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Monitoring should be continued and further evaluation carried out if uterine contractions, a nonreassuring fetal heart rate pattern, vaginal bleeding, significant uterine tenderness or irritability, serious maternal 248 Guidelines for Perinatal Care injury, or rupture of the amniotic membranes is present. Upon discharge, the patient should be instructed to return if she develops vaginal bleeding, leakage of fluid, decreased fetal movement, or severe abdominal pain. Consideration should be given to administering 300 micrograms of Rh (O) D immune globulin to all unsensitized Rh (O) D-negative pregnant patients who have experienced abdominal trauma. Labor and Delivery Considerations and Complications Assessment and Management of Fetal Pulmonary Maturation ^145^258 the decision to deliver before 39 weeks of gestation should be based on appropriate medical (maternal or fetal) indications when the risks of continu ing the pregnancy outweigh the risks of delivery. Because of the new appreciation of the neo natal and pediatric risks associated with delivery before 39 weeks of gestation, lung maturity is not an indication for delivery before 39 weeks of gestation. Only occasionally should the knowledge of pulmonary maturity be needed to proceed with a planned delivery before 39 weeks of gestation. Antenatal Corticosteroid Therapy For women at risk of preterm birth, enhancement of fetal pulmonary function with the use of antenatal steroids lessens the prevalence and severity of neonatal Obstetric and Medical Complications 249 respiratory distress syndrome and its sequelae. A single course of corticosteroids (betamethasone or dexamethasone) is recommended for pregnant women between 24 weeks and 34 weeks of gestation who are at risk of preterm delivery within 7 days. Sparse data exist on the efficacy of corticosteroid use before fetal age of viability, and such use is not recommended. A single rescue course of antenatal corticosteroids may be considered if the antecedent treatment was given more than 2 weeks prior, the gestational age is less than 32 6/7 weeks, and the woman is judged by the physician to be likely to give birth within the next week. However, regularly scheduled repeat courses or multiple courses (more than two) are not recommended. Births at the Threshold of Viability Early preterm birth or birth of an extremely low birth weight infant (less than 1,000 g), especially those weighing less than 750 g or less than 26 weeks of gesta tion, poses a variety of complex medical, social, and ethical considerations. The effect of such births on the infants, their families, the health care system, and society is profound. Although the prevalence of such births is less than 1%, they account for nearly one half of all cases of perinatal mortality. Family Counseling When extremely preterm birth is anticipated, the estimated gestational age and weight should be carefully assessed, the prognosis for the fetus should be deter mined, and each member of the health care team should make every effort to maintain a consistent theme in their discussion with family members regarding 250 Guidelines for Perinatal Care the assessment, prognosis, and recommendations for care. Counseling from a practitioner with additional experience and expertise in extremely preterm and extremely low birth weight infants may be appropriate. In general, parents of anticipated extremely preterm fetuses can be coun seled that infants delivered before 24 weeks of gestation are less likely to survive, and those who do are not likely to survive intact. Disabilities in mental and psychomotor development, neuromotor function, or sensory and communication function are present in approximately one half of extremely preterm fetuses. When the extremely preterm newborn does not survive, support should be provided to the family by physicians, nurses, and other staff after the infants death. Management Retrospective studies addressing obstetric management on outcomes of extremely premature neonates have failed to document a benefit of cesarean delivery over vaginal delivery. Maternal transport to a tertiary care center before delivery should be considered whenever possible. Management regarding the extent of resuscitative and supportive efforts should be based on gestational age and birth weight but should be further individualized based on the newborns condition at birth and the parents preferences. This information may be developed by each institution and should indicate the population used in determining estimates of survivability. Chorioamnionitis Chorioamnionitis or intra-amniotic infection is largely a clinical diagnosis that often is made presumptively during labor if a laboring woman develops a Obstetric and Medical Complications 251 fever for which there is no other obvious etiology. The classic signs and symp toms include maternal fever, maternal tachycardia, uterine tenderness, fetal tachycardia, and foul-smelling amniotic fluid. Common organisms that cause chorioamnionitis include gram-negative bacteria (particularly Escherichia coli), gram-positive bacteria (particularly group B streptococci and staphylococcus), and occasionally anaerobes. It is clear that neonates born to mothers with cho rioamnionitis have less infectious outcomes if their mother is treated in utero with appropriate antibiotics. Treatment for chorioamnionitis typically is the administration of ampicillin and gentamicin; treatment with only penicillin or ampicillin is never adequate for chorioamnionitis. Endocarditis Most cases of endocarditis are not attributable to an invasive procedure, but rather are the result of randomly occurring bacteremia from routine daily activi ties. Antibiotic prophylaxis may only prevent a small number of cases of infec tive endocarditis in women undergoing genitourinary procedures, and the risk of antibiotic-associated adverse events exceeds the benefit, if any, from prophy lactic antibiotic therapy. For these reasons, the American Heart Association and the American College of Cardiology no longer recommend infective endocar ditis prophylaxis for either vaginal delivery or cesarean delivery in the absence of infection, except possibly for the small subset of patients at highest potential risk of adverse cardiac outcomes who are undergoing vaginal delivery. Only cardiac conditions associated with the highest risk of adverse outcomes from endocarditis are appropriate for infective endocarditis prophylaxis, and this is primarily for patients undergoing dental procedures that involve manipulation of gingival tissue or the periapical region of teeth, or perforation of the oral mucosa (see Box 7-3. Mitral valve prolapse is not considered a lesion that ever needs infective endocarditis prophylaxis. In patients who have one of the high-risk conditions (see Box 7-3) and an established infection that could result in bacteremia, such as chorioamnionitis or pyelonephritis, the underlying infection should be treated to prevent infec tion or sepsis, but specific additional endocarditis prophylaxis is not recom mended. Multiple-dose combination regimens are no longer indicated or recommended for prophylaxis. Clinically, endome tritis is characterized by fever, uterine tenderness, malaise, tachycardia, abdomi nal pain, or foul-smelling lochia. Of these, fever is the most characteristic and may be the only sign early in the course of infection. Risk factors for postpar tum endometritis include cesarean delivery, prolonged rupture of membranes, Obstetric and Medical Complications 253 prolonged labor with multiple vaginal examinations, intrapartum fever, and lower socioeconomic status. Prophylaxis Against Postcesarean Infection the single most important risk factor for infection in the postpartum period is cesarean delivery. Antimicrobial prophylaxis is recommended for all cesarean deliveries unless the patient is already receiving an antibiotic regimen with appropriate coverage (eg, for chorioamnionitis), and such prophylaxis should be administered within 60 minutes before the start of the cesarean delivery. When this is not possible (eg, need for emergent delivery), prophylaxis should be administered as soon as possible after the incision is made. A single dose of a targeted antibiotic, such as a first-generation cephalo sporin, is the first-line antibiotic of choice, unless significant drug allergies are present. For women with a history of a significant penicillin or cephalosporin allergy (anaphylaxis, angioedema, respiratory distress, or urticaria), a single-dose combination of clindamycin with an aminoglycoside is a reasonable alternative choice for cesarean delivery prophylaxis. Patients with lengthy sur geries or those who experience excessive blood loss should receive an additional intraoperative dose of the antibiotic used for preincision prophylaxis. A woman with postpartum fever should be evaluated by pertinent history, physical exam ination, blood count, and urine culture. Blood cultures rarely influence thera peutic decisions but could be indicated if septicemia is suspected. Cervical, vaginal, or endometrial cultures need not be routinely performed because the results might not indicate the infecting organism. A combination of clindamycin and gentamicin, with the addition of ampicillin in refractory cases, is recommended for cost-effective therapy. Maternal Hemorrhage Hemorrhage remains one of the leading causes of maternal mortality world wide. One half of all maternal deaths occur within 24 hours of delivery and most commonly from excessive bleeding.

