Stereotactic radiosurgery (SRS) and stereotactic body radiation therapy (SBRT), also known as stereotactic ablative radiation therapy (SABR), are rapidly becoming accepted practice for the radiation ...therapy of certain tumors. Typically, SRS and SBRT involve the delivery of 1 or a few large-dose fractions of 8 to 30 Gy per fraction: a major paradigm shift from radiation therapy practice over the past 90 years, when, with relatively large amounts of normal tissues receiving high doses, the goal was to maximize tumor response for an acceptable level of normal tissue injury. The development of SRS and SBRT have come about because of technologic advances in image guidance and treatment delivery techniques that enable the delivery of large doses to tumors with reduced margins and high gradients outside the target, thereby minimizing doses to surrounding normal tissues. Because the results obtained with SRS and SBRT have been impressive, they have raised the question whether classic radiobiological modeling, and the linear-quadratic (LQ) model, are appropriate for large doses per fraction. In addition to objections to the LQ model, the possibility of additional biological effects resulting from endothelial cell damage, enhanced tumor immunity, or both have been raised to account for the success of SRS and SBRT. In this review, we conclude that the available preclinical and clinical data do not support a need to change the LQ model or to invoke phenomena over and above the classic 5 Rs of radiobiology and radiation therapy, with the likely exception that for some tumors high doses of irradiation may produce enhanced antitumor immunity. Thus, we suggest that for most tumors, the standard radiobiology concepts of the 5 Rs are sufficient to explain the clinical data, and the excellent results obtained from clinical studies are the result of the much larger biologically effective doses that are delivered with SRS and SBRT.
Neutron Matter from Low to High Density Gandolfi, Stefano; Gezerlis, Alexandros; Carlson, J
Annual review of nuclear and particle science,
10/2015, Letnik:
65, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Neutron matter is an intriguing nuclear system with multiple connections to condensed matter and astrophysics. Considerable progress has been made over the past 20 years in exploring the properties ...of pure neutron fluids. We begin by reviewing research exploring the behavior of very low density neutron matter, which forms a strongly paired superfluid and is thus similar to cold Fermi atoms, although at energy scales that differ by many orders of magnitude. We then review the behavior of higher-density neutron matter, discussing research that ties the study of neutron matter to the determination of the properties of neutron-rich nuclei and neutron star crusts. Finally, we review the impact that neutron matter at even higher densities has on the mass-radius relation of neutron stars, thereby making contact with astrophysical observations.
The dense matter equation of state (EOS) determines neutron star (NS) structure but can be calculated reliably only up to one to two times the nuclear saturation density, using accurate many-body ...methods that employ nuclear interactions from chiral effective field theory constrained by scattering data. In this work, we use physically motivated ansatzes for the speed of sound cS at high density to extend microscopic calculations of neutron-rich matter to the highest densities encountered in stable NS cores. We show how existing and expected astrophysical constraints on NS masses and radii from X-ray observations can constrain the speed of sound in the NS core. We confirm earlier expectations that cS is likely to violate the conformal limit of , possibly reaching values closer to the speed of light c at a few times the nuclear saturation density, independent of the nuclear Hamiltonian. If QCD obeys the conformal limit, we conclude that the rapid increase of cS required to accommodate a 2 M NS suggests a form of strongly interacting matter where a description in terms of nucleons will be unwieldy, even between one and two times the nuclear saturation density. For typical NSs with masses in the range of 1.2-1.4 M , we find radii between 10 and 14 km, and the smallest possible radius of a 1.4 M NS consistent with constraints from nuclear physics and observations is 8.4 km. We also discuss how future observations could constrain the EOS and guide theoretical developments in nuclear physics.
The Evolution of Brachiopoda Carlson, Sandra J
Annual review of earth and planetary sciences,
01/2016, Letnik:
44, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Brachiopods are (perhaps all too) familiar to any geology student who has taken an invertebrate paleontology course; they may well be less familiar to biology students. Even though brachiopods are ...among the most significant components of the marine fossil record by virtue of their considerable diversity, abundance, and long evolutionary history, fewer than 500 species are extant. Reconciling the geological and biological perspectives is necessary in order to test hypotheses, not only about phylogenetic relationships among brachiopods but also about their spectacular decline in diversity in the end-Permian mass extinction, which permanently reset their evolutionary trajectory. Studying brachiopod ontogeny and development, population genetics, ecology, physiology, and biogeography, as well as molecular systematics and phylogenomics, enables us to better understand the context of evolutionary processes over the short term. Investigating brachiopod morphological, taxonomic, and stratigraphic records over the Phanerozoic Eon reveals historical patterns of long-term macroevolutionary change, patterns that are simply unknowable from a biological perspective alone.
We investigate the impact of the nonzero neutrino splitting and elastic neutrino-nucleon collisions on fast neutrino oscillations. Our calculations confirm that a small neutrino mass splitting and ...the neutrino mass hierarchy have very little effect on fast oscillation waves. We also demonstrate explicitly that fast oscillations remain largely unaffected for the time/distance scales that are much smaller than the neutrino mean free path but are damped on larger scales. This damping originates from both the direct modification of the dispersion relation of the oscillation waves in the neutrino medium and the flattening of the neutrino angular distributions over time. Our work suggests that fast neutrino oscillation waves produced near the neutrino sphere can propagate essentially unimpeded which may have ramifications in various aspects of the supernova physics.
Forecasting the impacts of climate change on Aedes-borne viruses-especially dengue, chikungunya, and Zika-is a key component of public health preparedness. We apply an empirically parameterized model ...of viral transmission by the vectors Aedes aegypti and Ae. albopictus, as a function of temperature, to predict cumulative monthly global transmission risk in current climates, and compare them with projected risk in 2050 and 2080 based on general circulation models (GCMs). Our results show that if mosquito range shifts track optimal temperature ranges for transmission (21.3-34.0°C for Ae. aegypti; 19.9-29.4°C for Ae. albopictus), we can expect poleward shifts in Aedes-borne virus distributions. However, the differing thermal niches of the two vectors produce different patterns of shifts under climate change. More severe climate change scenarios produce larger population exposures to transmission by Ae. aegypti, but not by Ae. albopictus in the most extreme cases. Climate-driven risk of transmission from both mosquitoes will increase substantially, even in the short term, for most of Europe. In contrast, significant reductions in climate suitability are expected for Ae. albopictus, most noticeably in southeast Asia and west Africa. Within the next century, nearly a billion people are threatened with new exposure to virus transmission by both Aedes spp. in the worst-case scenario. As major net losses in year-round transmission risk are predicted for Ae. albopictus, we project a global shift towards more seasonal risk across regions. Many other complicating factors (like mosquito range limits and viral evolution) exist, but overall our results indicate that while climate change will lead to increased net and new exposures to Aedes-borne viruses, the most extreme increases in Ae. albopictus transmission are predicted to occur at intermediate climate change scenarios.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Carlson J A (2010) Histopathology56, 3–23 The histological assessment of cutaneous vasculitis
Vasculitis is defined as inflammation directed at vessels, which compromises or destroys the vessel wall ...leading to haemorrhagic and/or ischaemic events. Skin biopsy is the gold standard for the diagnosis of cutaneous vasculitis, whose manifestations include urticaria, infiltrative erythema, petechiae, purpura, purpuric papules, haemorrhagic vesicles and bullae, nodules, livedo racemosa, deep (punched out) ulcers and digital gangrene. These varied morphologies are a direct reflection of size of the vessels and extent of the vascular bed affected, ranging from a vasculitis affecting few superficial, small vessels in petechial eruptions to extensive pan‐dermal small vessel vasculitis in haemorrhagic bullae to muscular vessel vasculitis in lower extremity nodules with livedo racemosa. Skin biopsy, extending to subcutis and taken from the earliest, most symptomatic, reddish or purpuric lesion is crucial for obtaining a high‐yielding diagnostic sample. Based on histology, vasculitis can be classified on the size of vessels affected and the dominant immune cell mediating the inflammation (e.g. neutrophilic, granulomatous, lymphocytic, or eosinophilic). Disruption of small vessels by inflammatory cells, deposition of fibrin within the lumen and/or vessel wall coupled with nuclear debris allows for the confident recognition of small vessel, mostly neutrophilic vasculitis (also known as leukocytoclastic vasculitis). In contrast, muscular vessel vasculitis can be identified solely by infiltration of its wall by inflammatory cells. Extravasation of red blood cells (purpura) and necrosis are supportive, but not diagnostic of vasculitis as they are also seen in haemorrhagic and/or vaso‐occlusive disorders (pseudovasculitis). Vasculitic foci associated with extravascular granulomas (palisaded neutrophilic and granulomatous dermatitis), tissue eosinophilia, or tissue neutrophilia signal the risk for, or co‐existence of systemic disease. This essential histological information coupled with direct immunofluorescence and anti‐neutrophil cytoplasmic data and clinical findings enables more precise and accurate diagnosis of localized and systemic vasculitis syndromes.
Apoptosis is an evolutionarily conserved and tightly regulated cell death modality. It serves important roles in physiology by sculpting complex tissues during embryogenesis and by removing effete ...cells that have reached advanced age or whose genomes have been irreparably damaged. Apoptosis culminates in the rapid and decisive removal of cell corpses by efferocytosis, a term used to distinguish the engulfment of apoptotic cells from other phagocytic processes. Over the past decades, the molecular and cell biological events associated with efferocytosis have been rigorously studied, and many eat-me signals and receptors have been identified. The externalization of phosphatidylserine (PS) is arguably the most emblematic eat-me signal that is in turn bound by a large number of serum proteins and opsonins that facilitate efferocytosis. Under physiological conditions, externalized PS functions as a dominant and evolutionarily conserved immunosuppressive signal that promotes tolerance and prevents local and systemic immune activation. Pathologically, the innate immunosuppressive effect of externalized PS has been hijacked by numerous viruses, microorganisms, and parasites to facilitate infection, and in many cases, establish infection latency. PS is also profoundly dysregulated in the tumor microenvironment and antagonizes the development of tumor immunity. In this review, we discuss the biology of PS with respect to its role as a global immunosuppressive signal and how PS is exploited to drive diverse pathological processes such as infection and cancer. Finally, we outline the rationale that agents targeting PS could have significant value in cancer and infectious disease therapeutics.
The impact of the Oncotype Dx (ODX) breast cancer assay on adjuvant chemotherapy (ACT) treatment decisions has been evaluated in many previous studies. However, it can be difficult to interpret the ...collective findings, which were conducted in diverse settings with limited sample sizes. We conducted a systematic review and meta-analysis to synthesize the results and provide insights about ODX utility. Studies, identified from PubMed, Embase, ASCO, and SABCS, were included if patients had ER+, node −, early-stage breast cancer, reported use of ODX to inform actual ACT decisions. Information was summarized and pooled according to: (1) distribution of ODX recurrence scores (RS), (2) impact of ODX on ACT recommendations, (3) impact of ODX on ACT use, and (4) proportion of patients following the treatment suggested by the ODX RS. A total of 23 studies met inclusion criteria. The distribution of RS categories was 48.8 % low, 39.0 % intermediate, and 12.2 % high (21 studies, 4,156 patients). ODX changed the clinical-pathological ACT recommendation in 33.4 % of patients (8 studies, 1,437 patients). In patients receiving ODX, receipt of ACT were: 28.2 % overall, 5.8 % low, 37.4 % intermediate, and 83.4 % high. High RS patients were significantly more likely to follow the treatment suggested by ODX versus low RS patients RR: 1.07 (1.01–1.14). The pooled results are consistent with most individual studies to date. The increased proportion of intermediate scores relative to original estimates may have implications for the clinical utility and cost impacts of testing. In addition, low versus high RS patients were significantly more likely to follow the ODX results, suggesting a tendency toward less aggressive treatment, despite a high ODX RS. Finally, there was a lack of studies on the impact of ODX on ACT use versus standard approaches, suggesting that additional studies are warranted.
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