Developing research skills in medical students online using an active research study.

BACKGROUND: Developing research skills and scholarship are key components of medical education. The COVID-19 pandemic necessitated that all teaching be delivered online. We introduced an approach to small group teaching in the academic year 2020-2021 online which involved students in an active (ongoing) research study to develop their research skills. METHODS: We acquired student feedback to evaluate their perspectives quantitatively on development of research and scholarship skills, teaching content and format, and tutor performance using this teaching approach. In addition, we captured free text responses from both students and tutors on the positives and negatives of our course, and their suggested improvements. We also compared summative assessment marks for the online/active research course (2020-2021) with those obtained from previous (2017-2019) and subsequent (2021-2023) teaching sessions. RESULTS: Students were largely positive about most aspects of the online course utilising an active research study (n = 13). Students agreed that they were able to acquire research skills, particularly related to data analysis, transferable skills, and giving scientific presentations. A one-way ANOVA revealed no significant difference for assessment marks across all five teaching years (two years prior and two years following the online/active research course), indicating that the course achieved the learning outcomes. Students enjoyed the convenience of online teaching and the availability of course resources, but least liked the lack of in-person interaction and laboratory training. Tutors enjoyed the collaborative aspects of online teaching, but least liked the lack of face-to-face interactions with students. CONCLUSIONS: Our study demonstrates that delivering online teaching which involves students in active research engages and motivates them to develop their research and scholarship skills. We recommend that educators consider incorporating a current research study in their undergraduate courses as this can enhance the student learning experience as well as the research project itself.

The negative impact of COVID-19 on working memory revealed using a rapid online quiz.

Although coronavirus disease 2019 (COVID-19) affects the respiratory system, it can also have neurological consequences leading to cognitive deficits such as memory problems. The aim of our study was to assess the impact of COVID-19 on working memory function. We developed and implemented an online anonymous survey with a working memory quiz incorporating aspects of gamification to engage participants. 5428 participants successfully completed the survey and memory quiz between 8th December 2020 and 5th July 2021 (68.6% non-COVID-19 and 31.4% COVID-19). Most participants (93.3%) completed the survey and memory quiz relatively rapidly (mean time of 8.84 minutes). Categorical regression was used to assess the contribution of COVID status, age, time post-COVID (number of months elapsed since having had COVID), symptoms, ongoing symptoms and gender, followed by non-parametric statistics. A principal component analysis explored the relationship between subjective ratings and objective memory scores. The objective memory scores were significantly correlated with participants' own assessment of their cognitive function. The factors significantly affecting memory scores were COVID status, age, time post-COVID and ongoing symptoms. Our main finding was a significant reduction in memory scores in all COVID groups (self-reported, positive-tested and hospitalized) compared to the non-COVID group. Memory scores for all COVID groups combined were significantly reduced compared to the non-COVID group in every age category 25 years and over, but not for the youngest age category (18-24 years old). We found that memory scores gradually increased over a period of 17 months post-COVID-19. However, those with ongoing COVID-19 symptoms continued to show a reduction in memory scores. Our findings demonstrate that COVID-19 negatively impacts working memory function, but only in adults aged 25 years and over. Moreover, our results suggest that working memory deficits with COVID-19 can recover over time, although impairments may persist in those with ongoing symptoms.

A comparative experimental study of visual brain event-related potentials to a working memory task: virtual reality head-mounted display versus a desktop computer screen.

Virtual reality head mounted display (VR HMD) systems are increasingly utilised in combination with electroencephalography (EEG) in the experimental study of cognitive tasks. The aim of our investigation was to determine the similarities/differences between VR HMD and the computer screen (CS) in response to an n-back working memory task by comparing visual electrophysiological event-related potential (ERP) waveforms (N1/P1/P3 components). The same protocol was undertaken for VR HMD and CS with participants wearing the same EEG headcap. ERP waveforms obtained with the VR HMD environment followed a similar time course to those acquired in CS. The P3 mean and peak amplitudes obtained in VR HMD were not significantly different to those obtained in CS. In contrast, the N1 component was significantly higher in mean and peak amplitudes for the VR HMD environment compared to CS at the frontal electrodes. Significantly higher P1 mean and peak amplitudes were found at the occipital region compared to the temporal for VR HMD. Our results show that successful acquisition of ERP components to a working memory task is achievable by combining VR HMD with EEG. In addition, the higher amplitude N1/P1 components seen in VR HMD indicates the potential utility of this VR modality in the investigation of early ERPs. In conclusion, the combination of VR HMD with EEG/ERP would be a useful approach to advance the study of cognitive function in experimental brain research.