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Chapter of the National Association of Business Economics, New York, October 15, 2002. The Emergence and Diffusion of Publicly-Traded Professional Service Firms (draft paper, Faculty of Business, Simon Fraser University, September 2006), pp. Goldman Sachs, 2006 and 2009 10-K; Morgan Stanley, 2008 10-K; Merrill Lynch, 2005 and 2008 10-K. Technically, this deal had two unrated tranches below the equity tranche, also held by Citigroup and the hedge fund. Under the Com munity Reinvestment Act, low and moderate-income borrowers have income that is at most 80% of area median income. Senate Committee on Banking, Housing, and Urban Affairs, the Community Development, Credit Enhancement, and Regulatory Improvement Act of 1993, 103rd Cong. Prime borrowers are defined as those whose mortgages are financed by the government-sponsored enterprises. Federal Reserve Board, Morning Session of Public Hearing on Home Equity Lending, July 27, 2000, opening remarks by Governor Gramlich, p. Alan Greenspan, quoted in David Faber, And Then the Roof Caved In: How Wall Streets Greed and Stupidity Brought Capitalism to Its Knees (Hoboken, N. Gramlich Says Ex Colleague Blocked Crackdown On Predatory Lenders Despite Growing Concerns, Wall Street Journal, June 9, 2007. Fleckenstein and Frederick Sheeham, Greenspans Bubbles: the Age of Ignorance at the Federal Reserve (New York: McGraw-Hill, 2008), p. Current Account Deficit, re marks at the Sandridge Lecture, Virginia Association of Economics, Richmond, Virginia, March 10, 2005. The rules were issued in proposed form at Federal Reg ister 68 (August 5, 2003): 46119. The equity tranches were not offered for public sale but were retained by Citigroup. The ratings from the three agencies measure slightly different credit risk characteristics. S&P and Fitch base their ratings on the probability that a borrower will default; Moodys bases its ratings on the expected loss to the investor. Despite such differences, investors and regulators tend to view the ratings as roughly equivalent. Invoice from Moodys Investors Service to Susan Mills, Citigroup Global Markets Inc. Managers, Mortgage Companies, Happy to Keep Fuel Coming, Asset Securitization Report, May 23, 2005. Matt Tannin, Bear Stearns, email to Bella Borg-Brenner, Stillwater Capital, March 16, 2007; Greg Quental, Bear Stearns, email to Andrew Donnellan, Bear Stearns, et al. Of structured finance securities originally rated triple-A between 1984 and 2006, 56% retained their original rating 5 years later, 5% were downgraded, and 39% were withdrawn. Ann Rutledge is a principal in R&R Consult ing, a coauthor of Elements of Structured Finance (Oxford: Oxford University Press, 2010), and a former employee of Moodys Investor Service. In 2005, the Division of Market Regulation became the Division of Trading and Markets. Chris Swecker, Assistant Director Criminal Investigative Division Federal Bureau of Investigation, statement before the House Financial Services Subcommittee on Housing and Community Opportunity, 108th Cong. Raymond McDaniel, quoted in the transcript of Moodys Managing Directors Town Hall Meeting, September 11, 2007. Keith Johnson, former president and chief operating officer of Clayton Holdings, Inc.


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Lymphoma, melanoma and mesothelioma may also present initially as a malignant pleural effusion of unknown primary. Diagnosis of a malignant effusion of unknown or occult primary is challenging but the identification of the primary tumor is now more successful thanks to advances in diagnostic imaging techniques and commercially available high-quality antibodies. Cytologic Findings in Metastatic Cancers Common cytologic features of most metastatic malignancies in serous effusions include increased cellularity and a distinct non-mesothelial population of enlarged cells that have enlarged nuclei with irregular nuclear contours, high nuclear:cytoplasmic ratio, coarse chromatin, multiple prominent nucleoli, increased mitosis, atypical mitosis and presence of tridimensional tumor cell clusters. Routinely stained smears of malignant effusions with well-differentiated cancer may permit a proper classification of the cancer cells into 4 broad categories: epithelial, lymphomatous, melanocytic and sarcomatous malignancies. Among the carcinomas, tumor cells with squamous or glandular differentiation and anaplastic cancers of small and large cell types can be cytologically typed with confidence in the majority of cases. These specific antigenic expressions will be mentioned in each carcinoma discussed below. However, cells exfoliated from metastatic adenocarcinomas often display considerable overlapping features. Malignant Epithelial Tumors Bronchogenic Carcinoma Bronchogenic cancers account for about 30% of all pleural malignant effusions, and adenocarcinoma is the most common tumor. Cells exfoliated from a bronchogenic adenocarcinoma tend to occur singly and in irregular clusters and show prominent nucleoli, cytoplasmic vacuolization; and multinucleation may be seen. Pleural effusion in a bronchogenic adenocarcinoma showing single and clustered malignant glandular cells. A bronchioloalveolar carcinoma invading the overlaying pleura exfoliates single and clustered malignant glandular cells in associated effusion. A bronchioloalveolar carcinoma showing single and clustered malignant glandular cells. The tumor cells display enlarged nuclei, coarse chromatin and prominent single or multiple nucleoli. Isolated pleomorphic malignant cells with prominent nucleoli from a bronchogenic large cell carcinoma. Cells from a non-keratinizing or poorly differentiated tumor are commonly seen in large syncytial clusters and show a thin, ill-defined cytoplasm. However, single tumor cells with dense and thick or thin cytoplasm are noted in some cases of the poorly differentiated tumor. In other cases cells exfoliated from a poorly differentiated tumor shows cells indistinguishable from those of a lung adenocarcinoma. Pleural effusion from a metastatic well-differentiated squamous cell carcinoma showing single and clustered malignant squamous cells with keratinized cytoplasm. Pleural effusion from a metastatic poorly differentiated squamous cell carcinoma showing large irregular syncytial clusters of non-keratinizing cells. Pleural effusion from a metastatic poorly differentiated squamous cell carcinoma, small cell type, showing small tumor cells with hyperchromatic nuclei present singly and in small clusters. Small cell carcinoma showing clustered small tumor cells with scant cytoplasm, hyperchromatic nuclei and nuclear molding. Tumor cells from a ductal carcinoma are usually monomorphic, have irregular nuclei, multiple nucleoli and a non-vacuolated cytoplasm. They may resemble reactive and atypical mesothelial cells, and they are typically seen in abundant three dimensional, large cell balls or morulae (>50 cells) and papillae. Pleural effusion from metastatic mammary duct carcinoma showing single and clustered monomorphic glandular cells. Metastatic lobular carcinoma of the breast usually shows small epithelial tumor cells with hyperchromatic nuclei that are present singly and in small chains. Single intracytoplasmic vacuoles containing mucinous droplets compressing tumor cell nuclei are seen. The cancer cells may be mistaken for cells derived from a metastatic signet-ring cell carcinoma. Gastrointestinal carcinoma Well and moderately differentiated gastrointestinal adenocarcinomas usually show in effusions cohesive clusters of malignant glandular cells with intracytoplasmic vacuoles admixed with single tumor cells with similar features. A poorly differentiated adenocarcinoma yields large cells with vacuolated cytoplasm, pleomorphic nuclei and prominent nucleoli dispersed singly and in small clusters. Poorly differentiated gastric adenocarcinoma in ascitic fluid showing single and clustered malignant glandular cells with prominent nucleoli. Some tumor cells have a large intracytoplasmic vacuole pushing their nuclei to the cell periphery, creating malignant signet-ring cells. Single malignant glandular cells with signet-ring configuration are most commonly derived from a diffuse carcinoma or signet-ring cell carcinoma of the stomach. The peritoneal effusion displays thick mucinous material, clustered malignant epithelial cells and proliferated capillary blood vessels. Ovarian carcinoma Tumor cells derived from a serous carcinoma of the ovary are typically seen in papillary clusters, and psammoma bodies are often present. It should be born in mind that cells from a papillary carcinoma of the lung and thyroid may also show psammoma bodies. Other Carcinomas Urothelial carcinoma, high-grade of the urinary tract exfoliates its cells singly and in cohesive clusters. The tumor cells show granular, well-defined cytoplasm, oval nuclei, granular chromatin and prominent nucleoli. These cells may show intracytoplasmic bile pigment granules, intercellular bile plugs and intracytoplasmic globular inclusions. Renal Cell Carcinoma of clear cell type yields cohesive tumor cell clusters with clear or granular cytoplasm and oval, large nuclei with prominent nucleoli. Neuroendocrine Carcinoma may arise from the bronchial tree, pancreas, bowels and several other anatomic sites. It exfoliates medium-sized polygonal cells with oval nuclei with stipple chromatin, conspicuous nucleoli and granular cytoplasm. They are commonly present in groups and large clusters with moderate cohesiveness. They are a group of tumors of different histologic types, and except for mature teratoma. Endodermal sinus tumor (yolk sac tumor) cells show, in addition, a positive reaction with alpha-fetoprotein antibody. Squamous cells, in small numbers, are usually represent a contaminant but can be tumor related. A metastatic dysgerminoma to the lung shows in pleural effusion single and loosely clustered large malignant cells with variable, defined cytoplasm and large, round or oval nuclei with prominent nucleoli. These tumors are the commonest non-epithelial malignant tumors associated with a positive effusion. Hodgkin lymphoma, depending on its 45 histologic variant, may exfoliate lymphocytes and eosinophils in addition to its diagnostic Reed-Sternberg cells. Non-Hodgkin lymphomas shed tumor cells varying from benign-appearing lymphoid cells similar to matures lymphocytes in small lymphocytic lymphoma/ chronic lymphocytic leukemia to atypical enlarged lymphoid cells with nuclear indentations and protrusions in higher grade lymphomas. Cells of a chronic myelogenous leukemia consist of mature and immature myelogenous cells without a "leukemic hiatus", as seen in an acute myelogenous leukemia. High-grade tumor showing large cells with pleomorphic nuclei and vacuolated cytoplasm. Multiple myeloma involving the pleura shows single cancer cells with eccentrically located nuclei with cart-wheel chromatin clumping. Intracytoplasmic melanin pigment granules, intranuclear cytoplasmic inclusions and macronucleoli are commonly present. Pleural effusion from a cutaneous melanoma metastatic to the lung: A & B: single and clustered tumor cells showing a large intranuclear cytoplasmic inclusion. The tumor cells tend to have a round configuration and loose their original shapes in tissue sections. Osteogenic sarcoma usually shows rounded large malignant cells with macronucleoli. Cells from a chondrosarcoma display abundant, well-defined cytoplasm and macronucleoli. Ewing sarcoma yields small polygonal cells with oval nuclei and glycogen-rich cytoplasm singly and in rosettes.

