Laser-Induced Coulomb Explosion Imaging of Aligned Molecules and Molecular Dimers.

We discuss how Coulomb explosion imaging (CEI), triggered by intense femtosecond laser pulses and combined with laser-induced alignment and covariance analysis of the angular distributions of the recoiling fragment ions, provides new opportunities for imaging the structures of molecules and molecular complexes. First, focusing on gas phase molecules, we show how the periodic torsional motion of halogenated biphenyl molecules can be measured in real time by timed CEI, and how CEI of one-dimensionally aligned difluoroiodobenzene molecules can uniquely identify four structural isomers. Next, focusing on molecular complexes formed inside He nano-droplets, we show that the conformations of noncovalently bound dimers or trimers, aligned in one or three dimensions, can be determined by CEI. Results presented for homodimers of CS2, OCS, and bromobenzene pave the way for femtosecond time-resolved structure imaging of molecules undergoing bimolecular interactions and ultimately chemical reactions.

Annexin A1 restores cerebrovascular integrity concomitant with reduced amyloid-ß and tau pathology.

Alzheimer's disease, characterized by brain deposits of amyloid-ß plaques and neurofibrillary tangles, is also linked to neurovascular dysfunction and blood-brain barrier breakdown, affecting the passage of substances into and out of the brain. We hypothesized that treatment of neurovascular alterations could be beneficial in Alzheimer's disease. Annexin A1 (ANXA1) is a mediator of glucocorticoid anti-inflammatory action that can suppress microglial activation and reduce blood-brain barrier leakage. We have reported recently that treatment with recombinant human ANXA1 (hrANXA1) reduced amyloid-ß levels by increased degradation in neuroblastoma cells and phagocytosis by microglia. Here, we show the beneficial effects of hrANXA1 in vivo by restoring efficient blood-brain barrier function and decreasing amyloid-ß and tau pathology in 5xFAD mice and Tau-P301L mice. We demonstrate that young 5xFAD mice already suffer cerebrovascular damage, while acute pre-administration of hrANXA1 rescued the vascular defects. Interestingly, the ameliorated blood-brain barrier permeability in young 5xFAD mice by hrANXA1 correlated with reduced brain amyloid-ß load, due to increased clearance and degradation of amyloid-ß by insulin degrading enzyme (IDE). The systemic anti-inflammatory properties of hrANXA1 were also observed in 5xFAD mice, increasing IL-10 and reducing TNF-α expression. Additionally, the prolonged treatment with hrANXA1 reduced the memory deficits and increased synaptic density in young 5xFAD mice. Similarly, in Tau-P301L mice, acute hrANXA1 administration restored vascular architecture integrity, affecting the distribution of tight junctions, and reduced tau phosphorylation. The combined data support the hypothesis that blood-brain barrier breakdown early in Alzheimer's disease can be restored by hrANXA1 as a potential therapeutic approach.

Twelve tips for engaging learners in online discussions.

Educators play a critical role in designing, facilitating and delivering an online medical education experience. Their teaching decisions and practices shape learners' experiences and affect their achievements. This is true even in large-scale, open educational contexts such as Massive Open Online Courses (MOOCs), which are designed based on self-regulated and collaborative learning. Thus, it is particularly important to explore the ways in which educators can effectively support online or blended learning through their interactions with learners. The 12 tips in this article aim to provide medical educators with guidelines for creating engaging online discussions that both support and challenge learners' understanding. The advice draws on a recent study examining the experiences and activities of 24 educators in MOOC discussion areas, and how their learners engaged with them. It provides practical recommendations on facilitating online discussions, producing engaging discussion tasks, and creating a balanced educator presence.

Multi-channel photodissociation and XUV-induced charge transfer dynamics in strong-field-ionized methyl iodide studied with time-resolved recoil-frame covariance imaging.

The photodissociation dynamics of strong-field ionized methyl iodide (CH3I) were probed using intense extreme ultraviolet (XUV) radiation produced by the SPring-8 Angstrom Compact free electron LAser (SACLA). Strong-field ionization and subsequent fragmentation of CH3I was initiated by an intense femtosecond infrared (IR) pulse. The ensuing fragmentation and charge transfer processes following multiple ionization by the XUV pulse at a range of pump-probe delays were followed in a multi-mass ion velocity-map imaging (VMI) experiment. Simultaneous imaging of a wide range of resultant ions allowed for additional insight into the complex dynamics by elucidating correlations between the momenta of different fragment ions using time-resolved recoil-frame covariance imaging analysis. The comprehensive picture of the photodynamics that can be extracted provides promising evidence that the techniques described here could be applied to study ultrafast photochemistry in a range of molecular systems at high count rates using state-of-the-art advanced light sources.

