HABITAT : a longitudinal multilevel study of physical acitvity change in mid-aged adults

Purpose. To explore the role of the neighborhood environment in supporting walking Design. Cross sectional study of 10,286 residents of 200 neighborhoods. Participants were selected using a stratified two-stage cluster design. Data were collected by mail survey (68.5% response rate). Setting. The Brisbane City Local Government Area, Australia, 2007. Subjects. Brisbane residents aged 40 to 65 years. Measures. Environmental: street connectivity, residential density, hilliness, tree coverage, bikeways, and street lights within a one kilometer circular buffer from each resident’s home; and network distance to nearest river or coast, public transport, shop, and park. Walking: minutes in the previous week categorized as < 30 minutes, ≥ 30 < 90 minutes, ≥ 90 < 150 minutes, ≥ 150 < 300 minutes, and ≥ 300 minutes. Analysis. The association between each neighborhood characteristic and walking was examined using multilevel multinomial logistic regression and the model parameters were estimated using Markov chain Monte Carlo simulation. Results. After adjustment for individual factors, the likelihood of walking for more than 300 minutes (relative to <30 minutes) was highest in areas with the most connectivity (OR=1.93, 99% CI 1.32-2.80), the greatest residential density (OR=1.47, 99% CI 1.02-2.12), the least tree coverage (OR=1.69, 99% CI 1.13-2.51), the most bikeways (OR=1.60, 99% CI 1.16-2.21), and the most street lights (OR=1.50, 99% CI 1.07-2.11). The likelihood of walking for more than 300 minutes was also higher among those who lived closest to a river or the coast (OR=2.06, 99% CI 1.41-3.02). Conclusion. The likelihood of meeting (and exceeding) physical activity recommendations on the basis of walking was higher in neighborhoods with greater street connectivity and residential density, more street lights and bikeways, closer proximity to waterways, and less tree coverage. Interventions targeting these neighborhood characteristics may lead to improved environmental quality as well as lower rates of overweight and obesity and associated chromic disease.

Exploration and exploitation : the interplay between knowledge and continuous innovation

In rapidly changing environments, organisations require dynamic capabilities to integrate, build and reconfigure resources and competencies to achieve continuous innovation. Although tangible resources are important to promoting the firm’s ability to act, capabilities fundamentally rest in the knowledge created and accumulated by the firm through human capital, organisational routines, processes, practices and norms. The exploration for new ideas, technologies and knowledge – to one side – and – on the other one – the exploitation of existing and new knowledge is essential for continuous innovation. Firms need to decide how best to allocate their scarce resources for both activities and at the same time build dynamic capabilities to keep up with changing market conditions. This in turn, is influenced by the absorptive capacity of the firm to assimilate knowledge. This paper presents a case study that investigates the sources of knowledge in an engineering firm in Australia, and how it is organised and processed. As information pervades the firm from both internal and external sources, individuals integrate knowledge using both exploration and exploitation approaches. The findings illustrate that absorptive capacity can encourage greater leverage for exploration potential leading to radical innovation; and reconfiguring exploitable knowledge for incremental improvements. This study provides an insight for managers in quest of improving knowledge strategies and continuous innovation. It also makes significant theoretical contributions to the literature through extending the concepts of

Axial length charges during accommodation in myopes and emmetropes

Purpose: To investigate the influence of accommodation upon axial length (and a comprehensive range of ocular biometric parameters), in populations of young adult myopic and emmetropic subjects. Methods: Forty young adult subjects had ocular biometry measured utilizing a non-contact optical biometer (Lenstar LS 900) based upon the principle of optical low coherence reflectometry, under three different accommodation demands (0 D, 3 D and 6 D). Subjects were classified as emmetropes (n=19) or myopes (n=21) based upon their spherical equivalent refraction (mean emmetropic refraction -0.05 ± 0.27DS and mean myopic refraction -1.82 ± 0.84 DS). Results: Axial length changed significantly with accommodation, with a mean increase of 11.9 ± 12.3 µm and 24.1 ± 22.7 µm for the 3 D and 6 D accommodation stimuli respectively. A significant axial elongation associated with accommodation was still evident even following correction of the axial length data for potential error due to lens thickness change. The mean ‘corrected’ increase in axial length was 5.2 ± 11.2 µm, and 7.4 ± 18.9 µm for the 3 D and 6 D stimuli respectively. There was no significant difference between the myopic and emmetropic populations in terms of the magnitude of change in axial length with accommodation, regardless of whether the data were corrected or not. A number of other ocular biometric parameters, such as anterior chamber depth, lens thickness and vitreous chamber depth also exhibited significant change with accommodation. The myopic and emmetropic populations also exhibited no significant difference in the magnitude of change in these parameters with accommodation. Conclusions: The eye undergoes a significant axial elongation associated with a brief period of accommodation, and the magnitude of this change in eye length increases for larger accommodation demands, however there is no significant difference in the magnitude of eye elongation in myopic and emmetropic subjects.

