• Title/Summary/Keyword: Tree hospital

Search Result 255, Processing Time 0.034 seconds

Calpain-10 SNP43 and SNP19 Polymorphisms and Colorectal Cancer: a Matched Case-control Study

  • Hu, Xiao-Qin;Yuan, Ping;Luan, Rong-Sheng;Li, Xiao-Ling;Liu, Wen-Hui;Feng, Fei;Yan, Jin;Yang, Yan-Fang
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.14 no.11
    • /
    • pp.6673-6680
    • /
    • 2013
  • Objective: Insulin resistance (IR) is an established risk factor for colorectal cancer (CRC). Given that CRC and IR physiologically overlap and the calpain-10 gene (CAPN10) is a candidate for IR, we explored the association between CAPN10 and CRC risk. Methods: Blood samples of 400 case-control pairs were genotyped, and the lifestyle and dietary habits of these pairs were recorded and collected. Unconditional logistic regression (LR) was used to assess the effects of CAPN10 SNP43 and SNP19, and environmental factors. Both generalized multifactor dimensionality reduction (GMDR) and the classification and regression tree (CART) were used to test gene-environment interactions for CRC risk. Results: The GA+AA genotype of SNP43 and the Del/Ins+Ins/Ins genotype of SNP19 were marginally related to CRC risk (GA+AA: OR = 1.35, 95% CI = 0.92-1.99; Del/Ins+Ins/Ins: OR = 1.31, 95% CI = 0.84-2.04). Notably, a high-order interaction was consistently identified by GMDR and CART analyses. In GMDR, the four-factor interaction model of SNP43, SNP19, red meat consumption, and smoked meat consumption was the best model, with a maximum cross-validation consistency of 10/10 and testing balance accuracy of 0.61 (P < 0.01). In LR, subjects with high red and smoked meat consumption and two risk genotypes had a 6.17-fold CRC risk (95% CI = 2.44-15.6) relative to that of subjects with low red and smoked meat consumption and null risk genotypes. In CART, individuals with high smoked and red meat consumption, SNP19 Del/Ins+Ins/Ins, and SNP43 GA+AA had higher CRC risk (OR = 4.56, 95%CI = 1.94-10.75) than those with low smoked and red meat consumption. Conclusions: Though the single loci of CAPN10 SNP43 and SNP19 are not enough to significantly increase the CRC susceptibility, the combination of SNP43, SNP19, red meat consumption, and smoked meat consumption is associated with elevated risk.

Economic Evaluation and Budget Impact Analysis of the Surveillance Program for Hepatocellular Carcinoma in Thai Chronic Hepatitis B Patients

  • Sangmala, Pannapa;Chaikledkaew, Usa;Tanwandee, Tawesak;Pongchareonsuk, Petcharat
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.15 no.20
    • /
    • pp.8993-9004
    • /
    • 2014
  • Background: The incidence rate and the treatment costs of hepatocellular carcinoma (HCC) are high, especially in Thailand. Previous studies indicated that early detection by a surveillance program could help by down-staging. This study aimed to compare the costs and health outcomes associated with the introduction of a HCC surveillance program with no program and to estimate the budget impact if the HCC surveillance program were implemented. Materials and Methods: A cost utility analysis using a decision tree and Markov models was used to compare costs and outcomes during the lifetime period based on a societal perspective between alternative HCC surveillance strategies with no program. Costs included direct medical, direct non-medical, and indirect costs. Health outcomes were measured as life years (LYs), and quality adjusted life years (QALYs). The results were presented in terms of the incremental cost-effectiveness ratio (ICER) in Thai THB per QALY gained. One-way and probabilistic sensitivity analyses were applied to investigate parameter uncertainties. Budget impact analysis (BIA) was performed based on the governmental perspective. Results: Semi-annual ultrasonography (US) and semi-annual ultrasonography plus alpha-fetoprotein (US plus AFP) as the first screening for HCC surveillance would be cost-effective options at the willingness to pay (WTP) threshold of 160,000 THB per QALY gained compared with no surveillance program (ICER=118,796 and ICER=123,451 THB/QALY), respectively. The semi-annual US plus AFP yielded more net monetary benefit, but caused a substantially higher budget (237 to 502 million THB) than semi-annual US (81 to 201 million THB) during the next ten fiscal years. Conclusions: Our results suggested that a semi-annual US program should be used as the first screening for HCC surveillance and included in the benefit package of Thai health insurance schemes for both chronic hepatitis B males and females aged between 40-50 years. In addition, policy makers considered the program could be feasible, but additional evidence is needed to support the whole prevention system before the implementation of a strategic plan.

