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This article shows how fractures in the Si3N4 layer, which comprises the top layer of semiconductor devices encapsulated utilizing a lead-on-chip (LOC) packaging technique, are influenced by changes in the lead-frame materials and thermal-cycling test conditions. Using thermal-cycling tests, it was found that fractures in the Si 3 N 4 layer are the most sensitive to changes in the lead-frame materials at the early stage of thermal-cycling, between -65sup>oC and 150sup>oC. Through SEM examinations and stress simulations, this work shows that adopting a copper lead-frame with a CTE-value similar to that of a package body effectively prevents filler-driven Si3N4 damage, providing semiconductor devices with better reliability margins during thermal-cycling.

Early detection and treatment is important to reduce mortality from lung cancer. Based on the positive results of lung cancer-related mortality reduction from large randomized trials of low-dose chest computed tomography (LDCT)-based screening in high-risk populations, LDCT-based screening programs have been implemented in several countries including Republic of Korea. This review focus on the current evidence and state of the art of LDCT-based lung cancer screening, and further discuss the ongoing efforts to develop more efficient screening programs worldwide. This article includes recent updates on the identification of high-risk population eligible for screening and management for screen-detected nodules. Additionally, aspects on future research direction would be addressed.

The major challenges in pancreatic ductal adenocarcinoma (PDAC) management are local or distant metastasis and limited targeted therapeutics to prevent it. To identify a druggable target in tumor secretome and to explore its therapeutic intervention, we performed a liquid chromatography–tandem mass spectrometry (LC-MS/MS)–based proteomic analysis of tumors obtained from a patient-derived xenograft model of PDAC. Galectin-3 binding protein (Gal-3BP) is identified as a highly secreted protein, and its overexpression is further validated in multiple PDAC tumors and primary cells. Knockdown and exogenous treatment of Gal-3BP showed that it is required for PDAC cell proliferation, migration, and invasion. Mechanistically, we revealed that Gal-3BP enhances galectin-3–mediated epidermal growth factor receptor signaling, leading to increased cMyc and epithelial-mesenchymal transition. To explore the clinical impact of these findings, two antibody clones were developed, and they profoundly abrogated the metastasis of PDAC cells in vivo. Altogether, our data demonstrate that Gal-3BP is an important therapeutic target in PDAC, and we propose its blockade by antibody as a therapeutic option for suppressing PDAC metastasis.

BACKGROUND: Although low-dose computed tomography (LDCT) screening is known to be effective for the detection of lung cancers localized in peripheral lung regions at a curable stage, limited data is available regarding the characteristics and outcomes of central lung cancers diagnosed in a screening cohort. This study aimed to determine whether LDCT screening could effectively detect central lung cancers at an early stage and offer survival benefits. METHODS: We analyzed 52,615 adults who underwent lung cancer screening with LDCT between May 2003 and Dec 2019 at a tertiary center in South Korea. Characteristics and outcomes of those diagnosed with lung cancer, stratified by screen-detection status and cancer location, were evaluated. RESULTS: A total of 352 individuals (281 screen-detected, 71 non-screen-detected) were diagnosed with lung cancer. Compared to screen-detected cancers, non-screen-detected cancers tended to be centrally-located (11.4% vs. 64.8%, P

The success of the human activity recognition (HAR) algorithm of a wearable inertial sensor depends on the extraction of good temporal dynamics from the sequential motor movement of humans. In the past, a heuristic method was used for the feature extraction process. Recently, deep neural network (DNN)-based studies, in which this process is automatically performed in the model, have shown good results. The performance of the DNN models is good and almost all processes are automated; however, they have some limitations—data-imbalance problems in the dataset and the small data decrease the performance. In this study, the HAR public dataset was improved by introducing an oversampling technique-based data-augmentation algorithm, and a stacking ensemble model with a one-dimensional convolutional neural network and a bidirectional gated recurrent unit as the head was used for classification. The HAR public dataset used Wireless sensor data mining (WISDM) and the University of California, Irvine human activity recognition using smartphones data set (UCI-HAR). Consequently, the proposed model showed better performance than that of previous studies for both datasets. The accuracy of the proposed model was 99.49% and 99.48%; the F1-score of the model was 99.84% and 99.78%, respectively.

