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In south-central Ontario, tunnel channels are primary targets for groundwater exploration due to their potential to contain confined, water-bearing, coarse-grained sediment fills. Despite extensive hydrogeologic and geologic exploration within these features, a comprehensive depositional model that illustrates the spatial distribution of coarse- and fine- grained sediment in tunnel-channel complexes is absent. Work in the Zephr area, north of ORM, presents new subsurface data to improve understanding of this geologic setting and to add to geologic models of these channel systems. Findings result from combined geology, sedimentology, geophysics (seismic profiling) and sediment drilling (mud rotary and continuous core) to better our understanding the shallow channel setting north of ORM, including: 1) spatial distribution of coarse- and fine-grained sediments in tunnel-channels; 2) the architecture of tunnel-channel sequences in confluence zones. Preferred aquifer targets aquifer units in the Zephyr area are identified in areas of channel confluence and channel bends. Channel aquifers are confined by 3.9 to 28.5 m thick deposits of rhythmically bedded silt and clay.

IntroductionThe purpose of this pilot study was to assess for biomarkers indicative of passing intense physical training and establishing normative values within the tactical athlete population. Unfortunately, none of the biomarkers assessed were indicative of passing training, however, glucose, blood urea nitrogen, and creatine kinase (CK) levels stood out as abnormal. CK levels are commonly used in conjunction with muscle pain and/or myoglobinurea to diagnose exertional rhabdomyolysis (ER) in athletes and the military population. However, research shows that high CK levels may not correlate with acute kidney failure in ER.Materials and MethodsAfter IRB approval and informed consent, blood samples were obtained from 21 volunteers during two phases of the combat control training pipeline: the first phase (12 participants) was 2 hours of daily physical training followed by 8 hours of academics, and the second phase (nine volunteers) a grueling, 72 hour, intense training cycle (stress inoculation training, SIT) with a historic pass rate of only 50%. Biomarkers were also tracked 48 hours after cessation of SIT.ResultsNone of the biomarkers assessed showed a correlation with passing SIT, but high CK levels were well above the diagnostic threshold for ER—as high as 28,000 u/L. At a single point in time, a significant correlation did not exist between CK and others markers associated with rhabdomyolysis. Across time, partial correlations controlling for subject did exist between CK and other markers.ConclusionsIn our low-powered case control study (pilot study), a nonpathologic elevation of CK is prevalent in high-intensity military training, but not shown to correlate with values associated with acute kidney injury. We assume that real-time collection of these markers could be used once sensors are capable of real-time collection and have the potential for diagnostic affordance. When measured in a between subjects design, our study showed a lack of significance when correlating markers of acute renal injury and elevation of CK. However, when utilized for tracking purposes (within subjects design), the results do show a positive correlation between CK and renal failure biomarkers—specifically only at high physiological stress points.

Sample return missions to Phobos are the subject of future exploration plans. Given the proximity of Phobos to Mars, Mars’ potential to have supported life, and the possibility of material transfer from Mars to Phobos, careful consideration of planetary protection is required. If life exists, or ever existed, on Mars, there is a possibility that material carrying organisms could be present on Phobos and be collected by a sample return mission such as the Japanese Martian Moons eXplorer (MMX). Here we describe laboratory experiments, theoretical modelling and statistical analysis undertaken to quantify whether the likelihood of of a sample from Phobos material containing unsterilized material transferred from Mars is less than 10-6, the threshold to transition between restricted and unrestricted sample return classification for planetary protection. We have created heat, impact and radiation sterilisation models based on the Phobos environment, and through statistical analyses investigated the level of sterilisation expected for martian material transferred to Phobos. These analyses indicate that radiation is the major sterilisation factor, sterilising the Phobos surface over timescales of millions of years. The specific events of most relevance in the Phobos sample return context are the ‘young’ cratering events on Mars that result in Zunil-sized craters, which can emplace a large mass of martian material on Phobos, in a short period of time, thus inhibiting the effects of radiation sterilisation. Major unknowns that cannot yet be constrained accurately enough are found to drive the results – the most critical being the determination of exact crater ages to statistical certainty, and the initial biological loading on Mars prior to transfer. We find that, when taking a conservative perspective and assuming the best-case scenario for organism survival, for a 100 g sample of the Phobos regolith to be below the planetary protection requirement for unrestricted sample return, the initial biological loading on Mars must be 3cfu kg-1. For the planned MMX mission, a ∼10 g sample to be obtained from a 25-30 mm diameter core as planned would require an initial martian biological loading to be 4cfu kg-1, in order to remain compliant with the planetary protection threshold.

