ASBESTOS-RELATED PULMONARY DISEASES

Asbestos-related pulmonary diseases are a group of diseases that are associated with exposure to asbestos with subsequent development of a clinical condition attributed to the exposure. This document is an attempt to provide a brief overview of asbestos and the mechanism of its effects in humans, an overview of the more common asbestos-related pulmonary diseases, diagnostic considerations in individuals alleging asbestos-related pulmonary diseases, and application of the information to the Ohio Workers' Compensation System.


OVERVIEW OF ASBESTOS

Physical Properties and Effects in Humans


Asbestos is a term applied to a family of naturally occurring, flexible, silicate minerals that are resistant to heat and many chemicals.[1] The properties of relative heat and chemical resistance has lead to widespread use in the 20th Century of asbestos in many processes and products including insulation materials, building materials such as vinyl asbestos floor tile, linings of furnaces, filtration systems, asbestos cement products, and as spray products for acoustical, thermal, or fireproofing purposes. Therefore, asbestos is commonly found throughout the work and non-work environments. Identification of asbestos fibers in samples of lung tissue, lung lavage samples or sputum, documents past exposure, but not necessarily the source of the exposure or whether asbestos-related disease is present. While individuals with asbestos-related disease may have higher concentrations of fibers in tissue samples, there is considerable overlap and laboratory variation so that asbestos fiber count has limited usefulness.


Once inhaled, the body attempts to remove fibers by several pathways including mucociliary transport through the airways, the lymphatic system, or through degradation of the fibers by macrophages. The fundamental disease process is the induction of inflammation resulting in fibrosis and/or cancer of the lung and pleural space. The fibrosis process is the result of the inflammatory reaction and repair processes by the body’s defense system to remove asbestos fibers. These reactions lead to permanent scarring and fibrosis. The cancer processes are the result of damage to target cells with genetic mutations through a variety of molecular injuries.


The pathogenicity of asbestos fibers may be affected by the dose (concentration and duration of exposure), fiber type, fiber dimensions, durability of the fiber, and surface chemicals that may be present on the fiber. Several studies have shown that the toxicity of asbestos fibers is related to the fibrous nature of the mineral. Both fiber diameter and length are important. In general, fibers with diameters > 3mm in diameter and > 200mm in length do not penetrate the lower lung. Fibers shorter than approximately 3mm in length are usually phagocytosed by macrophages or removed by the lymphatic system. Therefore, fibers less than 3 mm in diameter and longer than 8 mm are more likely to penetrate the lower lung and are more difficult for host defense mechanisms to remove. Fibers of this size are more likely to initiate cellular and molecular events leading to fibrosis or carcinogenesis.

[1] Begin R, Samet GM, and Shaikh RA: “Asbestos” in Harber P, Schenker MB, and Balmes JR: Occupational and Environmental Respiratory Disease Mosby-Year Book, Inc., St. Louis, 1996, pp 293-321.



There is a latency period of several years between initial exposure and onset of clinical disease. The latency period is variable. Individuals who are no longer occupationally exposed to asbestos may develop asbestos-related diseases years after their removal from occupational exposure. Current OSHA regulations and industrial processes have tried to limit exposure by substitution of other materials, monitoring with limits on the concentration of fibers permitted per cc of air in the workplace, use of personal protective equipment when exposed to asbestos fibers in significant concentrations, and required periodic medical monitoring of exposed workers for asbestos-related diseases.


There is little doubt that the "dose" both in terms of concentration and duration of exposure is important with higher concentration and longer duration of exposure more likely to increase the probability of development of an asbestos-related disease. However, exact dose-response curves can not be reasonably determined due to variability among type of fibers, variability of host response systems, questionable exposure histories, and that the radiographic findings are not specific to asbestos-related disease

Mesothelioma and Children

Mesothelioma and Children

When people think of mesothelioma, they typically picture an older adult who has been exposed to asbestos. Yet this disease can, in rare cases, also strike children. Because the prognosis is poor, doctors need to carefully diagnose mesothelioma in their youngest patients.