4-Carbamoylpiperidinium phenylacetate hemihydrate

In the structure of the title compound, C6H13N2O+ C8H7O2- . 0.5H2O, the asymmetric unit comprises two isonipecotamide cations, two phenylacetate anions and a water molecule of solvation. The hydrogen-bonding environments for both sets of ion pairs are essentially identical with the piperidinium and amide 'ends' of each cation involved in lateral heteromolecular hydrogen-bonded cyclic N---H...O associations [graph set R2/2(11)] which incorporate a single carboxyl O-atom acceptor. These cyclic motifs enclose larger R5/5(21) cyclic systems forming sheet substructures which lie parallel to (101) and are linked across b by the single water molecule via water O---H...O(carboxyl) associations to give a two-dimensional duplex-sheet structure

Organometallic macrocyclic chemistry. 8.(1) : an unusual metallacycle derived from phosphine−alkynyl thioether coupling

The α,ω-diyne 4,7,10-trithiatrideca-2,11-diyne reacts with [RuCl2(PPh3)3] and KPF6 to form the phosphonio-substituted metallatricyclic salt [RuCl(PPh3){κ4C,S,S′,S′′-S(C≡CMe)C2H4SC2H4SC(PPh3)CMe}]PF6 arising from the activation of one alkynyl group toward nucleophilic attack by extraneous phosphine.

Comparison of Nucleotide Sequences between Northern and Southern Philippine Isolates of Rice Grassy Stunt Virus Indicates Occurrence of Natural Genetic Reassortment

Rice grassy stunt virus is a member of the genus Tenuivirus, is persistently transmitted by a brown planthopper, and has occurred in rice plants in South, Southeast, and East Asia (similar to North and South America). We determined the complete nucleotide (nt) sequences of RNAs 1 (9760 nt), 2 (4069 nt), 3 (3127 nt), 4 (2909 nt), 5 (2704 nt), and 6 (2590 nt) of a southern Philippine isolate from South Cotabato and compared them with those of a northern Philippine isolate from Laguna (Toriyama et al., 1997, 1998). The numbers of nucleotides in the terminal untranslated regions and open reading frames were identical between the two isolates except for the 5′ untranslated region of the complementary strand of RNA 4. Overall nucleotide differences between the two isolates were only 0.08% in RNA 1, 0.58% in RNA 4, and 0.26% in RNA 5, whereas they were 2.19% in RNA 2, 8.38% in RNA 3, and 3.63% in RNA 6. In the intergenic regions, the two isolates differed by 9.12% in RNA 2, 11.6% in RNA 3, and 6.86% in RNA 6 with multiple consecutive nucleotide deletion/insertions, whereas they differed by only 0.78% in RNA 4 and 0.34% in RNA 5. The nucleotide variation in the intergenic region of RNA 6 within the South Cotabato isolate was only 0.33%. These differences in accumulation of mutations among individual RNA segments indicate that there was genetic reassortment in the two geographical isolates; RNAs 1, 4, and 5 of the two isolates came from a common ancestor, whereas RNAs 2, 3, and 6 were from two different ancestors.