Changing Medical Education, Overnight: The Curricular Response to COVID-19 of Nine Medical Schools.

Issue: Calls to change medical education have been frequent, persistent, and generally limited to alterations in content or structural re-organization. Self-imposed barriers have prevented adoption of more radical pedagogical approaches, so recent predictions of the 'inevitability' of medical education transitioning to online delivery seemed unlikely. Then in March 2020 the COVID-19 pandemic forced medical schools to overcome established barriers overnight and make the most rapid curricular shift in medical education's history. We share the collated reports of nine medical schools and postulate how recent responses may influence future medical education. Evidence: While extraneous pandemic-related factors make it impossible to scientifically distinguish the impact of the curricular changes, some themes emerged. The rapid transition to online delivery was made possible by all schools having learning management systems and key electronic resources already blended into their curricula; we were closer to online delivery than anticipated. Student engagement with online delivery varied with different pedagogies used and the importance of social learning and interaction along with autonomy in learning were apparent. These are factors known to enhance online learning, and the student-centered modalities (e.g. problem-based learning) that included them appeared to be more engaging. Assumptions that the new online environment would be easily adopted and embraced by 'technophilic' students did not always hold true. Achieving true distance medical education will take longer than this 'overnight' response, but adhering to best practices for online education may open a new realm of possibilities. Implications: While this experience did not confirm that online medical education is really 'inevitable,' it revealed that it is possible. Thoughtfully blending more online components into a medical curriculum will allow us to take advantage of this environment's strengths such as efficiency and the ability to support asynchronous and autonomous learning that engage and foster intrinsic learning in our students. While maintaining aspects of social interaction, online learning could enhance pre-clinical medical education by allowing integration and collaboration among classes of medical students, other health professionals, and even between medical schools. What remains to be seen is whether COVID-19 provided the experience, vision and courage for medical education to change, or whether the old barriers will rise again when the pandemic is over.

Twelve tips for integrating massive open online course content into classroom teaching.

Massive open online courses (MOOCs) are a novel and emerging mode of online learning. They offer the advantages of online learning and provide content including short video lectures, digital readings, interactive assignments, discussion fora, and quizzes. Besides stand-alone use, universities are also trying to integrate MOOC content into the regular curriculum creating blended learning programs. In this 12 tips article, we aim to provide guidelines for readers to integrate MOOC content from their own or from other institutions into regular classroom teaching based on the literature and our own experiences. We provide advice on how to select the right content, how to assess its quality and usefulness, and how to actually create a blend within your existing course.

Alignment and Imaging of the CS_{2} Dimer Inside Helium Nanodroplets.

The carbon disulphide (CS_{2}) dimer is formed inside He nanodroplets and identified using fs laser-induced Coulomb explosion, by observing the CS_{2}^{+} ion recoil velocity. It is then shown that a 160 ps moderately intense laser pulse can align the dimer in advantageous spatial orientations which allow us to determine the cross-shaped structure of the dimer by analysis of the correlations between the emission angles of the nascent CS_{2}^{+} and S^{+} ions, following the explosion process. Our method will enable fs time-resolved structural imaging of weakly bound molecular complexes during conformational isomerization, including formation of exciplexes.

Femtosecond laser induced Coulomb explosion imaging of aligned OCS oligomers inside helium nanodroplets.

Dimers and trimers of carbonyl sulfide (OCS) molecules embedded in helium nanodroplets are aligned by a linearly polarized 160 ps long moderately intense laser pulse and Coulomb exploded with an intense 40 fs long probe pulse in order to determine their structures. For the dimer, recording of 2D images of OCS+ and S+ ions and covariance analysis of the emission directions of the ions allow us to conclude that the structure is a slipped-parallel shape similar to the structure found for gas phase dimers. For the trimer, the OCS+ ion images and the corresponding covariance maps reveal the presence of a barrel-shaped structure (as in the gas phase) but also other structures not present in the gas phase, most notably a linear chain structure.

The development of a pragmatic, clinically driven ultrasound curriculum in a UK medical school.

Whether ultrasound (US) should be incorporated into a medical undergraduate curriculum remains a matter of debate within the medical education arena. There are clear potential benefits to its early introduction particularly with respect to the study of living anatomy and physiology in addition to the learning of clinical skills and procedures required for the graduate clinical practice. However, this needs to be balanced against what is perceived as an added value in addition to financial and time constraints which may potentially lead to the sacrifice of other aspects of the curriculum. Several medical schools have already reported their experiences of teaching US either as a standalone course or as a fully integrated vertical curriculum. This article describes and discusses the initial experience of a UK medical school that has taken the steps to develop its own pragmatic vertical US curriculum based on clinical endpoints with the intent of using US to enhance the learning experience of students and equipping them with the skills required for the safe practice as a junior doctor.

Flipped classroom or an active lecture?

Recent changes in anatomy education have seen the introduction of flipped classrooms as a replacement to the traditional didactic lecture. This approach utilizes the increasing availability of digital technology to create learning resources that can be accessed prior to attending class, with face-to-face sessions then becoming more student-centered via discussion, collaborative learning, and problem-solving activities. Although this approach may appear intuitive, this viewpoint commentary presents a counter opinion and highlights a simple alternative that utilizes evidence-based active learning approaches as part of the traditional lecture. The active lecture takes the traditional lecture, and (1) ensures the lecture content is relevant and has clear objectives, (2) contains lecture material that is designed according to the latest evidence-base, (3) complements it with additional supplementary material, (4) creates space to check prior understanding and knowledge levels, and (5) utilizes suitable technology to facilitate continual engagement and interaction. Clin. Anat. 31:118-121, 2018. © 2017 Wiley Periodicals, Inc.

Twelve tips for developing and delivering a massive open online course in medical education.

Massive open online courses (MOOCs) are a novel mode of online learning. They are typically based on higher education courses and can attract a high number of learners, often in the thousands. They are distinct from on-campus education and deliver the learning objectives through a series of short videos, recommended readings and discussion fora, alongside automated assessments. Within medical education the role of MOOCs remains unclear, with recent proposals including continuing professional development, interprofessional education or integration into campus-based blended learning curricula. In this twelve tips article, we aim to provide a framework for readers to use when developing, delivering and evaluating a MOOC within medical education based on the literature and our own experience. Practical advice is provided on how to design the appropriate curriculum, engage with learners on the platform, select suitable assessments, and comprehensively evaluate the impact of your course.

Communication: Three-fold covariance imaging of laser-induced Coulomb explosions.

We apply a three-fold covariance imaging method to analyse previously acquired data [C. S. Slater et al., Phys. Rev. A 89, 011401(R) (2014)] on the femtosecond laser-induced Coulomb explosion of spatially pre-aligned 3,5-dibromo-3',5'-difluoro-4'-cyanobiphenyl molecules. The data were acquired using the "Pixel Imaging Mass Spectrometry" camera. We show how three-fold covariance imaging of ionic photofragment recoil trajectories can be used to provide new information about the parent ion's molecular structure prior to its Coulomb explosion. In particular, we show how the analysis may be used to obtain information about molecular conformation and provide an alternative route for enantiomer determination.

A holistic model for evaluating the impact of individual technology-enhanced learning resources.

BACKGROUND: The use of technology within education has now crossed the Rubicon; student expectations, the increasing availability of both hardware and software and the push to fully blended learning environments mean that educational institutions cannot afford to turn their backs on technology-enhanced learning (TEL). The ability to meaningfully evaluate the impact of TEL resources nevertheless remains problematic. AIMS: This paper aims to establish a robust means of evaluating individual resources and meaningfully measure their impact upon learning within the context of the program in which they are used. METHODS: Based upon the experience of developing and evaluating a range of mobile and desktop based TEL resources, this paper outlines a new four-stage evaluation process, taking into account learner satisfaction, learner gain, and the impact of a resource on both the individual and the institution in which it has been adapted. RESULTS: A new multi-level model of TEL resource evaluation is proposed, which includes a preliminary evaluation of need, learner satisfaction and gain, learner impact and institutional impact. Each of these levels are discussed in detail, and in relation to existing TEL evaluation frameworks. CONCLUSIONS: This paper details a holistic, meaningful evaluation model for individual TEL resources within the specific context in which they are used. It is proposed that this model is adopted to ensure that TEL resources are evaluated in a more meaningful and robust manner than is currently undertaken.

Preservation of cranial nerves during removal of the brain for an enhanced student experience in neuroanatomy classes.

