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Purpose: We investigated the mammographic, sonographic, and pathologic findings in metaplastic carcinoma of the breast., Methods: The mammographic (n = 16) and sonographic (n = 11) findings in 16 patients with metaplastic carcinoma of the breast were analyzed retrospectively along with pathologic findings. Whenever possible, results of preoperative fine-needle aspiration biopsy and immunohistochemical studies were obtained., Results: All patients presented with a palpable breast mass. The mean size of the lesions at pathologic examination was 4.2 cm. On mammography, 15 patients had a mass (1 patient had 2 masses), and 1 patient had only clustered microcalcifications without an associated mass. The mean longest diameter of the 16 masses on mammography was 4.6 cm. Eleven lesions (69%) were round to ovoid in shape, 13 lesions (81%) showed ill-defined or obscured margins, and 10 lesions (63%) showed associated architectural distortion. On sonography, 6 (55%) of 11 lesions were round to ovoid, 9 lesions (82%) had well-defined margins, and 6 lesions (55%) showed complex echogenicity with solid and cystic components. At pathologic examination, 4 of these 6 lesions showed hemorrhagic or cystic necrosis. Axillary lymph nodes were positive in 6 (40%) of 15 patients in whom axillary node dissection was performed., Conclusions: Metaplastic carcinoma of the breast manifests as a rapidly growing, mammographically ill-defined round mass with associated architectural distortion on mammograms. Complex echogenicity with solid and cystic components may be seen sonographically and is related to hemorrhagic or cystic necrosis seen pathologically., (Copyright 2000 John Wiley & Sons, Inc.)

Atrial natriuretic peptide (ANP) is a cardiac hormone that elicits a profound diuresis, natriuresis, and hypotension. As a preliminary study toward ANP gene therapy of cardiovascular disorders, we have cloned a cDNA for mouse preproANP and carried out expression studies in muscle cells. The expression cassette, which was flanked by ITRs from AAV-2, consisted of HCMV IE enhancer/promoter, preproANP gene, and polyadenylation signal from bovine growth hormone. We transfected this expression vector into primary skeletal myoblasts and examined the following points: (1) secretion of immunoreactive ANP, (2) biological activity, and (3) nature of secreted ANP(s). The conditioned media from cells transfected with ANP vector had significantly higher levels of irANP in comparison to mock control. The secreted irANP had biological activity as confirmed by the elevated level of intracellular cGMP in human umbilical vein endothelial cells. Reverse-phase HPLC analysis showed that the processed form of ANP was the predominant form. These results demonstrate that preproANP gene could be ectopically expressed and correctly processed in skeletal myoblasts, which has implications for development of muscle-based ANP gene therapy., (Copyright 2000 Academic Press.)

A novel methodology for the synthesis of poly(ethylene glycol) (PEG) prodrugs of amino-containing compounds has been developed which is based on the trimethyl lock lactonization reaction. These PEG-modified double prodrugs are water soluble, and by selective modification of the specifier or trigger, plasma half-lives can be adjusted at will to result in a wide range of values. Facile syntheses of ester, carbonate, and carbamate functionalities were accomplished and combined with greater or lesser degrees of steric hindrance in the spacer group, or on the aromatic framework, to achieve predictable ranges of drug concentration in plasma. In vivo screening of PEG prodrugs was done using a M109 syngeneic solid mouse tumor model. One of the PEG-daunorubicin prodrugs, with a half-life of 2 h, was evaluated in an in vivo solid tumor panel and found to be more efficacious against ovarian tumors (SKOV3) than equivalent amounts of daunorubicin.

