Realizing High Brightness Quasi-2D Perovskite Light-Emitting Diodes with Reduced Efficiency Roll-Off via Multifunctional Interface Engineering.

Quasi-2D perovskites have recently flourished in the field of luminescence due to the quantum-confinement effect and the efficient energy transfer between different n phases resulting in exceptional optical properties. However, owing to the lower conductivity and poor charge injection, quasi-2D perovskite light-emitting diodes (PeLEDs) typically suffer from low brightness and high-efficiency roll-off at high current densities compared to 3D perovskite-based PeLEDs, which is undoubtedly one of the most critical issues in this field. In this work, quasi-2D PeLEDs with high brightness, reduced trap density, and low-efficiency roll-off are successfully demonstrated by introducing a thin layer of conductive phosphine oxide at the perovskite/electron transport layer interface. The results surprisingly show that this additional layer does not improve the energy transfer between multiple quasi-2D phases in the perovskite film, but purely improves the electronic properties of the perovskite interface. On the one hand, it passivates the surface defects of the perovskite film; on the other hand, it promotes electron injection and prevents hole leakage across this interface. As a result, the modified quasi-2D pure Cs-based device shows a maximum brightness of > 70,000 cd m-2 (twice that of the control device), a maximum external quantum efficiency (EQE) of > 10% and a much lower efficiency roll-off at high bias voltages.

Enhancing the Performance of Quasi-2D Perovskite Light-Emitting Diodes Using Natural Cyclic Molecules with Distinct Phase Regulation Behaviors.

In this study, two natural small molecules, α-cyclodextrin (α-CD) and ß-cyclodextrin (ß-CD), are used as additives to improve the performance of quasi-2D PEA2Csn-1PbnBr3n+1 (n = 3, herein) PeLEDs. Both of them are shown to efficiently passivate the quasi-2D perovskite films to afford improved film quality and morphology, but they exhibit distinct phase regulation behaviors possibly due to their different pore sizes. It reveals that α-CD effectively suppresses the formation of the low-n phases (n ≤ 2), while ß-CD better regulates the phase with a medium-n value (n = 3). Because of effectively suppressing the formation of low-n phases, the CD-assisted quasi-2D perovskite films possess facilitated exciton energy transfer and reduced nonradiative recombination. Consequently, the optimized α-CD-derived PeLED shows the highest luminance (Lmax) of 37,825 cd/m2 with an external quantum efficiency (EQE) of 3.81%, while the ß-CD-derived PeLED delivers a lower Lmax of 24,793 cd/m2 with an EQE of 3.09%. Compared to the pristine device, Lmax is enhanced by 6.3 and 3.8 times for α-CD- and ß-CD-based PeLEDs, respectively, and EQE is enhanced by ∼4.8 times for both devices; besides, both CD-assisted devices also exhibit improved color purity and a lower bias dependency of electroluminescent intensity.

Comparable outcomes of recycled autografts and allografts for reconstructions in patients with high-grade osteosarcoma.

PURPOSE: This retrospective, single-centre study compares the clinical and radiographic outcomes of limb reconstruction using recycled autografts to that using allografts. METHODS: Patients with histopathologically verified high-grade osteosarcoma treated with wide bone resection and limb reconstruction using allografts or recycled autografts from January 1998 through December 2012 were retrospectively screened for enrolment eligibility. The final study cohort included 255 patients (allograft, 91; recycled autograft, 164). Data regarding post-operative complications, salvage treatment, and graft survival were collected. A modified International Society of Limb Salvage classification system was used to evaluate the radiographic findings. RESULTS: The time to graft-host union did not differ significantly between the two graft types. Patients receiving recycled autografts had fewer complications compared than did those receiving allografts (recycled autografts vs. allograft: structural failure, 4.3 vs. 13.2%; late infection, 2.4 vs. 7.7%; all p < 0.05). Complications occurred most frequently during the first three years after surgery, and the majority were manageable. The five year limb survival rate did not differ significantly between the two graft types (91.3 vs. 94.0%; p = 0.752). No local oncological recurrence was observed within the recycled autografts. CONCLUSION: Recycled autografts and allografts are feasible options for biological limb reconstructions in terms of complications and graft survival after wide resection of osteosarcoma.