Doctors don’t know what causes mesothelioma in children. Although a high number of adults with the disease have a history of asbestos exposure, this isn’t the case in children. “The latent period of asbestos exposure in mesothelioma patients can be many years,” explains Cesar A. Moran, MD, professor of Pathology in the Department of Pathology at MD Anderson Cancer Center in Houston, Texas. “Children have not lived long enough to be in that ballpark.”


Dr. Moran and his colleagues recently published a study in the journal, Histopathology, in which they looked at the cases of eight children with mesothelioma. All of the children had cancer in the abdominal cavity lining (peritoneal mesothelioma). Most adults with the disease have pleural mesothelioma, which affects the lining of the lung.


Because this cancer is so rare in children, it can be challenging to diagnose. “For most physicians, the diagnosis of mesothelioma [in children] is low on the list,” Dr. Moran says. Children with mesothelioma tend to complain of the same symptoms: pain, bloating, and fluid build-up in the abdomen. Moran says that it is important to rule out other types of lesions in this location before making an unequivocal diagnosis of mesothelioma in a child.


In this study, all of the children had a biopsy (removing a sample of tissue for examination) to determine the type and severity of their cancer. Diagnosing mesothelioma also typically involves radiological scans of the abdomen, as well as immunohistochemical studies, in which the cells are examined to look for specific cancer markers. “You have to do immunohistochemical tests to make sure you aren’t dealing with another tumor that has metastasized [spread] into the peritoneum,” according to Dr. Moran.


Treating mesothelioma presents another challenge to doctors. No standard therapy exists, even for adults with the disease. Surgery and chemotherapy may be used in adult patients. Similar treatments may be tried in children, but regardless of which treatment is used, the outlook is generally poor.


Currently there is very limited research on peritoneal mesothelioma in children to guide doctors in diagnosis and treatment, and what little research does exist is conflicting. Because this cancer is so rare in children, additional research should be done in adult patients to learn more about this disease, says Dr. Moran. “From adults, we can make more meaningful conclusions, and the results may be applied to the pediatric population,” he says.


Source:Moran CA, Albores-Saavedra J, Suster S. Primary peritoneal mesotheliomas in children: a clinicopathological and immunohistochemical study of eight cases. Histopathology. 2008;52:824-830.

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Is there any treatment that may help?

Mesothelioma responds very little to the normal cancer treatments such as chemotherapy and radiotherapy. There are a number of trials being run in an attempt to improve treatment but nothing has been found to cure this disease. Any treatment offered depends on several factors. These should include patient choice, how well someone is, and how advanced the disease is.

The initial most helpful treatment is that which deals with symptoms. Removing fluid from around the lung can help to relieve breathlessness. Firstly the fluid may be drained either by drawing off fluid or inserting a small drainage tube. However the fluid often reaccumulates and the chest physician or surgeon may perform a procedure called a ‘Pleurodesis’ This is an attempt to stick the lung surface to the chest wall by inserting sterile talc into the pleural space. This may be done by a surgeon using ‘key hole surgery’ otherwise called VATS - Video Assisted Thoracoscopic
Surgery.

How is Mesothelioma diagnosed?

Early diagnosis is difficult and in most cases the first obvious sign is sudden breathlessness caused by an accumulation of fluid in the pleural space - a pleural effusion. It may be accompanied by other symptoms such as chest pain. Scans and X-rays can provide strong evidence to support the diagnosis especially coupled with a history of asbestos exposure. However, other diseases can produce these symptoms and to be certain of a correct diagnosis more investigations often need to be carried out. Scans, Fluid taken for laboratory examination, possibly needle biopsy or keyhole surgery to take a biopsy (a small sample of tissue) are likely to be carried out to help with the confirmation of the diagnosis. These tests and results may take several weeks to complete.

What causes Mesothelioma?

Exposure to asbestos is responsible for the majority of cases. There are thought to be possibly other unknown causes. It has previously been a rare disease but is now occurring more frequently because of the heavy use of asbestos in the post-war years. For most people diagnosed withMesothelioma the exposure happened 20-40 years previously. (It may in some instances be a longer or a shorter interval than this.) Sometimes the asbestos exposure may have been very brief and not always easy to identify. Mesothelioma is however more common in people who have had repeated exposure, usually in a work environment. There are several types of asbestos all of which have been known to cause Mesothelioma.

