Type 304 stainless steel is a metastable austenitic stainless steel that undergoes strain induced transformation from austenite to α′ martensite during deformation at room temperature. Role of prior ...deformation, by rolling at room temperature and at 200 °C (a temperature at which the strain induced martensitic transformation does not occur), on the subsequent room temperature tensile deformation behaviour of the austenite phase is investigated. The changes in dislocation density of the parent phase and the volume fraction of the martensite formed due to deformation were estimated by X-ray diffraction line profile analysis of data obtained from Beam Line - 12 of the Indus 2 synchrotron. The contrast caused by dislocations in the austenite phase has been addressed using the modified Williamson-Hall method. The character of dislocations changes from screw to edge above a critical equivalent strain of ~0.14. The influence of martensite formation on the increase in dislocation density in the austenite phase is confirmed from XRDLPA. An alternative approach to determine dislocation density is proposed which is independent of elastic constants of the material and is found to correlate well with the values determined by the Williamson-Smallman approach. The results obtained from XRDLPA are corroborated with EBSD analysis. It is also seen that the composite strength of the steel, which has undergone different levels of deformation, is related to the changes in dislocation density of austenite and volume fraction of martensite based on Taylor's equation enabling correlation of structure-property.
•Deformation induced change in dislocation density (ρ) and character are studied by XRDLPA.•Strengthening due to α′ martensite and ρ in austenite are related through rule of mixtures.•SIM contributes to strengthening by introducing extra dislocations into γ phase.•Results from EBSD analysis corroborate the findings of XRDLPA.•Alternative approach to determine ρ from different forms of mWH equation is proposed.
Background Clinicians vary markedly in their ability to detect murmurs during cardiac auscultation and identify the underlying pathological features. Deep learning approaches have shown promise in ...medicine by transforming collected data into clinically significant information. The objective of this research is to assess the performance of a deep learning algorithm to detect murmurs and clinically significant valvular heart disease using recordings from a commercial digital stethoscope platform. Methods and Results Using >34 hours of previously acquired and annotated heart sound recordings, we trained a deep neural network to detect murmurs. To test the algorithm, we enrolled 962 patients in a clinical study and collected recordings at the 4 primary auscultation locations. Ground truth was established using patient echocardiograms and annotations by 3 expert cardiologists. Algorithm performance for detecting murmurs has sensitivity and specificity of 76.3% and 91.4%, respectively. By omitting softer murmurs, those with grade 1 intensity, sensitivity increased to 90.0%. Application of the algorithm at the appropriate anatomic auscultation location detected moderate-to-severe or greater aortic stenosis, with sensitivity of 93.2% and specificity of 86.0%, and moderate-to-severe or greater mitral regurgitation, with sensitivity of 66.2% and specificity of 94.6%. Conclusions The deep learning algorithm's ability to detect murmurs and clinically significant aortic stenosis and mitral regurgitation is comparable to expert cardiologists based on the annotated subset of our database. The findings suggest that such algorithms would have utility as front-line clinical support tools to aid clinicians in screening for cardiac murmurs caused by valvular heart disease. Registration URL: https://clinicaltrials.gov; Unique Identifier: NCT03458806.
Background and aim
There are efficacy and safety concerns related to teneligliptin treatment. A systematic review of randomized controlled trials (RCTs) was undertaken to comprehensively profile the ...efficacy and safety of teneligliptin in the treatment of type 2 diabetes mellitus (T2DM).
Methods
Thirteen studies were chosen from a search of scientific databases for RCTs using teneligliptin as a monotherapy or as an adjunct to other glycemic agents with pre-specified inclusion criteria. We calculated weighted mean differences (WMDs) and 95% confidence intervals (CIs) in each included trial and pooled the data using a random-effects model.