We investigated the effect of Helicobacter pylori eradication on sideropenic refractory anaemia in adolescent girls with H. pylori-associated antral gastritis without evidence of haemorrhage or clinical symptoms other than sideropenic anaemia. We conducted an open therapeutic trial in 21 adolescent girls aged 15-17 y with sideropenic refractory anaemia, which was defined as iron-deficiency anaemia refractory to oral iron therapy for 3 mo. All subjects underwent gastroduodenal endoscopy. Thirteen patients with confirmed H. pylori infection were given a 2-wk course of triple therapy and 6 wk of oral ferrous sulfate. We compared the mean levels of haemoglobin and serum ferritin among the "initial sample" (the time when the sampling was done before treatment with oral iron), "before eradication" (the time prior to triple therapy for eradication after subjects had been given oral iron for 3 mo) and "after eradication" (the time when the follow-up endoscopy was performed) data in 11 subjects in whom H. pylori infection was eradicated. Haemoglobin levels (g/dl) were 8.6+/-1.9, 8.6+/-1.4 and 11.3+/-2.3, respectively. Serum ferritin levels (microg/l) were 4.6+/-2.4, 4.2+/-2.3 and 17.5+/-6.7, respectively. After eradication of H. pylori, mean levels of haemoglobin (p = 0.0002) and serum ferritin (p = 0.0002) showed a prominent increase between "before eradication" and "after eradication". In conclusion, adolescent girls with sideropenic refractory anaemia should be evaluated for H. pylori infection. If H. pylori infection is coexistent, its eradication along with iron supplementation could correct the anaemia.

The purpose of this study was to determine whether Helicobacter pylori infection can contribute to growth deficit, especially in pubescent children who need large amounts of iron for growth. A structured questionnaire was sent to the parents of 532 healthy children aged 10 to 15 years (mean 12.9) to obtain demographic information on the parents and the environment. Of the 532 questionnaires sent out, 375 (70.5%; 170 girls and 205 boys) were returned. After collecting blood samples from participants, haemoglobin, serum iron, total iron binding capacity, serum ferritin, and serum IgG antibodies to H pylori were measured. The effects of risk factors such as H pylori infection, iron deficiency anaemia, sex, socioeconomic status, type of house, and crowding index on growth were analysed using multiple regression analysis. Of 63 H pylori positive children, 18 (28.6%) were below the 25th centile values for height, compared with 63 of 312 (20.2%) H pylori negative children. The prevalence rate of H pylori infection was 15.5% (53 of 343) in children without iron deficiency anaemia and 31.3% (10 of 32) in those affected. The relative risk of short stature was 2.2 (95% confidence interval (CI), 1.0 to 4.8) for iron deficiency anaemia, and 1.4 (95% CI, 0.8 to 2.4) for H pylori infection. The mean height was significantly lower in the group having both H pylori infection and iron deficiency anaemia. Therefore, H pylori infection accompanied by iron deficiency anaemia, rather than H pylori infection per se, might delay pubertal growth.

Low molecular weight Poly(ethylene glycol) (PEG) (< 20,000)-drug conjugates, prepared over a 20-year period, have been scrutinized and their properties and efficacy reviewed. No commercial products have thus far been reported for these types of compounds. However, during the past 5 years a renaissance in the field of PEG-(anticancer) drug conjugates has taken place, initiated by the use of higher molecular weight PEGs (> 20,000), especially 40,000, which is estimated to have a plasma circulating half-life of approximately 8-9 h. This recent resuscitation of small organic molecule delivery by high molecular weight PEG conjugates was founded on meaningful in vivo testing using established tumor models and has led to a clinical candidate. Recent applications of high molecular weight PEG prodrug strategies to amino-containing drugs are also detailed.

Early diagnosis and treatment of Takayasu arteritis is important in prevention of serious complications. Spin-echo magnetic resonance imaging (MRI) can depict early wall thickening of the aorta and cine MRI can evaluate aortic valve function. Significant enhancement in and around the aorta and carotid arteries is observed on postcontrast MR images in acute phase Takayasu arteritis. In the chronic phase, contrast enhancement in the aortic wall stronger than in the myocardium suggests activity of the disease. Breath-hold contrast-enhanced three-dimensional MR angiography is very effective in noninvasive evaluation of luminal change of aortitis. Contrast-enhanced MRI and MR angiography have an important role in early diagnosis, activity determination, and follow-up of Takayasu arteritis. MRI and MR angiography can be utilized for initial diagnosis of Takayasu arteritis and replace catheterization angiography. J. Magn. Reson. Imaging 1999;10:751-757., (Copyright 1999 Wiley-Liss, Inc.)

One of the biological functions of lactoferrin is the modulation of the host defense systems, including cytokine production and immune responses. We have tested the effect of lactoferrin on the productions of tumor necrosis factor-alpha and nitric oxide in some cells. Lactoferrin itself did not induce either tumor necrosis factor-alpha production or nitric oxide production, but lipopolysaccharide-stimulated tumor necrosis factor-alpha production of macrophages and monocytes were inhibited by lactoferrin treatment combined with stimulant. The induction of nitric oxide synthesis in stimulated macrophages and vascular smooth muscle cells was not affected by the lactoferrin., (Copyright 1999 Wiley-Liss, Inc.)