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KitaiT, Kaji S,YamamuroA, Tani T, Kinoshita M, EharaN, Kobori A, Kim K, Kita T, 273. Traumatic aortic injury score ography in patients with acute aortic intramural hematoma. Role of transesophageal echocardiography in the diagnosis ulcers: indications to endovascular treatment. Comparative effectiveness of the treatments for thoracic aortic transection [cor Presentation, complications, and natural history of penetrating atherosclerotic rected]. Penetratingathero aortic injury: a lesion associated with advancing diagnostic techniques. Endovascular repair of traumatic thoracic aortic injury: sectionsextendingintoinvolvingtheaorticroot. CatheterCardiovascInterv2000;51: clinical practice guidelines of the Society for Vascular Surgery. Clamp-and-sewtechniquefortraumaticinjuriesofthe aortic aneurysm patientsmore commonly haveconcurrentthoracic aortic aneur aorta: 20-year experience. Endovascularrepair compared with operative repairof traumatic rupture of the thoracicaorta: a non case-control analysis of hospital episode statistics. Eur J Vasc Endovasc Surg 2013; systematic review and a plea for trauma-speci c reporting guidelines. The limitations of thoracic Society of C, European Association for Cardio-Thoracic S, Vahanian A, Al eri O, endovascular aortic repair in altering the natural history of blunt aortic injury. Familial thoracic aortic aneurysms and dissections: incidence, of blunt traumatic thoracic aortic injuries. Aortic Detectionofdissectionoftheaorticintimaandmediaafterangioplastyofcoarcta dilatation patterns and rates in adults with bicuspid aortic valves: a comparative tionoftheaorta. Anangiographic,computertomographic,andechocardiographic study with Marfan syndrome and degenerative aortopathy. Jondeau G, Detaint D, Tubach F, Arnoult F, Milleron O, Raoux F, Delorme G, type A aortic dissection following thoracic aortic endografting. J Vasc Surg 2010; Mimoun L, Krapf L, Hamroun D, Beroud C, Roy C, Vahanian A, Boileau C. Comparison of clinical presentations indicates a change in the epidemiology of the disease. Aboyans V, Kownator S, La tte M, Brochet E, Emmerich J, Tribouilloy C, La tte S, in patients with bicuspid aortic valves. Survival after open versus endovascular thoracic aortic aneurysm eurysm: two population-based studies. Medical treatment for small abdominal aortic ology determines midterm outcome after endovascular repair of the thoracic aneurysms. Ann Thorac Surg 2011;91: inhibitors and aortic rupture: a population-based case-control study. Theeffectofazithromycin Thelifetimeprevalenceofabdominalaorticaneurysmsamongsiblingsofaneurysm and Chlamydophilia pneumonia infection on expansion of small abdominal aortic patientsiseightfoldhigherthanamongsiblingsofspouses:ananalysisof187aneur aneurysms: a prospective randomized double-blind trial. EurHeartJ2009;30: endovascular vs open repair of abdominal aortic aneurysm: a randomized trial. Long-term operative cardiovascular mortality in noncardiac surgery: validation of the Lee comparison of endovascular and open repair of abdominal aortic aneurysm. A randomized controlled trial of endovascular aneurysm Derivation and prospective validation of a simple index for prediction of cardiac repair versus open surgery for abdominal aortic aneurysms in low to risk of major noncardiac surgery. Resection of an aneurysm of the abdominal endovascular stent graft repair of abdominal aortic aneurysms: a meta-analysis of aorta: reestablishment of the continuity by a preserved human arterial graft, with randomized trials. Endovascu larsuitabilityandoutcomeafteropensurgeryforrupturedabdominalaorticaneur tured abdominal aortic aneurysms: a multicenter randomizedcontrolled trial. Predictorsofabdominalaorticaneurysmsacenlargementafterendovas Systematic reviewand meta-analysis of sex differences in outcome after interven cular repair. Association endovascular repair of abdominal aortic aneurysms and possible bene ts of low between sex and perioperative mortality following endovascular repair for rup pro le delivery systems. De Rango P, Verzini F, Parlani G, Cieri E, Simonte G, Farchioni L, Isernia G, Cao P. Safety of chronic anticoagulation therapy after endovascular abdominal aneurysm 390. Arterial anomalies in arterial tortuosity syndrome: a and addressing cardiovascular risk in adults with Turner syndrome. AorticdilatationanddissectioninTurner terial tortuosity syndrome: clinical and molecular ndings in 12 newly identi ed syndrome. Mutations in the facilitative cause of growth failure in children with short stature. Progression rate and early surgical experience in individuals with Marfan syndrome. Zhu L, Vranckx R, Khau Van Kien P, Lalande A, Boisset N, Mathieu F, Wegman M, 429. Mutations in smooth muscle Loeys-Dietz: a new syndrome of aggressive thoracic aortic aneurysm disease. Mutations Cormier-Daire V, Rio M, Lyonnet S, Plauchu H, Lacombe D, Chevallier B, in myosin light chain kinase cause familial aortic dissections. Genetic and complications in patients with bicuspid aortic valve with and without coarctation environmentalcontributionstoabdominalaorticaneurysmdevelopmentinatwin of the aorta. Aneurysmsoftheabdominalaorta: predictors of ascending aortic dilatation in association with a congenital bicuspid familialandgeneticaspectsinthreehundredthirteenpedigrees. Aprospectivestudytoassessthefrequencyof aortic valves are associated with aortic dilatation out of proportion to coexistent familial clustering of congenital bicuspid aortic valve. Familialcongenitalbicuspidaorticvalve: tation in young men with normally functioning bicuspid aortic valves. Familial thoracic dilatationamongyoungcompetitiveathletes:echocardiographicscreeningof1929 aortic dilation and bicommissural aortic valve: a prospective analysis of natural athletes between 15 and 34 years of age. Echocardiographic anatomy of Evaluation of bicuspid aortic valve and aortic coarctation with 4D ow magnetic ascendingaortadilatation:correlationswithaorticvalvemorphologyandfunction. Naturalhistoryofascendingaorticaneurysmsinthesettingofanunre Ascending aortic diameters in congenital aortic stenosis: cardiac magnetic reson placed bicuspid aortic valve. Naturalhistoryofasymptomaticpatients absence of restenosis and prosthetic material. When to operate on the bicuspid valve patient with a modestly dilated ascending 492. Atheroscleroticdiseaseoftheaorticarchandtheriskof aortic aneurysm after aortic valve replacement for bicuspid versus tricuspid ischemic stroke. Thoracicaorticaneurysmassociatedwith perative ultrasonographic evaluation of the ascending aorta in 100 consecutive congenital bicuspid aortic valve. Atheroscleroticdiseaseofthe of stroke during heart surgery with and without aortic arch endarterectomy. Transcatheter aortic-valve implantation for coronaryangiographyorinterventionandtheimpactonmajorbleedingandische aortic stenosis in patients who cannot undergo surgery.