Content and functionality of alcohol and other drug websites : results of an online survey

Background: There is a growing trend for individuals to seek health information from online sources. Alcohol and other drug (AOD) use is a significant health problem worldwide, but access and use of AOD websites is poorly understood. ----- ----- Objective: To investigate content and functionality preferences for AOD and other health websites. Methods: An anonymous online survey examined general Internet and AOD-specific usage and search behaviors, valued features of AOD and health-related websites (general and interactive website features), indicators of website trustworthiness, valued AOD website tools or functions, and treatment modality preferences. ----- ----- Results: Surveys were obtained from 1214 drug (n = 766) and alcohol website users (n = 448) (mean age 26.2 years, range 16-70). There were no significant differences between alcohol and drug groups on demographic variables, Internet usage, indicators of website trustworthiness, or on preferences for AOD website functionality. A robust website design/navigation, open access, and validated content provision were highly valued by both groups. While attractiveness and pictures or graphics were also valued, high-cost features (videos, animations, games) were minority preferences. Almost half of respondents in both groups were unable to readily access the information they sought. Alcohol website users placed greater importance on several AOD website tools and functions than did those accessing other drug websites: online screening tools (χ²2 = 15.8, P < .001, n = 985); prevention programs (χ²2 = 27.5, P < .001, n = 981); tracking functions (χ²2 = 11.5, P = .003, n = 983); self help treatment programs (χ²2 = 8.3, P = .02, n = 984); downloadable fact sheets for friends (χ²2 = 11.6, P = .003, n = 981); or family (χ²2 = 12.7, P = .002, n = 983). The most preferred online treatment option for both the user groups was an Internet site with email therapist support. Explorations of demographic differences were also performed. While gender did not affect survey responses, younger respondents were more likely to value interactive and social networking features, whereas downloading of credible information was most highly valued by older respondents. ----- ----- Conclusions: Significant deficiencies in the provision of accessible information on AOD websites were identified, an important problem since information seeking was the most common reason for accessing these websites, and, therefore, may be a key avenue for engaging website users in behaviour change. The few differences between AOD website users suggested that both types of websites may have similar features, although alcohol website users may more readily be engaged in screening, prevention and self-help programs, tracking change, and may value fact sheets more highly. While the sociodemographic differences require replication and clarification, these differences support the notion that the design and features of AOD websites should target specific audiences to have maximal impact.

Categorisation of activities of daily living of lower limb amputees during short-term use of a portable kinetic recording system : a preliminary study

The purpose of this preliminary study was to determine the relevance of the categorization of the load regime data to assess the functional output and usage of the prosthesis of lower limb amputees. The objectives were a) to introduce a categorization of load regime, b) to present some descriptors of each activity, and c) to report the results for a case. The load applied on the osseointegrated fixation of one transfemoral amputee was recorded using a portable kinetic system for 5 hours. The periods of directional locomotion, localized locomotion, and stationary loading occurred 44%, 34%, and 22% of recording time and each accounted for 51%, 38%, and 12% of the duration of the periods of activity, respectively. The absolute maximum force during directional locomotion, localized locomotion, and stationary loading was 19%, 15%, and 8% of the body weight on the anteroposterior axis, 20%, 19%, and 12% on the mediolateral axis, and 121%, 106%, and 99% on the long axis. A total of 2,783 gait cycles were recorded. Approximately 10% more gait cycles and 50% more of the total impulse than conventional analyses were identified. The proposed categorization and apparatus have the potential to complement conventional instruments, particularly for difficult cases.

Malnutrition and clinical outcomes in elderly patients from a Singapore acute hospital

