Volumetric modulated arc therapy for synchronous bilateral whole breast irradiation – A case study

PurposeThe treatment planning of bilateral breast irradiation (BBI) is a challenging task. The overlapping of tangential fields is usually unavoidable without compromising the target coverage. The purpose of this study was to investigate the technical feasibility and benefits of a single isocentre volumetric modulated arc therapy (VMAT) in BBI.Methods and materialsTwo women with bilateral breast cancer were included in this case study. The first patient (Pat#1) underwent a bilateral breast-conserving surgery and sentinel lymph node biopsy. The second patient (Pat#2) underwent a bilateral ablation and axillary lymph node dissection. Planning target volumes (PTV) and organs at risk were delineated on CT images. VMAT plans were created with four (two for both sides, Pat#1) or two (one for each breast, Pat#2) separate VMAT fields. Subsequently, traditional tangential field plans were generated for each patient and the dosimetric parameters were compared.ResultsThe treatment times of the patients with VMAT were less than 15 min with daily CBCT imaging. When compared to the standard tangential field technique, the VMAT plans improved the PTV dose coverage and dose homogeneity with improved sparing of lungs and heart. With traditional field arrangement, the overlapping of the tangential fields was inevitable without significantly compromising the target coverage, whereas with VMAT the hotspots were avoided. The patients were treated with the VMAT technique and no acute skin toxicity was observed with either of the patients.ConclusionsA single isocentre VMAT technique has been implemented clinically for BBI. With the VMAT techniques, the dose delivery was quick and the hotspots in the field overlapping areas were avoided. The PTV dose coverage was superior in VMAT plans when compared with conventional tangential technique plans.     

Allergy symptoms in relation to alder and birch pollen concentrations in Finland

In order to study allergic people responding to daily changes in pollen concentrations, we compared personal diary data on allergic symptoms and the use of allergy medicines to daily pollen counts during the two unequal alder and birch pollen seasons of 2009 and 2010. Almost 90% of the 61 subjects with physician-diagnosed birch pollinosis developed conjunctival, nasal or other symptoms during the peak birch pollination. Most subjects (95%) also reported symptoms during the alder pollination. Despite a delay between the most severe symptoms and the pollen peaks and the increased risk of allergy symptoms between the alder and birch pollen peaks at much lower pollen concentrations, the number of subjects with allergy symptoms correlated with the daily pollen concentrations in both years (r ₀₉ = 0.35, r ₁₀ = 0.36, p < 0.01). The positive correlation was even stronger (r ₀₉ = 0.69, r ₁₀ = 0.74, p < 0.001) in relation to the cumulative sum of daily concentrations. The use of allergy medicines precisely followed the abundance of allergy symptoms in both years (r ₀₉ = 0.96, r ₁₀ = 0.70, p < 0.001). We conclude that there is a fair correlation between the daily allergy symptoms and the particular pollen concentrations, but the risk of developing symptoms at low, moderate and high concentrations is affected by the progression of the pollen season.     

BDNF Depresses Excitability of Parvalbumin-Positive Interneurons through an M-Like Current in Rat Dentate Gyrus

In addition to their classical roles in neuronal growth, survival and differentiation, neurotrophins are also rapid regulators of excitability, synaptic transmission and activity-dependent synaptic plasticity. We have recently shown that mature BDNF (Brain Derived Neurotrophic Factor), but not proBDNF, modulates the excitability of interneurons in dentate gyrus within minutes. Here, we used brain slice patch-clamp recordings to study the mechanisms through which BDNF modulates the firing of interneurons in rat dentate gyrus by binding to TrkB receptors. Bath application of BDNF (15 ng/ml) under current-clamp decreased the firing frequency (by 80%) and input resistance, blocking the delayed firing observed at near-threshold voltage ranges, with no changes in resting membrane potential or action potential waveform. Using TEA (tetraethylammonium), or XE991(a Kv7/KCNQ channel antagonist), the effect of BDNF was abolished, whereas application of retigabine (a Kv7/KCNQ channel opener) mimicked the effect of BDNF, suggesting that the M-current could be implicated in the modulation of the firing. In voltage-clamp experiments, BDNF increased the M-like current amplitude with no change in holding current. This effect was again blocked by XE991 and mimicked by retigabine, the latter accompanied with a change in holding current. In agreement with the electrophysiology, parvalbumin-positive interneurons co-expressed TrkB receptors and Kv7.2/KCNQ2 channels. In conclusion, BDNF depresses the excitability of interneurons by activating an M-like current and possibly blocking Kv1 channels, thereby controlling interneuron resting membrane potential and excitability.     

