The impact of inter-fraction set-up errors on the probability of pulmonary and cardiac complication in left-sided breast cancer patients

Purpose This study evaluated the impact of patient set-up errors on the probability of pulmonary and cardiac complications in the irradiation of left-sided breast cancer. Methods and Materials Using the CMS XiO Version 4.6 (CMS Inc., St Louis, MO) radiotherapy planning system's NTCP algorithm and the Lyman -Kutcher-Burman (LKB) model, we calculated the DVH indices for the ipsilateral lung and heart and the resultant normal tissue complication probabilities (NTCP) for radiation-induced pneumonitis and excess cardiac mortality in 12 left-sided breast cancer patients. Results Isocenter shifts in the posterior direction had the greatest effect on the lung V20, heart V25, mean and maximum doses to the lung and the heart. Dose volume histograms (DVH) results show that the ipsilateral lung V20 tolerance was exceeded in 58% of the patients after 1cm posterior shifts. Similarly, the heart V25 tolerance was exceeded after 1cm antero-posterior and left-right isocentric shifts in 70% of the patients. The baseline NTCPs for radiation-induced pneumonitis ranged from 0.73% - 3.4% with a mean value of 1.7%. The maximum reported NTCP for radiation-induced pneumonitis was 5.8% (mean 2.6%) after 1cm posterior isocentric shift. The NTCP for excess cardiac mortality were 0 % in 100% of the patients (n=12) before and after setup error simulations. Conclusions Set-up errors in left sided breast cancer patients have a statistically significant impact on the Lung NTCPs and DVH indices. However, with a central lung distance of 3cm or less (CLD <3cm), and a maximum heart distance of 1.5cm or less (MHD<1.5cm), the treatment plans could tolerate set-up errors of up to 1cm without any change in the NTCP to the heart.

Site classification and estimation of surface level seismic hazard using geophysical data and probabilistic approach

This paper presents the site classification of Bangalore Mahanagar Palike (BMP) area using geophysical data and the evaluation of spectral acceleration at ground level using probabilistic approach. Site classification has been carried out using experimental data from the shallow geophysical method of Multichannel Analysis of Surface wave (MASW). One-dimensional (1-D) MASW survey has been carried out at 58 locations and respective velocity profiles are obtained. The average shear wave velocity for 30 m depth (Vs(30)) has been calculated and is used for the site classification of the BMP area as per NEHRP (National Earthquake Hazards Reduction Program). Based on the Vs(30) values major part of the BMP area can be classified as ``site class D'', and ``site class C'. A smaller portion of the study area, in and around Lalbagh Park, is classified as ``site class B''. Further, probabilistic seismic hazard analysis has been carried out to map the seismic hazard in terms spectral acceleration (S-a) at rock and the ground level considering the site classes and six seismogenic sources identified. The mean annual rate of exceedance and cumulative probability hazard curve for S. have been generated. The quantified hazard values in terms of spectral acceleration for short period and long period are mapped for rock, site class C and D with 10% probability of exceedance in 50 years on a grid size of 0.5 km. In addition to this, the Uniform Hazard Response Spectrum (UHRS) at surface level has been developed for the 5% damping and 10% probability of exceedance in 50 years for rock, site class C and D These spectral acceleration and uniform hazard spectrums can be used to assess the design force for important structures and also to develop the design spectrum.

Development of a model based on Bayesian networks to estimate the probability of sheep lice presence at shearing

This paper describes the development of a model, based on Bayesian networks, to estimate the likelihood that sheep flocks are infested with lice at shearing and to assist farm managers or advisers to assess whether or not to apply a lousicide treatment. The risk of lice comes from three main sources: (i) lice may have been present at the previous shearing and not eradicated; (ii) lice may have been introduced with purchased sheep; and (iii) lice may have entered with strays. A Bayesian network is used to assess the probability of each of these events independently and combine them for an overall assessment. Rubbing is a common indicator of lice but there are other causes too. If rubbing has been observed, an additional Bayesian network is used to assess the probability that lice are the cause. The presence or absence of rubbing and its possible cause are combined with these networks to improve the overall risk assessment.

Exact calculations of survival probability for diffusion on growing lines, disks, and spheres: The role of dimension

Unlike standard applications of transport theory, the transport of molecules and cells during embryonic development often takes place within growing multidimensional tissues. In this work, we consider a model of diffusion on uniformly growing lines, disks, and spheres. An exact solution of the partial differential equation governing the diffusion of a population of individuals on the growing domain is derived. Using this solution, we study the survival probability, S(t). For the standard nongrowing case with an absorbing boundary, we observe that S(t) decays to zero in the long time limit. In contrast, when the domain grows linearly or exponentially with time, we show that S(t) decays to a constant, positive value, indicating that a proportion of the diffusing substance remains on the growing domain indefinitely. Comparing S(t) for diffusion on lines, disks, and spheres indicates that there are minimal differences in S(t) in the limit of zero growth and minimal differences in S(t) in the limit of fast growth. In contrast, for intermediate growth rates, we observe modest differences in S(t) between different geometries. These differences can be quantified by evaluating the exact expressions derived and presented here.

Survival probability for a diffusive process on a growing domain

We consider the motion of a diffusive population on a growing domain, 0 < x < L(t ), which is motivated by various applications in developmental biology. Individuals in the diffusing population, which could represent molecules or cells in a developmental scenario, undergo two different kinds of motion: (i) undirected movement, characterized by a diffusion coefficient, D, and (ii) directed movement, associated with the underlying domain growth. For a general class of problems with a reflecting boundary at x = 0, and an absorbing boundary at x = L(t ), we provide an exact solution to the partial differential equation describing the evolution of the population density function, C(x,t ). Using this solution, we derive an exact expression for the survival probability, S(t ), and an accurate approximation for the long-time limit, S = limt→∞ S(t ). Unlike traditional analyses on a nongrowing domain, where S ≡ 0, we show that domain growth leads to a very different situation where S can be positive. The theoretical tools developed and validated in this study allow us to distinguish between situations where the diffusive population reaches the moving boundary at x = L(t ) from other situations where the diffusive population never reaches the moving boundary at x = L(t ). Making this distinction is relevant to certain applications in developmental biology, such as the development of the enteric nervous system (ENS). All theoretical predictions are verified by implementing a discrete stochastic model.

Relative host plant species use by the lantana biological control agent Aconophora compressa (Membracidae) across its native and introduced ranges

Aconophora compressa Walker (Hemiptera: Membracidae) was released in 1995 against the weed lantana in Australia, and is now found on multiple host plant species. The intensity and regularity at which A. compressa uses different host species was quantified in its introduced Australian range and also its native Mexican range. In Australia, host plants fell into three statistically defined categories, as indicated by the relative rates and intensities at which they were used in the field. Fiddlewood (Citharexylum spinosum L.: Verbenaceae) was used much more regularly and at higher densities than any other host sampled, and alone made up the first group. The second group, lantana (Lantana camara L.: Verbenaceae; pink variety) and geisha girl (Duranta erecta L.: Verbenaceae), were used less regularly and at much lower densities than fiddlewood. The third group, Sheena’s gold (another variety of D. erecta), jacaranda (Jacaranda mimosifolia D. Don: Bignoniaceae) and myoporum (Myoporum acuminatum R. Br.: Myoporaceae), were used infrequently and at even lower densities. In Mexico, the insect was found at relatively low densities on all hosts relative to those in Australia. Densities were highest on L. urticifolia, D. erecta and Tecoma stans (L.) Juss. ex Kunth (Bignoniaceae), which were used at similar rates to one another. It was found also on a few other verbenaceous and non-verbenaceous host species but at even lower densities. The relative rate at which Citharexylum spp. and L. urticifolia were used could not be assessed in Mexico because A. compressa was found on only one plant of each species in areas where these host species co-occurred. The low rate at which A. compressa occurred on fiddlewood in Mexico is likely to be an artefact of the short-term nature of the surveys or differences in the suites of Citharexylum and Lantana species available there. These results provide further incentive to insist on structured and quantified surveys of non-target host use in the native range of potential biological control agents prior to host testing studies in quarantine.

Improving the estimation of probability of bidder participation in procurement auctions

Anticipating the number and identity of bidders has significant influence in many theoretical results of the auction itself and bidders’ bidding behaviour. This is because when a bidder knows in advance which specific bidders are likely competitors, this knowledge gives a company a head start when setting the bid price. However, despite these competitive implications, most previous studies have focused almost entirely on forecasting the number of bidders and only a few authors have dealt with the identity dimension qualitatively. Using a case study with immediate real-life applications, this paper develops a method for estimating every potential bidder’s probability of participating in a future auction as a function of the tender economic size removing the bias caused by the contract size opportunities distribution. This way, a bidder or auctioner will be able to estimate the likelihood of a specific group of key, previously identified bidders in a future tender.

On the probability of dizygotic twins being concordant for two alleles at multiple polymorphic loci

Accurate determination of same-sex twin zygosity is important for medical, scientific and personal reasons. Determination may be based upon questionnaire data, blood group, enzyme isoforms and fetal membrane examination, but assignment of zygosity must ultimately be confirmed by genotypic data. Here methods are reviewed for calculating average probabilities of correctly concluding a twin pair is monozygotic, given they share the same genotypes across all loci for commonly utilized multiplex short tandem repeat (STR) kits.

Estimating Resource Requirements to Staff a Response to a Medium to Large Outbreak of Foot and Mouth Disease in Australia

A recent report to the Australian Government identified concerns relating to Australia's capacity to respond to a medium to large outbreak of FMD. To assess the resources required, the AusSpread disease simulation model was used to develop a plausible outbreak scenario that included 62 infected premises in five different states at the time of detection, 28 days after the disease entered the first property in Victoria. Movements of infected animals and/or contaminated product/equipment led to smaller outbreaks in NSW, Queensland, South Australia and Tasmania. With unlimited staff resources, the outbreak was eradicated in 63 days with 54 infected premises and a 98% chance of eradication within 3 months. This unconstrained response was estimated to involve 2724 personnel. Unlimited personnel was considered unrealistic, and therefore, the course of the outbreak was modelled using three levels of staffing and the probability of achieving eradication within 3 or 6 months of introduction determined. Under the baseline staffing level, there was only a 16% probability that the outbreak would be eradicated within 3 months, and a 60% probability of eradication in 6 months. Deployment of an additional 60 personnel in the first 3 weeks of the response increased the likelihood of eradication in 3 months to 68%, and 100% in 6 months. Deployment of further personnel incrementally increased the likelihood of timely eradication and decreased the duration and size of the outbreak. Targeted use of vaccination in high-risk areas coupled with the baseline personnel resources increased the probability of eradication in 3 months to 74% and to 100% in 6 months. This required 25 vaccination teams commencing 12 days into the control program increasing to 50 vaccination teams 3 weeks later. Deploying an equal number of additional personnel to surveillance and infected premises operations was equally effective in reducing the outbreak size and duration.

Acute and chronic effects of dietary nitrate supplementation on blood pressure and the physiological responses to moderate-intensity and incremental exercise