A Study on Improvement through Functionality Evaluation on Botanic Gardens and Arboreta in Korea (식물원·수목원 기능성 평가를 통한 개선방안 연구)

  • Kang, Hyun Kyung;Kim, Sun Hae;Kweon, Min-Hoon;Bang, Kwang Ja;Kim, Kwang Doo
    • Journal of the Korean Society of Environmental Restoration Technology
    • /
    • v.15 no.3
    • /
    • pp.29-43
    • /
    • 2012
  • This study evaluated 23 botanic gardens and arboretums under two main categories including professional group and operational group. As for professional group, the main difference between the functions of botanic gardens and arboretums was analyzed. In the case of operational group compared professional group respectively, on categories including importance of function and implementation, seeking to provide fundamental data of botanic gardens and arboretums by enhancing the quality of visitors and examining functional differences. The result of a difference in arboretums' function between professional and operational groups, the study analyzed the importance of botanic gardens and arboretums in terms of detailed categories such as research, education, collection, display, retention, and service for visitors. As a result, professional group showed retention 4.32>education 4.11>research 4.09>service for visitors 4.05, and operational group showed retention 3.70>service 3.52>education 3.41>research 3.37, indicating that both groups had retention as the most selected answer. Looking closely at the functions of the currently implemented detailed categories of botanic gardens and arboretums, such as research, education, collection, display, retention, and service for visitors, the study showed that 91.3% selected rare species and individual multiplication for research function, 78.3% chose education of natural ecosystem for children for education, 73.9% answered space for experiencing nature for display, and 73.9% also replied managon, diof rare species, reproduction, and retention of native plants' species for retention category, and service for visitors showed 95.7% for implementation. The study could not clearly point out the influence between predictors due to absence of an established comprehensive evaluation model. Also, it analyzed and reviewed comparison of functions of professional group and operational group, but in the future, it should conduct study on a systemic and objective classification of botanic gardens and arboretums to clearly examine the difference in views between groups, which also requires, at the same time, study on management policy of botanic gardens and arboretums or suggesting guidelines that suit types of forms, and also study on facilities and program development that can be applied to each class.

Treatment of Flail Chest and a Fixation Technique of Flail Segments (Flail Chest 의 치료와 늑골고정술)

  • 김근호
    • Journal of Chest Surgery
    • /
    • v.8 no.1
    • /
    • pp.37-44
    • /
    • 1975
  • Authors have reviewed the records of seven patients of multiple rib fractures with severe flail chest who were admitted to Hanyang University Hospital during the 3 years period from 1972 through 1975. Of the seven patients studied, automobile accidents led to the injuries in 4 cases, two patients were injured in fall from a tree and on the ox-heading. All who had a blunt trauma without any open wound on the chest. The numbers of the fractured ribs accounted for 6 to 9 of the ribs including double fractures from 3 to 5 ribs. The left side fractures occurred in the 6 patients and in the right only one patient. Thus the flail segment was more often located in the left antero-lateral position than in the right lateral position [the ratio was 6:1].. All cases had associated injuries. The injuries and multiple fractures were the most common associated injuries occurring in four and five of the patients respectively. The patients were classified as having associated head injuries when they were admitted in comatose or semicomatose state. When a major degree of instability of the thoracic cage exists, adequate respiratory change is not possible. For this reason the tracheostomy was performed in five patients in an acutely injured patient with flail chest only after an endotracheal tube has been inserted or after an endotracheal suction. All patients had secondary complications in the pleural cavity, such as hemothorax or hemopneumothorax with or without intrapulmonary hemorrhage and subcutaneous emphysema. Therefore, closed thoracostomy was performed in five patients in the emergency room. The thoracotomy was required in four patients: immediate operation without closed thoracostomy was performed in two patients and the thoracotomy was indicated in two patients after closed thoracostomy, because of increasing intrathoracic hemorrhage. As to the fixation of the flail segments, authors employed two techniques; one was towel clip traction of the flail segments and the other was intramedullary insertion of Kirschner`s wire in to the double fractured rib fragments for the fixation of the flail segments [Kirschner`s wire fixation]. Because` of an different results in the course of treatment between two techniques, data from patients with towel clip traction was compared with those from patients with thoracotomy and Kirschner`s wire fixation of the flail segments. Of the three patients with towel clip traction, two patients required bronchoscopic toilet due to lung atelectasis which developed because of inadequate motion of thoracic cage and poor expectoration. This was in contrast to the four patients with thoracotomy and Kirschner`s wire fixation, who didn`t these complication because of adequate motion of the thoracic cage and subsequent good expectoration.

