Novel neoadjuvant therapy regimens are warranted for oral squamous cell carcinoma (OSCC). In this phase I trial (NCT04393506), 20 patients with locally advanced resectable OSCC receive three cycles of camrelizumab  and apatinib  before surgery. The primary endpoints are safety and major pathological response . Secondary endpoints include 2-year survival rate and local recurrence rate (not reported due to inadequate follow-up). Exploratory endpoints are the relationships between PD-L1 combined positive score  and other immunological and genomic biomarkers and response. Neoadjuvant treatment is well-tolerated, and the MPR rate is 40% (8/20), meeting the primary endpoint. All five patients with CPS ˃10 achieve MPR. Post-hoc analysis show 18-month locoregional recurrence and survival rates of 10.5% (95% CI: 0%–24.3%) and 95% (95% CI: 85.4%–100.0%), respectively. Patients achieving MPR show more CD4+ T-cell infiltration than those without MPR (P = 0.02), and decreased CD31 and ɑ-SMA expression levels are observed after neoadjuvant therapy. In conclusion, neoadjuvant camrelizumab and apatinib is safe and yields a promising MPR rate for OSCC. In patients with locally advanced resectable oral squamous cell carcinoma (OSCC), the risk of recurrence and metastasis following treatment is high. Here, a phase I clinical trial reports safety and pathological response of neoadjuvant camrelizumab and apatinib in patients with locally advanced resectable OSCC. Even after intensive treatments, patients remain at high risk of recurrence or metastasis2. In recent years, neoadjuvant therapy before surgery has been shown to reduce the burden of locoregional disease, resulting in improved surgical outcomes; to reduce the risk of distant metastases; and to predict prognosis based on the pathological response in various solid tumours3. However, its role in the treatment of OSCC remains ambiguous. Neoadjuvant chemotherapy using cisplatin plus fluorouracil (PF) or docetaxel plus cisplatin plus fluorouracil (TPF) regimens has been explored in patients with OSCC but has not demonstrated survival benefits beyond those provided by standard treatment5. Thus, exploring effective neoadjuvant therapeutic approaches for locally advanced resectable OSCC remains an urgent need.For patients with locally advanced resectable oral squamous cell carcinoma (OSCC), surgery with adjuvant radiotherapy or chemoradiotherapy has been recommended as the standard treatment7. Preclinical data suggest that when the tumour is in place, neoadjuvant immunotherapy stimulates the release of tumour antigens and enhances T-cell priming, thereby resulting in stronger effects than those of adjuvant therapy8. In the neoadjuvant setting, immune checkpoint blockade has shown promising results against many other tumour types12. However, for OSCC or HNSCC, neoadjuvant anti-programmed cell death-1 (PD-1) monotherapy has shown a relatively low major pathological response (MPR) rate (4.3% for pembrolizumab in HNSCC and 8% for nivolumab in OSCC)14.Immune checkpoint blockade has been demonstrated to have clinically meaningful antitumor activity in recurrent/metastatic head and neck squamous cell carcinoma 18. The combination of camrelizumab (an anti-PD-1 antibody) and apatinib (a VEGFR inhibitor) has shown favourable antitumor activity and manageable safety in various types of advanced cancers22. However, this combination has not been studied in patients with locally advanced resectable OSCC.Targeted drugs against vascular endothelial growth factor receptor (VEGFR) or that inhibit angiogenesis have been shown to relieve immunosuppression through blood vessel normalisation and the oxygen metabolism pathway, thereby having a synergistic effect with anti-PD-1 immunotherapy and concurrently diminishing the risk of immune-related adverse effectsHere, we show that in patients with locally advanced resectable OSCC, the chemo-free combination of camrelizumab and apatinib as neoadjuvant therapy produces a promising MPR rate with a manageable safety profile.From April to December 2020, 21 patients were enroled, and one patient withdrew at the beginning of treatment. The characteristics of the 21 enroled patients are listed in Table N = 8, 40%), thrombocytopenia  and proteinuria . No neoadjuvant therapy-related grade 3 or above AEs were observed  were hyperbilirubinemia (ed Table  and 2. Tp = 0.00003), meeting the primary endpoint.Assessments of the pathological efficacy indicated that MPR was achieved in eight patients . The MPR rate in this trial was statistically significantly higher than the null rate of 7%  were performed based on imaging examinations before and after neoadjuvant therapy. The radiographic response indicated three patients with partial response (PR), ten patients with stable disease (SD), and six patients with progressive disease (PD)  of patients, with the characteristics of necrosis, multinucleated giant cells, and calcification. In the only patient who achieved pathological complete response (pCR) in the primary tumour, pCR in one lymph node was also observed , and an originally unplanned post hoc analysis of 18-month locoregional recurrence and survival rates was conducted. Two patients who did not receive adjuvant radiotherapy had contralateral neck lymph node metastasis and local recurrence. The estimated 18-month locoregional recurrence rate was 10.5% (95% CI: 0–24.3%). One patient died, and the estimated 18-month overall survival rate was 95% (95% CI: 85.4–100.0%).We systematically reviewed the pathological features of resected specimens and proposed immune-related pathological response criteria (irPRC) for neoadjuvant therapy in OSCC. We observed the following characteristics of the immune-related pathological regression bed in OSCC: multinucleated giant cell infiltration, dystrophic calcification, tumour-infiltrating lymphocytes (TIL), foamy macrophages, neovascularization, proliferative fibrosis, tertiary lymphoid structure, and dense plasma cells. In two patients who achieved MPR, tertiary lymphoid structure was observed in the tumours after neoadjuvant therapy . One patient with CPS = 90 who achieved radiographic PR was pathologically confirmed to have achieved pCR  and pathological response was examined. All five patients with a CPS value ˃10 achieved MPR Fig. . The numpCR Fig. .TP53 , followed by TERT  and CDKN2A   and the CD8+ /FoxP3+ ratio (p = 0.002) and decreases in the number of CD3+ (p = 0.03) and FoxP3+ (p = 0.03) cells from before to after neoadjuvant therapy . The most frequently mutated gene was 0%) Fig. . No sign0%) Fig. . MultiplOne patient from the non-MPR group was found to exhibit tumour progression on radiographic evaluation, with a change in growth kinetics exceeding 50% and new neck lymph node metastasis, and was confirmed to exhibit disease hyperprogression  and ɑ-SMA (a marker of pericytes) expression levels were observed after neoadjuvant therapy, thus confirming the antiangiogenic effect in tumours Fig. . No signOur results provide the first evidence that neoadjuvant therapy using a chemo-free combination of camrelizumab and apatinib is well tolerated in patients with OSCC, with an MPR of 40%.23. We observed no grade 3–4 neoadjuvant therapy-related AEs, which might be due to the short course of camrelizumab and apatinib administration. Furthermore, the safety that was observed in our trial seems to be superior to that observed in other neoadjuvant chemotherapy regimens used in OSCC trials, such as neoadjuvant chemotherapy with the TPF regimen (9–38% grade 3–4 therapy-related AEs)25 or targeted therapies (25–61.6% grade 3–4 therapy-related AEs)27. Recent neoadjuvant immunotherapy studies in head and neck cancer showing favourable side effects further supported the superior safety of neoadjuvant immunotherapy29. Since previous studies reported that anti-VEGF(R) therapies could increase the risk of bleeding31, we set a time interval of 5 days between apatinib administration and surgery to reduce the risk of complications during subsequent surgery. Although the surgery-related AEs observed in our study were considered unrelated to neoadjuvant therapy, trials with larger sample sizes are necessary to definitively indicate the effects of neoadjuvant anti-PD-1 plus anti-VEGFR therapy on surgery.The safety profile of camrelizumab and apatinib in the neoadjuvant setting was mostly consistent with that previously reported in advanced cancers25, pembrolizumab monotherapy (4.3–20.5%) and nivolumab monotherapy (5.9%) in HPV-unrelated HNSCC32, and nivolumab monotherapy (8%) or nivolumab combined with ipilimumab (20%) in OSCC, although cross-study comparisons should be made with caution13. In another neoadjuvant therapy trial for HNSCC, the cisplatin/docetaxel/durvalumab/tremelimumab combination in a neoadjuvant setting showed a superior pathological response in terms of pCR (48%) but also had a higher rate of grade 3–4 AEs (68%)33. One trial using immune radiotherapy in a neoadjuvant setting achieved a high MPR rate (86%) in HNSCC, thus supporting the further evaluation of the addition of stereotactic body radiation therapy to neoadjuvant immunotherapy34. The results from this study suggested that a high CPS might predict MPR from neoadjuvant therapy with camrelizumab and apatinib. Due to the limited sample size, the predictive value of CPS for anti-PD-1 plus anti-VEGFR therapy that was observed in this study must be validated in a larger study. The concept of using CPS to guide the choice of neoadjuvant immunotherapy was consistent with principles suggested for recurrent/metastatic HNSCC35.In addition to safety, pathological efficacy, including MPR, is a crucial criterion for proposing neoadjuvant therapy in OSCC or HNSCC. The combination of camrelizumab and apatinib showed a promising MPR (40%), as compared with chemotherapy with PF (33%) or TPF (27.7%) in OSCC37, in OSCC or HNSCC, irPRC have not been well defined. In previous neoadjuvant immunotherapy trials, the pathological response has been described as featuring a “visible regressed tumour” in addition to “inflammation, giant cell reaction and acellular keratin” and has been quantified as occurring in “a percentage of the overall tumour bed ”29. Regardless of the assessment method that is used, the definition of the tumour regression bed after neoadjuvant therapy is key, especially in tumours that have significantly shrunk. Based on the criteria for determining the range of the immunotherapy-induced tumour regression bed proposed in lung cancer37, we systematically evaluated the features of tumours from different oral cavity sites in this trial, thus providing a reference for irPRC for subsequent neoadjuvant immunotherapy in OSCC.In all the reported neoadjuvant immunotherapy trials for OSCC or HNSCC, the pathological response varied in terms of MPR ratios, and the assessment procedures also varied. Unlike in non-small cell lung carcinoma and melanoma37. In agreement with findings from a study using nivolumab, a similar response was found between primary sites and lymph nodes38. Nodal upstaging occurred in four patients in our study, and all the corresponding primary tumours did not achieve MPR; therefore, this finding suggests that lymph nodes should be monitored more frequently during neoadjuvant treatment.The irPRC we proposed for OSCC did not include the pathological response characteristics for neck lymph node metastasis. We found only one lymph node with confirmed tumour regression, whereas a different reaction occurred in another lymph node from the same patient. As described in a previous lung cancer study, the limitations of nodal disease assessment have been attributed to sampling issues39. In pathological re-evaluation of the resected lesions, the RECIST 1.1 criteria did not show sufficient sensitivity in response assessment in our trial. Among the eight patients who achieved MPR, only three showed PR on radiographic scans. One patient with a radiographic PD lesion in our trial was further pathologically confirmed to have achieved MPR, thus indicating the importance of the re-evaluation of progression after immunotherapy. This finding was consistent with the radiographic response analysis of neoadjuvant immunotherapy in lung cancer, in which 30% of patients with SD nearly achieved pCR40. In future neoadjuvant therapy trials, other modified methods for radiographic response evaluation should be proposed, such as the criteria used in the window of opportunity, in which a size reduction ˃10%, rather than 30%, might be defined as indicating a “radiographic responder”38.Because of the short period of 2 weeks between the last neoadjuvant immunotherapy and surgery, radiographic re-evaluation based on modified RECIST 1.1 criteria for immune-based therapeutics (iRECIST) could not be performed in this study42, TP53 was found to be the most frequently mutated gene in our study. In agreement with findings from other neoadjuvant immunotherapy trials for OSCC or HNSCC42, neither the mutated gene enrichment nor the degree and features of baseline TIL infiltration predicted MPR in our study. The limited sample size and the heterogeneity between biopsy and surgically resected tissues might be the reason, although we matched the biopsy and surgically resected tissues by the clinical tumour sites and features, as well as the microscopic tumour cell proportion. However, higher levels of CD4+ T-cell infiltration were observed in resected tumours that achieved MPR. However, an abnormal increase in the level of CD163+ cell infiltration was observed in HPD tumours. A higher level of CD4+ cells was associated with better outcomes of neoadjuvant therapy, and M2 macrophages in the tumour microenvironment have been reported to be associated with the occurrence of HPD44. Further analyses of our tumour samples are urgently needed to explore the underlying mechanisms.Consistent with previous reports46. However, the expression of angiogenesis markers showed no differences between the MPR and non-MPR groups, and this paradoxical finding might be due to the small sample size of our trial. However, the multiple steps of the cancer immunity cycle and multiple signalling pathways have been found to be affected when combining antiangiogenic agents with anti-PD-1 therapy. Antiangiogenic therapy can inhibit angiogenic signalling and result in normalisation of the tumour vasculature to diminish the immunosuppression exerted by immunosuppressive cells , as well as inhibit the expression of PD-1 and regulate apoptotic pathways in cytotoxic CD8+ T cells, thereby improving the efficacy of immunotherapy48. Huang et al. also reported that crosstalk between tumour vascular normalisation and immune reprogramming pathways exists and plays a vital role in responses49. In addition, the LTβR signalling pathway and angiogenic pathway ANGPT2/Tie2 have been reported to be modulated after combinatory treatment with an antiangiogenic agent and anti-PD-1 antibody50. In our trial, whether apatinib affects other pathways or other cell types when combined with camrelizumab deserves further investigation.The expression of angiogenesis markers following apatinib treatment, including CD31 and ɑ-SMA, was inhibited by neoadjuvant therapy in this trial, which is similar to previously reported preclinical results52, whether they might result in long-term survival improvement remains to be confirmed in this and other neoadjuvant immunotherapy trials. In addition, since sufficient baseline tumour tissues were not available for all patients, definitive conclusions regarding biomarkers remain ambiguous. Further in-depth analysis of biomarkers in patient tumours and blood  should be performed in our ongoing randomised trial (NCT05069857) and other ongoing neoadjuvant trials51.The limitations of this trial mainly include the small sample size and single-arm design, which lacked a control arm. Nevertheless, the primary endpoint MPR rate was promising in spite of small sample size. It is important to emphasise that although MPR or even pCR have been considered candidate early surrogate endpoints for survival in the neoadjuvant settingIn conclusion, this pilot trial showed that neoadjuvant therapy using a chemo-free combination of camrelizumab and apatinib was well tolerated in patients with OSCC. The MPR rate was promising, and CPS might be a signal predictor. These results suggest that further neoadjuvant therapy trials for OSCC using anti-PD-1 plus anti-VEGFR should be conducted.This single-centre, open-label phase I trial was performed at the Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine in Shanghai, China. Eligible patients were aged 18–75 years, had histopathologically confirmed locally advanced OSCC with a clinical stage of III or IVA , and had an Eastern Cooperative Oncology Group performance status of 0 to 2. Patients were enroled between April 2020, and December 2020. The full eligibility criteria are provided in the trial protocol  on d1, d15, and d29 and oral apatinib (250 mg) daily, starting on d1 and ending on the 5th day before surgery. Standard radical surgery was planned on d42–45. Adjuvant radiotherapy or chemoradiotherapy was planned within 6 weeks after surgery, according to the pathological stage.The standard operation procedure of determining the regression bed induced by neoadjuvant immunotherapy in oral cancer was proposed. Briefly, before neoadjuvant therapy, the baseline tumour bed was recorded by photographing and radiographic examination. Marks using tattoo or methylene blue were placed 0.5 cm from the palpable margins of the tumour. After neoadjuvant therapy, features of the tumour were also recorded before surgery. The resection range was determined by the baseline tumour bed even if the tumour shrank after neoadjuvant therapy. In this case, we connected the original marking points as a reference for the determination of surgical safety margins (0.5–1.0 cm away from the marking points) and pathological tumour bed.52, haematoxylin and eosin-stained (H&E) slides of sections of the residual tumour were assessed by pathologists blinded to the patient information. Slices of at least 1 section per 3 mm of the greatest tumour diameter were obtained during sampling. The standard operating procedure of slide preparation is shown in Supplementary Figs. According to a previous study37, the tumour bed was defined as the areas of “residual viable tumour + necrosis + regression bed”  cells was evaluated by H&E staining of all slides. According to a previous study53. Surgery-related AEs were assessed using the guidelines of the Clavien‒Dindo Classification of Surgical Complications54.The primary endpoints were safety and MPR rate . The 2-year survival rate  and local recurrence rate  were the secondary endpoints, which were not reported due to inadequate follow-up. AEs were assessed according to the Common Terminology Criteria for Adverse Events (version 5.0). Neoadjuvant therapy-related AEs were managed mainly according to the American Society of Clinical Oncology Clinical Practice GuidelinesProgrammed cell death-ligand 1 (PD-L1) expression was evaluated with a PD-L1 immunohistochemistry (IHC) 22C3 pharmDx assay . CPS was defined as the total number of PD-L1-stained cells  divided by the total number of viable tumour cells, multiplied by 100.The Akoya OPAL Polaris 7-Colour Automation IHC kit (NEL871001KT) was used to evaluate TIL. Formalin-fixed, paraffin-embedded (FFPE) tumour slides were deparaffinized in a BOND RX system (Leica Biosystems) and then sequentially incubated with primary antibodies targeting CD163 , CD68 , PD-1 , CD3 , CD4 , CD8 , CD56 , CD20 , FOXP3  and Pan-CK  (Akoya Biosciences). Then, the cells were incubated with secondary antibodies and corresponding reactive Opal fluorophores. Nuclei acids were stained with DAPI. Slides incubated with primary and secondary antibodies without fluorophores were used as negative controls.After staining, slides were scanned using a Vectra Polaris Quantitative Pathology Imaging System (Akoya Biosciences) at 20 nm wavelength intervals from 440 nm to 780 nm with a fixed exposure time and an absolute magnification of ×200. All scans for each slide were then superimposed to obtain a single image. Multilayer images were imported into inForm v.2.4.8 (Akoya Biosciences) for quantitative image analysis. The tumour parenchyma and stroma were differentiated by Pan-CK staining. The quantities of various cell populations were expressed as the number of stained cells per square millimetre in all nucleated cells.CD31  and α-SMA (pericytes) staining were performed to evaluate vascular normalisation. The antibodies used were anti-CD31 #ab178981 , Alexa Fluor 594 donkey anti-rabbit lgG(H + L) #A21207 , anti-alpha smooth muscle actin [1A4] #ab7817  and Alexa Fluor 488 donkey anti-mouse lgG(H + L) # A21202  in addition to DAPI . The obtained slices were observed by confocal fluorescence microscopy . The fluorescence intensity was analysed by ImageJ software.Formalin-fixed paraffin-embedded tissue sections were evaluated for tumour cell content using H&E staining. Only samples with a tumour content of ≥20% were eligible for subsequent analyses. Genomic DNA was isolated from tissue samples using the ReliaPrep™ FFPE gDNA Miniprep System (Promega) and quantified using the Qubit™ dsDNA HS Assay Kit (Thermo Fisher Scientific) following the manufacturer’s instructions. DNA extracts (30–200 ng) were sheared to 250 bp fragments using an S220 focused ultrasonicator (Covaris). For targeted capture, indexed libraries were subjected to probe-based hybridisation with a customised NGS panel targeting 733 cancer-related genes.HGF signalling, EGFR/RAS/BRAF signalling, CDK signalling, AKT/mTOR/PI3K signalling, FGFR signalling, p53 signalling, epigenetic/chromatin remodelling, DNA damage and repair/telomere stability, and NOTCH signalling. Other clinical trial drug target and TERT promoter hot spot mutations were also shown in the genomic landscape.The captured libraries were loaded onto a NovaSeq 6000 platform (Illumina) for 100 bp paired-end sequencing with a mean sequencing depth of 1000. Tumour mutational burden was defined as the number of nonsynonymous somatic single nucleotide variants (SNVs) and indels in examined coding regions, with driver mutations excluded. All SNVs and indels in the coding region of targeted genes, including missense, silent, stop gain, stop loss, in-frame and frameshift mutations, were considered. The “maftools” package was used to examine the genomic landscape. Copy number variation analysis was performed using an in-house developed pipeline. A fold-change threshold of 1.6 and 0.6 in DNA copy number was set as the cut-off for amplification and deletion, respectively. The key pathway-related genes were visualised, including those involved in 14) to 30% using a one-sided exact test with a significance level  of 0.050.A sample size of 20 evaluable patients was required to achieve 90% power to detect an increase in the MPR rate from 7% , GraphPad Prism software (version 9.1.2) and SAS (version 9.4).In an unplanned post hoc analysis, the 18-month overall survival rate and local recurrence rate was evaluated with the Kaplan‒Meier method. The CIs were calculated with the Brookmeyer–Crowley method for survival and recurrence rates and calculated with the Clopper–Pearson method for the MPR rate. The Further information on research design is available in the Supplementary InformationReporting SummaryPeer Review File


Computed tomography revealed diffuse oedematous thickening of the whole gastric wall, despite the absence of duodenum obstruction and a small amount of ascites (Figure A 74‐year‐old Japanese man who had received one cycle of azacitidine for myelodysplastic syndrome and regularly used proton pump inhibitors was hospitalised with sudden‐onset stomach ache and fever. He had been administrated meropenem and micafungin for febrile neutropenia during the azacitidine therapy until 3 days before admission. Clinical laboratory data on admission showed: white blood cell count, 0.7 × 10PG is a rare entity as a differential diagnosis of acute abdomen and often lethal acute infection of the stomach. Prompt antibiotic therapy based on early diagnosis is required. As mucosal injury due to gastric cancer, peptic ulcer or endoscopic procedure is regarded as the main cause of PG, few cases of PG with haematological malignancies have been reported. Even in this patient who was regularly using proton pump inhibitors and had no history of endoscopic manipulation, the initial onset of AML can on rare occasions cause fatal infection such as PG due to neutropenia. As with our patient, a rare but potentially fatal gastric infection can be an initial feature of AML, due to the severe neutropenia resulting from AML, despite the continuous use of proton pump inhibitors and the lack of prior endoscopic manipulation.No funding was recieved.The authors declare that they have no conflict of interest.SL, KF and HT contributed to the conception and the design of the study. SL contributed to the literature review and the writing of the manuscript. MK, HM, TH, and HT contributed to the revision of the manuscript. KF contributed to figure creation. SL and KF confirm the authenticity of all the raw data. All authors approved of the final manuscript version submitted for publication.In accordance with our institution's ethics board, written consent forms are not required as less than 10 cases are reported.


Fibre-reinforced polymer materials (FRP) are increasingly used to reinforce structural elements. Due to this, it is possible to increase the load-bearing capacity of polymer, wooden, concrete, and metal structures. In this article, the authors collected all the crucial aspects that influence the behaviour of concrete elements reinforced with FRP. The main types of FRP, their characterization, and their impact on the load-carrying capacity of a composite structure are discussed. The most significant aspects, such as type, number of FRP layers including fibre orientation, type of matrix, reinforcement of concrete columns, preparation of a concrete surface, fire-resistance aspects, recommended conditions for the lamination process, FRP laying methods, and design aspects were considered. Attention and special emphasis were focused on the description of the current research results related to various types of concrete reinforced with FRP composites. To understand which aspects should be taken into account when designing concrete reinforcement with composite materials, the main guidelines are presented in tabular form. Nowadays, concrete is the most common building material . More anHowever, the correct process for strengthening concrete structures depends on a number of factors. The first factor is the choice of the type of FRP composite fibres taking into account the environmental impact to which the reinforced element is exposed. The second is the selection of the matrix co-creating the composite structure in which the fibres/mats/tapes will be embedded. Other equally important factors determining the quality of the reinforcement made are: the orientation of the fibres in the composite, the course of the lamination process, preparation of the concrete substrate, and protection of the composite against the effects of an aggressive environment such as physical and chemical factors. Bearing the above aspects in mind and the fact that the reinforcement of concrete structures with the use of composite materials has developed rapidly in recent years ,7, the aThe reinforcement of concrete structures with the use of composite materials has developed rapidly in recent years. In order to provide information on FRP for concrete reinforcement contractors, the authors provided a short description of composites and FRP composites. Examples of how FRP composites can be used in the civil engineering industry are presented.Composites are based on two or more fundamental materials, and when combined, they have properties other than individual constituent materials. According to Rajczyk and Stachecki , composiTo maintain the entire system in a compact form (combines reinforcement);To transfer external loads to the reinforcement;To provide appropriate strength;To influence the chemical and thermal properties;To protect reinforcement against mechanical damage;To give products a specific shape.A composite consists of a matrix and a second component (reinforcement) placed in it, which has much better mechanical properties . The majTo improve strength properties;To increase resistance to abrasion;To reduce thermal expansion;To increase resistance to thermal shock;To stop the propagation of cracks;To increase the load-bearing capacity of structures.The major functions of the inner reinforcement are:Fibre-reinforced polymer (FRP) is a composite material made of a polymer matrix reinforced with fibres . Due to Steel, concrete, and wood are the basic structural materials that are widely used in civil engineering. The FRP technique could be perfectly adapted to improve the properties of these materials and change the load-bearing capacity of structural elements. FRP materials can be used for various types of reinforcements. There are no significant restrictions in the strengthening of elements with complex geometry such as beams, chimneys, columns, walls, columns, silos, and supporting structures for pipelines and gas pipelines. Due to their properties , FRPs have been used in a wide range of applications, including pavements, industrial floors, tunnel linings, slope stabilization, impact-resistant structures, and structures sensitive to earthquakes . IncreasIncrease resistance to the seismic loads of masonry structures;Increase the strength of concrete and reinforced columns;Replace missing reinforcements;Enable the reassignment of buildings;Increase the strength of individual elements and the entire structure;Improve the load capacity of a structure that is weakened due to structural errors;Adapt the load capacity of a structure to the applicable standards and requirements;Enhancement of service loads;Increase service life and durability;Improve resistance to seismic loads.FRP materials can be used in reinforced steel, concrete, and wooden and brick constructions to:The correct process for strengthening concrete structures depends on a number of factors. From the choice of the type of FRP composite fibres and the matrix up to lamination process, the authors presented the most important factors influencing the effectiveness of structural strengthening.The mechanical and physical properties of the most common fibres used in FRP laminates are presented in Carbon fibres (CF) are one of the most common fibres used to reinforce engineering structures, and are characterized by chemical and thermal resistance. One of the major important aspects regarding CF is the permissible temperature to use them up to even 2000 °C, in contrast to glass or aramid fibres ,32. AcceBasalt fibres (BF) are produced by melting crumpled basalt rocks at a high temperature equal to 1400 °C. BF have better physical and mechanical properties than glass fibres. The cost of BF is lower than CF and much more expensive than glass fibres.Aramid fibres (AF) are characterised by excellent chemical, mechanical, and physical properties at high temperatures. Unfortunately, AF have a very low resistance to ultraviolet light. Under the influence of long sunlight, the strength properties of these fibres may drop by more than 50%. Kevlar fibres and modified AF with chains including p-disubstituted benzene are characterised by much better mechanical properties than standard AF.Glass fibres (GF) are chemical fibres obtained from water glass, and sometimes also from melted glass. Changes in the amount of raw materials, such as clay for alumina, sand for silica, colemanite for boron oxide, or calcite for calcium oxide enable the obtainment of different types of glass fibres. The advantages of GF are mainly their high mechanical strength, lightness, and resistance to aggressive environments. GF are available in a variety of forms and shapes, which is why they are widely used in engineering. The stress–strain characteristics for FRP materials and steel are presented in The orientation of fibres in FRP composites has the most significant influence on the load-bearing capacity of reinforced concrete structures. Creating mats from carbon fibres allows the fibres in the mats to be freely arranged and different weaves to be created. For ordered fibres, the material properties are strongly anisotropic and the Young’s modulus and strength are a function of the volume fractions of the fibres and the matrix. In addition, the modulus of elasticity and strength in the ordering direction are much greater than in the direction perpendicular to the ordering. If the fibres are arranged in an orthogonal way, there are directions of ordering and disorder called anisotropy. In this case, the best mechanical properties occur under load along the fibres. Disordered fibres are characterized by isotropic properties and an ultimate breaking strength lower than in the case of materials with ordered fibres. The different orientation of carbon fibres in composite manufactured from three CFRP laminates is presented in Every contractor knows that proper installation is the key process, no matter the technology. This paragraph will be especially useful for contractors, seeking information on FRP installation. The efficiency of strengthening structural elements depends on the correct fibre lamination process. There are two methods for carrying out the process of strengthening engineering objects using FRP fibres and epoxy resin: the wet lay-up and the dry lay-up.The name ‘wet lay-up method’ comes from the status of the FRP at the time of application in its final position. In this method, part of the epoxy resin is applied directly to the FRP reinforcement, while the other part of the resin, with a thixotropic agent, is used to reinforce the concrete substrate. At the beginning, the structural element should be reinforced with epoxy resin with a thixotropic agent  should be prepared in a proper way. CS must be dry, clean, and free of surface moisture. The laitance, dust, curing compounds, oils, waxes, foreign particles, impregnations, and other coatings must be removed from the concrete surface. For the best results, sandblasting, grinding or shot blasting are recommended. An unprepared concrete surface is presented in Grinding is surface finishing with abrasive tools, which results in high dimensional and shape accuracy, as well as low roughness. The material from which grinding wheels are made of is most often diamond, corundum, boron carbide, or silicon carbide. Sandblasting is a technological process that consists of cleaning or shaping the surface with abrasive material (sand) in a stream of compressed air or liquid. The sanding effect is similar to grinding; however, the surface being cleaned is more even and obtains the required roughness. Shot blasting is a similar technology to sanding. In this method, instead of sand, special metal shots are used . Most often, the shots can be recovered and reused. Research was carried out by the authors  to invesThe humidity of concrete surfaces in the lamination process is one of the key factors affecting the quality of the concrete substrate and it further affects the joint between the main structure and the outer reinforcement. Before commencing the process of strengthening the structure, it is necessary to define the moisture content of the concrete substrate, and determine the dew point temperature (DPT) and relative humidity. Most manufacturers of composite materials and resins specify the maximum substrate moisture content to be 4–5% by weight. The temperature, however, must be at least a few °C above the DPT. Too high humidity of the concrete surface may reduce the penetration depth of the epoxy resin and reduce the adhesion of the binder to the concrete.It is also very important that the resin should be at the ambient temperature where the lamination takes place and during the process. Adverse changes may occur in the laminate, which may result in its permanent under-hardening at temperatures below 10 °C. At temperatures above 40 °C, the resin gels too quickly, preventing the FRP fibres from oversaturating.Due to the major disadvantage of epoxy resin, i.e., low resistance at high temperature, structural elements reinforced with an organic matrix should be protected against direct impact of high temperature and fire. Damage due to fire/high temperatures is one of the major destructive aspects that cause deterioration of reinforced concrete structures  and concThe main reason for protecting the reinforced concrete structure against the effects of sunlight and elevated temperatures is the relatively low glass transition temperature of most epoxy resins, which ranges from 40 °C to 50 °C . This leThe main way of protecting structural elements is by properly insulating them using non-combustible mineral wool or cement mortar. A five-centimetre layer of mineral wool on an FRP composite with epoxy resin can protect the FRP composite from a rising resin temperature above the glass transition temperature for 120 min. A layer of cement mortar of a few centimetres on the FRP composite provides fire protection for a minimum of 240 min .Ultrasonic testing involves introducing ultrasonic waves into the object, which are reflected by material discontinuities, as well as bent and scattered on their edges . The purIn scientific publications, a lot of information can be found on the effectiveness of reinforcing concrete elements using FRP composites in the form of sheet, with regards to the strength of concrete. However, the strengthening may vary depending on the concrete used. The authors reviewed the literature concerning FRP composites on concrete with the division into concrete and FRP type. It has been proven that, as the number of reinforcement layers increases, the strength of the elements increases. Furthermore, as the compressive strength of concrete decreases, the effectiveness of the reinforcement increases.Analysed research confirmed that epoxy resin is more commonly used than cement matrix, due to load-bearing efficiency (adhesion properties in the case of the cement matrix is low).As the number of FRP laminates increases, the load-bearing capacity of a reinforced concrete structure increases. However, the research showed that three layers are enough to obtain 100% or more greater compressive strength in comparison with the reference concrete.Technological parameters and their major influence on the efficiency of reinforcing concrete structures with FRP laminates are presented in Fibre-reinforced polymer materials (FRP) are increasingly used to reinforce structural elements . Due to In terms of technical wear and resisting chemical actions, carbon fibre-reinforced polymer composites seem to be the most suitable. They are insensitive to chloride ions (the same as aramid fibre-reinforced polymer composites) and have better fatigue strength due to no water absorption . They are less durable than others, due to high chemical sensitivity to an alkali environment. Glass and aramid can hydrolyse, especially in the presence of the high alkalinity in concrete. The interface between the reinforcement and concrete also plays a great role in terms of durability. Resin-dominated mechanisms are responsible for the transfer of shear and transverse forces, thus effecting the bond . Howeverfuf and the effective strain Ɛfd to prevent immediate debonding failure can be determined as follows:According to the American Concrete Institute (ACI 440.2R-08) , the ultAs shown in Concrete structures built several decades ago often require repair and reinforcement. In order to ensure their further, safe exploitation, they can be reinforced with composite materials, which have developed rapidly in recent years. This paper discussed the main factors affecting the efficiency of reinforcing concrete structures with FRP materials. The authors presented the most important factors influencing the effectiveness of structural strengthening.Limitations in the current paper result from the analysed reinforced material, which is concrete. Therefore, the work focuses on the most important aspects that must be taken into account by designers of concrete structure reinforcements. The authors summarized the applications of various types of FRP materials in concrete structures. This technical note will be helpful to a wide range of concrete reinforcement contractors, providing necessary information on FRP from the design stage to installation. This can contribute to ensuring further, satisfying and safe performance of concrete structures. Bearing in mind a responsible approach to sustainable construction, in a future work, the authors wish to focus on the analysis of the use of recycled polymer fibres for the reinforcement of concrete structures. This research will undoubtedly follow the current global trend in which the re-incorporation of waste materials into the structure is desirable.


Throat swabs were collected from 205 AP patients for two purposes: (i) the detection of four common respiratory viruses associated with AP via reverse-transcription real-time PCR (qRT-PCR); and (ii) bacterial identification using matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS). Bacterial isolates were then subjected to antibiotic susceptibility screening and McIsaac scoring was calculated post-prescription based on GP selection of criteria. Generalized estimating equations analysis with multiple logistic regression was conducted to identify factors associated with presence of virus and antibiotic prescription. The results showed that 95.1% (195/205) of patients had at least one of the four viruses, with rhinovirus (88.5%) being the most prevalent, followed by adenovirus (74.9%), influenza A virus (4.6%) and enterovirus (2.1%). A total of 862 non-repetitive colonies were isolated from the culture of throat swabs from 205 patients who were positive for bacteria. From a total of 22 genera, Streptococcus constitutes the most prevalent bacteria genus (40.9%), followed by Neisseria (20%), Rothia (13.0%), Staphylococcus (11%) and Klebsiella (4.9%). Only 5 patients carried group A beta-hemolytic streptococci (GABHS). We also report the presence of vancomycin-resistant S. aureus or VRSA  among which one isolate is a multidrug-resistant methicillin-resistant S. aureus (MDR-MRSA), while 54.1% (n = 111) were found to carry at least one antibiotic-resistant bacteria species. Application of the McIsaac scoring system indicated that 87.8% (n = 180) of patients should not be prescribed antibiotics as the majority of AP patients in this study had viral pharyngitis. The antibiotic prescription appropriateness by applying post-prescription McIsaac scoring was able to rule out GABHS pharyngitis in this sample with a GABHS culture-positive sensitivity of 40% (n = 2/5) and specificity of 90% (180/200). In conclusion, antibiotic-resistant throat isolates and over-prescription of antibiotics were observed and McIsaac scoring system is effective in guiding GPs to determine occurrences of viral pharyngitis to reduce unnecessary antibiotic prescription.Acute pharyngitis (AP) is a common reason for private primary care consultations, thus providing an avenue for widespread antibiotic intake among the community. However, there is limited data on the antibiotic prescription appropriateness and resistance information in the Malaysian private primary care setting, therefore, this study aimed to investigate the prevalence of isolated viruses and bacteria, antibiotic resistance patterns, antibiotic prescription patterns and appropriateness by general practitioners (GPs) and factors affecting antibiotic resistance and antibiotic prescription patterns. To investigate, a cross-sectional study was conducted among 205 patients presenting with AP symptoms at private primary care clinics in central Malaysia from 3 Antibiotic resistance has predominantly been a clinical problem in hospital settings, but data from over the past two decades showed that antibiotic resistance in bacteria is spreading and rising in the community, and subsequently increase of community-acquired infections that are more difficult to identify and treat –3. MoreoStreptococcus pyogenes [Upper respiratory tract infections (URTIs) account for 60% of all antibiotic prescriptions in the primary care setting  and is tpyogenes –19, the S. aureus isolates was detected in nasal and throat of healthy food handlers and community-acquired methicillin-resistant S. aureus (CA-MRSA) was found to be able to remain persistently in human throat [The human upper respiratory tract is a primary ecological site for various bacteria including members of the phyla Firmicutes, Actinobacteria, Bacteroidetes, Proteobacteria and Fusobacteria . Colonizn throat ,23. ThisConsidering that GABHS pharyngitis is the most common reason for the indication of antibiotics, scoring systems such as the Centor criteria and McIsaac score have been developed to predict the likelihood of GABHS pharyngitis with respect to aid in antibiotic prescribing . The risThere is a dearth of information on antibiotic resistance among the general community in Malaysia especially patients who receive medical care from private primary healthcare providers for infectious diseases. Therefore, this study aims to investigate the prevalence of isolated viruses and bacteria, resistance patterns of pathogens found in human throat, antibiotic prescription patterns and appropriateness by GPs, factors affecting antibiotic resistance and antibiotic prescription patterns in AP patients.2 (P x q)/ d2. Considering: estimated prevalence of bacterial acute pharyngitis in adults [This cross-sectional study was conducted at a total of 17 private primary care clinics in the Klang Valley which consists of the urban areas of the state of Selangor as well as the federal territories of Putrajaya and Kuala Lumpur  using convenience sampling. The minimum sample size was 187, calculated using Daniel’s formula , N = Z2 n adults  of 14.2%rd January 2016 to 30th November 2016. Convenience sampling was used in this study as this method is least expensive and able to produce results quickly. In addition, primary care clinics are the convenient sites for recruitment given the population of interest with sore throat always warrant a visit to the primary care clinic. Furthermore, private clinics provide more than 71.9%  of primary care services for general population in Malaysia [Approval to conduct this study was granted by the Medical Research and Ethics Committee (MREC), Ministry of Health, Malaysia (reference number KKM/NIHSEC/P15–847), with the National Medical Research Register (NMRR) Approval No. NMRR-15-928-25596. Written informed consent was obtained from all participants. Convenience sampling was conducted from 3General practitioners (GPs) were each given an information sheet about this research study and materials for participants comprising of (i) patient information sheet and patient consent form; (ii) patient questionnaire, and (iii) two throat swabs, one