Diabetes mellitus (DM) is common and recognized as a risk factor for developing non-small cell lung cancer (NSCLC) while the prognostic evaluation is still controversial. As immunotherapy is widely used in clinical practice, its efficacy and survival should be investigated in patients with DM.We retrospectively recruited 266 locally advanced and metastatic NSCLC patients who received pembrolizumab alone or in combination with chemotherapy. Patients' clinicopathological data, including age, history of DM, hemoglobin A1c (HbA1c), genetic tumor profiling, and survival data were collected. Associations between clinical characteristics and survival were evaluated by univariate and multivariate analyses.In this cohort, 15.04% (40/266) of the patients had a history of DM. Fifty-nine (22.2%) patients had a HbA1c level ≥6.5%. A total of 169 (63.5%) patients received 1st-line therapy, and 97 (36.5%) received 2nd- or subsequent-line therapy. Patients with high (≥6.5%) HbA1c and lower (35 g/L) albumin levels at baseline had worse survivals, and epidermal growth factor receptor (Among patients treated with 1st-line immunotherapy, a higher HbA1c level (≥6.5%) indicated dismal OS, while history of DM, baseline blood glucose levels, and glucose changes during the treatment process were not significantly associated with any of the outcomes.

In this study, we demonstrate a simple and effective way to fabricate functionally graded TiNi-based alloys with linear variations of composition and martensitic transformation behavior. Ti50Ni50 and Ti50Ni35Cu15 alloy strips were fabricated through a melt overflow process. The compositionally graded diffusion couple was fabricated by annealing two strips of different alloy compositions after being placed face to face in a pressing graphite mold. The mechanical properties and martensitic transformation behaviour of the diffusion couple were analysed by tensile test and DSC. The compositionally graded specimens exhibited unique superelastic property and wide martensitic formation temperature range. Such mechanical and thermal behaviors of the compositionally graded TiNi-based alloy offer good function and controllability for actuators.

Background Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome-coronavirus-2. Consensus suggestions can standardise care, thereby improving outcomes and facilitating future research. Methods An International Task Force was composed and agreement regarding courses of action was measured using the Convergence of Opinion on Recommendations and Evidence (CORE) process. 70% agreement was necessary to make a consensus suggestion. Results The Task Force made consensus suggestions to treat patients with acute COVID-19 pneumonia with remdesivir and dexamethasone but suggested against hydroxychloroquine except in the context of a clinical trial; these are revisions of prior suggestions resulting from the interim publication of several randomised trials. It also suggested that COVID-19 patients with a venous thromboembolic event be treated with therapeutic anticoagulant therapy for 3 months. The Task Force was unable to reach sufficient agreement to yield consensus suggestions for the post-hospital care of COVID-19 survivors. The Task Force fell one vote shy of suggesting routine screening for depression, anxiety and post-traumatic stress disorder. Conclusions The Task Force addressed questions related to pharmacotherapy in patients with COVID-19 and the post-hospital care of survivors, yielding several consensus suggestions. Management options for which there is insufficient agreement to formulate a suggestion represent research priorities., For patients with acute COVID-19 pneumonia who require oxygen support, the International Task Force made suggestions for remdesivir and dexamethasone, but against hydroxychloroquine. Post-discharge management of COVID-19 survivors is a research priority. https://bit.ly/32B96uI

This work illustrates a mechanism for mitigating filler-induced reliability degradation in semiconductor devices assembled utilizing an LOC (lead-on-chip) package technique. Based on the mechanism, this article provides two fundamental solutions to solve the filler-driven problem in semiconductor products. First of all, in order to avoid filler-driven pattern damage during thermal-cycling, the maximum filler size in the plastic package body should have a diameter smaller than half of the inter-distance between the device pattern and it’s overlying lead-frame. Second, for effective prevention of filler-induced failure, the minimum distance between the polyimide coverage and each pad should be maintained to have a dimension that corresponds to the polyimide thickness. This article conclusively shows that the proper combination of two solutions can allow semiconductor products to have better reliability margins in use.