Increased cardio-ankle vascular index values in patients with acute branch retinal vein occlusion.

Purpose: Patients with retinal vein occlusions (RVOs) are at increased risk of cardiovascular disease. Arterial stiffness is an independent risk factor for cardiovascular events. Our aim is to evaluate the arterial stiffness in patients with acute branch retinal vein occlusion (BRVO) by using cardio-ankle vascular index (CAVI). Methods: This prospective study included 42 patients (18 male, mean age 57.5 ± 11.3) with acute BRVO and a matched control group (by age, sex, and presence of hypertension) with 70 (26 male, mean age 54.4 ± 9.4) patients. All patients and control subjects underwent complete ocular examination and CAVI measurement. BRVO was diagnosed based on clinical examination. Results: There were no significant differences between baseline clinical and demographic characteristics, echocardiographic measurements of left ventricular ejection fraction, systolic and diastolic blood pressure, and body mass index of the BRVO and control group. Both right and left CAVI values were found significantly higher in BRVO group (7.94 ± 1.53 vs 7.28 ± 1.25, P < 0.05 and 8.06 ± 1.41 vs 7.30 ± 1.26, P < 0.05, respectively). There were no significant difference in right and left ankle-brachial index values between the groups (1.05 ± 0.10 vs 1.06 ± 0.08, P = 0.46 and 1.04 ± 0.12 vs 1.05 ± 0.08, P = 0.46, respectively). Conclusion: Arterial stiffness is an important mediator of cardiovascular diseases. We found that CAVI which is a novel marker of the arterial stiffness is increased in patients with acute BRVO compared to controls.

Marker-free optical stereo motion tracking for in-bore MRI and PET-MRI application.

PURPOSE: Prospective motion correction is arguably the "silver bullet" solution for magnetic resonance imaging (MRI) studies impacted by motion, applicable to almost any pulse sequence and immune from the spin history artifacts introduced by a moving object. In prospective motion correction, the magnetic field gradients and radio frequency waveforms are adjusted in real time in response to measured head motion so as to maintain the head in a stationary reference frame relative to the scanner. Vital for this approach are accurate and rapidly sampled head pose measurements, which may be obtained optically using cameras. However, most optical methods are limited by the need to attach physical markers to the skin, which leads to decoupling of head and marker motion and reduces the effectiveness of correction. In this work we investigate the feasibility and initial performance of a stereo-optical motion tracking method which does not require any attached markers. METHODS: The method relies on detecting distinctive natural features or amplified features (using skin stamps) directly on the forehead in multiple camera views, and then deriving pose estimates via a 3D-2D registration between the skin features and a database of forehead landmarks. To demonstrate the feasibility and potential accuracy of the marker-free method for discrete (step-wise) head motion, we performed out-of-bore and in-bore experiments using robotically and manually controlled phantoms in addition to in-bore testing on human volunteers. We also developed a convenient out-of-bore test bed to benchmark and optimize the motion tracking performance. RESULTS: For out-of-bore phantom tests, the pose estimation accuracy (compared to robotic ground truth) was 0.14 mm and 0.23 degrees for incremental translation and rotation, respectively. For arbitrary motion, the pose accuracy obtained using the smallest forehead feature patch was equivalent to 0.21 ± 0.11 mm positional accuracy in the striatum. For in-bore phantom experiments, the accuracy of rigid-body motion parameters (compared to wireless MR-sensitive markers) was 0.08-0.41 ± 0.18 mm/0.05-0.3 ± 0.12 deg and 0.14-0.16 ± 0.12 mm/0.08-0.17 ± 0.08 deg for the small and large feature patches, respectively. In vivo results in human volunteers indicated sub-millimeter and sub-degree pose accuracy for all rotations and translations except the depth direction (max error 1.8 mm) when compared to a registration-based approach. CONCLUSIONS: In both bench-top and in vivo experiments we demonstrate the feasibility of using very small feature patches directly on the skin to obtain high accuracy head pose measurements needed for motion-correction in MRI brain studies. The optical technique uses in-bore cameras and is consistent with the limited visibility of the forehead afforded by head coils used in brain imaging. Future work will focus on optimization of the technique and demonstration in prospective motion correction.