Dietary nitrate (NO3−) supplementation with beetroot juice (BR) over 4–6 days has been shown to reduce the O2 cost of submaximal exercise and to improve exercise tolerance. However, it is not known whether shorter (or longer) periods of supplementation have similar (or greater) effects. We therefore investigated the effects of acute and chronic NO3− supplementation on resting blood pressure (BP) and the physiological responses to moderate-intensity exercise and ramp incremental cycle exercise in eight healthy subjects. Following baseline tests, the subjects were assigned in a balanced crossover design to receive BR (0.5 l/day; 5.2 mmol of NO3−/day) and placebo (PL; 0.5 l/day low-calorie juice cordial) treatments. The exercise protocol (two moderate-intensity step tests followed by a ramp test) was repeated 2.5 h following first ingestion (0.5 liter) and after 5 and 15 days of BR and PL. Plasma nitrite concentration (baseline: 454 ± 81 nM) was significantly elevated (+39% at 2.5 h postingestion; +25% at 5 days; +46% at 15 days; P < 0.05) and systolic and diastolic BP (baseline: 127 ± 6 and 72 ± 5 mmHg, respectively) were reduced by ∼4% throughout the BR supplementation period (P < 0.05). Compared with PL, the steady-state V̇o2 during moderate exercise was reduced by ∼4% after 2.5 h and remained similarly reduced after 5 and 15 days of BR (P < 0.05). The ramp test peak power and the work rate at the gas exchange threshold (baseline: 322 ± 67 W and 89 ± 15 W, respectively) were elevated after 15 days of BR (331 ± 68 W and 105 ± 28 W; P < 0.05) but not PL (323 ± 68 W and 84 ± 18 W). These results indicate that dietary NO3− supplementation acutely reduces BP and the O2 cost of submaximal exercise and that these effects are maintained for at least 15 days if supplementation is continued.

Postglacial climate changes and vegetation responses in northern Europe

Postglacial climate changes and vegetation responses were studied using a combination of biological and physical indicators preserved in lake sediments. Low-frequency trends, high-frequency events and rapid shifts in temperature and moisture balance were probed using pollen-based quantitative temperature reconstructions and oxygen-isotopes from authigenic carbonate and aquatic cellulose, respectively. Pollen and plant macrofossils were employed to shed light on the presence and response rates of plant populations in response to climate changes, particularly focusing on common boreal and temperate tree species. Additional geochemical and isotopic tracers facilitated the interpretation of pollen- and oxygen-isotope data. The results show that the common boreal trees were present in the Baltic region (~55°N) during the Lateglacial, which contrasts with the traditional view of species refuge locations in the south-European peninsulas during the glacial/interglacial cycles. The findings of this work are in agreement with recent paleoecological and genetic evidence suggesting that scattered populations of tree species persisted at higher latitudes, and that these taxa were likely limited to boreal trees. Moreover, the results demonstrate that stepwise changes in plant communities took place in concert with major climate fluctuations of the glacial/interglacial transition. Postglacial climate trends in northern Europe were characterized by rise, maxima and fall in temperatures and related changes in moisture balance. Following the deglaciation of the Northern Hemisphere and the early Holocene reorganization of the ice-ocean-atmosphere system, the long-term temperature trends followed gradually decreasing summer insolation. The early Holocene (~11,700-8000 cal yr BP) was overall cool, moist and oceanic, although the earliest Holocene effective humidity may have been low particularly in the eastern part of northern Europe. The gradual warming trend was interrupted by a cold event ~8200 cal yr BP. The maximum temperatures, ~1.5-3.0°C above modern values, were attained ~8000-4000 cal yr BP. This mid-Holocene peak warmth was coupled with low lake levels, low effective humidity and summertime drought. The late Holocene (~4000 cal yr BP-present) was characterized by gradually decreasing temperatures, higher lake levels and higher effective humidity. Moreover, the gradual trends of the late Holocene were probably superimposed by higher-frequency variability. The spatial variability of the Holocene temperature and moisture balance patterns were tentatively attributed to the differing heat capacities of continents and oceans, changes in atmospheric circulation modes and position of sites and subregions with respect to large water bodies and topographic barriers. The combination of physical and biological proxy archives is a pivotal aspect of this work, because non-climatic factors, such as postglacial migration, disturbances and competitive interactions, can influence reshuffling of vegetation and hence, pollen-based climate reconstructions. The oxygen-isotope records and other physical proxies presented in this work manifest that postglacial climate changes were the main driver of the establishment and expansion of temperate and boreal tree populations, and hence, large-scale and long-term vegetation patterns were in dynamic equilibrium with climate. A notable exception to this pattern may be the postglacial invasion of Norway spruce and the related suppression of mid-Holocene temperate forest. This salient step in north-European vegetation history, the development of the modern boreal ecosystem, cannot be unambiguously explained by current evidence of postglacial climate changes. The results of this work highlight that plant populations, including long-lived trees, may be able to respond strikingly rapidly to changes in climate. Moreover, interannual and seasonal variation and extreme events can exert an important influence on vegetation reshuffling. Importantly, the studies imply that the presence of diffuse refuge populations or local stands among the prevailing vegetation may have provided the means for extraordinarily rapid vegetation responses. Hence, if scattered populations are not provided and tree populations are to migrate long distances, their capacity to keep up with predicted rates of future climate change may be lower than previously thought.

