRs that took place during the period of hospitalization, and in particular any serious reactions, or reactions that resulted in hospital admission. This is necessary to guide therapeutic management after discharge and to avoid readministration of the offending drugs.In 1992, a small study was carried out to analyze whether any information regarding ADRs notified to the Spanish pharmacovigilance program from May 1990 to May 1991 appeared in patient medical records. They analyzed a total of 18 notified ADRs . In two Thus, with these previous reports in mind, the aim of the present study was to analyze the degree to which spontaneously reported ADRs were mentioned in the discharge reports of patients from our hospital, and to determine the factors associated with their mention. A secondary objective was to analyze whether any kind of therapeutic decision was taken, or whether a recommendation was made regarding the offending drug(s) at the time of hospital discharge. An observational retrospective study to identify ADRs that were spontaneously reported to the pharmacovigilance program at the VHUH during 2017 and 2018 was carried out. Only spontaneously reported ADRs that occurred during hospitalization, that required emergency care at the Emergency Unit, or that led to hospital admission were included in the study. ADRs notified by outpatient hospital care were excluded due to the fact that no discharge reports are generally produced for such patients. The study protocol was approved by the VHUH Ethics Committee (15 May 2019).Demographics and clinical characteristics of the patient;Drug treatments, with special emphasis on those suspected to be involved in the ADR causality: indication, dose, time of exposure, and potential labelling with an inverted black triangle at the time of prescription;Spontaneously reported ADRs: type of ADR, seriousness, medical assistance required, reporting clinical department, and ADR outcome;Discharge reports: any mention of the spontaneously reported ADRs and any therapeutic decision and/or recommendation regarding the offending drug at discharge.For each spontaneously reported ADR included in the analysis, the following information was collected in a structured datasheet by reviewing the notification produced along with the electronic medical record of the corresponding patient: Analysis of the association between the spontaneously reported ADRs and the different treatments being taken by the corresponding patients was performed using the algorithm of the Spanish Pharmacovigilance System ,15. Medicines were classified according to the 2020 Anatomical Therapeutic Chemical (ATC) Classification system . ADRs weInformation regarding any medicines under additional monitoring, such as those commercialized with inverted black triangles at the time of prescription, was obtained from the website of the European Medicines Agency. p value was ≤0.05. Statistical analysis was performed using the IBM SPSS Statistics version 20 statistical package .Descriptive results for the categorical variables are shown as distributions of the frequencies and proportions. Comparisons of the categorical variables were carried out using the Chi-square test. To examine the association between the mention of an ADR in a discharge report and any associated factors, bivariant analysis was performed. The mentioning of ADRs in the discharge reports examined herein was considered to be the dependent variable, while some characteristics of the ADRs , the pharmacovigilance causality algorithm , and the drugs suspected to be involved in the ADRs  were the independent variables. Statistical significance was considered when the A total of 389 reports of suspected ADRs were received during the study period. Of these, 103 were excluded because they were notified from the outpatient department of the hospital. Thus, a total of 286 reports of suspected ADRs from 271 patients were included in the analysis. It should be noted here that two different reports were notified for thirteen patients because they had two different episodes of ADRs during the same hospital admission. In addition, two different reports of suspected ADRs were notified for two patients during two different hospital admissions each. Of the patients, 136 (50.2%) were female, 208 (77%) were adults (median (min–max) age = 64 (18–97) years), and 61 (22%) were children (median (min–max) age = 7 years (1 month–17 years)). There were also two fetuses (1%) (see The highest numbers of reports of suspected ADRs were notified by the Intensive Care Unit and the Pediatric department with 60 (21%) reports each. Additional information regarding the reporting clinical services, any hospital assistance required following the ADRs, and the seriousness of each ADR are shown in The most frequent suspected ADRs were nervous system disorders, followed by those related to metabolism and nutrition, the gastrointestinal system, hepatobiliary, and the blood and lymphatic system see . The ATC subgroup most frequently involved in the ADRs was antibacterial agents for systemic use, and this subgroup was followed by psycholeptic medications, antineoplastic agents, and immunosuppressants see in . In 39 rWhen assessing the causality of ADRs, in 43 reports (15%) the ADR was previously unknown for at least one suspected drug. In 37 reports (13%), an alternative cause different from at least one involved drug could not be ruled out. For a total of 238 reports of suspected ADRs (83.2%), information relating to the corresponding ADR was present in the discharge report. In contrast, for 48 (16.8%) reports, no reference to the ADR was present. The evaluated associations between the presence of information relating to the ADRs in the discharge reports and several different factors are listed in As indicated, information regarding the ADRs was more commonly included in the discharge reports in the cases of serious ADRs, and in particular when alternative causes could be ruled out. Although a higher proportion of ADR reporting was found when the reporting and discharge services coincided, the difference was not of statistical significance. Indeed, no statistically significant association was found for any of the other evaluated variables see . Finally, As shown, in both situations, when the ADR was mentioned in the discharge report, the offending drug(s) was withdrawn or was withdrawn and substituted by another drug in a high percentage of reports . However, in 40% of cases, when alternative causes could be ruled out, no explicit recommendation regarding readministration of the offending drug was made in the discharge report. This percentage was