An investigation of the Eigenvalue Calibration Method (ECM) using GASP for non-imaging and imaging detectors

Polarised light from astronomical targets can yield a wealth of information about their source radiation mechanisms, and about the geometry of the scattered light regions. Optical observations, of both the linear and circular polarisation components, have been impeded due to non-optimised instrumentation. The need for suitable observing conditions and the availability of luminous targets are also limiting factors. GASP uses division of amplitude polarimeter (DOAP) (Compain and Drevillon) to measure the four components of the Stokes vector simultaneously, which eliminates the constraints placed upon the need for moving parts during observation, and offers a real-time complete measurement of polarisation. Results from the GASP calibration are presented in this work for both a 1D detector system, and a pixel-by-pixel analysis on a 2D detector system. Following Compain et al. we use the Eigenvalue Calibration Method (ECM) to measure the polarimetric limitations of the instrument for each of the two systems. Consequently, the ECM is able to compensate for systematic errors introduced by the calibration optics, and it also accounts for all optical elements of the polarimeter in the output. Initial laboratory results of the ECM are presented, using APD detectors, where errors of 0.2% and 0.1{\deg} were measured for the degree of linear polarisation and polarisation angle respectively. Channel-to-channel image registration is an important aspect of 2-D polarimetry. We present our calibration results of the measured Mueller matrix of each sample, used by the ECM. A set of Zenith flat-field images were recorded during an observing campaign at the Palomar 200 inch telescope in November 2012. From these we show the polarimetric errors from the spatial polarimetry indicating both the stability and absolute accuracy of GASP.Comment: Accepted for publication in Experimental Astronom

CATHEDRAL: A Fast and Effective Algorithm to Predict Folds and Domain Boundaries from Multidomain Protein Structures

We present CATHEDRAL, an iterative protocol for determining the location of previously observed protein folds in novel multidomain protein structures. CATHEDRAL builds on the features of a fast secondary-structure–based method (using graph theory) to locate known folds within a multidomain context and a residue-based, double-dynamic programming algorithm, which is used to align members of the target fold groups against the query protein structure to identify the closest relative and assign domain boundaries. To increase the fidelity of the assignments, a support vector machine is used to provide an optimal scoring scheme. Once a domain is verified, it is excised, and the search protocol is repeated in an iterative fashion until all recognisable domains have been identified. We have performed an initial benchmark of CATHEDRAL against other publicly available structure comparison methods using a consensus dataset of domains derived from the CATH and SCOP domain classifications. CATHEDRAL shows superior performance in fold recognition and alignment accuracy when compared with many equivalent methods. If a novel multidomain structure contains a known fold, CATHEDRAL will locate it in 90% of cases, with <1% false positives. For nearly 80% of assigned domains in a manually validated test set, the boundaries were correctly delineated within a tolerance of ten residues. For the remaining cases, previously classified domains were very remotely related to the query chain so that embellishments to the core of the fold caused significant differences in domain sizes and manual refinement of the boundaries was necessary. To put this performance in context, a well-established sequence method based on hidden Markov models was only able to detect 65% of domains, with 33% of the subsequent boundaries assigned within ten residues. Since, on average, 50% of newly determined protein structures contain more than one domain unit, and typically 90% or more of these domains are already classified in CATH, CATHEDRAL will considerably facilitate the automation of protein structure classification

Mechanical suppression of osteolytic bone metastases in advanced breast cancer patients: A randomised controlled study protocol evaluating safety, feasibility and preliminary efficacy of exercise as a targeted medicine