Fluorescence histochemical observations on the intrinsic adrenergic innervation and monoamine-containing cells of the feline pancreas,with special reference to the terminal main pancreatic duct of wirsung

Summary Intrinsic adrenergic innervation of the pancreas of the cat was studied using two fluorescence histochemical methods. Special emphasis was focused on the monoaminergic regulation of the mechanisms responsible for dynamically active suction-pressure pumping at the choledocho-pancreatico-duodenal junction, consisting of a labyrinthine reservoir chamber surrounded by a contractile mantle of smooth muscle, described recently (Kyösola, 1976). In that junction area, a rich distribution of single varicose fluorescing nerve fibers and small nerve fascicles, both free (i.e., unrelated to the blood vessels) and forming typical perivascular nerve plexuses, as well as large ganglia of nonfluorescing nerve cells surrounded by fluorescing baskets of varicose nerves were observed in the connective, fat, and pancreatic tissues, as well as between the smooth muscle bundles of the contractile smooth muscle mantle surrounding the reservoir chamber and its minor compartments. The epithelial lining of the labyrinthine duct system contained some solitary brightly yellow fluorescing enterochromaffin cells. In addition, two other categories of fluorescing cells were observed: (1) Small rounded cells with a relatively large rounded nucleus, and exhibiting a clearly bluish, usually granular, fluorescence varying from weak to intense; (2) Larger cells exhibiting quite a weak, clearly greenish to greenish-yellow fluorescence, either gathered in homogeneous clusters or mingled with the cells of the former type into heterogeneous cells clusters. These two cell types were clearly distinguishable from each other, but intermediate cell types were also seen. Thus, a continuous scale of fluorescing cells was observed, the color of the fluorescence varying from clearly bluish to greenish-yellow, the intensity of the fluorescence varying from intense to weak (respectively, in general), and the size ranging from small to large (respectively). These cells, probably heterotopic alpha cells of the islets of Langerhans, were frequently in quite close proximity to the smooth muscle surrounding the contractile labyrinthine system or its minor compartments. On the other hand, they were frequently in close proximity to quite large thin-walled sinusoid-type blood vessels. At least some of these fluorescing cells were surrounded by fluorescing varicose nerves, suggesting the existence of a neuroendocrine link. Scattered among these fluorescing cells, and also gathered into small clusters, were nonfluorescing nerve cells interconnected with fluorescing varicose nerves. The fluorescing cells of the endocrine pancreas, similarly, could be arbitrarily classified into two main categories, although intermediate cell types were observed as well: (1) Small rounded cells with a large, ovoid to rounded, centrally placed nucleus, and exhibiting a moderate to intense granular cytoplasmic fluorescence. The color of the fluorescence varied from yellow-green to blue-green, and there were considerable differences also in the fluorescence intensity. (2) Mixed irregularly with the type (1) cells were cells with more or less the same cytologic characteristics, but slightly larger, and exhibiting a rather homogeneous weak yellow fluorescence. Sometimes the fluorescence intensity was so weak that it was hardly discernible. These cells were packed densely and irregularly with the type (1) cells within the clusters, and no clear-cut spatial organization between these two cell types was observed. In the wall of the main pancreatic duct of Wirsung, both free and perivascular fluorescing nerves were seen within the different layers, including the (distally incomplete) smooth muscle layer. The epithelial lining of the duct contained enterochromaffin cells, sometimes located so deeply in the epithelial invaginations that they were in close proximity to the smooth muscle. The distribution of fluorescing nerves in the exocrine pancreas was sparse. Typical enterochromaffin cells exhibiting a bright yellow granular cytoplasmic fluorescence were scattered either solitarily or in small groups in the epithelial lining of the acini and of the small excretory ducts. Blue-green fluorescing varicose adrenergic axons were some-times seen to connect enterochromaffin cells or groups of them located in different acini. Scattered within the parenchyme of the exocrine pancreas were clusters of nonfluorescing nerve cells surrounded by typical baskets of fluorescing varicose terminal ramifications of adrenergic axons. In the endocrine pancreas, similarly, only a relatively sparse distribution of fluorescing nerves was observed among the islet cells and surrounding clusters of them. However, groups of islet cells were observed to be interconnected by fluorescing varicose nerves coursing through or near nonfluorescing ganglia, suggesting an integrative neural connection between pancreatic islets and nonadrenergic ganglia via adrenergic nerves.     

