18F-FDG PET/CT assessment of histopathologically confirmed mediastinal lymph nodes in non-small cell lung cancer using a penalised likelihood reconstruction

Purpose To investigate whether using a Bayesian penalised likelihood reconstruction (BPL) improves signal-to-background (SBR), signal-to-noise (SNR) and SUVmax when evaluating mediastinal nodal disease in non-small cell lung cancer (NSCLC) compared to ordered subset expectation maximum (OSEM) reconstruction. Materials and methods 18F-FDG PET/CT scans for NSCLC staging in 47 patients (112 nodal stations with histopathological confirmation) were reconstructed using BPL and compared to OSEM. Node and multiple background SUV parameters were analysed semi-quantitatively and visually. Results Comparing BPL to OSEM, there were significant increases in SUVmax (mean 3.2–4.0, p<0.0001), SBR (mean 2.2–2.6, p<0.0001) and SNR (mean 27.7–40.9, p<0.0001). Mean background SNR on OSEM was 10.4 (range 7.6–14.0), increasing to 12.4 (range 8.2–16.7, p<0.0001). Changes in background SUVs were minimal (largest mean difference 0.17 for liver SUVmean, p<0.001). There was no significant difference between either algorithm on receiver operating characteristic analysis (p=0.26), although on visual analysis, there was an increase in sensitivity and small decrease in specificity and accuracy on BPL. Conclusion BPL increases SBR, SNR and SUVmax of mediastinal nodes in NSCLC compared to OSEM, but did not improve the accuracy for determining nodal involvement

Prostate Stereotactic Ablative Radiation Therapy Using Volumetric Modulated Arc Therapy to Dominant Intraprostatic Lesions

PurposeTo investigate boosting dominant intraprostatic lesions (DILs) in the context of stereotactic ablative radiation therapy (SABR) and to examine the impact on tumor control probability (TCP) and normal tissue complication probability (NTCP).Methods and MaterialsTen prostate datasets were selected. DILs were defined using T2-weighted, dynamic contrast-enhanced and diffusion-weighted magnetic resonance imaging. Four plans were produced for each dataset: (1) no boost to DILs; (2) boost to DILs, no seminal vesicles in prescription; (3) boost to DILs, proximal seminal vesicles (proxSV) prescribed intermediate dose; and (4) boost to DILs, proxSV prescribed higher dose. The prostate planning target volume (PTV) prescription was 42.7 Gy in 7 fractions. DILs were initially prescribed 115% of the PTVProstate prescription, and PTVDIL prescriptions were increased in 5% increments until organ-at-risk constraints were reached. TCP and NTCP calculations used the LQ-Poisson Marsden, and Lyman-Kutcher-Burman models respectively.ResultsWhen treating the prostate alone, the median PTVDIL prescription was 125% (range: 110%-140%) of the PTVProstate prescription. Median PTVDIL D50% was 55.1 Gy (range: 49.6-62.6 Gy). The same PTVDIL prescriptions and similar PTVDIL median doses were possible when including the proxSV within the prescription. TCP depended on prostate α/β ratio and was highest with an α/β ratio = 1.5 Gy, where the additional TCP benefit of DIL boosting was least. Rectal NTCP increased with DIL boosting and was considered unacceptably high in 5 cases, which, when replanned with an emphasis on reducing maximum dose to 0.5 cm3 of rectum (Dmax0.5cc), as well as meeting existing constraints, resulted in considerable rectal NTCP reductions.ConclusionsBoosting DILs in the context of SABR is technically feasible but should be approached with caution. If this therapy is adopted, strict rectal constraints are required including Dmax0.5cc. If the α/β ratio of prostate cancer is 1.5 Gy or less, then high TCP and low NTCP can be achieved by prescribing SABR to the whole prostate, without the need for DIL boosting

Developing a class solution for Prostate Stereotactic Ablative Body Radiotherapy (SABR) using Volumetric Modulated Arc Therapy (VMAT)

Background and purpose To develop a class solution for prostate Stereotactic Ablative Radiotherapy (SABR) using Volumetric Modulated Arc Therapy (VMAT). Materials and methods Seven datasets were used to compare plans using one 360° arc (1FA), one 210° arc (1PA), two full arcs and two partial arcs. Subsequently using 1PA, fifteen datasets were compared using (i) 6 mm CTV–PTV margins, (ii) 8 mm CTV–PTV margins and (iii) including the proximal SV within the CTV. Monaco™ 3.2 (Elekta™) was used for planning with the Agility™ MLC system (Elekta™). Results Highly conformal plans were produced using all four arc arrangements. Compared to 1FA, 1PA resulted in significantly reduced rectal doses, and monitor units and estimated delivery times were reduced in six of seven cases. Using 6 mm CTV–PTV margins, planning constraints were met for all fifteen datasets. Using 8 mm margins required relaxation of the uppermost bladder constraint in three cases to achieve adequate coverage, and, compared to 6 mm margins, rectal and bladder doses significantly increased. Including the proximal SV required relaxation of the uppermost bladder and rectal constraints in two cases, and rectal and bladder doses significantly increased. Conclusions Prostate SABR VMAT is optimal using 1PA. 6 mm CTV–PTV margins, compatible with daily fiducial-based IGRT, are consistently feasible in terms of target objectives and OAR constraints

