Compression use during an exercise intervention and associated changes in breast cancer-related lymphoedema

Aim This study assessed the association between compression use and changes in lymphoedema observed in women with breast cancer-related lymphoedema who completed a 12 week exercise intervention. Methods This work uses data collected from a 12 week exercise trial, whereby women were randomly allocated into either aerobic-based only (n=21) or resistance-based only (n=20) exercise. Compression use during the trial was at the participant’s discretion. Differences in lymphoedema (measured by L-Dex score and inter-limb circumference difference [%]) and associated symptoms between those who wore, and did not wear compression during the 12 week intervention were assessed. We also explored participants’ reasons surrounding compression during exercise. Results No significant interaction effect between time and compression use for lymphoedema was observed. There was no difference between groups over time in the number or severity of lymphoedema symptoms. Irrespective of compression use, there were trends for reductions in the proportion of women reporting severe symptoms, but lymphoedema status did not change. Individual reasons for the use of compression, or lack thereof, varied markedly. Conclusion Our findings demonstrated an absence of a positive or negative effect from compression use during exercise on lymphoedema. Current and previous findings suggest the clinical recommendation that garments must be worn during exercise is questionable, and its application requires an individualised approach.

Genome-wide linkage analysis of multiple measures of neuroticism of 2 large cohorts from Australia and the Netherlands

CONTEXT People meeting diagnostic criteria for anxiety or depressive disorders tend to score high on the personality scale of neuroticism. Studying this personality dimension can give insights into the etiology of these important psychiatric disorders. OBJECTIVES To undertake a comprehensive genome-wide linkage study of neuroticism using large study samples that have been measured multiple times and to compare the results between countries for replication and across time within countries for consistency. DESIGN Genome-wide linkage scan. SETTING Twin individuals and their family members from Australia and the Netherlands. PARTICIPANTS Nineteen thousand six hundred thirty-five sibling pairs completed self-report questionnaires for neuroticism up to 5 times over a period of up to 22 years. Five thousand sixty-nine sibling pairs were genotyped with microsatellite markers. METHODS Nonparametric linkage analyses were conducted in MERLIN-REGRESS for the mean neuroticism scores averaged across time. Additional analyses were conducted for the time-specific measures of neuroticism from each country to investigate consistency of linkage results. RESULTS Three chromosomal regions exceeded empirically derived thresholds for suggestive linkage using mean neuroticism scores: 10p 5 Kosambi cM (cM) (Dutch study sample), 14q 103 cM (Dutch study sample), and 18q 117 cM (combined Australian and Dutch study sample), but only 14q retained significance after correction for multiple testing. These regions all showed evidence for linkage in individual time-specific measures of neuroticism and 1 (18q) showed some evidence for replication between countries. Linkage intervals for these regions all overlap with regions identified in other studies of neuroticism or related traits and/or in studies of anxiety in mice. CONCLUSIONS Our results demonstrate the value of the availability of multiple measures over time and add to the optimism reported in recent reviews for replication of linkage regions for neuroticism. These regions are likely to harbor causal variants for neuroticism and its related psychiatric disorders and can inform prioritization of results from genome-wide association studies.