Significantly reducing blood loss via a peri-articular injection of tranexamic acid during total knee arthroplasty: a retrospective study.

BACKGROUND: The administration of an intra-articular injection (IAI) of tranexamic acid (TXA) has been demonstrated to be effective in reducing both blood loss and transfusion rate during total knee arthroplasty (TKA); however, few studies have reported the efficiency of a peri-articular injection (PAI) of TXA. We studied the efficiency of a PAI of TXA in reducing blood loss during TKA. METHODS: Fifty patients undergoing primary simultaneous bilateral TKA were enrolled in this retrospective study. The right knee received a PAI of 1 g of TXA (Group I), and the left knee received an IAI of 1 g of TXA (Group II). The clinical outcome measures were a change in blood loss from Hemovac drains and surgical time. RESULTS: The decrease in blood loss from the Hemovac was significantly lower in Group I (460.1 ± 36.79 vs. 576.0 ± 34.01, P < 0.001) than in Group II, and no significant difference in surgical times was observed. The blood transfusion rate in the present study was 16 %. CONCLUSIONS: A PAI of TXA may reduce blood loss more efficiently than an IAI of TXA during TKA without increased complications such as surgical site infection, poor wound healing, skin necrosis, pulmonary embolism, and deep vein thrombosis.

Alveolar soft part sarcoma: Clinical presentation, treatment, and outcome in a series of 13 patients.

BACKGROUND: Alveolar soft part sarcoma (ASPS) is a rare soft tissue tumor that typically affects young patients. Similar to other soft tissue sarcomas, it has high pulmonary metastasis ability, whereas compared with other soft tissue sarcomas, it has high brain metastasis ability. Because of the rarity of the disease, most studies on ASPS have been case reports and small series studies. METHOD: We performed a retrospective study to evaluate the clinical and pathological features and oncological results in a consecutive series of patients with localized or metastatic ASPS treated at our institute between 1994 and 2014. Demographics, location, severity of disease, treatment provided, progression-free survival, and overall survival were evaluated. RESULTS: A total of 13 patients were investigated. The most common locations of primary tumor were the thigh (n = 6, 47%), followed by the flank (n = 3, 23%), forearm (n = 2, 15%), and calf (n = 2, 15%). Three patients were initially diagnosed as having hemangiomas elsewhere. These patients received unplanned intralesional excision. All the patients received wide tumor resection at our institute. Over the average follow-up period of 80.5 months (range: 36-133 months), the 5-year overall survival rate was 67.5%. Four patients were continuously disease free (31%), six were living with disease (46%), and three died of disease (23%). Of nine patients who presented with distant pulmonary metastasis, two had bony and brain metastases. The 5-year survival rate was 66.7% in patients who received chemotherapy and those who did not (p = 0.941). CONCLUSION: The treatment strategy for ASPS is wide resection, and postoperative chemotherapy may be crucial for long-term survival. In addition, this type of tumor has a high distant metastasis rate at the time of diagnosis, particularly in the lungs and brain.

Dual-Signal Microbial Biosensor for the Detection of Dopamine without Inference from Other Catecholamine Neurotransmitters.

Dopamine, one of catecholamine neurotransmitters, plays an important role in many brain functions and behavioral responses. In this study, we developed a novel dual-signal whole-cell biosensor for the detection of dopamine through the generation of red fluorescent proteins and 6-decarboxylated betaxanthin pigments. The proposed system responses specifically to dopamine with a detection limit of 1.43 µM. Furthermore, a combination of dual output signals makes it possible to reduce the interference from other catecholamine neurotransmitters, including L-DOPA, epinephrine, and norepinephrine.

Preoperative nomogram to predict the likelihood of complications after radical nephroureterectomy.