  • PDF

Treatment of Pulmonary Sequestration with Thoracoscopic Approach (폐분리증의 치료와 흉강경적 절제술의 경험)

  • Cho, Min-Jeng;Kim, Tae-Hoon;Kim, Dae-Yeon;Kim, Seong-Chul;Kim, In-Koo
    • Advances in pediatric surgery
    • /
    • v.16 no.2
    • /
    • pp.154-161
    • /
    • 2010
  • Pulmonary sequestration (PS) is a rare congenital malformation of the lower respiratory tract. The anomaly is characterized by absence of communication with the tracheobronchial tree and isolated blood supply from an anomalous systemic vessels. With the utilization of antenatal ultrasound, the diagnosis of asymptomatic neonatal PS has increased. Treatment options include observation, arterial embolization and surgical resection. The aim of the present study is to review the clinical course of PS and to share our experience with thoracoscopic resection. A total of 96 patients with PS were treated at Asan Children's Hospital between 1999 and 2010. The diagnosis of PS was established by CT in the cases managed by observation or embolization, and by tissue pathology in the surgical cases. Medical records and radiographic images were retrospectively reviewed. Thirty-nine patients were managed by embolization and 30 patients by surgery. The remaining 27 patients have been under observation without any procedures. Among 27 observation patients, 1 patient regressed completely and 10 patients were lost to follow up. Of the 39 embolizations patients, 2 had their lesion regress and sepsis was suspected after embolization. In 1 patient, the microcoil migrated to the iliac artery during the embolization procedure, and another patient developed renal abscess caused by renal artery embolization. Among 30 surgical cases, resection by thoracotomy was performed in 27 at the Department of Thoracic Surgery, and thoracoscopic resection in 3 at the Division of Pediatric Sugery. Only one wound complication ocurred. We conclud that surgical excision should be recommended for pulmonary sequestration, whether the sequestration is symptomatic or not because of the risk of infection, the low rate of natural regress, poor compliance, severe complications after embolization, and to exclude other pathology. In summary, thoracoscopic resection of the pulmonary sequestration is feasible, efficacious, safe and cosmetically superior even in neonatal period.

  • PDF

The Hope, Burden, and Family Function in Mothers of Children with Cancer (암 환아 어머니의 희망, 부담감과 가족기능)

  • Park Ho Ran;Park Sun Nam;Jung Kyang Hee;Kim Hae Ja
    • Child Health Nursing Research
    • /
    • v.7 no.1
    • /
    • pp.51-61
    • /
    • 2001
  • The purpose of the descriptive correlation study was to examine relations among the hope, the burden and the family function in mothers caring for children with cancer. 145 mothers completed the three questionaires of the study divided into tree sections: a) The Hope Scale, b) The Burden Scale, c) FACES-Ⅲ. The collected data was analysed with t-test, ANOVA, Scheffe test and Pearson correlation coefficients. The results were as follows: 1) The average age of mothers of children with cancer was 35.6 years old and the ages between 30 to 39 were the most abundant. 57.3% of the mothers had an education level of below high school education and 66.0% had religion. The average age of the children was 8.6 years old. Ages between 1 to 7 were the most and 60.8% were diagnosed as leukemia. 2) Regarding the section of degree of burden, mothers of children with cancer marked 2.6 out of 5, and the degree of hope 3.2 out of 4. The result for family function came out to be 3.5 out of 5, an average of family cohesion of 3.9 and family adaptation of 3.1. 3) There were significantly less burden to the mothers who were living together with a spouse compared to the mothers who were not. Also mothers who replied that they preserved good health came out to be exposed to less burden compared to the mothers who did not. In analysing hope according to the general characteristics of mothers of children with cancer, mothers who were employed marked high in the degree of hope compared to unemployed mothers. Furthermore, the degree of family cohesion marked higher with mothers who had higher education of college graduate, mothers with religion and mothers with a monthly family income of over ₩3,000,000, compared to the group of mothers with lower education of high school graduate, non-religious or with a monthly family income of less than ₩1,000,000. 4) Excluding the fact that the group sorted with children diagnosed as leukemia marked a perceivably high score regarding family cohesion, compared to groups with other cancers, the degree of burden, hope and family cohesion did not show any noticeable difference according to characteristics of children with different cancers. 5) In the correlation of the hope, the burden and the family function regarding the mothers of children with cancer, the burden did not have any manifest relationship with hope or family function. However, the degree of hope and family function cohesion had a direct proportional relationship, as family cohesion marked higher when the degree of hope were high.

