Effects of age, breast density, ethnicity, and estrogen replacement therapy on screening mammographic sensitivity and cancer stage at diagnosis: review of 183,134 screening mammograms in Albuquerque, New Mexico

PURPOSE: To examine how common patient factors affect screening mammographic sensitivity and cancer stage at diagnosis. MATERIALS AND METHODS: The authors used a population-based database of 183,134 screening mammograms and a statewide tumor registry to identify 807 breast cancers detected at screening mammography. RESULTS: Sensitivity varied significantly with ethnicity, use of estrogen replacement therapy, mammographic breast density, and age. Sensitivity was 54% (13 of 24) in women younger than 40 years, 77% (121 of 157) in women aged 40-49 years, 78% (224 of 286) in women aged 50-64 years, and 81% (277 of 340) in women older than 64 years. Sensitivity was 68% (162 of 237) for dense breasts and 85% (302 of 356) for nondense breasts and 74% (180 of 244) in estrogen replacement therapy users and 81% (417 of 513) in nonusers. Sensitivity was most markedly reduced with the combination of dense breasts and estrogen replacement therapy use; there was little difference when only one factor was present. Median cancer size and the percentage of early cancers showed little change with any factors. CONCLUSION: Age is a minor determinant of mammographic sensitivity in women aged 40 years or older. Sensitivity is substantially decreased with the combination of higher breast density and estrogen replacement therapy use. There was not a notable shift in cancer outcomes in the groups with lower mammographic sensitivity. These data do not support different screening recommendations in women aged 40-49 years or in estrogen replacement therapy users.     

Implementing CS1 with embedded instructional research design in laboratories

Closed laboratories are becoming an increasingly popular approach to teaching introductory computer science courses. Unlike open laboratories that tend to be an informal environment provided for students to practice their skills with attendance optional, closed laboratories are structured meeting times that support the lecture component of the course, and attendance is required. This paper reports on an integrated approach to designing, implementing, and assessing laboratories with an embedded instructional research design. The activities reported here are parts of a departmentwide effort not only to improve student learning in computer science and computer engineering (CE) but also to improve the agility of the Computer Science and Engineering Department in adapting the curriculum to changing technologies, incorporate research, and validate the instructional strategies used. This paper presents the design and implementation of the laboratories and the results and analysis of student performance. Also described in this paper is cooperative learning in the laboratories and its impact on student learning.     

A Catalyst‐Directed Remote Stereogenic Center Switch During the Site‐Selective Aldol Desymmetrization of Cyclohexanone‐Based Diketones

Site‐selectivity, differentiating members of the same functional group type on one substrate, is an emerging tactic for shortened advanced building block and biomolecule synthesis. Despite its potential, site‐selectivity remains less studied and especially so for ketone‐based substrates. During this work ketone site‐selectivity has been coupled with the chiral amine‐catalyzed aldol desymmetrization of 4‐keto‐substituted cyclohexanones, allowing three stereogenic centers to form in the aldol product while leaving the acyclic ketone unreacted. Unique here, compared to all previous 4‐substituted cyclohexanone desymmetrizations, is the first access to synthetically useful quantities of an epimeric (remote stereogenic center) aldol product. To demonstrate the value of these aldol products, we show their elaboration into eight keto‐acetonide and one keto‐lactone products. All compounds were isolated as single diastereomers and in high ee (≥96%). These efforts represent the first full characterization of aldol products with type III, Figure 2, relative stereochemistry, regardless of the enantiomer formed.

     

Protein engineering loops in aspartic proteinases: site-directed mutagenesis, biochemical characterization and X-ray analysis of chymosin with a replaced loop from rhizopuspepsin

The loop exchange mutant chymosm 155–164 rhizopuspepsinwas expressed in Trichoderma reesei and exported into the mediumto yield a correctly folded and active product. The biochemicalcharacterization and crystal structure determination at 2.5Å resolution confirm that the mutant enzyme adopts a nativefold. However, the conformation of the mutated loop is unlikethat in native rhizopuspepsin and involves the chelation ofa water molecule in the loop. Kinetic analysis using two syntheticpeptide substrates (six and 15 residues long) and the naturalsubstrate, milk, revealed a reduction in the activity of themutant enzyme with respect to the native when acting on boththe long peptide substrate and milk. This may be a consequenceof the different charge distribution of the mutated loop, itsincreased size and/or its different conformation.     