OBJECTIVES: To construct a nomogram based on preoperative variables to better predict the likelihood of complications occurring within 30 days of radical nephroureterectomy (RNU). PATIENTS AND METHODS: The charts of 731 patients undergoing RNU at eight academic medical centres between 2002 and 2014 were reviewed. Preoperative clinical, demographic and comorbidity indices were collected. Complications occurring within 30 days of surgery were graded using the modified Clavien-Dindo scale. Multivariate logistic regression determined the association between preoperative variables and post-RNU complications. A nomogram was created from the reduced multivariate model with internal validation using the bootstrapping technique with 200 repetitions. RESULTS: A total of 408 men and 323 women with a median age of 70 years and a body mass index of 27 kg/m2 were included. A total of 75% of the cohort was white, 18% had an Eastern Cooperative Oncology Group (ECOG) performance status ≥2, 20% had a Charlson comorbidity index (CCI) score >5 and 50% had baseline chronic kidney disease (CKD) ≥ stage III. Overall, 279 patients (38%) experienced a complication, including 61 events (22%) with Clavien grade ≥ III. A multivariate model identified five variables associated with complications, including patient age, race, ECOG performance status, CKD stage and CCI score. A preoperative nomogram incorporating these risk factors was constructed with an area under curve of 72.2%. CONCLUSIONS: Using standard preoperative variables from this multi-institutional RNU experience, we constructed and validated a nomogram for predicting peri-operative complications after RNU. Such information may permit more accurate risk stratification on an individual cases basis before major surgery.

Critical analysis of 30 day complications following radical nephroureterectomy for upper tract urothelial carcinoma.

INTRODUCTION: Patients with upper tract urothelial carcinoma (UTUC) are often elderly and comorbid owing to associated risk factors for developing this malignancy. Perioperative complications may be significant in such a surgical population. We define the incidence and risk factors associated with perioperative complications occurring within 30 days of radical nephroureterectomy (RNU). MATERIALS AND METHODS: Medical records of 92 consecutive patients undergoing RNU were reviewed. Complications occurring within 30 days of surgery were graded using the modified Clavien-Dindo classification. The number, severity, and type of complications were recorded. Minor complications were classified as Clavien II or less, while major complications were Grade III or greater. Univariate and multivariate analyses determined variables associated with complications. RESULTS: Fifty-seven men and 35 women with a median age of 70 years were included. Three-quarters of the cohort underwent a minimally invasive RNU and 45% had a regional lymph node dissection. Final pathology noted that 53% had muscle-invasive and 70% had high grade UTUC. Overall, 35 patients (38%) experienced complications within 30 days of RNU including 11 (12%) with major complications. Ten patients (11%) had multiple complications. Hematologic, gastrointestinal, and infectious etiologies comprised over 75% of complications. On univariate analysis, patient age, ECOG performance status, surgical approach, non-organ confined disease, and cardiac history were associated with complications. In a multivariate model including these variables, only ECOG ≥ 2 (OR 3.9, 95% CI 1.6-7.4, p < 0.001) was independently associated with post-RNU complications. CONCLUSION: Almost 40% of patients in this cohort experienced a perioperative complication after RNU. One-third of complications were Clavien III or greater. Poor performance status conferred a four-fold greater risk of a perioperative complication. Such knowledge may guide patient counseling and surgical expectations for the postoperative period.

Rationale and timing of perioperative chemotherapy for upper-tract urothelial carcinoma.

Radical surgery alone for high-risk upper-tract urothelial carcinoma (UTUC) is often inadequate for long-term cancer control. Numerous studies implicate failure presumably attributable to metastatic disease. Therefore, multimodal therapy by way of perioperative chemotherapy is integral to improve cancer outcomes and disease-specific survival. Despite this apparent reality, there is lack of consensus regarding which patients will need additional therapy, optimal timing for delivery of agents, and specific regimens to be utilized. Progress is being made, however, to explore these issues both by extrapolation from the bladder cancer literature as well as studying outcomes from retrospective UTUC series. Prospectively accruing studies for both neoadjuvant and adjuvant chemotherapy will likely mature in the next 5 years thereby providing higher level data to better guide standard of care.

High rates of advanced disease, complications, and decline of renal function after radical nephroureterectomy.

OBJECTIVES: Recurrences remain common following radical nephroureterectomy (RNU) for locally advanced upper-tract urothelial carcinoma (UTUC). We review a cohort of RNU patients to identify the incidence of locally advanced disease, decline in renal function, complications, and utilization of adjuvant chemotherapy (AC). METHODS: Institutional databases from 7 academic medical centers identified 414 RNU patients treated between 2003 and 2012 who had not received neoadjuvant chemotherapy. Glomerular filtration rate was estimated using the Modification of Diet in Renal Disease equation. Complications were classified according to the modified Clavien system. Cox proportional hazard modeling and Kaplan-Meier analysis determined factors associated with cancer-specific survival. RESULTS: Of 414 patients, 177 (43%) had locally advanced disease, including 118 pT3N0/Nx, 13 pT4N0/Nx, and 46 pTanyN+. Estimated 3- and 5-year cancer-specific survival was 47% and 34%, respectively. Only 31% of patients with locally advanced UTUC received AC. Mean estimated glomerular filtration rate declined from 59 to 51 ml/min/1.73 m(2) following RNU, including a new-onset decline below 60 and 45 ml/min/1.73 m(2) in 25% and 15% of patients, respectively (P<0.001 for both). Complications occurred in 46 of 177 (26%) patients, of which one-quarter were grade III or IV. Increasing age (Hazard Ratio (HR) 1.4, P = 0.03), positive surgical margins (HR 2.1, P = 0.01), and positive lymph nodes (HR 4.3, P<0.001) were associated with an increased risk of death from UTUC, whereas receipt of AC (HR 0.85, P = 0.05) was associated with a decrease in UTUC mortality. CONCLUSIONS: Under one-third of RNU patients with locally advanced UTUC cancers received AC. Perioperative complications and decline in renal function may have contributed to this low rate. Such data further underscore the need for continued discussion regarding the use of chemotherapy in a neoadjuvant setting for appropriately selected patients with UTUC.

Significant variability in 10-year cumulative radiation exposure incurred on different surveillance regimens after surgery for pT1 renal cancers: yet another reason to standardize protocols?

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The topic of radiation safety has been hotly debated not only in the mainstream media, but also in the urological literature. Radiation exposure has been examined in urological diseases such as testicular cancer and urinary stone disease, with resultant recommendations for modifying surveillance imaging. Radiation risk with respect to surveillance regimens after RCC surgery has yet to be examined. We consider this largely to be a result of RCC typically affecting older patients in whom cumulative radiation exposure may be less of a consideration. However, current population data emphasize that RCC diagnosis and therapy have an increasing impact upon younger patients with a longer life expectancy after treatment. Therefore, radiation considerations in this cohort of patients may be significant. OBJECTIVE: To determine the 10-year cumulative radiation exposure incurred on different surveillance imaging protocols after surgery for pT1 renal cell carcinoma (RCC). MATERIALS AND METHODS: The PubMed database was queried for surveillance protocols after surgery for RCC. There were two index lesions that were selected: (i) pT1a 3 cm, Fuhrman 2, clear cell and (ii) pT1b 5 cm, Fuhrman 3, clear cell. Exposure for single-phase chest computed tomography (CT), abdominal CT and chest X-ray were 7, 8 and 0.1 mSV, respectively. Calculations assumed biphasic CT scans, negative surgical margins and an Eastern Cooperative Oncology Group status of ≤1. RESULTS: In total, 12 published surveillance regimens were identified. For the first lesion (pT1a, clear cell, Fuhrman 2), we observed significant variability in the proposed regimens, ranging from no imaging to several CT scans of both chest and abdomen. Cumulative incurred radiation exposure for this index patient was in the range 0-102 mSv (mean, 34 mSv). When considering the second tumour (pT1b, clear cell, Fuhrman 3), all studies recommended some form of follow-up imaging, although regimens once again varied from annual chest X-ray to multiple CT scans of chest and abdomen. Cumulative incurred radiation exposure in this scenario was in the range 0.5-450 mSv (mean, 89 mSV). CONCLUSIONS: Surveillance protocols after surgery for early-stage RCC result in widely divergent levels of radiation exposure. Such considerations are increasingly paramount given concerns of radiation-induced secondary malignancies and present another reason to standardize follow-up protocols.

Residual fragments following ureteroscopic lithotripsy: incidence and predictors on postoperative computerized tomography.

