Regional and annual patterns in respiratory virus co-infection etiologies and antibiotic prescriptions for pediatric mycoplasma pneumoniae pneumonia.

OBJECTIVE: Mycoplasma pneumoniae (M. pneumoniae) pneumonia is the second-most common cause of community-acquired pneumonia (CAP). This study aimed at investigating into the prevalence of macrolide-resistant M. pneumoniae (MRMP) with respiratory virus co-infection and the antibiotic prescriptions in children with CAP in four provinces in Korea, and to assess the variations in the findings across regions and throughout the year. PATIENTS AND METHODS: This prospective study was conducted in 29 hospitals in Korea between July 2018 and June 2020. Among the enrolled 1,063 children with CAP, all 451 patients with M. pneumoniae underwent PCR assays of M. pneumoniae and respiratory viruses, and the presence of point mutations of residues 2063 and 2064 was evaluated. RESULTS: Gwangju-Honam (88.6%) showed the highest prevalence of MRMP pneumonia, while Daejeon-Chungcheong (71.3%) showed the lowest, although the differences in prevalence were not significant (p=0.074). Co-infection of M. pneumoniae pneumonia and respiratory virus was observed in 206 patients (45.4%), and rhinovirus co-infection (101 children; 22.2%) was the most frequent. The prevalence of MRMP pneumonia with respiratory virus co-infection and the antibiotic prescriptions differed significantly among the four provinces (p < 0.05). The monthly rate of MRMP pneumonia cases among all cases of M. pneumoniae pneumonia and tetracycline or quinolone prescriptions did not differ significantly among the four regions (trend p > 0.05) during the study period. CONCLUSIONS: The prevalence of M. pneumoniae pneumonia with virus co-infection and antibiotic prescriptions could differ according to region, although the MRMP pneumonia rate showed no difference within Korea.

The Safety of Intra-arterial Tirofiban during Endovascular Therapy after Intravenous Thrombolysis.

BACKGROUND AND PURPOSE: The safety and efficacy of tirofiban during endovascular therapy in patients undergoing intravenous thrombolysis with recombinant IV tPA remain unclear. This study aimed to investigate the safety and efficacy of intra-arterial tirofiban use during endovascular therapy in patients treated with IV tPA. MATERIALS AND METHODS: Using a multicenter registry, we enrolled patients with acute ischemic stroke who underwent endovascular therapy. Safety outcomes included postprocedural parenchymal hematoma type 2 and/or thick subarachnoid hemorrhage, intraventricular hemorrhage, and 3-month mortality. Efficacy outcomes included the successful reperfusion rate, postprocedural reocclusion, and good outcomes at 3 months (mRS scores of 0-2). The tirofiban effect on the outcomes was evaluated using a multivariable analysis while adjusting for potential confounders. RESULTS: Among enrolled patients, we identified 314 patients with stroke (279 and 35 patients in the no tirofiban and tirofiban groups, respectively) due to an intracranial artery occlusion who underwent endovascular therapy with intravenous thrombolysis. A multivariable analysis revealed no association of intra-arterial tirofiban with postprocedural parenchymal hematoma type and/or thick subarachnoid hemorrhage (adjusted OR, 1.07; 95% CI, 0.20-4.10; P = .918), intraventricular hemorrhage (adjusted OR, 0.43; 95% CI, 0.02-2.85; P = .467), and 3-month mortality (adjusted OR, 0.38; 95% CI, 0.04-1.87; P = .299). Intra-arterial tirofiban was not associated with good outcome (adjusted OR, 2.22; 95% CI, 0.89 -6.12; P = .099). CONCLUSIONS: Using intra-arterial tirofiban during endovascular therapy after IV tPA could be safe.

Incidence of oral anticoagulant interruption among stroke patients with atrial fibrillation and subsequent stroke.

