What does "Advanced" mean in 2023? reflecting on 10 years of the ESTRO advanced Skills in modern radiotherapy course.

The roles and responsibilities of radiation therapists (RTTs) are many and varied. Professional expectations are influenced by the technology available, as well as the level of autonomy RTTs have in their daily practice. This professional range requires RTTs to possess a unique set of ever evolving skills, posing challenges from an educational perspective. Teaching these "advanced skills" has been the ambition the ESTRO Advanced Skills in Modern Radiotherapy course. In the 10th year of this course, the Faculty look back and reflect on how our programme has evolved and what it has achieved.

Influence of inter-observer delineation variability on radiomic features of the parotid gland.

PURPOSE: This study aimed to quantify the variability in the values of radiomic features extracted from a right parotid gland (RPG) delineated by a series of independent observers. METHODS: This was a secondary analysis of anonymous data from a delineation workshop. Inter-observer variability of the RPG from 40 participants was quantified using DICE similarity coefficient (DSC) and Hausdorff distance (HD). An additional contour was generated using Varian SmartSegmentation. Radiomic features extracted include four shape features, six histogram features, and 32 texture features. The absolute mean paired percentage difference (PPD) in feature values from the expert and participants were ranked . Feature robustness was classified using pre- determined thresholds. RESULTS: 63% of participants achieved a DSC > 0.7, the auto- segmentation DSC was 0.76. The average HD for the participants was 16.16 mm ± 0.66 mm, and 15.16 mm for the auto-segmentation. 48% (n = 20) and 33% (n = 14) of features were deemed to be robust with a mean absolute PPD < 5%, for the auto-segmentation and manual delineations respectively; the majority of which were from the grey-run length matrix family. 7% (n = 3) of features from the auto- segmentation and 10% (n = 4) from the manual contours were deemed to be unstable with a mean absolute PPD > 50%. The value of the most robust feature was not related to DSC and HD. CONCLUSION: Inter-observer delineation variability affects the value of the radiomic features extracted from the RPG. This study identifies the radiomic features least sensitive to these uncertainties. Further investigation of the clinical relevance of these features in prediction of xerostomia is warranted.

The Pivotal Role of the Therapeutic Radiographer/Radiation Therapist in Image-guided Radiotherapy Research and Development.

The ability to personalise radiotherapy to fit the individual patient and their diagnosis has been realised through technological advancements. There is now more opportunity to utilise these technologies and deliver precision radiotherapy for more patients. Image-guided radiotherapy (IGRT) has enabled users to safely and accurately plan, treat and verify complex cases; and deliver a high dose to the target volume, while minimising dose to normal tissue. Rapid changes in IGRT have required a multidisciplinary team (MDT) approach, carefully deciding optimum protocols to achieve clinical benefit. Therapeutic radiographer/radiation therapists (RTTs) play a pivotal role in this MDT. There is already a great deal of evidence that illustrates the contribution of RTTs in IGRT development; implementation; quality assurance; and maintaining training and competency programmes. Often this has required the RTT to undertake additional roles and responsibilities. These publications show how the profession has evolved, expanding the scope of practice. There are now more opportunities for RTT-led IGRT research. This is not only undertaken in the more traditional aspects of practice, but in recent times, more RTTs are becoming involved in imaging biomarkers research and radiomic analysis. The aim of this overview is to describe the RTT contribution to the ongoing development of IGRT and to showcase some of the profession's involvement in IGRT research.

Avatrombopag increases platelet count but not platelet activation in patients with thrombocytopenia resulting from liver disease.

Essentials Thrombopoietin (TPO) lowers the threshold for platelet activation. TPO receptor agonists (RAs) may therefore also lead to platelet activation. Patients with chronic liver disease and thrombocytopenia participated in a randomized trial. The TPO-RA avatrombopag did not increase platelet activation in vivo or reactivity in vitro. BACKGROUND: The thrombopoietin (TPO) receptor agonist (TPO-RA) avatrombopag has recently been Food and Drug Administration-approved for the treatment of thrombocytopenia in patients with chronic liver disease (CLD) scheduled for a procedure. The TPO receptor c-mpl is expressed on the platelet surface, and TPO lowers the threshold for platelet activation. TPO-RAs may therefore also lead to platelet activation. OBJECTIVES: To evaluate the effects of avatrombopag on platelet activation. PATIENTS/METHODS: CLD patients with thrombocytopenia participated in a randomized, double-blind, placebo-controlled, parallel-group study. No patient received a platelet transfusion within 10 days of study blood draws. Platelet activation was evaluated with whole blood flow cytometry (which, unlike other methods, is accurate in thrombocytopenic samples). RESULTS: Avatrombopag, but not placebo, increased platelet counts. As measured by platelet surface P-selectin and activated glycoprotein IIb-IIIa: (i) the numbers of circulating activated platelets were not increased in avatrombopag-treated patients as compared with placebo-treated patients; and (ii) platelet reactivity to low and high concentrations of ADP and thrombin receptor-activating peptide was not increased in avatrombopag-treated patients as compared with placebo-treated patients. CONCLUSIONS: In this randomized, double-blind, placebo-controlled, parallel-group study of CLD patients with thrombocytopenia, avatrombopag increased platelet counts but did not increase platelet activation in vivo or platelet reactivity in vitro.

