Multilevel determinants of breast cancer survival : association with geographic remoteness and area-level socioeconomic disadvantage

A major priority for cancer control agencies is to reduce geographical inequalities in cancer outcomes. While the poorer breast cancer survival among socioeconomically disadvantaged women is well established, few studies have looked at the independent contribution that area- and individual-level factors make to breast cancer survival. Here we examine relationships between geographic remoteness, area-level socioeconomic disadvantage and breast cancer survival after adjustment for patients’ socio- demographic characteristics and stage at diagnosis. Multilevel logistic regression and Markov chain Monte Carlo simulation were used to analyze 18 568 breast cancer cases extracted from the Queensland Cancer Registry for women aged 30 to 70 years diagnosed between 1997 and 2006 from 478 Statistical Local Areas in Queensland, Australia. Independent of individual-level factors, area-level disadvantage was associated with breast-cancer survival (p=0.032). Compared to women in the least disadvantaged quintile (Quintile 5), women diagnosed while resident in one of the remaining four quintiles had significantly worse survival (OR 1.23, 1.27, 1.30, 1.37 for Quintiles 4, 3, 2 and 1 respectively).) Geographic remoteness was not related to lower survival after multivariable adjustment. There was no evidence that the impact of area-level disadvantage varied by geographic remoteness. At the individual level, Indigenous status, blue collar occupations and advanced disease were important predictors of poorer survival. A woman’s survival after a diagnosis of breast cancer depends on the socio-economic characteristics of the area where she lives, independently of her individual-level characteristics. It is crucial that the underlying reasons for these inequalities be identified to appropriately target policies, resources and effective intervention strategies.

A new method to detect loss of heterozygosity using cohort heterozygosity comparisons

Background Loss of heterozygosity (LOH) is an important marker for one of the 'two-hits' required for tumor suppressor gene inactivation. Traditional methods for mapping LOH regions require the comparison of both tumor and patient-matched normal DNA samples. However, for many archival samples, patient-matched normal DNA is not available leading to the under-utilization of this important resource in LOH studies. Here we describe a new method for LOH analysis that relies on the genome-wide comparison of heterozygosity of single nucleotide polymorphisms (SNPs) between cohorts of cases and un-matched healthy control samples. Regions of LOH are defined by consistent decreases in heterozygosity across a genetic region in the case cohort compared to the control cohort. Methods DNA was collected from 20 Follicular Lymphoma (FL) tumor samples, 20 Diffuse Large B-cell Lymphoma (DLBCL) tumor samples, neoplastic B-cells of 10 B-cell Chronic Lymphocytic Leukemia (B-CLL) patients and Buccal cell samples matched to 4 of these B-CLL patients. The cohort heterozygosity comparison method was developed and validated using LOH derived in a small cohort of B-CLL by traditional comparisons of tumor and normal DNA samples, and compared to the only alternative method for LOH analysis without patient matched controls. LOH candidate regions were then generated for enlarged cohorts of B-CLL, FL and DLBCL samples using our cohort heterozygosity comparison method in order to evaluate potential LOH candidate regions in these non-Hodgkin's lymphoma tumor subtypes. Results Using a small cohort of B-CLL samples with patient-matched normal DNA we have validated the utility of this method and shown that it displays more accuracy and sensitivity in detecting LOH candidate regions compared to the only alternative method, the Hidden Markov Model (HMM) method. Subsequently, using B-CLL, FL and DLBCL tumor samples we have utilised cohort heterozygosity comparisons to localise LOH candidate regions in these subtypes of non-Hodgkin's lymphoma. Detected LOH regions included both previously described regions of LOH as well as novel genomic candidate regions. Conclusions We have proven the efficacy of the use of cohort heterozygosity comparisons for genome-wide mapping of LOH and shown it to be in many ways superior to the HMM method. Additionally, the use of this method to analyse SNP microarray data from 3 common forms of non-Hodgkin's lymphoma yielded interesting tumor suppressor gene candidates, including the ETV3 gene that was highlighted in both B-CLL and FL.

