Risk factors for melanoma by anatomical site: an evaluation of aetiological heterogeneity.

BACKGROUND: Melanoma aetiology has been proposed to have two pathways, which are determined by naevi and type of sun exposure and related to the anatomical site where melanoma develops. OBJECTIVES: We examined associations with melanoma by anatomical site for a comprehensive set of risk factors including pigmentary and naevus phenotypes, ultraviolet radiation exposure and polygenic risk. METHODS: We analysed harmonized data from 2617 people with incident first invasive melanoma and 975 healthy controls recruited through two population-based case-control studies in Australia and the UK. Questionnaire data were collected by interview using a single protocol, and pathway-specific polygenic risk scores were derived from DNA samples. We estimated adjusted odds ratios using unconditional logistic regression that compared melanoma cases at each anatomical site with all controls. RESULTS: When cases were compared with control participants, there were stronger associations for many naevi vs. no naevi for melanomas on the trunk, and upper and lower limbs than on the head and neck (P-heterogeneity < 0·001). Very fair skin (vs. olive/brown skin) was more weakly related to melanoma on the trunk than to melanomas at other sites (P-heterogeneity = 0·04). There was no significant difference by anatomical site for polygenic risk. Increased weekday sun exposure was positively associated with melanoma on the head and neck but not on other sites. CONCLUSIONS: We found evidence of aetiological heterogeneity for melanoma, supporting the dual pathway hypothesis. These findings enhance understanding of risk factors for melanoma and can guide prevention and skin examination education and practices.

High variability in anatomic patterns of cutaneous photodamage: a population-based study.

BACKGROUND: Skin cancer is strongly associated with photodamaged skin, but body sites are often referred to as 'exposed' or 'unexposed' to sun without recognizing extent of site-specific variation. OBJECTIVES: To assess whole-body patterns of photodamage in an Australian population. METHODS: A random sample of adult residents of Queensland underwent imaging across 10 body sites. Photodamage was graded from images using an ordinal photonumeric scale. We used cluster analysis to identify whole-body photodamage patterns and prevalence proportion ratios (PPRs) to assess associated factors. RESULTS: Of 190 adults (median age 52; 58% males), 58% showed severe or moderate-to-severe photodamage on most body sites. A higher proportion of woman had severe photodamage on the arms (upper: P = 0.002, lower: P = 0.034). A higher proportion of men had moderate or severe photodamage on the lower back (P = 0.004). We identified four photodamage patterns: 'severe general' (n = 24, 13%), 'moderate-severe general' (n = 86, 45%), 'moderate-severe v-neck' (n = 40, 21%) and 'mild-moderate upper body' (n = 12, 6%). All participants with 'severe-general' photodamage were >50 years and more likely to have past skin cancer (PPR: 2.54, 95% CI: 1.44-4.49) than those with 'moderate-severe v-neck' photodamage. Those with 'moderate-severe general' photodamage showed similar associations and were more likely female (PPR: 1.33, 95% CI: 1.04-1.69). Past or current smoking was associated with having higher levels of photodamage, with no smokers in those with 'mild-moderate upper body' photodamage. CONCLUSIONS: Moderate-to-severe photodamage across much of the body is common in Queensland adults and associated with age, sex, past skin cancer and smoking. Assuming a universal pattern of site-specific sun exposure could lead to spurious correlations, while accurate and objective assessment of site-specific photodamage can add to understanding of the development of sun-associated skin cancers, in particular site-specific skin carcinogenesis. Additionally, degree of site-specific photodamage has the potential to assist skin cancer screening.

Development and external validation study of a melanoma risk prediction model incorporating clinically assessed naevi and solar lentigines.