Multiplexed ion beam imaging (MIBI) for characterization of the tumor microenvironment across tumor types.

An ability to characterize the cellular composition and spatial organization of the tumor microenvironment (TME) using multiplexed IHC has been limited by the techniques available. Here we show the applicability of multiplexed ion beam imaging (MIBI) for cell phenotype identification and analysis of spatial relationships across numerous tumor types. Formalin-fixed paraffin-embedded (FFPE) samples from tumor biopsies were simultaneously stained with a panel of 15 antibodies, each labeled with a specific metal isotope. Multi-step processing produced images of the TME that were further segmented into single cells. Frequencies of different cell subsets and the distributions of nearest neighbor distances between them were calculated using this data. A total of 50 tumor specimens from 15 tumor types were characterized for their immune profile and spatial organization. Most samples showed infiltrating cytotoxic T cells and macrophages present amongst tumor cells. Spatial analysis of the TME in two ovarian serous carcinoma images highlighted differences in the degree of mixing between tumor and immune cells across samples. Identification of admixed PD-L1+ macrophages and PD-1+ T cells in an urothelial carcinoma sample allowed for the detailed observations of immune cell subset spatial arrangement. These results illustrate the high-parameter capability of MIBI at a sensitivity and resolution uniquely suited to understanding the complex tumor immune landscape including the spatial relationships of immune and tumor cells and expression of immunoregulatory proteins.

A within-coil optical prospective motion-correction system for brain imaging at 7T.

PURPOSE: Motion artifact limits the clinical translation of high-field MR. We present an optical prospective motion correction system for 7 Tesla MRI using a custom-built, within-coil camera to track an optical marker mounted on a subject. METHODS: The camera was constructed to fit between the transmit-receive coils with direct line of sight to a forehead-mounted marker, improving upon prior mouthpiece work at 7 Tesla MRI. We validated the system by acquiring a 3D-IR-FSPGR on a phantom with deliberate motion applied. The same 3D-IR-FSPGR and a 2D gradient echo were then acquired on 7 volunteers, with/without deliberate motion and with/without motion correction. Three neuroradiologists blindly assessed image quality. In 1 subject, an ultrahigh-resolution 2D gradient echo with 4 averages was acquired with motion correction. Four single-average acquisitions were then acquired serially, with the subject allowed to move between acquisitions. A fifth single-average 2D gradient echo was acquired following subject removal and reentry. RESULTS: In both the phantom and human subjects, deliberate and involuntary motion were well corrected. Despite marked levels of motion, high-quality images were produced without spurious artifacts. The quantitative ratings confirmed significant improvements in image quality in the absence and presence of deliberate motion across both acquisitions (P < .001). The system enabled ultrahigh-resolution visualization of the hippocampus during a long scan and robust alignment of serially acquired scans with interspersed movement. CONCLUSION: We demonstrate the use of a within-coil camera to perform optical prospective motion correction and ultrahigh-resolution imaging at 7 Tesla MRI. The setup does not require a mouthpiece, which could improve accessibility of motion correction during 7 Tesla MRI exams.

Rigid Motion Correction for Brain PET/MR Imaging using Optical Tracking.

A significant challenge during high-resolution PET brain imaging on PET/MR scanners is patient head motion. This challenge is particularly significant for clinical patient populations who struggle to remain motionless in the scanner for long periods of time. Head motion also affects the MR scan data. An optical motion tracking technique, which has already been demonstrated to perform MR motion correction during acquisition, is used with a list-mode PET reconstruction algorithm to correct the motion for each recorded event and produce a corrected reconstruction. The technique is demonstrated on real Alzheimer's disease patient data for the GE SIGNA PET/MR scanner.

Reduced field of view echo-planar imaging diffusion tensor MRI for pediatric spinal tumors.

