BackgroundActive engagement with feedback is crucial for feedback to be effective and improve students' learning and achievement. Medical students are provided feedback on their development in the... Show moreBackgroundActive engagement with feedback is crucial for feedback to be effective and improve students' learning and achievement. Medical students are provided feedback on their development in the progress test (PT), which has been implemented in various medical curricula, although its format, integration and feedback differ across institutions. Existing research on engagement with feedback in the context of PT is not sufficient to make a definitive judgement on what works and which barriers exist. Therefore, we conducted an interview study to explore students' feedback use in medical progress testing.MethodsAll Dutch medical students participate in a national, curriculum-independent PT four times a year. This mandatory test, composed of multiple-choice questions, provides students with written feedback on their scores. Furthermore, an answer key is available to review their answers. Semi-structured interviews were conducted with 21 preclinical and clinical medical students who participated in the PT. Template analysis was performed on the qualitative data using a priori themes based on previous research on feedback use.ResultsTemplate analysis revealed that students faced challenges in crucial internal psychological processes that impact feedback use, including 'awareness', 'cognizance', 'agency' and 'volition'. Factors such as stakes, available time, feedback timing and feedback presentation contributed to these difficulties, ultimately hindering feedback use. Notably, feedback engagement was higher during clinical rotations, and students were interested in the feedback when seeking insights into their performance level and career perspectives.ConclusionOur study enhanced the understanding of students' feedback utilisation in medical progress testing by identifying key processes and factors that impact feedback use. By recognising and addressing barriers in feedback use, we can improve both student and teacher feedback literacy, thereby transforming the PT into a more valuable learning tool. Show less
Comparative neurobiology allows us to investigate relationships between phylogeny and the brain and understand the evolution of traits. Bats constitute an attractive group of mammalian species for... Show moreComparative neurobiology allows us to investigate relationships between phylogeny and the brain and understand the evolution of traits. Bats constitute an attractive group of mammalian species for comparative studies, given their large diversity in behavioural phenotypes, brain morphology, and array of specialised traits. Currently, the order Chiroptera contains over 1,450 species within 21 families and spans ca. 65 million years of evolution. To date, 194 Neotropical bat species (ca. 13% of the total number of species around the world) have been recorded in Central America. This study includes qualitative and quantitative macromorphological descriptions of the brains of 12 species from six families of Neotropical bats. These analyses, which include histological neuronal staining of two species from different families (Phyllostomus hastatus and Saccopteryx bilineata), show substantial diversity in brain macromorphology including brain shape and size, exposure of mesencephalic regions, and cortical and cerebellar fissure depth. Brain macromorphology can in part be explained by phylogeny as species within the same family are more similar to each other. However, macromorphology cannot be explained by evolutionary time alone as brain differences between some phyllostomid bats are larger than between species from the family Emballonuridae despite being of comparable diverging distances in the phylogenetic tree. This suggests that faster evolutionary changes in brain morphology occurred in phyllostomids — although a larger number of species needs to be studied to confirm this. Our results show the rich diversity in brain morphology that bats provide for comparative and evolutionary studies. Show less
Immunotherapy with immune-checkpoint inhibitors (ICIs) and targeted therapy with BRAF and MEK inhibitors have revolutionized the treatment of melanoma over the past decade. Despite these... Show moreImmunotherapy with immune-checkpoint inhibitors (ICIs) and targeted therapy with BRAF and MEK inhibitors have revolutionized the treatment of melanoma over the past decade. Despite these breakthroughs, the 5-year survival rate of patients with advanced-stage melanoma is at most 50%, emphasizing the need for additional therapeutic strategies. Adoptive cell therapy with tumour-infiltrating lymphocytes (TILs) is a therapeutic modality that has, in the past few years, demonstrated long-term clinical benefit in phase II/III trials involving patients with advanced-stage melanoma, including those with disease progression on ICIs and/or BRAF/MEK inhibitors. In this Review, we summarize the