  • PDF

Prevalence and Genotypes of Transfusion-Transmitted Virus in Children with Hepatitis and Normal Control (정상 소아와 간염 환자에서 Transfusion-Transmitted Virus의 감염상태와 유전자형)

  • Chung, Ju Young;Han, Tae Hee;Hwang, Eung Soo;Ko, Jae Sung;Seo, Jeong Kee
    • Pediatric Gastroenterology, Hepatology & Nutrition
    • /
    • v.8 no.2
    • /
    • pp.202-212
    • /
    • 2005
  • Purpose: Transfusion transmitted virus (TTV) is a newly discovered virus and to date the contribution of TTV to liver disease remains unclear. Little is known about the frequency of TTV infection in children in Korea. The purpose of this study was to investigate the prevalence and genotypic distribution of TTV carried by healthy children and patients with hepatitis in Korea. Methods: Eighty eight of healthy children and three groups of patients with hepatitis-14 patients with chronic hepatitis B, 12 patients with chronic hepatitis C and 25 patients with hepatitis of unknown etiology-were tested. TTV DNA was detected by semi-nested PCR using primer sets generated from N-22 region and from 5' noncoding region (NCR) of the viral genome. PCR products derived from 8 patients with hepatitis and from 11 healthy children were sequenced and a phylogenetic tree was constructed. Results: TTV was found by PCR with N22 primer in 11.3% of healthy children, 28.5% of children with hepatitis B, 25% of children with hepatitis C, 24% of children with hepatitis of unknown etiology. TTV DNA was found by PCR with 5'NCR primer in 32.9% of healthy children, 71.4% of patients with chronic hepatitis B, in 50% of patients with hepatitis C and in 48% of patients with hepatitis of unknown etiology. TLMV DNA was found in 48.9% of healthy children, 21.4% of patients with hepatitis B, 16.6% of patients with hepatitis C, 40% of patients with hepatitis of unknown etiology. Among the sequenced isolates, 10(52%) belonged to genotype 1 (G1) and others belonged to genotype 2 (G2) or genotype 3 (G3). Among the G1 sequences, 7 were grouped as G1a. Conclusion: TTV infection was common in healthy children and in patients with hepatitis. But, the prevalence of TTV DNA by 5'NCR primer was relatively high in patients with hepatitis B and there may be some association between TTV and hepatitis B virus infection. G1 was the major genotype of the studied population.

  • PDF

Clinical Manifestations of 15 Cases of Pulmonary Sequestration (폐격리증 15예의 임상양상에 관한 고찰)

  • Park, Kwang-Joo;Kim, Eun-Sook;Kim, Hyung-Jung;Chang, Joon;Ahn, Chul-Min;Kim, Sung-Kyu;Lee, Won-Young;Kim, Sang-Jin;Lee, Doo-Yun
    • Tuberculosis and Respiratory Diseases
    • /
    • v.44 no.2
    • /
    • pp.401-408
    • /
    • 1997
  • Background : Pulmonary sequestration is a rare congenital malformation, which is manifested by formation of nonfunctioning lung tissue lacking normal communication with the tracheobronchial tree. The preoperative diagnostic rate has been relatively low, and without consideration of pulmonary sequestration, unexpected bleeding from aberrant vessels may be a serious problem during the operation. The purpose of our study is to describe the clinical features of pulmonary sequestration based on a review of 15 cases treated by operation. Method : Fifteen patients with pulmonary sequestration who had undergone surgical treatment from 1991 through May 1996 at Yongdong Severance Hospital and Severance Hospital were reviewed retrospectively. Results : The mean age of the patients was 22.5 years (range 5~57), and male to female ratio was 9 : 6. Clinical presentations varied from recurrent respiratory infections such as fever, cough, and sputum or chest pain to no symptom. The chest simple X-rays showed multicystic shadow(10/15) and solid mass-like shadow(5/15). The chest CT scans, done in twelve cases, showed multicystic lesion with or without lung infiltration(8/12), solid mass-like lesion(4/12), The chest MRIs, done in three cases, revealed the aberrant arteries originating from descending aorta(2/3). Aortograms, done in four cases, showed the aberrant arteries originating from descending thoracic aorta(2/4), abdominal aorta(I/4), and intercostal artery(1/4). and the venous returns were via the pulmonary veins. Pulmonary sequestration was considered preoperatively in six patients of fifteen. Other preliminary diagnosis were lung tumor(3/15), lung abscess(21/15), bronchiectasis(2/15), and mediastinal tumor(2/15). In the operative findings, twelve cases were of intralobar type and three cases of extralobar type. The left lower lobe was most often affected(9/15) and one extralobar sequestration was in the pericardium. The aberrant arteries originated from descending thoracic aorta(6/15), abdominal aorta(1/15), internal thoracic arteries (2/15), intercostal artery(1/15), pericardiophrenic artery(1/15), but in four cases, the origins could not be defined. There was no mortality or complication postoperatively. Conclusion : In our study, preoperative diagnostic rate was relatively low, and clinical features were similar to previous reports. Preoperative vigorous diagnostic approach including aortography is strongly advocated not only for its diagnostic value, but also for accurate localization of the aberrant vessels, which is major concern to surgical procedure.

  • PDF

Clinical Study of Corrosive Esophagitis (부식성 식도염에 관한 임상적 고찰)

  • 이원상;정승규;최홍식;김상기;김광문;홍원표
    • Proceedings of the KOR-BRONCHOESO Conference
    • /
    • 1981.05a
    • /
    • pp.6-7
    • /
    • 1981
  • With the improvement of living standard and educational level of the people, there is an increasing awareness about the dangers of toxic substances and lethal drugs. In addition to the above, the governmental control of these substances has led to a progressive decrease in the accidents with corrosive substances. However there are still sporadic incidences of suicidal attempts with the substances due to the unbalance between the cultural development in society and individual emotion. The problem is explained by the fact that there is a variety of corrosive agents easily available to the people due to the considerable industrial development and industrialization. Salzen(1920), Bokey(1924) were pioneers on the subject of the corrosive esophagitis and esophageal stenosis by dilatation method. Since then there had been a continuing improvement on the subject with researches on various acid(Pitkin, 1935, Carmody, 1936) and alkali (Tree, 1942, Tucker, 1951) corrosive agents, and the use of steroid (Spain, 1950) and antibiotics. Recently, early esophagoscopic examination is emphasized on the purpose of determining the way of the treatment in corrosive esophagitis patients. In order to find the effective treatment of such patients in future, the authors selected 96 corrosive esophagitis patients who were admitted and treated at the ENT department of Severance hospital from 1971 to March, 1981 to attempt a clinical study. 1. Sex incidence……male: female=1 : 1.7, Age incidence……21-30 years age group; 38 cases (39.6%). 2. Suicidal attempt……80 cases(83.3%), Accidental ingestion……16 cases (16.7%). Among those who ingested the substance accidentally, children below ten years were most numerous with nine patients. 3. Incidence acetic acid……41 cases(41.8%), lye…20 cases (20.4%), HCI……17 cases (17.3%). There was a trend of rapid rise in the incidence of acidic corrosive agents especially acetic acid. 4. Lavage……57 cases (81.1%). 5. Nasogastric tube insertion……80 cases (83.3%), No insertion……16 cases(16.7%), late admittance……10 cases, failure…4 cases, other……2 cases. 6. Tracheostomy……17 cases(17.7%), respiratory problems(75.0%), mental problems (25.0%). 7. Early endoscopy……11 cases(11.5%), within 48 hours……6 cases (54.4%). Endoscopic results; moderate mucosal ulceration…8 cases (72.7%), mild mucosal erythema……2 cases (18.2%), severe mucosal ulceration……1 cases (9.1%) and among those who took early endoscopic examination; 6 patients were confirmed mild lesion and so they were discharged after endoscopy. Average period of admittance in the cases of nasogastric tube insertion was 4 weeks. 8. Nasogastric tube indwelling period……average 11.6 days, recently our treatment trend in the corrosive esophagitis patients with nasogastric tube indwelling is determined according to the finding of early endoscopy. 9. The No. of patients who didn't given and delayed administration of steroid……7 cases(48.9%): causes; kind of drug(acid, unknown)……12 cases, late admittance……11 cases, mild case…9 cases, contraindication……7 cases, other …8 cases. 10. Management of stricture; bougienage……7 cases, feeding gastrostomy……6 cases, other surgical management……4 cases. 11. Complication……27 cases(28.1%); cardio-pulmonary……10 cases, visceral rupture……8 cases, massive bleeding……6 cases, renal failure……4 cases, other…2 cases, expire and moribund discharge…8 cases. 12. No. of follow-up case……23 cases; esophageal stricture……13 cases and site of stricture; hypopharynx……1 case, mid third of esophagus…5 cases, upper third of esophagus…3 cases, lower third of esophagus……3 cases pylorus……1 case, diffuse esophageal stenosis……1 case.