This paper reports on the synthesis and in vivo oncolytic activity of a series of water-soluble acyl derivatives of polyethylene glycol (PEG) conjugated podophyllotoxin. Some analogs of the polymer conjugate showed significantly better activity in a murine leukemia model than native podophyllotoxin suspended in an intralipid emulsion. Additionally, when tested intravenously against a solid lung tumor (A549) model, some conjugated analogs were equivalent to the podophyllotoxin/intralipid emulsion, while those compounds demonstrating slower rates of plasma hydrolysis (in vitro) appeared to cause greater toxicity. There appeared to be an overall correlation between the in vivo antitumor activity of the conjugate and its rate of hydrolysis in vitro, with those showing faster release possessing greater antitumor activity. In conclusion, the solubilization and predictable release of podophyllotoxin from a PEG carrier was achieved and resulted in some derivatives demonstrating, at a minimum, equivalency with podophyllotoxin when administered on an equal molar basis. Further studies may be warranted to assess the PEG-conjugates pharmacokinetics and therapeutic indices in leukemic models.

A general methodology for synthesizing poly(ethylene glycol) (PEG) prodrugs of amino-containing compounds has been developed and constitutes the basis for solubilization of insoluble drugs, extending plasma circulating half-lives and, in the case of anticancer agents, apparent tumor accumulation. Thus, we have successfully designed PEG conjugated specifiers or "triggers" as part of a double-prodrug strategy that relies, first, on enzymatic separation of PEG followed by the classical and rapid 1,4- or 1, 6-benzyl elimination reaction releasing the amine (drug) bound in the form of a carbamate. The prodrug trigger was comprised of ester, carbonate, carbamate, or amide bonds in order to secure predictable rates of hydrolysis. Further refinement of the hydrolysis was accomplished by the introduction of steric hindrance through the use of ortho substituents on the benzyl component of the prodrug. This modification led to longer circulating plasma half-lives of the final tripartate form. The "ortho" effect also had the beneficial effect of directing nucleophilic attack almost exclusively to the activated benzyl 6-position of the heterobifunctional intermediates. In vivo testing of the PEG daunorubicin prodrugs (transport forms) prepared in the course of this study ultimately identified the type 1 carbamate (34b), with a circulating t(1/2) of 4 h, as the most effective derivative for solid tumor growth inhibition.

Objective: The objective of our study is to describe the mammographic and sonographic appearances of granulomatous mastitis., Conclusion: Granulomatous mastitis can mimic breast carcinoma clinically and mammographically, but the sonographic appearance of multiple clustered, often contiguous tubular hypoechoic lesions that are sometimes associated with a large hypoechoic mass should suggest the possibility of granulomatous mastitis.

Background: A few cases relating H. pylori infection to iron-deficiency anemia have been described recently. We investigated the role of H. pylori infection in iron-deficiency anemia in preadolescent children and adolescents., Patients and Methods: We conducted a double-blind, placebo-controlled therapeutic trial in 43 subjects (mean age, 15.4 years) with iron-deficiency anemia. Endoscopy was performed, and biopsy specimens were examined by urease test and histological analysis. Twenty-two of 25 H. pylori-positive patients were assigned randomly to three groups. Group A patients were given oral ferrous sulfate and a 2-week course of bismuth subcitrate, amoxicillin, and metronidazole. Group B patients were given placebo for iron and a 2-week course of triple therapy. Group C patients were given oral ferrous sulfate and a 2-week course of placebo. Iron status was reassessed 4 weeks and 8 weeks after the 2-week regimen ended., Results: Of the 43 subjects with iron-deficiency anemia, 25 (58.1%) had H. pylori in the antrum. Group A and B subjects, who received eradication therapy, showed a significant increase in hemoglobin level as compared with group C subjects at 8 weeks after therapy (p = .0086)., Conclusions: Treatment of H. pylori infection was associated with more rapid response to oral iron therapy as compared with the use of iron therapy alone. Such treatment also led to enhanced iron absorption even in those subjects who did not receive oral iron therapy.