Harvest strategy evaluations and co-management for the Moreton Bay Trawl Fishery

Non-Technical Summary Seafood CRC Project 2009/774. Harvest strategy evaluations and co-management for the Moreton Bay Trawl Fishery Principal Investigator: Dr Tony Courtney, Principal Fisheries Biologist Fisheries and Aquaculture, Agri-Science Queensland Department of Agriculture, Fisheries and Forestry Level B1, Ecosciences Precinct, Joe Baker St, Dutton Park, Queensland 4102 Email: tony.courtney@daff.qld.gov.au Project objectives: 1. Review the literature and data (i.e., economic, biological and logbook) relevant to the Moreton Bay trawl fishery. 2. Identify and prioritise management objectives for the Moreton Bay trawl fishery, as identified by the trawl fishers. 3. Undertake an economic analysis of Moreton Bay trawl fishery. 4. Quantify long-term changes to fishing power for the Moreton Bay trawl fishery. 5. Assess priority harvest strategies identified in 2 (above). Present results to, and discuss results with, Moreton Bay Seafood Industry Association (MBSIA), fishers and Fisheries Queensland. Note: Additional, specific objectives for 2 (above) were developed by fishers and the MBSIA after commencement of the project. These are presented in detail in section 5 (below). The project was an initiative of the MBSIA, primarily in response to falling profitability in the Moreton Bay prawn trawl fishery. The analyses were undertaken by a consortium of DAFF, CSIRO and University of Queensland researchers. This report adopted the Australian Standard Fish Names (http://www.fishnames.com.au/). Trends in catch and effort The Moreton Bay otter trawl fishery is a multispecies fishery, with the majority of the catch composed of Greasyback Prawns (Metapenaeus bennettae), Brown Tiger Prawns (Penaeus esculentus), Eastern King Prawns (Melicertus plebejus), squid (Uroteuthis spp., Sepioteuthis spp.), Banana Prawns (Fenneropenaeus merguiensis), Endeavour Prawns (Metapenaeus ensis, Metapenaeus endeavouri) and Moreton Bay bugs (Thenus parindicus). Other commercially important byproduct includes blue swimmer crabs (Portunus armatus), three-spot crabs (Portunus sanguinolentus), cuttlefish (Sepia spp.) and mantis shrimp (Oratosquilla spp.). Logbook catch and effort data show that total annual reported catch of prawns from the Moreton Bay otter trawl fishery has declined to 315 t in 2008 from a maximum of 901 t in 1990. The number of active licensed vessels participating in the fishery has also declined from 207 in 1991 to 57 in 2010. Similarly, fishing effort has fallen from a peak of 13,312 boat-days in 1999 to 3817 boat-days in 2008 – a 71% reduction. The declines in catch and effort are largely attributed to reduced profitability in the fishery due to increased operational costs and depressed prawn prices. The low prawn prices appear to be attributed to Australian aquacultured prawns and imported aquacultured vannamei prawns, displacing the markets for trawl-caught prawns, especially small species such as Greasyback Prawns which traditionally dominated landings in Moreton Bay. In recent years, the relatively high Australian dollar has resulted in reduced exports of Australian wild-caught prawns. This has increased supply on the domestic market which has also suppressed price increases. Since 2002, Brown Tiger Prawns have dominated annual reported landings in the Moreton Bay fishery. While total catch and effort in the bay have declined to historically low levels, the annual catch and catch rates of Brown Tiger Prawns have been at record highs in recent years. This appears to be at least partially attributed to the tiger prawn stock having recovered from excessive effort in previous decades. The total annual value of the Moreton Bay trawl fishery catch, including byproduct, is about $5 million, of which Brown Tiger Prawns account for about $2 million. Eastern King Prawns make up about 10% of the catch and are mainly caught in the bay from October to December as they migrate to offshore waters outside the bay where they contribute to a large mono-specific trawl fishery. Some of the Eastern King Prawns harvested in Moreton Bay may be growth overfished (i.e., caught below the size required to maximise yield or value), although the optimum size-at-capture was not determined in this study. Banana Prawns typically make up about 5% of the catch, but can exceed 20%, particularly following heavy rainfall. Economic analysis of the fishery From the economic survey, cash profits were, on average, positive for both fleet segments in both years of the survey. However, after the opportunity cost of capital and depreciation were taken into account, the residual owner-operator income was relatively low, and substantially lower than the average share of revenue paid to employed skippers. Consequently, owner-operators were earning less than their opportunity cost of their labour, suggesting that the fleets were economically unviable in the longer term. The M2 licensed fleet were, on average, earning similar boat cash profits as the T1/M1 fleet, although after the higher capital costs were accounted for the T1/M1 boats were earning substantially lower returns to owner-operator labour. The mean technical efficiency for the fleet as a whole was estimated to be 0.67. That is, on average, the boats were only catching 67 per cent of what was possible given their level of inputs (hours fished and hull units). Almost one-quarter of observations had efficiency scores above 0.8, suggesting a substantial proportion of the fleet are relatively efficient, but some are also relatively inefficient. Both fleets had similar efficiency distributions, with median technical efficiency score of 0.71 and 0.67 for the M2 and T1/M1 boats respectively. These scores are reasonably consistent with other studies of prawn trawl fleets in Australia, although higher average efficiency scores were found in the NSW prawn trawl fleet. From the inefficiency model, several factors were found to significantly influence vessel efficiency. These included the number of years of experience as skipper, the number of generations that the skipper’s family had been fishing and the number of years schooling. Skippers with more schooling were significantly more efficient than skippers with lower levels of schooling, consistent with other studies. Skippers who had been fishing longer were, in fact, less efficient than newer skippers. However, this was mitigated in the case of skippers whose family had been involved in fishing for several generations, consistent with other studies and suggesting that skill was passed through by families over successive generations. Both the linear