BACKGROUND: Melanoma risk prediction models could be useful for matching preventive interventions to patients' risk. OBJECTIVES: To develop and validate a model for incident first-primary cutaneous melanoma using clinically assessed risk factors. METHODS: We used unconditional logistic regression with backward selection from the Australian Melanoma Family Study (461 cases and 329 controls) in which age, sex and city of recruitment were kept in each step, and we externally validated it using the Leeds Melanoma Case-Control Study (960 cases and 513 controls). Candidate predictors included clinically assessed whole-body naevi and solar lentigines, and self-assessed pigmentation phenotype, sun exposure, family history and history of keratinocyte cancer. We evaluated the predictive strength and discrimination of the model risk factors using odds per age- and sex-adjusted SD (OPERA) and the area under curve (AUC), and calibration using the Hosmer-Lemeshow test. RESULTS: The final model included the number of naevi ≥ 2 mm in diameter on the whole body, solar lentigines on the upper back (a six-level scale), hair colour at age 18 years and personal history of keratinocyte cancer. Naevi was the strongest risk factor; the OPERA was 3·51 [95% confidence interval (CI) 2·71-4·54] in the Australian study and 2·56 (95% CI 2·23-2·95) in the Leeds study. The AUC was 0·79 (95% CI 0·76-0·83) in the Australian study and 0·73 (95% CI 0·70-0·75) in the Leeds study. The Hosmer-Lemeshow test P-value was 0·30 in the Australian study and < 0·001 in the Leeds study. CONCLUSIONS: This model had good discrimination and could be used by clinicians to stratify patients by melanoma risk for the targeting of preventive interventions. What's already known about this topic? Melanoma risk prediction models may be useful in prevention by tailoring interventions to personalized risk levels. For reasons of feasibility, time and cost many melanoma prediction models use self-assessed risk factors. However, individuals tend to underestimate their naevus numbers. What does this study add? We present a melanoma risk prediction model, which includes clinically-assessed whole-body naevi and solar lentigines, and self-assessed risk factors including pigmentation phenotype and history of keratinocyte cancer. This model performs well on discrimination, the model's ability to distinguish between individuals with and without melanoma, and may assist clinicians to stratify patients by melanoma risk for targeted preventive interventions.

Associations of pigmentary and naevus phenotype with melanoma risk in two populations with comparable ancestry but contrasting levels of ambient sun exposure.

BACKGROUND: People at high risk of developing melanoma are usually identified by pigmentary and naevus phenotypes. OBJECTIVE: We examined whether associations of these phenotypes with melanoma risk differed by ambient sun exposure or participant characteristics in two population-based, case-control studies with comparable ancestry but different ambient sun exposure. METHODS: Data were analysed from 616 cases and 496 controls from the Australian Melanoma Family Study and 2012 cases and 504 controls from the Leeds (UK) case-control study. Questionnaire, interview and dermatological skin examination data were collected using the same measurement protocols. Relative risks were estimated as odds ratios using unconditional logistic regression, adjusted for potential confounders. RESULTS: Hair and skin colour were the strongest pigmentary phenotype risk factors. All associations of pigmentary phenotype with melanoma risk were similar across countries. The median number of clinically assessed naevi was approximately three times higher in Australia than Leeds, but the relative risks for melanoma associated with each additional common or dysplastic naevus were higher for Leeds than Australia, especially for naevi on the upper and lower limbs. Higher naevus counts on the head and neck were associated with a stronger relative risk for melanoma for women than men. The two countries had similar relative risks for melanoma based on self-reported naevus density categories, but personal perceptions of naevus number differed by country. There was no consistent evidence of interactions between phenotypes on risk. CONCLUSIONS: Classifying people at high risk of melanoma based on their number of naevi should ideally take into account their country of residence, type of counts (clinical or self-reported), body site on which the naevus counts are measured and sex. The presence of naevi may be a stronger indicator of a genetic predisposition in the UK than in Australia based on less opportunity for sun exposure to influence naevus development.

Effects and moderators of psychosocial interventions on quality of life, and emotional and social function in patients with cancer: An individual patient data meta-analysis of 22 RCTs.

OBJECTIVE: This individual patient data (IPD) meta-analysis aimed to evaluate the effects of psychosocial interventions (PSI) on quality of life (QoL), emotional function (EF), and social function (SF) in patients with cancer, and to study moderator effects of demographic, clinical, personal, and intervention-related characteristics. METHODS: Relevant studies were identified via literature searches in 4 databases. We pooled IPD from 22 (n = 4217) of 61 eligible randomized controlled trials. Linear mixed-effect model analyses were used to study intervention effects on the post-intervention values of QoL, EF, and SF (z-scores), adjusting for baseline values, age, and cancer type. We studied moderator effects by testing interactions with the intervention for demographic, clinical, personal, and intervention-related characteristics, and conducted subsequent stratified analyses for significant moderator variables. RESULTS: PSI significantly improved QoL (ß = 0.14,95%CI = 0.06;0.21), EF (ß = 0.13,95%CI = 0.05;0.20), and SF (ß = 0.10,95%CI = 0.03;0.18). Significant differences in effects of different types of PSI were found, with largest effects of psychotherapy. The effects of coping skills training were moderated by age, treatment type, and targeted interventions. Effects of psychotherapy on EF may be moderated by cancer type, but these analyses were based on 2 randomized controlled trials with small sample sizes of some cancer types. CONCLUSIONS: PSI significantly improved QoL, EF, and SF, with small overall effects. However, the effects differed by several demographic, clinical, personal, and intervention-related characteristics. Our study highlights the beneficial effects of coping skills training in patients treated with chemotherapy, the importance of targeted interventions, and the need of developing interventions tailored to the specific needs of elderly patients.

Variations in outcomes for Indigenous women with breast cancer in Australia: A systematic review.

This systematic review examines variations in outcomes along the breast cancer continuum for Australian women by Indigenous status. Multiple databases were systematically searched for peer-reviewed articles published from 1 January 1990 to 1 March 2015 focussing on adult female breast cancer patients in Australia and assessing survival, patient and tumour characteristics, diagnosis and treatment by Indigenous status. Sixteen quantitative studies were included with 12 rated high, 3 moderate and 1 as low quality. No eligible studies on referral, treatment choices, completion or follow-up were retrieved. Indigenous women had poorer survival most likely reflecting geographical isolation, advanced disease, patterns of care, comorbidities and disadvantage. They were also more likely to be diagnosed when younger, have advanced disease or comorbidities, reside in disadvantaged or remote areas, and less likely to undergo mammographic screening or surgery. Despite wide heterogeneity across studies, an overall pattern of poorer survival for Indigenous women and variations along the breast cancer continuum of care was evident. The predominance of state-specific studies and small numbers of included Indigenous women made forming a national perspective difficult. The review highlighted the need to improve Indigenous identification in cancer registries and administrative databases and identified key gaps notably the lack of qualitative studies in current literature.

A systematic review of inequalities in psychosocial outcomes for women with breast cancer according to residential location and Indigenous status in Australia.

BACKGROUND: The aim of this systematic review was to examine variations in psychosocial outcomes by residential location and Indigenous status in women diagnosed with breast cancer (BC) in Australia. METHODS: Systematic searches were undertaken using multiple databases covering articles between 1 January 1990 and 1 March 2015 focusing on adult women with BC in an Australian setting and measuring quality of life (QOL), psychological distress or psychosocial support. RESULTS: Thirteen quantitative and three qualitative articles were included. Two quantitative and one qualitative article were rated high quality, seven moderate and the remaining were low quality. No studies examining inequalities by Indigenous status were identified. Non-metropolitan women were more likely to record lower QOL relating to breast cancer-specific concerns and reported a lack of information and resources specific to their needs. Continuity of support, ongoing care and access to specialist and allied health professionals were major concerns for non-metropolitan women. Non-metropolitan women identified unmet needs in relation to travel, fear of cancer recurrence and lack of psychosocial support. CONCLUSIONS: Overall, there was a lack of evidence relating to variations in psychosocial outcomes for women with BC according to residential status or Indigenous status. While the review identified some specific concerns for non-metropolitan women with BC, it was limited by the lack of good quality studies using standardised measures. Copyright © 2016 John Wiley & Sons, Ltd.

