Proteomic analysis of biomarkers associated with immunotherapy in murine tumour models

Emergence of proteomics and high-throughput technologies has allowed the identification of protein expression patterns of disease that potentially hold clinical importance in predictive medicine. The analysis of complex data generated by these technologies incorporates the use of computer algorithms for data mining and identification of important protein biomarkers. Such candidate biomarkers can potentially be used for diagnosis, prognosis and monitoring a variety of diseases as well as the prediction of therapy response. Mass spectrometry has been used widely, for the discovery and quantitation of disease associated biomarkers using a variety of samples such as serum and tissue. In particular, matrix assisted laser desorption/ionisation time of flight mass spectrometry (MALDI-TOF MS) has been used to generate proteomic profiles or “fingerprints” from serum to distinguish patients at different clinical stages of disease. Currently, early stage disease is difficult to diagnose in most cancers as current cancer markers have limited sensitivity and specificity. In advanced stage metastatic disease, treatment options are limited, although it is recognised that some patients may benefit from immunotherapy and in particular vaccine therapy. The use of animal models is critical to evaluate the efficacy of immunotherapies and to investigate tumour immunity in general and the mechanisms involved in tumour progression. These models provide an in vivo environment which cannot be reproduced in vitro, which results in more accurate and reliable information on the host response to immunotherapy and the mechanisms involved

Comparison of electronic versus conventional assessment methods in ophthalmology residents; a learner assessment scholarship study

Background: Assessment is a necessary part of training postgraduate medical residents. The implementation of methods located at the �shows how� level of Miller�s pyramid is believed to be more effective than previous conventional tools. In this study, we quantitatively compared electronic and conventional methods in assessing ophthalmology residents. Methods: In this retrospective study, eight different conventional methods of assessment including residents� attendance, logbook, scholarship and research skills, journal club, outpatient department participation, Multiple Choice Question (MCQ), Objective Structured Clinical Examination (OSCE), and professionalism/360-degree (as one complex) were used to assess 24 ophthalmology residents of all grades. Electronic media consisting of an online Patient Management Problem (e-PMP), and modified electronic OSCE (me-OSCE) tests performed 3 weeks later were also evaluated for each of the 24 residents. Quantitative analysis was then performed comparing the conventional and electronic assessment tools, statistically assessing the correlation between the two approaches. Results: Twenty-four ophthalmology residents of different grades were included in this study. In the electronic assessment, average e-PMP scores (48.01 ± 12.40) were much lower than me-OSCE (65.34 ± 17.11). The total average electronic score was 56.67 ± 11.28, while the total average conventional score was 80.74 ± 5.99. Female and male residents� average scores in the electronic and conventional method were (59.15 ± 12.32 versus 83.01 ± 4.95) and (55.19 ± 10.77 versus 79.38 ± 6.29), respectively. The correlation between modified electronic OSCE and all conventional methods was not statistically significant (P-value >0.05). Correlation between e-PMP and six conventional methods, consisting of professionalism/360-degree assessment tool, logbook, research skills, Multiple Choice Questions, Outpatient department participation, and Journal club active participation was statistically significant (P-value < 0.05). The overall correlation between conventional and electronic methods was significant (P-value = 0.017). Conclusion: In this study, we conclude that electronic PMP can be used alongside all conventional tools, and overall, e-assessment methods could replace currently used conventional methods. Combined electronic PMP and me-OSCE can be used as a replacement for currently used gold-standard assessment methods, including 360-degree assessment. © 2021, The Author(s)

Motion Rail: A Virtual Reality Level Crossing Training Application

This paper presents the development and usability testing of a Virtual Reality (VR) based system named 'Motion Rail' for training children on railway crossing safety. The children are to use a VR head mounted device and a controller to navigate the VR environment to perform a level crossing task and they will receive instant feedback on pass or failure on a display in the VR environment. Five participants consisting of two male and three females were considered for the usability test. The outcomes of the test was promising, as the children were very engaging and will like to adopt this training approach in future safety training

Rationalising the role of Keratin 9 as a biomarker for Alzheimer’s disease

Keratin 9 was recently identified as an important component of a biomarker panel which demonstrated a high diagnostic accuracy (87%) for Alzheimer’s disease (AD). Understanding how a protein which is predominantly expressed in palmoplantar epidermis is implicated in AD may shed new light on the mechanisms underlying the disease. Here we use immunoassays to examine blood plasma expression patterns of Keratin 9 and its relationship to other AD-associated proteins. We correlate this with the use of an in silico analysis tool VisANT to elucidate possible pathways through which the involvement of Keratin 9 may take place. We identify possible links with Dickkopf-1, a negative regulator of the wnt pathway, and propose that the abnormal expression of Keratin 9 in AD blood and cerebrospinal fluid may be a result of blood brain barrier dysregulation and disruption of the ubiquitin proteasome system. Our findings suggest that dysregulated Keratin 9 expression is a consequence of AD pathology but, as it interacts with a broad range of proteins, it may have other, as yet uncharacterized, downstream effects which could contribute to AD onset and progression

A statistical method for display and segmentation of 3D image data

A new method for visualisation and segmentation of vessel structures in 3D magnetic resonance angiography (MRA) images is presented. This method uses a simple statistical model of the information stored along parallel rays within the data set to derive a 2D projection image. Although similar to the maximum image projection (MIP) method, the new method uses a single parameter to achieve a higher contrast-to-noise ratio at a modest computational cost. The same idea is employed to provide a means of segmenting a 3D data set in order to derive a region of support for the purpose of reconstructing image sequences with high temporal resolution

MR images from fewer data

There is a strong motivation to reduce the amount of acquired data necessary to reconstruct clinically useful MR images, since less data means faster acquisition sequences, less time for the patient to remain motionless in the scanner and better time resolution for observing temporal changes within the body. We recently introduced an improvement in image quality for reconstructing parallel MR images by incorporating a data ordering step with compressed sensing (CS) in an algorithm named `PECS'.1 That method requires a prior estimate of the image to be available. We are extending the algorithm to explore ways of utilising the data ordering step without requiring a prior estimate. The method presented here first reconstructs an initial image x1 by compressed sensing (with sparsity enhanced by SVD), then derives a data ordering from x1, R01, which ranks the voxels of x1 according to their value. A second reconstruction is then performed which incorporates minimisation of the rst norm of the estimate after ordering by R01, resulting in a new reconstruction x2. Preliminary results are encouraging

Imposing spatio-temporal support in magnetic resonance angiographic imaging

A method to improve time resolution in 3D contrast-enhanced magnetic resonance angiography (CE-MRA) is proposed. A temporal basis based on prior knowledge of the contrast flow dynamics is applied to a sequence of image reconstructions. In CE-MRA a contrast agent (gadolinium) is injected into a peripheral vein and MR data is acquired as the agent arrives in the arteries and then the veins of the region of clinical interest. The acquisition extends over several minutes. Information is effectively measured in 3D k-space (spatial frequency space) one line at-atime. That line may be along a Cartesian grid line in k-space, a radial line or a spiral trajectory. A complete acquisition comprises many such lines but in order to improve temporal resolution, reconstructions are made from only partial sets of k-space data. By imposing a basis for the temporal changes, based on prior expectation of the smoothness of the changes in contrast concentration with time, it is demonstrated that a significant reduction in artifacts caused by the under-sampling of k-space can be achieved. The basis is formed from a set of gamma variate functions. Results are presented for a simulated set of 2D spiral-sampled CE-MRA data

Nikotinposer - indhold og miljøkonsekvenser

Posemateriale og indhold. Nikotinposer er typisk fremstillet af en form for semi-syntetisk cellulose (såsom viskose fleece) hvortil der er tilsat et bindemiddel i form af en (bionedbrydelig) polymer, som smelter ved opvarmning og dermed forsegler posens kanter. Indholdet i poserne består ifølge produkternes varedeklarationer af nikotin, stabilisatorer og fortykningsmidler, pH regulerende midler, fugtmidler, smagsstoffer, sødemidler og konserveringsmidler. Ifølge studier beskrevet i litteraturen er der desuden påvist indhold af formaldehyd og ammonium i nogle nikotinposer.Nikotinposer som mulig del af plastforurening. Nikotinposernes semi-syntetiske cellulose-baserede materiale har FTIR-spektre som er sammenlignelige med vådservietter, engangskarklude og cigaretfiltre, som består af henholdsvis viskose og celluloseacetat. Den største grad af lighed mellem spektre blev observeret for cigaretfiltre. På trods af, at cellulose er et naturligt og forholdsvis nedbrydeligt materiale, så vil modifikationer af denne grad påvirke materialets egenskaber og miljøskæbne herunder nedbrydelighed. Af samme grund kan nikotinposer, ligesom cigaretfiltre, potentielt anses som værende en form for semi-syntetisk polymer og dermed ’plast’. Dog er der en flydende overgang fra naturlige til syntetiske polymerer, hvilket udfordrer en entydig kategorisering af forskellige semi-syntetiske materialer, herunder brugte nikotinposer, som værende plastaffald. Nikotinposers miljøskæbne under miljørelevante forhold bør undersøges yderligere og bortskaffelse i naturen bør uanset minimeres.Risiko for mennesker og miljø. Generelle helbredsrisici ved påtænkt brug af nikotinposer indgår ikke i denne rapport, men referencer til relevante kilder fremgår af teksten. I stedet diskuteres potentielle effekter i miljøet. Nikotinposer udgør en potentiel risiko for dyr ved indtagelse. Der findes eksempler på nikotinforgiftning af hunde som har ædt henkastede brugte nikotinposer. Grundet forventet langsom nedbrydning under miljørealistiske forhold kan der over tid ske en akkumulering af nikotinposer i miljøet. Langsigtede konsekvenser af dette, samt risiko for nikotinforgiftning af dyr i naturen, bør undersøges nærmere.Nikotinposer i kontekst af genanvendelse og cirkulær økonomi. Bortskaffelse af tomme nikotinpose dåser med brugte nikotinposer udgør et potentielt problem i forhold til genanvendelse. Dåsen er ofte fremstillet af polypropylen og kan genanvendes. Dog skal de brugte nikotinposer, som opsamles i låget, bortskaffes separat. Dvs. at dåserne skal tømmes inden de sorteres som plastaffald. Det er dog plausibelt at dette ikke altid sker, og at 1) dåserne ikke tømmes inden de sorteres som plastaffald eller 2) dåserne bortskaffes i restaffald. Forbrugsvaner i forhold til bortskaffelse bør undersøges nærmere og behovet for yderligere oplysning af forbrugere kan overvejes på denne baggrund.Fremtidige undersøgelser. Henkastede nikotinposer er et stigende problem grundet stigende forbrug kombineret med uhensigtsmæssig forbrugeradfærd. På trods af at de fleste nikotinposer bliver opsamlet og bortskaffet korrekt, ender en fraktion stadig i miljøet. Fremtidige undersøgelser af brugen af nikotinposer blandt den danske befolkning kan med fordel inkludere spørgsmål om adfærd i forhold til bortskaffelse, for på denne måde at få et estimat af omfanget af henkastede nikotinposer i naturen og i det offentlige rum. Dette kan også give et forbedret grundlag for vurdering af eventuelle miljøkonsekvenser – både af posemateriale men også posernes indhold herunder nikotin