Studies on human perception have identified pelvis and torso motion as key discriminators between male and female gaits. However, while most observers would advocate that men and women walk differently, consistent findings and explanations of sex differences in gait kinematics across modern empirical studies are rare. In the present study we evaluated sex differences in whole body gait kinematics from a large sample of subjects (55 men, 36 women) walking at self selected speeds. We analyzed the data through comparisons of discrete metrics and whole curve analyses. Results showed that in the frontal plane, women walked with greater pelvic obliquity than men, but exhibited a more stable torso and head. Women had greater transverse plane pelvis and torso rotation as well as greater arm swing. Additional sex differences were noted at the hip and ankle. These kinematic results are in line with anectdotal observations and qualitative studies. In order to understand these observations and substantiate some of the explanations previously set forth in the biomechanics literature, we also explored possible reasons for dynamic sex effects, and suggested applications that may benefit from their consideration.

As social beings, much of our everyday lives are spent in interaction with others, yet the vast majority of gait studies examine solo walking without any distraction. It is largely unknown how walking in a dyad, both with and without talking, affects gait speed, cadence, and step length of adults; however, these same metrics dictate design parameters for widely varying fields from rehabilitation goals and ergonomic environments to animation models and surveillance objectives. This study examined the differences in spatiotemporal metrics between solo and paired walking for same- and opposite-sex pairs while using talking as a method of distraction. Results from 12 female-female (F-F), 10 female-male (F-M), and 12 male-male (M-M) pairs were analyzed. Significant changes from solo walking were only found with opposite-sex pairs (p0.05), with women (F-M/female) increasing speed and men (F-M/male) decreasing speed. Unlike solo walking, changes in speed during paired walking were driven by alterations to step length with very minimal change in cadence. When subjects were directed to talk while walking, both solo and as a pair, gait speed decreased significantly by 4-5%. Because significant changes were observed in paired versus solo walking, both with and without distraction, there may be reason to reevaluate and develop environment-specific rehabilitation goals and normative metrics.

Introduction: It is estimated that up to 30% of medical services in Canada are potentially unnecessary, not supported by current evidence or may cause patient harm. This type of practice negatively impacts patients and the healthcare system. Evidence suggests that medical education strongly impacts resource utilization in future practice. Our objective was to integrate Choosing Wisely (CW) recommendations into the undergraduate medical education curriculum to improve students understanding of resource stewardship in their pre-clerkship training. Methods: Post-course survey data and written feedback were collected from the Cumming School of Medicines 2019 class. Qualitative analysis of written feedback was used to identify perceived strengths and areas of improvement to inform additional changes for the 2020 class through a Plan-Do-Study-Act (PDSA) cycle. Results: The post-course survey was completed by 143 students. 60% reported the inclusion of CW improved their ability to develop a clinical management plan. Using the information gathered from the qualitative analysis, we made the following changes for the 2020 class: create an introductory lecture on resource stewardship, incorporate relevant CW recommendations into case study learning objectives, and create standardized slides on CW recommendations for lecturers. Feedback from the 2020 class revealed that the changes were well received and students reported feeling more comfortable with resource stewardship concepts. Conclusion: This data reveals that our efforts have increased students confidence in creating a management plan that integrates resource stewardship and patient safety, and elicited strong faculty support. We will continue to integrate these changes and to obtain student and faculty feedback to help inform additional iterative changes for the subsequent cohort. Our findings are valuable for other medical schools across Canada seeking to incorporate CW material.

Public health spans several disciplines dedicated to the improvement of the health and well-being of popula tions across the globe. This mission broadly focuses on prevention of illness, disease, and injury; utilization of appropriate health-care services; and addressing of health-care disparities. The pursuit of social justice underlies this goal. Core disciplines include epidemi ology, environmental health sciences, health policy and management, social and behavioral sciences, and biostatistics. These disciplines draw on a fundamental knowledge of biology, a basic familiarity with social sciences, and an appreciation of socioeconomic and cultural variance among different people. An undergraduate Public Health Studies (PHS) major gives students a unique opportunity to enter into the world of public health. According to a survey by the Association of Schools of Public Health in 2005,113 schools of public health (SPHs) reported that their uni versities offered undergraduate majors. These schools included Johns Hopkins University (JHU), George Washington University (GWU), Loma Linda University (LLU), University of North Carolina at Chapel Hill (UNC-CH), University of California at Berkeley (UC Berkeley), University of Washington (UW), and Tulane University (TU). Three of these universities?GWU, UW, and TU?as well as four other schools?Bos ton University (BU), University of California at Los Angeles (UCLA), University of Southern California (USC), and University of South Florida (USF)?offer minors in undergraduate public health. Six of these schools and an additional 13 universities with SPHs