even higher (60%) when alternative causes could not be ruled out, but the number of evaluated reports was small for this classification group. Importantly, these observations were made despite the fact that the ADRs were serious in the majority of these reports . As described above, during the course of this study at the VHUH, it was found that a high proportion of spontaneously reported ADRs was mentioned in the discharge reports of patients . In addition, it should be noted that associated factors that favored their mention were the seriousness of the ADR and the fact that alternative causes had been ruled out. It was also found that when an ADR was mentioned in a discharge report, the offending drug was frequently withdrawn or withdrawn and substituted by another drug at discharge. However, no explicit recommendations regarding the risks of readministration of the offending drug(s) tended to be made at the point of discharge in a relatively high percentage of reports, even when the ADRs were serious and all alternative causes different from the suspected drugs had been discarded. Although the percentages of spontaneously reported ADRs that are mentioned in discharge reports have been described in other studies, to the best of our knowledge, this is the first study to evaluate the factors associated with their mention.Although the present study found that a high proportion of spontaneously reported ADRs were mentioned in patient discharge reports, Altimiras et al.  and Van As an example ADR, metformin-associated lactic acidosis was one of the most frequent reported ADRs in our study. Increasing evidence suggests that the use of metformin in therapeutic doses is unlikely to cause lactic acidosis ,20,21. HAs factors associated with the inclusion of ADRs in hospital discharge reports, we identified the seriousness of the ADR, and the fact that alternative causes had been ruled out. In this context, we note that none of the above studies ,12,13 anIn the present study, the most frequent therapeutic decision taken when ADRs were mentioned in the hospital discharge reports was withdrawal of the offending drug(s) or substitution by another drug, even when alternative causes could not be ruled out. However, despite the seriousness of the majority of ADRs, often no recommendation relating to the risk of represcription of the offending drug was made at the point of discharge. Indeed, it is difficult to understand why no recommendations to avoid the offending drug(s) were made in these cases. In this context, it should be noted that a previous study reported that the transfer of information from hospital discharge to the primary care service was limited . In addiDue to the fact that the present study was carried out in only one center and the number of evaluated cases was limited, the study should be replicated in other centers with similar characteristics. In addition, this study was performed retrospectively, which could have limited the accuracy of the data. However, almost all information was obtained from hospital discharge reports, which are permanent documents stored in the electronic medical records of patients for facile consultation by medical professionals. Moreover, our group has a vast expertise in carrying out pharmacovigilance surveillance and in assessing hospital ADRs. As another limitation, stimulating the reporting of more serious ADRs and those related to new drugs could have had some influence on the profile of the notified ADRs in our study. However, although serious, the most frequent ADRs described in the present study were not related to new commercialized drugs. Overall, this study permitted the evaluation of how information related to ADRs is transferred at the point of patient discharge from our hospital, and it also allowed some areas of improvement to be identified.In summary, the present study identified that information regarding a high percentage of ADRs that have been spontaneously notified to the pharmacovigilance system is available in hospital discharge reports. It was also found that the only factors that predicted the inclusion of such information in hospital discharge reports were the seriousness of the ADR and whether causes different from the suspected drugs could be ruled out. Finally, it was observed that despite the majority of spontaneously reported ADRs being serious and alternative causes being ruled out, in a relatively high percentage of cases, no recommendations were made upon hospital discharge regarding represcription of the offending drug(s), despite the fact that the ADRs were mentioned in the discharge reports. Physicians should therefore be made aware that as a minimum recommendation, when causality is established and an ADR is serious, guidance regarding readministration of the offending drug(s) should be included in the hospital discharge reports, in addition to details relating to the ADR itself.


The term “metal marking” is widely used to define the common phenomenon of tableware glazes being damaged by metallic cutlery. Appearing as unaesthetic gray marks and scratches resulting from normal conditions of use, these defects deeply affect the performance of ceramic products, especially in intensive environments, such as in the hospitality industry. The scope of this article is to establish a comprehensive review of the phenomenon, focusing on the physical and chemical mechanisms involved in the process, and their interactions and consequences. It also intends to list the different methods normally followed to avoid or at least reduce this defect, in order to enhance the durability of porcelain dishware. This manuscript also provides a review of the different testing methods developed and used by the tableware industry and technical centers to quantify the ability of porcelain tableware to produce metal marks. To face the current lack of any international or at least national standard testing procedure that would permit a reliable comparison of products, a new metal marking test developed at the Technological Center for Ceramic and Glass (CTCV) is presented as an alternative to common tests normally based on knives as a marking tool. It is common to observe, in the bottom of ceramic plates or cups, where food and liquids are placed, unattractive gray or dark marks that are characteristic of regular contact with metal knives, spoons or forks with the product surface . These marks can also be accompanied by small cracks of the glaze and even scratches ,2. ScratProducers are occasionally confronted with this type of situation, and the mechanisms underlying this phenomenon have been the subject of a few in-depth