OBJECTIVE: Spine MRI is a diagnostic modality for evaluating pediatric CNS tumors. Applying diffusion-weighted MRI (DWI) or diffusion tensor imaging (DTI) to the spine poses challenges due to intrinsic spinal anatomy that exacerbates various image-related artifacts, such as signal dropouts or pileups, geometrical distortions, and incomplete fat suppression. The zonal oblique multislice (ZOOM)-echo-planar imaging (EPI) technique reduces geometric distortion and image blurring by reducing the field of view (FOV) without signal aliasing into the FOV. The authors hypothesized that the ZOOM-EPI method for spine DTI in concert with conventional spinal MRI is an efficient method for augmenting the evaluation of pediatric spinal tumors. METHODS: Thirty-eight consecutive patients (mean age 8 years) who underwent ZOOM-EPI spine DTI for CNS tumor workup were retrospectively identified. Patients underwent conventional spine MRI and ZOOM-EPI DTI spine MRI. Two blinded radiologists independently reviewed two sets of randomized images: conventional spine MRI without ZOOM-EPI DTI, and conventional spine MRI with ZOOM-EPI DTI. For both image sets, the reviewers scored the findings based on lesion conspicuity and diagnostic confidence using a 5-point Likert scale. The reviewers also recorded presence of tumors. Quantitative apparent diffusion coefficient (ADC) measurements of various spinal tumors were extracted. Tractography was performed in a subset of patients undergoing presurgical evaluation. RESULTS: Sixteen patients demonstrated spinal tumor lesions. The readers were in moderate agreement (kappa = 0.61, 95% CI 0.30-0.91). The mean scores for conventional MRI and combined conventional MRI and DTI were as follows, respectively: 3.0 and 4.0 for lesion conspicuity (p = 0.0039), and 2.8 and 3.9 for diagnostic confidence (p < 0.001). ZOOM-EPI DTI identified new lesions in 3 patients. In 3 patients, tractography used for neurosurgical planning showed characteristic fiber tract projections. The mean weighted ADCs of low- and high-grade tumors were 1201 × 10-6 and 865 × 10-6 mm2/sec (p = 0.002), respectively; the mean minimum weighted ADCs were 823 × 10-6 and 474 × 10-6 mm2/sec (p = 0.0003), respectively. CONCLUSIONS: Diffusion MRI with ZOOM-EPI can improve the detection of spinal lesions while providing quantitative diffusion information that helps distinguish low- from high-grade tumors. By adding a 2-minute DTI scan, quantitative diffusion information and tract profiles can reliably be obtained and serve as a useful adjunct to presurgical planning for pediatric spinal tumors.

Global Vascular Guidelines on the Management of Chronic Limb-Threatening Ischemia.

GUIDELINE SUMMARY: Chronic limb-threatening ischemia (CLTI) is associated with mortality, amputation, and impaired quality of life. These Global Vascular Guidelines (GVG) are focused on definition, evaluation, and management of CLTI with the goals of improving evidence-based care and highlighting critical research needs. The term CLTI is preferred over critical limb ischemia, as the latter implies threshold values of impaired perfusion rather than a continuum. CLTI is a clinical syndrome defined by the presence of peripheral artery disease (PAD) in combination with rest pain, gangrene, or a lower limb ulceration >2 weeks duration. Venous, traumatic, embolic, and nonatherosclerotic etiologies are excluded. All patients with suspected CLTI should be referred urgently to a vascular specialist. Accurately staging the severity of limb threat is fundamental, and the Society for Vascular Surgery Threatened Limb Classification system, based on grading of Wounds, Ischemia, and foot Infection (WIfI) is endorsed. Objective hemodynamic testing, including toe pressures as the preferred measure, is required to assess CLTI. Evidence-based revascularization (EBR) hinges on three independent axes: Patient risk, Limb severity, and ANatomic complexity (PLAN). Average-risk and high-risk patients are defined by estimated procedural and 2-year all-cause mortality. The GVG proposes a new Global Anatomic Staging System (GLASS), which involves defining a preferred target artery path (TAP) and then estimating limb-based patency (LBP), resulting in three stages of complexity for intervention. The optimal revascularization strategy is also influenced by the availability of autogenous vein for open bypass surgery. Recommendations for EBR are based on best available data, pending level 1 evidence from ongoing trials. Vein bypass may be preferred for average-risk patients with advanced limb threat and high complexity disease, while those with less complex anatomy, intermediate severity limb threat, or high patient risk may be favored for endovascular intervention. All patients with CLTI should be afforded best medical therapy including the use of antithrombotic, lipid-lowering, antihypertensive, and glycemic control agents, as well as counseling on smoking cessation, diet, exercise, and preventive foot care. Following EBR, long-term limb surveillance is advised. The effectiveness of nonrevascularization therapies (eg, spinal stimulation, pneumatic compression, prostanoids, and hyperbaric oxygen) has not been established. Regenerative medicine approaches (eg, cell, gene therapies) for CLTI should be restricted to rigorously conducted randomizsed clinical trials. The GVG promotes standardization of study designs and end points for clinical trials in CLTI. The importance of multidisciplinary teams and centers of excellence for amputation prevention is stressed as a key health system initiative.