BACKGROUND AND PURPOSE: We analyzed the incidence and causes of oral anticoagulant (OAC) cessation and subsequent stroke after OAC withdrawal in a cohort of Korean stroke patients with atrial fibrillation. METHODS: The Korean Atrial Fibrillation Evaluation Registry in Ischemic Stroke patients (K-ATTENTION) is a multicenter cohort study, merging stroke registries from 11 tertiary centers in Korea. The number of OAC interruption episodes and the reasons were reviewed from hospital records. Stroke after OAC withdrawal was defined when a patient experienced ischaemic stroke within 31 days after OAC withdrawal. Clinical variables were compared between patients who experienced stroke recurrence during OAC interruption and those who did not experience recurrence. RESULTS: Among 3213 stroke patients with atrial fibrillation, a total of 329 episodes of OAC interruption were detected in 229 patients after index stroke (mean age 72.9 ± 8.3 years, 113 female patients). The most frequent reason for OAC withdrawal was poor compliance [103 episodes (31.3%)] followed by extracranial bleeding [96 episodes (29.2%)]. Stroke after OAC withdrawal was noted in 13 patients. Mean age, vascular risk factor profile and mean CHA2 DS2 -VASc score were not significantly different between patients with and without recurrent stroke. CONCLUSIONS: A considerable number of stroke patients with atrial fibrillation experienced temporary interruption of OAC after index stroke, which was associated with stroke recurrence of 4.0 cases per 100 interruption episodes.

High-resolution electrohydrodynamic inkjet printing of stretchable metal oxide semiconductor transistors with high performance.

As demands for high pixel densities and wearable forms of displays increase, high-resolution printing technologies to achieve high performance transistors beyond current amorphous silicon levels and to allow low-temperature solution processability for plastic substrates have been explored as key processes in emerging flexible electronics. This study describes electrohydrodynamic inkjet (e-jet) technology for direct printing of oxide semiconductor thin film transistors (TFTs) with high resolution (minimum line width: 2 µm) and superb performance, including high mobility (∼230 cm2 V-1 s-1). Logic operations of the amplifier circuits composed of these e-jet-printed metal oxide semiconductor (MOS) TFTs demonstrate their high performance. Printed In2O TFTs with e-jet printing-assisted high-resolution S/D electrodes were prepared, and the direct printing of passivation layers on these channels enhanced their gate-bias stabilities significantly. Moreover, low process temperatures (<250 °C) enable the use of thin plastic substrates; highly flexible and stretchable TFT arrays have been demonstrated, suggesting promise for next-generation printed electronics.

Effect of Intracranial Atherosclerotic Disease on Endovascular Treatment for Patients with Acute Vertebrobasilar Occlusion.

BACKGROUND AND PURPOSE: Although intracranial atherosclerotic disease is often encountered during endovascular treatment for acute vertebrobasilar occlusions, its clinical implication is not well-known. We aimed to evaluate whether intracranial atherosclerotic disease influences the clinical outcomes following endovascular treatment of acute vertebrobasilar occlusive stroke. MATERIALS AND METHODS: Fifty-one patients with acute vertebrobasilar occlusive stroke were included. The onset-to-groin puncture time was ≤12 hours, and aspiration- or stent-based thrombectomy was used as the primary treatment method. Following primary endovascular treatment, intracranial atherosclerotic disease (IAD group) was angiographically diagnosed when a fixed focal stenosis was observed at the occlusion site, whereas embolism (embolic group) was diagnosed if no stenosis was observed. Clinical and treatment variables were compared in both groups, and IAD was evaluated as a prognostic factor for clinical outcomes. RESULTS: The baseline NIHSS score tended to be lower (14 versus 22, P = .097) in the IAD group (n = 19) than in the embolic group (n = 32). The procedural time was longer in the IAD group (96 versus 61 minutes, P = .002), despite similar rates of TICI 2b-3 (89.5% versus 87.5%, P = 1.000). The NIHSS score at 7 days was higher (21 versus 8, P = .060) and poor outcomes (mRS 4-6 at 3 months) were more frequent in the IAD group (73.7% versus 43.8%, P = .038). IAD (odds ratio, 5.469; 95% CI, 1.09-27.58; P = .040) was independently associated with poor outcomes. CONCLUSIONS: An arterial occlusion related to IAD was associated with a longer procedural time and poorer clinical outcome. Further studies are warranted to elucidate the appropriate endovascular strategy.

Muscle profiling to improve the value of retail meat cuts.