Older adults, especially those acutely ill, are vulnerable to developing malnutrition due to a range of risk factors. The high prevalence and extensive consequences of malnutrition in hospitalised older adults have been reported extensively. However, there are few well-designed longitudinal studies that report the independent relationship between malnutrition and clinical outcomes after adjustment for a wide range of covariates. Acutely ill older adults are exceptionally prone to nutritional decline during hospitalisation, but few reports have studied this change and impact on clinical outcomes. In the rapidly ageing Singapore population, all this evidence is lacking, and the characteristics associated with the risk of malnutrition are also not well-documented. Despite the evidence on malnutrition prevalence, it is often under-recognised and under-treated. It is therefore crucial that validated nutrition screening and assessment tools are used for early identification of malnutrition. Although many nutrition screening and assessment tools are available, there is no universally accepted method for defining malnutrition risk and nutritional status. Most existing tools have been validated amongst Caucasians using various approaches, but they are rarely reported in the Asian elderly and none has been validated in Singapore. Due to the multiethnicity, cultural, and language differences in Singapore older adults, the results from non-Asian validation studies may not be applicable. Therefore it is important to identify validated population and setting specific nutrition screening and assessment methods to accurately detect and diagnose malnutrition in Singapore. The aims of this study are therefore to: i) characterise hospitalised elderly in a Singapore acute hospital; ii) describe the extent and impact of admission malnutrition; iii) identify and evaluate suitable methods for nutritional screening and assessment; and iv) examine changes in nutritional status during admission and their impact on clinical outcomes. A total of 281 participants, with a mean (+SD) age of 81.3 (+7.6) years, were recruited from three geriatric wards in Tan Tock Seng Hospital over a period of eight months. They were predominantly Chinese (83%) and community-dwellers (97%). They were screened within 72 hours of admission by a single dietetic technician using four nutrition screening tools [Tan Tock Seng Hospital Nutrition Screening Tool (TTSH NST), Nutritional Risk Screening 2002 (NRS 2002), Mini Nutritional Assessment-Short Form (MNA-SF), and Short Nutritional Assessment Questionnaire (SNAQ©)] that were administered in no particular order. The total scores were not computed during the screening process so that the dietetic technician was blinded to the results of all the tools. Nutritional status was assessed by a single dietitian, who was blinded to the screening results, using four malnutrition assessment methods [Subjective Global Assessment (SGA), Mini Nutritional Assessment (MNA), body mass index (BMI), and corrected arm muscle area (CAMA)]. The SGA rating was completed prior to computation of the total MNA score to minimise bias. Participants were reassessed for weight, arm anthropometry (mid-arm circumference, triceps skinfold thickness), and SGA rating at discharge from the ward. The nutritional assessment tools and indices were validated against clinical outcomes (length of stay (LOS) >11days, discharge to higher level care, 3-month readmission, 6-month mortality, and 6-month Modified Barthel Index) using multivariate logistic regression. The covariates included age, gender, race, dementia (defined using DSM IV criteria), depression (defined using a single question “Do you often feel sad or depressed?”), severity of illness (defined using a modified version of the Severity of Illness Index), comorbidities (defined using Charlson Comorbidity Index, number of prescribed drugs and admission functional status (measured using Modified Barthel Index; MBI). The nutrition screening tools were validated against the SGA, which was found to be the most appropriate nutritional assessment tool from this study (refer section 5.6) Prevalence of malnutrition on admission was 35% (defined by SGA), and it was significantly associated with characteristics such as swallowing impairment (malnourished vs well-nourished: 20% vs 5%), poor appetite (77% vs 24%), dementia (44% vs 28%), depression (34% vs 22%), and poor functional status (MBI 48.3+29.8 vs 65.1+25.4). The SGA had the highest completion rate (100%) and was predictive of the highest number of clinical outcomes: LOS >11days (OR 2.11, 95% CI [1.17- 3.83]), 3-month readmission (OR 1.90, 95% CI [1.05-3.42]) and 6-month mortality (OR 3.04, 95% CI [1.28-7.18]), independent of a comprehensive range of covariates including functional status, disease severity and cognitive function. SGA is therefore the most appropriate nutritional assessment tool for defining malnutrition. The TTSH NST was identified as the most suitable nutritional screening tool with the best diagnostic performance against the SGA (AUC 0.865, sensitivity 84%, specificity 79%). Overall, 44% of participants experienced weight loss during hospitalisation, and 27% had weight loss >1% per week over median LOS 9 days (range 2-50). Wellnourished (45%) and malnourished (43%) participants were equally prone to experiencing decline in nutritional status (defined by weight loss >1% per week). Those with reduced nutritional status were more likely to be discharged to higher level care (adjusted OR 2.46, 95% CI [1.27-4.70]). This study is the first to characterise malnourished hospitalised older adults in Singapore. It is also one of the very few studies to (a) evaluate the association of admission malnutrition with clinical outcomes in a multivariate model; (b) determine the change in their nutritional status during admission; and (c) evaluate the validity of nutritional screening and assessment tools amongst hospitalised older adults in an Asian population. Results clearly highlight that admission malnutrition and deterioration in nutritional status are prevalent and are associated with adverse clinical outcomes in hospitalised older adults. With older adults being vulnerable to risks and consequences of malnutrition, it is important that they are systematically screened so timely and appropriate intervention can be provided. The findings highlighted in this thesis provide an evidence base for, and confirm the validity of the current nutrition screening and assessment tools used among hospitalised older adults in Singapore. As the older adults may have developed malnutrition prior to hospital admission, or experienced clinically significant weight loss of >1% per week of hospitalisation, screening of the elderly should be initiated in the community and continuous nutritional monitoring should extend beyond hospitalisation.