A three-season comparison of match performances among selected and unselected elite youth rugby league players

This is an author's accepted manuscript of an article published in Journal of Sports Sciences, 28 February 2014, available online: http:www.tandfonline.com/10.1080/02640414.2014.889838This study compared technical actions, movements, heart rates and perceptual responses of selected and unselected youth rugby league players during matches (under-15 to under-17). The players’ movements and heart rates were assessed using 5 Hz Global Positioning Systems (GPS), while their technical actions were analysed using video analysis. The maturity of each player was predicted before each season for statistical control. There were no differences (P > 0.05) between selected and unselected players in the under-15 or the under-17 age groups for any variables. However, in the under-16 group, the selected players (57.1 ± 11.9 min) played for longer than the unselected players (44.1 ± 12.3 min; P = 0.017; ES = 1.08 ± CI = 0.87), and covered more distance (5,181.0 ± 1063.5 m cf. 3942.6 ± 1,108.6m, respectively; P = 0.012; ES = 1.14 ± CI = 0.88) and high intensity distance (1,808.8 ± 369.3 m cf. 1,380.5 ± 367.7 m, respectively; P = 0.011; ES = 1.16 ± CI = 0.88). Although successful carries per minute was higher in the selected under-15 group, there were no other differences (P > 0.05) in match performance relative to playing minutes between groups. Controlling for maturity, the less mature, unselected players from the under-16 group performed more high-intensity running (P < 0.05). Our findings question the use of match- related measurements in differentiating between selected and unselected players, showing that later maturing players were unselected, even when performing greater high-intensity running during matches

Re-evaluating pretomanid analogues for Chagas disease:Hit-to-lead studies reveal both in vitro and in vivo trypanocidal efficacy

Phenotypic screening of a 900 compound library of antitubercular nitroimidazole derivatives related to pretomanid against the protozoan parasite Trypanosoma cruzi (the causative agent for Chagas disease) identified several structurally diverse hits with an unknown mode of action. Following initial profiling, a first proof-of-concept in vivo study was undertaken, in which once daily oral dosing of a 7-substituted 2-nitroimidazooxazine analogue suppressed blood parasitemia to low or undetectable levels, although sterile cure was not achieved. Limited hit expansion studies alongside counter-screening of new compounds targeted at visceral leishmaniasis laid the foundation for a more in-depth assessment of the best leads, focusing on both drug-like attributes (solubility, metabolic stability and safety) and maximal killing of the parasite in a shorter timeframe. Comparative appraisal of one preferred lead (58) in a chronic infection mouse model, monitored by highly sensitive bioluminescence imaging, provided the first definitive evidence of (partial) curative efficacy with this promising nitroimidazooxazine class

HMDB: the Human Metabolome Database

The Human Metabolome Database (HMDB) is currently the most complete and comprehensive curated collection of human metabolite and human metabolism data in the world. It contains records for more than 2180 endogenous metabolites with information gathered from thousands of books, journal articles and electronic databases. In addition to its comprehensive literature-derived data, the HMDB also contains an extensive collection of experimental metabolite concentration data compiled from hundreds of mass spectra (MS) and Nuclear Magnetic resonance (NMR) metabolomic analyses performed on urine, blood and cerebrospinal fluid samples. This is further supplemented with thousands of NMR and MS spectra collected on purified, reference metabolites. Each metabolite entry in the HMDB contains an average of 90 separate data fields including a comprehensive compound description, names and synonyms, structural information, physico-chemical data, reference NMR and MS spectra, biofluid concentrations, disease associations, pathway information, enzyme data, gene sequence data, SNP and mutation data as well as extensive links to images, references and other public databases. Extensive searching, relational querying and data browsing tools are also provided. The HMDB is designed to address the broad needs of biochemists, clinical chemists, physicians, medical geneticists, nutritionists and members of the metabolomics community. The HMDB is available at

From problems in the North to the problematic North : Northern devolution through the lens of history

Current debates about Northern English cities and their role in national economic strategies cannot be read simply through the lens of contemporary politics. We therefore take the Northern Powerhouse as our starting point in a chapter which traces a long history of policy and planning discourses about the North of England. We use David Russell’s chronology of key historical moments in which Northern English cities hold a particular charge in cultural narratives of the nation to guide our analysis of contemporaneous tensions in debates about planning and governance. A focus on representations about the North of England over the course of the last two centuries reveals four interlocking themes: namely the role of London in directing debates about the North; a tension between political and spatial approaches to planning; the characterisation of cities in the North of England as intrinsically problematic places; and the continued issue of poverty in these cities

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy