Prevention and treatment of radiotherapy-induced side effects

Radiotherapy remains a mainstay of cancer treatment, being used in roughly 50% of patients. The precision with which the radiation dose can be delivered is rapidly improving. This precision allows the more accurate targeting of radiation dose to the tumor and reduces the amount of surrounding normal tissue exposed. Although this often reduces the unwanted side effects of radiotherapy, we still need to further improve patients' quality of life and to escalate radiation doses to tumors when necessary. High-precision radiotherapy forces one to choose which organ or functional organ substructures should be spared. To be able to make such choices, we urgently need to better understand the molecular and physiological mechanisms of normal tissue responses to radiotherapy. Currently, oversimplified approaches using constraints on mean doses, and irradiated volumes of normal tissues are used to plan treatments with minimized risk of radiation side effects. In this review, we discuss the responses of three different normal tissues to radiotherapy: the salivary glands, cardiopulmonary system, and brain. We show that although they may share very similar local cellular processes, they respond very differently through organ-specific, nonlocal mechanisms. We also discuss how a better knowledge of these mechanisms can be used to treat or to prevent the effects of radiotherapy on normal tissue and to optimize radiotherapy delivery

Online Music Piracy: Are Lawsuits The Best Approach?

In the age of digital technology, perfect copies of sound recordings may be easily made and shared in violation of copyright law.  Music piracy in the form of illegal downloading is a worldwide phenomenon that has a significant impact on the music industry.   In response to the perceived threat to the music industry, lawsuits have been filed in the United States and abroad based on copyright infringement for illegally downloading music. This paper examines copyright law, case law, and recent litigation.  In the wake of legal efforts to curtail illegal downloading, a survey of 112 undergraduate students was conducted in an effort to determine whether the lawsuits filed by the music industry are a deterrent to downloading music.  Potential solutions are proposed and economic consequences discussed

Stateless Flow-Zone Switching Using Software-Defined Addressing

The trend toward cloudification of communication networks and services, with user data and applications stored and processed in data centers, pushes the limits of current Data Center Networks (DCNs), requiring improved scalability, resiliency, and performance. Here we consider a DCN forwarding approach based on software-defined addressing (SDA), which embeds semantics in the Medium Access Control (MAC) address and thereby enables new forwarding processes. This work presents Flow-Zone Switching (FZS), a loop-free location-based source-routing solution that eliminates the need for forwarding tables by embedding routing instructions and flow identifiers directly in the flow-zone software-defined address. FZS speeds the forwarding process, increasing the throughput and reducing the latency of QoS-sensitive flows while reducing the capital and operational costs of switching. This paper presents details of FZS and a performance evaluation within a complete DCN.This work was supported in part by the H2020 Europe/Taiwan Joint Action 5G-DIVE under Grant 859881, in part by the Spanish State Research Agency through the TRUE5G Project under Grant PID2019-108713RB-C52/AEI/10.13039/501100011033, and in part by the Comunidad de Madrid through the Project TAPIR-CM under Grant S2018/TCS-4496

Dynamical population synthesis: Constructing the stellar single and binary contents of galactic field populations

[abridged] The galactic field's late-type stellar single and binary population is calculated on the supposition that all stars form as binaries in embedded star clusters. A recently developed tool (Marks, Kroupa & Oh) is used to evolve the binary star distributions in star clusters for a few Myr so that a particular mixture of single and binary stars is achieved. On cluster dissolution the population enters the galactic field with these characteristics. The different contributions of single stars and binaries from individual star clusters which are selected from a power-law embedded star cluster mass function are then added up. This gives rise to integrated galactic field binary distribution functions (IGBDFs) resembling a galactic field's stellar content (Dynamical Population Synthesis). It is found that the binary proportion in the galactic field of a galaxy is larger the lower the minimum cluster mass, the lower the star formation rate, the steeper the embedded star cluster mass function and the larger the typical size of forming star clusters in the considered galaxy. In particular, period-, mass-ratio- and eccentricity IGBDFs for the Milky Way are modelled. The afore mentioned theoretical IGBDFs agree with independently observed distributions. Of all late-type binaries, 50% stem from M<300M_sun clusters, while 50% of all single stars were born in M>10^4M_sun clusters. Comparison of the G-dwarf and M-dwarf binary population indicates that the stars formed in mass-segregated clusters. In particular it is pointed out that although in the present model all M-dwarfs are born in binary systems, in the Milky Way's Galactic field the majority ends up being single stars. This work predicts that today's binary frequency in elliptical galaxies is lower than in spiral and in dwarf-galaxies. The period and mass-ratio distributions in these galaxies are explicitly predicted.Comment: 14 pages, 9 figures, accepted for publication in MNRA

Acyclovir-induced neurotoxicity in an immunocompromised patient

This is a case report of a 75-year-old immunocompromised male who developed encephalopathy while undergoing treatment for disseminated herpes zoster with peripheral nerve involvement. While his initial presentation involved primarily profound lower extremity weakness, he developed progressive confusion to the point of obtundation only after initiation of standard therapy with intravenous acyclovir. The evaluation of his altered mental status was largely unremarkable. It was only after his acyclovir was discontinued that his symptoms resolved and he returned to his baseline mental status. His presentation was most consistent with acyclovir-induced neurotoxicity, which can present in patients with renal impairment and those who are immunocompromised

HIV prevalence and undiagnosed infection among a community sample of gay and bisexual men in Scotland, 2005-2011: implications for HIV testing policy and prevention

&lt;b&gt;Objective&lt;/b&gt;&lt;p&gt;&lt;/p&gt; To examine HIV prevalence, HIV testing behaviour, undiagnosed infection and risk factors for HIV positivity among a community sample of gay men in Scotland.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Cross-sectional survey of gay and bisexual men attending commercial gay venues in Glasgow and Edinburgh, Scotland with voluntary anonymous HIV testing of oral fluid samples in 2011. A response rate of 65.2% was achieved (1515 participants).&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt;&lt;p&gt;&lt;/p&gt; HIV prevalence (4.8%, 95% confidence interval, CI 3.8% to 6.2%) remained stable compared to previous survey years (2005 and 2008) and the proportion of undiagnosed infection among HIV-positive men (25.4%) remained similar to that recorded in 2008. Half of the participants who provided an oral fluid sample stated that they had had an HIV test in the previous 12 months; this proportion is significantly higher when compared to previous study years (50.7% versus 33.8% in 2005, p&#60;0.001). Older age (&#62;25 years) was associated with HIV positivity (1.8% in those &#60;25 versus 6.4% in older ages group) as was a sexually transmitted infection (STI) diagnosis within the previous 12 months (adjusted odds ratio 2.13, 95% CI 1.09–4.14). There was no significant association between age and having an STI or age and any of the sexual behaviours recorded.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusion&lt;/b&gt;&lt;p&gt;&lt;/p&gt; HIV transmission continues to occur among gay and bisexual men in Scotland. Despite evidence of recent testing within the previous six months, suggesting a willingness to test, the current opt-out policy may have reached its limit with regards to maximising HIV test uptake. Novel strategies are required to improve regular testing opportunities and more frequent testing as there are implications for the use of other biomedical HIV interventions.&lt;p&gt;&lt;/p&gt

Friendship network characteristics are associated with physical activity and sedentary behavior in early adolescence

INTRODUCTION: There is limited understanding of the association between peer social networks and physical activity (PA), sedentary and screen-related behaviors. This study reports on associations between personal network characteristics and these important health behaviors for early adolescents. METHODS: Participants were 310 students, aged 11-13 years, from fifteen randomly selected Victorian primary schools (43% response rate). PA and sedentary behaviors were collected via accelerometer and self-report questionnaire, and anthropometric measures via trained researchers. Participants nominated up to fifteen friends, and described the frequency of interaction and perceived activity intensity of these friends. Personal network predictors were examined using regression modelling for PA and sedentary/screen behavior. RESULTS: Perceived activity levels of friends, and friendships with very frequent interaction were associated with outside-of-school PA and/or sedentary/screen time. Differences according to sex were also observed in the association between network characteristics and PA and sedentary time. A higher number of friends and greater proportion of same sex friends were associated with boys engaging in more moderate-to-vigorous PA outside of school hours. PA intensity during school-day breaks was positively associated with having a greater proportion of friends who played sports for girls, and a greater proportion of male friends for boys. CONCLUSION: Friendship network characteristics are associated with PA and sedentary/screen time in late childhood/early adolescence, and these associations differ by sex. The positive influence of very active peers may be a promising avenue to strengthen traditional interventions for the promotion of PA and reduction in screen time

Uranium(III) coordination chemistry and oxidation in a flexible small-cavity macrocycle

U(III) complexes of the conformationally flexible, small-cavity macrocycle trans-calix[2]benzene[2]pyrrolide (L)2–, [U(L)X] (X = O-2,6-tBu2C6H3, N(SiMe3)2), have been synthesized from [U(L)BH4] and structurally characterized. These complexes show binding of the U(III) center in the bis(arene) pocket of the macrocycle, which flexes to accommodate the increase in the steric bulk of X, resulting in long U–X bonds to the ancillary ligands. Oxidation to the cationic U(IV) complex [U(L)X][B(C6F5)4] (X = BH4) results in ligand rearrangement to bind the smaller, harder cation in the bis(pyrrolide) pocket, in a conformation that has not been previously observed for (L)2–, with X located between the two ligand arene rings

Squirrelpox virus: assessing prevalence, transmission and environmental degradation

Red squirrels (Sciurus vulgaris) declined in Great Britain and Ireland during the last century, due to habitat loss and the introduction of grey squirrels (Sciurus carolinensis), which competitively exclude the red squirrel and act as a reservoir for squirrelpox virus (SQPV). The disease is generally fatal to red squirrels and their ecological replacement by grey squirrels is up to 25 times faster where the virus is present. We aimed to determine: (1) the seropositivity and prevalence of SQPV DNA in the invasive and native species at a regional scale; (2) possible SQPV transmission routes; and, (3) virus degradation rates under differing environmental conditions. Grey (n = 208) and red (n = 40) squirrel blood and tissues were sampled. Enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qPCR) techniques established seropositivity and viral DNA presence, respectively. Overall 8% of squirrels sampled (both species combined) had evidence of SQPV DNA in their tissues and 22% were in possession of antibodies. SQPV prevalence in sampled red squirrels was 2.5%. Viral loads were typically low in grey squirrels by comparison to red squirrels. There was a trend for a greater number of positive samples in spring and summer than in winter. Possible transmission routes were identified through the presence of viral DNA in faeces (red squirrels only), urine and ectoparasites (both species). Virus degradation analyses suggested that, after 30 days of exposure to six combinations of environments, there were more intact virus particles in scabs kept in warm (25°C) and dry conditions than in cooler (5 and 15°C) or wet conditions. We conclude that SQPV is present at low prevalence in invasive grey squirrel populations with a lower prevalence in native red squirrels. Virus transmission could occur through urine especially during warm dry summer conditions but, more notably, via ectoparasites, which are shared by both species

Reprogramming the diseased brain

Direct conversion of astrocytes to dopamine neurons in vivo offers fresh optimism for the development of improved Parkinson's therapie