Geographic remoteness, area-level socioeconomic disadvantage and inequalities in colorectal cancer survival in Queensland : a multilevel analysis

Background To explore the impact of geographical remoteness and area-level socioeconomic disadvantage on colorectal cancer (CRC) survival. Methods Multilevel logistic regression and Markov chain Monte Carlo simulations were used to analyze geographical variations in five-year all-cause and CRC-specific survival across 478 regions in Queensland Australia for 22,727 CRC cases aged 20–84 years diagnosed from 1997–2007. Results Area-level disadvantage and geographic remoteness were independently associated with CRC survival. After full multivariate adjustment (both levels), patients from remote (odds Ratio [OR]: 1.24, 95%CrI: 1.07-1.42) and more disadvantaged quintiles (OR = 1.12, 1.15, 1.20, 1.23 for Quintiles 4, 3, 2 and 1 respectively) had lower CRC-specific survival than major cities and least disadvantaged areas. Similar associations were found for all-cause survival. Area disadvantage accounted for a substantial amount of the all-cause variation between areas. Conclusions We have demonstrated that the area-level inequalities in survival of colorectal cancer patients cannot be explained by the measured individual-level characteristics of the patients or their cancer and remain after adjusting for cancer stage. Further research is urgently needed to clarify the factors that underlie the survival differences, including the importance of geographical differences in clinical management of CRC.

Sex-based comparisons of myofibrillar protein synthesis after resistance exercise in the fed state

Sex-based comparisons of myofibrillar protein synthesis after resistance exercise in the fed state. J Appl Physiol 112: 1805-1813, 2012. First published March 1, 2012; doi:10.1152/japplphysiol.00170.2012.- We made sex-based comparisons of rates of myofibrillar protein synthesis (MPS) and anabolic signaling after a single bout of high-intensity resistance exercise. Eight men (20 ± 10 yr, BMI = 24.3 ± 2.4) and eight women (22 ± 1.8 yr, BMI = 23.0 ± 1.9) underwent primed constant infusions of L-[ring-13C6]phenylalanine on consecutive days with serial muscle biopsies. Biopsies were taken from the vastus lateralis at rest and 1, 3, 5, 24, 26, and 28 h after exercise. Twenty-five grams of whey protein was ingested immediately and 26 h after exercise. We also measured exercise-induced serum testosterone because it is purported to contribute to increases in myofibrillar protein synthesis (MPS) postexercise and its absence has been hypothesized to attenuate adaptative responses to resistance exercise in women. The exercise-induced area under the testosterone curve was 45-fold greater in men than women in the early (1 h) recovery period following exercise (P < 0.001). MPS was elevated similarly in men and women (2.3- and 2.7-fold, respectively) 1-5 h postexercise and after protein ingestion following 24 h recovery. Phosphorylation of mTORSer2448 was elevated to a greater extent in men than women acutely after exercise (P = 0.003), whereas increased phosphorylation of p70S6K1Thr389 was not different between sexes. Androgen receptor content was greater in men (main effect for sex, P = 0.049). Atrogin-1 mRNA abundance was decreased after 5 h recovery in both men and women (P < 0.001), and MuRF-1 expression was elevated in men after protein ingestion following 24 h recovery (P = 0.003). These results demonstrate minor sex-based differences in signaling responses and no difference in the MPS response to resistance exercise in the fed state. Interestingly, our data demonstrate that exerciseinduced increases in MPS are dissociated from postexercise testosteronemia and that stimulation of MPS occurs effectively with low systemic testosterone concentrations in women.

Enhanced geoproof : improved geographic assurance for data in the cloud

The geographic location of cloud data storage centres is an important issue for many organisations and individuals due to various regulations that require data and operations to reside in specific geographic locations. Thus, cloud users may want to be sure that their stored data have not been relocated into unknown geographic regions that may compromise the security of their stored data. Albeshri et al. (2012) combined proof of storage (POS) protocols with distance-bounding protocols to address this problem. However, their scheme involves unnecessary delay when utilising typical POS schemes due to computational overhead at the server side. The aim of this paper is to improve the basic GeoProof protocol by reducing the computation overhead at the server side. We show how this can maintain the same level of security while achieving more accurate geographic assurance.

Geographic co-distribution of influenza virus subtypes H7N9 and H5N1 in humans, China

Human infection with a novel low pathogenicity influenza A(H7N9) virus in eastern China has recently raised global public health concerns (1). The geographic sources of infection have yet to be fully clarified, and confirmed human cases from 1 province have not been linked to those from other provinces. While some studies have identified epidemiologic characteristics of subtype H7N9 cases and clinical differences between these cases and cases of highly pathogenic influenza A(H5N1), another avian influenza affecting parts of China (2–4), the spatial epidemiology of human infection with influenza subtypes H7N9 and H5N1 in China has yet to be elucidated. To test the hypothesis of co-distribution of high-risk clusters of both types of infection, we used all available data on human cases in mainland China and investigated the geospatial epidemiologic features...

