You escaped! How did you learn during gameplay?

This study investigates the influence of the educational game design elements immersion, collaboration and debriefing, on fostering learning with educational escape rooms. We based the design of the escape room on an educational game design framework that aligns the learning goal and the game goal, that is, escaping from the room. One-hundred-and-twenty-six students, aged between 16 and 20 played the escape room. Measures for learning were pre-and post-tests. The game experience was measured through questionnaires, classroom observations and interviews with students and teachers. The results show a knowledge gain between pre-and post-test. Correlational analysis showed that all three design elements contributed to students' appreciation of the escape room, whereas only immersion had a direct contribution to knowledge gain. Based on the qualitative data it appeared that the used escape boxes contributed most to perceived immersion. Immersion helps students focus on each other and the tasks. Also, a narrative with distinct roles for each student helped to evoke immersion. Unexpectedly, these roles also scaffolded collaboration except for students in the school that engaged in a collaborative learning pedagogy. The study confirms the usability of the framework for game designs, based on theories for the design of physical and hybrid educational games. Practitioner notes What is already known about this topic The escape room as a learning environment appeals to teachers of different disciplines, ages, gender and teaching experiences. Teachers implement escape rooms to create active (hybrid) learning spaces, where learners need a combination of knowledge and skills to solve the subject-based activities. Students and teachers perceive that while participating in escape rooms, students are more engaged, active and learn more compared to regular classes. The assumption is that escape rooms support collaboration and automatically collaborative learning. Review studies on educational escape rooms show that a systematic evaluation is usually absent, disputable or indicates no knowledge gain. Teachers design their educational escape rooms based on digital escape games and/or their experience as players of escape rooms. For digital educational games, important game design aspects are researched. Three main challenges in designing educational games are (1) the participants' transition from the real world to the game world, (2) the alignment of game design aspects and educational aspects and (3) the transfer from attained experiences and knowledge back into the real world. What this paper adds This paper evaluates an educational game design framework for escape rooms, focussing on the above-mentioned main challenges in designing educational games. It investigates the influence of the educational game design elements immersion, collaboration and debriefing, on fostering learning with a hybrid educational escape room. It informs that all three design elements contributed to students' appreciation of the escape room, whereas only immersion had a direct contribution to knowledge gain. The used hybrid escape boxes contributed most to the immersion; scaffolding students to focus on each other and the tasks. Students' collaboration was successfully fostered. However, it scarcely led to collaborative learning during gameplay, due to lack of discussion and reflection needed for deeper understanding. Implications for practice and/or policy The educational escape game framework would help educators creating immersive games, which not only confront learners with meaningful contexts but also give learning gains. The educational escape game framework would help researchers focussing on important and difficult aspects of designing and implementing educational escape rooms to develop and research more effective escape rooms. In guidelines on creating immersion in educational escape games, the notion of physical objects is lacking. In this hybrid escape room, the physical objects such as escape boxes were the most powerful in creating immersion. In addition, the use of sound design in escape games in classrooms seems overrated. Debriefing after the gameplay is perceived necessary to discuss common misunderstandings, to make connections between the topics in various puzzles and to add more content to interest high-achieving students

Pollitt syndrome patients carry mutation in TTDN1

Complete human genome sequencing was used to identify the causative mutation in a family with Pollitt syndrome (MIM #. 275550), comprising two non-consanguineous parents and their two affected children. The patient's symptoms were reminiscent of the non-photosensitive form of recessively inherited trichothiodystrophy (TTD). A mutation in the TTDN1/. C7orf11 gene, a gene that is known to be involved in non-photosensitive TTD, had been excluded by others by Sanger sequencing. Unexpectedly, we did find a homozygous single-base pair deletion in the coding region of this gene, a mutation that is known to cause non-photosensitive TTD. The deleterious variant causing a frame shift at amino acid 93 (C326delA) followed the right mode of inheritance in the family and was independently validated using conventional DNA sequencing. We expect this novel DNA sequencing technology to help redefine phenotypic and genomic variation in patients with (mono) genetic disorders in an unprecedented manner

Pharmacological validation of targets regulating CD14 during macrophage differentiation

The signalling receptor for LPS, CD14, is a key marker of, and facilitator for, pro-inflammatory macrophage function. Pro-inflammatory macrophage differentiation remains a process facilitating a broad array of disease pathologies, and has recently emerged as a potential target against cytokine storm in COVID19. Here, we perform a whole-genome CRISPR screen to identify essential nodes regulating CD14 expression in myeloid cells, using the differentiation of THP-1 cells as a starting point. This strategy uncovers many known pathways required for CD14 expression and regulating macrophage differentiation while additionally providing a list of novel targets either promoting or limiting this process. To speed translation of these results, we have then taken the approach of independently validating hits from the screen using well-curated small molecules. In this manner, we identify pharmacologically tractable hits that can either increase CD14 expression on non-differentiated monocytes or prevent CD14 upregulation during macrophage differentiation. An inhibitor for one of these targets, MAP2K3, translates through to studies on primary human monocytes, where it prevents upregulation of CD14 following M-CSF induced differentiation, and pro-inflammatory cytokine production in response to LPS. Therefore, this screening cascade has rapidly identified pharmacologically tractable nodes regulating a critical disease-relevant process

