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1.
Ann R Coll Surg Engl ; 105(4): 314-322, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35486133

RESUMO

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic led to hospitals in the UK substituting face-to-face (FtF) clinics with virtual clinic (VC) appointments. We evaluated the use of virtual two-week wait (2-ww) lower gastrointestinal (LGI) clinic appointments, conducted using telephone calls at a district general hospital in England. METHODS: Patients undergoing index outpatient 2-ww LGI clinic assessment between 1 June 2019 and 31 October 2019 (FtF group) and 1 June 2020 and 31 October 2020 (VC group) were identified. Relevant data were obtained using electronic patient records. Compliance with national cancer waiting time targets was assessed. Environmental and financial impact analyses were performed. RESULTS: In total, 1,531 patients were analysed (median age=70, male=852, 55.6%). Of these, 757 (49.4%) were assessed virtually via telephone; the remainder were seen FtF (n=774, 50.6%). Ninety-two (6%, VC=44, FtF=48) patients had malignant pathology and 64 (4.2%) had colorectal cancer (CRC); of these, 46 (71.9%, VC=26, FtF=20) underwent treatment with curative intent. The median waiting times to index appointment, investigation and diagnosis were significantly lower following VC assessment (p<0.001). The cancer detection rates (p=0.749), treatments received (p=0.785) and median time to index treatment for CRC patients (p=0.156) were similar. A significantly higher proportion of patients were seen within two weeks of referral in the VC group (p<0.001). VC appointments saved patients a total of 9,288 miles, 0.7 metric tonnes of CO2 emissions and £7,482.97. Taxpayers saved £80,242.00 from VCs. No formal complaints were received from patients or staff in the VC group. CONCLUSION: Virtual 2-ww LGI clinics were effective, safe and were associated with tangible environmental and financial benefits.


Assuntos
COVID-19 , Neoplasias Colorretais , Humanos , Masculino , Idoso , Encaminhamento e Consulta , COVID-19/epidemiologia , Telefone , Agendamento de Consultas , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/terapia
2.
J Exp Med ; 147(4): 1065-77, 1978 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-306404

RESUMO

The technique of antigen-driven, 5-bromo-deoxyuridine and light suicide has been adapted to eliminate the precursors of cytotoxic effector cells both for alloantigen and for 2,4,6-trinitrophenyl(TNP)-modified stimulator and target cells. Using this technique, the following observations have been made. Precursors of killer cells specific for alloantigen can be suicided independently of precursors of killer cells specific for TNP-modified self cells. The loss of activity during this procedure is not due to either specific or nonspecific suppressor cells, as judged by mixing experiments. With responder cells from F1 animals, it has been possible to show that precursors specific for TNP-modified cells from one parent are suicided independently of precursors specific for TNP-modified cells of the other parent, but only if the parental strains differ in the K and D regions of the H-2 complex. Cells of F1 mice derived from K and D identical, I region different, parental strains were specifically suicided by TNP-modified stimulator cells from either parent. However, the cross-reactive killing of TNP-self targets induced by stimulation with allogeneic cells is not eliminated by first suiciding with TNP-parental cells, suggesting that the precursors of these two types of TNP-self killer cells are different. This is compatible with reported differences in their specificity, as confirmed in this report. Finally, deletion of alloreactive cells by this technique reveals little or no reactivity specific for TNP-modified allogeneic stimulator cells. In summary, these results strongly suggest that recognition of self MHC antigens is preprogrammed in peripheral T cells of normal animals, and is not acquired during the immunization process. They also suggest that cells specific for modified alloantigen are relatively rare in the strains of mice studied.