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Others in this quintile are largely northern European countries, Australia and the United States. The lowest quintile includes Asian and other developing countries that have contributed data to the analysis. Furthermore, it also appears that populations with historically low incidence (Asia, south Europe) may be experiencing accelerated growth in these diseases. International studies are very similar to Canadian findings with respect to other aspects of epidemiology, specifically age of onset and prevalence by age. Findings from the recent broad American database study found reasonably similar results for incidence and prevalence in the pediatric population. Figure 13 shows the pattern with respect to incidence, and once again, Canadian rates are in the top quintile (top 20%. It is reasonable to assume that the risk of death is similar in European and North American countries, given a uniformly high standard of medical care and life expectancy. There are very low rates of death in younger people, even for those with severe disease. This means that it is necessary to study a very large group of people, and/ or study them for a very long period of time, in order to identify any trends of increased death. Seven of these studies have found an increased risk of death, while three studies have reported a slightly lower risk of death. When faced with conflicting results from multiple studies, researchers can conduct a meta-analysis. This is a statistical technique which combines data from multiple independent studies to generate a more precise estimate. Studies which are similar in methods and in quality can be combined, with more weight given to studies which include more patients (and less weight given to smaller studies. Crohns and Colitis Australia conducted another meta-analysis, using these studies: three studies reporting an increased risk, and five studies reporting a decreased risk. There is a 47% increased risk of death, and an increased risk of colorectal cancer. Many young adults are starting careers, seriously dating/engaged and travelling the world. These activities carry a lot of stress without the addition of a chronic auto-immune disease. Current drugs are more expensive but can prevent hospitalizations and improve health outcomes. This may be related to increased specialist care and more aggressive use of medication to control disease. A conservative estimate based on international measurements is $101 million in Canada in 2012. Typically, these include: hospitalizations, surgeries, emergency department visits, physician services, medications, laboratory tests and procedures, allied health care professional visits (for example, physiotherapist, occupational therapist, dietitian, chiropractor, massage therapist), social services (home health care, meal delivery, transit for handicapped, etc. With increasing disease activity and flares, medications are increased and hospitalizations for surgery become common. People who have severe disease may require high levels of care, including home health care and (very rarely) institutional care. One limitation with this research is that prices and patterns of use for health care services reflect local health care systems and practices. While there can be considerable similarity across countries, the most reliable way to measure direct medical costs in Canada is to use research conducted in Canada. During times of increasing symptoms and higher disease activity, most patients will require increased doses or additional medications to reduce symptoms, prevent complications, and return to remission. For disease flares, corticosteroids are powerful drugs to control the immune system and induce remission. However, these drugs have long-term safety concerns, so it is not desirable to stay on these drugs for prolonged periods of time. For long-term control, people are treated with medications such as immune modifiers and 5-aminosalicylates to control their disease on an ongoing basis. They are much more expensive than conventional, older drugs, given the complicated way that they are produced, but they are also quite effective, especially for people who have responded well to other drugs. Drug claims data across public and private payers showed that costs for the most recent year (2011) totaled $460 million. There has been steady and significant growth in drug costs over the past several years, as biologicals have become the standard of care for people with more severe disease. However, at least for the biologicals, most people cannot afford to pay out of pocket, so these products are almost all paid within drug plans. It was conservative to exclude drug costs that are borne by the individual, although they may be significant and a burden to the person and family. An average-sized adult can expect to be billed approximately $4,333 for each infusion66, and infusions are given every 6 to 8 weeks which can lead to individual patient costs approximately $20,000 to $50,000 per year depending upon the dose and frequency of treatment. Many health insurance policies have out-of-pocket maximums that limit a patients expenses. But those maximums vary greatly, leaving many insured individuals to face thousands of dollars in annual expenses. In Canada, ten provincial and two territorial drug plans pay 46% of that total, private insurance and workplace health plans 36%, and uninsured patients 18%, according to the Canadian Institute for Health Information67 people who receive them incur high levels of health care costs. However, Canadian research shows that biological-users required substantial health care resources before they receive biologicals. There were important differences in costs across the country, with per-capita drug costs twice as large in some provinces as in others. This could reflect differences in treatment practices or differences in access (funding) available for the biological drugs. There was also a three fold difference in the percentage of drug costs that was paid for by public plans versus private plans. This is due to the differences between the provincially-administered public drug plans, in both the type of drug that is funded and the extent of the population that is covered. Although Canada has universal health care, drugs are outside of the system in most provinces. Everyone may access physicians, specialists, emergency rooms and hospitals, but not everyone has the same opportunity for drug coverage. The most expensive cases fell into four categories: people in their first year post-diagnosis ($6,611), those who were hospitalized overnight ($13,494), those who had surgery ($18,749), and those using infliximab ($31,440. The Manitoba study was essential for the estimation of inpatient hospitalization, outpatient hospitalization (same-day stays and procedures), and physician visits. After subtracting drug costs, the average cost for these three items was $2,260 in 2005/6, or $2,521 per person in 2012 dollars. Of this amount, 67% was due to hospitalization, 22% to doctor visits, and 10% to outpatient visits. A considerable amount of hospitalization occurs within the first years of diagnosis of disease. Specialist care from the outset of the disease is associated with these trends to reduced surgery and more aggressive use of medication to manage disease. Finally, children are more likely to receive immunomodulatory and biological therapy than previously. Often, they are reported without enough detail in order to accurately convert data to a current Canadian cost. As mentioned earlier, patterns of care in other countries are not necessarily the same as in Canada. However, international studies are needed to get an estimate of these other costs, because there are no Canadian sources. We can piece together estimates from other countries where they do not overlap with any other resources. Drug costs were the single largest component of cost, followed by inpatient hospitalization.

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Aggressive patent enforcement might reduce the number of outlets for genetic testing, and for those not covered by health plans covering payment to Athena Diagnostics, this would reduce access. It therefore appears that access depends on an unstable intellectual property regime and the vicissitudes of payment contracts between health insurers and health care plans, on one hand, and different testing labs, on the other. Genetic testing for hearing loss also illustrates several other features of intellectual property and genetic testing. Most of the patents for commonly tested genes are owned by academic institutions and licensed to Athena Diagnostics. The patenting and licensing practices of academic institutions are therefore linked to both the benefits and problems associated with having a single major provider. The case also illustrates the penumbra effect of exclusive rights to some mutations leveraging testing for others, although it is also clear from this case that the effect is incomplete since multiple providers are offering tests. Faherty, Michael Henry, Wayne Grody, Iris Schrijver, Sherri Bale, Michael Hopkins, Ignacio del Castillo, and Michael Watson for the Secretarys Advisory Committee on Genetics, Health, and Society. SyndromicDisorders:K nownG enes,G eneticTests,andPatents PatentH older Patternof A ge of Test (Patent Disorder Type Inh eritance G enes O nset Relative F requency Prevalence A vailable D -34 A ppendix V :PatentA pplicationsforhighthroughputhearing lossdiagnostic testing Patent/A pplication N o. A ssignee Inventors Publication/F ileDate T itle V ictoriaSiem ering, U S20070009887A 1 N one H enrikD ahl 2007-01-11/2003-11-18 G enotyping of deafnessbyoligonucleotidem icroarray analysis U S20070134691A 1 N one IrisSchrijveretal. ThirdW ave D orn,E rin; 2004-10-14 /2004-01-09 Connex inalleledetectionassays U S20040203035A 1 Technologies, K wiatkowski,R obertJ Inc. D obrowolskiandZhiliL inwereem ployeesof N eoG enScreening IncwhichwasacquiredbyPediatrix M edicalG roup andrenam ed Pediatrix Screening in2003. You noted that a letter had been sent to John Compton on November 11, 2002 regarding this issue. We had moved to 207 Perry Parkway the previous month and our mail was not being forwarded by the post office. We have reviewed the two patents to which your letter of September 11, 2006 refer (5,998,147 and 6,485,908. These two patents specifically make claims regarding detecting mutations in the Connexin 26 gene comprising a deletion of a nucleotide from nucleotides 30 to 32 or a deletion of 38 base pairs beginning at position 30 (mutations described as being involved in autosomal recessive prelingual non syndromic deafness. Functional defects of Cx26 resulting from a heterozygous missense mutation in a family with dominant deaf-mutism and palmoplantar keratoderma. Since the body lacks a natural way to rid itself of the excess iron, it accumulates over time, resulting in organ damage, particularly in the heart, liver, and pancreas. In extreme cases, hemochromatosis can even lead to death, usually due to heart or liver failure. In addition, the variability and non-specific nature of symptoms can make diagnosis difficult, raising the possibility that patients, especially those with no family history, may be diagnosed too late. Screening primary care patients for hereditary hemochromatosis with trasnferrin saturation and serum ferritim level: systematic review for the American College of Physicians. Hemochromatosis and the enigma of misplaced iron: implications for infectious disease and survival. Despite this, universal genetic screening has not been recommended for several reasons. The path to the current state, however, involved transitional periods of turbulence that centered on exclusive licensing of a genetic diagnostic test. Screening for hereditary hemochromatosis: a clinical practice guideline from the American College of Physicians. The clinical utility of those tools, including genetic testing, evolves over time. Lessons Learned Research the Mercator Genetics business plan was centered on the identification of candidate genes for a number of complex diseases including asthma, schizophrenia, cardiovascular disease and prostate cancer, all of which presumably had a diagnostic market. Dennis Drayna, co-founder of Mercator Genetics, notes that the company was conceived and initially funded on an agenda much broader than hemochromatosis gene discovery or diagnostic testing alone. Two additional groups (one in France and another in Australia, which were both in non-profit institutions) were