Platelet Function in ITP, Independent of Platelet Count, Is Consistent Over Time and Is Associated with Both Current and Subsequent Bleeding Severity.

BACKGROUND: Treatment decisions for patients with immune thrombocytopenia (ITP) are difficult because patients with similarly low platelet counts differ in their bleeding tendency. We recently reported that platelet function tests, independent of platelet count, are associated with concurrent bleeding severity, suggesting that these tests may be useful indicators of future bleeding in ITP. OBJECTIVES: To test this hypothesis, we evaluated the consistency of these platelet function tests over time and their association with subsequent bleeding severity. METHODS: Bleeding score and platelet biomarkers were evaluated in a cross-sectional study of children with ITP at two visits separated by a median of 10 months. RESULTS AND CONCLUSIONS: Correlations between Visit 1 and Visit 2 results for immature platelet fraction, circulating and agonist-stimulated platelet surface P-selectin, and activated GPIIb-IIIa and GPIbα indicated consistency of the platelet phenotype over time. Consistent with our previous findings, platelet biomarkers at each visit were significantly associated with the concurrent bleeding score. Furthermore, increased P-selectin on circulating platelets and reduced agonist-stimulated P-selectin and activated GPIIb-IIIa-positive platelets at Visit 1 were significantly associated with bleeding scores at Visit 2 and remained significantly associated with bleeding severity after adjustment for platelet count. These results suggest a mechanistic link between desensitization of agonist receptors and increased bleeding severity. In summary, platelet function in ITP, independent of platelet count, is consistent over time and is associated with both concurrent and subsequent bleeding severity. These findings support further evaluation of platelet function testing to help guide patient management in ITP.

Early-stage development of novel cyclodextrin-siRNA nanocomplexes allows for successful postnebulization transfection of bronchial epithelial cells.

BACKGROUND: Successful delivery of small interfering RNA (siRNA) to the lungs remains hampered by poor intracellular delivery, vector-mediated cytotoxicity, and an inability to withstand nebulization. Recently, a novel cyclodextrin (CD), SC12CDClickpropylamine, consisting of distinct lipophilic and cationic subunits, has been shown to transfect a number of cell types. However, the suitability of this vector for pulmonary siRNA delivery has not been assessed to date. To address this, a series of high-content analysis (HCA) and postnebulization assays were devised to determine the potential for CD-siRNA delivery to the lungs. METHODS: SC12CDClickpropylamine-siRNA mass ratios (MRs) were examined for size and zeta potential. In-depth analysis of nanocomplex uptake and toxicity in Calu-3 bronchial epithelial cells was examined using IN Cell(®) HCA assays. Nebulized SC12CDClickpropylamine nanocomplexes were assessed for volumetric median diameter (VMD) and fine particle fraction (FPF) and compared with saline controls. Finally, postnebulization stability was determined by comparing luciferase knockdown elicited by SC12CDClickpropylamine nanocomplexes before and after nebulization. RESULTS: SC12CDClickpropylamine-siRNA complexation formed cationic nanocomplexes of ≤200 nm in size depending on the medium and led to significantly higher levels of siRNA associated with Calu-3 cells compared with RNAiFect-siRNA-treated cells at all MRs (p<0.001, n=3×4), with evidence of toxicity only at MRs 50-100. Nebulization of SC12CDClickpropylamine nanocomplexes using the Aeroneb(®) Pro resulted in VMDs of ∼4 µm and FPFs of ∼57% at all MRs. SC12CDClickpropylamine-siRNA-mediated luciferase knockdown was found to be 39.8±3.6% at MR=20 before and 35.6±4.55% after nebulization, comparable to results observed using unnebulized commercial transfection reagent, RNAiFect. CONCLUSIONS: SC12CDClickpropylamine nanocomplexes can be effectively nebulized for pulmonary delivery of siRNA using Aeroneb technology to mediate knockdown in airway cells. To the best of our knowledge, this is the first study examining the suitability of SC12CDClickpropylamine-siRNA nanocomplexes for pulmonary delivery. Furthermore, this work provides an integrated nanomedicine-device combination for future in vitro and in vivo preclinical and clinical studies of inhaled siRNA therapeutics.

The eyes have it: an exploration of eye movements in action disorganisation syndrome.

We examined eye movements in a patient, FK, who has action disorganisation syndrome (ADS), as he performed the everyday task of making a cup of tea. We compared his eye movements with those of a person with Alzheimer's disease and with healthy volunteers. Despite showing very disorganised behaviour many aspects of FK's eye movements were relatively normal. However, unlike normal participants FK made no advance glances to objects that were about to be used, and he made increased numbers of fixations to irrelevant objects during the task. There were also differences in the durations of his eye movements during correct actions and during his perseverative and task-addition responses. We discuss the implications for understanding ADS and the cognitive processes required for correctly performing everyday tasks.

Medical students' attitudes towards abortion: a UK study.

BACKGROUND: There is little research into medical students' or doctors' attitudes to abortion, yet knowing this is important, as policy makers should be aware of the views held by professionals directly involved in abortion provision and changing views may have practical implications for the provision of abortion in the future. METHODS: We surveyed 300 medical students about their views on abortion, their beliefs about the status of the fetus and the rights of the mother, their attitude towards UK law and their willingness to be involved in abortion provision as qualified doctors. RESULTS: 62% of medical students were pro-choice, 33% pro-life and 7% undecided. Students' views correlated with gender, year of study and holding a religious belief. Their beliefs about abortion, the status of the fetus and the rights of women significantly correlated with their attitudes towards the UK law and their willingness to be involved in abortion provision. Students' willingness to be involved in abortion provision was related to their views on abortion, the extent of participation required, the circumstances of the pregnancy and the stage of pregnancy. CONCLUSIONS: The percentage of pro-choice students was lower than that found in research on general practitioners' attitudes to abortion. It is unclear whether this is because students become more pro-choice as they progress through their medical career or because there is genuinely a change in attitudes to abortion.

Hierarchies, similarity, and interactivity in object recognition: "category-specific" neuropsychological deficits.

Category-specific impairments of object recognition and naming are among the most intriguing disorders in neuropsychology, affecting the retrieval of knowledge about either living or nonliving things. They can give us insight into the nature of our representations of objects: Have we evolved different neural systems for recognizing different categories of object? What kinds of knowledge are important for recognizing particular objects? How does visual similarity within a category influence object recognition and representation? What is the nature of our semantic knowledge about different objects? We review the evidence on category-specific impairments, arguing that deficits even for one class of object (e.g., living things) cannot be accounted for in terms of a single information processing disorder across all patients; problems arise at contrasting loci in different patients. The same apparent pattern of impairment can be produced by damage to different loci. According to a new processing framework for object recognition and naming, the hierarchical interactive theory (HIT), we have a hierarchy of highly interactive stored representations. HIT explains the variety of patients in terms of (1) lesions at different levels of processing and (2) different forms of stored knowledge used both for particular tasks and for particular categories of object.

The role of semantic knowledge and working memory in everyday tasks.

We present a single case study of a patient, HG, who was severely impaired on routine everyday tasks, such as cleaning his teeth and preparing a cup of tea. We used the Action Coding System developed by Schwartz et al. (1991) to provide quantitative and qualitative measures of his performance in a number of experimental manipulations: (a) with task-congruent objects only, (b) with task-congruent objects and semantic distractors, (c) with a set of written commands to follow, (d) when he was given one command at a time, (e) when he was shown how the task should be performed before starting himself, and (f) when the task was divided into smaller subgoals. In general, the majority of HG's errors were step omissions, perseverations, sequence errors, and semantic errors. These semantic errors are particularly interesting since HG was able to name, gesture to, and define all the objects when they were presented in isolation or in task-congruent arrays. We suggest that semantic errors may arise for a number of reasons: (1) impaired access from semantic memory to a network representing action schema, (2) degradation of stored schema, and (3) behavior that is abnormally driven by the goal, by preceding actions, or by salient objects rather than by an appropriate association between these elements in working memory.

Visual processing in patients with Frégoli syndrome.

We investigated four paranoid schizophrenic patients diagnosed with Frégoli delusion, and four matched psychotic controls. Neuropsychological testing included visual and verbal recognition memory, in addition to a comparison of left and right hemispheric processing of two different classes of stimuli, animate and inanimate objects. Performance on the recognition memory test failed to discriminate between the two psychotic groups on the basis of facial recognition, however, the patients with Frégoli delusion failed to show the right hemisphere processing advantage for the animate class of stimuli found for the set of norms and also present in the psychotic control group. These results are discussed in the context of both current theories of the delusional misidentification syndromes in general, and models of facial recognition in particular.

Refractory semantics in global aphasia: on semantic organisation and the access-storage distinction in neuropsychology.

A single case study is reported of a global aphasic patient, JM, with impaired access to semantic information which was particularly severe for the class of proper names. JM's ability to perform matching tasks with printed words and pictures to auditory words deteriorated when items were repeated, especially when the response-stimulus interval was short. Performance was also inconsistent across items. The effect of repeated testing on items generalised to other, previously untested members of the same category. Despite this, JM was able to access general semantic information about stimuli from the affected categories (e.g. to categorise boys' and girls' names), and showed good ability to access an input lexicon concerning these stimuli. There was also a close relationship between the categories affected when he was tested with pictures and printed words. We propose that JM's deficit can be attributed to his semantic system entering an abnormal refractory state once semantic access for a particular item has been achieved, and with this stage being isolated from the procedures providing access to stored lexical knowledge. Furthermore, the representations affected seem common to pictures and printed words. We discuss the implications of the results for understanding the nature of semantic representations in general and for proper names in particular, and for the distinction between access and storage deficits in neuropsychology.

A survey of instructional technology in dental education.

Little is known about current use of hardware and non-hardware instructional technologies in dental education. To address this area, the investigators designed a questionnaire to assess support for the development of instructional technology and determine the extent to which different instructional technologies are used in North American dental schools. Responses were received from 59 of 65 dental schools (91 percent). Respondents at most schools judged the administration at their school to be supportive of the development of instructional technology, but in general, did not feel faculty were enthusiastic about or rewarded for developing innovative methods. The most common computer-based application involves testing and record keeping, which is used extensively in about half the dental schools. Individualized instruction and paper and pencil simulations are used in at least some courses at a majority of dental schools. Schools with available support services apply certain technologies to a significantly greater extent than schools without available support services.

Dental student recruitment.

A seven-step student recruitment program employed in a dental school is described. The program comprises (1) a marketing survey, (2) a plan based upon information derived from the survey, (3) recruiting materials, (4) a "Recruitment Partners" program using alumni throughout the state, (5) publicity in state high schools and colleges, (6) recruiting in target high schools and colleges, and (7) a mailing list for follow-up with prospective applicants. The initial response to the program has been encouraging. The recruiting materials have been well received, more than 100 alumni dentists are now serving as active Recruitment Partners and are using the recruiting materials in their local high schools and colleges, and over 300 reply cards have been received from interested high schools and college students. A final evaluation of the program in three years will assess its impact on the number of dental school applicants.

Recent population redistribution in Ghana.

PIP: Examined in this paper is population change with particular reference to spatial distribution. Thus, emphasis is on movement of people rather than on natural increase due to births and deaths. Analysis is based upon national census data for 1960 and 1970 and is carried out at macro and meso levels. Administrative regions and local authority areas are utilized as units of observation. Population distribution in Ghana is described for 1960 and 1970 and the difference in the 2 spatial patterns is analysed. The main hypothesis tested is that change in population size of the larger unit areas is a function of internal migration, immigration, emigration and degree of urbanization. Following tests of this hypothesis, interregional migration is isolated as a very important factor producing change. A subtheme of the discussion is the relationship between population change and a selected age group, 25 to 44 years. This cohort is of particular interest because it has been observed in many studies that most migrants fall within this age category. A significant drop in the proportion of total population aged 25 to 44 years between 1960 and 1970, is evident on the examination of census statistics, for the entire national population, for regions and even for urban areas. It is hypothesized that this marked decrease is a reflection of increased or accelerated movement of persons. Tests of this hypothesis reveal that factors, urbanisation and immigration/emigration combined with interregional migration, seem to have significant association with the observed decrease in the proportion of total population aged 25 to 44 years. Since the age structure for urban areas also exhibits this trait, it is concluded that immigration/emigration is more relevant. It is strongly suggested that the mass exodus of foreigners from Ghana following the 1969 enforcement of the Aliens Act is in some way connected with this demographic phenomenon. In the absence of relevant data, this is not conclusively proved in the paper although supporting evidence is put forward. Finally, brief comments are made on implications of this study for future research as well as for future national development strategy.^ieng