Nutrition and meat quality are always important to consumers, but vary by individual muscle or muscle groups in retail meat cuts. Muscle profiling of nutrient content and palatability for all retail beef cuts is necessary to suggest healthy and tasty beef cuts and to inform consumers of the benefits of beef consumption. The current paper reviews numerous studies that provide muscle profiles for nutrients and palatability attributes of muscles or muscle groups in retail beef cuts. The composition of nutrients including protein, fat, moisture, vitamins, and minerals in beef cuts is documented as well as the nutritive role as a part of a healthy diet. In addition, this review presents knowledge in relation to innovative carcass fabrication and value-added cuts to improve the value of beef carcass. Finally, the current work emphasize the palatability assessment of individual beef muscles, and concludes that all retail beef cuts should be merchandised for proper cooking according to the palatability profiles of beef muscles.

Impact of time-to-reperfusion on outcome in patients with poor collaterals.

BACKGROUND AND PURPOSE: The relationship between reperfusion and clinical outcome is time-dependent, and the effect of reperfusion on outcome can vary on the basis of the extent of collateral flow. We aimed to identify the impact of time-to-reperfusion on outcome relative to baseline angiographic collateral grade in patients successfully treated with endovascular revascularization for acute large-vessel anterior circulation stroke. MATERIALS AND METHODS: Two hundred seven patients were selected for analysis from our prospectively maintained registry. Inclusion criteria were M1 MCA ± ICA occlusions, onset-to-puncture time within 8 hours, and successful endovascular reperfusion. Baseline angiographic collateral grades were independently evaluated and dichotomized into poor (0-1) versus good (2-4). Multivariable analyses were performed to identify the effect of collateral-flow adequacy on favorable outcome on the basis of onset-to-reperfusion time and puncture-to-reperfusion time. RESULTS: In the poor collateral group, the odds of favorable outcome significantly dropped for patients with onset-to-reperfusion time of >300 minutes or puncture-to-reperfusion time of >60 minutes (onset-to-puncture time: ≤300, 59% versus >300, 32%; OR, 0.24; P = .011; puncture-to-reperfusion time: ≤60, 73% versus >60, 32%; OR, 0.21, P = .011), whereas the probability of favorable outcome in the good collateral group was not significantly influenced by onset-to-reperfusion time or puncture-to-reperfusion time. In the subgroup lesion-volume growth analysis by using DWI, the effect of puncture-to-reperfusion time of >60 minutes was significantly greater compared with the effect of puncture-to-reperfusion time of <60 minutes in the poor collateral group (ß = 41.6 cm(3), P = .001). CONCLUSIONS: Time-to-reperfusion including onset-to-reperfusion time and puncture-to-reperfusion time in patients with poor collaterals is an important limiting factor for favorable outcome in a time-dependent fashion. Future trials may benefit from a noninvasive imaging technique to detect poor collaterals along with a strategy for rapid reperfusion.

Forced arterial suction thrombectomy with the penumbra reperfusion catheter in acute basilar artery occlusion: a retrospective comparison study in 2 Korean university hospitals.

BACKGROUND AND PURPOSE: A performance of forced arterial suction thrombectomy was not reported for the treatment of acute basilar artery occlusion. This study compared revascularization performance between intra-arterial fibrinolytic treatment and forced arterial suction thrombectomy with a Penumbra reperfusion catheter in patients with acute basilar artery occlusion. MATERIALS AND METHODS: Fifty-seven patients with acute basilar artery occlusion were treated with intra-arterial fibrinolysis (n = 25) or forced arterial suction thrombectomy (n = 32). Baseline characteristics, successful revascularization rate, and clinical outcomes were compared between the groups. RESULTS: Baseline characteristics, the frequency of patients receiving intravenous recombinant tissue plasminogen activator, and mean time interval between symptom onset and femoral puncture did not differ between groups. The forced arterial suction thrombectomy group had a shorter procedure duration (75.5 minutes versus 113.3 minutes, P = .016) and higher successful revascularization rate (88% versus 60%, P = .017) than the fibrinolysis group. Fair outcome, indicated by a modified Rankin Scale 0-3, at 3 months was achieved in 34% of patients undergoing forced arterial suction thrombectomy and 8% of patients undergoing fibrinolysis (P = .019), and the mortality rate was significantly higher in the fibrinolysis group (25% versus 68%, P = .001). Multiple logistic regression analysis identified the forced arterial suction thrombectomy method as an independent predictor of fair outcome with adjustment for age, sex, initial NIHSS score, and the use of intravenous recombinant tissue plasminogen activator (odds ratio, 7.768; 95% CI, 1.246-48.416; P = .028). CONCLUSIONS: In acute basilar artery occlusion, forced arterial suction thrombectomy demonstrated a higher revascularization rate and improved clinical outcome compared with traditional intra-arterial fibrinolysis. Further clinical trials with the newer Penumbra catheter are warranted.

