tbuckley/cabot-search huggingface dataset:
Extrapolation of Experimental Data from Animals to Man
Authors: G. N. Krasovskii
Journal: Environmental Health Perspectives (1976)

Conditions for extrapolating toxicologic data from animals to man were studied. In the search for general regularities associated with the comparative sensitivity of humans and various species of animals to toxins, it was shown that the toxicity parameters of compounds and the biological constants of mammals correlate with body weight. This relationship is well described by a rectilinear regression equation which holds for more than 100 of the most diverse mammalian biological constants. The toxicity parameters for 80% of the substances also are subordinated to this regularity. This made it possible to develop a computational method for extrapolating toxicologic data from animals to the "average" man. In order to increase the reliability of extrapolation, it is necessary to take into consideration the limits of variability of sensitivity of various population contingents to the effect of chemical compounds, estimate the accuracy of establishing the threshold and no-effect doses of substances under chronic experiment conditions with animals and determine the maximally possible error associated with extrapolating experimental data to the "average" man. In this respect, it is advisable to use a coefficient of reserve whose value should not be less than 10 in order to ensure safe conditions for the transfer of the results of toxicologic studies to public health practice.
Refugees in Thailand and short-term medical aid
Authors: G. Smilkstein
Journal: JAMA (1981)

IN THAILAND, approximately 400,000 refugees reside in camps within the country and along its borders with Cambodia (Kampuchea) and Laos. The number of refugees is too great for the government of Thailand to manage alone. Each refugee camp requires a support system that includes an administrative and work force responsible for such items as food, water, sanitation, housing, and health care. When the Cambodian refugees fled to Thailand in large numbers last fall, the health care problems were staggering.<sup>1,2</sup>A medical organization was needed to (1) prevent epidemics of cholera and typhoid; (2) treat a large number of patients with marasmus, kwashiorkor, malaria, tuberculosis, and war injuries; and (3) promote health by providing an adequate diet for the refugees, especially children and pregnant and lactating women. <h3>An Instant Refugee Camp</h3> Under the administrative guidance of the Thai Ministry of Interior and the United Nations High Commission for Refugees, a
Medical Licensure Statistics
Journal: JAMA (1966)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Energy expenditure, sex, and endogenous fuel availability in humans
Authors: Søren Nielsen, ZengKui Guo, Jeanine B. Albu, Samuel Klein, Peter C. O’Brien, Michael D. Jensen
Journal: Journal of Clinical Investigation (2003)

Adipose tissue lipolysis supplies circulating FFAs, which largely meet lipid fuel needs; however, excess FFAs, can contribute to the adverse health consequences of obesity. Because “normal” FFA release has not been well defined, average (mean of 4 days) basal FFA release and its potential regulation factors were measured in 50 lean and obese adults (25 women). Resting energy expenditure (REE), but not body composition, predicted most of the interindividual variation in FFA release. There was a significant, positive linear relationship between palmitate release and REE; however, women released approximately 40% more FFA than men relative to REE. Neither plasma palmitate concentrations nor respiratory quotient by indirect calorimetry differed between men and women. Glucose release rates were not different in men and women whether related to REE or fat free mass. These findings indicate that nonoxidative FFA clearance is greater in women than in men. This could be an advantage at times of increased fuel needs. We conclude that “normal” adipose tissue lipolysis is different in men and women and that the fuel export role of adipose tissue in obesity will need to be reassessed.
Phase III randomized trial of primary chemotherapy with doxorubicin/cyclophosphamide (AC) vs docetaxel/capecitabine (TX) for stage II/III breast cancer (BC): Interim analysis
Authors: H. G. Lee, J. J. Lee, K.-H. Jung, Y. Kwon, E. H. Shin, K.-W. Chung, K. H. Shin, E.-A. Kim, E. S. Lee, J. Ro
Journal: Journal of Clinical Oncology (2004)

