Compilation of somatic mutations of the CDKN2 gene in human cancers : non-random distribution of base substitutions

The CDKN2 gene, encoding the cyclin-dependent kinase inhibitor p16, is a tumour suppressor gene that maps to chromosome band 9p21-p22. The most common mechanism of inactivation of this gene in human cancers is through homozygous deletion; however, in a smaller proportion of tumours and tumour cell lines intragenic mutations occur. In this study we have compiled a database of over 120 published point mutations in the CDKN2 gene from a wide variety of tumour types. A further 50 deletions, insertions, and splice mutations in CDKN2 have also been compiled. Furthermore, we have standardised the numbering of all mutations according to the full-length 156 amino acid form of p16. From this study we are able to define several hot spots, some of which occur at conserved residues within the ankyrin domains of p16. While many of the hotspots are shared by a number of cancers, the relative importance of each position varies, possibly reflecting the role of different carcinogens in the development of certain tumours. As reported previously, the mutational spectrum of CDKN2 in melanomas differs from that of internal malignancies and supports the involvement of UV in melanoma tumorigenesis. Notably, 52% of all substitutions in melanoma-derived samples occurred at just six nucleotide positions. Nonsense mutations comprise a comparatively high proportion of mutations present in the CDKN2 gene, and possible explanations for this are discussed.

DEM test, visagraph eye movement recordings, and reading ability in children

Purpose. To determine how Developmental Eye Movement (DEM) test results relate to reading eye movement patterns recorded with the Visagraph in visually normal children, and whether DEM results and recorded eye movement patterns relate to standardized reading achievement scores. Methods. Fifty-nine school-age children (age = 9.7 ± 0.6 years) completed the DEM test and had eye movements recorded with the Visagraph III test while reading for comprehension. Monocular visual acuity in each eye and random dot stereoacuity were measured and standardized scores on independently administered reading comprehension tests [reading progress test (RPT)] were obtained. Results. Children with slower DEM horizontal and vertical adjusted times tended to have slower reading rates with the Visagraph (r = -0.547 and -0.414 respectively). Although a significant correlation was also found between the DEM ratio and Visagraph reading rate (r = -0.368), the strength of the relationship was less than that between DEM horizontal adjusted time and reading rate. DEM outcome scores were not significantly associated with RPT scores. When the relative contribution of reading ability (RPT) and DEM scores was accounted for in multivariate analysis, DEM outcomes were not significantly associated with Visagraph reading rate. RPT scores were associated with Visagraph outcomes of duration of fixations (r = -0.403) and calculated reading rate (r = 0.366) but not with DEM outcomes. Conclusions.DEM outcomes can identify children whose Visagraph recorded eye movement patterns show slow reading rates. However, when reading ability is accounted for, DEM outcomes are a poor predictor of reading rate. Visagraph outcomes of duration of fixation and reading rate relate to standardized reading achievement scores; however, DEM results do not. Copyright © 2011 American Academy of Optometry.

Sit versus stand : can sitting be accurately identified using MTI accelerometer data?

High levels of sitting have been linked with poor health outcomes. Previously a pragmatic MTI accelerometer data cut-point (100 count/min-1) has been used to estimate sitting. Data on the accuracy of this cut-point is unavailable. PURPOSE: To ascertain whether the 100 count/min-1 cut-point accurately isolates sitting from standing activities. METHODS: Participants fitted with an MTI accelerometer were observed performing a range of sitting, standing, light & moderate activities. 1-min epoch MTI data were matched to observed activities, then re-categorized as either sitting or not using the 100 count/min-1 cut-point. Self-report demographics and current physical activity were collected. Generalized estimating equation for repeated measures with a binary logistic model analyses (GEE), corrected for age, gender and BMI, were conducted to ascertain the odds of the MTI data being misclassified. RESULTS: Data were from 26 healthy subjects (8 men; 50% aged <25 years; mean BMI (SD) 22.7(3.8)m/kg2). MTI sitting and standing data mode was 0 count/min-1, with 46% of sitting activities and 21% of standing activities recording 0 count/min-1. The GEE was unable to accurately isolate sitting from standing activities using the 100 count/min-1 cut-point, since all sitting activities were incorrectly predicted as standing (p=0.05). To further explore the sensitivity of MTI data to delineate sitting from standing, the upper 95% confidence interval of the mean for the sitting activities (46 count/min-1) was used to re-categorise the data; this resulted in the GEE correctly classifying 49% of sitting, and 69% of standing activities. Using the 100 count/min-1 cut-point the data were re-categorised into a combined ‘sit/stand’ category and tested against other light activities: 88% of sit/stand and 87% of light activities were accurately predicted. Using Freedson’s moderate cut-point of 1952 count/min-1 the GEE accurately predicted 97% of light vs. 90% of moderate activities. CONCLUSION: The distributions of MTI recorded sitting and standing data overlap considerably, as such the 100 count/min -1 cut-point did not accurately isolate sitting from other static standing activities. The 100 count/min -1 cut-point more accurately predicted sit/stand vs. other movement orientated activities.