The association between objectively measured neighborhood features and walking in middle-aged adults

Purpose: To explore the role of the neighborhood environment in supporting walking Design: Cross sectional study of 10,286 residents of 200 neighborhoods. Participants were selected using a stratified two-stage cluster design. Data were collected by mail survey (68.5% response rate). Setting: The Brisbane City Local Government Area, Australia, 2007. Subjects: Brisbane residents aged 40 to 65 years. Measures Environmental: street connectivity, residential density, hilliness, tree coverage, bikeways, and street lights within a one kilometer circular buffer from each resident’s home; and network distance to nearest river or coast, public transport, shop, and park. Walking: minutes in the previous week categorized as < 30 minutes, ≥ 30 < 90 minutes, ≥ 90 < 150 minutes, ≥ 150 < 300 minutes, and ≥ 300 minutes. Analysis: The association between each neighborhood characteristic and walking was examined using multilevel multinomial logistic regression and the model parameters were estimated using Markov chain Monte Carlo simulation. Results: After adjustment for individual factors, the likelihood of walking for more than 300 minutes (relative to <30 minutes) was highest in areas with the most connectivity (OR=1.93, 99% CI 1.32-2.80), the greatest residential density (OR=1.47, 99% CI 1.02-2.12), the least tree coverage (OR=1.69, 99% CI 1.13-2.51), the most bikeways (OR=1.60, 99% CI 1.16-2.21), and the most street lights (OR=1.50, 99% CI 1.07-2.11). The likelihood of walking for more than 300 minutes was also higher among those who lived closest to a river or the coast (OR=2.06, 99% CI 1.41-3.02). Conclusion: The likelihood of meeting (and exceeding) physical activity recommendations on the basis of walking was higher in neighborhoods with greater street connectivity and residential density, more street lights and bikeways, closer proximity to waterways, and less tree coverage. Interventions targeting these neighborhood characteristics may lead to improved environmental quality as well as lower rates of overweight and obesity and associated chromic disease.

Some reflections about P2M : the place of the mirror

The purpose of this paper is to provide some insights about P2M, and more specifically, to develop some thoughts about Project Management seen as a Mirror, a place for reflection…, between the Mission of organisation and its actual creation of Values (with s: a source of value for people, organisations and society). This place is the realm of complexity, of interactions between multiple variables, each of them having a specific time horizon and occupying a specific place, playing a specific role. Before developing this paper I would like to borrow to my colleague and friend, Professor Ohara, the following, part of a paper going to be presented at IPMA World Congress, in New Delhi later this year in November 2005. “P2M is the Japanese version of project & program management, which is the first standard guide for education and certification developed in 2001. A specific finding of P2M is characterized by “mission driven management of projects” or a program which harness complexity of problem solving observed in the interface between technical system and business model.” (Ohara, 2005, IPMA Conference, New Delhi) “The term of “mission” is a key word in the field of corporate strategy, where it expresses raison d’être or “value of business”. It is more specifically used for expressing “the client needs” in terms of a strategic business unit. The concept of mission is deemed to be a useful tool to share essential content of value and needs in message for complex project.” (Ohara, 2005, IPMA Conference, New Delhi) “Mission is considered as a significant “metamodel representation” by several reasons. First, it represents multiple values for aspiration. The central objective of mission initiative is profiling of ideality in the future from reality, which all stakeholders are glad to accept and share. Second, it shall be within a stretch of efforts, and not beyond or outside of the realization. Though it looks like unique, it has to depict a solid foundation. The pragmatic sense of equilibrium between innovation and adaptation is required for the mission. Third, it shall imply a rough sketch for solution to critical issues for problems in reality.” (Ohara, 2005, IPMA Conference, New Delhi) “Project modeling” idea has been introduced in P2M program management. A package of three project models of “scheme”, “system” and “service” are given as a reference type program. (Ohara, 2005, IPMA Conference, New Delhi) If these quotes apply to P2M, they are fully congruent with the results of the research undertaken and the resulting meta-model & meta-method developed by the CIMAP, ESC Lille Research Centre in Project & Program Management, since the 80’s. The paper starts by questioning the common Project Management (PM) paradigm. Then discussing the concept of Project, it argues that an alternative epistemological position should be taken to capture Page 2 / 11 the very nature of the PM field. Based on this, a development about “the need of modelling to understand” is proposed grounded on two theoretical roots. This leads to the conclusion that, in order to enables this modelling, a standard approach is necessary, but should be understood under the perspective of the Theory of Convention in order to facilitate a situational and contextual application.