Maternal exposure to high doses of trichloroethylene (TCE) and its oxidative metabolites, trichloroacetic acid (TCA) and dichloroacetic acid (DCA), has been implicated in eye malformations in fetal rats, primarily micro-/anophthalmia. Subsequent to a cardiac teratology study of these compounds ( Fisher et al. 2001 , Int. J. Toxicol. 20:257–267), their potential to induce ocular malformations was examined in a subset of the same experimental animals. Pregnant, Sprague-Dawley Crl:CDR BR rats were orally treated on gestation days (GDs) 6 to 15 with bolus doses of either TCE (500 mg/kg/day), TCA (300 mg/kg/day), DCA (300 mg/kg/day), or all- trans retinoic acid (RA; 15 mg/kg/day). The heads of GD 21 fetuses were not only examined grossly for external malformations, but were sectioned using a modified Wilson’s technique and subjected to computerized morphometry that allowed for the quantification of lens area, globe area, medial canthus distance, and interocular distance. Gross ocular malformations were essentially absent in all treatment groups except for the RA group in which 26% of fetuses exhibited micro-/anophthalmia. Using the litter as the experimental unit of analysis, lens area, globe area, and interocular distance were statistically significantly reduced in the DCA treatment group. Statistically significant reductions in lens and globe areas also occurred in the RA treatment group, all four ocular measures were reduced in the TCA treatment group but none significantly so, and TCE was without effect. Because DCA, TCA, and RA treatments were associated with significant reductions in fetal body weight (bw), data were also statistically analyzed after bw adjustment. Doing so dramatically altered the results of treatment group comparisons, but the severity of bw reduction and the degree of change in ocular measures did not always correlate. This suggests that bw reduction may not be an adequate explanation for all the changes observed in ocular measures. Thus, it is unclear whether DCA specifically disrupted ocular development even under these provocative exposure conditions. Clearly, however, if TCE is capable of disrupting ocular development in the Sprague-Dawley rat, a higher dose than that employed in the present study is required.

Trichloroethylene (TCE), trichloroacetic acid (TCA), and dichloroacetic acid (DCA) are commonly found as groundwater contaminants in many regions of the United States. Cardiac birth defects in children have been associated with TCE, and laboratory studies with rodents report an increased incidence of fetal cardiac malformations resulting from maternal exposures to TCE, TCA, and DCA. The objective of this study was to orally treat pregnant CDR(CD) Sprague-Dawley rats with large bolus doses of either TCE (500 mg/kg), TCA (300 mg/kg), or DCA (300 mg/kg) once per day on days 6 through 15 of gestation to determine the effectiveness of these materials to induce cardiac defects in the fetus. All- trans retinoic acid (RA) dissolved in soybean oil was used as a positive control. Soybean oil is commonly used as a dosing vehicle for RA teratology studies and was also used in this study as a dosing vehicle for TCE. Water was used as the dosing vehicle for TCA and DCA. Fetal hearts were examined on gestation day (GD) 21 by an initial in situ, cardiovascular stereomicroscope examination, and then followed by a microscopic dissection and examination of the formalin-fixed heart. The doses selected for TCA and DCA resulted in a modest decrease in maternal weight gain during gestation (3% to 8%). The fetal weights on GD 21 in the TCA and DCA treatment groups were decreased 8% and 9%, respectively, compared to the water control group and 21% in the RA treatment group compared to soybean oil control group. The heart malformation incidence for fetuses from the TCE-, TCA-, and DCA-treated dams did not differ from control values on a per fetus or per litter basis. The rate of heart malformations, on a per fetus basis, ranged from 3% to 5% for TCE, TCA, and DCA treatment groups compared to 6.5% and 2.9% for soybean oil and water control groups. The RA treatment group was significantly higher with 33% of the fetuses displaying heart defects. For TCE, TCA, and DCA treatment groups 42% to 60% of the litters contained at least one fetus with a heart malformation, compared to 52% and 37% of the Utters in the soybean oil and water control groups. For the RA treatment group, 11 of 12 litters contained at least one fetus with a heart malformation. Further research is needed to quantify the spontaneous rates of heart defects for vehicle control rats and to explain the disparity between findings in the present study and other reported findings on the fetal cardiac teratogenicity of TCE, TCA, and DCA.

The nitrogen dynamics of storm runoff was studied using throughfall trenches on slopes with thin soils in a white pine forest catchment near Dorset, Ontario. Hydrologic data were combined with analysis of isotopic signatures and nitrogen chemistry in throughfall, soil water, and hillslope runoff. Two hypotheses were tested: (1) macropore preferential flow pathways are a source of nitrate flushing in storm runoff, and (2) the nitrogen chemistry of subsurface storm flow is controlled by the mixing of event water fluxes via macropores with preevent soil water. Most flow occurred at the soil-bedrock interface on the slopes, and the use of 18O indicated that a considerable fraction of event water moved vertically to bedrock via preferential flow paths. Despite high levels of inorganic N in throughfall, subsurface runoff N losses during autumn storms were dominated by dissolved organic nitrogen, and little nitrate flushing occurred via preferential flow paths. Comparisons of observed NO3- and NH4+ concentrations versus concentrations predicted from the mixture of event and preevent water in subsurface flow did not support hypothesis 2 and instead indicated depletion of inorganic N. Low rates of N mineralization and negligible nitrification in surface 0–0.1 m soil during June–October suggested high biological utilization of a limited soil N supply. Laboratory experiments in which soil cores were leached with solutions containing NO3- and bromide confirmed that the organic Ae horizon was a sink for NO3-. These data suggest that the biogeochemistry of the organic horizon can regulate patterns of inorganic N loss in subsurface runoff moving by preferential flow pathways in forest soils.

