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Genetic testing is now warranted for an increasing number of heritable disorders where information on mutation status may provide a positive impact on individuals' "need to know", as well as inform prognosis, lifestyle or reproductive choices. Where testing is offered, positive and negative results are largely unequivocal and meaningful genetic counseling can be offered. For parkin, functional and frequency data is presently limited; physicians and patients should note that some genetic test results, such as heterozygote and some compound heterozygote, may not be able to be clinically interpreted at this time. Unequivocal Parkin disease PARK2 ; test results include homozygous deletions or compound heterozygote findings consisting of non-consecutive exon deletions or duplications, or premature termination mutations. An unequivocal Parkin disease PARK2 ; result can confirm a suspected diagnosis, provide information on prognosis, and offer information to facilitate accurate genetic counseling.

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With respect to stock options grants having an exercise price equal to the market price of our Common Stock on the date of grant, such options generally gain value only to the extent our stock price exceeds the option exercise price during the life of the option. Generally, a portion of the options vest over a period of time and expire no later than ten years, and in some cases five years after grant. Executives will generally be subject to limitations in selling the option stock immediately due to securities law considerations, and therefore will have an incentive to increase shareholder value. Timing Policies with Respect to Options We have no plan or practice to time option grants in coordination with the release of non-public information and we do not time the release of non-public information to affect the value of executive compensation. Option grant dates for options issued to new executive officers will likely be the date of their employment or execution of their agreements. Any such options may be issued at a discount to take into account the limited public float and the wide ranges in our stock price. Restricted Stock Units Another component of our executive compensation program is the grant of RSUs under our 2005 RSU Plan. A RSU represents a contingent obligation to deliver a share of our common stock to the holder of the RSU on a distribution date. Each RSU award made to our executives in 2005 vests one-third 1 3 ; upon grant and the balance in equal monthly increments on the first day of each month beginning January 1, 2006 and ending December 1, 2007. We will issue the vested shares underlying the RSU awards on the earlier of i ; a Change of Control as defined in our 2005 RSU Plan ; , or ii ; in four annual installments starting on January 1, 2011. In the event of a Change of Control, our issuance of the vested shares shall be made in a lump sum distribution. In the absence of a Change of Control, the issuance of the vested shares shall be made in four 4 ; equal installments on each of January 1, 2011, January 1, 2012, January 1, 2013 and January 1, 2014. Upon our distribution of the vested shares underlying the RSU awards, the recipients must submit to us the par value of $0.01 per share. In 2005, we granted Messrs. Reddick, Spivey, Clemens, Seiser and Emigh RSU awards with respect to 8, 250, 000, 6, 660, 000, 4, 400, 000, 1, 650, 000 and 1, 375, 000 underlying shares, respectively. In the case of Messrs. Reddick, Spivey and Clemens, such awards are reflected in their employment agreements. The vesting during 2006 of the RSUs granted in 2005 is reflected in the "Stock Awards" column of the Summary Compensation Table, below. Termination Severance Benefits The employment agreement of each of Messrs. Reddick, Clemens and Spivey provides severance benefits under certain circumstances. The severance benefits provided to each such executive differs, but includes payments of a pro rata bonus or non equity incentive compensation, one to two years of salary and one to two years of benefits. See "Employment Agreements" and "Quantifying Termination Change of Control Payments" in this Item 11. We believe severance arrangements for the highest level officers help them to focus on their respective job functions even while we are experiencing some financial difficulties and gives them comfort that we will not lightly terminate their employment. We believe these severance benefits were necessary to be able to initially hire and to retain these executives. In turn Messrs. Reddick, Spivey and Clemens have agreed after their employment with us ends under certain circumstances not to compete or solicit our employees for hire for a limited period of time. We believe that such non-compete and non-solicit provisions are important to protect our business. The severance benefits are standard in employment contracts and were the results of negotiations between us and our executives. The other executive officers named in the Summary Compensation Table the "named executive officers" ; have no contractual severance benefits if terminated by the Company other than acceleration of shares underlying RSUs. Retirement Plans Beginning in 1998, we have maintained a 401 k ; plan that allows us to make both discretionary and matching contributions, but we have not done so since inception. We have no pension plans or non-qualified deferred compensation plans and, as a result, the columns relating to such plans in the Summary Compensation Table are blank. Change in Control Currently unexercisable options vest with respect to all underlying shares upon a change of control as defined in employment agreements, in the case of Messrs. Reddick, Spivey and Clemens and in stock option agreements, in the case of Messrs. Emigh and Seiser ; for all named executive officers. In addition, RSUs vest with respect to all underlying shares upon a change of control and are distributed upon a change of control provided the requirements of Section 409 of the.