Pancreatic neuroendocrine tumors (PanNETs) are frequently detected on endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) specimens. The conventional methods for evaluating the Ki-67 labeling index (Ki67LI) in EUS-FNAB specimens are laborious, and their results are difficult to interpret. More practical and easy methods for evaluating the Ki67LI in PanNETs from EUS-FNAB specimens is increasing in need.We used double Ki-67 and synaptophysin (double Ki-Syn) antibody cocktail; Ki67LI, total Ki-67 positive cells, and total tumor cells were counted and compared with those detected on conventional single Ki-67 immunostaining (single Ki-67) of 96 PanNETs [Grade 1 (G1), 68 cases (71%); G2, 26 (27%); G3, 2 (2%)] from EUS-FNAB specimens.The tumor grading between double Ki-Syn and single Ki-67 immunolabeling was highly concordant (correlation, 0.95; Fisher's exact test, P 0.001). Seven EUS-FNAB specimens (7%) had discrepant results, of which 2 were removed through surgical resection and showed the same tumor grade as that detected on double Ki-Syn immunolabeling. Fifty-four specimens (56%) had higher Ki-67 positive tumor cell counts on single Ki-67 immunolabeling. Sixty-two specimens (65%) had higher total tumor cell counts on double Ki-Syn immunolabeling. The number of specimens with less than 500 total counted tumor cells were significantly reduced when double Ki-Syn immunolabeling was applied [P = 0.046; single Ki-67, 17 specimens (18%); double Ki-Syn, 9 specimens (9%)].Double Ki-Syn immunolabeling enables the accurate counting of the number of proliferating tumor cells without including inflammatory and contaminant epithelial cells compared with single Ki-67 immunolabeling in PanNETs from EUS-FNAB specimens.

Background: There is little information on the optimal storage conditions for recovery of nontuberculous Mycobacterium spp. (NTM) from refrigerated sputum. Objectives: We investigated the storage duration that could increase the culture-positive rate of NTM isolates. Design: In this prospective study, we collected NTM isolates and clinical data from patients with repeated culture-positive NTM pulmonary disease (NTM-PD). Methods: From June 2020 to July 2021, the participants were instructed to randomly collect six sputum samples and immediately store them in a refrigerator at 4°C until the date of their clinic visit. At the outpatient visits, expectorated spot sputum samples were collected. Results: A total of 226 sputum samples were collected from 35 patients. The median duration of refrigeration was 6 days (maximum duration: 36 days). The overall culture-positive rate was 81.6%. While there was a trend for a higher culture positivity rate when stored for ⩽3 weeks, this was not significant compared with those stored for >3 weeks ( p = 0.610). According to sputum microscopy, smear-positive sputum was 100% isolated, but smear-negative samples had a culture-positive rate of 77.5%. Similarly, there was no significant association between sputum storage duration and culture positivity ( p = 0.511). In addition, the recovery rate of the refrigerated sputum was comparable with the collected spot expectorated sputum (82.6% versus 80.6%, p = 0.795), which is suggestive of the long-term viability of NTM in refrigerated sputum. Conclusion: Our data demonstrated the long-term viability of refrigerated NTM, and the culture positivity rate of these samples was comparable with the spot expectorated sputum. These results suggest that implementing sputum refrigeration would enhance convenience in diagnosing and following patients with NTM-PD. Plain language summary Easy way to diagnose NTM lung diseases Under usual circumstances, most patients with suspected NTM submit spontaneously expectorated sputum rather than induced sputum for the purpose of testing the causative organism. By collecting and storing sputum specimens for a longer period than before, it is expected that more sufficient and adequate collection of sputum specimens will be possible.