pursuing similar approaches to candidate gene identification and would likely have been successful in their efforts within months. However, the scale and focus of the positional cloning effort at Mercator, enabled by private R&D investment, probably gave their research group a competitive advantage. It is unclear, however, if this delay resulted from scientific issues, patenting activities, corporate strategy, or commercialization efforts by Mercator. It remains possible that such a delay may be the consequence of factors unrelated to patenting, such as the need for additional research or data prior to submission to peer reviewed journals, journal requests for additional data and experiments, delays in peer review, etc. Dennis Drayna, a senior author of the Nature Genetics paper, indicated that the latter was in fact true, and that Mercator Genetics made every attempt to expedite simultaneous paper submissions and patent filings. Substantial basic research, including identification of genes and mutations associated with other types of hemochromatosis has continued. It is likely that the prospect of revenues from population wide screening may have served as an incentive for test development. However, no test was marketed before Mercator went out of business and merged with Progenitor. We cannot assess whether alternatives were unimpeded in all cases, but at least some alternatives have developed. The patent-associated fees may have discouraged some 15 laboratories from entering the market, but testing is widely available from multiple sources. The organizations promoting awareness are not the patent-holders, and the motivation appears to be public health awareness. Out of 31 other laboratories that had not developed the test, 22 indicated patents were the primary reason for not doing so. Adoption by third party payers Patents do not appear to have had a direct or significant effect on decisions to cover the test by public or private insurance providers. However, most laboratories did continue offering the test as a 16 Information about the American Hemochromatosis Society can be found at. The effects that the reduction in number of laboratories had on patient access or consumer utilization cannot be determined. A large number of clinical laboratories offer the test in the price range of $160 $500. In the absence of quantitative data on how many tests are ordered per year and when and how often insurance coverage is denied, it is unclear to what extent third party adoption affects consumer utilization. The effect of patents on such coverage decisions, if any, was not mentioned by those offering tests or seeking reimbursement for them, and was not noted in payer coverage or reimbursement policies. The most common symptoms include joint pain, fatigue, lack of energy, abdominal pain, loss of sex drive, and heart problems (including both arrhythmia and cardiomyopathy, or loss of cardiac muscle function. Men are more likely to experience symptoms and experience them earlier in life, between the ages of 30 and 50. Several metabolic studies have suggested that the diabetes seen in hemochromatosis is more often insulin resistance of cirrhosis. Individuals with signs of iron overload could then be evaluated with genetic testing and other means for determining causes of iron overload. Most 23 patients are homozygous for the mutation, which is transmitted in an autosomal recessive manner. Another mutation, H63D, is the result of the substitution of an aspartic acid for a histidine at position 63. When H63D is inherited from one parent, it usually causes little increase in iron absorption and rarely leads to the development of hemochromatosis. Other mutations with less frequency and/or low penetrance have also been described, including V53M, V59M, H63H, Q127H, 26 Q283P, P168X, E168Q, E168X, and W168X. Environmental and genetic modifiers of the progression to fibrosis and cirrhosis in hemochromatosis. Genetic Tests for Hemochromatosis Several genetic tests are currently available for hemochromatosis. Several common testing methods for the presence of the C282Y and H63D mutations were used by 90 U. Some methods are more labor intensive than others, making them suitable only for research rather than diagnostic laboratories.

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Steps in Delivery Room Management At birth, the neonatal care team implements a sequence of steps to quickly assess and stabilize the infant in order to institute the appropriate intensity of newborn care. With careful consideration of risk factors, most newborns who will need resuscitation can be identified before birth. If the possible need for resuscitation is anticipated, additional skilled personnel should be recruited and the necessary equipment prepared. Assessment Newborns who do not require resuscitation should be identified by rapid assess ment of three characteristics: 1. The baby should be dried, placed skin to-skin with the mother, and covered with dry linen to maintain temperature. The decision to progress beyond the initial steps is determined by simultane ous assessment of two vital characteristics: 1) respirations (apnea, gasping, or Care of the Newborn 269 Yes, stay Routine care Birth Term gestation Neonatal resuscitation: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Part 15: neonatal resuscitation: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Palpation of the pulse at the base of the umbilical cord is the easiest and quickest method to determine the heart rate. If a pulse is not palpable, assessment of heart rate should be done by auscultating the precordial heart tones. Once positive pressure ventilation with or without supplemental oxygen administration is begun, assessment should consist of simultaneous evaluation of three vital characteristics: 1) heart rate, 2) respira tions, and 3) the state of oxygenation (the latter optimally determined by a pulse oximeter. Infants who require stabilization or resuscitation should be placed under a preheated radiant warmer. The radiant warmer will reduce heat loss and allow easy access to the newborn during resuscitation procedures. An infant older than 28 weeks of gestation who requires resuscitation should be dried completely with prewarmed towels and placed under a preheated radiant warmer. Very low birth weight (less than 1,500 g) preterm babies are likely to become hypothermic despite the use of traditional techniques for decreasing heat loss. Because infants younger than 28 weeks of gestation may become hypothermic while being dried, they should be immediately covered up to their necks in polyethylene wrap or a food-grade plastic bag and placed under a radiant warmer. The infants temperature must be monitored closely because overheating has been described when plastic wrap is used in combina tion with an exothermic mattress. When the newborn is vigorous (defined as having strong respiratory efforts, good muscle tone, and a heart rate greater than 100 beats per minute), there is no evidence that nasopharyngeal suctioning is neces sary. It is recommended that suctioning of the airway immediately after birth (including suctioning with a bulb syringe) should be reserved for babies who Care of the Newborn 271 have obvious airway obstruction that interferes with spontaneous breathing or who require positive pressure ventilation. The mouth should be suctioned before the nose so there is nothing to aspirate if the neonate gasps when the nose is suctioned. Vigorous suctioning of the posterior pharynx should be avoided because this may produce significant reflex bradycardia and may dam age the oral mucosa, leading to interference with suckling because of pain. When using suction from the wall or a pump, the suction pressure should be set so that negative pressure reads approximately 100 mm Hg when the suction tubing is blocked. The newborn can be positioned on either the back or the side, with the neck slightly extended. This position (known as the sniffing position) readily aligns the posterior pharynx, larynx, and trachea for optimal air entry, for both spontaneous breaths and bag and mask ventilation. However, if the infant does not have adequate respirations, some additional tactile stimulation may be needed. Acceptable methods of stimulation include slapping or flicking the soles of the feet, and gently rub bing the newborns back, trunk, or extremities. If the baby does not respond to one or two slaps, flicks to the feet, or rubbing of the back, positive pressure ventilation should be initiated. Published data indicate that positive pressure ventilation should be initiated with air in the term infant; however, the data regarding the preterm infant are less clear. The goal of resuscitation is to achieve an oxygen saturation value in the interquartile range of preductal saturations for each minute after birth measured in healthy term babies after vaginal birth at sea level (see table in Fig. In the term infant, these targets can, in most instances, be achieved by initiating resuscitation with air. The oxygen concentration may be titrated, if needed, to achieve an Spo2 in the 272 Guidelines for Perinatal Care target range. It is recommended that oximetry be used when resuscitation can be anticipated, supplemental oxygen is administered, positive pressure is administered for more than a few breaths, or when cyanosis appears to persist. Because many babies born at less than 32 weeks of gestation will not reach target saturations when resuscitated with air, blended oxygen and air may be given judiciously and pulse oximetry should ideally be used to guide adjust ments to the amount of oxygen given. The normal newborn breathes within seconds of delivery and usually has established regular respirations within 1 minute after delivery. A newborn who is apneic or is gasping or whose heart rate is less than 100 beats per minute requires positive pressure ventilation. For most newborns, bag and mask ventilation is effective, can serve to stimulate the initiation of spontane ous respirations, and is the only resuscitation maneuver required to establish regular respirations. If the heart rate does not increase with ventilation, poor ventilation due to failure to establish functional residual capacity should be suspected. In this case, corrective steps, such as opening the mouth, suctioning the orophar ynx, and increasing the pressure used to deliver breaths should be considered. If resuscitation was initiated with air or blended oxygen and air, and there is no improvement in heart rate after 90 seconds of effective ventilation, the oxygen concentration should be increased to 100%. Endotracheal intubation may be performed at various points during resus citation, depending on the clinical circumstances. Individuals not adept at intubation should obtain assistance and focus on providing effective positive pressure ventilation with a mask rather than using valuable time attempting to intubate. Care of the Newborn 273 Exhaled carbon dioxide detection is the recommended method to confirm endotracheal tube placement; however, critically ill infants with poor cardiac output and poor or absent pulmonary blood flow may not exhale sufficient carbon dioxide to be detected reliably and thus may give false-negative test results. As with bag and mask ventilation, effective assisted ventilation with an endotracheal tube should result in an increased heart rate. If the heart rate does not increase promptly above 60 beats per minute after at least 30 seconds of effective ventilation with oxygen, chest compressions should be instituted while ventilation is continued. There should be a 3:1 ratio of compressions to ventilations with approximately 90 compressions and 30 ventilations per minute. The use of medications for resuscitation of the newborn rarely is necessary in the delivery room and should be considered only after effective ven tilation and chest compressions have been established and the heart rate remains low. A list of drugs and volume expanders for resuscitation, with appropriate dosages, should be readily available, preferably in a prominent place in the resus citation area. The efficacy of endotracheal epinephrine is unproven, and use of this route results in lower and unpredictable blood levels that may not be effective. Physicians may choose to give an endotracheal tube dose while the umbilical venous catheter is being placed. An isotonic crystalloid solution (normal saline or Ringers lactate) or type O Rh-negative packed red blood cells (if fetal anemia is known or expected) is recommended for volume expansion in the delivery room.

