Atypical prostatic glandular proliferations on needle biopsy - Diagnostic implications, use of immunohistochemistry, and clinical significance

In recent times, PSA screening and a substantial increase in prostate needle biopsies have not only resulted in detection of minute foci of cancer but have also very likely resulted in increased detection of atypical glandular proliferations. Not uncommonly, there are only a limited number of atypical glands in these biopsies, and these require careful evaluation to enable an accurate diagnosis. We describe diagnostic implications, use of immunohistochemistry, and clinical significance of these lesions. Foci of atypical glands, also labeled atypical small acinar proliferation of uncertain significance, have features suspicious for but not diagnostic of cancer. Atypical foci include a broad group of lesions of differing clinical significance. These include benign, small acinar proliferations mimicking prostate cancer and atypical glandular proliferations suspicious for carcinoma. Definite diagnosis requires accurate histopathologic assessment and judicious use of immunohistochemistry. Patients with atypical glands on prostate needle biopsy have a high risk for harboring cancer and therefore have an increased risk for having cancer detected in subsequent biopsies.

Clinical outcomes from skin screening clinics within a community-based melanoma screening program

Background : Within a randomized trial of population screening for melanoma, primary care physicians conducted whole-body skin examinations and referred all patients with suspect lesions to their own doctor for further treatment. Objective: Our aim was to describe characteristics of skin screening participants, clinical screening diagnoses, management following referral, and specificity and yield of screening examinations. Methods: Information collected from consent forms, referral forms, and histopathological reports of lesions that had been excised or undergone biopsy was analyzed by means of descriptive statistics. Results: A total of 16,383 whole-body skin examinations resulted in 2302 referrals (14.1% overall; 15.5% men, 18.2% >= 50 years of age) for 4129 suspect lesions (including 222 suspected melanoma, 1101 suspected basal cell carcinomas [BCCs], 265 suspected squamous cell carcinomas [SCCs]). Histopathologic results were available for 94.8% of 1417 lesions excised and confirmed 33 melanomas (23 in men; 24 in participants ? 50 years of age), 259 BCCs, and 97 SCCs. The probability of detecting skin cancer of any type within the program was 2.4%. The estimated specificity of whole-body skin examinations for melanoma was 86.1% (95% confidence interval = 85.6-86.6). The positive predictive value (number of confirmed/number of lesions excised or biopsied x 100) for melanoma was 2.5%, 19.3% for BCC, and 7.2% for SCC (overall positive predictive value for skin cancer, 28.9%). Limitations: Follow-up of participants with a negative screening examination has not been conducted for the present investigation. Conclusions: The rate of skin cancer detected per 100 patients screened was higher than previously reported and men and attendees older than 50 years more frequently received a referral and diagnosis of melanoma. The specificity for detection of melanoma through whole-body skin examination by a primary care physician was comparable to that of other screening tests, including mammography.

Morphology of breast cancer as a means of triage of patients for BRCA1 genetic testing

Background: Women who have germline mutations in the BRCA1 gene are at substantially increased lifetime risk of developing breast and ovarian cancer but are otherwise normal. Currently. early age of onset of cancer and a strong family history are relied upon as the chief clues as to who should be offered genetic testing. Certain morphologic and immunohistochemical features are overrepresented in BRCA1-associated breast cancers but these differences have not been incorporated into the current selection criteria for genetic testing. Design: Each of the 4 pathologists studied 30 known cases of BRCA1- and BRCA2-associated breast cancer from kConFab families. After reviewing the literature, we agreed on a semiquantitative scoring system for estimating the chances of presence of an underlying BRCA1 mutation, based on the number of the reported prototypic features present. After a time lag of 12 months, we each examined a series of 62 deidentified cases of breast cancer, inclusive of cases of BRCA1-associated breast cancer and controls. The controls included cases of BRCA2-associated breast cancer and sporadic cases. Results: Our predictions had a sensitivity of 92%, specificity of 86%, positive predictive value of 61%, and negative predictive value of 98%. For comparison the sensitivity of currently used selection criteria are in the range of 25% to 30%. Conclusion: The inclusion of morphologic and immunohistochemical features of breast cancers in algorithms to predict the likelihood of presence of germline mutations in the BRCA1 gene improves the accuracy of the selection process.