The anatomy of the bill tip of kiwi and associated somatosensory regions of the brain : comparisons with shorebirds

Three families of probe-foraging birds, Scolopacidae (sandpipers and snipes), Apterygidae (kiwi), and Threskiornithidae (ibises, including spoonbills) have independently evolved long, narrow bills containing clusters of vibration-sensitive mechanoreceptors (Herbst corpuscles) within pits in the bill-tip. These ‘bill-tip organs’ allow birds to detect buried or submerged prey via substrate-borne vibrations and/or interstitial pressure gradients. Shorebirds, kiwi and ibises are only distantly related, with the phylogenetic divide between kiwi and the other two taxa being particularly deep. We compared the bill-tip structure and associated somatosensory regions in the brains of kiwi and shorebirds to understand the degree of convergence of these systems between the two taxa. For comparison, we also included data from other taxa including waterfowl (Anatidae) and parrots (Psittaculidae and Cacatuidae), non-apterygid ratites, and other probe-foraging and non probe-foraging birds including non-scolopacid shorebirds (Charadriidae, Haematopodidae, Recurvirostridae and Sternidae). We show that the bill-tip organ structure was broadly similar between the Apterygidae and Scolopacidae, however some inter-specific variation was found in the number, shape and orientation of sensory pits between the two groups. Kiwi, scolopacid shorebirds, waterfowl and parrots all shared hypertrophy or near-hypertrophy of the principal sensory trigeminal nucleus. Hypertrophy of the nucleus basorostralis, however, occurred only in waterfowl, kiwi, three of the scolopacid species examined and a species of oystercatcher (Charadriiformes: Haematopodidae). Hypertrophy of the principal sensory trigeminal nucleus in kiwi, Scolopacidae, and other tactile specialists appears to have co-evolved alongside bill-tip specializations, whereas hypertrophy of nucleus basorostralis may be influenced to a greater extent by other sensory inputs. We suggest that similarities between kiwi and scolopacid bill-tip organs and associated somatosensory brain regions are likely a result of similar ecological selective pressures, with inter-specific variations reflecting finer-scale niche differentiation.

Comparisons between youth of a parent with MS and a control group on adjustment, caregiving, attachment and family functioning

Few studies have examined the effects of parental MS on children, and those that have suffered from numerous methodological weaknesses, some of which are addressed in this study. This study investigated the effects of parental MS on children by comparing youth of a parent with MS to youth who have no family member with a serious health condition on adjustment outcomes, caregiving, attachment and family functioning. A questionnaire survey methodology was used. Measures included youth somatisation, health, pro-social behaviour, behavioural-social difficulties, caregiving, attachment and family functioning. A total of 126 youth of a parent with MS were recruited from MS Societies in Australia and, were matched one-to-one with youth who had no family member with a health condition drawn from a large community sample. Comparisons showed that youth of a parent with MS did not differ on any of the outcomes except for peer relationship problems: adolescent youth of a parent with MS reported lower peer relationship problems than control adolescents. Overall, results did not support prior research findings suggesting adverse impacts of parental MS on youth.

On Merging Business Process Management and Geographic Information Systems : Modeling and Execution of Ecological Concerns in Processes

Business Process Management describes a holistic management approach for the systematic design, modeling, execution, validation, monitoring and improvement of organizational business processes. Traditionally, most attention within this community has been given to control-flow aspects, i.e., the ordering and sequencing of business activities, oftentimes in isolation with regards to the context in which these activities occur. In this paper, we propose an approach that allows executable process models to be integrated with Geographic Information Systems. This approach enables process models to take geospatial and other geographic aspects into account in an explicit manner both during the modeling phase and the execution phase. We contribute a structured modeling methodology, based on the well-known Business Process Model and Notation standard, which is formalized by means of a mapping to executable Colored Petri nets. We illustrate the feasibility of our approach by means of a sustainability-focused case example of a process with important ecological concerns.

