Unintended cardiac irradiation during left-sided breast cancer radiotherapy

Objective: Cardiac irradiation during left-sided breast radiotherapy may lead to
deleterious cardiac side effects. Using image guided radiotherapy, it is possible
to exclude the heart from treatment fields and monitor reproducibility of virtual simulation (VS) fields at treatment delivery using electronic portal imaging (EPI). Retrospectively, we evaluate the incidence of cardiac irradiation at VS and subsequent unintended cardiac irradiation during treatment.

Methods: Patients receiving left-sided radiotherapy to the breast or chest wall,
treated with a glancing photon field technique during a four-month period, were
included. VS images and EPIs during radiotherapy delivery were visually assessed.
The presence of any portion of the heart within the treatment field at VS or during treatment was recorded. Central lung distance and maximum heart distance were recorded.

Results: Of 128 patients, 45 (35.1%) had any portion of the heart within the
planned treatment field. Of these, inclusion of the heart was clinically unavoidable in 25 (55.6%). Of those with no heart included in the treatment fields at VS, 41 (49.4%) had presence of the heart as assessed on EPI during treatment.

Conclusion: Unintended cardiac irradiation during left-sided breast radiotherapy treatment occurs in a sizeable proportion of patients.

Advances in knowledge: Despite the use of three-dimensional computed tomography simulation and cardiac shielding, sizeable proportions of patients receiving left-sided breast cancer radiotherapy have unintended cardiac irradiation.

Volumetric modulated arc therapy and breath-hold in image-guided locoregional left-sided breast irradiation

PURPOSE: To investigate the effects of using volumetric modulated arc therapy (VMAT) and/or voluntary moderate deep inspiration breath-hold (vmDIBH) in the radiation therapy (RT) of left-sided breast cancer including the regional lymph nodes.

MATERIALS AND METHODS: For 13 patients, four treatment combinations were compared; 3D-conformal RT (i.e., forward IMRT) in free-breathing 3D-CRT(FB), 3D-CRT(vmDIBH), 2 partial arcs VMAT(FB), and VMAT(vmDIBH). Prescribed dose was 42.56 Gy in 16 fractions. For 10 additional patients, 3D-CRT and VMAT in vmDIBH only were also compared.

RESULTS: Dose conformity, PTV coverage, ipsilateral and total lung doses were significantly better for VMAT plans compared to 3D-CRT. Mean heart dose (D(mean,heart)) reduction in 3D-CRT(vmDIBH) was between 0.9 and 8.6 Gy, depending on initial D(mean,heart) (in 3D-CRT(FB) plans). VMAT(vmDIBH) reduced the D(mean,heart) further when D(mean,heart) was still >3.2 Gy in 3D-CRT(vmDIBH). Mean contralateral breast dose was higher for VMAT plans (2.7 Gy) compared to 3DCRT plans (0.7 Gy).

CONCLUSIONS: VMAT and 3D-CRT(vmDIBH) significantly reduced heart dose for patients treated with locoregional RT of left-sided breast cancer. When Dmean,heart exceeded 3.2 Gy in 3D-CRT(vmDIBH) plans, VMAT(vmDIBH) resulted in a cumulative heart dose reduction. VMAT also provided better target coverage and reduced ipsilateral lung dose, at the expense of a small increase in the dose to the contralateral breast.

Orbits of operators commuting with the Volterra operator

Asymptotic estimates of the norms of orbits of certain operators that commute with the classical Volterra operator V acting on L-P[0,1], with 1 0, but also to operators of the form phi (V), where phi is a holomorphic function at zero. The method to obtain the estimates is based on the fact that the Riemann-Liouville operator as well as the Volterra operator can be related to the Levin-Pfluger theory of holomorphic functions of completely regular growth. Different methods, such as the Denjoy-Carleman theorem, are needed to analyze the behavior of the orbits of I - cV, where c > 0. The results are applied to the study of cyclic properties of phi (V), where phi is a holomorphic function at 0.

Spatial attentional bias as a marker of genetic risk, symptom severity, and stimulant response in ADHD

Attention-deficit hyperactivity disorder (ADHD) is a heritable childhood onset disorder that is marked by variability at multiple levels including clinical presentation, cognitive profile, and response to stimulant medications. It has been suggested that this variability may reflect etiological differences, particularly, at the level of underlying genetics. This study examined whether an attentional phenotype-spatial attentional bias could serve as a marker of symptom severity, genetic risk, and stimulant response in ADHD. A total of 96 children and adolescents with ADHD were assessed on the Landmark Task, which is a sensitive measure of spatial attentional bias. All children were genotyped for polymorphisms (30 untranslated (UTR) and intron 8 variable number of tandem repeats (VNTRs)) of the dopamine transporter gene (DAT1). Spatial attentional bias correlated with ADHD symptom levels and varied according to DAT1 genotype. Children who were homozygous for the 10-repeat allele of the DAT1 30-UTR VNTR displayed a rightward attentional bias and had higher symptom levels compared to those with the low-risk genotype. A total of 26 of these children who were medication naive performed the Landmark Task at baseline and then again after 6 weeks of stimulant medication. Left-sided inattention (rightward bias) at baseline was associated with an enhanced response to stimulants at 6 weeks. Moreover, changes in spatial bias with stimulant medications, varied as a function of DAT1 genotype. This study suggests an attentional phenotype that relates to symptom severity and genetic risk for ADHD, and may have utility in predicting stimulant response in ADHD.

Dopaminergic genotype biases spatial attention in healthy children

In everyday life, our sensory system is bombarded with visual input and we rely upon attention to select only those inputs that are relevant to behavioural goals. Typically, humans can shift their attention from one visual field to the other with little cost to perception. In cases of, unilateral neglect', however, there is a persistent bias of spatial attention towards the same side as the damaged cerebral hemisphere. We used a visual orienting task to examine the influence of functional polymorphisms of the dopamine transporter gene (DAT1) on individual differences in spatial attention in normally developing children. DAT1 genotype significantly influenced spatial bias. Healthy children who were homozygous for alleles that influence the expression of dopamine transporters in the brain displayed inattention for left-sided stimuli, whereas heterozygotes did not. Our data provide the first evidence in healthy individuals of a genetically mediated bias in spatial attention that is related to dopamine signalling.

The ventral habenulae of zebrafish develop in prosomere 2 dependent on Tcf7l2 function

The conserved habenular neural circuit relays cognitive information from the forebrain into the ventral mid- and hindbrain. In zebrafish, the bilaterally formed habenulae in the dorsal diencephalon are made up of the asymmetric dorsal and symmetric ventral habenular nuclei, which are homologous to the medial and lateral nuclei respectively, in mammals. These structures have been implicated in various behaviors related to the serotonergic/dopaminergic neurotransmitter system. The dorsal habenulae develop adjacent to the medially positioned pineal complex. Their precursors differentiate into two main neuronal subpopulations which differ in size across brain hemispheres as signals from left-sided parapineal cells influence their differentiation program. Unlike the dorsal habenulae and despite their importance, the ventral habenulae have been poorly studied. It is not known which genetic programs underlie their development and why they are formed symmetrically, unlike the dorsal habenulae. A main reason for this lack of knowledge is that the vHb origin has remained elusive to date.

Integral completeness of locally convex spaces

A locally convex space X is said to be integrally complete if each continuous mapping f: [0, 1] --> X is Riemann integrable. A criterion for integral completeness is established. Readily verifiable sufficient conditions of integral completeness are proved.