and log-linear regression models of total fishing effort against the marginal profit per hour performed reasonably well, explaining between 70 and 84 per cent of the variation in fishing effort. As the models had different dependent variables (one logged and the other not logged) this is not a good basis for model choice. A better comparator is the square root of the mean square error (SMSE) expressed as a percentage of the mean total effort. On this criterion, both models performed very similarly. The linear model suggests that each additional dollar of average profits per hour in the fishery increases total effort by around 26 hours each month. From the log linear model, each percentage increase in profits per hour increases total fishing effort by 0.13 per cent. Both models indicate that economic performance is a key driver of fishing effort in the fishery. The effect of removing the boat-replacement policy is to increase individual vessel profitability, catch and effort, but the overall increase in catch is less than that removed by the boats that must exit the fishery. That is, the smaller fleet (in terms of boat numbers) is more profitable but the overall catch is not expected to be greater than before. This assumes, however, that active boats are removed, and that these were also taking an average level of catch. If inactive boats are removed, then catch of the remaining group as a whole could increase by between 14 and 17 per cent depending on the degree to which costs are reduced with the new boats. This is still substantially lower than historical levels of catch by the fleet. Fishing power analyses An analysis of logbook data from 1988 to 2010, and survey information on fishing gear, was performed to estimate the long-term variation in the fleet’s ability to catch prawns (known as fishing power) and to derive abundance estimates of the three most commercially important prawn species (i.e., Brown Tiger, Eastern King and Greasyback Prawns). Generalised linear models were used to explain the variation in catch as a function of effort (i.e., hours fished per day), vessel and gear characteristics, onboard technologies, population abundance and environmental factors. This analysis estimated that fishing power associated with Brown Tiger and Eastern King Prawns increased over the past 20 years by 10–30% and declined by approximately 10% for greasybacks. The density of tiger prawns was estimated to have almost tripled from around 0.5 kg per hectare in 1988 to 1.5 kg/ha in 2010. The density of Eastern King Prawns was estimated to have fluctuated between 1 and 2 kg per hectare over this time period, without any noticeable overall trend, while Greasyback Prawn densities were estimated to have fluctuated between 2 and 6 kg per hectare, also without any distinctive trend. A model of tiger prawn catches was developed to evaluate the impact of fishing on prawn survival rates in Moreton Bay. The model was fitted to logbook data using the maximum-likelihood method to provide estimates of the natural mortality rate (0.038 and 0.062 per week) and catchability (which can be defined as the proportion of the fished population that is removed by one unit of effort, in this case, estimated to be 2.5 ± 0.4 E-04 per boat-day). This approach provided a method for industry and scientists to develop together a realistic model of the dynamics of the fishery. Several aspects need to be developed further to make this model acceptable to industry. Firstly, there is considerable evidence to suggest that temperature influences prawn catchability. This ecological effect should be incorporated before developing meaningful harvest strategies. Secondly, total effort has to be allocated between each species. Such allocation of effort could be included in the model by estimating several catchability coefficients. Nevertheless, the work presented in this report is a stepping stone towards estimating essential fishery parameters and developing representative mathematical models required to evaluate harvest strategies. Developing a method that allowed an effective discussion between industry, management and scientists took longer than anticipated. As a result, harvest strategy evaluations were preliminary and only included the most valuable species in the fishery, Brown Tiger Prawns. Additional analyses and data collection, including information on catch composition from field sampling, migration rates and recruitment, would improve the modelling. Harvest strategy evaluations As the harvest strategy evaluations are preliminary, the following results should not be adopted for management purposes until more thorough evaluations are performed. The effects, of closing the fishery for one calendar month, on the annual catch and value of Brown Tiger Prawns were investigated. Each of the 12 months (i.e., January to December) was evaluated. The results were compared against historical records to determine the magnitude of gain or loss associated with the closure. Uncertainty regarding the trawl selectivity was addressed using two selectivity curves, one with a weight at 50% selection (S50%) of 7 g, based on research data, and a second with S50% of 14 g, put forward by industry. In both cases, it was concluded that any monthly closure after February would not be beneficial to the industry. The magnitude of the benefit of closing the fishery in either January or February was sensitive to which mesh selectivity curve that was assumed, with greater benefit achieved when the smaller selectivity curve (i.e., S50% = 7 g) was assumed. Using the smaller selectivity (S50% = 7 g), the expected increase in catch value was 10–20% which equates to $200,000 to $400,000 annually, while the larger selectivity curve (S50% = 14 g) suggested catch value would be improved by 5–10%, or $100,000 to $200,000. The harvest strategy evaluations showed that greater benefits, in the order of 30–60% increases in the tiger annual catch value, could have been obtained by closing the fishery early in the year when annual effort levels were high (i.e., > 10,000 boat-days). In recent years, as effort levels have declined (i.e., ~4000 boat-days annually), expected benefits from such closures are more modest. In essence, temporal closures offer greater benefit when fishing mortality rates are high. A spatial analysis of Brown Tiger Prawn catch and effort was also undertaken to obtain a better understanding of the prawn population dynamics. This indicated that, to improve profitability of the fishery, fishers could consider closing the fishery in the period from June to October, which is already a period of low profitability. This would protect the