Nanostructured mesoporous bioglass coated zirconia scaffolds for bone tissue engineering

For the filling and reconstruction of non-healing bone defects, the application of porous ceramic scaffold as bone substitutes is considered to be a reasonable choice. In bone tissue engineering, an ideal scaffold must satisfy several criterias such as open porosity, having high compressive strength (it depends where in body, and if external fixatures are used) and the practicability for cell migration. Many researchers have focused on enhancing the mechanical properties of hydroxyapatite scaffolds by combining it with other biomaterials, such as bioglass and polymers. Nevertheless, there is still a lack of suitable scaffolds based on porous biomaterials. In this study, zirconia scaffolds from two different templates (polyurethane (PU) and Acrylonitrile Butadiene Styrene (ABS) templates) were successfully fabricated with dissimilar fabrication techniques. The scaffold surfaces were further modified with mesoporous bioglass for the purpose of bone tissue engineering. In the study of PU template scaffold, high porosity (~88%) sol-gel derived yttria-stabilized zirconia (YSZ) scaffold was prepared by a polyurethane (PU) foam replica method using sol-gel derived zirconia for the first time, and double coated with Mesoporous Bioglass (MBGs) coating. For the ABS template scaffold, two types of templates (cube and cylinder) with different strut spacings were used and fabricated by a 3D Rapid Prototyper. Subsequently, zirconia scaffolds with low porosity (63±2.8% to 68±2.5%) were fabricated by embedding the zirconia powder slurry into the ABS templates and burning out the ABS to produce a uniform porous structure. The zirconia scaffolds were double coated with mesoporous bioglass by dip coating for the first time. The porosities of the scaffolds were calculated before and after coating. The microstructures were then examined using scanning electron microscopy and the mechanical properties were evaluated using compressive test. Accordingly, relationships between microstructure, processing and mechanical behaviour of the porous zirconia was discussed. Scaffold biocompatibility and bioactivity was also evaluated using a bone marrow stromal cell (BMSC) proliferation test and a simulated body fluid test.

The molecular structure of the mineral sarmientite Fe2(AsO4,SO4)2(OH)6•5H2O : implications for arsenic accumulation and removal

Sarmientite is an environmental mineral; its formation in soils enables the entrapment and immobilisation of arsenic. The mineral sarmientite is often amorphous making the application of X-ray diffraction difficult. Vibrational spectroscopy has been applied to the study of sarmientite. Bands are attributed to the vibrational units of arsenate, sulphate, hydroxyl and water. Raman bands at 794, 814 and 831 cm−1 are assigned to the ν3 (AsO4)3− antisymmetric stretching modes and the ν1 symmetric stretching mode is observed at 891 cm−1. Raman bands at 1003 and 1106 cm−1 are attributed to vibrations. The Raman band at 484 cm−1 is assigned to the triply degenerate (AsO4)3− bending vibration. The high intensity Raman band observed at 355 cm−1 (both lower and upper) is considered to be due to the (AsO4)3−ν2 bending vibration. Bands attributed to water and OH stretching vibrations are observed.

Inferior field loss increases rate of falls in older adults with glaucoma

PURPOSE: To examine the visual predictors of falls and injurious falls among older adults with glaucoma. METHODS: Prospective falls data were collected for 71 community-dwelling adults with primary open-angle glaucoma, mean age 73.9 ± 5.7 years, for one year using monthly falls diaries. Baseline assessment of central visual function included high-contrast visual acuity and Pelli-Robson contrast sensitivity. Binocular integrated visual fields were derived from monocular Humphrey Field Analyser plots. Rate ratios (RR) for falls and injurious falls with 95% confidence intervals (CIs) were based on negative binomial regression models. RESULTS: During the one year follow-up, 31 (44%) participants experienced at least one fall and 22 (31%) experienced falls that resulted in an injury. Greater visual impairment was associated with increased falls rate, independent of age and gender. In a multivariate model, more extensive field loss in the inferior region was associated with higher rate of falls (RR 1.57, 95%CI 1.06, 2.32) and falls with injury (RR 1.80, 95%CI 1.12, 2.98), adjusted for all other vision measures and potential confounding factors. Visual acuity, contrast sensitivity, and superior field loss were not associated with the rate of falls; topical beta-blocker use was also not associated with increased falls risk. CONCLUSIONS: Falls are common among older adults with glaucoma and occur more frequently in those with greater visual impairment, particularly in the inferior field region. This finding highlights the importance of the inferior visual field region in falls risk and assists in identifying older adults with glaucoma at risk of future falls, for whom potential interventions should be targeted. KEY WORDS: glaucoma, visual field, visual impairment, falls, injury

