Keuzevakperikelen

Avontuurlijk ingesteld als wij zijn, wilden wij voor onze keuzevakken nu eens niet eenvoudig de Leidse Keuzevakkengids uitpluizen, maar afreizen naar Rotterdam om daar bij Bedrijfskunde keuzevakken te gaan volgen: hadden we het maar nooit gedaan

The rhythm of life: the perfect rhythm of morse code

Morse code is a unique exemplar of the inherent complexities of rhythm. Learning Morse code in wartime presented challenges to expedite skill acquisition. This thesis explored the strategies used to teach and learn Morse code in the second World War and investigated the resourceful techniques used by the WRANS in an empirical study. The first study investigated the teaching and learning strategies of wartime telegraphists to learn Morse code. Five WRANS described a series of techniques to learn Morse code, including rote learning and repetition, visualisation and pattern recognition, intoning and mnemonics, and music. Music provided effective training for the fundamental teaching and learning of Morse code by matching the rhythmical properties of Morse code to music. Music equipped Morse code operators with a unique approach to Morse code instruction. Learning Morse code with music was described as a way of making sense of the ‘rhythm’ and ‘shape’ of the Morse code letters and proved an invaluable aid to learning and teaching Morse code. The second study examined the effectiveness of learning Morse code with the aid of music. Novices formed two groups, Control Group (no music aid) and Music Group (with music aid). Results confirmed the effectiveness of music training in three Morse code letters, Q V, and A in two experiments, the first with known Morse code letters (Q V A) and the second with unknown letters. The Music Group accurately identified 90% of known and unknown Morse code letters compared to the Control Group who identified less then 50% of known and unknown Morse code letters. This thesis explored the transferable attributes of rhythm perception in music as a teaching and learning mechanism for Morse code. There is extensive research on the complex learning and retention of Morse code but the studies in this thesis have indicated that the ground-breaking wartime strategy of music and Morse code is a powerful duo. The investigation of learning and teaching strategies of the WRANS showed that musical rhythm influenced the skill acquisition of Morse code and the perceptual test suggests that current work in rhythm perception extends beyond music pedagogy and has further implications for all cognitive function

Using a runway paradigm to assess the relative strength of rats' motivations for enrichment objects

Laboratory animals should be provided with enrichment objects in their cages; however, it is first necessary to test whether the proposed enrichment objects provide benefits that increase the animals’ welfare. The two main paradigms currently used to assess proposed enrichment objects are the choice test, which is limited to determining relative frequency of choice, and consumer demand studies, which can indicate the strength of a preference but are complex to design. Here, we propose a third methodology: a runway paradigm, which can be used to assess the strength of an animal’s motivation for enrichment objects, is simpler to use than consumer demand studies, and is faster to complete than typical choice tests. Time spent with objects in a standard choice test was used to rank several enrichment objects in order to compare with the ranking found in our runway paradigm. The rats ran significantly more times, ran faster, and interacted longer with objects with which they had previously spent the most time. It was concluded that this simple methodology is suitable for measuring rats’ motivation to reach enrichment objects. This can be used to assess the preference for different types of enrichment objects or to measure reward system processes

Terugdringing fosfaatafspoeling van boerenland

De aanleiding van dit innovatieonderzoek was het groeiende inzicht dat een belangrijke transportroute van fosfaat van boerenland naar het oppervlaktewater bestaat uit oppervlakkige afspoeling. Na hevige neerslag stroomt water via greppels, of gewoon via het oppervlak naar de sloot. Als er net bemest is dan kan het wegstromende water een aanzienlijk deel van de mest meenemen naar de sloot. Boeren op slecht doorlatende gronden herkennen dit uit eigen observatie. De ‘snelle P route’ opent nieuwe mogelijkheden om fosfaat emissies te verkleinen. De vraag is dan hoe fosfaat uit, naar de sloot stromend water, gehaald kan worden zonder dat de afwatering van agrarische percelen gehinderd wordt? En dan liefst op een manier die boeren gemakkelijk in hun bedrijfsvoering kunnen inpassen, zodat de maatregelen daadwerkelijk kans van slagen hebbe

Induced protein degradation of histone deacetylases 3 (HDAC3) by proteolysis targeting chimera (PROTAC)

