Ventilation and Perfusion at the Alveolar Level: Insights From Lung Intravital Microscopy

Intravital microscopy (IVM) offers unique possibilities for the observation of biological processes and disease related mechanisms in vivo. Especially for anatomically complex and dynamic organs such as the lung and its main functional unit, the alveolus, IVM provides exclusive advantages in terms of spatial and temporal resolution. By the use of lung windows, which have advanced and improved over time, direct access to the lung surface is provided. In this review we will discuss two main topics, namely alveolar dynamics and perfusion from the perspective of IVM-based studies. Of special interest are unanswered questions regarding alveolar dynamics such as: What are physiologic alveolar dynamics? How do these dynamics change under pathologic conditions and how do those changes contribute to ventilator-induced lung injury? How can alveolar dynamics be targeted in a beneficial way? With respect to alveolar perfusion IVM has propelled our understanding of the pulmonary microcirculation and its perfusion, as well as pulmonary vasoreactivity, permeability and immunological aspects. Whereas the general mechanism behind these processes are understood, we still lack a proper understanding of the complex, multidimensional interplay between alveolar ventilation and microvascular perfusion, capillary recruitment, or vascular immune responses under physiologic and pathologic conditions. These are only part of the unanswered questions and problems, which we still have to overcome. IVM as the tool of choice might allow us to answer part of these questions within the next years or decades. As every method, IVM has advantages as well as limitations, which have to be taken into account for data analysis and interpretation, which will be addressed in this review

Far infrared CO and H2_2O emission in intermediate-mass protostars

Intermediate-mass young stellar objects (YSOs) provide a link to understand how feedback from shocks and UV radiation scales from low to high-mass star forming regions. Aims: Our aim is to analyze excitation of CO and H$_2$O in deeply-embedded intermediate-mass YSOs and compare with low-mass and high-mass YSOs. Methods: Herschel/PACS spectral maps are analyzed for 6 YSOs with bolometric luminosities of $L_\mathrm{bol}\sim10^2 - 10^3$ $L_\odot$. The maps cover spatial scales of $\sim 10^4$ AU in several CO and H$_2$O lines located in the $\sim55-210$ $\mu$m range. Results: Rotational diagrams of CO show two temperature components at $T_\mathrm{rot}\sim320$ K and $T_\mathrm{rot}\sim700-800$ K, comparable to low- and high-mass protostars probed at similar spatial scales. The diagrams for H$_2$O show a single component at $T_\mathrm{rot}\sim130$ K, as seen in low-mass protostars, and about $100$ K lower than in high-mass protostars. Since the uncertainties in $T_\mathrm{rot}$ are of the same order as the difference between the intermediate and high-mass protostars, we cannot conclude whether the change in rotational temperature occurs at a specific luminosity, or whether the change is more gradual from low- to high-mass YSOs. Conclusions: Molecular excitation in intermediate-mass protostars is comparable to the central $10^{3}$ AU of low-mass protostars and consistent within the uncertainties with the high-mass protostars probed at $3\cdot10^{3}$ AU scales, suggesting similar shock conditions in all those sources.Comment: Accepted to Astronomy & Astrophysics. 4 pages, 5 figures, 3 table

On Top of the Alveolar Epithelium: Surfactant and the Glycocalyx

Gas exchange in the lung takes place via the air-blood barrier in the septal walls of alveoli. The tissue elements that oxygen molecules have to cross are the alveolar epithelium, the interstitium and the capillary endothelium. The epithelium that lines the alveolar surface is covered by a thin and continuous liquid lining layer. Pulmonary surfactant acts at this air-liquid interface. By virtue of its biophysical and immunomodulatory functions, surfactant keeps alveoli open, dry and clean. What needs to be added to this picture is the glycocalyx of the alveolar epithelium. Here, we briefly review what is known about this glycocalyx and how it can be visualized using electron microscopy. The application of colloidal thorium dioxide as a staining agent reveals differences in the staining pattern between type I and type II alveolar epithelial cells and shows close associations of the glycocalyx with intraalveolar surfactant subtypes such as tubular myelin. These morphological findings indicate that specific spatial interactions between components of the surfactant system and those of the alveolar epithelial glycocalyx exist which may contribute to the maintenance of alveolar homeostasis, in particular to alveolar micromechanics, to the functional integrity of the air-blood barrier, to the regulation of the thickness and viscosity of the alveolar lining layer, and to the defence against inhaled pathogens. Exploring the alveolar epithelial glycocalyx in conjunction with the surfactant system opens novel physiological perspectives of potential clinical relevance for future research