Tumor spread through airspaces (STAS) is a recently determined pathologic phenomenon of lung cancer with significant prognostic impact. This study aimed to analyze the unexplored correlation between preoperative biopsy procedure and a higher risk of STAS and its impact on STAS-related outcomes in resected stage I non-small cell lung cancer (NSCLC).Does preoperative biopsy procedure affect the risk of STAS and STAS-related outcomes in surgically treated stage I NSCLC?We examined 2,169 patients who underwent surgery for pathologic stage I NSCLC from January 2011 through December 2019 at the Seoul National University Bundang Hospital, a tertiary center in South Korea. Factors including percutaneous needle biopsy (PCNB) and bronchoscopic biopsy were assessed for determining the association between preoperative biopsy procedure and an elevated risk of STAS. In addition, the impact of preoperative biopsy on STAS-related prognosis (recurrence and lung cancer-specific mortality) was evaluated with multivariate Cox regression analyses.STAS findings were positive in 638 of 2,169 patients (29.4%). An insignificant association was found between preoperative biopsy (both PCNB and bronchoscopic biopsy) and STAS. After adjustments for preoperative tumor biopsy, STAS was a significant risk factor for cancer recurrence (hazard ratio [HR], 1.72; 95% CI, 1.20-2.48). Additionally, sublobar resection remained a significant risk factor for recurrence (HR, 3.20; 95% CI, 1.65-6.21) and lung cancer-specific mortality (HR, 12.71; 95% CI, 3.68-43.92) in patients with positive STAS findings. However, this association was insignificant for patients without STAS. Preoperative biopsy was not a significant risk factor for either recurrence and mortality, regardless of STAS positivity.Preoperative biopsy in stage I NSCLC neither was associated with an elevated risk of STAS nor influenced the prognosis related to STAS. Physicians can be less apprehensive about performing preoperative biopsy in relationship to STAS.

In this study, a wearable inertial measurement unit system was introduced to assess patients via the Berg balance scale (BBS), a clinical test for balance assessment. For this purpose, an automatic scoring algorithm was developed. The principal aim of this study is to improve the performance of the machine-learning-based method by introducing a deep-learning algorithm. A one-dimensional (1D) convolutional neural network (CNN) and a gated recurrent unit (GRU) that shows good performance in multivariate time-series data were used as model components to find the optimal ensemble model. Various structures were tested, and a stacking ensemble model with a simple meta-learner after two 1D-CNN heads and one GRU head showed the best performance. Additionally, model performance was enhanced by improving the dataset via preprocessing. The data were down sampled, an appropriate sampling rate was found, and the training and evaluation times of the model were improved. Using an augmentation process, the data imbalance problem was solved, and model accuracy was improved. The maximum accuracy of 14 BBS tasks using the model was 98.4%, which is superior to the results of previous studies.

BACKGROUND: Electromagnetic navigation bronchoscopy (ENB) is an emerging technique for diagnosing pulmonary lesions. However, limited data is available on its sole utility under a least invasive setting without general anesthesia. We aimed to evaluate the diagnostic performance and safety of sole ENB under moderate sedation for diagnosing pulmonary lesions suspicious for lung cancer and to determine clinical factors associated with a better diagnostic yield. METHODS: We performed a retrospective analysis of consecutive patients who underwent sole ENB under moderate sedation for lung lesion biopsy between August 2016 and June 2021 at Seoul National University Bundang Hospital, a tertiary center in South Korea. Diagnostic yield of the ENB-guided biopsy, safety endpoints defined by the incidence and severity of associated complications, and factors associated with higher diagnostic yield were evaluated. RESULTS: A total of 94 patients were evaluated. The final diagnostic yield of ENB was 81.5% (75/92), excluding two indeterminate cases. The diagnostic yield ranged from 79.8% to 81.9% assuming all indeterminate cases were false-negatives (79.8%) and true-negatives (81.9%). The sensitivity and specificity for malignancy were 77.6% (ranging from 75.6% to 77.6%) and 100%, respectively. Any-grade pneumothorax occurred in 4.3% of the patients, and 2.1% developed pneumothorax requiring additional intervention. Multivariable analyses identified the presence of a class 2 bronchus sign as the only significant predictor for a higher diagnostic yield (odds ratio =4.83, 95% CI: 1.16–20.12). The diagnostic yield of ENB among those with class 2 bronchus sign was 89.8% (53/59). CONCLUSIONS: Sole ENB under moderate sedation for diagnosing pulmonary lesions displayed a good diagnostic yield and safety profile, thus confirming its utility in a least-invasive setting. Moreover, sole ENB could be possibly be superior to transthoracic needle aspiration for diagnosing lesions with class 2 bronchus sign accounting for similar yields and lower complication rates.