In 1982, a treatment protocol was instituted for the management of patients with clinical stage I adenocarcinoma of the endometrium. All pertinent historical, operative, and pathologic findings were reviewed by a multidisciplinary committee and 384 patients were prospectively assigned to either high- or low-risk categories. Patients were excluded from the study if they had clinically apparent extrauterine disease, clear cell or serous histologies, or microscopic ovarian metastasis. Patients were considered high-risk if they had one or more of the following factors: grade 3 tumor differentiation, myometrial invasion ⩾50% of the total wall thickness, pathologic cervical involvement, or adenosquamous histology. Two-hundred twenty-seven (59%) low-risk patients were followed without further treatment after surgery, while pelvic radiation was recommended for 157 (41%) high-risk patients. The 5-year relapse-free survival rates in the low- and high-risk groups were 95 and 81%, respectively. There were no treatment-related deaths. Severe or life threatening chronic radiotherapy complications occurred in 6 (5%) patients. Multivariate Cox analysis identified the following significant prognostic factors: grade, myometrial invasion, cervix involvement, and age. This treatment protocol represents a safe and effective method of managing patients with carcinoma of the endometrium and spares the need for radiation therapy in the low-risk patient.

Right whales were tagged in 1988 and 1989 with radio and sonic telemetry tags as part of a multidisciplinary investigation of right whales and their habitat in the Great South Channel region east of Cape Cod. The tags yielded data on the durations of 6456 dives and 6482 surfacings, as well as 23,538 measurements of the depth of a diving whale. Log-survivorship analysis of the 1988 data showed a clear separation between the durations of dives between blows within a single surfacing sequence or bout (intea-bout dives) and longer dives between surfacing sequences (interbout dives) at 27 s, which was also applied to the 1989 data. Inter-bout dives averaged 127.3 s, and were significantly longer in 1988 than in 1989. Inter-bout dives were significantly longer during the day than night in 1988, and longer at night in 1989. The average intea-bout dive duration was 11.8 s, with 1989 dives longer than those in 1988. Surface durations averaged 6.2 s, and were also significantly longer in 1989. Dive depths were recorded only in 1989. Mean dive depth was 7.3 m, and only 12 dives went deeper than 30 m. The typical right whale dive pattern in 1988 included relatively short surfacings, long dives during the day, and shorter dives at night. This correlated with strong diel vertical migration by the dense zooplankton patches on which they were presumed to be feeding based on indirect evidence-from near the surface at night to near the bottom during the day. The 1989 pattern included longer dives during the night, as well as some exceptionally long surfacings. Zooplankton in 1989 did not migrate vertically, and remained near the surface day and night in right whale feeding areas. Right whale dive patterns in the Great South Channel are closely correlated with the horizontal and vertical distributions and movements of dense patches of their zooplankton prey.

The largest study on post-allogeneic hematopoietic cell transplant lymphoproliferative disorder (PTLD) epidemiology showed a cumulative incidence of 1.7% in patients receiving antithymocyte globulin (ATG). We had noted an apparently higher incidence in our transplant recipients whose conditioning included ATG. Therefore, we formally determined the incidence of PTLD through chart review. We also evaluated whether counts of EBV-specific T lymphocytes measured by cytokine flow cytometry could identify patients at risk of developing PTLD. Among 307 allogeneic transplant recipients, 25 (8.1%) developed PTLD. This was biopsy proven in 11 patients, and was fatal in seven patients. Patient age, EBV serostatus, donor type/match or GVHD did not influence PTLD risk significantly. Median onset of PTLD was 55 (range, 28–770) days post transplant. Day 28 EBV-specific T lymphocyte counts were not significantly different in 11 patients who developed PTLD and 31 non-PTLD patients matched for published risk factors for PTLD. In summary, when using conditioning with thymoglobulin 4.5 mg/kg, the incidence of PTLD is relatively high and cannot be predicted by day 28 cytokine flow cytometry-determined EBV-specific T lymphocyte counts. Thus, in this scenario PTLD prevention may be warranted, for example, using EBV DNAemia monitoring with preemptive therapy.