607 Background: Recent data suggested docetaxel (T) when added preoperatively to enhance tumor response following AC, significantly improved pathologic tumor response and clinical outcomes. In metastatic BC, TX resulted in higher RR, TTP and OS compared with T alone. Therefore, a phase III study was designed to compare efficacy and toxicity of AC vs TX as primary chemotherapy for stage II/III BC. Methods: Patients (pts) with stage II/III BC without prior hormonal, chemo-, radiation therapy, or surgery (op) other than biopsy were eligible. Pts must have positive axillary LN by PET or sono guided diagnosis, adequate organ and hematologic profiles and good PS (ECOG 0/1). Randomization to receive preoperative AC x 4 (A 60mg/m2 i.v. d1/C 600 mg/m2 i.v. d1 q 3 wk) vs TX x 4 (T 75 mg/m2 i.v. d1/X 1,000mg/m2 p.o. BID d1–14 q 3 wk) was based on stage, ER status, and age. Postoperatively, therapy crosses over to the other arm. Further radiation ± tamoxifen is given. Assessment for clinical response was assisted by 3 serial sono results at baseline, after 2nd and 4th cycles. Results: Total 78 pts were enrolled from 8/02 to 11/03. Age (range 21–66yrs), stage II (56%), ER (54%), HER2 3+ (28%) were well balanced in 2 arms. Thus far, 32 pts in AC /33 in TX completed op. Clinically, 1 CR, 23 PR, 1 MR, 4 SD, 3 PD in AC arm vs 1 CR, 28 PR, 3 MR, 1 SD, 0 PD in TX arm were observed (p=0.03). pCR of primary tumor was 6.3%, AC vs 15.2%, TX (p=0.43), and in LN, 29% vs 27%. Relative dose intensity (%) were 97/96 in AC vs 95/90 in TX. Severe adverse events were G3/4 neutropenia (94 vs 77%), G3 vomiting (3% in AC) and G3 diarrhea, desquamation, hand-foot syndrome (3%, 5%, 8% in TX). 56.2% of pts in AC and 63.6% in TX underwent breast conserving op. Conclusions: Primary therapy with TX resulted in higher clinical response and pCR compared with AC in stage II/III BC at this interim analysis. Active accrual will continue and further updates will be presented. Supported by NCC grant-0210150, Aventis Pharma and Roche Korea. No significant financial relationships to disclose.
Symposium: Gut flora in IBD--practical importance 105-107
Authors: S Parry, J Barton, M Welfare, I Mohammed, L Cherkas, S Riley, T Spector, N Trudgill, S Lal, J Mclaughlin, G Giampaolo, G Dockray, A Varro, D Thompson, J Jones, D Kendall, P Millns, C Hawkey, S Dunlop, D Jenkins, R Spiller, L Gregory, L Yaguez, S Coen, E Amaro, S Smale, A Hobson, S Williams, Q Aziz, V Chudleigh, E Brennan, S Tarry, S Myers, S Lewis, G Smith, K Palmer, Z Khan, E Simpson, A Cole, I Macdonald, D Pye, A Austin, J Freeman
Journal: Gut (2002)

Introduction: Previous studies, many uncontrolled, suggest 4 to 32% of people develop irritable bowel syndrome (IBS) after ID.Little information is available on the development of other FGIDs after ID.Aim: To determine if patients with stool culture confirmed bacterial diarrhoea were more likely to develop gut symptoms consistent with a diagnosis of IBS, functional dyspepsia or functional diarrhoea at 3 and 6 month follow up compared with community controls.Methods: A prospective community-based case-control study over one year.Subjects with stool positive bacterial infectious diarrhoea and control subjects from the same primary care practice were invited to participate.The presence or not of IBS, functional dyspepsia or functional diarrhoea was diagnosed at the start and at follow up using self-complete Rome II modular questionnaires.The diagnosis of a baseline FGID excluded subjects from continuing.There were 128 cases and 219 community controls eligible and who consented to participate.Results: At follow up there was a higher incidence of FGIDs in the cases compared with controls, mainly due to a higher incidence of IBS (see table ).There was no difference in the incidence of functional dyspepsia between cases and controls.Conclusions: IBS and functional diarrhoea is diagnosed more frequently in people at three and six-month follow up after an episode of stool positive bacterial diarrhoea compared with community controls despite careful exclusion of people with pre-existing FGIDS and adds further support for the concept of post-infectious IBS.
A phase II study of aerosolized GM-CSF in the treatment of metastatic melanoma to the lung
Authors: S. N. Markovic, V. J. Suman, R. J. Dalton, J. B. Allred, W. K. Nevala, E. Celis, S. R. Alberts, T. R. Fitch, J. R. Egner, L. P. Ebbert
Journal: Journal of Clinical Oncology (2004)