Brown Tiger Prawn spawning stock, increase catch rates of all species in the lucrative pre-Christmas period (November–December), and provide fishers with time to do vessel maintenance, arrange markets for the next season’s harvest, and, if they wish, work at other jobs. The analysis found that the instantaneous rate of total mortality (Z) for the March–June period did not vary significantly over the last two decades. As the Brown Tiger Prawn population in Moreton Bay has clearly increased over this time period, an interesting conclusion is that the instantaneous rate of natural mortality (M) must have increased, suggesting that tiger prawn natural mortality may be density-dependent at this time of year. Mortality rates of tiger prawns for June–October were found to have decreased over the last two decades, which has probably had a positive effect on spawning stocks in the October–November spawning period. Abiotic effects on the prawns The influence of air temperature, rainfall, freshwater flow, the southern oscillation index (SOI) and lunar phase on the catch rates of the four main prawn species were investigated. The analyses were based on over 200,000 daily logbook catch records over 23 years (i.e., 1988–2010). Freshwater flow was more influential than rainfall and SOI, and of the various sources of flow, the Brisbane River has the greatest volume and influence on Moreton Bay prawn catches. A number of time-lags were also considered. Flow in the preceding month prior to catch (i.e., 30 days prior, Logflow1_30) and two months prior (31–60 days prior, Logflow31_60) had strong positive effects on Banana Prawn catch rates. Average air temperature in the preceding 4-6 months (Temp121_180) also had a large positive effect on Banana Prawn catch rates. Flow in the month immediately preceding catch (Logflow1_30) had a strong positive influence on Greasyback Prawn catch rates. Air temperature in the preceding two months prior to catch (Temp1_60) had a large positive effect on Brown Tiger Prawn catch rates. No obvious or marked effects were detected for Eastern King Prawns, although interestingly, catch rates declined with increasing air temperature 4–6 months prior to catch. As most Eastern King Prawn catches in Moreton Bay occur in October to December, the results suggest catch rates decline with increasing winter temperatures. In most cases, the prawn catch rates declined with the waxing lunar phase (high luminance/full moon), and increased with the waning moon (low luminance/new moon). The SOI explains little additional variation in prawn catch rates (~ <2%), although its influence was higher for Banana Prawns. Extrapolating findings of the analyses to long-term climate change effects should be interpreted with caution. That said, the results are consistent with likely increases in abundance in the region for the two tropical species, Banana Prawns and Brown Tiger Prawns, as coastal temperatures rise. Conversely, declines in abundance could be expected for the two temperate species, Greasyback and Eastern King Prawns. Corporate management structures An examination of alternative governance systems was requested by the industry at one of the early meetings, particularly systems that may give them greater autonomy in decision making as well as help improve the marketing of their product. Consequently, a review of alternative management systems was undertaken, with a particular focus on the potential for self-management of small fisheries (small in terms of number of participants) and corporate management. The review looks at systems that have been implemented or proposed for other small fisheries internationally, with a particular focus on self-management as well as the potential benefits and challenges for corporate management. This review also highlighted particular opportunities for the Moreton Bay prawn fishery. Corporate management differs from other co-management and even self-management arrangements in that ‘ownership’ of the fishery is devolved to a company in which fishers and government are shareholders. The company manages the fishery as well as coordinates marketing to ensure that the best prices are received and that the catch taken meets the demands of the market. Coordinated harvesting will also result in increased profits, which are returned to fishers in the form of dividends. Corporate management offers many of the potential benefits of an individual quota system without formally implementing such a system. A corporate management model offers an advantage over a self-management model in that it can coordinate both marketing and management to take advantage of this unique geographical advantage. For such a system to be successful, the fishery needs to be relatively small and self- contained. Small in this sense is in terms of number of operators. The Moreton Bay prawn fishery satisfies these key conditions for a successful self-management and potentially corporate management system. The fishery is small both in terms of number of participants and geography. Unlike other fisheries that have progressed down the self-management route, the key market for the product from the Moreton Bay fishery is right at its doorstep. Corporate management also presents a number of challenges. First, it will require changes in the way fishers operate. In particular, the decision on when to fish and what to catch will be taken away from the individual and decided by the collective. Problems will develop if individuals do not join the corporation but continue to fish and market their own product separately. While this may seem an attractive option to fishers who believe they can do better independently, this is likely to be just a short- term advantage with an overall long-run cost to themselves as well as the rest of the industry. There are also a number of other areas that need further consideration, particularly in relation to the allocation of shares, including who should be allocated shares (e.g. just boat owners or also some employed skippers). Similarly, how harvesting activity is to be allocated by the corporation to the fishers. These are largely issues that cannot be answered without substantial consultation with those likely to be affected, and these groups cannot give these issues serious consideration until the point at which they are likely to become a reality. Given the current structure and complexity of the fishery, it is unlikely that such a management structure will be feasible in the short term. However, the fishery is a prime candidate for such a model, and development of such a management structure in the future should be considered as an option for the longer term.