Clinical course of abdominal aortic aneurysms in Behçet disease: a retrospective analysis.

Arterial aneurysms are rare manifestations of Behçet Disease (BD) with high morbidity and mortality. This study aimed to investigate the clinical course of BD patients with abdominal aortic aneurysms (AAA). We retrospectively searched charts of BD patients, followed up between 1988 and 2011, to identify those with AAA with at least 6-month clinical and radiological follow-up data. Chart review revealed 12 patients (11 males) with AAA amongst 1224 patients; follow-up data from 11 patients were available. The most common symptoms were lower back and abdominal pain. The only pre-treatment complication was a spontaneous rupture. All but one patient received corticosteroid and cyclophosphamide pulses for the induction, and corticosteroid and azathioprine for the maintenance treatment; one patient received only the maintenance treatment. Two patients had surgical graft interposition, without postoperative complications. Seven patients had endovascular stenting; five of them (71.4%) showed radiological regression after 32.5 (13.4-53.8) months, while four (57%) had clinical improvement after 11.8 (0.2-29.4) months. However, one non-responsive patient developed stent infection and exsanguinated during percutaneous drainage, and one patient developed femoral artery pseudo-aneurysm at the catheter insertion site. Another patient developed a new aneurysm under the maintenance treatment. Medical treatment alone yielded radiological regression in one of two patients. Current immunosuppressive, surgical or endovascular approaches can provide clinical and radiological improvements lately in BD patients with AAA. Furthermore, complication rates seem to be high with interventional approaches. These findings suggest an unmet need for safer alternative treatments.

Results and functional outcomes of en-bloc resection and vascular reconstruction in extremity musculoskeletal tumors.

OBJECTIVES: This paper aims to evaluate the extremity function and vascular outcome after limb-sparing surgery for extremity musculoskeletal tumors invading vascular structure required reconstruction. METHODS: Of the 507 patients with musculoskeletal tumors, who underwent surgery between 2004 and 2007, 17 (3,3%) patients with major vessel involvement were included in the study. The mean age was 37.8 ± 14.5, with a female/male ratio of 8/9. Thirteen (76.4%) patients had Stage IIb disease, and 2 (11,7%) patients had Stage III disease. In 2 (11,7%) patients have locally aggressive tumor that had Stage 3. Fifteen (88.2%) of the cases involved lower extremity, whilst 2 (11.8%) of them involved upper extremity. An arterial reconstruction was carried out in all patients. Wide tumor resection and endoprosthetic reconstruction were performed in 6 (35.2%) patients. Other 11 (65.8%) patients were treated with wide resection and soft tissue reconstruction. Postoperative data included; perioperative morbidities such as bleeding, infection, graft thrombosis, rupture, metastatic local recurrence and mortality. Ankle brachial index (ABI) and color-flow-duplex-scan (CFDS) were done at the final follow-up of the study, in order to prove the efficacy of reconstruction. Functional outcome was evaluated with International Society of Limb Salvage (ISOLS) criteria. RESULTS: The mean follow-up was of 39 months (range 3-120). Perioperative complications were arterial graft thrombosis occurred in 3 (17.6%) patients treated acutely with thrombectomy, uncontrolled deep wound infection occurred in 2 patients whom extremities were amputated. The most frequent complication after surgery was limb edema according to possibly venous and lymphatic obstruction, staged as C1, C2 and C3 disease was established in 6 patients (two patients in each group), and 1 patient was classified as C6 disease. Three (17.6%) patients had local recurrence (1/3 patient died and 2/3 (11.7%) patients underwent transfemoral amputation). At the last follow-up, 9 (52.9%) patients were alive without evidence of disease, 8 (47.1%) patients were died due to primary disease. There were 8 (47.1%) patients alive with an intact limb. Although functional outcome scores were satisfactory, emotional acceptance scores were low. The limb salvage probability was 74.0%. CONCLUSION: Limb-sparing oncological surgery in musculoskeletal tumors with vascular invasion provides a satisfactory limb function, which may lead to an improved life quality. Arterial reconstruction has a high rate of patency in the long term. The surgeon should be aware of early perioperative complication related to vascular reconstruction and infection that effect on the rate of extremity survival. LEVEL OF EVIDENCE: Level IV, Therapeutic study.