Nucleic acid amplification testing for Neisseria gonorrhoeae: An ongoing challenge

Nucleic acid amplification tests (NAATs) for the detection of Neisseria gonorrhoeae became available in the early 1990s. Although offering several advantages over traditional detection methods, N. gonorrhoeae NAATs do have some limitations. These include cost, risk of carryover contamination, inhibition, and inability to provide antibiotic resistance data. In addition, there are sequence-related limitations that are unique to N. gonorrhoeae NAATs. In particular, false-positive results are a major consideration. These primarily stem from the frequent horizontal genetic exchange occurring within the Neisseria genus, leading to commensal Neisseria species acquiring N. gonorrhoeae genes. Furthermore, some N. gonorrhoeae subtypes may lack specific sequences targeted by a particular NAAT. Therefore, NAAT false-negative results because of sequence variation may occur in some gonococcal populations. Overall, the N. gonorrhoeae species continues to present a considerable challenge for molecular diagnostics. The need to evaluate N. gonorrhoeae NAATs before their use in any new patient population and to educate physicians on the limitations of these tests is emphasized in this review.

The effects of assessment type on verbal ratings of conditional stimulus valence and contingency judgments: Implications for the extinction of evaluative learning

Recent research on causal learning found (a) that causal judgments reflect either the current predictive value of a conditional stimulus (CS) or an integration across the experimental contingencies used in the entire experiment and (b) that postexperimental judgments, rather than the CS's current predictive value, are likely to reflect this integration. In the current study, the authors examined whether verbal valence ratings were subject to similar integration. Assessments of stimulus valence and contingencies responded similarly to variations of reporting requirements, contingency reversal, and extinction, reflecting either current or integrated values. However, affective learning required more trials to reflect a contingency change than did contingency judgments. The integration of valence assessments across training and the fact that affective learning is slow to reflect contingency changes can provide an alternative interpretation for researchers' previous failures to find an effect of extinction training on verbal reports of CS valence.

Utility of signs and symptoms of chronic cough in predicting specific cause in children

Background: Paediatricians rely on cough descriptors to direct them to the level of investigations needed for a child presenting with chronic cough, yet there is a lack of published data to support this approach. A study was undertaken to evaluate ( 1) whether historical cough pointers can predict which children have a specific cause for their cough and ( 2) the usefulness of chest radiography and spirometry as standard investigations in children with chronic cough. Methods: This was a prospective cohort study of children referred to a tertiary hospital with a cough lasting 3 weeks between June 2002 and July 2004. All included children completed a detailed history and examination using a standardised data collection sheet and followed a pathway of investigation until a diagnosis was made. Results: In 100 consecutively recruited children of median age 2.8 years, the best predictor of specific cough observed was a moist cough at the time of consultation with an odds ratio ( OR) of 9.34 (95% CI 3.49 to 25.03). Chest examination or chest radiographic abnormalities were also predictive with OR 3.60 ( 95% CI 1.31 to 9.90) and 3.16 (95% CI 1.32 to 7.62), respectively. The most significant historical pointer for predicting a specific cause of the cough was a parental history of moist cough ( sensitivity 96%, specificity 26%, positive predictive value 74%). Conclusions: The most useful clinical marker in predicting specific cough is the presence of a daily moist cough. Both chest examination and chest radiographic abnormalities are also useful in predicting whether children have a specific cause of their cough.

Validity of verbal autopsy procedures for determining cause of death in Tanzania

Objectives: To validate verbal autopsy (VA) procedures for use in sample vital registration. Verbal autopsy is an important method for deriving cause-specific mortality estimates where disease burdens are greatest and routine cause-specific mortality data do not exist. Methods: Verbal autopsies and medical records (MR) were collected for 3123 deaths in the perinatal/neonatal period, post-neonatal < 5 age group, and for ages of 5 years and over in Tanzania. Causes of death were assigned by physician panels using the International Classification of Disease, revision 10. Validity was measured by: cause-specific mortality fractions (CSMF); sensitivity; specificity and positive predictive value. Medical record diagnoses were scored for degree of uncertainty, and sensitivity and specificity adjusted. Criteria for evaluating VA performance in generating true proportional mortality were applied. Results: Verbal autopsy produced accurate CSMFs for nine causes in different age groups: birth asphyxia; intrauterine complications; pneumonia; HIV/AIDS; malaria (adults); tuberculosis; cerebrovascular diseases; injuries and direct maternal causes. Results for 20 other causes approached the threshold for good performance. Conclusions: Verbal autopsy reliably estimated CSMFs for diseases of public health importance in all age groups. Further validation is needed to assess reasons for lack of positive results for some conditions.

Public reporting of hospital outcomes based on administrative data: risks and opportunities

In the wake of findings from the Bundaberg Hospital and Forster inquiries in Queensland, periodic public release of hospital performance reports has been recommended. A process for developing and releasing such reports is being established by Queensland Health, overseen by an independent expert panel. This recommendation presupposes that public reports based on routinely collected administrative data are accurate; that the public can access, correctly interpret and act upon report contents; that reports motivate hospital clinicians and managers to improve quality of care; and that there are no unintended adverse effects of public reporting. Available research suggests that primary data sources are often inaccurate and incomplete, that reports have low predictive value in detecting outlier hospitals, and that users experience difficulty in accessing and interpreting reports and tend to distrust their findings.

The role of BNP testing in heart failure

Brain natriuretic peptide (BNP) levels are simple and objective measures of cardiac function. These measurements can be used to diagnose heart failure, including diastolic dysfunction, and using them has been shown to save money in the emergency department setting. The high negative predictive value of BNP tests is particularly helpful for ruling out heart failure. Treatment with angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, spironolactone, and diuretics reduces BNP levels, suggesting that BNP testing may have a role in monitoring patients with heart failure. However, patients with treated chronic stable heart failure may have levels in the normal range (i.e., BNP less than 100 pg per mL and N-terminal proBNP less than 125 pg per mL in patients younger than 75 years). Increases in BNP levels may be caused by intrinsic cardiac dysfunction or may be secondary to other causes such as pulmonary or renal diseases (e.g., chronic hypoxia). BNP tests are correlated with other measures of cardiac status such as New York Heart Association classification. BNP level is a strong predictor of risk of death and cardiovascular events in patients previously diagnosed with heart failure or cardiac dysfunction.

Brachial blood pressure but not carotid arterial waveforms predict cardiovascular events in elderly female hypertensives

Central arterial waveforms and related indices of large artery properties can be determined with relative ease. This would make them an attractive adjunct in the risk stratification for cardiovascular disease. Although they have been associated with some classical risk factors and the presence of coronary disease, their prospective value in predicting cardiovascular outcomes is unknown. The present study determined the relative predictive value for cardiovascular disease-free survival of large artery properties as compared with noninvasive brachial blood pressure alone in a population of elderly female hypertensive subjects. We measured systemic arterial compliance, central systolic pressure, and carotid augmentation index in a subset of female participants in the Second Australian National Blood Pressure Study ( untreated blood pressure 169/88 +/- 12/ 8 mm Hg). There were a total of 53 defined events during a median of 4.1 years of follow-up in 484 women with complete measurements. Although baseline blood pressures at the brachial artery predicted cardiovascular disease-free survival ( hazard ratio [HR], 2.3; 95% CI, 1.3 to 4.1 for pulse pressure >= 81 versus < 81 mm Hg; P = 0.01), no such relation was found for carotid augmentation index ( HR, 0.80; 95% CI, 0.44 to 1.44; P value not significant) or systemic arterial compliance ( HR, 1.25; 95% CI, 0.72 to 2.16; P value not significant). Blood pressure, but not noninvasively measured central arterial waveforms, predict outcome in the older female hypertensive patient. Thus, blood pressure measurement alone is superior to measurement of arterial waveforms in predicting outcome in this group.