Process visualization techniques for multi-perspective process comparisons

Organizations executing similar business processes need to understand the differences and similarities in activities performed across work environments. Presently, research interest is directed towards the potential of visualization for the display of process models, to support users in their analysis tasks. Although recent literature in process mining and comparison provide several methods and algorithms to perform process and log comparison, few contributions explore novel visualization approaches. This paper analyses process comparison from a design perspective, providing some practical visualization techniques as anal- ysis solutions (/to support process analysis). The design of the visual comparison has been tackled through three different points of view: the general model, the projected model and the side-by-side comparison in order to support the needs of business analysts. A case study is presented showing the application of process mining and visualization techniques to patient treatment across two Australian hospitals.

Bat species comparisons based on external morphology: A test of traditional versus geometric morphometric approaches

External morphology is commonly used to identify bats as well as to investigate flight and foraging behavior, typically relying on simple length and area measures or ratios. However, geometric morphometrics is increasingly used in the biological sciences to analyse variation in shape and discriminate among species and populations. Here we compare the ability of traditional versus geometric morphometric methods in discriminating between closely related bat species – in this case European horseshoe bats (Rhinolophidae, Chiroptera) – based on morphology of the wing, body and tail. In addition to comparing morphometric methods, we used geometric morphometrics to detect interspecies differences as shape changes. Geometric morphometrics yielded improved species discrimination relative to traditional methods. The predicted shape for the variation along the between group principal components revealed that the largest differences between species lay in the extent to which the wing reaches in the direction of the head. This strong trend in interspecific shape variation is associated with size, which we interpret as an evolutionary allometry pattern.

Crash risk perception of sleepy driving and its comparisons with drink driving and speeding: Which behavior is perceived as the riskiest?

- Objective Driver sleepiness is a major crash risk factor, but may be under-recognized as a risky driving behavior. Sleepy driving is usually rated as less of a road safety issue than more well-known risky driving behaviors, such as drink driving and speeding. The objective of this study was to compare perception of crash risk of sleepy driving, drink driving, and speeding. - Methods In total, 300 Australian drivers completed a questionnaire that assessed crash risk perceptions for sleepy driving, drink driving, and speeding. Additionally, the participants perception of crash risk was assessed for five different contextual scenarios that included different levels of sleepiness (low, high), driving duration (short, long), and time of day/circadian influences (afternoon, night-time) of driving. - Results The analysis confirmed that sleepy driving was considered a risky driving behavior, but not as risky as high levels of speeding (p < .05). Yet, the risk of crashing at 4 am was considered as equally risky as low levels of speeding (10 km over the limit). The comparisons of the contextual scenarios revealed driving scenarios that would arguably be perceived as quite risky due to time of day/circadian influences were not reported as high risk. - Conclusions The results suggest a lack of awareness or appreciation of circadian rhythm functioning, particularly the descending phase of circadian rhythm that promotes increased sleepiness in the afternoon and during the early hours of the morning. Yet, the results suggested an appreciation of the danger associated with long distance driving and driver sleepiness. Further efforts are required to improve the community’s awareness of the impairing effects from sleepiness and in particular, knowledge regarding the human circadian rhythm and the increased sleep propensity during the circadian nadir.

General ranked set sampling for efficient treatment comparisons

In treatment comparison experiments, the treatment responses are often correlated with some concomitant variables which can be measured before or at the beginning of the experiments. In this article, we propose schemes for the assignment of experimental units that may greatly improve the efficiency of the comparison in such situations. The proposed schemes are based on general ranked set sampling. The relative efficiency and cost-effectiveness of the proposed schemes are studied and compared. It is found that some proposed schemes are always more efficient than the traditional simple random assignment scheme when the total cost is the same. Numerical studies show promising results using the proposed schemes.

Three new Lasiodiplodia spp. from the tropics, recognized based on DNA sequence comparisons and morphology

Botryosphaeria rhodina (anamorph Lasiodiplodia theobromae) is a common endophyte and opportunistic pathogen on more than 500 tree species in the tropics and subtropics. During routine disease surveys of plantations in Australia and Venezuela several isolates differing from L. theobromae were identified and subsequently characterized based upon morphology and ITS and EF1-a nucleotide sequences. These isolates grouped into three strongly supported clades related to but different from the known taxa, B. rhodina and L. gonubiensis, These have been described here as three new species L. venezuelensis sp. nov., L. crassispora sp. nov. and L. rubropurpurea sp. nov. The three could be distinguished easily from each other and the two described species of Lasiodiplodia, thus confirming phylogenetic separations. Furthermore all five Lasiodiplodia spp. now recognized separated from Diplodia spp. and Dothiorella spp. with 100% bootstrap support.