7571
HLA-A28 and steroid-induced diabetes in renal transplant patients
Authors: D. S. David
Journal: JAMA (1980)

Between July 1971 and March 1977, steroid-induced diabetes (SD) developed postoperatively in 31 (10.8%) of 286 nondiabetic adult kidney transplant recipients who were observed for a total of 410 patient transplant years. There was a highly significant association between HLA-A28 and SD. There was no significant association between SD and B8 or Bw15. Age was also associated with SD. However, A28 was associated with SD even when corrected for age. A28 occurred more frequently in blacks than whites, 25.4% and 6.3%, respectively, and accounted for the higher incidence of SD in black adults. There were no significant associations between SD and patients' sex, donor source, number of short-term rejection treatments, or maintenance dose of corticosteroids. Steroid-induced diabetes had no adverse effects on graft or patient survival. (<i>JAMA</i>243:532-533, 1980)
HS和精神病住院治疗之间的相关性
Authors: K.R. Patel, S. Rastogi, V. Singam, H.H. Lee, A.Z. Amin, J.I. Silverberg
Journal: British Journal of Dermatology (2019)

化脓性汗腺炎是一种慢性疾病,其导致皮肤出现疼痛性液性或脓性肿块。汗腺炎影响全世界0.3~4.0%的人口。本研究的研究人员来自美国。他们的目的在于查明汗腺炎是否与精神病的可能性和成本升高相关。他们研究了2002~2012年间的美国全国住院病人样本(美国的一个全国性住院治疗数据库)。他们进行了统计学分析,以探索汗腺炎与精神病的关系。研究发现,汗腺炎与精神病住院治疗的可能性升高相关,包括:抑郁、自杀风险、焦虑、注意力缺陷或品行障碍、精神分裂症、人格障碍、物质使用障碍、适应障碍和发育障碍。另外作者还发现汗腺炎患者与精神病住院治疗相关的护理成本更高。总之,研究结果表明,汗腺炎患者更有可能住院治疗精神病,而且护理成本更高。
ASSUMPTIONS PERMITTED IN HYPOTHETICAL QUESTIONS.
Journal: JAMA (1894)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Hereditary polymorphic light eruption in American Indians. Photoprotection and prevention of streptococcal pyoderma and glomerulonephritis
Authors: R. M. Fusaro
Journal: JAMA (1980)

Hereditary polymorphic light eruption (HPLE) occurs in Indians of North and South America. Affected persons are sensitive to long ultraviolet radiation and therefore receive no substantial benefit from conventional sunscreens. We have treated 46 patients with HPLE at the Red Lake Reservation, Minn, with topically administered dihydroxyacetone and lawsone, orally given beta carotene, or both. Oral beta carotene afforded adequate photoprotection to 33 patients, and four additional patients were protected with the combined use of oral and topical agents. Epidemiologic studies support our proposals that HPLE is a causative factor in streptococcal pyoderma in the American Indian and may be associated with epidemics of streptococcal glomerulonephritis. (<i>JAMA</i>244:1456-1459, 1980)
Pediatric Nursing
Journal: JAMA (1949)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Unpublicized Results
Authors: Sherman M. Mellinkoff
Journal: New England Journal of Medicine (1969)

Freedom of the press is one of our country's indispensable blessings. The news media are the senses of a democracy. The senses are of value, as we all know, even when they include not only touch, sight and hearing, but also pain perception and smell. Thomas Jefferson correctly identified "eternal vigilance" as "the price of freedom," and vigilance without senses is difficult to imagine.Yet who in the medical profession has not lately been distressed by the spate of gaudy reporting that has attended medical progress as well as unproved experimentation? Lest anyone ask him who has not sinned to . . .
THE MICROCOCCUS TETRAGENUS.
Journal: JAMA (1899)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Bicentennial Year: Prelude
Journal: JAMA (1973)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The Practice of Dietetics
Journal: JAMA (1935)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Four weeks of aerobic and resistance training improves frailty in patients with liver cirrhosis-liver habilitation (Li-Hab) center outcome data
Authors: Varsha Shasthry, Jaya Benjamin, Rakesh Kumar, Naveen Aggarwal, Guresh Kumar, Arun Kumar Sood, Yogendrakumar Joshi, Shiv Kumar Sarin
Journal: Journal of Hepatology (2020)
American Art’s Dark Matter: A History of Uncirculation from Revolution to Empire
Authors: Brunet, François
Journal: Circulation (2017)