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I, however, exercised the inventiveness of the true aficionado and got to see it by telling my mother I was going to Davy Crockett, a Disney film which I felt I could summarize safely because I had most of the bubble-gum cards. So-called psychics like to prate of a "sixth sense," a vague term which sometimes means telepathy, sometimes precognition, sometimes God knows what, but if we have a sixth sense, it is probably just (some just! Fido may be able to follow a hundred scents of which we are completely unaware, but the little bugger is never going to be any good at checkers, or even Go Fish. When the lights go out and we find ourselves stranded in a shoal of darkness, reality itself has an unpleasant way of fogging in. When we cut off one avenue of sensory input, that sense simply shuts down (although it never shuts down 100 percent, of course; even in a dark room, we will see a trace pattern in front of our eyes, and in the most perfect silence we will hear a faint hum. Go see a film like Night of the Living Dead all alone (have you ever noticed how many people go to horror movies, not just in pairs or groups, but in actual packs Afterwards, get in your car, drive to an old, deserted, crumbling house-every town has at least one (except maybe Stepford, Connecticut, but they have their own problems there. Consider it as you sit there in the dark, unable to see what might be creeping up. This sort of thing can prove, by its very darkness, to be an enlightening experience. Tales of terror are customarily told "around the campfire" or at least after sundown, because what is laughable in the sunshine is often tougher to smile at by starlight. It was Michael Cantalupo, an assistant editor at Everest House (whose imprint you will find on the spine of this very volume) who reminded me of a gimmick used in the first-run engagements of Wait Until Dark, and in this context it bears an affectionate mention. Hepburn, in a final desperate effort to save her life, breaks every damned lightbulb in the apartment and hallway, so that she and the sighted Arkin will be on even terms. I never real *Now and then someone will run brilliantly counter to the tradition and produce a piece of what is sometimes called "sunlit horror. There are those tiny "dim-bulbs" set into the ceiling if the theater is one of the new breed, those gauche but somehow lovely electric flambeaux glowing along the walls in the older ones. In a pinch, you can always find your way back to your seat after using the bathroom by the light being thrown from the screen itself. Except that the climactic few minutes of Wait Until Dark are set entirely in that black apartment. Then there was the great "Nurse on Duty at All Performances" gimmick; there was the "You Must Have Your Blood Pressure Taken in the Lobby Before Viewing this Horrifying Film" gimmick (that one was used as part of the House on Haunted Hill promo), and all sorts of other gimmicks. The exact plot specifics of the Tingler, a film so exquisitely low budget that it probably made back its production costs after a thousand people had seen it, now escape me, but there was this monster (the Tingler, natch) that lived on fear. I know that must sound pretty fucking stupid, but in the film, it worked (although it probably helped to be eleven years old when you saw it. At one point the Tingler got into a movie theater, killed the projectionist, and somehow shorted out the electricity. At that moment in the theater where you were watching the movie, all the lights went out and the screen went dark. Now as it happened, the only thing that could get the Tingler to let go of your spine once it had attached itself was a good loud scream, which changed the quality of the adrenaline it fed on. And at this point, a narrator on the soundtrack cried out, "The Tingler is now in this theater! During one imported Italian turkey, the Night Evelyn Came Out of the Grave (nifty title! During Jack the Ripper, a 1960 example of "Hammer horror" written by Jimmy Sangster, the black and white film turned to gruesome color during the last five minutes, when the Ripper, who has unwisely chosen to hide in an elevator shaft, is squished under a descending car. There is an interesting similarity between the scene in which the little girl kills her mother with a garden trowel in Night of the Living Dead and the climactic scene in the Birds, where Tippi Hedren is trapped in the attic and attacked by crows, sparrows, and gulls. Both of these scenes are classic examples of how dark and light can be used selectively. We will remember, most of us, from our own childhoods that a lot of light had the power to vanquish imagined evils and fears, but sometimes a little light only made them worse. It was the streetlight outside that made the branches of a nearby tree look like witch fingers, or it was the moonlight streaming in the window that made the jumble of toys pushed away in the closet take on the aspect of a crouching. Hedren carries which provides this strobe effect (also mentioned in connection with Looking for Mr. If there had been no such thing as darkness, the makers of horror movies would have needed to invent it. Even the very worst horror movies sometimes achieve a moment or two of success on this level. Dennis Etchison, a fine writer in the genre, reminisced fondly with me on the phone one day not too long ago about a brief sequence in the Giant Spider Invasion where a lady drinks her morning hi-potency vitamin cocktail, all unknowing that a rather plump spider fell into the blender just before she turned it on. In the eminently forgettable film Squirm, there is that one unforgettable moment (for all two hundred of us who saw the picture) when the lady taking a shower looks up to see why the water stopped coming and sees a showerhead clogged with dangling nightcrawlers. In Maniac, directed by former soft-core filmmaker William Lustig, there is the incredible moment when the homicidal ding-dung (Joe Spinell) carefully scalps one of his victims; *I can remember, as a kid, one of my fellow kids asking me to imagine sliding down a long, polished bannister which suddenly and without warning turns into a razorblade. As noted previously, good horror movies often operate most powerfully on this "wanna-look-at-my-chewed-up-food But the gross-out is art, and it is important that we have an understanding of this. We identify with the woman who is unknowingly drinking the spider on a level that has nothing to do with her character; we identify with her solely as a human being in a situation which has suddenly turned rotten-in other words, the gross-out serves as the means of a last-ditch sort of identification when the more conventional and noble means of characterization have failed. The Man with the X-Ray Eyes marks the point where this strange two-step creature came out of its cocoon, I think. The screenplay was written by Ray Russell, the author of Sardonicus and a number of other novelsamong them the rather overripe Incubus and the much more successful Princess Pamela. In the Man with the X-Ray Eyes, Ray Milland plays a scientist who develops eyedrops which enable him to see through walls, clothing, playing-cards, you name it; a kind of super-Murine, if you will. Our eyes are one of those vulnerable chinks in the armor, one of those places where we can be had. But to the best of my knowledge, no horror movie has ever been made about a nose out of control, and while there has never been a film called the Crawling Ear, there was one called the Crawling Eye. We all understand that eyes are the most vulnerable of our sensory organs, the most vulnerable of our facial accessories, and they are (ick! So when Milland dons shades for the second half of the movie, we become increasingly nervous about what might be going on behind those shades. It is one of these power sources, I think, that Ray Milland begins to glimpse as his sight continues to improve at a steady, inexorable pace. Milland has seen through everything to the very edges of the universe and beyond, and what he has found there is driving him crazy.

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Add all ingredients to a large bowl and toss until all cauli ower pieces are coated. Total servings: 3 Nutritional facts per serving: Low-sodium Beef Taco Meat Calories: 133 kcal Homemade taco seasoning: Protein: 4 g 1 tbsp chili powder Sodium: 138 mg 2 tsp onion powder 1 tsp ground cumin 1 tsp garlic powder Gourmet Hamburgers 1 tsp paprika cup minced onions 1 tsp ground oregano tsp garlic powder Combine ingredients in a bowl and tsp dried basil mix together. Form into four 4 Add homemade taco seasoning (to taste) and 1-2 tbsp of round patties that are inch thick. Total servings: 4 Total servings: 4 Nutritional facts per serving (2 tacos): Nutritional facts per serving ~1 patty: Calories: 200 kcal Calories: 380 kcal Protein: 27 g Protein: 38 g Sodium: 78 mg Sodium: 124 mg Baked Chicken Thighs Tuna Salad 1 lb boneless, skinless chicken thighs (about 6 medium 1 can (120 g) tuna (canned in water, no salt added) thighs, thawed) 2 tbsp mayonnaise 1 tbsp sodium-free seasoning (e. Total servings: 1 Total servings: 3 Nutritional facts per serving (1 cup): Nutritional facts per serving (2 thighs): Calories: 355 kcal Calories: 260 kcal Protein: 30 g Protein: 40 g Sodium: 267 mg Sodium: 120 mg 28 Tangy Coleslaw Hamburger Soup 6 cups pre-chopped coleslaw mix (or chopped cabbage 1 lb ground beef and 1 shredded carrot) 1 onion, minced medium chopped green pepper 4 carrots, minced 3 celery ribs, thinly sliced Mix all of the above together in a large bowl. Add remaining ingredients and bring to a Total servings: 6 boil, stirring frequently. Once boiling, turn the heat to Nutritional facts per serving (1 cup): medium-low and simmer for 2 hours. Calories: 105 kcal Protein: 2 g Total servings: 6 Sodium: 19 mg Nutritional facts per serving (~1. Dash lemon and pepper salt-free spice mix Pizza Mix ingredients together in a medium bowl. Add margarine, sugar, and eggs and mix with a Total servings: 2 spatula until smooth. Add remaining ingredients and mix Nutritional facts per serving (1 small pita or large pita): well. Protein: 25 g Sodium: 320 mg Total servings: 13 Nutritional facts per serving (1 mu n): Calories: 185 kcal 29 Protein: 3 g Sodium: 154 mg Egg Salad Chicken Fried Rice 2 hard cooked eggs 1 tbsp canola oil 1 tbsp mayonnaise 1 tsp sesame oil (optional) stalk celery, chopped ne 2 tbsp chopped white onion tsp dry mustard cup frozen vegetable mixture (peas, corn, diced carrots) Dash paprika 1 cup leftover, cooked white rice 3 oz leftover, diced up cooked chicken Mix ingredients together in a medium bowl. Protein: 13 g Add leftover rice and chicken, stirring them into the mix Sodium: 201 mg until the rice is broken up. Southwest Egg Burrito 1 large tortilla (use lowest sodium content) Total servings: 2 2 eggs Nutritional facts per serving (1 cup): 1 tsp cooking oil Calories: 302 kcal 2 tbsp diced onions Protein: 19 g 2 tbsp red pepper, chopped into bitesize pieces Sodium:137 mg 2 tbsp frozen corn niblets 2 tbsp shredded cheese 1 tbsp salsa Cheese Omelet Optional protein booster: cup black beans (from can, 2-3 eggs rinsed prior to using) cup shredded mozzarella 1 spray of cooking spray Heat cooking oil in fry pan. Pour the mixture into a Add frozen corn kernels (and black beans) and cook until warmed and greased non-stick fry pan. Whisk 2 eggs in a medium bowl then pour Sprinkle cup shredded mozzarella cheese over entire into the pan. Transfer the cooked egg mixture to the center fold of the Fold one half over to the other half. Total servings: 1 Total servings: 1 Nutritional facts per serving (1 burrito): Nutritional facts per serving (1 omelet): Calories: 443 kcal Calories: 231 kcal Protein: 24 g Protein: 17 g Sodium: 382 mg Sodium: 233 mg Hummus Fruit Smoothie 15 oz can chickpeas, rinsed Blend together the following ingredients until the desired 1 garlic clove consistency is reached. Blend until the **If too thick, add water or juice to dilute mixture has a smooth consistency. Total servings: 1 Nutritional facts per serving (2 cups) with Total servings: 5 1 scoop whey protein powder: Nutritional facts per serving ( cup): Calories: 385 kcal Calories: 235 kcal Protein: 32 g Protein: 8 g Sodium: 177 mg 30 Sodium: 260 mg Black Bean Soup 1 tbsp olive oil cup chopped onion cup quinoa or rice 2 cups chicken or vegetable broth (no-salt-added) 2 lbs (40 oz or 2 large cans) black beans, rinsed 1tsp nely minced fresh garlic 1 tsp chili powder tsp ground cumin tsp red pepper akes 2 tbsp fresh cilantro, chopped 1 tbsp lime juice cup unsalted tortilla chips cup shredded cheddar cheese cup plain yogurt or sour cream Place the olive oil in a large saucepan over medium-high heat. Puree the cooked mixture with a hand blender or cool slightly and puree in 2 batches using a blender or food processor. Ladle the soup into wide-mouthed bowls and top with tortilla chips, cheddar cheese, and a dollop of yogurt. Tip: Adding 2-3 tsp of un avoured whey powder protein to each bowl provides 8-12 g of extra protein! Total servings: 6 Nutritional facts per serving (1 cups): Calories: 487 kcal Protein: 30 g Sodium: 395 mg 31 Chapter5 Using Meal Supplements Using nutritional meal supplements can improve the diet by ensuring a variety of essential nutrients are consumed. When choosing a meal supplement, it is important to nd one that is suitable, tasty, and convenient. For example, use after or instead of a meal if troubled by a poor appetite or getting full quickly. To make a "small meal" more nutritious, consider: Replacing milk with a vanilla avored meal supplement when eating hot or cold cereal Some suggestions for Adding a meal supplement to a fruit smoothie instead of juice choosing the best meal or milk supplement How can meal supplements be altered Energy/Calories: to taste better Here are some suggestions: If you have lost a lot of weight and muscle, choose a drink with 400 to 500 calories Mix chocolate or vanilla meal supplement with co ee or tea If your weight is stable or you are (hot or cold) overweight, choose a drink with 200 to Blend a sweet meal supplement with frozen fruit that is tart, 250 calories like berries Pour the supplement into a glass and add ice Protein: Add the supplement to ice cube or popsicle trays and freeze it Most drinks range in protein from 9 to 20 g for a fun, refreshing alternative Aim to choose drinks that have 10 g Dilute the supplement with other drinks: milk, soy or almond protein or more in each bottle milk, or water Sodium: Using food labels to choose the best After choosing the best options for meal supplement calories and protein, choose from the drink that has the lowest amount Check the "Nutrition Facts Label" for information about the of sodium calories, protein, and sodium per serving. Nutritional Serving Calorie Protein Sodium Calcium Highlights meal size (kcal) (g) (mg) (mg) supplement Ensure 1 bottle 235 9. However, liver fat can accumulate in overweight or obese people or those who have diabetes or high blood pressure. When losing weight, make small changes that can be easily maintained over a long Losing just 5-10% of current measured weight time. Tip Ask your healthcare practitioner or dietitian what your weight loss target is and how many calories per day you should be eating. If your weight has been stable to start with, a useful target is to decrease your caloric 34 intake by ~ 500 calories per day. My Weight: Date: ** Remember, there are online applications to track calories you eat in a day. Regardless of body size, you must continue eating well to prevent muscle loss and malnutrition in cirrhosis. To maintain muscle strength and assist the liver, protein intake must be maintained even when intentionally losing weight. Cooking methods: baking, boiling, or grilling Frying, deep frying, and any fried foods Cooking oils: olive oil, canola oil, soybean oil, peanut oil, Cooking with lard, butter, palm and coconut oil, or soft margarine made from the above oils baking margarine Fresh fruits and vegetables for snacks Baked goods, including pastries, cakes, cookies, doughnuts, and mu ns 2) Limit indulging in sugary foods and drinks Excess sugar is converted into fat worsening fatty liver disease and causing weight gain Added sugar should be less than 5-10% of the total energy per day As part of a 2,000 calorie per day diet, sugar intake should be no more than 25-50 g Check the Nutrition Fact Table on the food labels to learn the total sugar content per serving 3) Keep moving! In cirrhosis, it is important to participate in regular exercise to prevent muscle loss. Not eating for more than 8 hours increases the risk for unwanted weight and muscle mass loss. They are important to understand the clinical manifestations of hepatobiliary diseases. The signs, diagnostic procedures, and specific diseases associated with these syndromes are discussed. Normally, the flow in the biliary tree results from bile production in the proximal part and concentration of bile in the distal part. Only the flow of bile in the common bile duct is influenced by active transport due to peristalsis (gall bladder contractions and closure or relaxation of the sphincter of Oddi. The gallbladder does not contract suddenly, like the urinary bladder, but gradually over 1 to 2 hours. Bile acids are produced by the liver from cholesterol, which is a major route of cholesterol excretion. The 2 acids formed are cholic acid and che nodeoxycholic acid (the so-called primary bile acids. Bile acids are made hydrophilic before excretion into bile by conjugation with glycine and taurine. A small fraction of Department of Clinical Sciences of Companion Animals, University Utrecht, Yalelaan 108, P. Active bile acid excretion creates a huge concentration gradient between the cells and the canaliculi with a factor of 2,000. The osmotic gradient induced causes excretion of water into the canaliculi, which is a major driving force of the bile flow. When bile reaches the intestinal tract, conjugated bile acids are partly transformed by enteral bacteria in 2 ways. The secondary bile acids, deoxycholate and lithocho late, are produced by hydroxylation from cholic acid and chenodeoxycholic acid, respectively. Lithocholic acid is poorly absorbed, but it is hepatotoxic and may induce severe cholestasis. The small reabsorbed fraction is sulfated (tertiary sulfolithocholic acid) in the liver; in this form it is not reabsorbable in the next enteric cycle. Unconjugated bile acids are absorbed in the entire intes tinal tract by passive diffusion. All reabsorbed bile acids are transported to the liver by the portal blood flow, efficiently (90% in each passage) cleared by the liver, and if necessary reconjugated and then re-excreted into the canaliculi. Only a small fraction of the bile acid pool is lost in this enterohepatic circulation which cycles 10 to 15 times per day. Some bile production occurs by secretion by hepatocytes of Na1into the canaliculi, passively followed by water.