Mesothelioma

Information for people with Mesothelioma and their carers

What is Mesothelioma?
This is about the disease itself and is written in a ‘question and answer’ format to answer the most common questions asked about mesothelioma. I’m sure there are many more which are beyond the scope of this small booklet, but further sources of
information and advice are listed in part

Mesothelioma (also known as ‘diffuse’ or ‘malignant’ Mesothelioma) is a form of cancer, which affects the thin membranes which line the chest (pleural mesothelioma). Less commonly it can affect the linings of the abdomen (peritoneal mesothelioma). It may also surround the organs found within these cavities for example the heart, lung and intestines.

Pleural Mesothelioma
The pleural lining has two layers - an inner (visceral) layer which lines the lung and an outer (parietal) layer which lines the chest wall. The pleura produce fluid to lubricate the space between the two layers allowing the layers to slide comfortably over each other as we breathe.Pleural Mesothelioma causes the pleura to thicken. This may make it press on the lung or attach itself to the chest wall. Fluid, sometimes several litres, can collect between the two layers and cause
breathlessness. This is known as a Pleural effusion

Peritoneal Mesothelioma
The peritoneum also has two layers, the inner (visceral) layer which is next to the abdominal organs and the outer (parietal) layer which lines the abdominal wall. Peritoneal Mesothelioma causes the peritoneum to thicken and fluid to collect in the abdomen, this collection of fluid is called ascites and causes the abdomen to swell. Peritoneal Mesothelioma is much less common than Pleural Mesothelioma.

Asbestos in Older Homes


Asbestos in Older Homes

Asbestos has been a growing concern for city governments and the owners of public buildings for some time. In recent years, concerns about asbestos have become a growing issue among the owners of single family homes. These are some of the questions most commonly asked of asbestos abatement companies by the owners of private homes, and their best answers.

  1. How likely is my home to contain asbestos?

If your home was built after 1980, the chances that it contains asbestos or any materials that have asbestos added to them is very small. If your home was built or underwent major renovations between World War I and 1980, there’s a very good chance that there are materials in your home that contain asbestos.

  1. How dangerous is asbestos in my home?

While asbestos is a known carcinogen, it is only dangerous in the form of tiny airborne fibers. Asbestos is a mineral that easily separates into tiny fibers that are light enough to float in the air. Those fibers were often mixed into things like paint, cement and wood pulp to help make them fire resistant and increase their insulating properties. As long as those materials are in good repair, the chance of them releasing asbestos fibers is very small, and there is little health risk in living with them.

  1. Why is asbestos dangerous?

Breathing in asbestos fibers increases your risk of developing lung cancer, causes asbestosis – scarring of the lungs – and may lead to the development of mesothelioma, a rare cancer that is only found in people who were exposed to asbestos. For additional resources please see the resources at Asbestos.com

  1. When is asbestos dangerous to me or my family?

Asbestos containing materials can become dangerous to your family’s health when they are damaged or disturbed enough to release fibers of asbestos into the air.

  1. How can I tell if something in my home contains asbestos?

The only way to know for sure that a material in your home contains asbestos is to have it examined by a professional. It’s nearly impossible to identify asbestos by visual examination alone unless you have the experience and knowledge to identify specific brands and types of materials by sight. Even then, most professionals rely on a microscopic examination to determine whether a material contains asbestos.

If you suspect that something in your home is made of asbestos, you have two choices: you can assume that it contains asbestos and take the same precautions you would if you were certain that it did, or you can have it tested by a professional asbestos surveyor. Testing is not very expensive, and it could set your mind at east.

  1. Where might I find asbestos in my home?

Asbestos was used in thousands of different products that were used in home construction and consumer products. Among the most common places to find asbestos are:

- roofing and siding shingles made with asbestos cement

- insulation in homes built between 1930 and 1950

- textured paints used for decorative ceiling and wall coatings (banned in 1977)

- pipe insulation and caulking

- furnace or water heater blankets may contain asbestos

- the floor and walls under and behind stoves, fireplaces and heaters may be protected with asbestos containing millboard, asbestos paper or cement sheets containing asbestos

- the door gaskets in oil or coal furnaces may contain asbestos

- joint compound used to seal wallboard may contain asbestos

- resilient floor tiles or sheet vinyl flooring may have been made with or backed with asbestos containing materials