Results
Thirteen studies enrolled 2853 patients were identified. Teneligliptin treatment was associated with weight gain (vs. placebo, weighted mean difference (WMD) 0.28 kg; 95% CI − 0.20–0.77 kg;
I
2
= 86%;
P
= 0.25). Compared to monotherapy, add on therapy with teneligliptin showed significant improvement in FPG mg/dl levels (WMD − 16.75 mg/dl; 95% CI − 19.38 to − 14.13 mg/dl), HOMA-
β
(WMD 7.91; 95% CI 5.38–10.45) and HOMA-IR (WMD − 0.27; 95% CI − 0.46 to − 0.07). The improvement in HbA1c was greater with monotherapy (WMD − 8.88 mmol/mol; 95% CI − 9.59 to − 8.08 mmol/mol). There was no significant risk of any hypoglycemia with teneligliptin compared to placebo (OR 0.84; 95% CI 0.44–1.60;
I
2
= 0%;
P
= 0.60). However, the risk was 1.84 times high when combined with other glycemic agents. The risk of cardiovascular events was comparable, regardless of treatment duration when compared to placebo or any other active comparator (OR 0.79; 95% CI 0.40–1.57;
I
2
= 0%;
P
= 0.50). PROSPERO, CRD42022360785.
Conclusions
Teneligliptin is an effective and safe therapeutic option for patients with T2DM, both as monotherapy and as add-on therapy. However, additional large-scale, high-quality, long-term follow-up clinical trials with diverse ethnic populations are required to confirm its long-term efficacy and safety.
This paper develops an efficient methodology to perform reliability-based design optimization (RBDO) by decoupling the optimization and reliability analysis iterations that are nested in traditional ...formulations. This is achieved by approximating the reliability constraints based on the reliability analysis results. The proposed approach does not use inverse first-order reliability analysis as other existing decoupled approaches, but uses direct reliability analysis. This strategy allows a modular approach and the use of more accurate methods, including Monte-Carlo-simulation (MCS)-based methods for highly nonlinear reliability constraints where first-order reliability approximation may not be accurate. The use of simulation-based methods also enables system-level reliability estimates to be included in the RBDO formulation. The efficiency of the proposed RBDO approach is further improved by identifying the potentially active reliability constraints at the beginning of each reliability analysis. A vehicle side impact problem is used to examine the proposed method, and the results show the usefulness of the proposed method.
Summary
The phase 2, open‐label ACCORDION (ClinicalTrials.gov: NCT02349048) study investigated the efficacy, safety and pharmacokinetics of a 6‐ or 8‐week regimen of simeprevir, daclatasvir and ...sofosbuvir in treatment‐naïve patients with chronic hepatitis C virus (HCV) genotype (GT) 1 infection and either early‐stage fibrosis or compensated cirrhosis. Patients were assigned to treatment groups according to their fibrosis stage. Early‐stage fibrosis: simeprevir 150 mg, daclatasvir 60 mg, sofosbuvir 400 mg once daily for 6 weeks; compensated cirrhosis: same regimen for 8 weeks. The primary endpoint was sustained virologic response 12 weeks after the end of treatment (SVR12). Safety, tolerability and pharmacokinetics of simeprevir, daclatasvir and sofosbuvir were investigated. Sixty‐eight patients were treated (6‐week group: n = 59; 8‐week group: n = 9). SVR12 was achieved by 86.4% (51/59) of patients with early‐stage fibrosis and by 100% (9/9) of patients with cirrhosis. The main reason for not achieving SVR12 in the 6‐week group was viral relapse (11.9%; 7/59). One patient had on‐treatment failure due to an early withdrawal (lost to follow‐up due to incarceration). One patient with SVR12 in the 6‐week group had a late viral relapse at post‐treatment week 24. No clinically significant drug‐drug interactions were observed. Adverse events were reported in 63.2% of patients (43/68) and were mainly grade 1/2. None of these led to treatment discontinuation. The 3 direct‐acting antiviral regimens of simeprevir, daclatasvir and sofosbuvir were safe and well tolerated in treatment‐naïve, HCV GT1‐infected patients with early‐stage fibrosis or compensated cirrhosis.