Algorithms predicting tissue and blood partition coefficients (PCs) from solvent properties were compared to assess their usefulness in a petroleum mixture physiologically based pharmacokinetic/pharmacodynamic model. Measured blood:air and tissue:blood PCs for rat and human tissues were sought from literature resources for 14 prevalent jet fuel (JP-8) components. Average experimental PCs were compared with predicted PCs calculated using algorithms from 9 published sources. Algorithms chosen used solvent PCs (octanol:water, saline or water:air, oil:air coefficients) due to the relative accessibility of these parameters. Tissue:blood PCs were calculated from ratios of predicted tissue:air and experimental blood:air values (PCEB). Of the 231 calculated values, 27% performed within +/- 20% of the experimental PC values. Physiologically based equations (based on water and lipid components of a tissue type) did not perform as well as empirical equations (derived from linear regression of experimental PC data) and hybrid equations (physiological parameters and empirical factors combined) for the jet fuel components. The major limitation encountered in this analysis was the lack of experimental data for the selected JP-8 constituents. PCEB values were compared with tissue:blood PCs calculated from ratios of predicted tissue:air and predicted blood:air values (PCPB). Overall, 68% of PCEB values had smaller absolute % errors than PCPB values. If calculated PC values must be used in models, a comparison of experimental and predicted PCs for chemically similar compounds would estimate the expected error level in calculated values.

While vast numbers of image enhancing algorithms have already been developed, the majority of these algorithms have not been assessed in terms of their visual performance-enhancing effects using militarily relevant scenarios. The goal of this research was to apply a visual performance-based assessment methodology to evaluate six algorithms that were specifically designed to enhance the contrast of digital images. The image enhancing algorithms used in this study included three different histogram equalization algorithms, the Autolevels function, the Recursive Rational Filter technique described in Marsi, Ramponi, and Carrato 1 and the multiscale Retinex algorithm described in Rahman, Jobson and Woodell 2 . The methodology used in the assessment has been developed to acquire objective human visual performance data as a means of evaluating the contrast enhancement algorithms. Objective performance metrics, response time and error rate, were used to compare algorith m enhanced images versus two baseline conditions, original non-enhanced images and contrast-degrade d images. Observers completed a visual search task using a spatial-forced-choice paradigm. Observers searched images for a target (a military vehicle) hidden among foliage and then indicated in which quadrant of the screen the target was located. Response time and percent correct were measured for each observer. Results of the study and future directions are discussed. Keywords: image enhancement, psychophysical experiments, visual search, contrast enhancing algorithm.

Users of night vision goggles (NVGs) have reported differences in NVG noise across different as well as the same type of NVG. To better understand these differences, we attempted to characterize NVG noise by having subjects choose parameters in an NVG simulation to best match the noise in real NVGs. From our previous efforts, we observed interdependence of simulation parameters and variability across observers. This has lead us to use the method of paired comparisons as a process for characterizing NVG noise. The results suggest that people perceive NVG noise differently in terms of spatial, temporal, and contrast combinations. In addition, we provide a methodology for determining psychophysically the best parameter combinations in a simulation’s algorithm to match the real environment that the simulation represents.

This study was undertaken to determine the utility of a dynamic visual acuity assessment methodology for examining the effects of looking through a transparent component on visual performance. The different types of transparent components that can be investigated using this methodology include, but are not limited to, night vision goggles, tinted visors, laser eye protection spectacles, and aircraft windscreens. Transparency attributes that can be investigated include transmission coefficient, reflection coefficient, glare, light level, target contrast, target type, resolution, spectral transmission, haze, scratches, and distortion. The visual task may be a target detection or a target recognition type of task, performed with or without search. The methodology used in this study consists of smoothly and continuously decreasing the distance between the observer and a visual test target, until the observer can accurately perform the required visual task. In this study, the observer was required to visually search and detect a circular black dot in a quadrant, while viewing through a tinted visor. The lighting conditions were not at a level for which the tinted visor was intended to be used, so it was expected that the visor would reduce visual acuity instead of aiding visual performance, as it normally would be expected to do. The objective of the study was to determine the 95% reproducibility limit for the methodology. This limit was found to be on the order of 10% to 15%, which is quite good for an assessment of this type that involves human observers performing a visual task over an extended period. The methodology appears to be viable.

Automated gender recognition from whole body images is a challenging problem with multi-disciplinary utility. A greater understanding of potential feature components e.g., anthropometry, movement, etc. may help future feature selection algorithms better target effective features, reduce feature complexity, and increase algorithm generalisability. In this study we evaluated the potential of static anthropometric measurements for gender recognition. Utilising a large 3D body scan repository, we first captured novel measurements directly relevant to computer vision applications, and used these to create biologically guided feature sets. Linear discriminant analysis was used to classify gender across specific demographics to additionally evaluate the potentially confounding influences of race, age, and obesity. The effects of view angle were also preliminarily analysed. Classification results showed greater accuracy in the frontal plane than the sagittal plane, with models reaching 99% and 96% accuracy, respectively. Feature rankings and correlations are presented and discussed in relevance to future algorithms.

