Opportunistic dose amplification for proton and carbon ion therapy via capture of internally generated thermal neutrons

© 2018, The Author(s). This paper presents Neutron Capture Enhanced Particle Therapy (NCEPT), a method for enhancing the radiation dose delivered to a tumour relative to surrounding healthy tissues during proton and carbon ion therapy by capturing thermal neutrons produced inside the treatment volume during irradiation. NCEPT utilises extant and in-development boron-10 and gadolinium-157-based drugs from the related field of neutron capture therapy. Using Monte Carlo simulations, we demonstrate that a typical proton or carbon ion therapy treatment plan generates an approximately uniform thermal neutron field within the target volume, centred around the beam path. The tissue concentrations of neutron capture agents required to obtain an arbitrary 10% increase in biological effective dose are estimated for realistic treatment plans, and compared to concentrations previously reported in the literature. We conclude that the proposed method is theoretically feasible, and can provide a worthwhile improvement in the dose delivered to the tumour relative to healthy tissue with readily achievable concentrations of neutron capture enhancement drugs

Internal charge behaviour of nanocomposites

The incorporation of 23 nm titanium dioxide nanoparticles into an epoxy matrix to form a nanocomposite structure is described. It is shown that the use of nanometric particles results in a substantial change in the behaviour of the composite, which can be traced to the mitigation of internal charge when a comparison is made with conventional TiO2 fillers. A variety of diagnostic techniques (including dielectric spectroscopy, electroluminescence, thermally stimulated current, photoluminescence) have been used to augment pulsed electro-acoustic space charge measurement to provide a basis for understanding the underlying physics of the phenomenon. It would appear that, when the size of the inclusions becomes small enough, they act co-operatively with the host structure and cease to exhibit interfacial properties leading to Maxwell-Wagner polarization. It is postulated that the particles are surrounded by high charge concentrations in the Gouy-Chapman-Stern layer. Since nanoparticles have very high specific areas, these regions allow limited charge percolation through nano-filled dielectrics. The practical consequences of this have also been explored in terms of the electric strength exhibited. It would appear that there was a window in which real advantages accrue from the nano-formulated material. An optimum loading of about 10% (by weight) is indicated

Infrared based saliva screening test for COVID-19

Abstract: Severe acute respiratory syndrome coronavirus 2 has resulted in an unprecedented need for diagnostic testing that is critical in controlling the spread of COVID-19. We propose a portable infrared spectrometer with purpose-built transflection accessory for rapid point-of-care detection of COVID-19 markers in saliva. Initially, purified virion particles were characterized with Raman spectroscopy, synchrotron infrared (IR) and AFM-IR. A data set comprising 171 transflection infrared spectra from 29 patients testing positive for SARS-CoV-2 by RT-qPCR and 28 testing negative, was modeled using Monte Carlo Double Cross Validation with 50 randomized test and model sets. The testing sensitivity was 93 % (27/29) with a specificity of 82 % (23/28) that included positive samples on the limit of detection for RT-qPCR. Here, we demonstrate a proof-of-concept high throughput infrared COVID-19 test that is rapid, inexpensive, portable and utilizes sample self-collection thus minimizing the risk to healthcare workers and ideally suited to mass screening

Representations of sport in the revolutionary socialist press in Britain, 1988–2012

This paper considers how sport presents a dualism to those on the far left of the political spectrum. A long-standing, passionate debate has existed on the contradictory role played by sport, polarised between those who reject it as a bourgeois capitalist plague and those who argue for its reclamation and reformation. A case study is offered of a political party that has consistently used revolutionary Marxism as the basis for its activity and how this party, the largest in Britain, addresses sport in its publications. The study draws on empirical data to illustrate this debate by reporting findings from three socialist publications. When sport did feature it was often in relation to high profile sporting events with a critical tone adopted and typically focused on issues of commodification, exploitation and alienation of athletes and supporters. However, readers’ letters, printed in the same publications, revealed how this interpretation was not universally accepted, thus illustrating the contradictory nature of sport for those on the far left

Increased autophagy in EphrinB2-deficient osteocytes is associated with elevated secondary mineralization and brittle bone

Mineralized bone forms when collagen-containing osteoid accrues mineral crystals. This is initiated rapidly (primary mineralization), and continues slowly (secondary mineralization) until bone is remodeled. The interconnected osteocyte network within the bone matrix differentiates from bone-forming osteoblasts; although osteoblast differentiation requires EphrinB2, osteocytes retain its expression. Here we report brittle bones in mice with osteocyte-targeted EphrinB2 deletion. This is not caused by low bone mass, but by defective bone material. While osteoid mineralization is initiated at normal rate, mineral accrual is accelerated, indicating that EphrinB2 in osteocytes limits mineral accumulation. No known regulators of mineralization are modified in the brittle cortical bone but a cluster of autophagy-associated genes are dysregulated. EphrinB2-deficient osteocytes displayed more autophagosomes in vivo and in vitro, and EphrinB2-Fc treatment suppresses autophagy in a RhoA-ROCK dependent manner. We conclude that secondary mineralization involves EphrinB2-RhoA-limited autophagy in osteocytes, and disruption leads to a bone fragility independent of bone mass.Mineralized bone forms when collagen-containing osteoid accrues mineral crystals. This is initiated rapidly (primary mineralization), and continues slowly (secondary mineralization) until bone is remodeled. The interconnected osteocyte network within the bone matrix differentiates from bone-forming osteoblasts; although osteoblast differentiation requires EphrinB2, osteocytes retain its expression. Here we report brittle bones in mice with osteocyte-targeted EphrinB2 deletion. This is not caused by low bone mass, but by defective bone material. While osteoid mineralization is initiated at normal rate, mineral accrual is accelerated, indicating that EphrinB2 in osteocytes limits mineral accumulation. No known regulators of mineralization are modified in the brittle cortical bone but a cluster of autophagy-associated genes are dysregulated. EphrinB2-deficient osteocytes displayed more autophagosomes in vivo and in vitro, and EphrinB2-Fc treatment suppresses autophagy in a RhoA-ROCK dependent manner. We conclude that secondary mineralization involves EphrinB2-RhoA-limited autophagy in osteocytes, and disruption leads to a bone fragility independent of bone mass

Comprehensive vibrational spectroscopic investigation of trans,trans,trans-[Pt(N3)2(OH)2(py)2], a Pt(IV) diazido anticancer prodrug candidate

We report a detailed study of a promising photoactivatable metal-based anticancer prodrug candidate, trans,trans,trans-[Pt(N3)2(OH)2(py)2] (C1; py = pyridine), using vibrational spectroscopic techniques. Attenuated total reflection Fourier transform infrared (ATR-FTIR), Raman, and synchrotron radiation far-IR (SR-FIR) spectroscopies were applied to obtain highly resolved ligand and Pt-ligand vibrations for C1 and its precursors (trans-[Pt(N3)2(py)2] (C2) and trans-[PtCl2(py)2] (C3)). Distinct IR- and Raman-active vibrational modes were assigned with the aid of density functional theory calculations, and trends in the frequency shifts as a function of changing Pt coordination environment were determined and detailed for the first time. The data provide the ligand and Pt-ligand (azide, hydroxide, pyridine) vibrational signatures for C1 in the mid- and far-IR region, which will provide a basis for the better understanding of the interaction of C1 with biomolecules

Antitubercular therapy decreases nitric oxide production in HIV/TB coinfected patients

BACKGROUND: Nitric oxide (NO) production is increased among patients with human immunodeficiency virus (HIV) infection and also among those with tuberculosis (TB). In this study we sought to determine if there was increased NO production among patients with HIV/TB coinfection and the effect of four weeks chemotherapy on this level. METHODS: 19 patients with HIV/TB coinfection were studied. They were treated with standard four drug antitubercular therapy and sampled at baseline and four weeks. 20 patients with HIV infection, but no opportunistic infections, were disease controls and 20 individuals were healthy controls. Nitrite and citrulline, surrogate markers for NO, were measured spectrophotometrically. RESULTS: The mean age of HIV/TB patients was 28.4 ± 6.8 years and CD4 count was 116 ± 36.6/mm. Mean nitrite level among HIV/TB coinfected was 207.6 ± 48.8 nmol/ml. This was significantly higher than 99.7 ± 26.5 nmol/ml, the value for HIV infected without opportunistic infections and 46.4 ± 16.2 nmol/ml, the value for healthy controls (p value < 0.01). The level of HIV/TB coinfected NO in patients declined to 144.5 ± 34.4 nmol/ml at four weeks of therapy (p value < 0.05). Mean citrulline among HIV/TB coinfected was 1446.8 ± 468.8 nmol/ml. This was significantly higher than 880.8 ± 434.8 nmol/ml, the value for HIV infected without opportunistic infections and 486.6 ± 212.5 nmol/ml, the value for healthy controls (p value < 0.01). Levels of citrolline in HIV/TB infected declined to 1116.2 ± 388.6 nmol/ml at four weeks of therapy (p value < 0.05). CONCLUSIONS: NO production is elevated among patients with HIV infection, especially so among HIV/TB coinfected patients, but declines significantly following 4 weeks of antitubercular therapy

Factors influencing participation in controlled human infection models : a pooled analysis from six enteric fever studies [under peer review]

Background: Enteric fever is an acute febrile-illness caused by infection with the human-restricted Salmonella serovars Typhi and Paratyphi. Controlled human infection models (CHIM) of S. Typhi and Paratyphi infection are used to accelerate vaccine development and to better understand host-pathogen interactions. The primary motivations for participants to take part in these studies are unknown. We studied participant motivations, attitudes and the factors influencing CHIM study participation. Methods: Participant surveys were nested in six enteric fever CHIM studies conducted at a single centre in Oxford, UK, between 2011 and 2017. All eligible participants received one invitation to complete an anonymous, self-administered paper or online survey on either day 28 or 60 after challenge. A descriptive analysis was performed on these pooled data. All studies were included, to minimize selection bias. Results: Survey response rates varied from 33.0%-86.1%, yielding 201 participants. In the cohort, 113/198(57.0%) were educated to bachelor’s level, 61.6% were employed, 30.3% were students and 4.6% were unemployed. The most commonly cited motivations for CHIM study participation were a desire to contribute to the progression of medicine (170/201; 84.6%); the prospect of financial reimbursement (166/201; 82.6%) and curiosity about clinical trials (117/201; 57.2%). The majority of respondents (139/197; 70.6%) reported that most people advised them against participation. Conclusion: Motivation to participate in a CHIM study was multi-factorial and heavily influenced by internal drivers beyond monetary reimbursement alone. High educational attainment and employment may be protective factors against financial inducement; however, further research is needed, particularly with CHIM studies expanding to low-income and middle-income countries