Cutaneous analgesia before transradial access for coronary intervention to prevent radial artery spasm.

AIM: Transradial access (TRA) for coronary intervention is increasingly used in current clinical practice. The aim of the present study was to evaluate the hypothesis that cutaneous analgesia before TRA for coronary intervention at a puncture site 30 minutes before puncture can reduce patient discomfort and the incidence of radial artery spasm (RAS). METHODS: Patients (n=104) undergoing planned coronary interventions using TRA were prospectively randomized to receive either 1 mL of 1% lidocaine subcutaneously (n=52) (control group) or subcutaneous lidocaine plus 5% lidocaine cream (n=52) cutaneously 30 minutes before puncture (treatment group). The primary endpoint was angiographically or clinically confirmed RAS. Secondary endpoints were the occurrence of patient discomfort in the forearm during the procedure and access-site crossover to the femoral artery. Patient discomfort was quantified with a visual analogue scale (VAS) score. RESULTS: Fifty-two patients in the treatment group (60.5±9.4 years of age and 16 female) and 52 patients in the control group (60.4±9.7 years of age and 16 female) were included in the final analysis. Radial artery spasm occurrence decreased in the treatment group compared to the control group (26.9% vs 9.6%; p=0.04) accompanied by a VAS score of 3.7±1.8 in the treatment group and 4.9±2.0 in the control group; p=0.02. The access site crossover rate did not differ between the groups (7.6% vs 21.1%; p=0.09). CONCLUSION: Cutaneous analgesia before TRA for coronary interventions is associated with a substantial reduction in the RAS and the procedure-related level of patient discomfort.

Prospective motion correction using coil-mounted cameras: Cross-calibration considerations.

PURPOSE: Optical prospective motion correction substantially reduces sensitivity to motion in neuroimaging of human subjects. However, a major barrier to clinical deployment has been the time-consuming cross-calibration between the camera and MRI scanner reference frames. This work addresses this challenge. METHODS: A single camera was mounted onto the head coil for tracking head motion. Two new methods were developed: (1) a rapid calibration method for camera-to-scanner cross-calibration using a custom-made tool incorporating wireless active markers, and (2) a calibration adjustment method to compensate for table motion between scans. Both methods were tested at 1.5T and 3T in vivo. Simulations were performed to determine the required mechanical tolerance for repositioning of the camera. RESULTS: The rapid calibration method is completed in a short (<30 s) scan, which is carried out only once per installation. The calibration adjustment method requires no extra scan time and runs automatically whenever the system is used. The mechanical tolerance analysis indicates that most motion (90% reduction in voxel displacement) could be corrected even with far larger camera repositioning errors than are observed in practice. CONCLUSION: The methods presented here allow calibration of sufficient quality to be carried out and maintained with no additional technologist workload. Magn Reson Med 79:1911-1921, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Comparison of serum folate, 25-OH vitamin D, and calcium levels between pregnants with and without fetal anomaly of neural tube origin.

AIM: The aim of this study was to compare serum folate, vitamin B12, 25-OH vitamin D, and calcium levels between pregnants with and without fetal anomaly of neural tube origin. METHODS: One hundred seventy-eight pregnants were recruited for this study. Pregnants with and without sonographically detected fetal anomaly of neural tube origin were compared in terms of serum folate, vitamin B12, 25-OH vitamin D, and calcium levels. RESULTS: There were significant differences between groups with regard to age, serum 25 OH vitamin D, 1,25 OH vitamin D, folate, calcium, and B 12 levels. Multivariate regression analyses revealed significant associations between the serum 25 OH vitamin D level, age, and the neural tube defect (NTD). CONCLUSIONS: Vitamin D and the age of pregnants were significantly associated with the NTDs.