Background:
Progressive pseudorheumatoid dysplasia(PPRD) is considered as a degenerative genetic bone disorder. It is caused by loss of function mutation in WNT-1 inducible signaling pathway ...protein-3(WISP-3)
1
. WISP-3 gene function is required for the normal function of cartilage and skeletal development. The patients are normal at birth and start developing symptoms around 3-6 years of age
2
. The disease is characterised by stiffness, pain, deformity due to enlargement of the ends of short and long bones. Often, such patients are misdiagnosed as Juvenile idiopathic arthritis(JIA). In general, PPRD being considered as non-inflammatory disease, immunosuppressants or disease modifying anti rheumatic drugs(DMARDS) like methotrexate treatment are not used for treatment.
Objectives:
We report a patient with characteristic findings of PPRD but with coexisting clinical and imaging evidence of inflammation.
Methods:
16 year old male boy born of third degree consanguineous asymptomatic parents presented with progressive swelling, deformity of bilateral small and large joints of upper and lower limbs. He also had pain in both hip and knee for past two years. Pain is associated with difficulty in walking and squatting. On examination he had bony enlargement around bilateral elbow, wrist, proximal and distal interphalangeal joints(Figure 1A). He also had restriction of bilateral hip movements and swelling of bilateral knee with effusion. He had exaggerated lumbar lordosis and flexion deformity of bilateral hip, knee. His blood counts, ESR, CRP were normal. Analysis of Knee joint synovial fluid showed cell count of 200/mm3 with no crystals and sterile culture. USG knee showed evidence of synovial thickening with increased power Doppler signals. Skeletal survey showed typical findings of PPRD with enlargement of epiphysis and osteoarthritis changes(Figure 1B). MRI hip showed minimal effusion, synovial thickening, edema with STIR hyperintensity and enlargement of bilateral femoral epiphysis. MRI knee showed minimal effusion, marrow edema in patella(Figure 1C, arrow head), femoral condyle, diffuse synovial thickening with contrast enhancement(Figure 1D, arrow) and deformed patellar contour. Immunological tests showed negative RF, ACPA and positive ANA(Hep2) speckled 4+. Immunoblot for ENA was negative. His ophthalmological evaluation showed no evidence of uveitis.
Figure 1.
Clinical picture showing typical hand deformity and swelling at bone ends(A), hand radiograph showing epiphyseal enlargement(B), MRI knee T2 STIR showing bone marrow edema(arrow head) in patella(C) and synovial thickening(arrow) with contrast enhancement in fat saturated T1 MRI with contrast.
Results:
Patient tested positive for homozygous mutation in WISP-3 gene. He was treated with ibuprofen and supportive measures. Orthopedic consultation obtained and planned for hip, knee replacement during follow up. Follow up imaging and acute phase response was advised after three months.
Conclusion:
Although PPRD was classically described as a degenerative disease, the findings presented in our case show coexisting inflammation. Bone marrow edema in weight bearing areas, synovial effusion may be explained as part of cartilage degeneration like in osteoarthritis but synovial hypertrophy with contrast enhancement, power Doppler signals in ultrasound, ANA positivity may be signs of coexisting inflammatory or autoimmune phenomenon.
References:
1Hurvitz JR, Suwairi WM et al. Mutations in the CCN gene family member WISP3 cause progressive pseudorheumatoid dysplasia. Nat Genet. 1999 Sep;23(1):94-8. doi: 10.1038/12699. PMID: 10471507.
2Garcia Segarra N, Mittaz L et al. The diagnostic challenge of progressive pseudorheumatoid dysplasia (PPRD): a review of clinical features, radiographic features, and WISP3 mutations in 63 affected individuals. Am J Med Genet C Semin Med Genet. 2012 Aug 15;160C(3):217-29. doi: 10.1002/ajmg.c.31333. Epub 2012 Jul 12. PMID: 22791401.