Histone deacetylases (HDACs) play important roles in inflammatory diseases like asthma and chronic obstructive pulmonary disease (COPD). Unravelling of and interfering with the functions of specific isoenzymes contributing to inflammation provides opportunities for drug development. Here we synthesize proteolysis targeting chimeras (PROTACs) for degradation of class I HDACs in which o-aminoanilide-based class I HDAC inhibitors are tethered to the cereblon ligand pomalidomide. One of these PROTACs, denoted HD-TAC7, showed promising degradation effects for HDAC3 with a DC50 value of 0.32 μM. In contrast to biochemical evidence using siRNA, HD-TAC7 showed a minimal effect on gene expression in LPS/IFNγ-stimulated RAW 264.7 macrophages. The lack of effect can be attributed to downregulation of the NF-κB subunit p65, which is a known side effect of pomalidomide treatment. Altogether, we describe a novel PROTAC that enables selective downregulation of HDAC3 levels, however we note that concomitant downregulation of the NF-κB subunit p65 can confound the biological outcome

Philippine crocodile attacks on humans in the Northern Sierra Madre

Conservation Biology - ol

Benefit of adjuvant chemotherapy on recurrence free survival per consensus molecular subtype in stage III colon cancer

The consensus molecular subtype (CMS) classification divides colon tumors into four subtypes holding promise as a predictive biomarker. However, the effect of adjuvant chemotherapy on recurrence free survival (RFS) per CMS in stage III patients remains inadequately explored. With this intention, we selected stage III colon cancer (CC) patients from the MATCH cohort (n = 575) and RadboudUMC (n = 276) diagnosed between 2005 and 2018. Patients treated with and without adjuvant chemotherapy were matched based on tumor location, T- and N-stage (n = 522). Tumor material was available for 464 patients, with successful RNA extraction and CMS subtyping achieved in 390 patients (surgery alone group: 192, adjuvant chemotherapy group: 198). In the overall cohort, CMS4 was associated with poorest prognosis (HR 1.55; p =.03). Multivariate analysis revealed favorable RFS for the adjuvant chemotherapy group in CMS1, CMS2, and CMS4 tumors (HR 0.19; p =.01, HR 0.27; p &lt;.01, HR 0.19; p &lt;.01, respectively), while no significant difference between treatment groups was observed within CMS3 (HR 0.68; p =.51). CMS subtyping in this non-randomized cohort identified patients with poor prognosis and patients who may not benefit significantly from adjuvant chemotherapy.</p

Reintroduction of captive-bred Philippine crocodiles

Conservation Biology - ol

A Situational Alignment Framework for PACS

This paper reports the outcomes of a study on an integrated situational alignment framework for picture archiving and communication systems (PACS) labeled as PISA. Following the design research cycle, complementary validation methods and pilot cases were used to assess the proposed framework and its operationalized survey. In this paper, the authors outline (a) the process of the framework’ development, (b) the validation process with its underlying iterative steps, (c) the outcomes of pilot cases, and (d) improvement opportunities to refine and further validate the PISA framework. Results of this study support empirical application of the framework to hospital enterprises in order to gain insights into their PACS maturity and alignment. We argue that the framework can be applied as a valuable tool for assessments, monitoring and benchmarking purposes and strategic PACS planning

Machine learning-based somatic variant calling in cell-free DNA of metastatic breast cancer patients using large NGS panels

Abstract Next generation sequencing of cell-free DNA (cfDNA) is a promising method for treatment monitoring and therapy selection in metastatic breast cancer (MBC). However, distinguishing tumor-specific variants from sequencing artefacts and germline variation with low false discovery rate is challenging when using large targeted sequencing panels covering many tumor suppressor genes. To address this, we built a machine learning model to remove false positive variant calls and augmented it with additional filters to ensure selection of tumor-derived variants. We used cfDNA of 70 MBC patients profiled with both the small targeted Oncomine breast panel (Thermofisher) and the much larger Qiaseq Human Breast Cancer Panel (Qiagen). The model was trained on the panels’ common regions using Oncomine hotspot mutations as ground truth. Applied to Qiaseq data, it achieved 35% sensitivity and 36% precision, outperforming basic filtering. For 20 patients we used germline DNA to filter for somatic variants and obtained 245 variants in total, while our model found seven variants, of which six were also detected using the germline strategy. In ten tumor-free individuals, our method detected in total one (potentially germline) variant, in contrast to 521 variants detected without our model. These results indicate that our model largely detects somatic variants