Highly efficient infrared optical nonlinearity of a wide-bandgap chalcogenide Li(2)CdGeS(4).

A quaternary chalcogenide Li(2)CdGeS(4) is an excellent candidate for a nonlinear optical (NLO) material exhibiting wide transparency spanning from its fundamental band edge (3.15 eV) to the terahertz regime (23.5 µm). Strong optical nonlinearity of Li(2)CdGeS(4) has been investigated over a wide spectral range (λ=1.064-3.3 µm) based on second- and third-harmonic generation. The compound has a high damage threshold at λ=1.064 µm because of saturable three-photon absorption, and is phase-matchable for λ>1.5 µm with χ(2) ≃50 pm/V. It also exhibits strong third-order nonlinearity of χ(3) ≃10(5) pm(2)/V(2). Li(2)CdGeS(4) is promising for high-power NLO applications in the broad infrared spectrum.

Clinical presentation, management, and survival in dogs with persistent atrial standstill in the United Kingdom.

OBJECTIVES: To investigate the clinical and echocardiographic presentation of dogs with persistent atrial standstill (PAS), identify variables measured at first presentation that could predict their survival, and document the progression of the disease after pacing. MATERIALS AND METHODS: Retrospective study of medical records of dogs diagnosed with PAS at three referral hospitals of the United Kingdom over seven years. RESULTS: Twenty-six dogs were diagnosed with PAS during the study period. Median age of the population was three years (range: seven months-12.5 years). The most common clinical sign was syncope (14/26). Twenty-four dogs received artificial pacemakers (PM). Major complications after PM implantation were observed in four dogs (four/24). Serial echocardiographic examinations showed that cardiac dimensions of PAS dogs with left atrial or left ventricular dilation at first presentation did not return to reference range after pacing. Further dilation of the cardiac chambers, recurrence of congestive heart failure (CHF), or development of new episodes of CHF were documented in seven, four, and 10 PAS dogs, respectively, despite pacing. Median survival time for cardiac-related deaths after PM implantation was 1512 days (18-3207). Neither CHF nor echocardiographic variables at presentation predicted survival after PM implantation in PAS dogs. CONCLUSIONS: Persistent atrial standstill (PAS) is an uncommon bradyarrhythmia, occurring in young adult dogs. Affected dogs were often presented with syncope. Whilst syncope resolved, cardiac remodeling persisted after PM implantation. Long-term survival was favorable after PM implantation and was not predicted by congestive status or cardiac chamber size at first presentation.

A robust method for approximate visual robot localization in feature-sparse sewer pipes.

Buried sewer pipe networks present many challenges for robot localization systems, which require non-standard solutions due to the unique nature of these environments: they cannot receive signals from global positioning systems (GPS) and can also lack visual features necessary for standard visual odometry algorithms. In this paper, we exploit the fact that pipe joints are equally spaced and develop a robot localization method based on pipe joint detection that operates in one degree-of-freedom along the pipe length. Pipe joints are detected in visual images from an on-board forward facing (electro-optical) camera using a bag-of-keypoints visual categorization algorithm, which is trained offline by unsupervised learning from images of sewer pipe joints. We augment the pipe joint detection algorithm with drift correction using vision-based manhole recognition. We evaluated the approach using real-world data recorded from three sewer pipes (of lengths 30, 50 and 90 m) and benchmarked against a standard method for visual odometry (ORB-SLAM3), which demonstrated that our proposed method operates more robustly and accurately in these feature-sparse pipes: ORB-SLAM3 completely failed on one tested pipe due to a lack of visual features and gave a mean absolute error in localization of approximately 12%-20% on the other pipes (and regularly lost track of features, having to re-initialize multiple times), whilst our method worked successfully on all tested pipes and gave a mean absolute error in localization of approximately 2%-4%. In summary, our results highlight an important trade-off between modern visual odometry algorithms that have potentially high precision and estimate full six degree-of-freedom pose but are potentially fragile in feature sparse pipes, versus simpler, approximate localization methods that operate in one degree-of-freedom along the pipe length that are more robust and can lead to substantial improvements in accuracy.

