Advances in critical care therapies for patients with cardiogenic shock (CS), including temporary mechanical circulatory support and multidisciplinary shock teams, have led to improved survival to hospital discharge, ranging from 60% to 70%. After their index hospitalization, however, survivors of CS may continue to face cardiac as well as extracardiac sequelae of these therapies and complications for years to come. Most studies in CS have focused primarily on survival, with limited data on long-term recovery measures among survivors. In other forms of critical illness, research indicates that many intensive care unit survivors experience impairments in multiple domains, such as cognitive function, physical ability, and mental health. These impairments, collectively referred to as Post-Intensive Care Syndrome, in turn impact survivors' quality of life and future prognosis. This review identifies unique aspects of CS-related survivorship, highlights lessons learned from other forms of critical illness, and outlines future research directions to determine specific strategies to enhance recovery and survivorship after CS.

SBRT is a promising treatment for primary RCC, however radiographic surveillance of the disease post-treatment is not well characterized. In this study of patients enrolled in a Phase II protocol, there appears to be a transient radiographic increase in the size of primary tumors followed by stability and decline. Further investigations will guide the timing and need for salvage treatment for post- SBRT RCC.

In $$\textbf{ZF}$$ , the well-known Fichtenholz–Kantorovich–Hausdorff theorem concerning the existence of independent families of X of size $$|{\mathcal {P}} (X)|$$ is equivalent to the following portion of the equally well-known Hewitt–Marczewski–Pondiczery theorem concerning the density of product spaces: “The product $${\textbf{2}}^{{\mathcal {P}}(X)}$$ has a dense subset of size |X|”. However, the latter statement turns out to be strictly weaker than $$\textbf{AC}$$ while the full Hewitt–Marczewski–Pondiczery theorem is equivalent to $$\textbf{AC}$$ . We study the relative strengths in $$\textbf{ZF}$$ between the statement “X has no independent family of size $$|{\mathcal {P}}(X)|$$ ” and some of the definitions of “X is finite” studied in Levy’s classic paper, observing that the former statement implies one such definition, is implied by another, and incomparable with some others.

Purpose: Treatment of fast-growing, human papillomavirus-negative, head and neck cancers (HNCs) remains challenging from the perspectives of both tumor control and late sequelae. In this study, we use systematic radiobiological optimization to identify fractionation schemes that markedly improve the radiotherapeutic effectiveness balance between tumor control probability (TCP) and late normal tissue complication probability (LNTCP), as compared with standard fractionation. Methods and Materials: We track the development after each treatment fraction of both tumor control and late sequelae. Toward the end of the treatment, accelerated repopulation of fast-growing HNC tumors means that further fractions minimally improve TCP but result in major LNTCP increases, providing the potential for optimization of the TCP-LNTCP balance. We used a recent improved model of accelerated repopulation, calibrated with extensive HNC clinical trials data, to identify optimally effective treatment regimens that both increase TCP and significantly decrease LNTCP. For comparison, we also used standard repopulation models. Results: An optimized hypofractionated schedule of 18 x 3.0 Gy is predicted to substantially increase TCP, particularly for late-stage HNC tumors (eg, similar to 35% to 49% for late-stage tumors) while decreasing high-grade LNTCP (eg, similar to 13% to <2%), as compared with a standard 35 x 2.0 Gy protocol. In addition, the treatment time is reduced from 47 to 24 days. Twice-daily treatments of 1.8 Gy per fraction provide still better outcomes. The hypofractionation predictions are robust, being almost independent of the details of the repopulation model. Conclusions: Hypofractionation or its close variant, accelerated hyperfractionation, efficiently overcomes tumor repopulation in fast-growing tumors and can be optimized toward the end of treatment when repopulation causes the TCP to increase only very slowly while LNTCP increases rapidly. Radiobiological modeling suggests that optimized 3.0 Gy per fraction hypofractionation (or 1.8 Gy per fraction, 2 fractions per weekday, accelerated hyperfractionation) is considerably more effective for HNC tumor control and for reduction of late effects than standard 2.0-Gy fractionation. (C) 2019 Elsevier Inc. All rights reserved.

Animal and clinical experiments in France in the 1920's suggested that radiotherapy delivered in a number of daily dose fractions, spread out over a period of several weeks, resulted in better tumor control for a given level of normal tissue toxicity than the application of the radiation in a single large dose. In the 1980's it was shown that there is a systematic difference in the fractionation dependence of late responding normal tissues and early responding tissues both normal and malignant, probably due to a difference in the proportion of dividing cells. In 1999, it was pointed out that, while this was true of most tumors, it was generally not the case for prostate cancer because it is particularly slow growing. Using data from both external beam radiotherapy and brachytherapy it was shown that prostate cancer responds to fractionation in a manner more similar to a late responding tissue than an early responding tissue. This led to the conclusion that much smaller numbers of fractions than usually used (with an appropriately reduced total dose) should be equally effective in treating prostate cancer, but with the associated advantages in cost, logistics and patient convenience. Many large scale randomized clinical trials have been completed in the past 18 years to test this concept, the conclusion being that that moderate hypofractionation, typically involving 15 to 25 fractions with doses per fraction of 2.5 to 3.5 Gy, is not inferior to conventional fractionation patterns involving 40 to 45 fractions with doses per fraction around 2 Gy. More recently extreme hypofractionation is being investigated, typically involving 4 to 7 fractions with much higher doses per fraction. It is too early to draw conclusions about extreme hypofractionation, but early toxicity results raise concerns.

It is now more than 18 years since Brenner and Hall (1) and, in the same year, Duchesne and Peters (2), independently suggested that there was a strong radiobiological rationale, specific to prostate cancer, for hypofractionating prostate cancer radiation therapy. In short, this was because the slow-growing nature of most prostate cancers results in their response to changes in fractionation being similar to those of the surrounding late-responding normal tissues. Consequently, as compared with standard 40-45 fraction treatment protocols for prostate cancer radiation therapy, smaller numbers of higher-dose fractions (with an appropriately reduced total dose) would be expected to be as clinically effective but would potentially have advantages in terms of patient convenience, economics and logistics.

Background and purpose Accelerated repopulation (AR) can compromise tumor control after conventional radiotherapy for fast-growing tumors. Standard AR models assume it begins at a fixed time, with repopulation rates independent of the number of clonogens killed. We investigate the validity and significance of an alternative model where onset-time and rate of AR depend on the number of clonogens killed, and thus on dose and dose-fractionation. Materials and methods We analyzed tumor control (TCP) from randomized trials for head and neck cancer (HNC, 7283 patients), featuring wide ranges of doses, times, and fractionation-schemes. We used the linear-quadratic model with the standard dose-independent AR model, or with an alternative dose-dependent model, where AR onset and rate depend on clonogen killing. Results The alternative dose-dependent model of AR provides significantly-improved descriptions of a wide range of randomized clinical data, relative to the standard dose-independent model. This preferred model predicts that, for currently-used HNC fractionation schemes, the last 5 fractions do not increase TCP, but simply compensate for increased accelerated repopulation. Conclusions The preferred dose-dependent AR model predicts that, for standard fractionation schemes currently used to treat HNC, the final week (5 fractions) could be eliminated without compromising TCP, but resulting in significantly decreased late sequelae due to the lower overall dose.

World events, including the threat of radiological terrorism and the fear of nuclear accidents, have highlighted an urgent need to develop medical countermeasures to prevent or reduce radiation injury. Similarly, plans for manned spaceflight to a near-Earth asteroid or journey to Mars raise serious concerns about long-term effects of space radiation on human health and the availability of suitable therapeutic interventions. At the same time, the need to protect normal tissue from the deleterious effects of radiotherapy has driven considerable research into the design of effective radioprotectors. For more than 70 years, animal models of radiation cataract have been utilized to test the short and long-term efficacy of various radiation countermeasures. While some compounds, most notably the Walter Reed (WR) class of radioprotectors, have reported limited effectiveness when given before exposure to low-LET radiation, the human toxicity of these molecules at effective doses limits their usefulness. Furthermore, while there has been considerable testing of eye responses to X- and gamma irradiation, there is limited information about using such models to limit the injurious effects of heavy ions and neutrons on eye tissue. A new class of radioprotector molecules, including the sulfhydryl compound PrC-210, are reported to be effective at much lower doses and with far less side effects. Their ability to modify ocular radiation damage has not yet been examined. The ability to non-invasively measure sensitive, radiation-induced ocular changes over long periods of time makes eye models an attractive option to test the radioprotective and radiation mitigating abilities of new novel compounds.

Gioacchino Failla was initially appointed to operate the radon plant at Memorial Hospital in 1916. What to most people would have been a part-time temporary position was to him a career. He was not satisfied to simply fabricate radon seeds, he wanted to understand the physics and biology of the radiation emitted by the progeny of radium. His was not the first medical physics group in the United States, though it was one of the earliest, but it was the first to put such emphasis on the biological effects. After more than 28 years at Memorial Hospital, Failla moved his research group to Columbia University Medical Center and his pioneering work, blending physics and biology, has continued to date at Columbia by those that he trained or inspired, under three directors that followed him.

The value of legumes in high input pastures has come into question in recent years. High sowing rates of grasses (> 20 kg/ha) and the regular use of nitrogen fertilisers are contributing factors to the declining composition of legumes in pastures. However, legumes can be an important component of a mixed pasture sward, through their ability to fix atmospheric nitrogen and their high nutritive value. This study evaluated the dry matter (DM) contribution of legumes to irrigated mixed swards receiving either a nil nitrogen or a 40kg N/ha nitrogen treatment following each defoliation event. The experiment was sown with 29 pasture treatments consisting of mixed swards and monocultures of 5 grass species (perennial ryegrass cv. Base, tall fescue Festuca arundinacea cv. Quantum II MaxP, coloured brome Bromus coloratus cv. Exceltas, cocksfoot Dactylis glomerata cv. Megatas and phalaris Phalaris hybrid cv. Advanced AT) and 4 legume species (white clover cv. Bounty, red clover Trifolium pratense cv. Rubitas, strawberry clover Trifolium fragiferum cv. Palestine and Caucasian clover Trifolium ambiguum cv. Kuratas). The clover contribution (%) to production increased significantly (P<0.05) in nil-nitrogen treatments compared with pasture mixes receiving nitrogen. The application of high rates of N fertilisers can inhibit significant contributions of legumes to overall production. White clover proved to be well adapted and the results of this study suggest it would difficult to justify the sole use of any alternative species tested.

The increase in irrigable land in the Midlands region of Tasmania presents an opportunity to increase animal production, whether it is lamb, dairy or beef. However, challenges including low rainfall ( 27°C) and duplex winter wet soils in this region put into question the suitability of the traditional intensive pasture base of perennial ryegrass Lolium perenne and white clover Trifolium repens. This study evaluated the performance of alternative grass and legume species under high input management for diversifying the feedbase in this region. The experiment was sown with 29 pasture treatments consisting of mixed swards and monocultures of 5 grass species (perennial ryegrass, tall fescue Festuca arundinacea, coloured brome Bromus coloratus, cocksfoot Dactylis glomerata and phalaris Phalaris hybrid) and 4 legume species (white clover, red clover Trifolium pratense, strawberry clover Trifolium fragiferum and Caucasian clover Trifolium ambiguum). The experiment was fully irrigated and nitrogen was applied at 40 kg N/ ha following each harvest event. Dry matter (DM) yield was assessed at six defoliation events between November 2014 and April 2015. Perennial ryegrass and coloured brome were the best performed grasses, with coloured brome only significantly (P<0.05) lower than perennial ryegrass on one of the six harvest dates. The addition of the 4 clover cultivars to each of the 5 grass swards made no significant difference to yield except where white clover was in combination with phalaris. This study highlights the potential of coloured brome as an alternative to perennial ryegrass in high input systems although its tolerance of waterlogging, typical in the Midlands region requires further evaluation.