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This indicator suggests the importance estuarine wetlands, it does list several factors that have led of atmospheric deposition of mercury as a stressor to coastal to overall wetland loss, including development and conver water condition, as well as historical activities that released sion to deepwater. Ultimately, trends in wetland extent afect ecological trends in the condition of coastal waters vary. However, coastal habitat still con but substantial portion of the nations estuarine areas. As the Hypoxia results are consistent with indicators that show evidence of in Gulf of Mexico and Long Island Sound indicator (p. Nutrient stressors cannot be attributed entirely to human activities; for example, the Gulf of Mexico hypoxic zone Limitations, Gaps, and Challenges results in part from natural mixing parameters, and trends in Although the seven indicators discussed here provide a good the extent of hypoxic zones show large year-to-year variations overview of many important aspects of coastal extent and related to factors like climate (Hypoxia in Gulf of Mexico and condition, there are a few key limitations to their temporal Long Island Sound indicator, p. For example, the four indicators derived distribution of hypoxia in Long Island Sound suggests, the from the National Coastal Condition Report do not provide nations coastal waters can experience eutrophic efects that information about trends over time, as there are insufcient are very closely related to human activities (e. Smaller percent of the bays, sounds, and estuarine surface area in the systems are more likely to use ground water, particularly United States, while Hawaii, the Caribbean, and the Pacifc in regions with limited surface water resources. If drinking water contains unsafe levels One challenge in assessing coastal waters is that some aspects of contaminants, this contaminated water can cause a range of condition vary naturally from one area to another. Among the potential efects example, some rivers naturally carry a heavy load of sediments or nutrients into coastal waters, while benthic community are gastrointestinal illnesses, nervous system or reproductive efects, and chronic diseases such as cancer. Industrial wastes can contaminate drinking water sources if injected into containment wells or discharged into surface waters, as can 3. As ground water travels through rock and soil, it can pick up naturally occurring contaminants such as arsenic, other heavy metals, or radionuclides. Water and Their Effects Some aquifers are naturally unsuitable for drinking because the local geology happens to include high levels of on Human Health Human wastes from sewage and septic systems can carry harmful microbes into drinking 3. Major contaminants include Giardia, Cryptosporidium, water per day, including water used to make cofee, tea, and and E. Health consequences of the more common remove many chemical and biological contaminants from illnesses can include symptoms such as gastrointestinal distress the water, it may also result in the presence of certain (stomach pain, vomiting, diarrhea), headache, fever, and kidney disinfection byproducts that may themselves be harmful, failure, as well as various infectious diseases such as hepatitis. Finished water can also become A number of factors determine whether the presence of con contaminated after it enters the distribution system, either taminants in drinking water will lead to adverse health efects. Other processes required depend on the physical, of exposure to certain metals, solvents, and pesticides can microbiological, and chemical characteristics and the types include chronic conditions such as cancer, which can develop of contaminants present in the source water (e. Higher doses over remove turbidity and biological contaminants, treatment to shorter periods of time can result in a variety of biological remove organic chemicals and inorganic contaminants such as responses, including toxicity, mutagenicity, and teratogenic metals, and corrosion control to reduce the presence of corro ity (birth defects. Short-term results might include cosmetic sion byproducts such as lead at the point of use. For example, certain disinfection byproducts have been associated this section presents an indicator that tracks trends in the total with cancer, developmental, and reproductive risks, but the population served by community water systems for which extent of this association is still uncertain. Thus, compliance is based on averages of seasonal, annual, or less What the Data Show frequent sampling. Several new standards went into efect after of persons served by systems with reported violations of December 31, 2001. These were the frst new drinking standards covering surface water treatment, microbial water standards to take efect during the period of record contaminants (microorganisms that can cause disease), and (beginning in 1993. Monthly Population Estimates for the United States: April 1, 2000 to September 1, 2007. Safe Drinking Water Act 30 anni that between 1999 and 2001, states were not reporting versary fact sheet: Drinking water monitoring, compli 35 percent of all health-based violations, which refects a ance, and enforcement. Safe Drinking Water Act 30th anniver though these are separate from the health-based viola sary fact sheet: Glossary. Conversely, the data could also overstate the portion of the population receiving water in vio 3. Other challenges relate to the interpretation of the Drinking Recreational Waters Water indicator (p. For example, trends can be con founded by the fact that water quality standards and treatment and Their Effects on requirements change over time. As described in the indicator summary, the indicator does not address the quality of drinking water other than that obtained 3. Information that would provide a more complete the nations rivers, lakes, and coastal waters are used for many characterization of drinking water quality includes National diferent forms of recreation. Examples include a picnic at does it show how many contaminants may be above stan the beach, hiking, nature viewing (e. People also engage in fshing standards were exceeded, or the duration of the violations and shellfshing as recreational activities. Private wells, cisterns, and other non condition fall into two main categories: public water supplies are not subject to federal regulation. Data are very limited for endemic water fall into the broad category of contaminants. Among the major sources are storm water and sediment enjoyment of recreation in or near the water. Some chemicals and pathogens ness when people are exposed through ingestion or skin or eye occur naturally, but their abundance may be infuenced by contact. Land use and land cover can infuence recreational condition in other ways as well. Boating also may pose the methodology and frequency of data collection vary among risks of exposure, although to a lesser extent. For pathogens, Challenges and information gaps for developing reliable the main route of exposure is by swallowing water, although National Indicators of recreational water condition are some infections can be contracted simply by getting polluted described in more detail in Section 3. In some cases, swimmers can develop illnesses or infections if an open wound is exposed to contaminated water. The most common illness is gastroenteritis, an infammation of the stomach Several challenges exist in assessing the condition of the and the intestines that can cause symptoms such as vomiting, nations recreational waters. Other minor illnesses include ear, eye, prehensive national system for collecting data on pathogen nose, and throat infections. While unpleasant, most swimming levels at beaches, a key concern in assessing the suitability of related illnesses are indeed minor, with no long-term efects. In addi However, in severely contaminated waters, swimmers can tion, data on the types and extent of health efects associ sometimes be exposed to serious and potentially fatal diseases ated with swimming in contaminated water are limited.


  • http://www.londoncancer.org/media/84331/london-cancer-head-and-neck-radiotherapy-protocol-march-2013.pdf
  • https://charliefoundation.org/wp-content/uploads/2014/07/Mary_Newport_MD_Presentation_May_2014.pdf
  • http://medinfo.psu.ac.th/nurse/paper_meeting/child_61/child_16.pdf
  • https://www.bayer.ca/omr/online/betaseron-pm-en.pdf

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