Current MR techniques enable both anatomical and functional evaluations of the heart. Although it is rarely used as a primary diagnostic tool in pediatric cardiology, it can be used as a valuable adjunct to echocardiography and angiography. MRI is particularly useful in clarification of morphology of complex congenital heart diseases. It is the most accurate method of determination of visceral and atrial situs. It is easy to evaluate the systemic and pulmonary venous connections that are very important for the Fontan type of operation, especially in patients with visceral heterotaxy. It facilitates demonstration of diminutive pulmonary arteries in patients with pulmonary atresia. It clearly demonstrates juxtaposition of the atrial appendages that is often missed by echocardiography. The anatomy of the twisted atrioventricular connections is much more clear in MRI than in echocardiography. It enables en face imaging of ventricular septal defect that provides a surgical view. We find en face imaging particularly helpful in patients with double inlet left ventricle and transposition of the great arteries where the size of the ventricular septal defect governs the blood flow into the aorta. It is often advantageous to echocardiography in defining the type of univentricular atrioventricular connections by demonstrating the position and topology of the rudimentary chamber in difficult cases. In double outlet right ventricle, the spatial relationship of the ventricular septal defect to the great arterial valves can be clearly defined by visualizing the ventricular septal defect and the outlet septum in the same imaging plane.

To propose a hypothesis about the embryogenesis of the subaortic left innominate vein, the authors reviewed the radiologic features of 14 patients diagnosed with subaortic left innominate vein made by computed tomography or magnetic resonance imaging scan. The authors retrospectively analyzed the level of the aortic arch, associated aortic arch anomalies, and the presence or absence of obliteration of the prevascular space. A high aortic arch was seen in 10 patients, five with a cervical, two with a right and, one with a double aortic arch. The prevascular space was occupied by the aortic arch, the great arteries, or both in all 10 patients with a high arch. In the remaining four patients with a normal aortic arch, the prevascular space was preserved, but abnormal elongation of the aortic segment between the left common carotid artery and the left subclavian artery was seen in three. The authors postulate that precardinal anastomosis can develop in any pathway where there is the available space. In the presence of abnormal elongation of the aortic arch and resultant widening of the subaortic space, the chance of the development of a subaortic left innominate vein increases.

We reviewed the sonographic findings of 42 benign papillary lesions of the breast and correlated them with pathologic findings. Sonography detected 95% of papillomas (22 intraluminal masses, four extraductal masses, nine purely solid masses, and five mixed type masses). The sonographic margins of the mass were well defined in 20 lesions and poorly defined in 14 lesions. Poorly defined margins on sonography were frequent in papillomas with pathologic pseudoinvasion and in juvenile papillomatosis. Most benign papillary lesions of the breast have the sonographic findings suggestive of intraductal origin. The sonographic findings of papillary lesions correlated well with pathologic findings.

The aim of this study was to evaluate whether MR could depict pulmonary arterial anatomy in more detail than routine angiography in patients with congenital interruption or acquired occlusion of the left pulmonary artery or pulmonary atresia. This study included 10 patients with tetralogy of Fallot (n=6) or pulmonary atresia with ventricular septal defect (n=3) or aorticopulmonary window (n=1) diagnosed by cardiac angiography and MR. Surgical confirmation was made in seven patients. Interruption of the proximal left pulmonary artery, diagnosed at the time of evaluation, was found in seven patients and acquired obstruction of the hilar pulmonary artery (PA) was found in two at cardiac angiography. In the remaining one patient with pulmonary atresia and an occluded palliative shunt, the central PA was not visualized at angiography. MR showed 3-6 mm-sized hilar PAs in five and a central PA in a patient with pulmonary atresia. In 4 of 6 (67%) surgically-proven patients with congenital or acquired left PA obstruction, the status of the PA distal to the obstruction was correctly diagnosed with MR. In conclusion, MR is an effective modality in depicting sizable PAs when routine angiography fails to visualize the PA anatomy.

Conventional angiography has been used for diagnosis of Takayasu arteritis (TA). In early stage of TA, subtle inflammatory wall thickening of the aorta and its branches without significant stenosis may be the only morphologic change of TA. Magnetic resonance (MR) imaging appears to be useful in the diagnosis of early stage TA by visualizing concentric wall thickening of the vessels. T2-weighted images may show bright signal of edema in and around the inflamed vessel. Contrast media-enhanced MR shows enhanced wall of vessels even in chronic stage, which may indicate the activity of TA at the tissue level. MR angiography allows us noninvasive assessment of the vascular tree and it may replace conventional angiography.