Background Surgical resection is usually recommended for the treatment of pulmonary sclerosing pneumocytoma (PSP). However, no comparative study has demonstrated that surgical resection leads to improved outcomes. We aimed to compare all-cause mortality between patients with PSP who underwent surgery or did not and those without PSP. Methods Participants aged ≥18 years who had pathologically diagnosed PSP between 2001 to 2018, at 3 hospitals were included. Randomly selected (up to 1:5) age-, sex-, and smoking status-matched controls without PSP who were randomly selected from those who underwent health checkups including chest CT were included. Mortality was compared using Kaplan–Meier estimates and Cox proportional hazards regression models. Literature review of studies reporting PSP was also conducted. Results This study included 107 patients with PSP (surgery:non-surgery, 80:27) and 520 matched controls. There were no cases of lymph node or distant metastasis, recurrence, or mortality from PSP. No significant difference in all-cause mortality risk was observed between the PSP surgery, PSP non-surgery, and non-PSP groups (log rank test P = 0.78) (PSP surgery vs. non-PSP: adjusted hazards ratio [aHR], 1.80; 95% confidence interval [CI], 0.22–14.6; PSP non-surgery vs. non-PSP: aHR, 0.77; 95% CI, 0.15–3.86; PSP surgery vs. PSP non-surgery: aHR, 2.35; 95% CI, 0.20–28.2). In the literature review, we identified 3469 patients with PSP from 355 studies. Only 1.33% of these patients reported metastasis, recurrence, or death. Conclusions All-cause mortality did not differ between patients with PSP and those without, irrespective of undergoing surgery. Our study and the literature review suggest that PSP has less impact on increased mortality risk.

This paper proposes a data valuation algorithm for inertial measurement unit-based human activity recognition (IMU-based HAR) data based on meta reinforcement learning. Unlike previous studies that received feature-level input, the algorithm in this study added a feature extraction structure to the data valuation algorithm, and it can receive raw-level inputs and achieve excellent performance. As IMU-based HAR data are multivariate time-series data, the proposed algorithm incorporates an architecture capable of extracting both local and global features by inserting a transformer encoder after the one-dimensional convolutional neural network (1D-CNN) backbone in the data value estimator. In addition, the 1D-CNN-based stacking ensemble structure, which exhibits excellent efficiency and performance on IMU-based HAR data, is used as a predictor to supervise model training. The Berg balance scale (BBS) IMU-based HAR dataset and the public datasets, UCI-HAR, WISDM, and PAMAP2, are used for performance evaluation in this study. The valuation performance of the proposed algorithm is observed to be excellent on IMU-based HAR data. The rate of discovering corrupted data is higher than 96% on all datasets. In addition, classification performance is confirmed to be improved by the suppression of discovery of low-value data.

Research on vitamin D in patients with nontuberculous mycobacterial (NTM) pulmonary disease (PD) is limited. We aimed to compare the vitamin D parameters of patients with NTM-PD to those of a healthy control group, and to assess the possible predictive markers for a clinical response. We prospectively enrolled 53 patients with NTM-PD between January 2014 and December 2016. The clinical data and vitamin D indices, including total, free, bioavailable 25-(OH)D, and vitamin D binding protein (VDBP) genotyping, were measured at baseline and six months after enrollment. An external dataset of 226 healthy controls was compared with the NTM-PD group. The mean age of subjects was 53 years, 54.5% were male. The NTM-PD group was older, predominantly female, and had a lower body mass index (BMI) than the controls. The proportion of patients with vitamin D concentration &lt, 50 nmol/L was 52.8% in the NTM-PD group and 54.9% in the control group (p = 0.789). The bioavailable 25-(OH)D concentrations of the NTM-PD group and the controls were similar (6.9 nmol/L vs. 7.6 nmol/L, p = 0.280). In the multivariable analysis, bioavailable 25-(OH)D concentrations were associated with NTM-PD, adjusting for age, sex, BMI, and VDBP levels. Bioavailable 25-(OH)D concentrations were significantly associated with susceptibility to NTM-PD, but not with treatment outcomes. Lower bioavailable 25-(OH)D might be a risk factor for NTM-PD.