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Diagnosis Radiological diagnosis requires evidence of asymmetrical joint space narrowing, marginal osteophytes, subchondral bone sclerosis, or subchondral cyst formation. The first sign of OA is osteophyte formation, followed by loss of cartilage. However, fewer than 50% of subjects with radiographic OA have clinical symptoms. The clinical diagnosis of OA is suspected in patients with joint tenderness, boney nodules, joint crepitus, and limitations in movement, then confirmed by radiology. Routine laboratory tests are normal and are only helpful in ruling out related conditions. Administrative databases are likely to be unreliable for accurately identifying patients with a diagnosis of OA. A study in a Massachusetts health maintenance organization found that among patients with an administrative diagnosis of OA only 62% were determined as having definite OA on chart review. On the other hand, 18% of those without an administrative diagnosis actually had definite OA. Epidemiology Estimating incidence and prevalence is difficult because OA can be defined either clinically or radiographically. Furthermore, the threshold for abnormality in radiographs has varied among studies, and radiographic screening studies usually focus on one or a few joints and not all possibly affected joints. Finally, various studies have often omitted or undersampled patients older than 75 years of age. Incidence and prevalence are strongly correlated with age. Before age 50, men have a higher frequency of OA than women, but incidence accelerates in women after menopause. After age 50, some women develop "menopausal OA", a rapidly progressive generalized OA. Osteoarthritis prevalence by clinical examination was assessed in the National Health and Nutrition Examination Survey NHANES ; I in a sample of 6913 United States adults age 2574. On the basis of these examinations, 12.1% of the population in that age group had OA. The population-based National Health Examination Survey in 196062 included hand and foot radiographs. Results indicated OA was rare in people younger than 25 years of age, but by ages 6574 almost all people had some evidence of OA in the hands and about half had evidence in the feet. The incidence of new OA defined radiographically in people older than 45 years of age is about 2% per year, whereas the incidence of symptomatic OA in the same population is about 1% per year. Defining OA as symptoms plus radiographic change, studies in northern England found that 6.2% of adults older than 35 years of age had knee OA and 12.2% of women did. Among adults 55 years of age and older the prevalence of hip OA was 5.5% in men and 3.6% in women. In the Framingham Heart Study OA study, 9.5% of people age 6393 had symptomatic knee OA, with a higher prevalence in women 11.4% ; than men 6.8% ; . Prognosis The natural history of OA is highly variable. Most patients with radiographically mild OA have a stable course and do not progress to severe joint damage. In one study, 63 patients were followed for 11 years and more than half showed no radiological deterioration in their knees Pharmacotherapy Self-Assessment Program, 4th Edition 229, for instance, use of combivent. ANTI-ASTHMATIC AGENTS . 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This was conducted in the following way: i ; Developing and piloting the data extraction forms The demonstration project commenced with the operationalisation of the indicators through the development of data abstraction forms DAFs ; and a detailed manual for each of the study conditions. The process was straightforward for some of the indicators, requiring just one or two questions, but was complex for others, requiring multiple questions to determine the appropriateness of the indicators to an individual patient. Pilot work to test the DAFs and manuals was undertaken in four practices. The aim of this work was to test and further develop the DAFs and to provide training for the researchers in extracting data from medical records and in the use of practice-based computer systems. This stage of the demonstration project also provided an opportunity to refine the indicator set, with some indicators being removed due to the difficulties experienced in extracting the relevant data from the patient records. The inter-rater reliability of the extraction process was also piloted at this stage. This resulted in alterations to the data extraction forms to improve the clarity of question wording and ordering, the establishment of more explicit inclusion criteria for some conditions and the removal of some `uncollectable' indicators. A total of 4 indicators were removed during these preliminary stages table 5 ; . Table 5: Indicators removed during the preliminary stages of the project. 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