PURPOSE: Residual fragments following ureteroscopy for calculi may contribute to stone growth, symptoms or additional interventions. We reviewed our experience with ureteroscopy for calculus disease to define the incidence and establish factors predictive of residual fragments. MATERIALS AND METHODS: Records associated with 667 consecutive ureteroscopic lithotripsy procedures for upper urinary calculi were reviewed. In 265 procedures (40%) computerized tomography was done between 30 and 90 days postoperatively. They comprised the study group. Residual fragments were defined as any residual ipsilateral stone greater than 2 mm. RESULTS: Included in the study were 121 men and 127 women with a mean age of 47 years. Mean target stone diameter was 7.6 mm. The stone location was the kidney in 30% of cases, ureter in 50%, and kidney and ureter in 20%. Residual fragments were detected on computerized tomography after 101 of 265 procedures (38%). Pretreatment stone size was associated with residual fragments at a rate of 24%, 40% and 58% for stones 5 or less, 6 to 10 and greater than 10 mm, respectively (p <0.001). Additionally, stone location in the kidney (p <0.001) or the kidney and ureter (p = 0.044), multiple calculi (p = 0.003), longer operative time (p = 0.008) and exclusive use of flexible ureteroscopy (p = 0.029) were associated with residual fragments. In a multivariate model only pretreatment stone diameter greater than 5 mm was independently associated with residual fragments after ureteroscopy (diameter 6 to 10 and greater than 10 mm OR 2.03, p = 0.03 and OR 3.74, p = 0.003, respectively). CONCLUSIONS: Of patients who underwent ureteroscopic lithotripsy for calculi 38% had residual fragments by computerized tomography criteria, including more than 50% with stones 1 cm or greater. Such data may guide expectations regarding the success of ureteroscopy in attaining stone-free status.

Complications following prostate needle biopsy requiring hospital admission or emergency department visits - experience from 1000 consecutive cases.

OBJECTIVE: • To review a contemporary cohort of patients undergoing a transrectal ultrasound-guided prostate needle biopsy (TRUS PNBx) at a single centre to determine the incidence of major complications necessitating hospital admission or emergency department (ED) visits. PATIENTS AND METHODS: • The charts of 1000 consecutive patients undergoing TRUS PNBx were reviewed. • All patients received peri-procedural antibiotic prophylaxis with either ciprofloxacin or co-trimoxazole. • Hospital admission and ED visits within 30 days of the procedure were identified for indication, management and outcome. • Patient comorbidities and biopsy characteristics were reviewed for association with complications. RESULTS: • Of the 1000 patients, 25 (2.5%) had post-biopsy complications requiring hospital admission or an ED visit. • Indications included twelve patients (1.2%) with urosepsis, eight (0.8%) with acute urinary retention requiring urethral catheterization, four (0.4%) with gross haematuria requiring bladder irrigation for <24 h, and one (0.1%) with a transient ischaemia attack 1 day after biopsy. • Patients with urosepsis had an average hospitalization of 5 days, and 75% carried quinolone-resistant Escherichia coli organisms. • All patients with urinary retention had catheters removed within 10 days. No patients with haematuria required a blood transfusion. • No demographic or biopsy variables were particularly associated with development of a post-procedure complication. CONCLUSIONS: • In this large contemporary series of TRUS PNBx, we observed a 2.5% rate of major complications requiring hospital admission or an ED visit. • No clinical or biopsy variables were directly associated with development of complications. • These data may be valuable when counselling patients before biopsy.

Variable prostate-specific antigen management patterns by nonurologist providers at a tertiary care medical center.

OBJECTIVES: To determine prostate-specific antigen (PSA) management patterns of nonurologist providers. Urologists are involved in the management of men's prostate health. In practice, nonurology providers are more likely to see patients in the screening setting. METHODS: Survey questions were designed to evaluate a nonurologist's approach to PSA screening. The survey instrument was distributed to physicians and physician extenders in fields of internal medicine and family practice at a tertiary-care medical center. RESULTS: Of 116 nonurologist providers, 86 (74%) completed the survey. There was variability with respect to the age at which to screen the index patient (asymptomatic white man without a prostate cancer family history): 16% initiated screening at 41-50 years of age and 77% at 51-60 years. Additionally, heterogeneity was found with regard to categorizing an elevated PSA level, with 62% of providers using an absolute PSA cutoff of >4 ng/mL and only 27% citing age-specific criteria. When diagnosing an asymptomatic man with an elevated PSA level, most providers will recheck PSA in 3-6 months (38%) or initiate a trial of empiric antibiotics (30%). Only a smaller fraction will refer the patient to a urologist (21%) or repeat PSA test immediately within 2-4 weeks (11%). CONCLUSIONS: We noted variability in PSA management patterns by nonurologists. Only 27% of providers used age-specific criteria, and almost 70% managed an elevated value by rechecking at a delayed interval or initiating a trial of antibiotics. This suggests that education might be necessary to create uniformity in PSA screening amongst nonurologists.