scientific studies ,3,4,5,6.Thus, this work focuses first on the physical mechanisms, which are considered to be responsible for the glaze deterioration, from metal particles deposition onto the glazes surface to the development of cracks and scratches. It intends to explain how the physical and chemical characteristics of glazes and metallic utensils affect the performance regarding metal marking, but also to highlight the interrelationship between the several phenomena occurring during the progressive degradation of the tableware surface, especially glaze aging from mechanical and chemical stress.Ceramic tableware is an expanding market that includes all ceramic dishes, cups, and bowls mainly used for catering services and for domestic purposes. A representative part of the ceramic tableware production is in fact absorbed by the food service industry sector—HOtels, REstaurants and CAtering—generally abbreviated with the HORECA acronym, widely used in European countries. This sector is extremely important for ceramic producers and is characterized by high and rigorous quality requirements, forcing companies to adapt and/or develop solutions in order to fulfill the final customer’s needs in terms of design, aesthetics, performance, and functionality. In fact, ceramic products used in this sector are subjected to intensive use and subsequently exposed to frequent attack, such as metal marking, mechanical wear-especially on the rim, due to repeated shocks during manipulation, but also on the plate bottom due to handling and stacking-and surface degradation caused by the aggressive washing with chemical detergents. Consequently, in order to enter or to strengthen their position into these strategic markets, companies are continually working on the development of new glazes to provide new designs and colors (such as reactive glazes) and, at the same time, to obtain better performance, especially concerning the metal marking occurrence. The growing importance of metal marking is shown by major retailer’s efforts to develop in-house tight test procedures and acceptance criteria of products about their performance toward contact with cutlery. This necessity is actually due to the glaring absence of an international metal marking standard test. In its recent specification for domestic and hospitality use of ceramic tableware  , the BriAn adequate comparison between products tested according different methodsThe development of an accurate and reliable database to provide technical information on the performance of products.This lack of standardization led to a wide variety of internal procedures, developed by companies, technical laboratories, or even customers. Together with the subjectivity of samples evaluation, it prohibits:As a standard test method to determine the metal marking resistance is needed to evaluate the performance and the behavior of ceramic tableware when in contact with cutlery, a review of usual tests attributes showing their limitations is then presented. As a result of the knowledge acquired in Research and Development projects for development of improved metal marking resistance tableware and respective characterization, a new test was implemented at Technological Center for Ceramic and Glass (CTCV) in order to reduce the drawbacks and subjectivity of actual available tests and which is already used by some national companies. The standardization process at Portuguese national level is in progress.A first mention of the phenomenon known as metal marking can be found in scientific literature in the early 20th century . In thisMetal marks: Deposition of steel  particles from a metallic kitchen or table utensil  susceptible to lose matter through mechanical action  on the tableware surface susceptible to fix these particles. Generally, smooth metal particles can be durably fixed onto the surface and thus difficult to remove, while harder particles have more difficulty to adhere to the surface and can be removed more easily. This problem tends to happen when the glaze is rougher and harder (but not mandatory) than the cutlery material and the gravity of the defect depends on the force applied with the utensil.Scratches and cracks: Degradation of the glaze surface under the mechanical action of cutlery made of harder material (friction) and/or under high applied pressure. Cracks and loss of glaze material (chipping) create some roughness and/or decoration degradation of the tableware, and can also cause the pulling out and deposition of metallic particles on the glaze asperities. Scratches and cracks cause irreversible surface deterioration.Presently, the term “metal marking” normally refers to the gray or dark lines, but also encompasses the damages caused to the glaze, including cracks and scratches resulting from the use of metal utensils  . Thus, tA schematic description of metal marking phenomenon is presented in primary metal marks, are illustrated by SEM in The main reasons generally mentioned for metal marks are the roughness and hardness of glazes surface and the presence of hard crystalline particles in the glaze, coming from recrystallization processes during firing or already included in the glaze composition for special purposes, such as zircon in opaque glazes ,2,9. Locsecondary metal marks. Scratches with other origins also contribute to this kind of mechanism. In particular, scratching resulting from the stacking of the plates, as the rough unglazed foot of the plate wears out the plate bottom where utensils will slide on afterwards [Even on a relatively new glaze, the pressure applied during the movement of the utensil can be strong enough to start damaging the glaze, forming Hertzian cone cracks. As it can be seen a, these terwards .Mechanical properties of the glaze are definitely essential to understand the cracking and scratching mechanisms. However, studies showed that there are a wide range of parameters that have to be taken into account, considering that several attributes of both marked object and marking utensil influence directly the phenomenon, listed in In the early 1930s, Geller and Creamer  publisheThe nature of glaze influences directly the metal marking behavior. Matte and opaque glazes, consisting of well-dispersed crystalline phases in the vitreous matrix, are easily marked due to their inherent roughness but, on the other hand, they are normally relatively easy to clean. The resistance to primary metal marking of glossy glazes depends on the level of glaze opacity, directly related to the quantity of opacifiers crystals in the glaze ,2,3. On 2, SnO2 and TiO2—have an influence on metal marking resistance [4) is an excellent, economical opacifier agent widely used in ceramic industry, due to its high refractive index. However, its presence in opaque glazes is largely associated with primary metal marking resistance [4 into glazes can be made by addition of zircon particles into the raw glaze, or through the formation zircon during firing from zirconium-based compounds such as zirconia (ZrO2). It influences directly the presence and morphology of zircon at the glaze surface, as several studies of zircon crystallization during firing shows [Type and size of crystal phases used as opacifiers—such as ZrOsistance . For inssistance . The intng shows ,14,15. AAs for zircon, the presence of devitrification areas or small crystals on the glazed surface affects the friction coefficient and is responsible for a higher hardness than the one observed in cutlery. Indeed, the presence of crystalline particles on the glazed surface locally alters the microhardness of the glaze structure, as the vitreous matrix hardness varies normally between 350 and 750 Hv (Vickers hardness) . Zircon tertiary metal marking occurs at a much later stage of the tableware lifetime, and arises from the progressive degradation of glaze properties due to prolonged use . In particular, repeated washes with detergents , quite aggressive, mainly used in the hospitality industry, promote aging of the glaze, demonstrating that the alkali attack the silicate glass matrix, leaving the crystals unchanged [Unlike primary and secondary metal marking, nchanged . It has nchanged . The effOptimization of process and glaze compositions, orProtection of glaze surface by thin coatings.Efforts of tableware companies and glaze suppliers to obtain better performance to metal marking are essentially based on:As a first approach, developments in producing environment are based on replication of glazes with excellent metal marking performance, even if, in most cases, the reason for its good behavior remains elusive. As companies normally own hundreds of glazes due the wide variety of colors, effects and final aspects, it is worth trying to take advantage of the composition frame of a good glaze for an extended range of formulation with different additive and pigments necessary to provide the final glaze aesthetics. Some adjustment of glaze and even body composition may also be made in order to optimize the hardness of the vitreous phase, working on the silica content for instance , or on tAs already mentioned, developments based on glaze formulation are conducted in a way to reduce the crystalline particles incorporation or formation: the firing process modification to limit the cristobalite crystallization, the particle size reduction of quartz , and theThe main methodologies followed to improve products are summarized in 2O3) in a traditional celadon glaze and by controlling the reducing fired atmosphere, with the objective to reduce the roughness of the glaze and increase its hardness. The high melting point of celadon glaze leads to low viscous behavior, causing high surface roughness, and thus poor performance in metal marking. They observed a combination of surface roughness decrease and a hardness increase, as the frit content increased and the atmosphere reduced, respectively. Wear resistance tests using a stainless steel ball performed in order to evaluate metal marking resistance showed a strong reduction in metal marking behavior with increasing frit content, resulting from the reduction of friction coefficient. At the same time, the higher hardness led to a lower tendency to crack and scratch.Despite a lack of information disclosure for commercial purposes from companies, some recent studies showed several interesting developments for glazes improvements. In their study, Pee  improvedIn another study, Güngör and Altun  investigSome solutions based on technology developed not specifically for metal marking, but for scratch resistance, chemical resistance, and easy-cleaning purposes, for instance, are sometimes applied with a metal marking reduction purpose. The main drawback is the durability of such solutions, as they are normally based on an organic matrix loaded with functional nanoparticles. The limited duration of effects and price restrict the spread of these products in the industry, as well as some concerns about health consequences. Inorganic thin layers, based for instance on sol–gel techniques, are also investigated, namely for surface cleanability—associated with surface smoothness—but their application is limited due to the additional costs and also difficult industrial implementation in more traditional industries, such as tableware companies .A metal marking test aims to reproduce and simulate the interaction between a metallic object that is drawn across the glazed surface, reproducing the food cutting movement performed by a knife, or a spoon stirring the coffee into a cup for example, in a laboratory environment under controlled conditions. Metal marking resistance is a crucial parameter to evaluate the performance of ceramic tableware and as it is one of the most required specifications from retailers and customers, it is inconceivable that no standardized method is currently available. Consequently, ceramics companies are obliged to develop their own routine tests to control their daily production, as well as research and development laboratories for investigation purposes ,2,3. SomTo date, the BS 8456:2015 specification about domestic and hospitality use of ceramic tableware articles intended for contact with foodstuffs  containsOur knowledge and practice of a wide range of existing in-house private tests established by companies and retailers-that cannot be disclosed publically show us that it is not worth it to compare products tests following different procedures and evaluation criteria. Thus, a uniform methodology is needed to be clearly set out to perform a metal marking test. A precise definition of a large set of parameters  will guaSample preparation .Glazed surface marking with a metallic utensil: knife, spoon, fork or even a steel ball.Marks and scratches evaluation  and classification.Despite the existence of different test protocols used by different entities, the steps to be followed are similar and are related to:Optionally,4.Aging procedure following dishwashing resistance test.5.Additional surface marking, evaluation, and classification.Sample size is not always specified by procedures. In most cases, the test is realized on no more than three specimens, which is clearly not representative of the normal fluctuation of final glaze properties, considering that even if industrial furnaces’ temperature control and homogeneity are becoming better and better, it is normally considered that each item loaded in the furnace has its own thermal history. Thus, samples must be representative of the production batch, in order to obtain representative results. In a project involving CTCV on the development of improved glaze for metal marking, it was decided to test all the plates fired during the same firing cycle, with the same glaze, considering five cars in a row, representing 450 plates. The metal marking test followed included a final evaluation based on a 4-scale classification . The final results showed a wide dispersion of results, with around half of the plates considered resistant to metal marking (classification 2 and 3) and the other half rejected . The stuNormally tableware is simply washed with water and detergent and cleaned with a cloth or dried in oven. Nonetheless a careful cleaning of samples before metal marking test is required, in order to eliminate any possible contaminations (dust particles or grease). Karlsson et al.  showed tThe main source of discrepancy that affects the tests repeatability and reproducibility is related to marking utensils. Each procedure uses different metallic utensils to perform metal marking test: knives are mostly used, but also forks, spoons, styli, or even spheres. In what concerns cutlery, material type  and composition, geometry and wear properties must be considered for the right selection. Even if they are sometimes used, the actual trend is to drop out tests with forks and spoons, as well as other materials besides steel. Above all this, the main drawback is that cutlery is not produced as standard product, meaning that no cutlery producer can supply batches of utensils that can be considered identical, considering that for example, knives production involves nearly 40 unitary operations. It is important also to consider that the knife production can suffer modifications along the time or its production could be also discontinued.In any case, it is recommended that the selection of cutlery meet the requirements of the reference standard on stainless steel cutlery for articles in contact with food , in partOnce the knife utensil is selected, the next parameter to control is the pressure applied on the ceramic surface during a metal marking test. This parameter depends on the geometry of the serrated edge , the edge relative position in relation to the glazed surface, and the edge wear. The glaze’s irregularities also contribute to making it impossible to know exactly the total effective contact surface which defines the applied pressure. In conclusion, alternative marking items based on standards materials, such as indenters, styli, or steel balls ,7, allowEven if some tests are based on manual marking realized by an operator, this practice must be dropped out for evident non-reproducibility reasons, at a moment where equipment for automatic or semi-automatic are available on the market. Metal marking testing machines are composed of an arm where the marking utensil is fixed and a support to fix the sample to be tested, in order to avoid any relative movement from the maker during the test. Depending on the model, the moving part can be either the arm or the support. The linear movements (back and forth) on the glazed surface are realized automatically or manually, and the number of back and forth movement varies from 1 to more than 10 in some cases. The linear movement can be done from rim to rim or with a specified distance. It is suggested to avoid marks to cross each other in order to prevent an excess stress and wear at crossing points that may influence a further degradation around the area and conduct to bad interpretation.2 area, meaning that local applied pressure can reach up to more than 800 MPa, in line with values referred by Blanc [2 to 0.50 mm2, and as one may consider that one to three teeth can be in contact with the surface at the same time, it means that pressure can be as local as few MPa. The combination of several scenarios  with the 0.27 mm2 average worn area/tooth showed that an average 80 MPa is applied on the glaze.Loads placed on the arm and correctly balanced control the applied force. In a real situation, the force required to cut food ranges between 20 and 50 N . In pracby Blanc . It was Before evaluation, samples should be cleaned with water and detergent to remove metal particles that have not embedded in the substrate, and then dried.One last relevant limitation of metal marking test is related to the evaluation of marks and scratches, and the consequent classification. Normally, a high level of subjectivity is associated when a visual assessment is made. Development of automatic quantification of marks through image analysis would certainly bring higher consistency to evaluation procedure. Evaluation scales are normally focused on the extreme scenarios: “no marks” and “severe marks” and on intermediate classification, such as slight or distinct marks, or even marks removed by washing. These intermediate judgments are the most difficult to assess, even with reference standards, because mark intensity  and its The evaluation of metal marking resistance over time, by simulation of controlled chemical degradation (washings with detergents) followed by metal marking test, is an optional procedure that permits obtaining valuable information on the durability of products, as it shows the tendency to tertiary metal making. For this, it is suggested to submit samples to an accelerating aging, according to procedure standards for domestic and hotel tableware, respectively ,25.Based on the experience acquired on metal marking tests, CTCV has developed a new procedure, based on standardized stainless steel balls, in order to offer a test that can be widely used and to respond to the growing necessity of a trustful and uniform standard. The choice of these marking utensils was driven by the need to reduce inaccuracies and provide a better control and reproducibility. National and international producers and retailers have used the procedure since 2020.With the commercial equipment  used at The knife action is thus simulated by the movement of two different ø 2.5 mm standardized stainless steel balls, normally produced for mechanical application such as bearings, and thus easy to obtain on the market. AISI 420 ball with hardness 53–60 HRC and AISI 304 with hardness < 39 HRC were selected to represent most common hard and soft cutlery steel, respectively. The test is based on the principle of one ball, one specimen. The ball is fixed on the conic adapter (any rotation is