AIMS Mucinous cystic neoplasms (MCNs) of the pancreas are cystic neoplasms lined by mucinous lining epithelium (MLE) with associated ovarian-type stroma. Although a non-MLE (NMLE) can be observed in some MCNs, whether cystic neoplasms with ovarian-type stroma and NMLE should be classified as MCNs or separately designated is debated. METHODS AND RESULTS To test this, NMLEs were defined as flat or cuboidal epithelial cells without intracytoplasmic mucin. A total of 112 MCNs were reviewed, and the epithelium was classified as NMLE or MLE. A total of 110 females and two males with a mean age of 46.5 ± 12.3 years were included in this study. At least focal NMLE was noted in 76.8% (86/112) of MCNs. The mean percentage of the neoplastic epithelium that was NMLE in these 86 cases was 46%. NMLE was predominant (>50%) in 38.4% (43/112) of cases. MCNs with NMLE were smaller (42 ± 21 mm) than those with MLE (60 ± 36 mm, P

The aim of this study is to clarify whether the combined evaluation of resting hyperinflation and emphysema confers any additional advantages in terms of predicting clinical outcomes in chronic obstructive pulmonary disease (COPD) patients. We included COPD patients from the Korean Obstructive Lung Disease (KOLD) cohort. Patients with a residual volume/total lung capacity (RV/TLC) over the upper limit of normal were defined as having resting hyperinflation, and those with an emphysema index >10% were defined as having emphysema. We investigated the impacts of resting hyperinflation and emphysema on exacerbations and mortality. A total of 310 COPD patients were analyzed over a mean of 61.1 months. After adjustment for covariates, resting hyperinflation was an independent predictor of earlier exacerbation (HR = 1.66, CI = 1.24–2.22), more frequent exacerbation (IRR = 1.35, CI = 1.01–1.81), and higher mortality (HR = 2.45, CI = 1.16–5.17) risk. Emphysema was also significantly associated with earlier exacerbation (HR = 1.64, CI = 1.15–2.35), and higher mortality (HR = 3.13, CI = 1.06–9.27) risk. Participants with both resting hyperinflation and emphysema had an additively higher risk of earlier exacerbations (HR = 1.71, 95% CI = 1.26–2.33) and mortality (HR = 3.75, 95% CI = 1.81–7.73) compared with those in other groups. In conclusion, resting hyperinflation and emphysema had additional worse impacts on exacerbations and mortality in COPD patients.

BACKGROUND AND AIMS Chromophobe hepatocellular carcinoma (HCC) is a newly included subtype of HCC in the 5th edition of the WHO classification with distinctive histological features (chromophobic cytoplasm with anaplastic nuclei and pseudocyst formation) and is strongly associated with the alternative lengthening of telomeres (ALT) phenotype. However, the clinicopathologic characterization and molecular features of chromophobe HCC are unknown. METHODS To comprehensively characterize chromophobe HCC, whole exome sequencing, copy number variation, and transcriptomic analyses were performed in 224 surgically resected HCC cases. Additionally, telomere-specific fluorescence in situ hybridization was used to assess ALT. These genomic profiles and ALT status were compared with clinicopathological features among subtypes of HCC, particularly chromophobe HCC and conventional HCC. RESULTS Chromophobe HCC was observed in 10.3% (23/224) cases and, compared to conventional HCC, was more frequent in females (P = .023). The overall and recurrence-free survival outcomes were similar between patients with chromophobe HCC and conventional HCC. However, chromophobe HCC displayed significantly more upregulated genes involving cell cycle progression and DNA repair. Additionally, ALT was significantly enriched in chromophobe HCC (87%; 20/23) compared to conventional HCC (2.2%, 4/178; P

Histopathology relies upon the staining and sectioning of biological tissues, which can be laborious and may cause artefacts and distort tissues. Here, we demonstrate label-free volumetric imaging of thick-tissue slides, exploiting refractive index distributions as intrinsic imaging contrast. The present method systematically exploits label-free quantitative phase imaging techniques, volumetric reconstruction of intrinsic refractive index distributions in tissues, and numerical algorithms for the seamless stitching of multiple 3D tomograms and for reducing scattering-induced image distortion. We demonstrate demonstrated label-free volumetric imaging of thick tissues with the field of view of 2 mm × 1.75 mm × 0.2 mm with a spatial resolution of 170 nm × 170 nm × 1200 nm. The number of optical modes, calculated as the reconstructed volume divided by the size of the point spread function, was approximately 20 Giga voxels. We have also demonstrated that different tumour types, and a variety of precursor lesions and pathologies can be visualized with the present method.Abstract Figure

We realized multiscale label-free volumetric histopathology of thick-tissue slides. The present method exploits label-free volumetric reconstruction of intrinsic refractive index distributions in tissues, and numerical algorithms for seamless stitching and reduction of scattering-induced image distortion.