Maitotoxin-4, a Novel MTX Analog Produced by Gambierdiscus excentricus

Maitotoxins (MTXs) are among the most potent toxins known. These toxins are produced by epi-benthic dinoflagellates of the genera Gambierdiscus and Fukuyoa and may play a role in causing the symptoms associated with Ciguatera Fish Poisoning. A recent survey revealed that, of the species tested, the newly described species from the Canary Islands, G. excentricus, is one of the most maitotoxic. The goal of the present study was to characterize MTX-related compounds produced by this species. Initially, lysates of cells from two Canary Island G. excentricus strains VGO791 and VGO792 were partially purified by (i) liquid-liquid partitioning between dichloromethane and aqueous methanol followed by (ii) size-exclusion chromatography. Fractions from chromatographic separation were screened for MTX toxicity using both the neuroblastoma neuro-2a (N2a) cytotoxicity and Ca2+ flux functional assays. Fractions containing MTX activity were analyzed using liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) to pinpoint potential MTX analogs. Subsequent non-targeted HRMS analysis permitted the identification of a novel MTX analog, maitotoxin-4 (MTX4, accurate mono-isotopic mass of 3292.4860 Da, as free acid form) in the most toxic fractions. HRMS/MS spectra of MTX4 as well as of MTX are presented. In addition, crude methanolic extracts of five other strains of G. excentricus and 37 other strains representing one Fukuyoa species and ten species, one ribotype and one undetermined strain/species of Gambierdiscus were screened for the presence of MTXs using low resolution tandem mass spectrometry (LRMS/MS). This targeted analysis indicated the original maitotoxin (MTX) was only present in one strain (G. australes S080911_1). Putative maitotoxin-2 (p-MTX2) and maitotoxin-3 (p-MTX3) were identified in several other species, but confirmation was not possible because of the lack of reference material. Maitotoxin-4 was detected in all seven strains of G. excentricus examined, independently of their origin (Brazil, Canary Islands and Caribbean), and not detected in any other species. MTX4 may therefore serve as a biomarker for the highly toxic G. excentricus in the Atlantic area

Not surgical technique, but etiology, contralateral MRI, prior surgery, and side of surgery determine seizure outcome after pediatric hemispherotomy

Objective: We aimed to assess determinants of seizure outcome following pediatric hemispherotomy in a contemporary cohort. Methods: We retrospectively analyzed the seizure outcomes of 457 children who underwent hemispheric surgery in five European epilepsy centers between 2000 and 2016. We identified variables related to seizure outcome through multivariable regression modeling with missing data imputation and optimal group matching, and we further investigated the role of surgical technique by Bayes factor (BF) analysis. Results: One hundred seventy seven children (39%) underwent vertical and 280 children (61%) underwent lateral hemispherotomy. Three hundred forty-four children (75%) achieved seizure freedom at a mean follow-up of 5.1 years (range 1 to 17.1). We identified acquired etiology other than stroke (odds ratio [OR] 4.4, 95% confidence interval (CI) 1.1–18.0), hemimegalencephaly (OR 2.8, 95% CI 1.1–7.3), contralateral magnetic resonance imaging (MRI) findings (OR 5.5, 95% CI 2.7–11.1), prior resective surgery (OR 5.0, 95% CI 1.8–14.0), and left hemispherotomy (OR 2.3, 95% CI 1.3–3.9) as significant determinants of seizure recurrence. We found no evidence of an impact of the hemispherotomy technique on seizure outcome (the BF for a model including the hemispherotomy technique over the null model was 1.1), with comparable overall major complication rates for different approaches. Significance: Knowledge about the independent determinants of seizure outcome following pediatric hemispherotomy will improve the counseling of patients and families. In contrast to previous reports, we found no statistically relevant difference in seizure-freedom rates between the vertical and horizontal hemispherotomy techniques when accounting for different clinical features between groups

Dutch combat operation experiences in Iraq and Afghanistan

_Introduction:_ The Combined Joined Task Force - Operation Inherent Resolve is the military intervention of Iraq and Coalition Forces in the battle against Islamic State of Iraq and Syria (ISIS). Al Assad Airbase (AAAB) is one of the key airbases. It contains a Role 2 Medical Treatment Facility, primarily to perform Damage Control Surgery in Coalition Forces, Iraqi National Security Forces and Local Nationals. We present a six month medical exposure in order to provide insight into the treatment of casualties and to optimize medical planning of combat operations and (pre-/post-) deployment training. _Patients and methods:_ This is a cohort study of casualties that were admitted to the Role 2 Medical Treatment Facility AAAB from November 2017 to April 2018. Their mechanisms and types of injury are described and compared to those sustained in Uruzgan, Afghanistan between 2006–2010. Additionally, they are compared to the caseload in the Dutch civilian medical centers of the medical specialist team at AAAB. _Results:_ There were significant differences in both mechanism and type of injury between Coalition Forces and Iraqi Security Forces (p = 0.0001). Coalition Forces had 100% disease and non-battle injuries, where Iraqi Security Forces had 86% battle injuries and 14% non-battle casualties. The most common surgical procedures performed were debridement of wounds (38%), (exploratory) laparotomy (10%) and genital procedures (7%). The surgical caseload in Uruzgan, Afghanistan was significantly different in aspect and quantity, being 4.1 times higher. When compared to the workload at home all team members had at least a tenfold lower workload than in their civilian hospitals. _Discussion:_ The deployed surgical teams were scarcely exposed to casualties at AAAB, Iraq. These low workload deployments could cause a decline in surgical skills. Military medical planning should be tailormade and should include adjusting length of stay, (pre-/post-)deployment refresher training and early consultation of military medical specialists. Future research should focus on optimizing this process by investigating fellowships in combat matching trauma centers, regional and international collaboration and refresher training possibilities to maintain the expertise of the acute military care provider