Knowledge management in law enforcement : knowledge views for patrolling police officers

This paper describes and classifies different types of knowledge that are a part of police patrol officer's practice. Even though an investigation usually forces a police officer to apply several different knowledge types, this paper discusses different forms of professional knowledge separately to enable categorisation.

Determinants of rapid weight gain during infancy: Baseline results from the NOURISH randomised controlled trial.

Background: Rapid weight gain in infancy is an important predictor of obesity in later childhood. Our aim was to determine which modifiable variables are associated with rapid weight gain in early life. Methods: Subjects were healthy infants enrolled in NOURISH, a randomised, controlled trial evaluating an intervention to promote positive early feeding practices. This analysis used the birth and baseline data for NOURISH. Birthweight was collected from hospital records and infants were also weighed at baseline assessment when they were aged 4-7 months and before randomisation. Infant feeding practices and demographic variables were collected from the mother using a self administered questionnaire. Rapid weight gain was defined as an increase in weight-for-age Z-score (using WHO standards) above 0.67 SD from birth to baseline assessment, which is interpreted clinically as crossing centile lines on a growth chart. Variables associated with rapid weight gain were evaluated using a multivariable logistic regression model. Results: Complete data were available for 612 infants (88% of the total sample recruited) with a mean (SD) age of 4.3 (1.0) months at baseline assessment. After adjusting for mother's age, smoking in pregnancy, BMI, and education and infant birthweight, age, gender and introduction of solid foods, the only two modifiable factors associated with rapid weight gain to attain statistical significance were formula feeding [OR=1.72 (95%CI 1.01-2.94), P= 0.047] and feeding on schedule [OR=2.29 (95%CI 1.14-4.61), P=0.020]. Male gender and lower birthweight were non-modifiable factors associated with rapid weight gain. Conclusions: This analysis supports the contention that there is an association between formula feeding, feeding to schedule and weight gain in the first months of life. Mechanisms may include the actual content of formula milk (e.g. higher protein intake) or differences in feeding styles, such as feeding to schedule, which increase the risk of overfeeding. Trial Registration: Australian Clinical Trials Registry ACTRN12608000056392

Social influences on Chinese drivers : cultural context and traffic law enforcement

Reducing road crashes and associated trauma is a critical focus as the Decade of Action for Road Safety commences. China is one of many rapidly-motorizing nations to experience recent increases in private-vehicle ownership and an associated escalation in novice drivers. Unfortunately, however, China also experiences a high rate of death and injury from road crashes. Several key pieces of legislation have been introduced in recent decades in China to deal with these changes. While managing the legal aspects of road use is important, social influences on driver behaviour may offer additional avenues for promoting safe driving, particularly in a culture where such factors carry high importance. To date, there is limited research on the role of social influence factors on driver behaviour in China, yet we know that Chinese society is strongly based on social rules, customs, and relationships. There is reason to assume therefore, that road use and driving-related issues may also be strongly influenced by social relationships. One previous study that has investigated such issues highlighted the need to consider culturally-specific issues such as interpersonal networks and social hierarchy when examining driver behaviour in China (Xie & Parker, 2002). Those authors suggested that there are some concepts relating to Chinese driving culture that may not necessarily have been identified from research conducted in western contexts and that research conducted in China must be considered in light of such concepts. The current paper reports qualitative research conducted with Beijing drivers to investigate such social influence factors. Findings indicated that family members, friends, and driving instructors appear influential on driver behaviour and that some novice drivers seek additional assistance after obtaining their licence. The finding relating to the influence of driving instructors was not surprising, given the substantial number of new drivers in China. In Beijing, driving instruction is conducted off-road in purpose-specific driving facilities rather than on the road network. Once licensed, it is common for new drivers to have little or no experience driving in complex traffic situations. This learning situation is unlikely to provide all the skills necessary to successfully negotiate crowded city streets and assess the related risk associated with such driving. Therefore, it was not surprising to find that one reported strategy to assist new drivers was to employ the services of an ‘accompanying driver’ to provide ongoing driving instruction once licensed. In more highly motorised countries supervised practice is part of a graduated licensing system where it is compulsory for new drivers to be supervised by a more experienced driver for a requisite period of time before progressing to solo driving. However, as this system is not in place in China, it appears that some drivers seek out and pay for additional support once they commence on-road driving. Additionally, strategies to avoid detection and penalties for inappropriate road use were discussed, many of which involve the use of a third person. These findings indicate potential barriers to implementing effective traffic enforcement and highlight the importance of understanding culturally-specific social factors relating to driver behaviour.

