Androgen levels increase by intratumoral de novo steroidogenesis during progression of castration-resistant prostate cancer

Although systemic androgen deprivation prolongs life in advanced prostate cancer, remissions are temporary because patients almost uniformly progress to a state of a castration-resistant prostate cancer (CRPC) as indicated by recurring PSA. This complex process of progression does not seem to be stochastic as the timing and phenotype are highly predictable, including the observation that most androgen-regulated genes are reactivated despite castrate levels of serum androgens. Recent evidence indicates that intraprostatic levels of androgens remain moderately high following systemic androgen deprivation therapy, whereas the androgen receptor (AR) remains functional, and silencing the AR expression following castration suppresses tumor growth and blocks the expression of genes known to be regulated by androgens. From these observations, we hypothesized that CRPC progression is not independent of androgen-driven activity and that androgens may be synthesized de novo in CRPC tumors leading to AR activation. Using the LNCaP xenograft model, we showed that tumor androgens increase during CRPC progression in correlation to PSA up-regulation. We show here that all enzymes necessary for androgen synthesis are expressed in prostate cancer tumors and some seem to be up-regulated during CRPC progression. Using an ex vivo radiotracing assays coupled to high-performance liquid chromatography-radiometric/mass spectrometry detection, we show that tumor explants isolated from CRPC progression are capable of de novo conversion of [(14)C]acetic acid to dihydrotestosterone and uptake of [(3)H]progesterone allows detection of the production of six other steroids upstream of dihydrotestosterone. This evidence suggests that de novo androgen synthesis may be a driving mechanism leading to CRPC progression following castration.

Identity and text : developing self-conscious readers

Globalisation and societal change suggest the language and literacy skills needed to make meaning in our lives are increasing and changing radically. Multiliteracies are influencing the future of literacy teaching. One aspect of the pedagogy of multiliteracies is recruiting learners’ previous and current experiences as an integral part of the learning experience. This paper examines the implications of results from a project that examined student responses to a postmodern picture book, in particular, ways teachers might develop students’ self-knowledge about reading. It draws on Freebody and Luke’s Four Resources Model of Reading and recently developed models for teaching multiliteracies.

The speed paradox : the misalignment between driver attitudes and speeding behaviour

This paper reports on a study investigating preferred driving speeds and frequency of speeding of 320 Queensland drivers. Despite growing community concern about speeding and extensive research linking it to road trauma, speeding remains a pervasive, and arguably, socially acceptable behaviour. This presents an apparent paradox regarding the mismatch between beliefs and behaviours, and highlights the necessity to better understand the factors contributing to speeding. Utilising self-reported behaviour and attitudinal measures, results of this study support the notion of a speed paradox. Two thirds of participants agreed that exceeding the limit is not worth the risks nor is it okay to exceed the posted limit. Despite this, more than half (58.4%) of the participants reported a preference to exceed the 100km/hour speed limit, with one third preferring to do so by 10 to 20 km/hour. Further, mean preferred driving speeds on both urban and open roads suggest a perceived enforcement tolerance of 10%, suggesting that posted limits have limited direct influence on speed choice. Factors that significantly predicted the frequency of speeding included: exposure to role models who speed; favourable attitudes to speeding; experiences of punishment avoidance; and the perceived certainty of punishment for speeding. These findings have important policy implications, particularly relating to the use of enforcement tolerances.

In-vehicle avatars to elicit social response and change driving behaviour

Social and psychological theories have provided a plethora of evidence showing that the physical difficulty to express appropriate social interactions between drivers expresses itself in aggression, selfish driving and anti-social behaviour. Therefore there is a need to improve interactions between drivers and allow clearer collective decision making between them. Personal characteristics and the driving situations play strong roles in driver’s aggression. Our approach is centered around the driving situation as opposed to focusing on personality characteristics. It examines aggression and manipulates contextual variables such as driver’s eye contact exchanges. This paper presents a new unobtrusive in-vehicle system that aims at communicating drivers’ intentions, elicit social responses and increasing mutual awareness. It uses eye gaze as a social cue to affect collective decision making with the view to contribute to safe driving. The authors used a driving simulator to design a case control experiment in which eye gaze movements are conveyed with an avatar. Participants were asked to drive through different types of intersections. An avatar representing the head of the other driver was displayed and driver behaviour was analysed. Significant eye gaze pattern difference where observed when an avatar was displayed. Drivers cautiously refer to the avatar when information is required on the intention of others (e.g. when they do not have the right of way). The majority of participants reported the perception of “being looked at”. The number of glances and time spent gazing at the avatar did not indicate an unsafe distraction by standards of in-vehicle device ergonomic design. Avatars were visually consulted primarily in less demanding driving situations, which underlines their non-distractive nature.

Assessment of lifetime cumulative sun exposure using a self-administered questionnaire : reliability of two approaches

Few studies have evaluated the reliability of lifetime sun exposure estimated from inquiring about the number of hours people spent outdoors in a given period on a typical weekday or weekend day (the time-based approach). Some investigations have suggested that women have a particularly difficult task in estimating time outdoors in adulthood due to their family and occupational roles. We hypothesized that people might gain additional memory cues and estimate lifetime hours spent outdoors more reliably if asked about time spent outdoors according to specific activities (an activity-based approach). Using self-administered, mailed questionnaires, test-retest responses to time-based and to activity-based approaches were evaluated in 124 volunteer radiologic technologist participants from the United States: 64 females and 60 males 48 to 80 years of age. Intraclass correlation coefficients (ICC) were used to evaluate the test-retest reliability of average number of hours spent outdoors in the summer estimated for each approach. We tested the differences between the two ICCs, corresponding to each approach, using a t test with the variance of the difference estimated by the jackknife method. During childhood and adolescence, the two approaches gave similar ICCs for average numbers of hours spent outdoors in the summer. By contrast, compared with the time-based approach, the activity-based approach showed significantly higher ICCs during adult ages (0.69 versus 0.43, P = 0.003) and over the lifetime (0.69 versus 0.52, P = 0.05); the higher ICCs for the activity-based questionnaire were primarily derived from the results for females. Research is needed to further improve the activity-based questionnaire approach for long-term sun exposure assessment. (Cancer Epidemiol Biomarkers Prev 2009;18(2):464–71)

Empirical measurement of the Enright phenomenon, a distortion of perceived driving speed

Purpose: In 1970, Enright observed a distortion of perceived driving speed, induced by monocular application of a neutral density (ND) filter. If a driver looks out of the right side of a vehicle with a filter over the right eye, the driver perceives a reduction of the vehicle’s apparent velocity, while applying a ND filter over the left eye increases the vehicle’s apparent velocity. The purpose of the current study was to provide the first empirical measurements of the Enright phenomenon. Methods: Ten experienced drivers were tested and drove an automatic sedan on a closed road circuit. Filters (0.9 ND) were placed over the left, right or both eyes during a driving run, in addition to a control condition with no filters in place. Subjects were asked to look out of the right side of the car and adjust their driving speed to either 40 km/h or 60 km/h. Results: Without a filter or with both eyes filtered subjects showed good estimation of speed when asked to travel at 60 km/h but travelled a mean of 12 to 14 km/h faster than the requested 40 km/h. Subjects travelled faster than these baselines by a mean of 7 to 9 km/h (p < 0.001) with the filter over their right eye, and 3 to 5 km/h slower with the filter over their left eye (p < 0.05). Conclusions: The Enright phenomenon causes significant and measurable distortions of perceived driving speed under realworld driving conditions.

Influence of presbyopic corrections on driving-related eye and head movements

Purpose: To investigate whether wearing different presbyopic refractive corrections alters the pattern of eye and head movements when searching for dynamic targets in driving-related traffic scenes. Methods: Eye and head movements of 20 presbyopes (mean age = 56.2 ± 5.7 years), who had no experience of wearing presbyopic corrections or were unadapted wearers were recorded using the faceLABTM eye and head tracker, while wearing five different corrections: single vision lenses (SV), progressive addition lenses (PALs), bifocal spectacles (BIF), monovision and multifocal contact lenses (MTF CLs) in random order (within-subjects comparison). Recorded traffic scenes of suburban roads and expressways with edited targets were viewed as dynamic stimuli. Results: The magnitude of eye and head movements was significantly greater for SV, BIF and PALs than monovision and MTF CLs (p < 0.001). In addition, BIF wear led to more eye movements than PAL wear (p = 0.017), while PAL wear resulted in greater head movements than SV wear (p = 0.018). The ratio of eye to head movement was smaller for PALs than all other groups (p < 0.001). The number of saccades made to fixate a target was significantly higher for BIF and PALs than monovision or MTF CLs (p < 0.05). Conclusions: Different presbyopic corrections can alter eye and head movement patterns. Wearing spectacles such as BIF and PALs produced relatively greater eye and head movements and saccades when viewing dynamic targets. The impact of these changes in eye and head movement patterns may have implications for driving performance under real world driving conditions.