An approach to palaeoseismicity in the Olkiluoto (sea) area during the early Holocene

Olkiluoto Island is situated in the northern Baltic Sea, near the southwestern coast of Finland, and is the proposed location of a spent nuclear fuel repository. This study examined Holocene palaeoseismicity in the Olkiluoto area and in the surrounding sea areas by computer simulations together with acoustic-seismic, sedimentological and dating methods. The most abundant rock type on the island is migmatic mica gneiss, intruded by tonalites, granodiorites and granites. The surrounding Baltic Sea seabed consists of Palaeoproterozoic crystalline bedrock, which is to a great extent covered by younger Mesoproterozoic sedimentary rocks. The area contains several ancient deep-seated fracture zones that divide it into bedrock blocks. The response of bedrock at the Olkiluoto site was modelled considering four future ice-age scenarios. Each scenario produced shear displacements of fractures with different times of occurrence and varying recovery rates. Generally, the larger the maximum ice load, the larger were the permanent shear displacements. For a basic case, the maximum shear displacements were a few centimetres at the proposed nuclear waste repository level, at proximately 500 m b.s.l. High-resolution, low-frequency echo-sounding was used to examine the Holocene submarine sedimentary structures and possible direct and indirect indicators of palaeoseismic activity in the northern Baltic Sea. Echo-sounding profiles of Holocene submarine sediments revealed slides and slumps, normal faults, debris flows and turbidite-type structures. The profiles also showed pockmarks and other structures related to gas or groundwater seepages, which might be related to fracture zone activation. Evidence of postglacial reactivation in the study area was derived from the spatial occurrence of some of the structures, especial the faults and the seepages, in the vicinity of some old bedrock fracture zones. Palaeoseismic event(s) (a single or several events) in the Olkiluoto area were dated and the palaeoenvironment was characterized using palaeomagnetic, biostratigraphical and lithostratigraphical methods, enhancing the reliability of the chronology. Combined lithostratigraphy, biostratigraphy and palaeomagnetic stratigraphy revealed an age estimation of 10 650 to 10 200 cal. years BP for the palaeoseismic event(s). All Holocene sediment faults in the northern Baltic Sea occur at the same stratigraphical level, the age of which is estimated at 10 700 cal. years BP (9500 radiocarbon years BP). Their movement is suggested to have been triggered by palaeoseismic event(s) when the Late Weichselian ice sheet was retreating from the site and bedrock stresses were released along the bedrock fracture zones. Since no younger or repeated traces of seismic events were found, it corroborates the suggestion that the major seismic activity occurred within a short time during and after the last deglaciation. The origin of the gas/groundwater seepages remains unclear. Their reflections in the echo-sounding profiles imply that part of the gas is derived from the organic-bearing Litorina and modern gyttja clays. However, at least some of the gas is derived from the bedrock. Additional information could be gained by pore water analysis from the pockmarks. Information on postglacial fault activation and possible gas and/or fluid discharges under high hydraulic heads has relevance in evaluating the safety assessment of a planned spent nuclear fuel repository in the region.