5†Tear proteins in premature babies at risk of retinopathy of prematurity.

This feasibility study aimed to investigate the feasibility of collecting and analysing tear proteins from preterm infants at risk of retinopathy of prematurity (ROP). Additionally, we sought to identify any tear proteins which might be implicated in the pathophysiology of ROP.Eligible infants were those undergoing ROP screening without other ocular pathology. Tear samples were obtained by Schirmer's test strips coincident with routine ROP screening. Mass spectrometry was used for proteomic analysis. All participants' parents gave written, informed consent.Samples were collected from 12 infants, including two sets of twins. Gestation ranged from 25+6 to 31+1 weeks. Median postnatal age at sampling was 30.5 days (range 19 to 66). One infant developed self-limiting ROP. An adequate sample for protein analysis was obtained from each infant. 701 proteins were identified; 261 proteins identified in the majority of tear samples, including several common tear proteins, were used for analyses.Increased risk of ROP as determined by G-ROP prediction criteria was associated with an increase in lactate dehydrogenase B (LDH-B) chain protein in tears. Older, more mature infants demonstrated increased concentration of immunoglobulin complexes within their tear samples and two sets of twins in the cohort showed exceptionally similar proteomes, supporting validity of the analysis.Tear sampling by Schirmer test strips and subsequent proteomic analysis in preterm infants is feasible. A larger study is required to investigate the potential use of tear proteomics in early identification of ROP.

[Compartment syndrome: an atypical presentation as a cause of Henoch-Schönlein purpura]. / Síndrome compartimental: una presentación atípica como causa de la púrpura de Henoch-Schönlein.

INTRODUCTION: there are few case reports available that describe compartment syndrome as a complication of Henoch-Schönlein purpura. CASE REPORT: we report the case of a 17-year-old patient with bilateral compartment syndrome of the foot as an atypical presentation of Henoch-Schönlein purpura. A case like this has not been reported before. CONCLUSION: although the patient had an extremely rare clinical presentation, the viability and functionality of the limbs was preserved even after six months of follow-up thanks to an early diagnosis and surgical treatment.

INTRODUCCIÓN: en la literatura existen escasos reportes de caso del desarrollo de síndrome compartimental como una potencial complicación de la púrpura de Henoch-Schönlein. CASO CLÍNICO: se presenta el caso clínico de una paciente de 17 años con un cuadro de síndrome compartimental bilateral en pies como presentación atípica de la púrpura de Henoch-Schönlein, nunca antes descrita en la literatura. CONCLUSIÓN: con una rápida sospecha diagnóstica y un tratamiento quirúrgico con fasciotomías, se consiguió preservar la viabilidad de las extremidades y su funcionalidad a los seis meses de seguimiento, a pesar de tratarse de una presentación sumamente atípica de la patología en cuestión.

Geographic remoteness and risk of advanced colorectal cancer at diagnosis in Queensland: a multilevel study.

BACKGROUND: We examine the relationships between geographic remoteness, area disadvantage and risk of advanced colorectal cancer. METHODS: Multilevel models were used to assess the area- and individual-level contributions to the risk of advanced disease among people aged 20-79 years diagnosed with colorectal cancer in Queensland, Australia between 1997 and 2007 (n=18,561). RESULTS: Multilevel analysis showed that colorectal cancer patients living in inner regional (OR=1.09, 1.01-1.19) and outer regional (OR=1.11, 1.01-1.22) areas were significantly more likely to be diagnosed with advanced cancer than those in major cities (P=0.045) after adjusting for individual-level variables. The best-fitting final model did not include area disadvantage. Stratified analysis suggested this remoteness effect was limited to people diagnosed with colon cancer (P=0.048) and not significant for rectal cancer patients (P=0.873). CONCLUSION: Given the relationship between stage and survival outcomes, it is imperative that the reasons for these rurality inequities in advanced disease be identified and addressed.

Body-site distribution of skin cancer, pre-malignant and common benign pigmented lesions excised in general practice.

