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Cyclins D 1 (cD 1 ) and E (cE) are G 1 phase cyclins believed to participate in the pathogenesis of malignancy. Overexpression of cD 1 has been reported to influence prognosis in squamous cell carcinomas (SCC) of the larynx, but was not significant in a limited study of non-small cell lung cancers (NSCLC). Altered expression of cE has been proposed as another potential prognostic marker in malignancy but its possible role in NSCLC has not been elucidated. In order to determine the prognostic value of cD 1 and cE in NSCLC, paraffinembedded sections of 467 NSCLC were immunostained with monoclonal antibody to cD 1 (1:500, PharMingen, San Diego, CA) and 400 NSCLC with MA to cE (1:2500, PharMingen) using an enhanced sensitivity avidin-biotin complex technique. The number of tumor cells with nuclear and/or cytoplasmic immunopositivity was graded on a scale of: 0 ‫؍‬ less than 1%, 1 ‫؍‬ 1 to 10%, 2 ‫؍‬ 10 to 25%, 3 ‫؍‬ 25 to 50%, 4 ‫؍‬ 50 to 75%, 5 ‫؍‬ more than 75%. Results were correlated with survival by KaplanMeier survival plot using Stat-View software (Abacus Concepts, Berkeley, CA). Overall, 426 NSCLC with cD 1 and 360 NSCLC with cE had adequate follow-up (median, 76 mo) for survival analysis. Both cyclins independently showed significance in prognosis of SCC but not other cell types. For cD 1 , absence of immunostaining was associated with worse prognosis than any immunopositivity for all stages of SCC (P ‫؍‬ .025). For cE, Stage I and II SCC with less than 50% immunopositivity had a worse prognosis (P ‫؍‬ .029). Of 70 Stage I and II SCC immunostained for both monoclonal antibodies, 55% of patients with tumors that demonstrated both absence of cD 1 staining and cE immunopositivity in less than 50% of cells were dead at 5 years compared to 35% of patients with tumors that demonstrated positive staining with cD 1 and cE immunopositivity in more than 50% of cells. These results strongly suggest cD 1 and cE can independently predict prognosis in early stage SCC. Worse prognosis was associated with loss of expression, consistent with mechanisms other than overexpression of these cyclins in the progression of SCC.

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Background: Expression of p53, cyclin D1, p21 (WAF1) and Ki-67 (MIB1) was evaluated in oral squamous cell carcinoma (OSCC) to test whether levels of these markers at invasive tumour fronts (ITFs) could predict the development of local recurrence. Materials and Methods: Archived paraffin-embedded specimens from 51 patients with T1/T2 tumours were stained immunohistochemically and analysed quantitatively. Local recurrence-free survival was tested with Kaplan-Meier survival plots (log-rank test) using median values to define low and high expression groups and with a Cox's proportional hazards model in which the expression scores were entered as continuous variables. Results: The assessment of expression of all markers was highly reliable, univariate analysis showing that patients with clear surgical margins, with low cyclin D1 and high p21 expression at the ITF had the best local recurrence-free survival. Multivariate analysis showed that these three parameters were independent prognostic factors but that neither p53 nor MIB1 expression were of prognostic value. Conclusions: Assessment of p53, cyclin D1, p21 (WAF1), and Ki-67 (MIB1) at the ITF could help to predict local recurrence in early stage oral squamous cell carcinoma cases.

Calbindin D28k (Ca-D28k) acts as a buffering system to maintain cellular calcium homeostasis and is thought to play a role in inhibiting apoptosis. The goals of this study were to assess CA-D28k expression in lung carcinomas and to correlate these results with patient survival.A total of 452 lung carcinomas were immunostained with a monoclonal antibody specific for Ca-D28K using an avidin-biotin peroxidase technique. The number of cells with nuclear staining was graded semiquantitatively into one of five groups: 0, fewer than 10%, 10 to 25%, more than 25 to 50%, more than 50 to 75%, and more than 75%. Results were correlated with patient survival using KaplanMeier survival curves.A total of 335 of 452 (74%) lung carcinomas were positive for Ca-D28k. There was no statistically significant difference in the prevalence of Ca-D28k expression in tumors of different histologic type. Kaplan-Meier survival analysis revealed that for patients with adenocarcinoma, those with Ca-D28k-positive tumors had a better overall survival than patients with Ca-D28k-negative tumors (P ‫؍‬ .036). This difference was also significant for patients with Stages I and II adenocarcinomas (P ‫؍‬ .033). No statistically significant difference in prognosis was observed for patients with Stages III and IV adenocarcinomas or for patients with other lung carcinoma types of varying stage.Ca-D28k is commonly expressed in lung carcinomas of all histologic types. For patients with localized adenocarcinoma of the lung, Ca-D28k expression correlated with improved survival. No correlation between Ca-D28k expression and patient survival was found for disseminated adenocarcinoma and for other histologic types of lung carcinoma.