A randomised trial has previously been repeated in which 437 women with node positive breast cancer received either a 12-week chemohormonal regimen consisting of cyclophosphamide, methotrexate, fluorouracil, vincristine, prednisone, adriamycin and tamoxifen or 36 weeks of CMFVP. The present analysis concerns the local recurrence rates for the 122 lumpectomy patients who did not receive breast irradiation. The cumulative rate of local breast recurrence was greater in the 12-week than the 36-week group, P = 0.02. Similarly, in the lumpectomy patients, the cumulative rate of distant recurrence was greater in the 12-week than the 36-week group, P = 0.04. In conclusion, our results suggest that adjuvant chemotherapy impacts on local breast recurrence in a similar manner to other sites in Stage II breast cancer patients treated by lumpectomy without radiation. Despite the use of a conventional 36-week adjuvant chemotherapy regimen, the local breast recurrence rate was substantial.

Three experiments examined effects of temporally interleaved sequences of relevant and irrelevant information on selective attending to relevant visual items (letter pairs). In a serial monitoring task, viewers judged the physical match (same, different) of successive letter pairs in the relevant sequence under instructions to ignore irrelevant items. Irrelevant information comprised either visual information or tones. In all experiments the relative timing of relevant and irrelevant items was manipulated in slow visual sequences. Other manipulations included spatial formatting of irrelevant visual items (central vs displaced) and attentional set (speed vs accuracy). Results indicated that interleaved irrelevant information produced interference (slowed performance) relative to performance levels with relevant items alone only in certain timing conditions; in other conditions facilitation (faster responding occurred).

Purpose: To obtain the proper dynamic leaf gap (DLG) of a Millennium 120 MLC such that the calculated dose matches the measured. Methods: The DLG for round leaves is often measured via extrapolating the size of fields formed by sweeping synchronized MLC leaves to the size under which the measured dose equals the MLC transmission. In this situation, the tongue and groove effect would be minimal. However, practical IMRT fields are formed by non‐synchronized MLC leaves. Therefore, we measured doses from both synchronized and non‐synchronized dynamic fields. Each non‐synchronized field had fixed but different neighbouring leaf extensions (tongue‐and‐grove, T&G). The DLG was obtained for each set. Doses calculated with various values of DLG and transmission rate (TR) were compared with the measured dose. The relative discrepancies were put into a lookup table as function of gap and T&G. The table was used to estimate the pass rate of patient IMRT plans, in which each field was decomposed into sub‐fields. Each sub‐field was formed by a pair of opposite leaves. The T&G was calculated from the neighbouring leaves formed the sub‐field. Results: The extrapolated DLG was 1.8, 1.6, 1.7, 2.5 and 1.6mm for the T&G 0, 5, 10, 15 and 20mm, respectively. The MLC TR was 1.6%. For typical patient IMRT plans, the T&G values were broadly distributed from 0 to 20mm but with median around 15mm. From investigating many combinations of TR and T&G, we see the pass rate was extremely sensitive to the combination, and the highest pass rate went to the combination of transmission 1.6% and T&G 2.3mm. This Result excellently agreed with IMRT QA. Conclusion: The extrapolated DLG depends on the T&G. The proper value of DLG can be estimated from the study of non‐synchronized sweeping gaps and T&G distributions in typical patient IMRT plans.

368 Background: 5-Fluorouracil (5FU) and mitomycin-C (MMC) chemoradiation for anal cancer is associated with high rates of acute morbidity. We have previously shown that dose-painted IMRT (DP-IMRT) significantly reduces grade 3+ GI and dermatologic acute toxicity, as compared to the RTOG 9811 5FU/MMC arm, which used non-conformal radiation techniques. We now report on the two-year outcomes of this DP-IMRT approach. Methods: T2-4N0-3M0 anal canal cancers received 5FU (1,000 mg/m2/day 96 hour infusion) and MMC (10 mg/m2 bolus) days 1 and 29 of DP-IMRT prescribed as follows - T2N0: 42 Gy elective nodal and 50.4 Gy anal tumor planning target volumes (PTVs), 28 fractions; T3-4N0-3: 45 Gy elective nodal, 50.4 Gy ≤ 3 cm and 54 Gy > 3 cm metastatic nodal and 54 Gy anal tumor PTVs, 30 fractions. The following two-year outcomes were assessed: local-regional (LRF) and colostomy failures (CF) using the cumulative incidence method, and disease-free (DFS), overall (OS) and colostomy-free survivals (CFS) using the Kaplan-Meier method. Results: Of 63 accrued patients, 52 were analyzable. Median age was 58 years; 81% female; 54% stage II; 25% IIIA; 21% IIIB. Median follow-up was 23.2 months (0.2-33). Two-year LRF, CF, DFS and 95% confidence intervals are 20% (9%, 31%), 8% (0.4%, 15%) and 77% (62%, 86%), respectively. The causes of death for the 7 patients that died are: anal cancer in 5, morbidity in one and second primary outside the radiation field in one. Two-year comparison data from the RTOG 9811 5FU/MMC arm are shown in the table below. Conclusions: DP-IMRT with 5FU/MMC for the treatment of anal canal cancer yields similar two-year outcomes as the RTOG 9811 conventional radiation, 5FU/MMC arm. Because of the associated acute toxicity sparing, DP-IMRT will be used as the platform, and may allow for radiation dose escalation, in future RTOG anal canal trials. Supported by RTOG U10 CA21661, CCOP U10 CA3742 and ATC U24 CA 81647 NCI grants. [Table: see text] No significant financial relationships to disclose.