Developmental stability and leadership effectiveness

Developmental stability is the degree to which we can withstand environmental or genetic stressors during development. Fluctuating asymmetry (FA), concerns the extent to which the right and left side of the body is asymmetrical and is one way to measure developmental stability. Two studies were carried out that examined both the predictive value of leader FA with leadership behaviors and its role in facilitating group performance. The first study examined the hypothesis that a leader's FA is correlated with scores on the Multifactor Leadership Questionnaire (MLQ). The results revealed individuals with a more asymmetrical morphology scored higher on the transformational, but not transactional, dimensions of leadership behavior. A second study examined the hypothesis that asymmetrical morphology and leadership effectiveness would share a positive relationship. In this study participants who led a business game exercise, revealed a positive relationship between FA and self-reported well-being and task satisfaction. Importantly, there was also a positive correlation between the leader's FA score and group performance. The role that developmental stability may play in leadership effectiveness is discussed in the wider context of evolutionary psychology.

Status and professional association councils. Available in 4 volumes.

This thesis examines the predictive value of a conceptual distinction between status-seeking associations and status-maintaining associations for enhancing understanding of ten selected professional associations and of the attitudes, values, behaviour and policies of their governing organs. Thirty four specific hypotheses have been tested by such research methods as questionnaires administered to individuals and associations, participant observation and an examination of association minutes and publications. Certain hypotheses have been found to be valid for particular matched pairs and/or groups of associations. The findings of the study suggest that the present conceptualisation of profession, the individual professional, professionalism, professionalisation, professional status and that relating to the role of the professions in society needs to be refined and modified in varying degrees in application to accounting associations, business graduate associations and management associations. The concept of the `ideal type' profession is shown to be of limited value in understanding certain aspects of the activities of business graduate and management associations. The findings of the study suggest that in future the professional associations examined may attach less importance to their qualifying role and lay more stress upon their representational role. The professional association faces a managerial challenge to adjust and adapt to a range of `external' pressures and `internal' demands from members and may increasingly need to be regarded as an organisation that possesses certain combinations or sets of characteristics rather than as a type of organisation that possesses a particular or relatively exclusive set. With a blurring of the distinction between the professional and state sector vocational education, and a growing customer/market orientation associated with the changing nature of work, membership of a professional association may, in future, come to be associated rather more with securing access to a relevant range of services and less with qualification for a particular career.

Waveform type evaluation in congenital nystagmus

Congenital nystagmus is an ocular-motor disorder characterised by involuntary, conjugated and bilateral to and fro ocular oscillations. In this study a method to recognise automatically jerk waveform inside a congenital nystagmus recording and to compute foveation time and foveation position variability is presented. The recordings were performed with subjects looking at visual targets, presented in nine eye gaze positions; data were segmented into blocks corresponding to each gaze position. The nystagmus cycles were identified searching for local minima and maxima (SpEp sequence) in intervals centred on each slope change of the eye position signal (position criterion). The SpEp sequence was then refined using an adaptive threshold applied to the eye velocity signal; the outcome is a robust detection of each slow phase start point, fundamental to accurately compute some nystagmus parameters. A total of 1206 slow phases was used to compute the specificity in waveform recognition applying only the position criterion or adding the adaptive threshold; results showed an increase in negative predictive value of 25.1% using both features. The duration of each foveation window was measured on raw data or using an interpolating function of the congenital nystagmus slow phases; foveation time estimation less sensitive to noise was obtained in the second case. © 2010.

People consider reliability and cost when verifying their autobiographical memories

Because memories are not always accurate, people rely on a variety of strategies to verify whether the events that they remember really did occur. Several studies have examined which strategies people tend to use, but none to date has asked why people opt for certain strategies over others. Here we examined the extent to which people's beliefs about the reliability and the cost of different strategies would determine their strategy selection. Subjects described a childhood memory and then suggested strategies they might use to verify the accuracy of that memory. Next, they rated the reliability and cost of each strategy, and the likelihood that they might use it. Reliability and cost each predicted strategy selection, but a combination of the two ratings provided even greater predictive value. Cost was significantly more influential than reliability, which suggests that a tendency to seek and to value "cheap" information more than reliable information could underlie many real-world memory errors. © 2013 Elsevier B.V.

Gait Measurements and Motor Recovery after Stroke

2000 Mathematics Subject Classification: 62P10, 92C20