Comparing the medium-term effects of exercise or dietary restriction on appetite regulation and compensatory responses

Previous studies have shown that exercise (Ex) interventions create a stronger coupling between energy intake (EI) and energy expenditure (EE) leading to increased homeostasis of the energy-balance (EB) regulatory system compared to a diet intervention where an un-coupling between EI and EE occurs. The benefits of weight loss from Ex and diet interventions greatly depend on compensatory responses. The present study investigated an 8-week medium-term Ex and diet intervention program (Ex intervention comprised of 500kcal EE five days per week over four weeks at 65-75% maximal heart rate, whereas the diet intervention comprised of a 500kcal decrease in EI five days per week over four weeks) and its effects on compensatory responses and appetite regulation among healthy individuals using a between- and within-subjects design. Effects of an acute dietary manipulation on appetite and compensatory behaviours and whether a diet and/or Ex intervention pre-disposes individuals to disturbances in EB homeostasis were tested. Energy intake at an ad libitum lunch test meal after a breakfast high- and low-energy pre-load (the high energy pre-load contained 556kcal and the low energy pre-load contained 239kcal) were measured at the Baseline (Weeks -4 to 0) and Intervention (Weeks 0 to 4) phases in 13 healthy volunteers (three males and ten females; mean age 35 years [sd + 9] and mean BMI 25 kg/m2 [sd + 3.8]) [participants in each group included Ex=7, diet=5 (one female in the diet group dropped out midway), thus, 12 participants completed the study]. At Weeks -4, 0 and 4, visual analogue scales (VAS) were used to assess hunger and satiety and liking and wanting (L&W) for nutrient and taste preferences using a computer-based system (E-Prime v1.1.4). Ad libitum test meal EI was consistently lower after the HE pre-load compared to the LE pre-load. However, this was not consistent during the diet intervention however. A pre-load x group interaction on ad libitum test meal EI revealed that during the intervention phase the Ex group showed an improved sensitivity to detect the energy content between the two pre-loads and improved compensation for the ad libitum test meal whereas the diet group’s ability to differentiate between the two pre-loads decreased and showed poorer compensation (F[1,10]=2.88, p-value not significant). This study supports previous findings of the effect Ex and diet interventions have on appetite and compensatory responses; Ex increases and diet decreases energy balance sensitivity.

Interocular symmetry in myopic anisometropia

Purpose: To investigate the interocular symmetry of optical, biometric and biomechanical characteristics between the fellow eyes of myopic anisometropes. Methods: Thirty-four young, healthy myopic anisometropic adults (≥ 1 D spherical equivalent difference between eyes) without amblyopia or strabismus were recruited. A range of biometric and optical parameters were measured in both eyes of each subject including; axial length, ocular aberrations, intraocular pressure (IOP), corneal topography and biomechanics. Ocular sighting dominance was also measured. Results: Mean absolute spherical equivalent anisometropia was 1.70 ± 0.74 D and there was a strong correlation between the degree of anisometropia and the interocular difference in axial length (r = 0.81, p < 0.001). The more and less myopic eyes displayed a high degree of interocular symmetry for the majority of biometric, biomechanical and optical parameters measured. When the level of anisometropia exceeded 1.75 D, the more myopic eye was more likely to be the dominant sighting eye than for lower levels of anisometropia (p=0.002). Subjects with greater levels of anisometropia (> 1.75 D) also showed high levels of correlation between the dominant and non-dominant eyes in their biometric, biomechanical and optical characteristics. Conclusions: Although significantly different in axial length, anisometropic eyes display a high degree of interocular symmetry for a range of anterior eye biometrics and optical parameters. For higher levels of anisometropia, the more myopic eye tends to be the dominant sighting eye.