Postpartum diet quality in Australian women following a gestational diabetes pregnancy

BACKGROUND/OBJECTIVES: To describe the diet quality of a national sample of Australian women with a recent history of gestational diabetes mellitus (GDM) and determine factors associated with adherence to national dietary recommendations. SUBJECTS/METHODS: A postpartum lifestyle survey with 1499 Australian women diagnosed with GDM p3 years previously. Diet quality was measured using the Australian recommended food score (ARFS) and weighted by demographic and diabetes management characteristics. Multinominal logistic regression analysis was used to determine the association between diet quality and demographic characteristics, health seeking behaviours and diabetes-related risk factors. RESULTS: Mean (±s.d.) ARFS was 30.9±8.1 from a possible maximum score of 74. Subscale component scores demonstrated that the nuts/legumes, grains and fruits were the most poorly scored. Factors associated with being in the highest compared with the lowest ARFS quintile included age (odds ratio (OR) 5-year increase=1.40; 95% (confidence interval) CI:1.16–1.68), tertiary education (OR=2.19; 95% CI:1.52–3.17), speaking only English (OR=1.92; 95% CI:1.19–3.08), being sufficiently physically active (OR=2.11; 95% CI:1.46–3.05), returning for postpartum blood glucose testing (OR=1.75; 95% CI:1.23–2.50) and receiving riskreduction advice from a health professional (OR=1.80; 95% CI:1.24–2.60). CONCLUSIONS: Despite an increased risk of type 2 diabetes, women in this study had an overall poor diet quality as measured by the ARFS. Women with GDM should be targeted for interventions aimed at achieving a postpartum diet consistent with the guidelines for chronic disease prevention. Encouraging women to return for follow-up and providing risk reduction advice may be positive initial steps to improve diet quality, but additional strategies need to be identified.

The relationship between CFH and ARMS2 genotypes and neuroretinal function in persons without age-related macular degeneration

Purpose: To determine whether neuroretinal function differs in healthy persons with and without common risk gene variants for age- related macular degeneration (AMD) and no ophthalmoscopic signs of AMD, and to compare those findings in persons with manifest early AMD. Methods and Participants: Neuroretinal function was assessed with the multifocal electroretinogram (mfERG) (VERIS, Redwood City, CA,) in 32 participants (22 healthy persons with no clinical signs of AMD and 10 early AMD patients). The 22 healthy participants with no AMD were risk genotypes for either the CFH (rs380390) and/or ARMS2 (rs10490920). We used a slow flash mfERG paradigm (3 inserted frames) and a 103 hexagon stimulus array. Recordings were made with DTL electrodes; fixation and eye movements were monitored online. Trough N1 to peak P1 (N1P1) response densities and P1-implicit times (IT) were analysed in 5 concentric rings. Results: N1P1 response densities (mean ± SD) for concentric rings 1-3 were on average significantly higher in at-risk genotypes (ring 1: 17.97 nV/deg2 ± 1.9, ring 2: 11.7 nV/deg2 ±1.3, ring 3: 8.7 nV/deg2 ± 0.7) compared to those without risk (ring 1: 13.7 nV/deg2 ± 1.9, ring 2: 9.2 nV/deg2 ±0.8, ring 3: 7.3 nV/deg2 ± 1.1) and compared to persons with early AMD (ring 1: 15.3 nV/deg2 ± 4.8, ring 2: 9.1 nV/deg2 ±2.3, ring 3 nV/deg2: 7.3± 1.3) (p<0.5). The group implicit times, P1-ITs for ring 1 were on average delayed in the early AMD patients (36.4 ms ± 1.0) compared to healthy participants with (35.1 ms ± 1.1) or without risk genotypes (34.8 ms ±1.3), although these differences were not significant. Conclusion: Neuroretinal function in persons with normal fundi can be differentiated into subgroups based on their genetics. Increased neuroretinal activity in persons who carry AMD risk genotypes may be due to genetically determined subclinical inflammatory and/or histological changes in the retina. Assessment of neuroretinal function in healthy persons genetically susceptible to AMD may be a useful early biomarker before there is clinical manifestation of AMD.