for bacterial identification  and the other for virus detection (Greiner Bio-One), together with their respective transport media.Eligible patients were Malaysians aged 18 years old and above with signs and symptoms of sore throat with fever. Patients who had antibiotic treatment within the past 2 weeks, had been hospitalized within the last 30 days, who had complicated pharyngitis such as peritonsillar abscesses (PTA), Lemierre disease or Vincent’s angina, immunosuppression or history of acute rheumatic fever and severe comorbidity were excluded from the study. GPs were requested to complete the patient questionnaire including patient’s demographics, history and duration of sore throat with fever within last 12 months, current throat infection, history and duration of antibiotics use within last 12 months, whether patients had finished the course of antibiotics prescribed in last sore throat infection, any antibiotics prescribed for current throat infection, type and dosage of antibiotics given and patients’ clinical symptoms and signs of current sore throat infection. The questionnaire also contained the 5 McIsaac criteria, however the antibiotic prescriptions by GPs was done based on sign and symptoms and the McIsaac scoring was calculated post-prescription based on GP selection of criteria. Throat swabs were taken by GPs by swabbing both sterile cotton swabs from the right tonsillar area across the posterior pharynx to the left tonsillar area and back across to the right tonsillar area in each patient. One of the swabs  was immediately stored in Amies transport medium  at room temperature whereas the other swab  was stored in phosphate buffered saline at 4°C, both were transported and processed at the laboratory within 24 hours of collection.TM Real-Time PCR System . A total of 4 human respiratory viruses were detected, including human adenovirus (hAdv), human rhinovirus (hRV), influenza A virus (FluA) and human enterovirus (hEV). For every 20 μL reaction (one reaction for each virus), consist of 10 μL of 2x SensiFAST Probe Hi-ROX Mix , 0.8 μL of each 10 μM virus forward and reverse primer, 0.2 μL of 10 μM FAM-labeled virus probe, 0.8 μL of each 10 μM GAPDH  forward and reverse primer, 0.2 μL of 10 μM JOE-labeled GAPDH probe . No-template controls were included by substituting the reverse transcription reaction with UltraPure™ DNase/RNase-Free water. AmpliRun® Enterovirus 71 RNA, Amplirun® Novel Influenza A H1N1 RNA control, Amplirun® Rhinovirus RNA control, Amplirun® Adenovirus DNA control were used as the positive controls. A FAM-positive signal  indicated a positive sample (presence of a virus), while a sample was considered negative (absence of a virus) with a negative FAM signal  but positive JOE signal. All independent PCR reactions were performed in technical triplicates to obtain average cycle threshold (Ct) values using a StepOnePlusTM Real-Time PCR System .Viral DNA and RNA were co-extracted from the viral swabs using the GeneJET Viral DNA and RNA Purification Kit . Reverse transcription was carried out immediately using the SensiFAST cDNA synthesis kit  according to the manufacturer’s instructions. For each sample, reverse transcription was performed in a 40 μL reaction volume containing 2 μL of reverse transcriptase, 8 μL of 5x TransAmp Buffer and 30 μL of extracted nucleic acids. Real-time PCR was performed in a StepOnePlus2. One to five single colonies with distinct morphologies  were sub-cultured on TSAB agar and screened on the Microflex matrix-assisted laser desorption/ionisation-time of flight mass spectrometry (MALDI-TOF MS) Biotyper system  using the Bruker FlexControl software version 3.3 (Build 108) and analysed using the Bruker MALDI Biotyper Real Time Classification software .Throat swabs for bacterial identification were inoculated on Tryptic Soy Agar with 5% sheep’s blood (TSAB)  and incubated for 24 hrs at 37°C with 5% CO2 according to specifications in the Clinical and Laboratory Standards Institute (CLSI) guidelines [Staphylococcus aureus (ATCC 25923 and ATCC 29213), Escherichia coli (ATCC 25922), Streptococcus pneumoniae (ATCC 49619) and Pseudomonas aeruginosa (ATCC 27853) were purchased and used as the reference strains in this study.The bacterial isolates were subjected to AST using Kirby-Bauer disc diffusion method on Mueller Hinton agar with or without sheep blood and broth microdilution method using cation-adjusted Mueller Hinton broth (CAMHB) with or without lysed horse blood at 37°C with or without 5% COidelines . The ATCE. coli ATCC 25922 for inoculum density standardization.Briefly, three to five single colonies of each isolate were selected from LB or Nutrient agar streak plates  after overnight incubation at 37°C and transferred to 2 ml of 0.9% saline solution. The turbidity of bacterial suspension was adjusted to be equivalent to 0.5 McFarland to yield approximately 1.5 x 108 CFU/mL of Antibiotic susceptibility testing was performed using selected antibiotics See . The resDescriptive statistics were used to describe patient’s demographic data , antibiotic resistance patterns of bacterial clinical isolates and GPs’ antibiotic prescription patterns (reported as counts and percentages). Antibiotic prescription appropriateness was determined according to antibiotics prescribed by GPs based on GABHS-positive culture isolated from patients’ throat and McIsaac score See . GeneralOf the 219 pairs of throat swab collected from patients, 11 pairs of throat swabs were excluded from analysis due to leakage of transport medium from throat swabs stored in 1x PBS, while another 3 patients’ throat swabs were excluded because they were not Malaysian. Thus, a total of 205 throat swabs were processed for viral nucleic acid isolation and bacterial culture and identification respectively.The mean age of 205 AP patients was 34.45±9.89 years and majority were middle-aged to elderly adults (≥31 years old). More than half of the subjects in this study (55.6%) were male and Chinese (69.3%) . More thThe majority of the AP in this study appear to be of viral aetiology. Among the 4 respiratory viruses investigated in this study of 205 AP patients, 95.1% (n = 195) had at least one respiratory virus. Human rhinovirus  was the most frequently detected virus followed by human adenovirus, , influenza A  and human enterovirus . Out of the 195 patients in which at least one viruses was detected, the majority  had rhinovirus and adenovirus co-infections, while the presence of either adenovirus or rhinovirus was detected in 4.6% (n = 9) and 17.9% (n = 35) of patients. Patients’ age, gender and ethnicity were not significantly associated with presence of viruses detected in AP patients .Streptococcus constitutes the most prevalent bacteria genus (40.9%) in this study of 205 acute pharyngitis patients, followed by Neisseria (20%), Rothia (13%), Staphylococcus (11%) and Klebsiella (4.9%). The frequency of microorganisms identified from 205 AP patients is listed in A total of 22 genera were identified in the pharyngeal microbiome of 205 AP patients . From thStreptococcus salivarius , Neisseria flavescens , Rothia mucilaginosa , Staphylococcus aureus  and Streptococcus pneumoniae . Interestingly, the bacterial etiological agent of AP warranting antibiotic prescription, Group A beta-hemolytic streptococci or Streptococcus pyogenes (GABHS) was found in only 5 AP patients in this study.The top 5 species in the acute pharyngitis microbiome are: Streptococcus and Staphylococcus genera were resistant to most of the antibiotics tested in this study (7 out of 19 types of antibiotics)  . Of the S. aureus (VRSA) (n = 9), a first from the Malaysian community setting, where 5 out of these 9 VRSA isolates were also found to be methicillin-resistant S. aureus (MRSA) and one of these 5 is multidrug resistant (MDR).Out of the 205 AP patients, 111 were found to carry at least one antibiotic-resistant bacteria species, where within this group, 76.6% (n = 85), 75.7% (n = 84) and 55.9% (n = 62) of them carried resistant bacteria towards cefotaxime, ceftriaxone and penicillin V antibiotics respectively. Alarmingly, we report findings of vancomycin-resistant More than half of the patients (n = 120/205) were prescribed with antibiotics with the frequency of antibiotic prescription by GPs is shown in MALDIT-OF MS result has identified a total of 5 AP patients with non-repetitive GABHS-positive isolates and 4 out of 5 AP patients were prescribed with antibiotics. The overall appropriateness, including GABHS-positive patients who received antibiotics and GABHS-negative patients who did not receive antibiotics, was 42.9% (88/205) , where 4In this study, 58.5% (n = 120/205) of patients were prescribed antibiotics by the GPs. AP patients with sore throat lasting 49–72 hours had four times higher odds of being prescribed with antibiotics compared with those who had a sore throat duration of only 24 hours prior to consulting a doctor, while for those with more than 72 hours, the odds were six time higher. AP patients with symptoms or signs of fever, tonsillar swelling or exudate and runny nose were significantly associated with antibiotic prescription by GPs. The odds of AP patients given antibiotics for fever was 2.4 times higher than those without fever. The odds of AP patients being prescribed with antibiotics by GPs with the presence of tonsillar swelling or exudate was 5.8 times higher than those without tonsillar swelling or exudate. The odds of AP patients with runny nose being prescribed with antibiotics by GPs was 0.4 times odds of being prescribed antibiotics among those without runny nose .Streptococcus (40.9%), followed by Neisseria (20.0%), Rothia (13.0%), Staphylococcus (11.0%), Klebsiella (4.9%), Enterobacter (2.7%), Acinetobacter (2.1%) and Pseudomonas (1.5%), are the top 7 most prevalent bacteria. According to analysis of the pharyngeal microbiome within the Human Microbiome Project, Gao et al. [Prevotella, Capnocytophaga, Campylobacter, Veillonella, Streptococcus, Neisseria and Haemophilus. Our study did not investigate anaerobic bacteria profiles and thus was not able to identify species such as those of the genera Veillonella. Nonetheless, there is a potential shift in the general landscape of microflora towards Streptococcus and Neisseria as the predominant genera in the AP pharyngeal microbiome. High rates of antibiotic-resistant bacteria were observed in urinary tract infections in primary care in the community in several Asian regions such as Indonesia, Hong Kong and Singapore [Our study found that in AP patients, o et al.  reportedingapore –38, howeS. aureus in throat carriage has been frequently reported [et al. [The finding of VRSA in the Malaysian community is disturbing as vancomycin has been recommended as first-line therapy for MRSA infections in Malaysia . The sprreported –43and coreported  while Ri [et al.  revealedAbout 50% to 80% of acute