Penalization of aperture complexity in inversely planned volumetric modulated arc therapy

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134774/1/mp2566.pd

Use of plan quality degradation to evaluate tradeoffs in delivery efficiency and clinical plan metrics arising from IMRT optimizer and sequencer compromises

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135043/1/mp8118.pd

Quantumâ inspired algorithm for radiotherapy planning optimization

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153600/1/mp13840.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153600/2/mp13840_am.pd

The impact of a high‐definition multileaf collimator for spine SBRT

PurposeAdvanced radiotherapy delivery systems designed for high‐dose, high‐precision treatments often come equipped with high‐definition multi‐leaf collimators (HD‐MLC) aimed at more finely shaping radiation dose to the target. In this work, we study the effect of a high definition MLC on spine stereotactic body radiation therapy (SBRT) treatment plan quality and plan deliverability.Methods and MaterialsSeventeen spine SBRT cases were planned with VMAT using a standard definition MLC (M120), HD‐MLC, and HD‐MLC with an added objective to reduce monitor units (MU). M120 plans were converted into plans deliverable on an HD‐MLC using in‐house software. Plan quality and plan deliverability as measured by portal dosimetry were compared among the three types of plans.ResultsOnly minor differences were noted in plan quality between the M120 and HD‐MLC plans. Plans generated with the HD‐MLC tended to have better spinal cord sparing (3% reduction in maximum cord dose). HD‐MLC plans on average had 12% more MU and 55% greater modulation complexity as defined by an in‐house metric. HD‐MLC plans also had significantly degraded deliverability. Of the VMAT arcs measured, 94% had lower gamma passing metrics when using the HD‐MLC.ConclusionModest improvements in plan quality were noted when switching from M120 to HD‐MLC at the expense of significantly less accurate deliverability in some cases.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139989/1/acm212197.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139989/2/acm212197_am.pd

Model of Enterpreneurship and Social-cultural and Market Orientation of Small Business Owners in Poland

In the development of SMEs in Poland crucial meaning is legislation, steadily adapted to EU regulations, especially to the European Charter for Small Enterprises. Research conducted in Poland by many authors provide data for doing so, to confirm the hypothesis that among small businesses a vital role in shaping their work situation did not continue to play the market mechanisms and orientations, but mainly socio-cultural factors.W rozwoju MŚP w Polsce podstawowe znaczenie mają również uregulowania prawne, systematycznie dostosowywane do regulacji unijnych, zwłaszcza zaś do Europejskiej Karty Małych Przedsiębiorstw. Badania prowadzone w Polsce przez wielu autorów dostarczają danych ku temu, by potwierdzić tezę, że wśród drobnych przedsiębiorców decydującą rolę w kształtowaniu ich sytuacji pracy odgrywają nadal nie mechanizmy i orientacje rynkowe, ale przede wszystkim czynniki społeczno-kulturowe

A model combining age, equivalent uniform dose and IL-8 may predict radiation esophagitis in patients with non-small cell lung cancer

Background and purpose To study whether cytokine markers may improve predictive accuracy of radiation esophagitis (RE) in non-small cell lung cancer (NSCLC) patients. Materials and methods A total of 129 patients with stage I-III NSCLC treated with radiotherapy (RT) from prospective studies were included. Thirty inflammatory cytokines were measured in platelet-poor plasma samples. Logistic regression was performed to evaluate the risk factors of RE. Stepwise Akaike information criterion (AIC) and likelihood ratio test were used to assess model predictions. Results Forty-nine of 129 patients (38.0%) developed grade ≥2 RE. Univariate analysis showed that age, stage, concurrent chemotherapy, and eight dosimetric parameters were significantly associated with grade ≥2 RE (p < 0.05). IL-4, IL-5, IL-8, IL-13, IL-15, IL-1α, TGFα and eotaxin were also associated with grade ≥2 RE (p <0.1). Age, esophagus generalized equivalent uniform dose (EUD), and baseline IL-8 were independently associated grade ≥2 RE. The combination of these three factors had significantly higher predictive power than any single factor alone. Addition of IL-8 to toxicity model significantly improves RE predictive accuracy (p = 0.019). Conclusions Combining baseline level of IL-8, age and esophagus EUD may predict RE more accurately. Refinement of this model with larger sample sizes and validation from multicenter database are warranted