BACKGROUND: Concern about skin cancer is a common reason for people from predominantly fair-skinned populations to present to primary care doctors. OBJECTIVES: To examine the frequency and body-site distribution of malignant, pre-malignant and benign pigmented skin lesions excised in primary care. METHODS: This prospective study conducted in Queensland, Australia, included 154 primary care doctors. For all excised or biopsied lesions, doctors recorded the patient's age and sex, body site, level of patient pressure to excise, and the clinical diagnosis. Histological confirmation was obtained through pathology laboratories. RESULTS: Of 9650 skin lesions, 57·7% were excised in males and 75·0% excised in patients ≥ 50 years. The most common diagnoses were basal cell carcinoma (BCC) (35·1%) and squamous cell carcinoma (SCC) (19·7%). Compared with the whole body, the highest densities for SCC, BCC and actinic keratoses were observed on chronically sun-exposed areas of the body including the face in males and females, the scalp and ears in males, and the hands in females. The density of BCC was also high on intermittently or rarely exposed body sites. Females, younger patients and patients with melanocytic naevi were significantly more likely to exert moderate/high levels of pressure on the doctor to excise. CONCLUSIONS: More than half the excised lesions were skin cancer, which mostly occurred on the more chronically sun-exposed areas of the body. Information on the type and body-site distribution of skin lesions can aid in the diagnosis and planned management of skin cancer and other skin lesions commonly presented in primary care.

A Modular Digital Twinning Framework for Safety Assurance of Collaborative Robotics.

Digital twins offer a unique opportunity to design, test, deploy, monitor, and control real-world robotic processes. In this paper we present a novel, modular digital twinning framework developed for the investigation of safety within collaborative robotic manufacturing processes. The modular architecture supports scalable representations of user-defined cyber-physical environments, and tools for safety analysis and control. This versatile research tool facilitates the creation of mixed environments of Digital Models, Digital Shadows, and Digital Twins, whilst standardising communication and physical system representation across different hardware platforms. The framework is demonstrated as applied to an industrial case-study focused on the safety assurance of a collaborative robotic manufacturing process. We describe the creation of a digital twin scenario, consisting of individual digital twins of entities in the manufacturing case study, and the application of a synthesised safety controller from our wider work. We show how the framework is able to provide adequate evidence to virtually assess safety claims made against the safety controller using a supporting validation module and testing strategy. The implementation, evidence and safety investigation is presented and discussed, raising exciting possibilities for the use of digital twins in robotic safety assurance.

Trends in incidence of childhood cancer in Australia, 1983-2006.

BACKGROUND: There are few population-based childhood cancer registries in the world containing stage and treatment data. METHODS: Data from the population-based Australian Paediatric Cancer Registry were used to calculate incidence rates during the most recent 10-year period (1997-2006) and trends in incidence between 1983 and 2006 for the 12 major diagnostic groups of the International Classification of Childhood Cancer. RESULTS: In the period 1997-2006, there were 6184 childhood cancer (at 0-14 years) cases in Australia (157 cases per million children). The commonest cancers were leukaemia (34%), that of the central nervous system (23%) and lymphomas (10%), with incidence the highest at 0-4 years (223 cases per million). Trend analyses showed that incidence among boys for all cancers combined increased by 1.6% per year from 1983 to 1994 but have remained stable since. Incidence rates for girls consistently increased by 0.9% per year. Since 1983, there have been significant increases among boys and girls for leukaemia, and hepatic and germ-cell tumours, whereas for boys, incidence of neuroblastomas and malignant epithelial tumours has recently decreased. For all cancers and for both sexes combined, there was a consistent increase (+0.7% per year, 1983-2006) at age 0-4 years, a slight non-significant increase at 5-9 years, and at 10-14 years, an initial increase (2.7% per year, 1983-1996) followed by a slight non-significant decrease. CONCLUSION: Although there is some evidence of a recent plateau in cancer incidence rates in Australia for boys and older children, interpretation is difficult without a better understanding of what underlies the changes reported.