Eurasian large mammal dynamics in response to changing environments during the Late Neogene

Nisäkkäiden levinneisyyteen, niiden morfologisiin ja ekologisiin piirteisiin vaikuttavat ympäristön sekä lyhyet että pitkäkestoiset muutokset, etenkin ilmaston ja kasvillisuuden vaihtelut. Työssä tutkittiin nisäkkäiden sopeutumista ilmastonmuutoksiin Euraasiassa viimeisen 24 miljoonan vuoden aikana. Tutkimuksessa keskityttiin varsinkin viimeiseen kahteen miljoonaan vuoteen, jonka aikana ilmasto muuttui voimakkaasti ja ihmisen toiminta alkoi tulla merkittäväksi. Tämän takia on usein vaikea erottaa, kummasta em. seikasta jonkin nisäkäslajin sukupuutto tai häviäminen alueelta johtui. Aineistona käytettiin laajaa venäjänkielistä kirjallisuutta, josta löytyvät tiedot ovat kääntämättöminä jääneet aiemmin länsimaisen tutkimuksen ulkopuolelle. Työssä käytettiin myös NOW-tietokantaa, jossa on fossiilisten nisäkkäiden löytöpaikat sekä niiden iät.

Achieving a national sample of nursing homes: Balancing probability techniques and practicalities

Sampling design is critical to the quality of quantitative research, yet it does not always receive appropriate attention in nursing research. The current article details how balancing probability techniques with practical considerations produced a representative sample of Australian nursing homes (NHs). Budgetary, logistical, and statistical constraints were managed by excluding some NHs (e.g., those too difficult to access) from the sampling frame; a stratified, random sampling methodology yielded a final sample of 53 NHs from a population of 2,774. In testing the adequacy of representation of the study population, chi-square tests for goodness of fit generated nonsignificant results for distribution by distance from major city and type of organization. A significant result for state/territory was expected and was easily corrected for by the application of weights. The current article provides recommendations for conducting high-quality, probability-based samples and stresses the importance of testing the representativeness of achieved samples.

On probability-based inference under data missing by design

Whether a statistician wants to complement a probability model for observed data with a prior distribution and carry out fully probabilistic inference, or base the inference only on the likelihood function, may be a fundamental question in theory, but in practice it may well be of less importance if the likelihood contains much more information than the prior. Maximum likelihood inference can be justified as a Gaussian approximation at the posterior mode, using flat priors. However, in situations where parametric assumptions in standard statistical models would be too rigid, more flexible model formulation, combined with fully probabilistic inference, can be achieved using hierarchical Bayesian parametrization. This work includes five articles, all of which apply probability modeling under various problems involving incomplete observation. Three of the papers apply maximum likelihood estimation and two of them hierarchical Bayesian modeling. Because maximum likelihood may be presented as a special case of Bayesian inference, but not the other way round, in the introductory part of this work we present a framework for probability-based inference using only Bayesian concepts. We also re-derive some results presented in the original articles using the toolbox equipped herein, to show that they are also justifiable under this more general framework. Here the assumption of exchangeability and de Finetti's representation theorem are applied repeatedly for justifying the use of standard parametric probability models with conditionally independent likelihood contributions. It is argued that this same reasoning can be applied also under sampling from a finite population. The main emphasis here is in probability-based inference under incomplete observation due to study design. This is illustrated using a generic two-phase cohort sampling design as an example. The alternative approaches presented for analysis of such a design are full likelihood, which utilizes all observed information, and conditional likelihood, which is restricted to a completely observed set, conditioning on the rule that generated that set. Conditional likelihood inference is also applied for a joint analysis of prevalence and incidence data, a situation subject to both left censoring and left truncation. Other topics covered are model uncertainty and causal inference using posterior predictive distributions. We formulate a non-parametric monotonic regression model for one or more covariates and a Bayesian estimation procedure, and apply the model in the context of optimal sequential treatment regimes, demonstrating that inference based on posterior predictive distributions is feasible also in this case.