Utility of QuantiFERON-TB assay for prediction of tuberculosis development in kidney transplant patients in an intermediate-tuberculosis-burden country: lack of evidence for enhanced prediction for short-term tuberculosis development.

INTRODUCTION: Although a latent tuberculosis (TB) infection is a risk factor for active TB, the diagnosis of latent TB infection is difficult in end-stage renal disease patients. PATIENTS AND METHODS: We retrospectively compared the results of the QuantiFERON-TB (QFT) test and the tuberculin skin test in patients on the waiting list for kidney transplantation (KT), and investigated whether the QFT test can predict TB development in KT recipients in an intermediate-TB-burden country. RESULTS: The incidence of post-KT TB was 283 cases/100,000 patient-years among 1274 KT recipients at the Seoul National University Hospital. The overall standardized incidence ratio of TB was 4.358 compared with the general population. A past history of TB infection, smoking history, myocardial infarction after KT, and pneumocystis infection were significant predictors of subsequent TB development (adjusted odds ratios were 3.618, 2.959, 9.993, and 5.708, respectively). Among the 129 recipients who had the QFT test, 42 patients (32.5%) had positive a QFT. At a median follow-up of 8.4 ± 6.8 months, 1 patient with positive QFT results developed TB after KT, and 1 of the 87 patients with negative QFT results developed TB after KT. In both of these 2 cases, active TB developed despite isoniazid prophylaxis. Among 272 patients on the waiting list for KT, the tuberculin skin test and QFT were positive in 22.8% and 35.3%, respectively. The degree of agreement between the 2 tests was poor (κ = 0.352). CONCLUSIONS: The QFT test did not predict subsequent short-term TB development. Furthermore, a long-term and larger-scale study is needed to confirm our results.

Control of fresh meat quality through manipulation of muscle fiber characteristics.

Variations of fresh meat quality exist because the quality traits are affected by various intrinsic and extrinsic factors. Because the meat quality is basically dependent on muscle fiber characteristics, numerous studies have reported the relationship between quality traits and fiber characteristics. Despite intensive research, the relationship is yet to be fully established, however, the present knowledge suggests several potential ways to manipulate muscle fiber characteristics to improve meat quality. The present paper reviews the definition of fresh meat quality, meat quality traits and variations of meat quality. Also, this review presents recent knowledge underlying the relationship between fresh meat quality traits and muscle fiber characteristics. Finally, the present work proposes several potential factors including breed, genotype, sex, hormone, growth performance, diet, muscle location, exercise and ambient temperature that can be used to manipulate muscle fiber characteristics and subsequently meat quality in animals.

Optimal formation of genetically modified and functional pancreatic islet spheroids by using hanging-drop strategy.

BACKGROUND: Rejection and hypoxia are important factors causing islet loss at an early stage after pancreatic islet transplantation. Recently, islets have been dissociated into single cells for reaggregation into so-called islet spheroids. Herein, we used a hanging-drop strategy to form islet spheroids to achieve functional equivalence to intact islets. METHODS: To obtain single islet cells, we dissociated islets with trypsin-EDTA digestion for 10 minutes. To obtain spheroids, we dropped various numbers of single cells (125, 250, or 500 cells/30 µL drop) onto a Petri dish, that was inverted for incubation in humidified air containing 5% CO(2) at 37 °C for 7 days. The aggregated spheroids in the droplets were harvested for further culture. RESULTS: The size of the aggregated islet spheroids depended on the number of single cells (125-500 cells/30 µL droplet). Their morphology was similar to that of intact islets without any cellular damage. When treated with various concentrations of glucose to evaluate responsiveness, their glucose-mediated stimulation index value was similar to that of intact islets, an observation that was attributed to strong cell-to-cell interactions in islet spheroids. However, islet spheroids aggregated in general culture dishes showed abnormal glucose responsiveness owing to weak cell-to-cell interactions. Cell-to-cell interactions in islet spheroids were confirmed with an anti-connexin-36 monoclonal antibody. Finally, nonviral poly(ethylene imine)-mediated interleukin-10 cytokine gene delivered beforehand into dissociated single cells before formation of islet spheroids increased the gene transfection efficacy and interleukin-10 secretion from islet spheroids >4-fold compared with intact islets. CONCLUSION: These results demonstrated the potential application of genetically modified, functional islet spheroids with of controlled size and morphology using an hanging-drop technique.