  • PDF

Diagnostic Value of Serum CYFRA 21-1 in Lung Cancer (폐암에서 혈중 CYFRA 21-1의 진단적 가치)

  • Yoon, Hyun-Dae;Kim, Ki-Deok;Chung, Jin-Hong;Lee, Hyung-Woo;Lee, Kwan-Ho;Lee, Hyun-Woo;Cho, Ihn-Ho
    • Tuberculosis and Respiratory Diseases
    • /
    • v.42 no.2
    • /
    • pp.149-155
    • /
    • 1995
  • Background: Cytokeratin 19 is 40KD acidic molecule whose distribution is restricted to simple or pseudo-stratified epithelia, such as the epithelial layer of the bronchial tree. Immunohistochemical study have shown that cytokeratin 19 is overexpressed in lung carcinoma tissue. An immunoradiometric assay, CYFRA 21-1 has been developed using two monoclonal antibody, BM 19-21 and KS 19-1, reactive to different epitopes on cytokeratin 19. We studied the diagnostic value of CYFRA 21-1 in lung cancer. Method: The serum CYFRA 21-1 level using immunoradiometric kit(ELSA-CYFRA 21-1) was measured in 54 patients who admit to Yeungnam University Hospital from April, 1993 to August, 1994. Lung cancer group was 39 primary lung cancer patients(19 patients with squamous cell carcinoma, 11 patients with adenocarcinoma and 9 patients with small cell carcinoma). Control group was 15 patients with non malignant lung diseases(8 patients with pulmonary tuberculosis, 3 patients with chronic obstructive pulmonary disease, 2 patients with pneumonia and 2 patients with chronic obstructive pulmonary disease combined with pulmonary tuberculosis). Results: The mean serum value of CYFRA 21-1 was $20.2{\pm}4.7ng/ml$ in squamous cell carcinoma, $7.2{\pm}1.6ng/ml$ in adenocarcinoma and $15.5{\pm}4.7ng/ml$ in non-small cell lung cancer. The serum value of CYFRA 21-1 in control group was $1.7{\pm}0.5ng/ml$. All of the serum values of 3 histologic types were significantly higher than that of control group(p<0.01). The serum value of CYFRA 21-1 of squamous cell carcinoma was significantly higher than that of adenocarcinoma(p <0.05). Serum value of CYFRA 21-1 in small cell lung cancer was $2.9{\pm}0.9ng/ml$ and not significantly different compared with control group. Using cut off value of 3.3ng/ml, sensitivity and specificity was 11.1%, 65.2% in small cell lung cancer, 70.0%, 62.5% in non-small cell lung cancer, 73.7%, 75% in squamous cell carcinoma and 63.6%, 78.9% in adenocarcinoma, respectively. Conclusion: The serum levels of CYFRA 21-1 may be useful in diagnosis of non-small cell lung carcinoma, especially in squamous cell carcinoma with its high specificity.

  • PDF