Background: Skeletal metastases present a major challenge for clinicians, representing an advanced and typically incurable stage of cancer. Bone is also the most common location for metastatic breast carcinoma, with skeletal lesions identified in over 80% of patients with advanced breast cancer. Preclinical models have demonstrated the ability of mechanical stimulation to suppress tumour formation and promote skeletal preservation at bone sites with osteolytic lesions, generating modulatory interference of tumour-driven bone remodelling. Preclinical studies have also demonstrated anti-cancer effects through exercise by minimising tumour hypoxia, normalising tumour vasculature and increasing tumoural blood perfusion. This study proposes to explore the promising role of targeted exercise to suppress tumour growth while concomitantly delivering broader health benefits in patients with advanced breast cancer with osteolytic bone metastases. Methods: This single-blinded, two-armed, randomised and controlled pilot study aims to establish the safety, feasibility and efficacy of an individually tailored, modular multi-modal exercise programme incorporating spinal isometric training (targeted muscle contraction) in 40 women with advanced breast cancer and stable osteolytic spinal metastases. Participants will be randomly assigned to exercise or usual medical care. The intervention arm will receive a 3-month clinically supervised exercise programme, which if proven to be safe and efficacious will be offered to the control-arm patients following study completion. Primary endpoints (programme feasibility, safety, tolerance and adherence) and secondary endpoints (tumour morphology, serum tumour biomarkers, bone metabolism, inflammation, anthropometry, body composition, bone pain, physical function and patient-reported outcomes) will be measured at baseline and following the intervention. Discussion: Exercise medicine may positively alter tumour biology through numerous mechanical and nonmechanical mechanisms. This randomised controlled pilot trial will explore the preliminary effects of targeted exercise on tumour morphology and circulating metastatic tumour biomarkers using an osteolytic skeletal metastases model in patients with breast cancer. The study is principally aimed at establishing feasibility and safety. If proven to be safe and feasible, results from this study could have important implications for the delivery of this exercise programme to patients with advanced cancer and sclerotic skeletal metastases or with skeletal lesions present in haematological cancers (such as osteolytic lesions in multiple myeloma), for which future research is recommended. Trial registration: anzctr.org.au, ACTRN-12616001368426. Registered on 4 October 2016

An analysis of the prevalence of children with disabilities and disabling chronic illnesses in the Western health sub-district of Cape Town, and the services available for them

Children with disabling chronic illnesses are known to have complex and frequently unmet health care needs. Limited information exists in South Africa regarding the prevalence of children with disability, as well their needs and utilization of services. The purpose of the current study is twofold: (1) identify the number of children known with disability, or disabling chronic illnesses in the western health sub-district of Cape Town; (2) analyse the health services that currently exist for these children. A period prevalence survey was conducted between January 2010 and December 2011. Numerous sources of information were sought to identify as many children with disabling chronic illness as possible. These included the referral hospitals for the Western sub-district, namely Red Cross War Memorial Children's Hospital and New Somerset Hospital, as well as the institutions where children with disability are cared for or educated, and relevant non-profit organisations in the disability sector. Information was gathered between January 2011 and Sept 2012

Student attitudes to, and achievement, in an innovative and authentic biotechnology assessment based on a ‘consultancy Response to Tender’

In recent years, there has been a significant reappraisal of assessment in HE, with increased attention towards authentic assessments, which are defined as those that are ‘authentic or work relevant’, or that ‘change the nature of student engagement or participation’. This paper investigates the design, implementation, and evaluation of an undergraduate unit based around an authentic assessment – the delivery of which was atypical to previous student experience. The unit had a modular structure with three separate mini-projects, each student writing up one for the consultancy style ‘Response to Tender’ assessment. Quantitative data were analysed for in-person attendance, online engagement, and assessment mark, while student attitudes towards the assessment were collected via questionnaires. Students reported high satisfaction, appreciated the real-world applicability, and identified the unit as providing useful skills for the future, including employability. They appreciated the active learning approach employed, stating that the design and approach of the unit encouraged attendance. The evidence provided here shows that the adoption of authentic assessment approaches, with assessments clearly linked to real-world applicability, can lead to high student satisfaction and engagement, and a positive student and staff experience

Association of computed tomography measures of muscle and adipose tissue and progressive changes throughout treatment with clinical endpoints in patients with advanced lung cancer treated with immune checkpoint inhibitors

To investigate the association between skeletal muscle mass and adiposity measures with disease-free progression (DFS) and overall survival (OS) in patients with advanced lung cancer receiving immunotherapy, we retrospectively analysed 97 patients (age: 67.5 ± 10.2 years) with lung cancer who were treated with immunotherapy between March 2014 and June 2019. From computed tomography scans, we assessed the radiological measures of skeletal muscle mass, and intramuscular, subcutaneous and visceral adipose tissue at the third lumbar vertebra. Patients were divided into two groups based on specific or median values at baseline and changes throughout treatment. A total number of 96 patients (99.0 %) had disease progression (median of 11.3 months) and died (median of 15.4 months) during follow-up. Increases of 10 % in intramuscular adipose tissue were significantly associated with DFS (HR: 0.60, 95 % CI: 0.38 to 0.95) and OS (HR: 0.60, 95 % CI: 0.37 to 0.95), while increases of 10 % in subcutaneous adipose tissue were associated with DFS (HR: 0.59, 95 % CI: 0.36 to 0.95). These results indicate that, although muscle mass and visceral adipose tissue were not associated with DFS or OS, changes in intramuscular and subcutaneous adipose tissue can predict immunotherapy clinical outcomes in patients with advanced lung cancer