pharyngitis symptoms are viral in origin and including a diversity of viral pathogens, predominantly rhinovirus, influenza, adenovirus, coronavirus, and parainfluenza . In the Streptococcus pyogenes, is concerning owing to its associated severe complications such as acute rheumatic fever and glomerulonephritis [Neisseria species and Streptococcus species is suggested to play a role in offering protection from acquisition of GABHS infection. According to Crowe et al. [Neisseria spp. A few other studies proved similar [Streptococci was the sole microorganism that antagonized growth of GABHS among four indigenous organisms studied .The most common bacterial etiological agent of AP is GABHS, which causes 5% to 36% of cases of AP ,56. GABHephritis . Moreovee et al. , a few o similar ,59; inte similar ’s study et al. [et al. [Antibiotic treatment is of no proven benefit for AP of bacterial origin other than GABHS . Ideallyet al.  with amo [et al.  reportedThe main challenge of AP management is that fact that it is a very common reason for potentially inappropriate contact with antibiotics in the community and the potential for the community itself to be a self-propagating reservoir for antibiotic resistance throughout the ecosystem. Thus, the McIsaac scoring was developed to circumvent the need for GABHS testing in each presentation of AP to ascertain antibiotic prescription appropriateness. The Malaysian Clinical Practice Guidelines for Sore Throat Management  recommenet al. [Analysis of our results found that patients who had a fever of greater than 38°C or tonsillar swelling or exudates have higher odds of being prescribed antibiotics, even if they did not fulfil McIsaac scores of 3, 4 or 5. Linder and Singer  have alset al.  for URTIet al.  despite et al. [et al. [et al. [et al. [Noticeably, the high antibiotic prescribing patterns for URTIs seen in primary care settings are not only common in Malaysia, but also in other Asian countries as well, including China (83.7%), Japan (60.0%) and India (57.0%) –69. Simiet al.  and Teng [et al. . Prescri [et al.  and Nati [et al. , or othe [et al.  reported [et al.  suggestset al. [The McIsaac scoring system is an effective no-cost method towards managing AP in Malaysia in terms of reducing inappropriate antibiotic prescription. Thillaivanam et al.  reportedThe present study has a number of important features, whereby only AP patients were included while other studies usually include patients with URTIs such as rhinitis, cough, otitis media and common cold apart from pharyngitis. Our study also focused on the antibiotic resistance profiles of the throat microflora rather than only on GABHS-positivity and thus may provide useful information on the prevalence of antibiotic-resistant strains that could potentially cause invasive diseases. In addition, we have presented this study on AP patients in a Malaysian private primary care setting, which could serve as reference data in monitoring the antibiotic resistance patterns among the Malaysian community. That being said, the temporal relationships in a cross-sectional study such as this are ambiguous and makes causal inference difficult. In addition, the results may not be generalizable to public hospitals and clinics. Another limitation of the study is the small sample size that could cause large standard errors in the B coefficients, and hence, large 95% confidence intervals for the odds ratios. Also, the convenience sampling technique used in this study might be a limiting factor that could lead to biased estimates of antibiotic resistance and prescription practices among the GPs. Also, there was some detection bias in this study whereby only culturable microorganisms were identified via MADTI-TOF mass spectrometry. The virus detection used in this study was limited to detection of viral DNA and RNA but without cause and effect; on the other hand, culture method was used for bacteria resistance profiling. Other studies for detection of pathogens in URTIs were done using microbiome analysis using 16S or Next Generation Sequencing (NGS) and metagenomic analysis –74. TherS. aureus resistant to vancomycin (VRSA) and also to multiple antibiotics (MDR-VRSA) were identified in this study. The most common antibiotic prescribed was amoxicillin or amoxicillin-clavulanate, not the recommended first-line penicillin V. A high proportion of antibiotic prescription was seen in this study with the majority being inappropriate for acute pharyngitis showing symptoms of viral pharyngitis. Inappropriate antibiotic prescription was reduced when McIsaac scoring was applied, suggesting that appropriate antibiotic prescription for acute pharyngitis among private primary care practitioners can be improved with the simple use of the McIsaac clinical decision rule during diagnosis. Future studies could involve using the cohort study design to minimize bias and maximize accuracy in the estimates of antibiotic resistance and antibiotic prescription. The behavioral factors of GPs and patients could be included in future studies to improve the predictive model in determining the possible factors that may contribute to inappropriate antibiotic prescription practices.In conclusion, the majority of acute pharyngitis patients in the present study are likely of viral aetiology, with rhinovirus and adenovirus as the predominant viruses. Community-based S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.


The type of alkaline solution, the molarity of alkaline solutions, the weight ratio of alkaline solutions to slag, and the weight ratio of NaOH to Na2SiO3 are mix design parameters investigated in this study. The compressive strength reduction and weight loss were monitored from early ages up to 180 days. Moreover, an OPC concrete sample was produced as a reference.Long-term deterioration and durability concerns in harsh environments with acidic attacks are considered as the weaknesses of ordinary Portland cement (OPC) concrete. Although the performance of alkali-activated slag concrete (AASC) has been reported to be superior in acidic environments, there is a poor understanding regarding the impacts of diverse mix design parameters on AASC durability in an acidic environment. This research aims to understand the impact of mix design parameters on the durability of AASC in the sulfuric acid (H Absorption of H2S onto the moist upper surfaces of the concrete pipe results in the formation of one of the most prevalent acids in the environment, H2SO4, and other sulfur byproducts [3O), resulting in a significant drop in pH levels of pore solutions. A drop in the pH level of pore solution in OPC concrete results in the decomposition of calcium hydroxide (CH), calcium silicate hydrate (CSH), and ettringite at the pH of 12.6, 10.7, and 10.5, respectively [High energy consumption and carbon dioxide emission during production  and sodium hydroxide (NaOH) can produce alkali-activated slag concrete (AASC) that has been reported to have superior acid resistance performance [AAC is a cement-free concrete containing alumina-silica sources, such as fly ash and slag, and alkaline solutions ,15. Alkaformance ,17. Propformance . Slag isformance  that is formance .2SiO3 solution [2SiO3 with proper Na2O content and silica modulus creates high-strength AASC [2SiO3 and NaOH is recommended [2 emissions [A wide range of mix design parameters affects the acid resistance of AASC. The type of ion in alkali activator , the appsolution ,25,26. Pgth AASC ,25,26. Tommended ,28. AASCommended ,26,29. Amissions ,31,32, tmissions . In the mix design of AASC, molarity and type of alkaline solutions are two essential elements affecting the mechanical properties and durability of the product . In othe2SO4 of pH = 3 for up to six months, and variations in compressive strength and weight loss were recorded at 7, 14, 28, 90, 120, and 180 days. The results show that an increase in the alkaline solution to slag ratio increased compressive strength reduction and weight loss. In addition, the application of KOH-activated slag concrete negatively affected mechanical performance and increased the production cost of AASC.The ever-increasing demand for more durable concrete compared to OPC concrete validates the research for the performance of alternative binders in such a harsh environment. Acid-resistant concrete is needed in acidic environments such as sewer and agricultural structures, biogas plants, and marine structures. In the review of the existing literature, a limited number of studies focusing on a systematic approach to understanding the effect of AASC mix design parameters on its performance and durability in harsh acidic environments were identified. Moreover, the impacts of acid attacks on the short-term and long-term performance of AASC have been investigated. Nevertheless, there is a poor understanding regarding the impacts of diverse mix design parameters on AASC durability in the sulfuric acid environment. This research aims to understand the impact of four main mix design parameters: molarity of alkaline solutions, type of alkaline solution, the weight ratio of alkaline solutions to slag, and the weight ratio of alkaline solutions to sodium silicate, on the durability of AASC samples. The samples were submerged in H3, Blaine fineness of 400 m2/kg, the Al2O3/SiO2 weight ratio of 0.447, and CaO/SiO2 weight ratio of 1.079 was used as a silica-aluminate source. OPC concrete specimens were produced as reference concrete. 2O3)/SiO2) is an important parameter regarding the reactivity of GGBFS. It was reported that HM should be greater than 1.40 to guarantee a satisfactory hydration property [In this study, GGBFS with a specific gravity of 2.85 gr/cmproperty . In this2SiO3 or KOH and Na2SiO3 were used as alkaline solutions. To evaluate durability and the performance of AASC after acid attacks, both NaOH- and KOH-activated slag concrete were cast and monitored in this study. NaOH and KOH with a purity of 98% are white flake solids. They were dissolved in water to make a solution with a desirable concentration at least 15 min prior to the commencement of the mixing process. Three concentrations of 6, 10, and 14 were used for NaOH and KOH solutions. Na2SiO3 was in liquid form with a SiO2/Na2O ratio of 2.5, water mass content of 51%, and Na2O and SiO2 contents were 14% and 35%, respectively. Limestone aggregates are widely used in most projects in Iran due to their lower cost and abundance. Thus, coarse aggregate (crushed limestone) with a maximum aggregate size of 19.5 mm and fine aggregate (crushed sand) were used in this study. The aggregate grading was as per ASTM C33. A combination of NaOH (as the most commonly used activators) and Na2SiO3 (NO/NS). Based on these parameters, 15 mix designs and 540 cubic specimens (100mm × 100mm × 100 mm) were made. The mix design procedure of AASC was selected based on . In all NaOH and KOH solutions were prepared at desirable molarity prior to the mixing process and were added to the mixture in liquid form. It should be noted that alkaline solutions were made 30 min prior to addition to the mixture. Therefore, their temperature almost reached the ambient temperature. A sixty liters mixer was used for mixing the materials. The mixing process was as follows: First, aggregates and GGBFS were mixed for 3 min. Then, the alkaline solutions were gradually added to the blended materials. Finally, water and SP were added to the mixture. Subsequently, the materials were mixed for 5 min, and then, the mixture was allowed to rest for 1 min. Finally, the mixture was remixed for another 3 min. The prepared mixture was poured into cubic samples, and to minimize water evaporation, the molds were covered with plastic sheets in the first 24 h at a controlled temperature of 23 ± 2 Celsius. Reference OPC concrete samples were also made. OPC concrete samples were made using the same aggregates used in AASC mixtures. The water-to-cement ratio was set at 0.28, and the same SP was used to enhance the workability of specimens. OPC concrete samples were cured in water for 28 days before exposure to sulfuric acid and were designed to have comparable compressive strength (60 MPa at 28 days) to AASC specimens. 