Motor activity blocks the extrasynaptic expression of many genes in skeletal muscle, including those encoding ion channels, receptors, and adhesion molecules. Denervation reinduces transcription throughout the multinucleated myofiber, restoring the developmental pattern of expression, especially of the genes coding for the acetylcholine receptor. A screen for trans-acting factors binding to the enhancer region of the alpha-subunit gene of the acetylcholine receptor identified CTF4, a ubiquitously expressed and alternatively spliced chicken homologue of the human E protein transcription factor HTF4/HEB. Expression of the CTF4 locus closely parallels that of myogenin and acetylcholine receptor during development and maturation of skeletal muscle, but transcription is not similarly regulated by neuronal cues. Alternative splicing within the region encoding the transactivation domain generates two CTF4 isoforms with different tissue distributions, but similar binding affinities for the acetylcholine receptor alpha-subunit enhancer and similar transcriptional potential when complexed to myogenin. Direct injection of a myogenin, but not a MyoD, antisense expression vector into denervated skeletal muscle caused a significant decrease in the transcriptional activation of a depolarization-sensitive reporter gene. Similarly, injection of a CTF4, but less so of an E12, antisense expression vector impaired the denervation response, further implicating the involvement of a myogenin/CTF4 heterodimer in the expression of AChR genes in vivo.

An improved synthesis of the hindered PEG-camptothecin diester transport form has been achieved using the Mukaiyama reagent. We have also assessed the effect of changing the electronic configuration of the (d-position of PEG-camptothecin transport forms on the rates of hydrolysis of the pro-moiety, and attempted to correlate these differences to efficacy in two animal models. In addition to the simple substitution of N for O, other synthetic modifications of these atoms were accomplished by employing heterobifunctional linker groups. The half lives by disappearance (rates of hydrolysis) of the transport forms in buffer and rat plasma were determined. It was established that anchimeric assistance to hydrolytic breakdown of the pro-moiety occurs in a predictable manner for some of these compounds. Results for the new derivatives in a P388 murine leukemic model and HT-29 human colorectal xenograft study are also presented. The use of a glycine linker group was found to provide similar efficacy in rodent models to that of simple camptothecin 20-PEG ester, and displayed enhanced pharmacokinetics.

We experienced an unusual case of cardiac tamponde caused by a rupture of the coronary arteriovenous aneurysm in a 54-year-old woman. The patient was suffered from sudden chest pain and syncope, and was initially managed by pericardiocentesis following an echocardiogram which revealed a massive pericardial effusion with signs of cardiac tamponade. She was referred to our hospital under the impression of aortic dissection with cardiac tamponade. She underwent an emergency operation and was found to have a 2 x 2 cm sized bleeding cystic mass protruding from the proximal anterior descending coronary artery. The aneurysm was excised and the openings connected with the coronary artery and right ventricular outflow tract were closed with sutures from the inside of aneurysm. Subsequent coronary arteriography supported the diagnosis.

The purpose of this study was to determine the relationships between serum apolipoprotein concentration and family history of coronary or cerebral events in schoolchildren. In 269 primary schoolchildren aged 6-11 years (145 boys and 124 girls) we measured the blood concentrations of total cholesterol, apolipoproteins B and A-1, and lipoprotein(a), and questioned their parents about coronary or cerebral vascular events. Serum concentrations of apo B, A-1 and Lp(a) significantly increased with age. In children with serum cholesterol concentration > 5.18 mmol/L the concentrations of apo B, A-1, Lp(a) and apo B/apo A-1 ratio were significantly higher. The concentrations of total cholesterol, apo B, Lp(a), and apo B/apo A-1 ratio in the obese group (body weight 20% above the median body weight for age and height) differed significantly from those in the non-obese group. Serum concentrations of Lp(a) in the children who had positive family histories of coronary or cerebral events (geometric mean = 0.174 x/divided by 0.036g/L) and was significantly higher than that in the children with negative history (geometric mean = 0.086 x/divided by 0.36g/L). Family history was an independent and major contributor to high Lp(a). In evaluating children's lipid profiles, measurement of Lp(a) may help to identify children and their families at increased risk and this may facilitate the targeting of preventive measures.