Shortened menstrual cycles in LCD manufacturing workers.

BACKGROUND: Many chemical agents used in liquid crystal display (LCD) manufacturing have been evaluated in animal studies of female reproductive toxicity. Knowledge of their reproductive toxicity in humans is scant. AIMS: To determine the effect of organic solvents on menstrual cycle characteristics of workers in LCD manufacturing. METHODS: Cross-sectional study of female premenopausal workers in an LCD plant in Taiwan. Menstrual cycle characteristics were assessed from self-administered questionnaires, and chemical exposure was assessed using hand-held volatile organic compound (VOC) monitors with 24h canister sampling. RESULTS: There was a response rate of 94%, and the final study population after exclusions was 288. Canister sampling found many chemical compounds with potential reproductive effects in the fabrication areas of the plant. Concentrations of total VOC were higher in the panel and module fabrication areas than in other areas of the plant. The prevalence of short menstrual cycles (>24 days) was higher in panel workers (adjusted odds ratio [OR]: 7.68; 95% confidence interval [CI]: 1.51-39.15) and module workers (adjusted OR: 8.38; 95% CI: 1.72-40.95) than in array fabrication workers and office workers. CONCLUSIONS: We found evidence for a possible link between repeated exposure to multiple organic solvents such as ethanol and acetone and increased prevalence of short menstrual cycles in premenopausal women.

Effect of thermal annealing on the efficiency of heterojunction photovoltaic cells fabricated using poly(3-hexylthiophene) and methanofullerene, [6,6]-phenyl C61-butyric acid methyl ester.

The effects of thermal annealing on the efficiency of heterojunction photovoltaic (PV) cells that were fabricated using poly(3-hexylthiophene) (P3HT) and methanofullerene, [6,6]-phenyl C61-butyric acid methyl ester (PCBM) were investigated. The absorption spectra showed that the absorption intensity of the P3HT:PCBM layer that was annealed for 5 min had the highest value among the several samples with different annealing temperatures. The atomic force microscopy image showed that the P3HT:PCBM layer that was annealed for 5 min had the best surface morphology. The X-ray photoelectron spectroscopy demonstrated that the P3HT:PCBM layer that was annealed at 140 degrees C for 10 min enhanced the PCBM aggregation on the surface Al layer that was covered by the P3HT:PCBM layer. The efficiencies of the PV cells that were annealed at 3, 5, and 10 min were approximately 2.7, 4.2, and 3.5%, respectively. Based on the experiment results, the variations in the efficiency of the PV cells due their thermal treatment were described.

P-glycoprotein expression in canine mammary gland tumours related with myoepithelial cells.

P-glycoprotein is influential in chemotherapy-resistance in numerous cancers and has been widely studied in human breast cancer research, but is less studied in canine mammary gland tumour (MGT). The study was to evaluate P-glycoprotein expression and its localisations related with prognostic factors with monoclonal antibody C219, by immunohistochemistry (IHC) of 68 cases of canine malignant (n=54) and benign (n=14) MGT. Additional immunofluorescence (IF) and reverse transcriptase-polymerase chain reaction (RT-PCR) were also performed. There was a novel finding that P-glycoprotein expression with C219 localised at two different cell types: epithelial and myoepithelial cells. Myoepithelial localised tumours were 5 benign (35.5%) and 21 malignant (63.6%), while epithelial localised tumours were 12 cases, all malignant (36.5%). Unlike conventional belief, semi-quantitative evaluation of IHC intensity scores of C219 expression in malignant MGT was related with favourable histopathological parameters.

Application of PTFE membrane for ammonia removal in a membrane contactor.