current status of TIL therapies for patients with advanced-stage melanoma, including potential upcoming marketing authorization, the characteristics of TIL therapy products, as well as future strategies that are expected to increase the efficacy of this promising cellular immunotherapy.Despite dramatic progress over the past decade, only around 50% of patients with advanced-stage melanoma derive durable benefit from immune-checkpoint inhibitors (ICIs) and/or BRAF and MEK (BRAF/MEK) inhibitors. Over the past few years, adoptive cell therapy with tumour-infiltrating lymphocytes (TILs) has demonstrated encouraging efficacy including in patients with disease progression on ICIs or BRAF/MEK inhibitors. In this Review, the authors summarize the role of TIL therapies in the management of these patients and describe future research strategies that might improve safety or efficacy.Tumour-infiltrating lymphocyte (TIL) therapy shows consistent clinical activity in patients with advanced-stage melanoma, including after disease progression on or after immune-checkpoint inhibitors and BRAF plus MEK inhibitors, and is manageable in most patients.Selection of tumour-reactive T cells and improvements in T cell function during the manufacturing process are expected to further improve the clinical activity of TIL therapy while limiting toxicity.Further clinical implementation of TIL therapy will require the establishment of infrastructure for centralized TIL production or point-of-care manufacturing, as well as treatment by an experienced medical team.Centralized TIL production and treatment of patients at dedicated centres might be important to enhance the clinical feasibility of TIL therapy and will drive further technological innovation. Show less
ObjectiveThere is a continued need for improvement of second-line systemic treatment for metastatic and/or recurrent endometrial cancer.MethodsIn this phase II, open-label study, eligible patients... Show moreObjectiveThere is a continued need for improvement of second-line systemic treatment for metastatic and/or recurrent endometrial cancer.MethodsIn this phase II, open-label study, eligible patients had histologically or cytologically confirmed endometrial cancer, documented progressive disease, and a WHO performance status of <= 2. All participants received treatment with pazopanib 800 mg once daily until progression, unacceptable toxicity, or patient refusal. The primary endpoint was progression-free survival at 3 months, with secondary outcomes of overall response rate, progression-free survival, overall survival, and toxicity. The study was powered to demonstrate 50% progression-free survival at 3 months with alpha=0.05 and beta=80%.ResultsBetween January 2011 and February 2016, 60 eligible patients were included (intention-to-treat population). Median age was 68 (range, 53-85) years. Previous treatment included pelvic radiotherapy (58%), chemotherapy (90%), and hormonal therapy (43%). Three-month progression-free survival was 63.3% in the intention-to-treat population, with median progression-free survival and overall survival of 3.4 and 7.5 months, respectively. Overall response rate was 8.3%, and median follow-up 7.6 months. The most common grade 3 or higher adverse events were gastrointestinal toxicity in 21% of participants, including two patients with a gut perforation, one fatal gastrointestinal hemorrhage, one enterocutaneous fistula, and one fatal enterovaginal fistula. Extensive peritoneal disease existed in 80% of the patients with severe gastrointestinal toxicity. A definite correlation with previous radiotherapy could not be established.ConclusionsPazopanib met its primary endpoint of 3 months' progression-free survival in advanced endometrial cancer (63.3%), but response rates were modest. There may be a correlation for rare but severe gastrointestinal toxicity with previous treatments and/or disease site that has yet to be elucidated. Show less
The Indo-European u-stem nouns merged almost completely with the o-stems in all Slavic languages. In every Slavic language, their combined paradigm shows traces of both original sets of endings.... Show moreThe Indo-European u-stem nouns merged almost completely with the o-stems in all Slavic languages. In every Slavic language, their combined paradigm shows traces of both original sets of endings. The merger of the two paradigms began before the earliest attestations of Slavic, but the attested evidence allows us to determine that the paradigms must have been distinct in late Common Slavic. The original distribution between u- and o-stems was blurred when they started to merge. The endings were redistributed on the basis of phonological and semantic criteria. In this paper it is argued that a similar process took place in the accentuation of masculine o- and u-stems in Slavic. The accentual phenomena discussed here have alternatively been explained as reflexes of a Proto-Slavic accentual pattern referred to as accent paradigm d. Show less
Spiers, C.; Lubotsky, A.; Griffiths, A.; Silk, J.A. 2024