Assuntos
Antígenos H-2 , Haptenos , Linfócitos T/imunologia , Animais , Bromodesoxiuridina , Sobrevivência Celular , Citotoxicidade Imunológica , Antígenos H-2/genética , Heterozigoto , Imunidade Celular , Memória Imunológica , Células Matadoras Naturais/imunologia , Luz , Camundongos , Trinitrobenzenos/imunologia
3.
Am J Med Genet ; 43(1-2): 181-6, 1992.
Artigo em Inglês | MEDLINE | ID: mdl-1605190

RESUMO

Since 1985, we have provided coordinated DNA-based and cytogenetic prenatal analysis for couples at risk for offspring afflicted with the fragile X [fra(X)] syndrome. To date, 40 pregnancies have been studied (22 males, 18 females). There were 5 males and 3 females identified to be at high risk by DNA but only 2 males and one female were demonstrated to be cytogenetically expressing the fra(X) prenatally. Of the other 3 males, one was a cytogenetic false negative (i.e. confirmed fra(X)+ at termination of pregnancy). The other 2 remain fra(X)- and are developing normally (undetected recombinants or non-penetrant male carriers). All fetuses at low risk were carried to term and are reported to be normal.


Assuntos
Síndrome do Cromossomo X Frágil/diagnóstico , Diagnóstico Pré-Natal , Citogenética/estatística & dados numéricos , DNA/genética , Sondas de DNA , Erros de Diagnóstico , Feminino , Síndrome do Cromossomo X Frágil/genética , Expressão Gênica , Triagem de Portadores Genéticos , Humanos , Masculino , Linhagem , Gravidez , Diagnóstico Pré-Natal/estatística & dados numéricos , Sensibilidade e Especificidade
4.
Am J Med Genet ; 38(2-3): 453-5, 1991.
Artigo em Inglês | MEDLINE | ID: mdl-1673318

RESUMO

We have had experience with 260 prenatal diagnosis cases for the fragile X syndrome [fra(X)]; amniotic fluid was received in 230. There was a documented family history of fra(X) in 148 amniotic fluid cases. Our sample includes 91 males. Eleven were correctly identified as fra(X)-positive and 2 were false-negative. Eight of 57 females were fra(X) positive and one was a false-negative. CVS were received in 21 cases with a family history of fra(X), and there were 2 positive results in females and 3 false-negative results in males which were ultimately detected by means of molecular analysis or a subsequent amniotic fluid specimen. RFLPs were utilized in 29 cases (amniotic fluid and CVS); RFLPs identified 2 false-negative cytogenetic results in CVS. Two male fetuses were found to have a high probability of being affected by means of RFLPs, but on the basis of prenatal and postnatal negative fra(X) cytogenetic results and subsequent normal growth and development, they are either unaffected transmitting males or are double recombinants. Three female fetuses were also found to be cytogenetically negative in CVS but had a 90%, 93%, and 99% probability of being affected by RFLPs. On the basis of the data, it can be concluded: 1. Amniotic fluid experience is adequate to eliminate the "experimental" designation providing the limitations are understood and an experienced laboratory is involved. 2. Chorionic villus cells for cytogenetic analysis should still be considered experimental. 3. Negative results with CVS should be confirmed by molecular methods and/or by cytogenetic analysis of another tissue. 4. Multiple approaches can maximize reliability of fra(X) prenatal diagnosis.


Assuntos
Amniocentese , Amostra da Vilosidade Coriônica , Síndrome do Cromossomo X Frágil/diagnóstico , Líquido Amniótico/citologia , Células Cultivadas , Estudos de Avaliação como Assunto , Reações Falso-Negativas , Reações Falso-Positivas , Feminino , Sangue Fetal/citologia , Síndrome do Cromossomo X Frágil/genética , Síndrome do Cromossomo X Frágil/patologia , Marcadores Genéticos , Humanos , Masculino , Polimorfismo de Fragmento de Restrição , Gravidez
5.
Am J Med Genet ; 30(1-2): 347-54, 1988.
Artigo em Inglês | MEDLINE | ID: mdl-2902794

RESUMO

We have had experience with 160 prenatal diagnosis cases for the fragile X syndrome [fra(X)] or Martin-Bell Syndrome. In 140, amniotic fluid was utilized; 98 had a documented family history of fra(X). The 94 completed cases included 4 no growth; 56 males of which 7 were fra(X)-positive and 2 false-negative; 38 females of which 5 were fra(X) positive. There was no fra(X) positive result when a family history of mental retardation was not documented as fra(X). Molecular methods (RFLPs) were utilized in 10 amniotic fluid and 5 chorionic villus specimens (CVS). Percutaneous umbilical blood sampling was used in 2 negative cases and 1 fra(X) positive case because of timing, tissue culture failure or confirmation of another method. CVS were received in 13 cases, and RFLPs were utilized in 5 of the CVS cases. There was no positive fra(X) CVS chromosome result in males, 1 positive result in a female, but 2 false negatives were detected by RFLPs. On the basis of the results, it can be concluded that cytogenetic and molecular methods are complementary and best used together and that multiple approaches can enhance the efficiency and reliability of fra(X) prenatal diagnosis.