A genome-wide linkage scan provides evidence for both new and previously reported loci influencing common migraine

Latent class analysis was performed on migraine symptom data collected in a Dutch population sample (N = 12,210, 59% female) in order to obtain empirical groupings of individuals suffering from symptoms of migraine headache. Based on these heritable groupings (h(2) = 0.49, 95% CI: 0.41-0.57) individuals were classified as affected (migrainous headache) or unaffected. Genome-wide linkage analysis was performed using genotype data from 105 families with at least 2 affected siblings. In addition to this primary phenotype, linkage analyses were performed for the individual migraine symptoms. Significance levels, corrected for the analysis of multiple traits, were determined empirically via a novel simulation approach. Suggestive linkage for migrainous headache was found on chromosomes 1 (LOD = 1.63; pointwise P = 0.0031), 13 (LOD = 1.63; P = 0.0031), and 20 (LOD = 1.85; P = 0.0018). Interestingly, the chromosome 1 peak was located close to the ATP1A2 gene, associated with familial hemiplegic migraine type 2 (FHM2). Individual symptom analysis produced a LOD score of 1.97 (P = 0.0013) on chromosome 5 (photo/phonophobia), a LOD score of 2.13 (P = 0.0009) on chromosome 10 (moderate/severe pain intensity) and a near significant LOD score of 3.31 (P = 0.00005) on chromosome 13 (pulsating headache). These peaks were all located near regions previously reported in migraine linkage studies. Our results provide important replication and support for the presence of migraine susceptibility genes within these regions, and further support the utility of an LCA-based phenotyping approach and analysis of individual symptoms in migraine genetic research. Additionally, our novel "2-step" analysis and simulation approach provides a powerful means to investigate linkage to individual trait components.