The feasibility of a membrane contactor system for ammonia removal was studied. The mass transfer coefficient was used to quantitatively compare the effect of various operation conditions on ammonia removal efficiency. Effective removal of ammonia was possible with a Polytetrafluoroethylene (PTFE) membrane contactor system at all tested conditions. Among the various operation parameters, contact time and solution pH showed significant effect on the ammonia removal mechanism. The overall ammonia removal rate was not affected by influent suspended solution concentration unlike other pressure driven membrane filtration processes. Also the osmotic distillation phenomena which deteriorate the mass transfer efficiency can be minimized by preheating of influent wastewater. A membrane contactor system can be a possible alternative to treat high strength nitrogen wastewater by optimizing operation conditions such as stripping solution flow rate, influent wastewater temperature, and influent pH.

Identification of the DSPP mutation in a new kindred and phenotype-genotype correlation.

OBJECTIVE: Hereditary dentin defects can be grouped into three types of dentinogenesis imperfecta (DGI) and two types of dentin dysplasia. Tooth enamel is considered normal in patients with hereditary dentin defects, but is easily worn down and fractured due to DSPP mutation-induced altered dentin properties. The purposes of this study were to identify genetic cause of a family with type II DGI and enamel defects. MATERIALS AND METHODS: We identified a family with type II DGI and a unique form of hypoplastic enamel defect affecting occlusal third of the crown. Family members were recruited for the genetic analysis and DNA was obtained from peripheral whole blood. RESULTS: Mutational analysis revealed a T to A transversion in exon 3 of the DSPP (c.53T>A, p.V18D). Haplotype analysis showed that the same mutation arose separately in two different families having DGI with similar enamel defects, indicating that this phenotype is associated with this specific DSPP mutation. Clinical features suggest that enamel formation was affected in the affected individuals during early amelogenesis, in addition to the dentin defect. CONCLUSIONS: We observed that a DSPP gene mutation not only influences dentinogenesis but also affects early stage amelogenesis.

Direct thrombus retrieval using the reperfusion catheter of the penumbra system: forced-suction thrombectomy in acute ischemic stroke.

BACKGROUND AND PURPOSE: Although the PS has been the most promising mechanical thrombectomy device in terms of recanalization rates, even the PS cannot recanalize all cases of occlusion. Under such circumstances, we simply modified the PS, identified certain advantages, and applied this modification as a primary technique for recanalization. Here we describe and discuss the technical details and results of our preliminary experience. MATERIALS AND METHODS: This study included 22 consecutive patients with acute ischemic stroke secondary to large-artery occlusion who underwent modified thrombectomy by using the PS for recanalization. Direct wedging between the tip of the reperfusion catheter and the proximal part of the clot followed by forceful suction by using a 20- or 50-mL syringe is a unique feature of this technique. What is distinctive is that this does not require use of a separator or aspiration pump. RESULTS: All treated vessels (100%) were successfully recanalized. A TICI scale of 2b or 3 was achieved in 81.9% of patients. A 3-month favorable functional outcome (mRS score, 0-2) was achieved in 45.5% of patients. The only procedural complication was a transient dissection of the proximal ICA, which developed while advancing the guide catheter. CONCLUSIONS: Forced-suction thrombectomy is a simple modification of the PS. On the basis of our data, this technique allows safe and effective revascularization in acute large-vessel occlusion. Thus, for achieving the best outcome, the modified PS technique is proposed as a viable option for acute stroke management, either by itself or in conjunction with other devices or drugs.

FAM83H mutations cause ADHCAI and alter intracellular protein localization.

Mutations in a family with sequence similarity 83 member H (FAM83H) cause autosomal-dominant hypocalcification amelogenesis imperfecta (ADH CAI). All FAM83H ADHCAI-causing mutations terminate translation or shift the reading frame within the specific exon 5 segment that encodes from Ser(287) to Glu(694). Mutations near Glu(694) cause a milder, more localized phenotype. We identified disease-causing FAM83H mutations in two families with ADHCAI: family 1 (g.3115C>T, c.1993 C>T, p.Q665X) and family 2 (g.3151C>T, c.2029 C>T, p.Q677X). We also tested the hypothesis that truncation mutations alter the intracellular localization of FAM83H. Wild-type FAM83H and p.E694X mutant FAM83H fused to green fluorescent protein (GFP) localized in the cytoplasm of HEK293T cells, but the mutant FAM83H proteins (p.R325X, p.W460X, and p.Q677X) fused to GFP localized mainly in the nucleus with slight expression in the cytoplasm. We conclude that nuclear targeting of the truncated FAM83H protein contributes to the severe, generalized enamel phenotype.