A meta-analysis of pigmentary characteristics, sun sensitivity, freckling and melanocytic nevi and risk of basal cell carcinoma of the skin

Objective: To calculate pooled risk estimates of the association between pigmentary characteristics and basal cell carcinoma (BCC) of the skin. Methods: We searched three electronic databases and reviewed the reference lists of the retrieved articles until July 2012 to identify eligible epidemiologic studies. Eligible studies were those published in between 1965 and July 2012 that permitted quantitative assessment of the association between histologically-confirmed BCC and any of the following characteristics: hair colour, eye colour, skin colour, skin phototype, tanning and burning ability, and presence of freckling or melanocytic nevi. We included 29 studies from 2236 initially identified. We calculated summary odds ratios (ORs) using weighted averages of the log OR, using random effects models. Results: We found strongest associations with red hair (OR 2.02; 95% CI: 1.68, 2.44), fair skin colour (OR 2.11; 95% CI: 1.56, 2.86), and having skin that burns and never tans (OR 2.03; 95% CI: 1.73, 2.38). All other factors had weaker but positive associations with BCC, with the exception of freckling of the face in adulthood which showed no association. Conclusions: Although most studies report risk estimates that are in the same direction, there is significant heterogeneity in the size of the estimates. The associations were quite modest and remarkably similar, with ORs between about 1.5 and 2.5 for the highest risk level for each factor. Given the public health impact of BCC, this meta-analysis will make a valuable contribution to our understanding of BCC.

Two novel mutations and a previously unreported intronic polymorphism in the NOTCH3 gene

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary disease of small vessel caused by mutations in the NOTCH3 gene (NCBI Gene ID: 4854) located on chromosome 19p13.1. NOTCH3 consists of 33 exons which encode a protein of 2321 amino acids. Exons 3 and 4 were found to be mutation hotspots, containing more than 65% of all CADASIL mutations. We performed direct sequencing on an ABI 3130 Genetic Analyser to screen for mutations and polymorphisms on 300 patients who were clinically suspected to have CADASIL. First, exons 3 and 4 were screened in NOTCH3 and if there were no variations found, then extended CADASIL testing (exons 2, 11, 18 and 19) was offered to patients. Here we report two novel non-synonymous mutations identified in the NOTCH3 gene. The first mutation, located in exon 4 was found in a 49-year-old female and causes an alanine to valine amino acid change at position 202 (605C > T). The second mutation, located in exon 11, was found in a 66-year-old female and causes a cysteine to arginine amino acid change at position 579 (1735T > C). We also report a 46-year-old male with a known polymorphism Thr101Thr (rs3815188) and an unreported polymorphism NM_000435.2:c.679+60G>A observed in intron 4 of the NOTCH3 gene. Although Ala202Ala (rs1043994) is a common polymorphism in the NOTCH3 gene, our reported novel mutation (Ala202Val) causes an amino acid change at the same locus. Our other reported mutation (Cys579Arg) correlates well with other known mutations in NOTCH3, as the majority of the CADASIL-associated mutations in NOTCH3 generally occur in the EGF-like (epidermal growth factor-like) repeat domain, causing a change in the number of cysteine residues. The intronic polymorphism NM_000435.2:c.679+60G>A lies close to the intron–exon boundary and may affect the splicing mechanism in the NOTCH3 gene.