Cognitive Sparing during the Administration of Whole Brain Radiotherapy and Prophylactic Cranial Irradiation: Current Concepts and Approaches

Whole brain radiotherapy (WBRT) for the palliation of metastases, or as prophylaxis to prevent intracranial metastases, can be associated with subacute and late decline in memory and other cognitive functions. Moreover, these changes are often increased in both frequency and severity when cranial irradiation is combined with the use of systemic or intrathecal chemotherapy. Approaches to preventing or reducing this toxicity include the use of stereotactic radiosurgery (SRS) instead of WBRT; dose reduction for PCI; exclusion of the limbic circuit, hippocampal formation, and/or neural stem cell regions of the brain during radiotherapy; avoidance of intrathecal and/or systemic chemotherapy during radiotherapy; the use of high-dose, systemic chemotherapy in lieu of WBRT. This review discusses these concepts in detail as well as providing both neuroanatomic and radiobiologic background relevant to these issues

The need for flexibility when negotiating professional boundaries in the context of homecare, dementia and end of life

Professional boundaries may help care staff to clarify their role, manage risk and safeguard vulnerable clients. Yet there is a scarcity of evidence on how professional boundaries are negotiated in a non-clinical environment (e.g. the home) by the home-care workforce in the context of complex care needs (e.g. dementia, end of-life care). Through analysis of semi-structured interviews, we investigated the experiences of home-care workers (N = 30) and their managers (N = 13) working for a range of home-care services in the South-East and London regions of England in 2016–17. Findings from this study indicate that home-care workers and their managers have clear perceptions of job role boundaries, yet these are modified in dementia care, particularly at end of life which routinely requires adaptability and flexibility. As a lone worker in a client’s home, there may be challenges relating to safeguarding and risk to both clients and workers. The working environment exacerbates this, particularly during end-of-life care where emotional attachments to both clients and their family may affect the maintenance of professional boundaries. There is a need to adopt context-specific, flexible and inclusive attitudes to professional boundaries, which reconceptualise these to include relational care and atypical workplace conventions. Pre-set boundaries which safeguard clients and workers through psychological contracts may help to alleviate to some extent the pressure of the emotional labour undertaken by home-care workers

Directed Evolution of Gloeobacter violaceus Rhodopsin Spectral Properties

Proton-pumping rhodopsins (PPRs) are photoactive retinal-binding proteins that transport ions across biological membranes in response to light. These proteins are interesting for light-harvesting applications in bioenergy production, in optogenetics applications in neuroscience, and as fluorescent sensors of membrane potential. Little is known, however, about how the protein sequence determines the considerable variation in spectral properties of PPRs from different biological niches or how to engineer these properties in a given PPR. Here we report a comprehensive study of amino acid substitutions in the retinal binding pocket of Gloeobacter violacaeus rhodopsin (GR) that tune its spectral properties. Directed evolution generated 70 GR variants with absorption maxima shifted by up to +/- 80 nm, extending the protein’s light absorption significantly beyond the range of known natural PPRs. While proton pumping activity was disrupted in many of the spectrally shifted variants, we identified single tuning mutations that incurrred blue and red shifts of 42 nm and 22 nm, respectively, that did not disrupt proton pumping. Blue-shifting mutations were distributed evenly along the retinal molecule while red-shifting mutations were clustered near the residue K257, which forms a covalent bond with retinal through a Schiff base linkage. Thirty-four of the identified tuning mutations are not found in known microbial rhodopsins. We discovered a subset of red-shifted GRs that exhibit high levels of fluorescence relative to the wild-type protein

Darboux-integration of id\rho/dt=[H,f(\rho)]

A Darboux-type method of solving the nonlinear von Neumann equation $i\dot \rho=[H,f(\rho)]$, with functions $f(\rho)$ commuting with $\rho$, is developed. The technique is based on a representation of the nonlinear equation by a compatibility condition for an overdetermined linear system. von Neumann equations with various nonlinearities $f(\rho)$ are found to possess the so-called self-scattering solutions. To illustrate the result we consider the Hamiltonian $H$ of a one-dimensional harmonic oscillator and $f(\rho)=\rho^q-2\rho^{q-1}$ with arbitary real $q$. It is shown that self-scattering solutions possess the same asymptotics for all $q$ and that different nonlinearities may lead to effectively indistinguishable evolutions. The result may have implications for nonextensive statistics and experimental tests of linearity of quantum mechanics.Comment: revtex, 5 pages, 2 eps figures, submitted to Phys.Lett.A infinite-dimensional example is adde

20 questions on Adaptive Dynamics

Abstract Adaptive Dynamics is an approach to studying evolutionary change when fitness is density or frequency dependent. Modern papers identifying themselves as using this approach first appeared in the 1990s, and have greatly increased up to the present. However, because of the rather technical nature of many of the papers, the approach is not widely known or understood by evolutionary biologists. In this review we aim to remedy this situation by outlining the methodology and then examining its strengths and weaknesses. We carry this out by posing and answering 20 key questions on Adaptive Dynamics. We conclude that Adaptive Dynamics provides a set of useful approximations for studying various evolutionary questions. However, as with any approximate method, conclusions based on Adaptive Dynamics are valid only under some restrictions that we discuss

Hypoxia-induced bacterial translocation in the puppy

Because hypoxia is one of the most common major stresses to which a neonate is exposed, we postulated that it alone might be the cause of intestinal bacterial translocation, which could be the underlying etiology of neonatal sepsis. An animal model, in which hypoxia is the sole stress, was developed in our laboratory and tested in 18 puppies to determine the effect of hypoxia and reoxygenation on intestinal bacterial translocation. In group I (n = 8), following laparotomy and cannulation of the superior mesenteric vein (SMV), the FIO2 was decreased from 21% to 9% for 90 minutes followed by reoxygenation at 21% for 120 minutes. The abdomen was closed and the animals were allowed to recover. After 24 hours the mesenteric lymph nodes (MLNs), spleen, and liver were harvested for bacterial determination and the ileum and jejunum for histological evaluation. Group II (n = 7) was treated the same as group I with the FIO2 maintained at 21%. Group III (n = 3) animals were killed, without intervention, for bacterial analysis. In group I, the systemic PO2 decreased by 75%, SMV PO2 decreased by 64%, and oxygen delivery to the small bowel decreased by 80% in comparison with group II. The mean arterial pressure and cardiac output were not significantly different between group I and group II; however, the mucosal blood flow was decreased by 60% (P P P < .001). This study demonstrates that severe systemic hypoxia and subsequent reoxygenation does not initiate oxidant-mediated, lipid peroxidation injury to the small bowel mucosa, but does allow bacterial translocation to the MLNs. Thus, hypoxia-induced bacterial translocation could serve as a model for neonatal sepsis without apparent bowel injury.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30364/1/0000766.pd

The Impact Of State Policies On ACA Applications And Enrollment Among Low-Income Adults In Arkansas, Kentucky, And Texas

States are taking variable approaches to the Affordable Care Act (ACA) Medicaid expansion, Marketplace design, enrollment outreach, and application assistance. We surveyed nearly 3,000 low-income adults in late 2014 to compare experiences in three states with markedly different policies: Kentucky, which expanded Medicaid, created a successful state Marketplace, and supported outreach efforts; Arkansas, which enacted the private option and a federal-state partnership Marketplace, but with legislative limitations on outreach; and Texas, which did not expand Medicaid and passed restrictions on navigators. We found that application rates, successful enrollment, and positive experiences with the ACA were highest in Kentucky, followed by Arkansas, with Texas performing worst. Limited awareness remains a critical barrier: Fewer than half of adults had heard some or a lot about the coverage expansions. Application assistance from navigators and others was the strongest predictor of enrollment, while Latino applicants were less likely than others to successfully enroll. Twice as many respondents felt that the ACA had helped them as hurt them (although the majority reported no direct impact), and advertising was strongly associated with perceptions of the law. State policy choices appeared to have had major impacts on enrollment experiences among low-income adults and their perceptions of the ACA

Insurance Churning Rates For Low-Income Adults Under Health Reform: Lower Than Expected But Still Harmful For Many

Changes in insurance coverage over time, or “churning,” may have adverse consequences, but there has been little evidence on churning since implementation of the major coverage expansions in the Affordable Care Act (ACA) in 2014. We explored the frequency and implications of churning through surveying 3,011 low-income adults in Kentucky, which used a traditional expansion of Medicaid; Arkansas, which chose a “private option” expansion that enrolled beneficiaries in private Marketplace plans; and Texas, which opted not to expand. We also compared 2015 churning rates in these states to survey data from 2013, before the coverage expansions. Nearly 25 percent of respondents in 2015 changed coverage during the previous twelve months—a rate lower than some previous predictions. We did not find significantly different churning rates in the three states over time. Common causes of churning were job-related changes and loss of eligibility for Medicaid or Marketplace subsidies. Churning was associated with disruptions in physician care and medication adherence, increased emergency department use, and worsening self-reported quality of care and health status. Even churning without gaps in coverage had negative effects. Churning remains a challenge for many Americans, and policies are needed to reduce its frequency and mitigate its negative impacts

Dark Matter, Light Stops and Electroweak Baryogenesis

We examine the neutralino relic density in the presence of a light top squark, such as the one required for the realization of the electroweak baryogenesis mechanism, within the minimal supersymmetric standard model. We show that there are three clearly distinguishable regions of parameter space, where the relic density is consistent with WMAP and other cosmological data. These regions are characterized by annihilation cross sections mediated by either light Higgs bosons, Z bosons, or by the co-annihilation with the lightest stop. Tevatron collider experiments can test the presence of the light stop in most of the parameter space. In the co-annihilation region, however, the mass difference between the light stop and the lightest neutralino varies between 15 and 30 GeV, presenting an interesting challenge for stop searches at hadron colliders. We present the prospects for direct detection of dark matter, which provides a complementary way of testing this scenario. We also derive the required structure of the high energy soft supersymmetry breaking mass parameters where the neutralino is a dark matter candidate and the stop spectrum is consistent with electroweak baryogenesis and the present bounds on the lightest Higgs mass.Comment: 24 pages, 8 figures; version published in Phys.Rev.