Assuntos
Síndrome do Cromossomo X Frágil/diagnóstico , Diagnóstico Pré-Natal , Aberrações dos Cromossomos Sexuais/diagnóstico , Amniocentese , Amostra da Vilosidade Coriônica , Reações Falso-Negativas , Feminino , Sangue Fetal/citologia , Humanos , Masculino , Linhagem , Polimorfismo de Fragmento de Restrição , Gravidez
6.
Am J Med Genet ; 38(2-3): 305-10, 1991.
Artigo em Inglês | MEDLINE | ID: mdl-1673302

RESUMO

During the past 4 years (1985-1989), we have analyzed 171 cases in 50 fragile X [fra(X)] families by DNA linkage methods. Most (140 cases; 81%) were for carrier detection, both female (98 cases; 57%) and male (41 cases; 24%). Women who were obligate carriers of the fra(X) mutation accounted for an additional 6 "prior-to-pregnancy" cases. Four pregnancies have subsequently occurred with 3 having been successfully monitored (one male, 2 females). One pregnancy miscarried early prior to testing. Prenatal diagnoses (26 cases; 15%) accounted for the remainder of cases (15 males, 11 females). These will be discussed in the companion paper by Shapiro et al. (Am J Med Genet, 1991). A diagnosis in the cytogenetically uninformative carrier cases was reached in greater than 75% of analyses with a panel of 5 probes: 3 proximal (F9, DXS105, DXS98) and 2 distal (F8, DSX52). Five additional probes, 3 proximal (DXS10, DSX51, DSX102) and 2 distal (DSX15, DXS33), were used in cases that were resistant to analysis with the standard panel. In 60% of cases, flanking markers were identified (proximal and distal). Given this panel, only 5% of cases did not have any informative markers identified. Thus, molecular methods can provide a useful adjunct to cytogenetic analysis in most situations. An unusual association between the rare allele (A1) of DXS10 with the X chromosome carrying the fra(X) mutation was observed. This occurred in both male and female carriers in the uppermost generation tested. The basis for this association is uncertain at the present time.


Assuntos
Sondas de DNA , DNA/análise , Síndrome do Cromossomo X Frágil/genética , Triagem de Portadores Genéticos , Polimorfismo de Fragmento de Restrição , Diagnóstico Pré-Natal , Alelos , Estudos de Avaliação como Assunto , Feminino , Síndrome do Cromossomo X Frágil/diagnóstico , Frequência do Gene , Marcadores Genéticos , Testes Genéticos/métodos , Humanos , Masculino , Valor Preditivo dos Testes , Gravidez
8.
Genet Test ; 1(2): 137-44, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-10464638

RESUMO

This report describes a commercial laboratory's novel approach to providing genetic testing services to detect BRCA1 mutations in persons with hereditary breast/ovarian cancer. The approach involves the use of institutional review board (IRB)-approved protocols as a paradigm for conducting genetic testing in a commercial setting. We discuss the rationale for this approach and the key elements of the protocol. In addition, we provide data on the first 6 months of implementation of the protocol in 32 clinical sites. A phased testing approach was used, consisting of an allele-specific oligonucleotide assay for the 8 most common BRCA1 mutations, a protein truncation test of exon 11, and direct sequencing of the remaining regions of the gene. Data are presented on the yield of mutation carriers by category of family history and by stage of analysis.


Assuntos
Genes BRCA1 , Testes Genéticos/métodos , Mutação , Proteína BRCA2 , Neoplasias da Mama/genética , Análise Mutacional de DNA/métodos , Estudos de Avaliação como Assunto , Éxons , Feminino , Genes Supressores de Tumor , Humanos , Proteínas de Neoplasias/genética , Neoplasias Ovarianas/genética , Fatores de Transcrição/genética
9.
J R Soc Med ; 84(2): 84-6, 1991 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-1999820

RESUMO

Patients presenting with adenocarcinoma of the gallbladder within Newcastle upon Tyne over a 5 year period (1980-1985) were reviewed retrospectively. The mean age of patients on diagnosis was 74 years. Of the 29 patients diagnosed, two were detected after routine cholecystectomy. Laparotomy was performed in 21 patients (72%) of which only 14 patients had a cholecystectomy performed. Mean survival after surgery was 6.6 months with only one patient alive after 5 years. Metastatic disease was present in 72% of patients. The poor prognosis of carcinoma of the gallbladder reflects its late diagnosis and early metastasis to distant sites. Improvement in survival will depend upon early detection of in situ lesions and identification of at risk patients.


Assuntos
Adenocarcinoma/cirurgia , Neoplasias da Vesícula Biliar/cirurgia , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/mortalidade , Idoso , Idoso de 80 Anos ou mais , Inglaterra/epidemiologia , Feminino , Neoplasias da Vesícula Biliar/diagnóstico por imagem , Neoplasias da Vesícula Biliar/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Estudos Retrospectivos , Ultrassonografia
10.
Radiol Manage ; 14(3): 58-63, 1992.
Artigo em Inglês | MEDLINE | ID: mdl-10120117

RESUMO

The total quality management (TQM) revolution that is fueling the interest of CEOs and the JCAHO will present big leadership challenges to department administrators. Successfully implementing TQM concepts will require basic changes in operational methods and highly visible leadership commitment. Lasting change can only occur with a strategy that is understood by all employees and is periodically updated. Operational improvements will result from actions you take to better serve internal and external customers, as well as personal commitment from each employee. Quality teams are the core of TQM philosophy. Any strategy to implement TQM will require extensive training and/or study of quality improvement tools and methods, as well as a plan for managing cultural change. Aligning the department within the organization requires input from the rank and file as well as those at the executive level.


Assuntos
Garantia da Qualidade dos Cuidados de Saúde/organização & administração , Serviço Hospitalar de Radiologia/normas , Humanos , Liderança , Participação nas Decisões/organização & administração , National Institutes of Health (U.S.) , Objetivos Organizacionais , Técnicas de Planejamento , Radiografia/normas , Estados Unidos
14.
Somat Cell Mol Genet ; 11(5): 433-44, 1985 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-2994237

RESUMO

Chromosome-mediated gene transfer (CMGT) lines were shown to be convenient donors of genomic sequences from specific regions of the genome adjacent to selectable markers. Two libraries were prepared from CMGT lines carrying sequences spanning the long arm of the human X chromosome from HPRT (Xq26) to G6PD (Xq28). A series of 22 CMGT lines sharing the same selectable marker (HPRT) were used in conjunction with five standard translocation hybrids to provide fine-resolution regional mapping of the nonrepetitive X specific probes isolated from the libraries. The order of three human recombinant sequences with respect to known X-linked markers is: PGK (Xq13), 05-02 (DXS78); HPRT (Xq26), 07-03 (DXS79); surface antigen S11 (Xq27), 07-14 (DXS80); and G6PD (Xq28).


Assuntos
Mapeamento Cromossômico , DNA Recombinante , Cromossomo X , Animais , Sequência de Bases , Linhagem Celular , Clonagem Molecular , Enzimas de Restrição do DNA , Eletroforese em Gel de Ágar , Feminino , Marcadores Genéticos , Células HeLa , Humanos , Camundongos , Translocação Genética
15.
Prog Clin Biol Res ; 368: 59-72, 1991.
Artigo em Inglês | MEDLINE | ID: mdl-1682943

RESUMO

In our families, a determination of carrier or affected status was made in more than 75% of cases using a standard panel of five marker systems: three proximal (F9, DXS105, DXS98) and two distal (F8, DXS52). Five additional systems, three proximal (DXS10, DXS51, DXS102) and two distal (DXS15, DXS33), were used in cases resistant to analysis with the standard panel. In 60% of cases, flanking markers were identified (proximal and distal). Utilizing the complete panel, only 5% of cases did not have any informative markers identified. In order to facilitate the appropriate application of molecular methods, several simple rules should be followed by the genetic service provider when dealing with fra(X) families: 1. Cytogenetic prescreening of females may be helpful. Only negative or ambiguous fra(X) expression levels justify the labor-intensive DNA-based family studies. 2. At present, DNA-based studies are the only way to ascertain male carrier status. 3. Every effort should be made to perform DNA-based studies under maternal phase-known conditions. 4. Information should be collected and pedigrees prepared for both sets of maternal grandparents. 5. Fathers of female consultands should be directly DNA-typed to rule out non-paternity. 6. Genetic counseling should be conservative, i.e. the "worst" scenario presented to these families, in order to avoid underestimating the risk of transmission to the next generation.


Assuntos
Síndrome do Cromossomo X Frágil/diagnóstico , Triagem de Portadores Genéticos/métodos , Diagnóstico Pré-Natal/métodos , Células Cultivadas , Feminino , Síndrome do Cromossomo X Frágil/genética , Ligação Genética , Marcadores Genéticos , Humanos , Masculino , Linhagem , Polimorfismo de Fragmento de Restrição , Gravidez , Risco
16.
Cytogenet Cell Genet ; 39(2): 125-33, 1985.
Artigo em Inglês | MEDLINE | ID: mdl-4006514

RESUMO

Twenty-two HPRT-selected chromosome-mediated gene transfer lines were characterized by quantitative "dot" blotting. The range of human sequences in these lines extended from over 120,000 kb to less than 5,000 kb. One-half of these lines carried less than 16,000 kb.


Assuntos
Clonagem Molecular , Genes , Hipoxantina Fosforribosiltransferase/genética , Animais , Antígenos de Superfície/genética , Sequência de Bases , Linhagem Celular , Glucosefosfato Desidrogenase/genética , Células HeLa/enzimologia , Humanos , Isoenzimas/genética , Células L/enzimologia , Camundongos , Hibridização de Ácido Nucleico , Fosfoglicerato Quinase/genética
17.
Br J Urol ; 70(1): 84-9, 1992 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-1353396

RESUMO

Advances continue to be made in the treatment of the undescended testis, and treatment recommendations are continually changing. We reviewed 543 patients admitted for treatment of undescended testes in the 10-year period 1977 to 1986. The side and position of the testis were recorded, the patient's age at operation and the procedure carried out. The presence of an associated inguinal hernia was noted. The necessity for reoperation was recorded and predisposing factors sought. We found the mean age at operation to be 9.5 years and this decreased significantly over the study period. Dartos pouch orchiopexy was the commonest operation (69%). No significant link was found between the procedure performed or the presence of a hernia and the need for further procedures; 2.7% of patients required such further procedures. A coherent classification of position is lacking for abnormally descended testes. We report a classification which we used to tackle this situation.


Assuntos
Criptorquidismo/cirurgia , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Criptorquidismo/patologia , Humanos , Lactente , Irlanda , Masculino , Reoperação , Estudos Retrospectivos , Testículo/patologia , Testículo/cirurgia
18.
Biochem Med Metab Biol ; 50(2): 233-40, 1993 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8260200

RESUMO

Deficiency of alpha 1-antitrypsin (alpha 1AT), a common hereditary disorder of Caucasians, is associated with an increased risk for early-onset chronic obstructive pulmonary disease and childhood liver dysfunction. The two most common deficiency variants, PiS and PiS, are both single base-pair substitutions causing amino acid modifications, although neither mutation creates or destroys a naturally occurring restriction site. Dried blood specimens (DBS) submitted to the New York State Department of Health for mandated newborn screening tests were tested for alpha 1AT activity using a fluorometric elastase inhibition assay. A second DBS from specimens determined to be alpha 1AT deficient was phenotyped on an agarose isoelectric focusing gel. Genotypic confirmation was performed by amplifying, directly from a DBS, the regions of the DNA containing the S and Z mutation. The Z mutation was analyzed with a modified primer designed to create an artificial restriction site in the normal allele. TaqI digestion produces two bands, a 157- and a 22-bp fragment. The single base substitution in PiS individuals eliminates this TaqI restriction site, thus showing the same 179-bp fragment before and after digestion. A primer mismatch placed close to the S mutation creates a restriction site in the normal allele, producing a 100-bp product after TaqI digestion. The restriction site is abolished in individuals that carry the S mutation, with a 121-bp product observed before and after digestion. Of 11,081 specimens screened, 3 PiS neonates, all Caucasian, were detected by these methodologies for an estimated incidence of 1:2019 in the Caucasian or 1:3694 in the general population in New York State.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
alfa 1-Antitripsina/genética , alfa 1-Antitripsina/metabolismo , Sequência de Aminoácidos , Eletroforese em Gel de Ágar , Genótipo , Humanos , Recém-Nascido , Focalização Isoelétrica , Dados de Sequência Molecular , Mutagênese , Mutação , Elastase Pancreática/antagonistas & inibidores , Elastase Pancreática/sangue , Mutação Puntual , Reação em Cadeia da Polimerase , Espectrometria de Fluorescência
19.
Gastroenterology ; 91(2): 364-9, 1986 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-3721123

RESUMO

Recordings of esophageal manometry obtained from 18 healthy control subjects and 32 patients with gastroesophageal reflux disease both before and after fundoplication were assessed. Preoperatively, the patients had a mean lower esophageal sphincter pressure at rest that was significantly lower (p less than 0.001) than that observed in the control group. The amplitude of peristaltic contractions, elicited by wet swallows, varied along the length of the esophagus. In patients with gastroesophageal reflux disease, the mean amplitudes recorded from the upper, middle, and lower esophagus were significantly lower (p less than 0.001) than those recorded from control subjects. No significant differences were observed between those patients with (53%) and without preoperative endoscopic evidence of esophagitis. After antireflux surgery (modified Nissen fundoplication), the mean amplitude of peristaltic contractions increased significantly (p less than 0.001) at all levels of the esophagus and were not significantly different from control values. This study describes motor abnormalities in the body of the esophagus associated with gastroesophageal reflux disease. These may arise secondary to gastroesophageal reflux inasmuch as they disappear after fundoplication.


Assuntos
Junção Esofagogástrica/fisiopatologia , Fundo Gástrico/cirurgia , Refluxo Gastroesofágico/fisiopatologia , Adolescente , Adulto , Transtornos de Deglutição/etiologia , Seguimentos , Refluxo Gastroesofágico/cirurgia , Humanos , Manometria , Pessoa de Meia-Idade , Peristaltismo , Complicações Pós-Operatórias/etiologia , Pressão
20.
Proc Natl Acad Sci U S A ; 79(14): 4290-4, 1982 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-6956858

RESUMO

We used direct microinjection of poly(A)+RNA into individual hypoxanthine/guanine phosphoribosyltransferase-deficient or thymidine kinase-deficient cells and detected the specific in vivo translation products as an assay for human hypoxanthine/guanine phosphoribosyltransferase or thymidine kinase mRNAs. The incorporation of [3H]hypoxanthine or [3H]thymidine into cells in response to injected mRNA was assayed in situ by autoradiography. Methylmercuric hydroxide/agarose gel analysis showed that human hypoxanthine/guanine phosphoribosyltransferase mRNA contains approximately 1,530 nucleotides, which is twice the number required for its protein coding capacity. The mRNA for human cytoplasmic thymidine kinase is estimated to be approximately the same length; thus, the size of the cytosol thymidine kinase subunit can be predicted to be approximately 47,000 daltons, if the full coding capacity of its mRNA is utilized.


Assuntos
Hipoxantina Fosforribosiltransferase/genética , RNA Mensageiro/isolamento & purificação , Timidina Quinase/genética , Bioensaio , Humanos , Peso Molecular , Biossíntese de Proteínas
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