avoided) and can be easily removed between each specimen. After the test, it is also possible, but not mandatory, to determine the amount of steel loosed by the ball, in order to compare the metal marking performance and the amount of steel removed from the sphere. Nevertheless, some caution must be taken because the entire amount of steel removed could not be deposited on the surface, as a part could be eliminated during the washing step, or simply not adhere to the surface. The wear of AISI 304 and AISI 420 steel spheres after a metal marking test performed on a catering dishware can be observed in Scanning electron microcopy shows that the mechanical phenomenon occurring with knives is perfectly reproduced with steel balls, as shown in The test is carried out on a sample composed of 10 specimens, with the two types of balls used on each one of them. Under a 1 kgf load, 12 parallel tracks are made , with 12Specimens are then carefully cleaned with water and detergent, and dried. The evaluation is performed by two skilled operators, under standardized lighting conditions. An evaluation value is assigned to each individual track in function of the following mark severity criteria: 0: “no marks”, 1: “slight marks” and 2: “severe marks”.The minimum number of back and forth cycles (from 1 to 12) after which the average evaluation value of 1 is reached.mm is calculated based on a reverse cycle number weighted average of evaluation values. This parameter ranges between 0 (no marks) and 2 .As it was noticed that the previous classification does not always reflects the real performance of the product, a metal marking coefficient that integrates all individual evaluation value of the batch  was then introduced. The coefficient CThe final classification, for both steel grades, can then be chosen following two different approaches:Some companies are already using this procedure to control their product, allowing them to build their own database, as a wide range of in-house references are tested and compared. At the same time, studies are being made in order to optimize the testing conditions. A comparative study made on a batch of 15 different tableware products  produced by several companies.  and FiguThe objective was to test a representative range of produced tableware at national level.The CTCV test procedure was followed, and each sample constituted of five specimens.mm is achieved when testing with 0.4 kgf compared to 1 kgf. The objective is now to corroborate these results with metal marking performance of all these products in their normal daily use. To achieve this, we maintain a straight collaboration with companies, in order to analyze eventual reclamation from end-users.The analysis of results of Metal marking is a long-time transversal problem of ceramic tableware industry sector that deeply affects the product performance. The research and development work done by raw materials and ceramic producers to develop glazes with better performance in terms of metal marking is being embraced: extremely low roughness glazes, reduction of crystalline phases, chemical resistance, harder glazes, application of protective films or even replication of glazes with excellent metal marking performance. Despite all these efforts and also the use and care recommendation provided to users, it is impossible to control the conditions of service, the type of materials and the quality of the cutlery, the chemical detergents aggressiveness, the washing conditions, and the severe handling conditions typical of the hospitality industry.The actual lack of recognized standards, explained by the recurrent difficulties to establish reliable test protocols, represents an obvious limitation for the comparison between products, as existing tests do not guarantee trustworthy and reproducible results. It is expected that the recent test developed at CTCV can establish an alternative foreseeing the harmonization of metal marking performance tests. Future development works will aim to establish the effective relationship between laboratory test results and metal marking occurrence in real conditions of use.


This study is the first to conduct a comprehensive investigation of the effects of physical exercise on South Korean women with disabilities using the data of previous studies. This study performed a meta-analysis of the effect sizes of exercise programs for women with disabilities using Comprehensive Meta-Analysis 3.0 and a total of 16 papers with 154 participants. The largest effect sizes were found for changes in muscle strength (d = 2.407) for treatment effects, horseback riding (d = 3.080) for exercise type, 45–50 min (d = 3.080) for duration of a single exercise session, three times (d = 0.963) for frequency of exercise per week, 15 weeks (d = 1.974) for period of exercise and 45 times (d = 1.974) for total number of sessions. The results of this meta-analysis showed that exercise programs suitable for the individual-level characteristics of disabled individuals can and should be developed and implemented. People living with disabilities (PWDs) are regarded as the largest minority in the world, and they need to be included in public health programs . MoreoveSouth Korea has been maintaining very rapid economic growth, and it is one of the world’s high-income countries. However, it still lags behind in terms of the welfare of the disabled . South KThere are 2,633,000 PWDs in South Korea , which includes 1,110,000 women (42.2%), and this number is growing . In geneRegarding physical exercise, female PWDs may face disadvantages due to the physiological challenges associated with maintaining their good looks and limited leisure activity opportunities ,14. For Although physical exercise, per se, is meaningful, the effects of exercise may vary according to the exercise type. Physical exercises include weight-bearing exercises, resistance exercises and aerobic exercises . In weigIn general, physical exercise has marked effects on the health and vitality of PWDs. It reduces health problems and has a positive effect on healthy functioning . PhysicaHowever, other studies have reported different results regarding the effects of physical exercise among PWDs. Park  found thFemale PWDs have become increasingly interested in exercise in recent years; however, limited comprehensive analyses on the effects of physical exercise among this demographic have been conducted. There are also very few studies involving adequate surveys, analyses of exercise needs and assessments of participation in sports among female PWDs as an underprivileged population with special needs . TherefoWhat is the overall effectiveness of physical exercises performed by female PWDs as a dependent variable?What are the effect sizes by type of physical exercise  performed by female PWDs?What are the effect sizes for physical exercise among female PWDs by individual characteristics (disability type and age)?What are the effect sizes for physical exercise among female PWDs by program characteristics ?According to the Systematic Reviews and Meta-Analyses (PRISMA) guidelines , the proSouth Korean studies that assessed the effects of exercise among female PWDs in South Korea were collected and analyzed. The study employed a Population, Intervention, Comparison, Outcomes and Study (PICOS) design using a structured questionnaire to clarify key concepts of the research topic . The stuIn this study, to mitigate the problem with the representativeness of study findings when low-quality studies are combined in the meta-analysis, only those papers listed in the Korea Citation Index (KCI) were included in the meta-analysis. The criteria for the exclusion of papers were as follows: papers that did not include exercise treatment for female PWDs, papers not on the subject of female PWDs, papers that presented insufficient data showing the effects of exercise treatment for female PWDs and qualitative studies.Papers published from 2000 to 2020 were searched. This study searched for studies published on female PWDs in academic journals using the search engine of the Korea Education Research Information Service (RISS) and National Assembly Library of Korea (NALK). Search keywords were ‘women with disabilities’ and ‘women with disabilities, exercise’.In this study, two reviewers independently performed the procedures shown in The search yielded 1263 and 595 studies from RISS and NALK, respectively, making 1858 journal articles in total. The studies were reviewed using the procedure described in After undergoing the above-mentioned procedure, from among the 19 papers, 3 papers with insufficient data or qualitative methods were excluded. Finally, 16 studies were selected for the meta-analysis.Studies were coded for analyses of effect. Coding items included basic information about the study , research design (independent and dependent variables and measures) and associated variables. Coding was conducted by a researcher with meta-analysis experience and reviewed by a co-investigator according to agreed-upon guidelines. When individual studies required specific review, they were re-examined, and coding changes were made. After repeating this process, researchers reached an agreement on coded outcomes.r) and odds ratio.Effect size is a unit used for the synthesis and comparison of study results. Commonly used effect sizes include the standardized mean, correlation coefficient  of the homogeneity test was <0.10; therefore, the heterogeneity of the effect sizes was significant. This suggests that the random-effects model was appropriate. I-squared represents a ratio of actual variance to total variance: 25%, 50% and 75% indicate a small, moderate and very large level of heterogeneity, respectively. In this study, I-squared was 63.311, suggesting heterogeneity among the populations.In the present study, the Q-value was 342.423 , which iPrior to measuring the overall effect size, this study tested homogeneity to determine whether the results of individual studies were extracted from the same population. That is, it evaluated whether the effect sizes derived from individual studies could be regarded as being derived from the same population. In the homogeneity test, if individual studies are extracted from the same population and construed to be homogeneous while the results are statistically significant, effect sizes are estimated based on the random-effects model, which assumes the results of individual studies are from different populations. Under the random-effects model, studies with a small sample size are given a larger weight, while studies with a large sample size are given a smaller weight. The method of Hedge and Olkin  was usedIn this study, a total of 16 papers were included in the meta-analysis, and the number of participants was 154. The first studies on the effects of exercise performed by female PWDs were ,39,40. AThe overall effect size in this study was verified through the random-effects model because individual studies were found to be heterogeneous. The overall effect size was 0.808, and the 95% confidence interval was 0.665–0.950 . AccordiIn addition to the effect of exercise treatment in the papers included in the meta-analysis, regarding the control group, Song  examinedIn Ahn et al. , the subThe present study investigated the effects of physical exercise and their implications among female PWDs using a meta-analysis. Specifically, the effect sizes of physical exercises for female PWDs were compared by gathering the results of existing studies to examine the effect sizes of correlations. The meta-analysis included results from 16 studies.First, the results were examined in relation to the effect of physical exercise treatment of female PWDs and the effect sizes by exercise type. The effect size for the outcome of physical exercise was largest in changes in muscle strength, followed by psychological change. Both psychological and physical changes must be examined, and these changes are demonstrated through the results of this meta-analysis. The findings are in line with the idea that the lives of PWDs are multifaceted and affected by a multitude of circumstances, including societal, historical, family and community values. Additionally, exercise programs should include PWDs in this broad context .Regarding the type of physical exercise, the effect size was largest for horseback riding, followed by swimming classes and swimming programs. Horseback riding is challenging in terms of accessibility and affordability, while swimming is highly accessible. Furthermore, swimming is in high demand because it improves quality of life and leisure time while promoting health and enhancing physical strength. Kim and Kim  found a Second, regarding the effects by personal characteristics of female PWDs, effect sizes by disability type and age were examined. Regarding the type of disability, the effect size was largest among women with visual impairments. This may be because women with visual impairments have fewer physical difficulties than do women with other disabilities. The effect sizes were relatively small for mental disorders and intellectual disabilities. Top et al.  studied Regarding age, the effect size was largest among female PWDs in their 40s, followed by those in their 30s, 20s and 50s. This does not show a clear correlation between age and the effects of physical exercise. Additionally, the meta-analysis suggested that research on female PWDs in their 60s is lacking, despite its growing importance with the phenomenon of increased life expectancy in South Korean society.Third, regarding the effects by physical exercise composition for female PWDs, effect sizes by the duration of one physical exercise session, frequency of exercise per week, physical exercise period and total number of physical exercise sessions were examined. Regarding the duration of physical exercise sessions, the effect of physical exercise for female PWDs was largest when a session lasted 45–50 min. By contrast, the effect size was relatively small for 60 min sessions. The results suggest that the effect of physical exercise is greater when the duration of a session is up to 60 min. Regarding the frequency of sessions, the effect size was largest for sessions that occurred three times a week. The effect of exercise was smallest when sessions occurred once or five times a week.Regarding the period, the effect size was largest when exercises ran for 15 weeks. Son et al.  found thThe significance of the findings of this study can be divided into three points. First, this study can be considered to have theoretically contributed to the literature on exercise performed by female PWDs in that the findings of this study indicate that exercise performed by female PWDs has not only psychological effects, but also physical effects, and that the exercise effects of swimming using community spaces are large. This supports the notion that exercise performed by women with disabilities should be seen not only from the perspective of recovery from physiological damage, but also from a social perspective.Second, the findings of this study suggest that other exercise programs should be supported in order to enhance the physical exercise effects of the physically, mentally or intellectually disabled. This can be said to have laid a foundation for separately planning exercise programs for the mentally disabled and for the intellectually disabled.Third, this study can provide practical help in composing exercise programs for female PWDs because it concretely presents the duration, number of sessions and period appropriate for physical exercise effects in South Korea or in countries with similar welfare dimensions or cultural characteristics for female PWDs.In summary, these study results suggest that individual characteristics and environment affect the optimal level of exercise.In terms of limitations, since this study was conducted with a relatively small volume of study results, the generalizability of the study findings is limited. Therefore, it is thought that this study should be supplemented by follow-up studies when more studies on exercise programs for female PWDs are accumulated. In addition, there were limitations in comparing the effects of exercise according to gender, as studies on PWDs were conducted without distinguishing between men and women. This study investigated the effects of exercise among South Korean female PWDs and included no comparison with studies on male PWDs. Therefore, further research must be conducted among male PWDs to investigate the effect size of exercise for these PWDs.The study also lacked an analysis of the characteristics of South Korean culture in relation to exercise among female PWDs. In the future, studies should be conducted on exercise participation and opportunities for female PWDs in the context of South Korean culture. In addition, studies have shown that the reason for participating in sports or physical activity for long periods of time is the enjoyment of the activity itself rather than for maintaining health or physical training ,59,60,61In terms of conclusions, first, there is a lack of studies on female PWDs in South Korea. Regarding the theory of PWDs, studies on exercise performed by PWDs should apply either the medical model or the social model or both in combination. In South Korea, disabilities cause more difficulties to women when they lead their social lives. Therefore, it is more necessary to enable female PWDs to perform their activities more smoothly through physical exercise and to create conditions for their social activities. In addition, conditions under which female PWDs in South Korea can exercise more easily should be prepared. While the South Korean economy has grown rapidly, the budget for PWDs’ welfare is relatively insufficient. The problems of female PWDs should be seen as not only personal problems, but also important social and national issues, and the support process and system for female PWDs should be strengthened further.Second, it is worth noting that the correlation between the effect sizes and exercise treatments for female PWDs was strong and that the effect sizes by type of exercise treatment were large not only in terms of psychological changes, but also in terms of muscle strength. Therefore, it is necessary to develop and implement comprehensive exercise programs that can bring about physical and psychological changes through exercise performed by female PWDs in the future.Third, regarding the sizes of exercise effects by personal characteristics of female PWDs, the effects of exercise on the visually impaired were shown to be the largest, but the effects on women with mental disorders or intellectual disabilities were shown to be small. These findings can be said to be related to the physical/mental conditions for performing exercise. Therefore, it is necessary to develop exercise programs suitable for individual disability characteristics. Meanwhile, regarding exercise effect sizes by age, although exercises performed by female PWDs in their 40s showed large effects, effects were relatively small for those in their 20s and relatively large for those in their 30s and 50s. Therefore, exercise effects could not be considered to be correlated with age. These findings show that further studies on the correlation between age and exercise effects are necessary and that exercise programs must be developed and implemented by age.Finally, the effect sizes were largest when a session lasted 45–50 min, the frequency of sessions was three sessions per week, the period of exercise was 15 weeks and the total number of sessions was 45. In summary, the effect of exercise was greatest when PWDs exercised a total of 45 times over 15 weeks at three sessions per week and 45–50 min per session. This suggested that the effect of exercise among female PWDs is largest when they exercise every other day for approximately 3 months.