Environmental filtering and spatial effects on metacommunity organisation differ among littoral macroinvertebrate groups deconstructed by biological traits

We examined spatial and environmental effects on the deconstructed assemblages of littoral macroinvertebrates within a large lake. We deconstructed assemblages by three biological trait groups: body size, dispersal mode and oviposition behaviour. We expected that spatial effects on assemblage structuring decrease and environmental effects increase with increasing body size. We also expected stronger environmental filtering and weaker spatial effect on the assemblages of flying species compared with assemblages of non-flying species. Stronger effect of environmental filtering was expected on the assemblages with species attaching eggs compared with assemblages of species with free eggs. We used redundancy analysis with variation partitioning to examine spatial and environmental effects on the deconstructed assemblages. As expected, the importance of environmental filtering increased and that of spatial effects decreased with increasing body size. Opposite to our expectations, assemblages of non-flying species were more affected by environmental conditions compared to assemblages of flying species. Concurring with our expectations, the importance of environmental filtering was higher in structuring assemblages of species attaching eggs than in structuring those with freely laid eggs. The amount of unexplained variation was higher for assemblages with small-sized to medium-sized species, flying species and species with free eggs than those with large-sized species, non-flying species and species with attached eggs. Our observations of decreasing spatial and increasing environmental effects with increasing body size of assemblages deviated from the results of previous studies. These results suggest differing metacommunity dynamics between within-lake and among-lake levels and between studies covering contrasting taxonomic groups and body size ranges.     

A way forward with eco evo devo: an extended theory of resource polymorphism with postglacial fishes as model systems

A major goal of evolutionary science is to understand how biological diversity is generated and altered. Despite considerable advances, we still have limited insight into how phenotypic variation arises and is sorted by natural selection. Here we argue that an integrated view, which merges ecology, evolution and developmental biology (eco evo devo) on an equal footing, is needed to understand the multifaceted role of the environment in simultaneously determining the development of the phenotype and the nature of the selective environment, and how organisms in turn affect the environment through eco evo and eco devo feedbacks. To illustrate the usefulness of an integrated eco evo devo perspective, we connect it with the theory of resource polymorphism (i.e. the phenotypic and genetic diversification that occurs in response to variation in available resources). In so doing, we highlight fishes from recently glaciated freshwater systems as exceptionally well‐suited model systems for testing predictions of an eco evo devo framework in studies of diversification. Studies on these fishes show that intraspecific diversity can evolve rapidly, and that this process is jointly facilitated by (i) the availability of diverse environments promoting divergent natural selection; (ii) dynamic developmental processes sensitive to environmental and genetic signals; and (iii) eco evo and eco devo feedbacks influencing the selective and developmental environments of the phenotype. We highlight empirical examples and present a conceptual model for the generation of resource polymorphism – emphasizing eco evo devo, and identify current gaps in knowledge.     

Ecological speciation in postglacial European whitefish: rapid adaptive radiations into the littoral,pelagic, and profundal lake habitats

Understanding how a monophyletic lineage of a species diverges into several adaptive forms has received increased attention in recent years, but the underlying mechanisms in this process are still under debate. Postglacial fishes are excellent model organisms for exploring this process, especially the initial stages of ecological speciation, as postglacial lakes represent replicated discrete environments with variation in available niches. Here, we combine data of niche utilization, trophic morphology, and 17 microsatellite loci to investigate the diversification process of three sympatric European whitefish morphs from three northern Fennoscandian lakes. The morphological divergence in the gill raker number among the whitefish morphs was related to the utilization of different trophic niches and was associated with reproductive isolation within and across lakes. The intralacustrine comparison of whitefish morphs showed that these systems represent two levels of adaptive divergence: (1) a consistent littoral–pelagic resource axis; and (2) a more variable littoral–profundal resource axis. The results also indicate that the profundal whitefish morph has diverged repeatedly from the ancestral littoral whitefish morph in sympatry in two different watercourses. In contrast, all the analyses performed revealed clustering of the pelagic whitefish morphs across lakes suggesting parallel postglacial immigration with the littoral whitefish morph into each lake. Finally, the analyses strongly suggested that the trophic adaptive trait, number of gill rakers, was under diversifying selection in the different whitefish morphs. Together, the results support a complex evolutionary scenario where ecological speciation acts, but where both allopatric (colonization history) and sympatric (within watercourse divergence) processes are involved.     

A popular misapplication of evolutionary modeling to the study of human cooperation

To examine the evolutionary basis of a behavior, an established approach (known as the phenotypic gambit) is to assume that the behavior is controlled by a single allele, the fitness effects of which are derived from a consideration of how the behavior interacts, via life-history, with other ecological factors. Here we contrast successful applications of this approach with several examples of an influential and superficially similar line of research on the evolutionary basis of human cooperation. A key difference is identified: in the latter line of research the focal behavior, cooperation, is abstractly defined in terms of immediate fitness costs and benefits. Selection is then assumed to act on strategies in an iterated social context for which fitness effects can be derived by aggregation of the abstractly defined immediate fitness effects over a lifetime. This approach creates a closed theoretical loop, rendering models incapable of making predictions or providing insight into the origin of human cooperation. We conclude with a discussion of how evolutionary approaches might be appropriately used in the study of human social behavior.