Disclosure of Interests:
None declared
•Mass screening for loss of protective sensation can help prevent diabetic ulcers.•The Ipswich touch test is valid in people without diabetic foot ulceration history.•Its ease-of-use and cost-free ...nature makes it ideal for mass screening.•Repeating VibratipTM testing for the hallux, 3rd and 5th toe improves performance.•The use of VibratipTM for mass screening is not supported by our results.
The ability of the Ipswich touch test (IpTT) and VibratipTM to detect loss of protective sensation (LOPS) was tested against a neurothesiometer in an outpatient diabetic population without a history for ulceration. Our results support the use of the IpTT as a screening tool for LOPS, but not of VibratipTM.
Severe mitral regurgitation (MR) is a mitral valve disease that can lead to lifethreatening complications. MitraClip (MC) therapy is a percutaneous solution for patients who cannot tolerate surgical ...solutions. In MC therapy, a clip is implanted in the heart to reduce MR. To achieve optimal MC therapy, the cardiologist needs to foresee the outcomes of different scenarios for MC implantation, including the location of the MC. Although finite element (FE) modeling can simulate the outcomes of different MC scenarios, it is not suitable for clinical usage because it requires several hours to complete.
In this paper, we used machine learning (ML) to predict the outcomes of MC therapy in less than 1 s. Two ML algorithms were used: XGBoost, which is a decision tree model, and a feed-forward deep learning (DL) model. The MC location, the geometrical attributes of the models and baseline stress and MR were the features of the ML models, and the predictions were performed for MR and maximum von Mises stress in the leaflets. The parameters of the ML models were determined to achieve the minimum errors obtained by applying the ML models on the validation set.
The results for the test set (not used during training) showed relative agreement between ML predictions and ground truth FE predictions. The accuracy of the XGBoost models were better than DL models. Mean absolute percentage error (MAPE) for the XGBoost predictions were 0.115 and 0.231, and the MAPE for DL predictions were 0.154 and 0.310, for MR and stress, respectively.
The ML models reduced the FE runtime from 6 hours (on average) to less than 1 s. The accuracy of ML models can be increased by increasing the dataset size. The results of this study have important implications for improving the outcomes of MC therapy by providing information about the outcomes of MC implantation in real-time.
We present an elemental-abundance analysis of an extremely metal-poor (EMP; Fe/H <−3.0) star, SDSS J134338.67+484426.6, identified during the course of the Multi-object Apache Point Observatory ...Radial Velocity Exoplanet Large-area Survey spectroscopic pre-survey of some 20 000 stars to identify suitable candidates for exoplanet searches. This star, with an apparent magnitude V = 12.14, is the lowest metallicity star found in the pre-survey, and is one of only ∼20 known EMP stars that are this bright or brighter. Our high-resolution spectroscopic analysis shows that this star is a subgiant with Fe/H = −3.42, having ‘normal’ carbon and no enhancement of neutron-capture abundances. Strontium is underabundant, Sr/Fe = −0.47, but the derived lower limit on Sr/Ba indicates that Sr is likely enhanced relative to Ba. This star belongs to the sparsely populated class of α-poor EMP stars that exhibit low ratios of Mg/Fe, Si/Fe, and Ca/Fe compared to typical halo stars at similar metallicity. The observed variations in radial velocity from several epochs of (low- and high-resolution) spectroscopic follow-up indicate that SDSS J134338.67+484426.6 is a possible long-period binary. We also discuss the abundance trends in EMP stars for r-process elements, and compare with other magnesium-poor stars.
This paper develops a mathematical model for fatigue damage evolution in composite materials. The characteristics of damage growth in composite materials are studied and compared with those of damage ...growth in homogeneous materials. Continuum damage mechanics concepts are used to evaluate the degradation of composite materials under cyclic loading. A new damage accumulation model is proposed to capture the unique characteristics of composite materials. The proposed model is found to be more accurate than existing models, both in modelling the rapid damage growth early in life and near the end of fatigue life. The parameters for the proposed model are obtained with experimental data. A numerical example is implemented to illustrate that the proposed model is able to accurately fit several different sets of experimental data.
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