Summary Continuous inertial navigation systems (INS) for high-accuracy surveying canbe used to enhance quality control of survey data significantly. This papershows how to use the unique capabilities of these systems while retainingcompatibility with widely accepted quality-control methods. A system now in usein the North Sea provides concrete examples. Introduction Continuous INS's are desirable for fast, high-accuracy surveying. Theirrelative independence from inclination and latitude makes them particularlyuseful for surveying high-angle wells at high latitudes. A less obvious, butequally important, benefit of these systems is the improved quality control ofsurvey data possible both at the rig site and in the validation of systemperformance before and after surveying. In many applications, continuousinertial navigation is a mature technology for determining real-time positionand velocity, but this technology is new to surveying. The same innovationsthat make improved surveying possible can cause confusion when approached fromthe viewpoint of conventional surveying. We show where and how current methodsof survey-data quality control can be used with continuous INS's, introduce newtechniques, and point out pitfalls to be avoided. Background: Aided Strapdown Inertial Navigation An INS determines the position and velocity of a moving body in threedimensions by integrating measured components of the acceleration of the bodymathematically. A conventional directional survey system measures inclinationand azimuth angles at stations along the wellbore; positions are calculatedfrom these angles and from measured depths by assuming some shape for thewellbore between stations. Both a conventional system and an INS can be used todetermine positions. The main difference is that an INS does so more directly. An INS is better described as a positional surveying device than as adirectional one. A body moving in three dimensions does not provide a stablecoordinate system for performing integrations. There are two common solutionsto this problem. A gimbaled INS maintains a stationary platform for theaccelerometers with torque motors. The system uses the angular rate outputs ofgyros attached to the platform to control the motors. A strapdown INSmathematically platform to control the motors. A strapdown INS mathematicallytransforms the outputs of accelerometers attached to the body into a locallylevel coordinate system before performing integrations. The system uses theoutputs of gyros attached to the body to update continuously the transformationmatrix for converting from body coordinates to level coordinates. A strapdownsystem does mathematically what a gimbaled system does mechanically. Theruggedness and smaller size that come with eliminating gimbals make strapdownsystems desirable for survey applications. Fig. 1 shows the basic operation ofa strapdown INS. Because integration amplifies the effects of system errors, the outputs of an INS will drift increasingly with time. If uncontrolled, positional drift errors of roughly 500 mm/s [6,000 ft/hr] are typical. One wayto overcome drift errors is to stop the survey tool periodically. Whilestopped, the system uses the known zero velocity to update the integrators. This is the approach used with the large-diameter gimbaled system that, untilrecently, was the only INS commonly available for surveying. A differentapproach is necessary to overcome drift errors without stopping the surveytool. To survey continuously, an additional measurement independent of the INSis needed as a reference. For a wireline system, measured cable length is anappropriate choice. A cable-aided system compares this measurement with thecourse length calculated by the INS. A feedback loop uses the differencebetween the two values to prevent the buildup of errors. Cable aiding makesaccurate prevent the buildup of errors. Cable aiding makes accurate continuoussurveying possible with an INS. The navigation system can use a Kalman filterto implement cable aiding. A Kalman filter is an algorithm for optimallyestimating the error state of a system from measurements corrupted by noise. For surveying, the error state of the system includes errors in survey toolposition, velocity, and orientation; cable length parameters; and varioussensor parameters. By blending the two parameters; and various sensorparameters. By blending the two values of course length from the INS and thecable measurement, the filter can improve error estimates of all the navigationparameters. The navigation system then can correct these parameters for theestimated errors continuously. Kalman filters enhance the performance of INS'sin many ways. They reduce the effects of noise during alignment and navigation. They can blend pure INS outputs with independent measurements and withconstraints imposed by the application. They also generate real-timestatistical data related to the accuracy of estimated values. How well Kalmanfilters perform depends mainly on how well the system is modeled. Estimatesbased on bad assumptions are optimal only in a vacuous sense. Fortunately, modeling of aided INS's is well understood. Fig. 2 illustrates cable-aidednavigation. A navigation computer compensates sensor data for known erroreffects and calculates probe position, velocity, orientation, and the lineardistance traveled along the wellbore (the calculated course length). Thedifference between the measured cable length and the calculated course lengthis an error signal input into a Kalman filter. The filter inputs also includethe inertially computed lateral displacements of the probe in the wellbore, which should be zero. The Kalman filter uses the inputs to calculate correctionvalues to update the sensor compensation and inertial navigation data. Outputsfrom the computer include position components and uncertainties in the positiondata. Savage gives a detailed description of aided navigation. Cable aidingwith a Kalman filter is not a new idea. Sandia Natl. Laboratories developed anexperimental wellbore INS between 1979 and 1982. The system did not use cablemeasurements, but in a report on system software Wardlaw suggested cable aidingas a topic for further investigation. In other applications, odometer aiding isa direct analog of cable aiding and has been in use for many years. Although wehave discussed cable aiding for a strapdown INS, note that this technique alsocould be used with a gimbaled system. Similarly, zero-velocity updates can beapplied to a strapdown system as well as to a gimbaled one. Common Misunderstandings of Inertial Navigation There are two common misunderstandings in the survey industry about what an INS is and what it does. One is the assumption that an INS is either agyrocompass or an attitude reference system. SPEDE P. 100

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