Driving performance in persons with hemianopia and quadrantanopia assessed under in-traffic conditions

Purpose: To evaluate the on-road driving performance of persons with homonymous hemianopia or quadrantanopia in comparison to age-matched controls with normal visual fields. Methods: Participants were 22 hemianopes and eight quadrantanopes (mean age 53 years) and 30 persons with normal visual fields (mean age 52 years) and were either current drivers or aiming to resume driving. All participants completed a battery of tests of vision (ETDRS visual acuity, Pelli-Robson letter contrast sensitivity, Humphrey visual fields), cognitive tests (trials A and B, Mini Mental State Examination, Digit Symbol Substitution) and an on-road driving assessment. Driving performance was assessed in a dual-brake vehicle with safety monitored by a certified driving rehabilitation specialist. Backseat evaluators masked to the clinical characteristics of participants independently rated driving performance along a 22.7 kilometre route involving urban and interstate driving. Results: Seventy-three per cent of the hemianopes, 88 per cent of quadrantanopes and all of the drivers with normal fields received safe driving ratings. Those hemianopic and quadrantanopic drivers rated as unsafe tended to have problems with maintaining appropriate lane position, steering steadiness and gap judgment compared to controls. Unsafe driving was associated with slower visual processing speed and impairments in contrast sensitivity, visual field sensitivity and executive function. Conclusions: Our findings suggest that some drivers with hemianopia or quadrantanopia are capable of safe driving performance, when compared to those of the same age with normal visual fields. This finding has important implications for the assessment of fitness to drive in this population.

A regulatory analysis of international climate change regulation

The political challenges impeding the negotiation of a comprehensive multilateral agreement on international climate change have received a great deal of attention. A question that has gone somewhat overlooked is what essential components an effective regulatory scheme to reduce greenhouse gas emissions should contain. The objective of this article is to examine the regulatory architecture of current international arrangements relating to global climate change regulation. A systematic analysis of the structure, substantive composition, and administrative characteristics of the UNFCCC and Kyoto Protocol is undertaken. The analytical standard against which the agreements are examined is whether current international regulatory arrangements satisfy the basic requirements of regulatory coherence. The analysis identifies how the present scheme consists of a complex institutional structure that lacks a substantive regulatory core. The implications of the absence of functional and effective mechanisms to govern greenhouse gas emission reductions are considered in relation to the principles of good regulatory design. This, in turn, provides useful insights into how a better regulatory scheme might be designed.

Driving-related eye and head movements are changed by the type of presbyopic correction

Purpose: To investigate whether wearing different presbyopic vision corrections alters the pattern of eye and head movements when viewing dynamic driving-related traffic scenes. Methods: Participants included 20 presbyopes (mean age: 56±5.7 years) who had no experience of wearing presbyopic vision corrections (i.e. all were single vision wearers). Eye and head movements were recorded while wearing five different vision corrections: single vision lenses (SV), progressive addition spectacle lenses (PALs), bifocal spectacle lenses (BIF), monovision (MV) and multifocal contact lenses (MTF CL) in random order. Videotape recordings of traffic scenes of suburban roads and expressways (with edited targets) were presented as dynamic driving-related stimuli and digital numeric display panels included as near visual stimuli (simulating speedometer and radio). Eye and head movements were recorded using the faceLAB™ system and the accuracy of target identification was also recorded. Results: The magnitude of eye movements while viewing the driving-related traffic scenes was greater when wearing BIF and PALs than MV and MTF CL (p≤0.013). The magnitude of head movements was greater when wearing SV, BIF and PALs than MV and MTF CL (p<0.0001) and the number of saccades was significantly higher for BIF and PALs than MV (p≤0.043). Target recognition accuracy was poorer for all vision corrections when the near stimulus was located at eccentricities inferiorly and to the left, rather than directly below the primary position of gaze (p=0.008), and PALs gave better performance than MTF CL (p=0.043). Conclusions: Different presbyopic vision corrections alter eye and head movement patterns. In particular, the larger magnitude of eye and head movements and greater number of saccades associated with the spectacle presbyopic corrections, may impact on driving performance.

The skin awareness study : promoting thorough skin self-examination for skin cancer among men 50 years or older

Background: Incidence and mortality from skin cancers including melanoma are highest among men 50 years or older. Thorough skin self-examination may be beneficial to improve skin cancers outcomes.--------- Objectives: To develop and conduct a randomized-controlled trial of a video-based intervention to improve skin self-examination behavior among men 50 years or older.--------- Methods: Pilot work ascertained appropriate targeting of the 12-minute intervention video towards men 50 years or older. Overall, 968 men were recruited and 929 completed baseline telephone assessment. Baseline analysis assessed randomization balance and demographic, skin cancer risk and attitudinal factors associated with conducting a whole-body skin self-examination or receiving a whole-body clinical skin examination by a doctor during the past 12 months.--------- Results: Randomization resulted in well-balanced intervention and control groups. Overall 13% of men reported conducting a thorough skin self-examination using a mirror or the help of another person to check difficult to see areas, while 39% reported having received a whole-body skin examination by a doctor within the past 12 months. Confidence in finding time for and receiving advice or instructions by a doctor to perform a skin self-examination were among the factors associated with thorough skin self-examination at baseline.---------- Conclusions: Men 50 years or older can successfully be recruited to a video-based intervention trial with the aim reduce their burden through skin cancer. Randomization by computer generated randomization list resulted in good balance between control and intervention group and baseline analysis determined factors associated with skin cancer early detection behavior at baseline.