The ability of magnetic resonance (MR) imaging to depict cardiovascular structures is especially useful in patients with congenital heart disease (CHD). While MR imaging techniques that focus on cardiac function or blood flow have not been used frequently in the evaluation of CHD, MR imaging has been useful in morphologic diagnosis of CHD. Spin-echo MR imaging can depict relevant morphologic features of most types of CHD. MR imaging provides important diagnostic information in evaluation of right ventricular outflow tract obstruction (eg, pulmonary atresia), postoperative status, pulmonary venous anomalies, and complex ventricular anomalies. MR imaging can replace angiography in some situations, including evaluation of simple defects, right ventricular outflow tract obstruction, and postoperative status. MR imaging is the modality of choice in evaluation of aortic coarctation, interrupted aortic arch, and hemitruncus. MR images in three orthogonal planes are useful in analyzing the morphology and arrangement of cardiac segments in univentricular heart, criss-cross heart, and abnormal visceroatrial situs.

Total anomalous pulmonary venous connection is an uncommon congenital cardiovascular anomaly but one that occurs frequently in the asplenia syndrome. We present a rare type of total anomalous pulmonary venous connection in a 4-month-old baby with the asplenia syndrome. In this patient, all of the left pulmonary veins united to form a common pulmonary vein, which crossed the mediastinum and then proceeded in an intrapulmonary fashion in the right lung. A small pulmonary vein emerged from the right upper lobe and drained into the right superior vena cava. Nine other cases have been reported, four also with asplenia, five with otherwise normal cardiac anatomy apart from an atrial septal defect. The incidence of pulmonary venous obstruction is high, at least 70%. Two cases, both with a normal heart, had corrective surgery. One with no pulmonary venous obstruction was repaired successfully. Embryologically, this type of total anomalous pulmonary venous connection represents a developmental error early in embryonic development before the venous connection between the two lungs and the cardinal veins involute.

Anomalous origin of the right pulmonary artery from the ascending aorta is a rare congenital anomaly. Magnetic resonance imaging (MRI) was performed on three patients with anomalous origin of the right pulmonary artery from the ascending aorta. ECG-gated, T1-weighted, spin-echo MRIs and cine MRIs were obtained. In one patient, postoperative MRI was also obtained. Echocardiography and cardiac catheterization were performed in three patients and angiocardiography was performed in two. MRI clearly showed anomalous origin of the right pulmonary artery from the posterior aspect of the ascending aorta, as well as combined anomalies including patent ductus arteriosus, aortopulmonary window, and interruption of the aortic arch in all three patients. Echocardiography missed this anomaly in all three. We suggest that MRI is an accurate imaging modality in diagnosing anomalous origin of the right pulmonary artery from the ascending aorta, obviating the need to perform angiocardiography.

Ebstein's anomaly is an uncommon congenital developmental abnormality of the tricuspid valve that has a wide spectrum of pathologic anatomy. With the evolution of various surgical techniques, through assessment of the morphologic features and type of Ebstein's anomaly assumes greater practical importance. Although the diagnosis of Ebstein's anomaly is usually straightforward and is based on echocardiographic findings, there are limitations in defining pathologic anatomy in some cases. The purpose of this essay is to illustrate the MR findings in various types of Ebstein's anomaly.

Objective: A prospective MR study was undertaken in 13 patients with total anomalous pulmonary venous connection (TAPVC) to determine the value of MR in its detection., Materials and Methods: Echocardiography was performed in all cases and cardiac angiography was performed in eight patients before MRI., Results: Magnetic resonance detected TAPVC in four cases without prior echocardiographic and angiographic diagnosis. In seven surgically proven cases, the diagnostic accuracy of preoperative MR, echocardiography, and cardiac angiography was 100 (7 of 7), 57 (4 of 7), and 25% (1 of 4), respectively. In the remaining cases including three cases for postoperative evaluation, MR findings correlated well with those of echocardiography or angiography. The combination of axial and coronal MRI visualized 96% of the individual anomalous pulmonary veins and 100% of the common pulmonary veins. Stenosis of a common pulmonary vein (three cases) or the superior vena cava (one case) was identified on MR in all cases., Conclusion: Magnetic resonance is an effective modality in depicting TAPVCs.