- decorative plaster treatments on walls and ceilings may contain asbestos


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Advances in Radiation Therapy for Mesothelioma









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THE INCIDENCE OF MESOTHELIOMA IN AUSTRALIA 1997 to 1999































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MALIGNANT MESOTHELIOMA


A. PHILIPPE CHAHINIAN, MD
HARVEY I. PASS, MD


CLINICAL FEATURES
The onset of mesothelioma is usually insidious; a common pre-senting symptom is persistent localized pain.PLEURAL MESOTHELIOMA Chest pain or dyspnea is almost constant, although of varying degree.63,214 Pleural effusion is present initially inup to 95% of cases. 63 Later, tumor growth usually results in complete obliteration of the pleural space and encasement of the lung. 93,214,264Cough, weight loss, and fever are not uncommon. In contrast to benign mesothelioma, clubbing is rare and was seen only in 6% of cases. 51 Mediastinal invasion with dysphagia, phrenic nerve paralysis, pericar-dial effusion, and superior vena cava syndrome can occur. 225 Sponta- neous pneumothorax or hydropneumothorax and Horner’s syndrome have been described. 127,206 Progressive invasion of the chest wall often leads to intractable pain. Chest radiographs reveal a variable amount of fluid, with pleural thickening or pleural nodules, often several centimeters in diameter, imposing a scalloped appearance (Fig. 89.2). Predominance at the base is almost constant. In advanced cases, psilateral shift of the mediastinum and retraction of the involved hemithorax are characteristic, unless the tumor volume becomes very large.

63,93 The electro cardiogram (ECG) is abnormal in almost 90% of patients, showing various arrythmias (sinus tachycardia is the single most common change [42% of cases] but also premature atrial or ventricular contractions, atrial fibrillation, or flutter), conduction abnormalities (right-side bundle branch block, left hemiblocks), nonspecific ST-T changes, or left or right hypertrophy. 289 Computed tomography (CT) is most valuable in showing the extent of disease (including chest wall, mediastinum, pericardium, and diaphragm), relative amount of fluid and tumor, involvement of interlobar fissures, and retraction of the involved hemithorax (Fig. 89.3). In addition, signs of asbestos exposure, such as contralateral pulmonary fibrosis and/or pleural plaques, are seen in 50% of cases and pleural calcifications in 15%.202 Furtherstudies are needed to evaluate the role of magnetic resonance imaging (MRI). MRI has been better than CT in showing tumor spread into the fissures, diaphragm, and bony structures, whereas both procedures are equally effective to detect invasion into the chest wall, lung, and mediastinum.

145a Echocardiography is useful to reveal pericardial involve ment, especially if cardiac tamponade is suspected. 289 Uptake of gal lium 67GA citrate by mesothelioma tumors has been experimentally demonstrated, 273 and gallium scan was positive in 43 of 49 patients (88%) with pleural mesothelioma.265 Recently, the role of fluo rodeoxyglucose (FDG) positron emission tomography (PET) imaging has been examined in a cohort of 28 patients with suspected mesothelioma (confirmed in 22). 26b Standardized uptake values (SUVs) were determined from the most active tumor site in each patient. The mean SUV of the deceased patients was 6.6 +/- 2.9, compared with 3.2 +/- 1.6 among the combined survivors. The deceased patients had tumor SUVs that were highly correlated with duration of survival after the PET study. The survival distribution of the high-SUV group showed significantly shorter survivals, compared with the low-SUV group.

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MESOTHELIOMA IN AUSTRALIA INCIDENCE 1982 TO 2005 DEATHS 1997 TO 2006

Report summary
Data on the number of new cases of mesothelioma are collected nationally by the Australian Institute of Health and Welfare (AIHW) in the National Cancer Statistics Clearing House, via the State Cancer Registries. Information on deaths from mesothelioma is also collected by the AIHW as part of the National Mortality Database. Data are available from 1982 to 2005 for the number of new cases, and from 1997 to 2006 for the number of deaths.

New cases diagnosed
> In 2005 there were 597 new cases of mesothelioma diagnosed in Australia. Although this fgure is considerably higher than the 156 reported in 1982, the earliest data available, it is a reduction from the fgure of 645 new cases reported in 2003. Over the period since 1982 the large majority of new cases involved men: typically accounting for between 80% and 90% of new cases. > In 2005, the age-standardised rate of new cases of mesothelioma was 2.8 per 100 000 population. This rate has increased over time, from 1.2 cases in 1982. In 2005, the highest age-specifc incidence rate of new cases, 47 cases per 100 000 population, occurred among men aged 80–84 years.

Deaths due to mesothelioma
> In 2006 there were 486 deaths attributed to mesothelioma. Data on the number of deaths due to mesothelioma are available for the years 1997 to 2006. Refecting the incidence of new cases diagnosed, the overall number of deaths resulting from mesothelioma generally increased over the period between 1997 and 2006: reaching a maximum of 545 in 2004. > In 2006, the age-standardised rate of death due to mesothelioma was 2.3 deaths per 100 000 population.
The overall age-standardised rate has remained relatively stable over the 10 years for which data are available. Over the period the standardised rate has ranged between a minimum of 2.1 deaths per 100 000 population in 1999 and a maximum of 2.7 in 2001.

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Alternative Medicine? A History



Whether acupuncture from China, Ayurvedic therapies from India, or home opathy in Europe, in her scholarly book, Roberta Bivins presents the belief systems that gave rise to such ancient practices and then follows their subsequent problematic global voyages to other cultures. Neither an allopathic doctor nor an alternat ive pract it ioner, Bivins provides readers with a social examination of these “exotic” techniques, from moxabustion to mesmerism, and explains how each was int roduced (and then studied, simulated, ridiculed, or rejected) by Western physicians in Europe and the United States. The nearly four-century transcontinental propagation was
not always easy — especially when corresponding bel ief systems could not be t ranspor ted along
with the therapeutic techniques.

The basis of many premodern medical practices rested on the belief that the human body was
a microcosm of the universe. For instance, with out the benefit of anatomical dissection (which
was then amoral and illegal) or microscopic analysis (which was then unavailable), the cupunc
turists in ancient China believed there were 12 waterways in the body that mirrored the coun
try’s 12 great rivers and canals. Ayurvedic medical pract it ioners believed in a deep philosophical and cosmological spiritual world of reincarnation and karma. A person’s balanced and healthy interactions with the environment were necessary not only for the body but also for the soul. The translat ion of these principles and techniques f rom East to West paralleled the interaction of the cultures themselves, with all the inherent stereotyping, superstitions, and feelings of racial and cultural superiority. Ultimately, despite British imperialism or the medical profession’s turf wars, it was often the realities of — and the lack of therapies forepidemics of cholera and the plague, or ailments such as gout, that encouraged quick investigation and resulted in rejection or eventual co-optation of the unfamiliar treatments.

Of note, the authorities investigating and discounting alterative therapies were also often “borrowing” the practices for reintroduction as their own. One example was moxabustion, a therapy that uses heat and was apparently effective in the treatment of gout.

Therapy of Mesothelioma


Immune and Antitumor Effects of Transfected Interleukin-12Irina Caminschi, Eleni Venetsanakos, Clement C. Leong, Michael J. Garlepp, Bruce W. S. Robinson, and Bernadette Scott Department of Medicine, University of Western Australia; Australian Neuromuscular Research Institute,Queen Elizabeth II Medical Centre, Nedlands, Australia; and DNAX Research Institute, Palo Alto, California Malignant mesothelioma (MM) is a solid tumor of the mesothelium for which there is no curative treat- ment. MM appears to be sensitive to immunotherapeutic approaches, and one of the most powerful immu- nomodulatory cytokines with antitumor effects is interleukin (IL)-12.
We have previously shown in a mu- rine model of MM that systemic administration of recombinant IL-12 induces a potent anti-MM immune response.
The nature and accessibility of MM tumors means that they are suitable candidates for direct cy-
tokine and gene-transfer therapeutic approaches. Therefore, we undertook a study to assess the antitumor effects induced by the local production of IL-12 within MM tumors by transfecting a murine MM line with the genes for IL-12. The IL-12 transfectant (AB1–IL-12) did not produce tumors in normal mice, but did so in athymic nude mice, implicating T cells in the prevention of MM tumor growth. In mixing experi- ments, paracrine IL-12 production inhibited growth of untransfected MM cells provided that cells produc- ing IL-12 represented more than 50–80% of the inoculum. Furthermore, BALB/c mice previously chal- lenged with AB1–IL-12 were protected against rechallenge with parental AB1 tumor, indicating that the
transfectant induced long-term immunity. AB1–IL-12 induced systemic immunity that was effective at re-ducing the incidence of parental AB1 tumor at a distal site, but its effects were dose-dependent. Though both CD41 and CD81 cells infiltrated the rejecting tumor, CD81 effector cells were essential for protec-tion against development of parental AB1 tumor. This study shows that paracrine secretion of IL-12, gen-erated by gene transfer, can induce immunity against MM that can act locally and also at a distant site. In addition, there was no evidence of toxicity, which has been associated with the systemic administration of IL-12, indicating that this cytokine is a good candidate for experimental gene therapy in MM. Caminschi,
I., E. Venetsanakos, C. C. Leong, M. J. Garlepp, B. W. S. Robinson, and B. Scott. 1999. Cytokine
gene therapy of mesothelioma: immune and antitumor effects of transfected interleukin-12. Am. J. Respir. Cell Mol. Biol. 21:347–356.

Materials and Methods
Mice
BALB/c and BALB/c-nu/nu mice were obtained from the Animal Resource Center (Perth, Western Australia) and maintained under standard conditions at the animal facil- ity of the Department of Medicine, University of Western Australia.

Cell Lines
The establishment of the BALB/c mouse-derived MM tumor cell line AB1 has been described previously (23). Cell lines were maintained in RPMI 1640 medium (GIBCO, Grand Island, NY) supplemented with 5% fetal bovine serum (GIBCO), 20 mM 4-(2-hydroxyethyl)-1-piperazine-
N-2-ethanesulfonic acid, 200 mM L-glutamine (GIBCO), 0.05 mM mercaptoethanol, 100 mg/ml gentamicin, and 120 mg/ml of penicillin. Additionally, cell lines transfected with the bacterial neomycin phosphotransferase gene were maintained in medium containing G418 (Geneticin; GIBCO; 400 mg/ml). All cell cultures were grown at 378C in a 5% CO2 humidified atmosphere.


MESOTHELIOMA


Mesothelioma


The U.S. government reports that 70% to 80% of all cases of mesothelioma occur in people with a traceable history of exposure to asbestos. These numbers are from epidemiological surveys. There is a good chance that many of the remaining mesothelioma cases are also due to asbestos, but that the patient could not identify exactly where or when the asbestos fiber exposure occurred.

Mesothelioma is a very tough cancer. Most patients undergo surgery and chemotherapy. Sometimes radiation therapy is employed, including innovative techniques such as tomotherapy and intensity modulated radiation therapy. Oncologists use Brachytherapy for targeted radiation treatment of the tumor.

The antifolate drug pemetrexed (Alimta) in combination with cisplatin has been embraced by many mesothelioma specialists. Median survival time, even with good medical care, is fairly low.
Effusions into the bodily cavities is a common symptom. The chest, or pleural cavity, gets effusions, as well as the peritoneal (abdominal) cavity, depending on the site and shape of the tumor. Mesothelioma is classified as either pleural (the most common type) or peritoneal, depending on the location of the disease. (There are other types, but pleural and peritoneal are the most common.) To diagnose mesothelioma, the doctor takes a sample, usually of the pleural fluid, and conducts a biopsy in a lab. Immunohistochemical markers are employed in biopsy to distinguish mesothelioma from adenocarcinoma. These markers are usually glycoproteins.

Other markers can be detected in the blood to help identify mesothelioma. Soluble mesothelin-related (SMR) proteins released by mesothelioma cells are distinctive enough to show up in the blood, if the appropriate test is conducted. However, definitive diagnosis still requires a laboratory biopsy.

Tests and trials with gene therapy and immunotherapy are sometimes done on mesothelioma cases, but the standard cancer treatment modalities of surgery, radiation, and chemotherapy remain the most used techniques in mesothelioma treatment.

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