Range-edge effects promote clonal growth in peripheral populations of the one-sided wintergreen Orthilia secunda

Existing in suboptimal conditions is a frequent occurrence for species inhabiting the cusp of their ecological range. In range-edge populations of plants, the scarcity of suitable habitat may be reflected in small population sizes which may result in increased self-pollination and/or inbreeding and an increase in the incidence of clonal reproduction. These factors may result in a decrease in levels of genetic diversity and a loss of potential adaptive variation that may compromise species' ability to cope with changes in their environment, an issue that is particularly relevant today with the current concern surrounding global climate change and its effect on species' distributional ranges. In the present study, we have compared the levels of clonal reproduction in the one-sided wintergreen Orthilia secunda (L.) House in (1) populations from its main continuous distribution range, (2) populations occurring on the limits of the continuous range, and (3) peripheral populations outwith the species' continuous distribution range. Range-edge populations in Scotland and Sweden displayed significantly lower genotypic richness and diversity than those from the main area of the species' distribution in these countries. Populations from Ireland, which occur in the temperate zone rather than the boreal conditions that are the preferred habitat for the species, and which represent relict populations left over from cooler periods in the Earth's history, displayed no within-population genetic diversity, suggesting a complete lack of sexual reproduction. Furthermore, the genetic distinctiveness of the Irish populations, which contained alleles not found in either the Scottish or the Swedish populations, highlights the value of 'trailing edge' populations and supports the concept of 'parochial conservation', namely the conservation of species that are locally rare but globally common.

A comparison of stress intensity factors through crack closure integral and other approaches using eXtended element-free Galerkin method

In this paper, a new approach for extracting stress intensity factors (SIFs) by the extended element-free Galerkin method, through a crack closure integral (CCI) scheme, is proposed. The CCI calculation is used in conjunction with a local smoothing technique to improve the accuracy of the computed SIFs in a number of case studies of linear elastic fracture mechanics. The cases involve problems of mixed-mode, curved crack and thermo-mechanical loading. The SIFs by CCI, displacement and stress methods are compared with those based on the M-integral technique reported in the literature. The proposed CCI method involves very simple relations, and still gives good accuracy. The convergence of the results is also examined.

Modified crack closure integral technique for extraction of SIFs in meshfee methods

A new approach for extracting stress intensity factors (SIFs) by the element-free Galerkin (EFG) class of methods through a modified crack closure integral (MCCI) scheme is proposed. Its primary feature is that it allows accurate calculation of mode I and mode II SIFs with a relatively simple and straightforward analysis even when a coarser nodal density is employed. The details of the adoption of the MCCI technique in the EFG method are described. Its performance is demonstrated through a number of case studies including mixed-mode and thermal problems in linear elastic fracture mechanics (LEFM). The results are compared with published theoretical solutions and those based on the displacement method, stress method, crack closure integral in conjunction with local smoothing (CCI–LS) technique, as well as the M-integral method. Its advantages are discussed.

Crack propagation in non-homogenous materials: Evaluation of mixed-mode SIFs, T-stress and kinking angle using a variant EFG method

A new variant of the Element-Free Galerkin (EFG) method, that combines the diffraction method, to characterize the crack tip solution, and the Heaviside enrichment function for representing discontinuity due to a crack, has been used to model crack propagation through non-homogenous materials. In the case of interface crack propagation, the kink angle is predicted by applying the maximum tangential principal stress (MTPS) criterion in conjunction with consideration of the energy release rate (ERR). The MTPS criterion is applied to the crack tip stress field described by both the stress intensity factor (SIF) and the T-stress, which are extracted using the interaction integral method. The proposed EFG method has been developed and applied for 2D case studies involving a crack in an orthotropic material, crack along an interface and a crack terminating at a bi-material interface, under mechanical or thermal loading; this is done to demonstrate the advantages and efficiency of the proposed methodology. The computed SIFs, T-stress and the predicted interface crack kink angles are compared with existing results in the literature and are found to be in good agreement. An example of crack growth through a particle-reinforced composite materials, which may involve crack meandering around the particle, is reported.