Enhancing circulatory myokines and extracellular vesicle uptake with targeted exercise in patients with prostate cancer (the MYEX trial): A single-group crossover study

Introduction: Physical activity is associated with improved disease progression and cancer-specific survival in patients with prostate cancer (PCa). However, the mechanisms underlying these associations remain unclear, while the relative impact of exercise modes is unknown. This study aims to examine the differential impact of exercise mode on tumour-suppressive skeletal muscle-associated systemic molecules as well as their delivery mechanism. This study will compare the effects of the two main exercise modes, aerobic and resistance, on (1) circulatory myokine levels, (2) skeletal muscle-induced extracellular vesicle abundance and cargo contents, and (3) uptake of extracellular vesicles (EVs) in PCa cells in patients with localised or advanced PCa. Methods: A single-group cross-over design will be used for patients at opposite ends of the disease spectrum. A total of 32 patients (localised PCa, n = 16; metastatic castrate-resistant PCa, n = 16) will be recruited while capitalising on two ongoing studies. Ethics amendment has been approved for two ongoing trials to share data, implement the acute exercise sessions, and collect additional blood samples from patients. The patients will undertake two exercise sessions (aerobic only and resistance only) in random order one week apart. Blood will be collected before, after, and 30 min post-exercise. Circulating/EV-contained myokine levels (irisin, IL-6, IL-15, FGF-21, and SPARC) and plasma skeletal muscle-induced EVs will be measured using ELISA and flow cytometry. PCa cell line growth with or without collected plasma will be examined using PCa cell lines (LNCaP, DU-145, and PC-3), while evaluating cellular uptake of EVs. Ethics amendments have been approved for two capitalising studies to share data, implement acute exercise sessions and collect additional samples from the patients. Discussion: If findings show a differential impact of exercise mode on the establishment of an anti-cancer systemic environment, this will provide fundamental knowledge for developing targeted exercise prescriptions for patients with PCa across different disease stages. Findings will be reported in peer-reviewed publications and scientific conferences, in addition to working with national support groups to translate findings for the broader community. Trial registration: The registration for the two capitalising studies are NCT02730338 and ACTRN12618000225213

Posterior Malleolar Ankle Fractures: An Effort at Improving Outcomes.

BackgroundThere is increasing acceptance that the clinical outcomes following posterior malleolar fractures are less than satisfactory. We report our results of posterior malleolar fracture management based on the classification by Mason and Molloy.MethodsAll fractures were classified on the basis of computed tomographic (CT) scans obtained preoperatively. This dictated the treatment algorithm. Type-1 fractures underwent syndesmotic fixation. Type-2A fractures underwent open reduction and internal fixation through a posterolateral incision, type-2B fractures underwent open reduction and internal fixation through either a posteromedial incision or a combination of a posterolateral with a medial-posteromedial incision, and type-3 fractures underwent open reduction and internal fixation through a posteromedial incision.ResultsPatient-related outcome measures were obtained in 50 patients with at least 1-year follow-up. According to the Mason and Molloy classification, there were 17 type-1 fractures, 12 type-2A fractures, 10 type-2B fractures, and 11 type-3 fractures. The mean Olerud-Molander Ankle Score was 75.9 points (95% confidence interval [CI], 66.4 to 85.3 points) for patients with type-1 fractures, 75.0 points (95% CI, 61.5 to 88.5 points) for patients with type-2A fractures, 74.0 points (95% CI, 64.2 to 83.8 points) for patients with type-2B fractures, and 70.5 points (95% CI, 59.0 to 81.9 points) for patients with type-3 fractures.ConclusionsWe have been able to demonstrate an improvement in the Olerud-Molander Ankle Score for all posterior malleolar fractures with the treatment algorithm applied using the Mason and Molloy classification. Mason classification type-3 fractures have marginally poorer outcomes, which correlates with a more severe injury; however, this did not reach significance.Level of evidenceTherapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence