Radiation induced lichen planus - an uncommon side effect

Cutaneous lichen planus is classically characterized by violaceous, pruritic, planar papules and plaques, most commonly affecting the extremities. Lichen planus following radiation therapy is extremely rare and lichen planus following radiation therapy for prostate carcinoma has not been previously reported in the literature. We report a 66-year-old man who presented to the dermatology clinic with a symmetric pruritic eruption affecting the pelvic and gluteal region within two months of radiation therapy targeting the prostate and pelvic lymph nodes for prostate adenocarcinoma. The patient did not have a prior history of lichen planus. Physical examination demonstrated well demarcated, violaceous papules and plaques in a circumferential band-like distribution on the bilateral gluteal, lumbosacral, and pelvic region. In addition, he had a few discrete lesions on the calves and dorsal feet. Punch biopsy revealed an acanthotic epidermis with "saw-tooth" rete ridges and a lichenoid inflammatory infiltrate. A diagnosis of hypertrophic lichen planus was made, reinforcing the importance for clinicians to recognize radiation therapy as a risk factor for developing lichen planus despite no prior history of lichen planus

Magic of alpha : the chemistry of a remarkable bidentate phosphine, 1,2-bis(di-tert-butylphosphinomethyl)benzene

We thank the Fonds der Chemischen Industrie for a Kekulé Fellowship for a studentship and the Deutsche Forschungsgemeinschaft (DFG, project number 424535516) for support (J.V.). We are also very grateful to Lucite International for funding the work in St Andrews that is contained in this review.The bidentate phosphine ligand 1,2-bis(di-tert-butylphosphinomethyl)benzene (1,2-DTBPMB) has been reported over the years as being one of, if not the, best ligands for achieving the alkoxycarbonylation of various unsaturated compounds. Bonded to palladium, the ligand provides the basis for the first step in the commercial (Alpha) production of methyl methacrylate as well as very high selectivity to linear esters and acids from terminal or internal double bonds. The present review is an overview covering the literature dealing with the 1,2-DTBPMB ligand: from its first reference, its catalysis, including the alkoxycarbonylation reaction and its mechanism, its isomerization abilities including the highly selective isomerizing methoxycarbonylation, other reactions such as cross-coupling, recycling approaches, and the development of improved, modified ligands, in which some tert-butyl ligands are replaced by 2-pyridyl moieties and which show exceptional rates for carbonylation reactions at low temperatures.PostprintPeer reviewe

Impact of the Volkswagen emissions control defeat device on US public health

The US Environmental Protection Agency (EPA) has alleged that Volkswagen Group of America (VW) violated the Clean Air Act (CAA) by developing and installing emissions control system 'defeat devices' (software) in model year 2009–2015 vehicles with 2.0 litre diesel engines. VW has admitted the inclusion of defeat devices. On-road emissions testing suggests that in-use NO[subscript x] emissions for these vehicles are a factor of 10 to 40 above the EPA standard. In this paper we quantify the human health impacts and associated costs of the excess emissions. We propagate uncertainties throughout the analysis. A distribution function for excess emissions is estimated based on available in-use NO[subscript x] emissions measurements. We then use vehicle sales data and the STEP vehicle fleet model to estimate vehicle distance traveled per year for the fleet. The excess NO[subscript x] emissions are allocated on a 50 km grid using an EPA estimate of the light duty diesel vehicle NO[subscript x] emissions distribution. We apply a GEOS-Chem adjoint-based rapid air pollution exposure model to produce estimates of particulate matter and ozone exposure due to the spatially resolved excess NO[subscript x] emissions. A set of concentration-response functions is applied to estimate mortality and morbidity outcomes. Integrated over the sales period (2008–2015) we estimate that the excess emissions will cause 59 (95% CI: 10 to 150) early deaths in the US. When monetizing premature mortality using EPA-recommended data, we find a social cost of ~$450m over the sales period. For the current fleet, we estimate that a return to compliance for all affected vehicles by the end of 2016 will avert ~130 early deaths and avoid ~$840m in social costs compared to a counterfactual case without recall

Mapping In Vivo Tumor Oxygenation within Viable Tumor by 19F-MRI and Multispectral Analysis

AbstractQuantifying oxygenation in viable tumor remains a major obstacle toward a better understanding of the tumor microenvironment and improving treatment strategies. Current techniques are often complicated by tumor heterogeneity. Herein, a novel in vivo approach that combines 19F magnetic resonance imaging (19F-MRI)R1 mapping with diffusionbased multispectral (MS) analysis is introduced. This approach restricts the partial pressure of oxygen (pO2) measurements to viable tumor, the tissue of therapeutic interest. The technique exhibited sufficient sensitivity to detect a breathing gas challenge in a xenograft tumor model, and the hypoxic region measured by MS 19F-MRI was strongly correlated with histologic estimates of hypoxia. This approach was then applied to address the effects of antivascular agents on tumor oxygenation, which is a research question that is still under debate. The technique was used to monitor longitudinal pO2 changes in response to an antibody to vascular endothelial growth factor (B20.4.1.1) and a selective dual phosphoinositide 3-kinase/mammalian target of rapamycin inhibitor (GDC-0980). GDC-0980 reduced viable tumor pO2 during a 3-day treatment period, and a significant reduction was also produced by B20.4.1.1. Overall, this method provides an unprecedented view of viable tumor pO2 and contributes to a greater understanding of the effects of antivascular therapies on the tumor's microenvironment

Coherence Transition of Small Josephson Junctions Coupled to a Single-Mode Resonant Cavity: Connection to the Dicke Model

We calculate the thermodynamic properties of a collection of $N$ small Josephson junctions coupled to a single-mode resonant electromagnetic cavity, at finite temperature $T$, using several approaches. In the first approach, we include all the quantum-mechanical levels of the junction, but treat the junction-cavity interaction using a mean-field approximation developed previously for $T = 0$. In the other approaches, the junctions are treated including only the two lowest energy levels per junction, but with two different Hamiltonians. The first of these maps onto the Dicke model of quantum optics. The second is a modified Dicke model which contains an additional XY-like coupling between the junctions. The modified Dicke model can be treated using a mean-field theory, which in the limit of zero XY coupling gives the solution of the Dicke model in the thermodynamic limit using Glauber coherent states to represent the cavity. In all cases, for an $N$-independent junction-cavity coupling, there is a critical junction number $N$ above which there is a continuous transition from incoherence to coherence with decreasing $T$. If the coupling scales with $N$ so as to give a well-behaved thermodynamic limit, there is a critical minimum coupling strength for the onset of coherence. In all three models, the cavity photon occupation numbers have a non-Bose distribution when the system is coherent.Comment: 26 page

αEβ7 Integrin Identifies Subsets of Pro-Inflammatory Colonic CD4+ T Lymphocytes in Ulcerative Colitis.

Background and Aims The αEβ7 integrin is crucial for retention of T lymphocytes at mucosal surfaces through its interaction with E-cadherin. Pathogenic or protective functions of these cells during human intestinal inflammation, such as ulcerative colitis [UC], have not previously been defined, with understanding largely derived from animal model data. Defining this phenotype in human samples is important for understanding UC pathogenesis and is of translational importance for therapeutic targeting of αEβ7-E-cadherin interactions. Methods αEβ7+ and αEβ7- colonic T cell localization, inflammatory cytokine production and expression of regulatory T cell-associated markers were evaluated in cohorts of control subjects and patients with active UC by immunohistochemistry, flow cytometry and real-time PCR of FACS-purified cell populations. Results CD4+αEβ7+ T lymphocytes from both healthy controls and UC patients had lower expression of regulatory T cell-associated genes, including FOXP3, IL-10, CTLA-4 and ICOS in comparison with CD4+αEβ7- T lymphocytes. In UC, CD4+αEβ7+ lymphocytes expressed higher levels of IFNγ and TNFα in comparison with CD4+αEβ7- lymphocytes. Additionally the CD4+αEβ7+ subset was enriched for Th17 cells and the recently described Th17/Th1 subset co-expressing both IL-17A and IFNγ, both of which were found at higher frequencies in UC compared to control. Conclusion αEβ7 integrin expression on human colonic CD4+ T cells was associated with increased production of pro-inflammatory Th1, Th17 and Th17/Th1 cytokines, with reduced expression of regulatory T cell-associated markers. These data suggest colonic CD4+αEβ7+ T cells are pro-inflammatory and may play a role in UC pathobiology