American Art's Dark Matter: A History of Uncirculation from Revolution to EmpireJoAnne Marie ManciniCirculationShortly after the American Revolution, the engraver to the Comte d'Artois, Nicolas Ponce (1746–1831), and the royal engraver François Godefroy (1743–1819) published the Recueil d'estampes représentant les différents événemens [sic] de la guerre, qui a procuré l'indépendance...AuthorJoAnne Marie ManciniPublisherTerra Foundation for American ArtCopyright© 2017, Terra Foundation for American ArtRelated print edition pages: pp.42-75 https://doi.org/10.37862/aaeportal.00191.002 Stable URL: https://aaeportal.com/?id=-19912Copy Chapter subject tags:United States--History--Revolution, 1775-1783Prints--18th centuryPonce, Nicolas, 1746-1831Lodge, Henry Cabot, 1850-1924
Eosinophils Display an Activated Phenotype in Clinically Active Inflammatory Bowel Disease
Authors: CM Smyth, S Woods, A O'Grady, GJ Gleich, FE Murray, RW Costello
Journal: Endoscopy (2004)

Introduction: The role of the eosinophil, which is a common inflammatory cell in inflamed gastrointestinal mucosa in inflammatory bowel disease (IBD) is uncertain. Eosinophils may lead to symptoms through the release of toxic cationic proteins, or contribute to remodelling through the release of TGF-ß.
Abstract 501: The Measurement of Pulmonary Flow Reserve for Early Detection of Pulmonary Vascular Disease
Authors: Rahn Ilsar, Chirapan Chawantanpipat, Kim H Chan, Richard Waugh, Annemarie Hennessy, David S Celermajer, Martin K Ng
Journal: Circulation (2008)

Pulmonary vascular disease (PVD) is an insidious, fatal disorder, characterized by progressive microvascular obstruction. Current pulmonary artery pressure (PAP) based diagnosis of PVD is inadequate, as PAP only rises once &gt;50% of the microvasculature is destroyed. We propose a novel index of pulmonary flow reserve (PFR = maximal hyperemic divided by basal pulmonary blood flow) that may detect microvascular disease prior to rises in PAP. We aimed to validate Doppler flow velocity (v d ) use for PFR assessments, define the optimal maximal hyperemic stimulus for PFR assessments and compare PFR &amp; PAP during progressive microcirculatory obliteration, in a primate model. Doppler sensor guidewires (DSG) were placed in segmental pulmonary arteries (SPA) of 11 ketamine-anaesthetized baboons. Vessel diameter ( D ), v d &amp; hemodynamics were recorded at baseline &amp; after intra-SPA administration of saline, adenosine (50–500μg/kg/min), acetylcholine (ACh, 10 −8 –10 −6 M) and papaverine (3– 60mg). Increasing amounts of intra-SPA microspheres (diameter 40–120μm) progressively obliterated the microvasculature. Intra-SPA saline did not alter D or v d (p&gt;0.1) validating the use of local drug delivery. Adenosine induced dose-dependent increases in v d (22.5±2.3 v 32.7±4.8cm/s, baseline v 400–500μg/kg/min, p&lt;0.0001, plateau at 200μg/kg/min) and heart rate (HR, 92±4 v 100±4bpm, p&lt;0.04) while causing systemic hypotension (106±6 v 77±3mmHg, p&lt;0.0001). Papaverine induced increases in v d (23.9±1.1 v 34.6±4.0cm/s, baseline v 24mg, p&lt;0.0001) and HR (92±7 v 104±4bpm, p&gt;0.6). Neither agent affected mean PAP or D (p&gt;0.3). ACh induced small reductions in v d (p&lt;0.0001) possibly due to ketamine-interaction. Normal PFR values were 1.35±0.1 &amp; 1.39±0.1 using adenosine &amp; papaverine, respectively. Microsphere delivery significantly reduced PFR (1.54±0.26 v 1.18±0.09, baseline v 10 6 microspheres, p&lt;0.02) without affecting resting mean PAP (21±6 v 22±3mmHg, p&gt;0.7). Doppler based PFR assessments are feasible using adenosine or papaverine. PFR is capable of detecting microvascular obliteration of magnitude insufficient to raise PAP making it potentially valuable for diagnosis of early PVD.