A usability evaluation of medical software at an expert conference setting

Introduction

A usability test was employed to evaluate two medical software applications at an expert conference setting. One software application is a medical diagnostic tool (electrocardiogram [ECG] viewer) and the other is a medical research tool (electrode misplacement simulator [EMS]). These novel applications have yet to be adopted by the healthcare domain, thus, (1) we wanted to determine the potential user acceptance of these applications and (2) we wanted to determine the feasibility of evaluating medical diagnostic and medical research software at a conference setting as opposed to the conventional laboratory setting.

Methods

The medical diagnostic tool (ECG viewer) was evaluated using seven delegates and the medical research tool (EMS) was evaluated using 17 delegates that were recruited at the 2010 International Conference on Computing in Cardiology. Each delegate/participant was required to use the software and undertake a set of predefined tasks during the session breaks at the conference. User interactions with the software were recorded using screen-recording software. The ‘think-aloud’ protocol was also used to elicit verbal feedback from the participants whilst they attempted the pre-defined tasks. Before and after each session, participants completed a pre-test and a post-test questionnaire respectively.

Results

The average duration of a usability session at the conference was 34.69 min (SD = 10.28). However, taking into account that 10 min was dedicated to the pre-test and post-test questionnaires, the average time dedication to user interaction of the medical software was 24.69 min (SD = 10.28). Given we have shown that usability data can be collected at conferences, this paper details the advantages of conference-based usability studies over the laboratory-based approach. For example, given delegates gather at one geographical location, a conference-based usability evaluation facilitates recruitment of a convenient sample of international subject experts. This would otherwise be very expensive to arrange. A conference-based approach also allows for data to be collected over a few days as opposed to months by avoiding administration duties normally involved in laboratory based approach, e.g. mailing invitation letters as part of a recruitment campaign.Following analysis of the user video recordings, 41 (previously unknown) use errors were identified in the advanced ECG viewer and 29 were identified in the EMS application. All use errors were given a consensus severity rating from two independent usability experts. Out of a rating scale of 4 (where 1 = cosmetic and 4 = critical), the average severity rating for the ECG viewer was 2.24 (SD = 1.09) and the average severity rating for the EMS application was 2.34 (SD = 0.97). We were also able to extract task completion rates and times from the video recordings to determine the effectiveness of the software applications. For example, six out of seven tasks were completed by all participants when using both applications. This statistic alone suggests both applications already have a high degree of usability. As well as extracting data from the video recordings, we were also able to extract data from the questionnaires. Using a semantic differential scale (where 1 = poor and 5 = excellent), delegates highly rated the ‘responsiveness’, ‘usefulness’, ‘learnability’ and the ‘look and feel’ of both applications.

Conclusion

This study has shown the potential user acceptance and user-friendliness of the novel EMS and the ECG viewer applications within the healthcare domain. It has also shown that both medical diagnostic software and medical research software can be evaluated for their usability at an expert conference setting. The primary advantage of a conference-based usability evaluation over a laboratory-based evaluation is the high concentration of experts at one location, which is convenient, less time consuming and less expensive.     

Sequential cardiorespiratory patterns of anesthetic induction with ketamine in critically ill patients

Hemodynamic and O2 transport effects of ketamine anesthesia were evaluated in 22 critically ill patients. After placement of radial and pulmonary artery catheters, simultaneous measurement were made of cardiac output, intravascular pressures, arterial and mixed venous gases, saturations, pH, and Hct; cardiorespiratory values then were calculated for a preinduction control period and sequentially at frequent intervals over a 15-min observation period. In general, there was an early progressive increase in HR, cardiac index (CI), arterial and venous pressures, stroke work, and O2 delivery (DO2); O2 consumption (VO2) and O2 extraction (O2 Ext) decreased. In general, ketamine produced an inotropic cardiac response, but these responses were not uniform; a relatively small percentage had reduced pressures, flow, and reduced myocardial performance that were related to hypovolemia and associated medical conditions.     