A reanalysis of 409 European-Ancestry and African American schizophrenia pedigrees reveals significant linkage to 8p23.3 with evidence of locus heterogeneity

The detection and replication of schizophrenia risk loci can require substantial sample sizes, which has prompted various collaborative efforts for combining multiple samples. However, pooled samples may comprise sub-samples with substantial population genetic differences, including allele frequency differences. We investigated the impact of population differences via linkage reanalysis of Molecular Genetics of Schizophrenia 1 (MGS1) affected sibling-pair data, comprising two samples of distinct ancestral origin: European (EA: 263 pedigrees) and African-American (AA: 146 pedigrees). To exploit the linkage information contained within these distinct continental samples, we performed separate analyses of the individual samples, allowing for within-sample locus heterogeneity, and the pooled sample, allowing for both within-sample and between-sample heterogeneity. Significance levels, corrected for the multiple tests, were determined empirically. For all suggestive peaks, stronger linkage evidence was obtained in either the EA or AA sample than the combined sample, regardless of how heterogeneity was modeled for the latter. Notably, we report genomewide significant linkage of schizophrenia to 8p23.3 and evidence for a second, independent susceptibility locus, reaching suggestive linkage, 29 cM away on 8p21.3. We also detected suggestive linkage on chromosomes 5p13.3 and 7q36.2. Many regions showed pronounced differences in the extent of linkage between the EA and AA samples. This reanalysis highlights the potential impact of population differences upon linkage evidence in pooled data and demonstrates a useful approach for the analysis of samples drawn from distinct continental groups.

Within-family outliers: Segregating alleles or environmental effects? A linkage analysis of height from 5815 sibling pairs

Most information in linkage analysis for quantitative traits comes from pairs of relatives that are phenotypically most discordant or concordant. Confounding this, within-family outliers from non-genetic causes may create false positives and negatives. We investigated the influence of within-family outliers empirically, using one of the largest genome-wide linkage scans for height. The subjects were drawn from Australian twin cohorts consisting of 8447 individuals in 2861 families, providing a total of 5815 possible pairs of siblings in sibships. A variance component linkage analysis was performed, either including or excluding the within-family outliers. Using the entire dataset, the largest LOD scores were on chromosome 15q (LOD 2.3) and 11q (1.5). Excluding within-family outliers increased the LOD score for most regions, but the LOD score on chromosome 15 decreased from 2.3 to 1.2, suggesting that the outliers may create false negatives and false positives, although rare alleles of large effect may also be an explanation. Several regions suggestive of linkage to height were found after removing the outliers, including 1q23.1 (2.0), 3q22.1 (1.9) and 5q32 (2.3). We conclude that the investigation of the effect of within-family outliers, which is usually neglected, should be a standard quality control measure in linkage analysis for complex traits and may reduce the noise for the search of common variants of modest effect size as well as help identify rare variants of large effect and clinical significance. We suggest that the effect of within-family outliers deserves further investigation via theoretical and simulation studies.