Chronological age and age-related cognitive deficits are associated with an increase in multiple types of driving errors in late life

Objective: Older driver research has mostly focused on identifying that small proportion of older drivers who are unsafe. Little is known about how normal cognitive changes in aging affect driving in the wider population of adults who drive regularly. We evaluated the association of cognitive function and age, with driving errors. Method: A sample of 266 drivers aged 70 to 88 years were assessed on abilities that decline in normal aging (visual attention, processing speed, inhibition, reaction time, task switching) and the UFOV® which is a validated screening instrument for older drivers. Participants completed an on-road driving test. Generalized linear models were used to estimate the associations of cognitive factor with specific driving errors and number of errors in self-directed and instructor navigated conditions. Results: All errors types increased with chronological age. Reaction time was not associated with driving errors in multivariate analyses. A cognitive factor measuring Speeded Selective Attention and Switching was uniquely associated with the most errors types. The UFOV predicted blindspot errors and errors on dual carriageways. After adjusting for age, education and gender the cognitive factors explained 7% of variance in the total number of errors in the instructor navigated condition and 4% of variance in the self-navigated condition. Conclusion: We conclude that among older drivers errors increase with age and are associated with speeded selective attention particularly when that requires attending to the stimuli in the periphery of the visual field, task switching, errors inhibiting responses and visual discrimination. These abilities should be the target of cognitive training.

Multiple perspectives on engaging future engineers

Engaging future engineers is a central topic in everyday conversations on engineering education. Considerable investments have been made to make engineering more engaging, recruit and retain aspiring engineers, and to design an education to prepare future engineers. However, the impact of these efforts has been less than intended. It is imperative that the community reflects on progress and sets a more effective path for the future.

Ensuring Correctness During Process Configuration via Partner Synthesis

Variants of the same process can be encountered within one organization or across different organizations. For example, different municipalities, courts, and rental agencies all need to support highly similar processes. In fact, procurement and sales processes can be found in almost any organization. However, despite these similarities, there is also the need to allow for local variations in a controlled manner. Therefore, many academics and practitioners have advocated the use of configurable process models (sometimes referred to as reference models). A configurable process model describes a family of similar process models in a given domain. Such a model can be configured to obtain a specific process model that is subsequently used to handle individual cases, for instance, to process customer orders. Process configuration is notoriously difficult as there may be all kinds of interdependencies between configuration decisions. In fact, an incorrect configuration may lead to behavioral issues such as deadlocks and livelocks. To address this problem, we present a novel verification approach inspired by the “operating guidelines” used for partner synthesis. We view the configuration process as an external service, and compute a characterization of all such services which meet particular requirements via the notion of configuration guideline. As a result, we can characterize all feasible configurations (i. e., configurations without behavioral problems) at design time, instead of repeatedly checking each individual configuration while configuring a process model.

Safety, feasibility and effects of an individualised walking intervention for women undergoing chemotherapy for ovarian cancer : a pilot study

Background: Exercise interventions during adjuvant cancer therapy have been shown to increase functional capacity, relieve fatigue and distress and may assist rates of chemotherapy completion. These studies have been limited to breast, gastric and mixed cancer groups and it is not yet known if a similar intervention is even feasible among women with ovarian cancer. We aimed to assess safety, feasibility and potential effect of a walking intervention in women undergoing chemotherapy for ovarian cancer. Methods: Women newly diagnosed with ovarian cancer were recruited to participate in an individualised walking intervention throughout chemotherapy and were assessed pre-and post-intervention. Feasibility measures included session adherence, compliance with exercise physiologist prescribed walking targets and self-reported program acceptability. Changes in objective physical functioning (6 minute walk test), self-reported distress (Hospital Anxiety and Depression Scale), symptoms (Memorial Symptom Assessment Scale - Physical) and quality of life (Functional Assessment of Cancer Therapy - Ovarian) were calculated, and chemotherapy completion and adverse intervention effects recorded. Results: Seventeen women were enrolled (63% recruitment rate). Mean age was 60 years (SD = 8 years), 88% were diagnosed with FIGO stage III or IV disease, 14 women underwent adjuvant and three neo-adjuvant chemotherapy. On average, women adhered to > 80% of their intervention sessions and complied with 76% of their walking targets, with the majority walking four days a week at moderate intensity for 30 minutes per session. Meaningful improvements were found in physical functioning, physical symptoms, physical well-being and ovarian cancerspecific quality of life. Most women (76%) completed ≥85% of their planned chemotherapy dose. There were no withdrawals or serious adverse events and all women reported the program as being helpful. Conclusions: These positive preliminary results suggest that this walking intervention for women receiving chemotherapy for ovarian cancer is safe, feasible and acceptable and could be used in development of future work. Trial registration: ACTRN12609000252213