2SO4 bath. It should be noted that this curing time (two weeks) is enough for AASC samples to gain nearly 80% of their 180 days of compressive, as will be discussed in 2SO4 bath with a pH of 3. To keep the pH level constant, the pH of the bath was measured with strips pH meter twice a week. In case of disparity in pH level of the bath, H2SO4 98% was added.The molds were placed in a water bath for two weeks before transferring them to an H2SO4 solution with a pH of 3 for up to six months. The pH was selected based on [2SO4 bath. The compressive strength test was conducted as per EN 12390-3 at predetermined intervals. Furthermore, the chemical compositions of slag and Portland cement were measured using the X-ray fluorescence (XRF) test.As stated earlier, a standard procedure for assessing acid attacks on concrete is yet to emerge. In this study, the acid resistance of AASC and OPC concrete was tested by exposing the samples to an Hbased on ,21,35,43The general trend was that AASC gained considerably high strength in the early ages. If we consider the compressive strength at 180 days as the ultimate strength, samples containing KOH gained more than 80% of their final strength after two weeks. Higher molarity and A/S ratio of KOH-activated slag specimens resulted in the highest compressive strength. 2), almost 38%, two times more aluminum oxide (Al2O3), and roughly 40% lower calcium oxide (CaO) contents. Unlike Portland cement, CH is not a product in the AASC structure [Apart from N60404, the inclusion of NaOH also resulted in archiving at least 75% of the ultimate strength at 14 days. The results clearly indicated that selecting a proper mix design proportion for AASC would lead to having substantially high compressive strength values. The underlying reason is attributed to reaction kinetics and microstructure development in AASC. Compared to Portland cement, slag contains higher silica  in solution would potentially increase the CSH in the concrete leading to higher mechanical properties. Roughly 77% of NaOH and 52% of Na2SiO3 consist of water. The lowest NO/NS ratio (0.4) contains higher Na2SiO3 content due to its high viscosity and reduced concrete workability. Slag needs enough alkaline solution to react, and the excessive amount of alkaline, which consists of a considerable amount of water, causes capillary cavities in the microstructure and negatively impacts the compressive strength. In NaOH-activated slag samples with a molarity of 10 and A/S ratio of 0.4, the higher ratio of NO/NS reduced the strength after 90 days, as illustrated in OPC concrete needs sufficient water curing and time to progress its hydration products and form the concrete structure. However, AASC, given an alkaline solution for alumina silicate powder, substantially increases the rate and intensity of reactions leading to obtaining high mechanical properties in the early ages. The water absorption was also measured for AASC samples which were between 2.3% to 3.88%. The KOH-containing specimens showed higher water absorptions compared to NaOH-containing samples. The water absorption for KOH-activated slag concrete was more than 3%, and NaOH-activated slag had an average water absorption of 2.7%. 2SiO3 [2SiO3 or KOH and Na2SiO3. Brough et al. [Based on the literature review, the most commonly used activators are NaOH and Na2SiO3 ,18,31,49h et al. , Ye et ah et al. , and Parh et al.  reportedh et al. . Thus, sh et al. . The corHence, countless unfilled voids and cavities are created in microstructures that are mainly connected. When acid enters such a porous structure, cavities are filled with acid agents, and the acid moves through connected porosity all around the concrete structure leading to reactions with hydration components and severe deterioration . As a re2SiO3 performed better in the acidic environment than specimens containing KOH and Na2SiO3. Visual inspection clearly shows that samples containing NaOH and Na2SiO3. Secondly, at higher molarity, the rate of reaction and the amount of ionization of slag particles uncontrollably increased, leading to the formation of an irregular structure in concrete. 2SiO3 as a source of Si for the formation of CSH compared to the NO/NS ratio of 1, the impacts of irregular and weak microstructure were more significant than higher crystallization of slag particles. Another factor that should be taken into consideration is that the higher molarity means a higher production cost which is not favorable.The effects of molarity change were investigated in two NO/NS ratios of 1 and 3. In the NO/NS ratio of 3, 2SiO3. Second, a high amount of Na2SiO3, which means a lower NO/NS ratio, leads to low concrete workability. This is an essential fresh property. Workability can affect casting, molding, and even all properties of concrete because concrete owes its durability to chemical reactions that start in the early hours when the binder reacts with alkaline solutions.The impacts of the NO/NS ratios ranging from 0.4 to 3 on the performance of AASC samples immersed in sulfuric acid solution with pH = 3 were investigated at A/S = 0.4 and the three different NaOH molarities of 6, 10, and 14, as shown in 2SiO3 content and increases NaOH weight in a concrete mixture, causing the reduction of silica, and an increase in free water in the mixture results in the creation of a weak AASC microstructure.The effects of an increase in the A/S ratio from 0.4 to 0.6 on the compressive strength reduction at two molarities are shown in 3 to 345 Kg/m3 in one cubic meter of concrete, causing a reduction in the binder in the mixture.The main reasons for lower performance at a higher A/S ratio were insufficient binder volume in the mixture and excessive alkaline solutions consisting of free water. A higher A/S ratio led to a reduction of slag from 394 Kg/mOPC samples were used as a reference to better understand AASC performance in the acid attack. As shown in 2SO4 caused decomposition of aluminum and destruction of Si-O-Al in AASC concrete leading to reducing mechanical properties as well as weight loss. The underlying reason for such a superior performance is attributed to the different microstructure of these two concretes. Cement is the most expensive and most vulnerable ingredient in conventional concrete. The acid attack on OPC includes attacks on hydration products and converting calcium-containing phases such as CH, CSH, and calcium aluminate hydrate to calcium salt. This reaction causes expansion, cracking, and deterioration of conventional concrete. The CaO content in cement and slag is 63.50% and 36.52% . Hence, 3, SiO2, and CaO, which consist of roughly 78% of the composition. It also should be mentioned that the powder did not dry before conducting the XRF test. Water content in the samples justifies high (14.86%) loss of ignition (LOI) values. The high percentages of SO3 are due to exposure of samples to sulfuric acid. The results reveal that the SiO2, Al2O3, and CaO contents are reduced compared to the chemical composition of slag, which indicates that acid agents break the silica-aluminate bonds, and these phases are leached out of the structure.The XRF was conducted on the other layer, which was removed from the sample using sandpaper to determine its chemical composition. As discussed in the previous section, a soft white layer is formed on AASC samples after exposure to sulfuric acid. The XRF results are presented in 2SiO3 is economically desirable, it would not have any impact on either strength resistance or weight loss. In this study, the impacts of four mixed design parameters on the performance of AASC exposed to sulfuric acid attack were investigated. For this purpose, samples were cured in water and immersed in acid baths and were tested on the same days to determine the compressive strength reduction as well as weight loss. Moreover, an XRF test was also conducted to understand the phase changes before and after acid exposure. The tests were conducted on specimens at 7 days for up to 180 days. Moreover, an OPC sample was utilized as a reference. The results reveal that the compressive strength reduction and weight loss of AASC samples compared to OPC concrete were near one-fourth and one-tenth, respectively. The main hydration products of AASC before and after acid exposure were the same, and there were no signs of gypsum and ettringite. While an increase in the weight ratio of NaOH to Na2, Al2O3, and CaO contents indicated the breaking of silica-aluminate bonds in structure and leaching of these components out of the concrete. AASC samples cured in water reached a high compressive strength at early ages and gained more than 70% of final compressive strength (compressive strength at 180 days) after 7 days. The increase in the alkaline solution to slag ratio, which reduces the binder content, increased the compressive strength reduction and weight loss due to excessive alkaline solution in the mixture. This mixture has relatively high-water content. Furthermore, the application of KOH-activated slag concrete negatively affected mechanical performance and also increased the production cost of AASC. The reduction of SiOIn future works, the authors recommend performing chloride permeability and water impermeability tests. The microstructure of AASC after acid attacks using thermogravimetric analysis and SEM is encouraged. The feasibility of the production of precast anti-acid AASC tiles should be investigated. Furthermore, the same studies should be done on one-part alkali-activated materials apart from the two-part alkali-activated materials investigated in this study.


Developed and patented more than 30 years ago, the system of slabs with plastic inserts has become very popular, and it is used all over the world today due to the significantly reduced cost of building construction. Experimental tests have shown that the behaviour of simple bending voided slab structures with plastic inserts during loading is very similar to that of solid slabs. However, their deflection and crack resistance are both slightly inferior to those of solid slabs. When using pretensioned reinforcement, the deflection and crack resistance of voided slabs exceed the above parameters for solid slabs. However, when using plastic inserts to form inner voids in slabs, their cross-section along the span becomes variable. In determining the stiffness of such slab, a problem arises in estimating the moment-of-inertia when the cross-section is variable. To estimate the influence of the voids formed by the plastic inserts on the deflection of prestressed concrete slabs, bending tests of two life-size reinforced concrete slabs were performed. The bending results obtained during the experiment were compared with the results obtained from the numerical model and analytical calculations. The first hollow-core floor slabs were created in the 1950s. This was an innovative system that became very popular due to its advantages over older solid slab systems. The first voided slabs reduced the cost of building construction and the time required to complete buildings. However, due to tubular voids, the production of slabs could only take place in special factories for reinforced concrete structures, and only one-way slabs could be produced ,3. This Research has identified the main factors influencing the behaviour of voided slabs . One is An evaluation of the results of the field tests already performed showed that the bearing capacity of slabs with plastic void-forming inserts is slightly lower than that of solid slabs ,13,14,15Due to the reduced mechanical properties of voided slabs, various technological variants of slab production have been tested to find the optimal solution to reduce the self-weight of the slab, without losing the load-bearing capacity and stiffness. One way to increase the stiffness and load-bearing capacity of voided slabs is to change the reinforcement intensity. Tests have shown that voided slabs usually crack in the normal section, but hollow core slabs with a reinforcement intensity of 0.52% crack in the diagonal section .p) [In the search for other ways to increase the stiffness of voided slabs while maintaining reduced self-weight, it is advisable to use prestressing reinforcement instead of conventional reinforcement nets. Additionally, losses of prestress should be taken into account to avoid unnecessary reduction of stiffness and damages . Accordip)  ranging p) .Numerical studies of the slab were performed using a finite element modelling program . The infThe mentioned research mostly considered the behaviour of voided slabs, but the methodology for calculating the deflection was not provided. The stiffness calculation of solid slabs is quite simple, due to the solid cross-section. However, it is difficult to determine moment-of-inertia in slabs with void-forming inserts because the cross-sectional area is variable. We aimed to develop a methodology for calculating the deflection of voided slabs and to compare calculated deflections with deflections of experimental life-size prestressed voided reinforced slabs and numerical model deflection results.For the experimental test, two reinforced concrete floor slabs with pretensioned main longitudinal reinforcement were designed and manufactured. Below is a scheme of the production of the designed reinforced concrete slabs, with the intended arrangement of the elliptical plastic void-forming inserts and reinforcement bars and nets used .Sample preparation was performed sequentially according to the prepared slab scheme. First, a reinforcing (lower) net (T-1) was placed in the concreting moulds on the plastic blocks to form a 16 mm thick protective layer of concrete. Above the T-1 net, four reinforcement bars of 12-mm-diameter were placed and anchored into each slab . During After the anchoring of the reinforcements, plastic inserts were placed in the moulds of slabs, arranged in three rows of thirteen inserts in one row. The inserts were inserted into the longitudinal bars of the lower reinforcing net T-1. A second (upper) reinforcing net (T-2) was placed on the plastic inserts. The upper and lower reinforcement nets were interconnected by stirrups to maintain the design position of plastic inserts during concreting. For the T-1 and T-2, reinforcing nets were used with a 4-mm-diameter smooth surface S500 class reinforcement.The technical data of the two reinforced concrete floor slabs with pretensioned reinforcements intended for the study are given in In both reinforced concrete slabs prepared for testing, voids were formed by elliptical plastic inserts, Cobiax SL-M-160-180, manufactured by “Cobiax” in Cobiax International GmbH, Bielefeld, Germany . The insUsing plastic inserts of the selected size, the concrete content was reduced by 27.89% compared to the concrete content requirement of a solid slab. The preliminary technical characteristics of plastic inserts are given below .A concrete mix of class C30/37 was used for the production of the slabs. During the production of prestressed concrete slabs, concrete cubes (100 × 100 × 100 mm) were formed to determine the mechanical properties of concrete . ConcretDuring the experiment, the deflections and strains of the slab were measured in the compressive zone of the slab, in the tensile zone of the slab, and at the level of the working reinforcement of the slab. In the upper part of the slab, six strain gauges measured the compressive strains of the concrete area. Strains in the tensile area of the slab were measured by six strain gauges in the lower part of the slab. In these areas, the strain gauges were mounted in the area of the central insert. Eleven strain gauges were mounted to the slab wall at the level of the main reinforcement, between the load application points . At the ends of the slab, displacement gauges were attached to the pretensioned reinforcements to monitor their displacement. The deflections of the slab were recorded with deflection gauges placed on both sides of the slab, spread over the entire length of the slab: four at the supports; four under load transfer points, and two in the centre of the slab .Prestressed concrete voided slab tests were performed under static loading with the universal testing frame PLF 2MN, according to the four-point bending scheme. The load was transmitted to the slab through two rigid transverse beams at a distance of 1900 mm. The view of the tested slab is shown in A force-controlled static load test was performed under a constant speed of 0.5 kN/s. Every 5 kN the test was stopped and measurements were recorded.The slip of reinforcement at the ends of the slab was measured with mechanical strain gauges (I-34: I-41)  with an An experimental study showed that the development of cracks at certain cross-sectional areas depends on the level of load. Therefore, the calculation of the deflection is divided into stages that correspond to the opening of certain cracks. In the first stage, the deflection is calculated up to the opening of the crack in the cross-section with the void. In the second stage, the deflection is calculated until the crack opens in the solid cross-section . In the third stage, the deflection is calculated to the yielding of the tensile reinforcement.Three cross-sections were distinguished in the slab under consideration . SectionThe cross-section of the longitudinal fragment along the span is variable. Existing deflection calculation methods estimate the moment of inertia of the cross-section when the cross-section of the beam or slab along the span is not variable. The moment of inertia of the uncracked cross-section of the slab, when the cross-section is variable along the section III-III and I-I, is determined by the equation:The position of the centre of gravity of the cross-section highlighted in sections II-II  is deterThe moment of inertia of the transformed cross-section (II-II) is determined by:The position of the centre of gravity of the cross-section highlighted in sections III-III  is deterThe moment of inertia of the transformed cross-section (III-III) is determined by:k evaluates the loading type. The cracking moment can be calculated by the equation:mP is the prestress force; By setting the geometrical parameters of the cross-section, the deflection of the slab can be calculated until the cracking moment in the cross-section with the void is reached. Slab deflection from the external load until the moment  are not cracked:The depth ral axis  of the cUsed designations:If If I≤hf1.II , then thThe cracking moment in section III-III can be calculated by the equation:Deflection of the slab when the slab is cracked at the parts with the voids and in the solid cross-section parts :The following equation evaluates the mean curve when the parts with the voids and solid cross-section  are cracked:III of the neutral axis .The deflections calculated theoretically and by the finite element method were compared with the experimental ones in Relationships between bending moments and strains of prestressed concrete slabs were obtained from gauge readings during the experimental tests . The purThe diagram of the I-7 gauge a shows aAs can be seen from the diagrams above , tensileThe diagrams of the bending moments average strain values  show thaAt the bottom of the slab , from 54At the top of the slab , elasticThe amount of concrete was reduced by up to 28% in the prestressed concrete slabs with plastic elliptical inserts, compared to solid slabs, thus reducing the self-weight of the slab by up to 28%.A method for the deflection calculation of prestressed concrete slabs with plastic inserts was proposed. This method takes into account variations of the cross-section geometry along the span of the slab. Additionally, uncracked and cracked cross-sections are considered.The experimental results confirmed that the position of the neutral axis in the cracked sections (at the place of the inserts and between the inserts) was different. Therefore, the proposed method for deflection calculation allows estimation of the existing state of stress-strain in different cross-sections of the slab when different positions of the neutral axis in the cracked cross-sections are determined.The comparison of theoretical and experimental results showed that the proposed analytical method predicts the deflection of prestressed concrete voided slabs quite well up to the load level of 80% of failure load.


Immunoglobulin G4 (IgG4)-related dacryoadenitis is rarely resolved spontaneously without steroids. Here, we report a case of IgG4-related dacryoadenitis and extra-ophthalmic lesions with spontaneous regression.This is a clinical case report. A 56-years-old man had a 1-year and 7-month-old histories of neck and eyelid swelling, respectively. On the first examination, the lacrimal and submandibular glands were palpable bilaterally. Computed tomographic images showed enlargement of the lacrimal gland on both sides, right pulmonary hilar lymph node, and pancreas, and thickening of the abdominal aortic wall. Blood tests demonstrated elevated serum IgG4 level and positive hepatitis B surface antibody. Pathological examination of the biopsied lacrimal gland specimens revealed marked IgG4-positive plasma cell infiltration.The patient was monitored carefully without steroid administration. Serum IgG4 level had gradually decreased during follow-up period and reached the normal range 3 years after the biopsy. At 4-year follow-up, the lacrimal and submandibular glands were not palpable on either side. Computed tomographic images demonstrated no enlargement of the lacrimal gland, submandibular gland, or lymph nodes, and improvement of the enlarged pancreas and thickened abdominal aortic wall.Our case indicates that careful observation can be an option in selected cases with risks of steroid treatment or silent clinical course. Although the involved tissues include the lacrimal gland, orbital fat, extraocular muscles, trigeminal nerve, eyelid, sclera, lacrimal sac, and optic nerve,–4 the lacrimal gland involvement (dacryoadenitis) is most commonly encountered. Concomitant extra-ophthalmic IgG4-RD is sometimes seen. Steroid administration is the first-line treatment for IgG4-ROD, but a considerable number of patients with IgG4-ROD experience relapse after tapering of steroids.,6Immunoglobulin G4-related ophthalmic disease (IgG4-ROD) is a relatively common entity of Immunoglobulin G4 (IgG4)-related disease (IgG4-RD).,8 There have been only a few reported cases of spontaneous regression of IgG4-related dacryoadenitis.,8 Here, we report an additional case of IgG4-related dacryoadenitis and multiple organ involvement with spontaneous resolution.In contrast, although rare, IgG4-related dacryoadenitis is spontaneously resolved without steroids.This study was conducted in accordance with the tenets of the Declaration of Helsinki and its later amendments. Written informed consent for publication of identifiable face photos was obtained from the patient.A 56-years-old man presented with a 1-year history of bilateral neck swelling. The patient underwent biopsy of the submandibular gland lesions at an ENT clinic, and malignancy was ruled out. Bilateral eyelid swelling was noticed by his friends 3 months later. The patient denied any history of ocular or systemic diseases and the family history was not significant.On the first examination, his best-corrected visual acuity was 1.0 in both eyes, and intraocular pressure was 12 mm Hg. The lacrimal and submandibular glands were palpable on both sides  3 years after the biopsy. At 4-year follow-up, the lacrimal and submandibular glands remained non-palpable on both sides  were considered as negative influential factors in the clinical course of IgG4-ROD and IgG4-RD. This case indicates that spontaneous regression of IgG4-ROD and -RD can be expected even in cases with risk factors for poor clinical course of these entities.Previous studies demonstrated that sex, serum levels of C3, C4, and CH50, new-onset diabetes mellitus, and extensive multi-organ involvement were factors influencing the clinical course of patients with IgG4-RD without treatment. Other treatment options, including other medications, radiotherapy, and debulking should be considered when lesions deteriorate during observation.Spontaneous regression of multiple lesions in this case suggests that the wait-and-watch policy can be an option in selected cases with risks of steroid treatment or a silent clinical course. However, careful monitoring is necessary as a prolonged clinical course may cause dysfunction of the involved organs.In conclusion, we report a rare case of IgG4-related dacryoadenitis and extra-ophthalmic lesions that spontaneously regressed without steroids. Although wait-and-watch policy can be an option, patients should be carefully monitored for early therapeutic intervention when the lesions deteriorate.Conceptualization: Yasuhiro Takahashi.Formal analysis: Yasuhiro Takahashi.Investigation: Yasuhiro Takahashi.Methodology: Yasuhiro Takahashi.Project administration: Yasuhiro Takahashi.Supervision: Yasuhiro Takahashi.Validation: Yasuhiro Takahashi.Writing – original draft: Mayari Ito, Yasuhiro Takahashi.Writing – review & editing: Aric Vaidya, Hirohiko Kakizaki.