The purpose of this study was to assess how the perception of mass discrimination is affected by elevated Gz acceleration. Previous experiments studied mass discrimination under weightless conditions. Ten subjects were tested with the Dynamic Environment Simulator (DES) at Wright-Patterson Air Force Base. Masses of 105, 110, 115, 120, and 125 g were compared to a 100-g standard for delta Ms of 5, 10, 15, 20, and 25 g. The subject had to choose which mass felt heavier. This was done at 1, 2, and 4 Gz. Significant differences were found between each of the G levels, and the subjects made more errors at higher Gz. Significant differences were also found between each of the delta Ms, except between delta Ms of 20 and 25 g. Using regression lines, the difference limen was calculated at the 75% correct response level for each Gz. The Weber fraction was found by dividing the difference limen by the 100-g standard. Weber fraction of 0.085, 0.116, and 0.145 were found at 1, 2, and 4 Gz, respectively. Impairment to discrimination was shown by calculating the ratio of the Weber fraction of the elevated Gz to 1 Gz. This demonstrated an impairment to mass discrimination at 1.36 at 2 Gz and 1.71 at 4 Gz. Impairment of mass discrimination under elevated G indicates that loss of adaptation is more important than weight or mass constancy or any other factors which would increase gravitational sensory cues. This study attempted to show adaptation by comparing runs done on different days. To show aftereffect, intervals of 1 G were compared to each other. The study did not find any adaptation or aftereffect. When compared to previous studies done in weightlessness, microgravity was found to be more detrimental to mass discrimination than macrogravity, at least up to 4 Gz.

Traditionally, a number of variables have been used to predict outcome in patients with early-stage breast cancer. These tests are simple to perform and relatively inexpensive. Recently, a number of new factors, eg, tumor proliferative index, nuclear DNA content, and amplification or overexpression of growth-promoting genes or oncogenes have been identified as potential predictors of outcome in patients with breast cancer. There is now increasing pressure to introduce such tests into routine clinical practice. How does a clinical practitioner identify which test, or group of tests, best predicts adverse outcome and whether any more clinically useful information is provided than with the use of more traditional factors alone? The aim of a prognostic test in breast cancer is to predict which patients are destined to develop a recurrence of cancer and those who are not. The prognostic usefulness of a test can be expressed in terms of relative risk (RR), which is the ratio of the risk of breast cancer recurrence in patients who test positive to the risk in those who test negative. Methodologic guidelines that should be satisfied by a study evaluating the predictive ability of a test include the following: (1) Was an inception cohort assembled? (2) Was the referral pattern described? (3) Were laboratory and clinical outcomes assessed in a blinded fashion? (4) Was complete follow-up achieved? (5) Was adjustment for extraneous prognostic factors carried out? (6) Were appropriate statistical methods used? An approach is suggested to help the clinician choose the test, or combination of tests, likely to discriminate between "high-" and "low-risk" patients in his/her own practice. The decision regarding what particular threshold value (risk) defined by a prognostic test (or series of tests) warrants adjuvant therapy for an individual patient is a complex one but should be based on a clear presentation of the risks and benefits to the patient.

To determine whether the dose intensity of chemotherapeutic regimens correlates with the complete remission rate in adult patients with advanced-stage intermediate-grade lymphoma, reports of comparative trials of therapy were reviewed. Reports were identified using MEDLINE, through references from review articles, and through review of selected abstracts. Twenty-two studies including 14 randomized and eight cohort trials were analyzed to assess projected dose intensity. Four other studies were analyzed to assess the role of received dose intensity. Dose intensities were calculated using described methods and correlated with complete remission rates. Individual trials were assessed using "levels of evidence." A metaanalysis of randomized trials and a cross-trial analysis of all comparative trials using a weighted least squares linear regression were performed. Using levels of evidence, support was obtained for the hypothesis that dose intensity correlates with the remission rate from two trials in which dose intensity was "indirectly" tested. As these studies did not "directly" test dose intensity, confounding variables, including those arising from the assumptions made in calculating dose intensity, cannot be excluded. Metaanalysis showed a relative probability of achieving complete remission of 1.34 (95% confidence interval, 1.13 to 1.58) favoring the pooled arm of high dose intensity. Cross-trial analysis showed a relatively weak association between dose intensity and remission rate (r = .49, P = .0001). Two of four reports retrospectively assessing received dose intensity suggested that increased dose intensity is associated with superior remission rates. These analyses suggest that dose intensity may correlate with the remission rate in advanced-stage intermediate-grade lymphoma. However, properly designed trials directly testing dose intensity have not been performed and are needed to confirm this hypothesis.