Current status of ablative techniques for small renal masses.

The past few decades have witnessed a steady increase in the number of newly diagnosed small renal masses. Although historically managed by surgical resection, many of these small renal masses are now noted to be amenable to less invasive treatment modalities including thermal ablation or active surveillance. Contemporary series suggest that renal thermal ablation (including cryoablation or radiofrequency ablation), when selectively employed, can maintain oncologic efficacy comparable to extirpation while minimizing complications and treatment morbidity. Therefore, as the incidence of small renal masses in elderly comorbid patients rises, it is likely we will see ablative techniques assume a greater role in management.

The role of lymphadenectomy for upper tract urothelial carcinoma.

Regional lymphadenectomy, with both its diagnostic and therapeutic roles, serves as an integral component of the management of many malignancies. Extended pelvic lymph node dissection (LND) is the standard of care for urothelial carcinoma of the bladder, with the extent of lymphadenectomy correlating positively with cancer-related outcomes. Given their histologic similarities with bladder cancer, it is reasonable to hypothesize that a similar relationship exists for upper tract urothelial carcinomas (UTUCs). However, the data published to date have failed to consistently demonstrate a therapeutic benefit of regional LND for UTUC. As a consequence, utilization of regional lymphadenectomy remains at the discretion of the surgeon, the extent of LND lacks standardization, and its clinical utility continues to be debated. In order to better clarify the existing data, we present a review of the role of regional lymphadenectomy in patients with UTUC.

Serological screening and toxoplasmosis exposure factors among pregnant women in the Democratic Republic of Sao Tome and Principe.

The seroprevalence of Toxoplasma gondii infection among pregnant women in the Democratic Republic of Sao Tome and Principe (DRSTP) from November 2003 to March 2004 was determined by detection of serum anti-T. gondii antibodies. A short questionnaire interview for pregnant women was performed to investigate risk factors associated with T. gondii infection, including consumption of raw meat or unwashed vegetables, drinking unboiled water and keeping pets (cats and dogs). The overall seroprevalence of T. gondii infection was high (75.2%; 375/499). The older age group of > or =35 years had a significantly higher seroprevalence (85.7%; 54/63) than that of the younger age group of 15-25 years (70.4%; 178/253) (odds ratio 2.5, 95% CI 1.2-5.4; P=0.01). No significant difference in the seroprevalence of T. gondii infection was found between the pregnant women with and without exposure to the risk factors studied. However, among pregnant women with high antibody titers of > or =1:1024, it seemed likely that continual contact with pets and consumption of oocyst-contaminated water or raw unwashed vegetables rather than tissue cysts in meat was the primary route of infection. The incidence of congenital toxoplasmosis in unborn babies should be intensively monitored in the DRSTP.

Seroprevalence of Toxoplasma gondii infection among pre-schoolchildren aged 1-5 years in the Democratic Republic of Sao Tome and Principe, Western Africa.

The prevalence status of Toxoplasma gondii infection in children of the Democratic Republic of Sao Tome and Principe (DRSTP), Western Africa, is unknown to date. A serologic survey of T. gondii infection among pre-schoolchildren aged <5 years in the DRSTP was assessed by the latex agglutination (LA) test from November 2003 to March 2004. The overall seroprevalence of T. gondii infection was not low, reaching 21.49% (26/121). No significant gender difference in seroprevalence was found between boys (19.30%; 11/57) and girls (23.44%; 15/64) (chi2 = 0.31, P = 0.58). The older age group of 4-5 years had significantly higher seroprevalence (36.67%; 11/30) than the younger age group of <2 years (10.34%; 3/29) (chi2 = 5.64, P = 0.02). It was noteworthy that the majority of seropositive boys (90.91%; 10/11) or older children aged > or = 2 years (82.61%; 19/23) had high LA titres of > or = 1:1024, indirectly indicating acute Toxoplasma infection. This study is the first report indicating that T. gondii infection is not low in pre-schoolchildren aged <5 years in the DRSTP. Whether the DRSTP pre-schoolchildren acquire T. gondii infection through constant exposure to the parasite from their daily activities owing to poor environmental hygiene should be further evaluated.