IFN-alpha 2B enhances Th1 cytokine responses in bladder cancer patients receiving Mycobacterium bovis bacillus Calmette-Guérin immunotherapy

Combination therapy with intravesical bacillus Calmette-Guérin (BCG) plus IFN-alpha for superficial bladder cancer has been demonstrated to be more effective than either single agent alone in animal studies and of suggested greater efficacy in clinical studies. However, the mechanism by which IFN-alpha enhances BCG-mediated antitumor activity is poorly understood. Using PBMCs from bladder cancer patients, IFN-alpha was found to substantially enhance the efficacy of BCG to induce IFN-gamma production. Among 34 patients tested, 80% showed >4-fold increase. This effect of IFN-alpha was observed in both initial and memory responses to BCG. In addition, IFN-alpha up-regulated BCG-induced IL-12 and TNF-alpha and down-regulated BCG-induced IL-10. Neutralizing endogenous IL-10 or adding exogenous IL-12 provided further synergy for IFN-gamma production. In clinical practice, intravesical IFN-alpha 2B (50 million units (MU)/dose) was observed to accelerate urinary IFN-gamma production to low-dose BCG (one-tenth or one-third of a full dose) in patients treated with combination therapy compared with BCG alone. These results suggest that IFN-alpha is a potent BCG enhancer that polarizes the BCG-induced immune response toward the cellular immune pathway by promoting Th1 cytokine expression and reducing Th2 cytokine expression. This study provides an immunological basis for future rational use of IFN-alpha in conjunction with intravesical BCG for bladder cancer immunotherapy.     

Outcome of moderate carotid artery stenosis in patients who are asymptomatic

PURPOSE: The incidence rate of disease progression and stroke after the diagnosis of a moderate (50% to 79%) carotid stenosis was determined by means of color-flow duplex scanning. METHODS: During a 4-year period, 344 male veterans with moderate internal carotid artery stenoses, on one or both sides, were examined at regular intervals for a mean period of 25 months. Carotid color-flow scans were obtained semiannually. Clinical follow-up was performed to determine the incidence rate of amaurosis fugax, transient ischemic attacks, nonhemispheric symptoms, and strokes. RESULTS: New neurologic symptoms developed in 75 patients (21.8%). Fifty-one (14.8%) had ipsilateral symptoms during follow-up: 18 amaurosis fugax (5.2%), 14 transient ischemic attacks (4%), 5 nonhemispheric symptoms (1.4%), and 14 strokes (4%). Twenty-four patients (6.9%) had contralateral symptoms: 20 strokes (5.8%) and 4 transient ischemic attacks (1.2%). Life-table analysis showed that the annual rate of ipsilateral neurologic events was 8.1%, and the annual rate of stroke was 2.1%. Seventy-five patients (22%) died in the follow-up period. Disease progression to 80% to 99% stenosis or occlusion occurred in 71 of 458 vessels (15.5%). The internal carotid arteries that showed evidence of disease progression had a significantly higher initial peak systolic velocity (251 vs 190 cm/s; P <.0001) and end diastolic velocity (74 vs 52 cm/s; P < 0.0001). Black patients and patients with ischemic heart disease were at a higher risk for disease progression. We could not identify any atherosclerotic risk factors that reliably predicted patients in whom future ipsilateral neurologic symptoms were more likely to develop. However, there was an increased risk of stroke associated with progression of disease. CONCLUSION: Patients who are asymptomatic and who have moderate carotid stenoses are at significant risk for neurologic symptoms and death, but have a relatively low incidence rate of ipsilateral events. The initial flow characteristics in the stenotic vessel are predictive of future disease progression, but they are not helpful in identifying patients in whom symptoms will develop.