Randomized trials comparing high-dose methotrexate (HDMTX) plus leucovorin (LV) with standard-dose methotrexate (SDMTX) have not detected a therapeutic advantage for the HDMTX arm despite compelling evidence from experimental systems. We hypothesized that these negative trials might reflect modulation of the antitumor effect of methotrexate (MTX) by LV. To test this we randomized 61 patients with locally advanced and recurrent squamous cell head and neck cancer to receive SDMTX (40 mg/m2 weekly for 8 weeks) and either LV or placebo "rescue" starting 24 hours later. Of the 61 randomized patients, there were protocol violations in two cases, leaving 59 patients evaluable for response using standard criteria, and for toxicity using the Eastern Cooperative Oncology Group (ECOG) scale. Of the 29 patients randomized to MTX plus LV, there were five responders (17.2%) compared with 11 of 30 (36.7%) patients randomized to MTX plus placebo (P = .047). Response was influenced independently by age, gender, and by previous treatment. Toxicity overall was more severe in patients randomized to MTX plus placebo (P = .016). This was accounted for primarily by differences in toxicities related to bone marrow function (neutrophil and platelet counts), stomatitis, and elevations of liver function tests. MTX therapy was more often interrupted for toxicity in the placebo group (P = .007) and discontinued for progressive disease in the LV group (P = .07). These results indicate that at the doses of MTX and LV used, LV modulates the antitumor effect as well as the toxicity of MTX in patients with head and neck cancer.

AB is a 73 year old Caucasian male who was diagnosed with mild Hemophilia A in 2001. He is part of a large kindred of patients with mild Hemophilia A enrolled in a cohort study. His family history was strongly positive. He was referred at the age of 69 years by a family member. His baseline Factor VIII level was 0.10. AB’s past medical history is characteristic of mild Hemophilia A. As a child he suffered frequently from epistaxis. He bled extensively after lacerations. He had had three significant accidents during his adult years, each of which resulted in massive bleeding and multiple blood transfusions. He had had three dental extractions which resulted in significant bleeding during two of three procedures. He had a hydrocele repair without complications. In 1999, he was extensively investigated for melena with no cause. He had an episode of atrial fibrillation and a possible transient ischemic attack treated with warfarin and aspirin. AB reported significant joint swelling and decreased range of motion. He also reported that he had “a leaky heart valve’. His initial physical examination revealed significant musculoskeletal problems. He had decreased range of motion bilaterally in his hips. He had extensive swelling of both knees and decreased range motion of both ankles. There was a limb length discrepancy of 1.5 cm. AB denied severe joint pain in his lower limbs or the usual symptoms associated with hemophiliac arthropathy. His aPTT was prolonged but he had not had a Factor VIII level previously measured and had never been told that he had Hemophilia A. He received a trial of prophylactic Recombinant Factor VIII three times a week for two months and was referred to an orthopedic surgeon. He received a “Factor First” Identification card recommending he receive 4000 units Recombinant Factor VIII for a major bleed. However, he had great difficulty in accepting the diagnosis and neither he nor his family initially volunteered that he had Hemophilia on his next admission. In April, 2002, AB was admitted to ICU in a community hospital, in Diabetic Ketoacidosis, three weeks after a snowmobile accident. Retrospectively, he reported back pain which he managed with NSAIDS. He was unable to walk prior to his hospitalization. In ICU, he required daily transfusions of PRBC & FFP. Abdominal CT on admission reported a resolving iliopsoas hematomas after an upper gastrointestinal bleed he was transferred to the provincial tertiary care centre. Follow-up CT showed bilateral ilopsoas hemtomas with abscess formation. A CT guided aspiration confirmed the presence of Staphyloccus aureus and a left paravertebral abscess. Follow-up CT showed no improvement. A second CT guided aspiration was performed which showed vertebral body destruction of L3, L4 and L5, discitis and multiple abscess formation. AB underwent L3-S1 fusion with laminectomy and decompression of L3–L4 and L4–L5 with no complications. In total AB received 316,040 units of RF VIII during a 122 day period of hospitalization. In contrast, the other 60 patients enrolled in our study only used 656,515 in a 4-year period. FACTOR VIII PRODUCT USAGE 2001–2004 FACTOR VIII PRODUCT USAGE 2001–2004

There has been much speculation about the ecology and behavior of whales, largely because effective techniques were not available for tracking them underwater, or for recording their dive depths. Thus, I developed a new tag and used it to mark free-swimming whales to monitor and record their geographical and vertical movements in real time. The tag contained 2 transmitters. The sonic transmitter (50 kHz) allowed submerged whales to be tracked from ≤2 km, and it produced a pulse rate or pulse intervalcoded signal from which dive depths were recorded. A VHF radio transmitter (148.00 MHz band) allowed individuals to be tracked at the sea surface from 10's of km