Neuroanatomy teaching at the University of Leeds includes the examination of isolated brains by students working in small groups. This requires the prosected brains to exhibit all 12 pairs of cranial nerves. Traditional methods of removing the brain from the skull involve elevating the frontal lobes and cutting each cranial nerve as the brain is reflected posteriorly. This can leave a substantial length of each nerve attached to the skull base rather than to the removed brain. We have found a posterior approach more successful. In this study, five adult heads were disarticulated at the level of the thyroid cartilage and placed, prone, in a head stand. A wedge of bone from the occipital region was removed before the cerebellum and brainstem were elevated to visualize the cranial nerves associated with the medulla oblongata, cerebellopontine angle and mesencephalic-pontine junction prior to cutting them as close to the skull as possible. Five brains were successfully removed from the skull, each having a full complement of cranial nerves of good length attached to them. This approach significantly increases the length and number of cranial nerves remaining attached to the brain, which supports student education. For integration into head and neck dissection courses, careful consideration will be required to ensure the necks are suitably dissected and to decide whether the cranial nerves are best left attached to the skull base or brain.

Thematic analysis of stakeholder perceptions for co-creative healthcare XR resource design and development; traversing a minefield of opportunities.

Introduction: The expansive curricular volume of healthcare education makes a necessity the incorporation of innovative methods and immersive media in it. The core challenge in such approaches is the timely development of relevant immersive content such as Virtual, Augmented or Mixed Reality (VR/AR/MR) resources for healthcare topics. There is currently significant interest in the use of co-creative methods for streamlining immersive content development. Methods: A core research pursuit in this translational research field is the formulation of evidence-based, optimized workflows that streamline immersive content creation allowing for rapid expansion of innovative educational approaches in healthcare curricula. The purpose of this paper is to aggregate the perceptions of healthcare technologists and educators who participated in a series of co-creation sessions in order to elicit their best practice insights for design and development of XR educational resources using co-creative methods. Results: According to our thematic analysis, findings of the qualitative study demonstrated that a rigorous organizational approach is required to maintain a constructive exchange of information and to keep the design process alive for both content and technical experts. In addition, rapid prototype and display of co-created features can empower their contributions and help them design more efficiently. Discussion: Co-creative content production can benefit from adaption of existing frameworks and lightweight authoring environments that can facilitate generalized XR content development use cases.

Streamlining Tangible 3D Printed and Intangible XR Content Creation and Evaluation: The ENTICE Experience.

ENTICE aimed to use co-creative methodologies in order to build a solid creation pipeline for medical experiential content. The project has developed and evaluated immersive learning resources and tools aiming to support well-defined learning objectives using tangible and intangible resources (AR/VR/MR, 3D printing) that are highly sought in the fields of anatomy and surgery. In this paper the preliminary results from the evaluation of the learning resources and tools in 3 countries as well as the lessons learnt are presented towards to the improvement of the medical education process.

Tutorials in vibrational sum frequency generation spectroscopy. I. The foundations.

Interfaces between bulk media are often where critical molecular processes occur that can dictate the chemistry of an entire macroscopic system. Optical spectroscopy such as IR or Raman spectroscopy is often challenging to apply to interfaces due to contributions from bulk phases that dominate the spectra, masking any detail about the interfacial layer. Vibrational sum frequency generation (VSFG) spectroscopy is a nonlinear spectroscopy that allows vibrational spectra of molecules at interfaces to be directly measured. This Tutorial series is aimed at people entering the VSFG world without a rigorous formal background in optical physics or nonlinear spectroscopy. In this article, we present the fundamental theory of VSFG spectroscopy, with a focus on qualitative, intuitive explanation of the relevant physical phenomena, with minimal mathematics, to enable a newcomer to VSFG spectroscopy to quickly become conversant in the language and fundamental physics of the technique.

Tutorials in vibrational sum frequency generation spectroscopy. III. Collecting, processing, and analyzing vibrational sum frequency generation spectra.

In this Tutorial series, we aim to provide an accessible introduction to vibrational sum frequency generation (VSFG) spectroscopy, targeted toward people entering the VSFG world without a rigorous formal background in optical physics or nonlinear spectroscopy. In this article, we discuss in detail the processes of collecting and processing VSFG data, and user-friendly processing software (sfgtools) is provided for use by people new to the field. Some discussion of analyzing VSFG spectra is also given, specifically with a discussion of fitting homodyne VSFG spectra, and a discussion of what can be learned (both qualitatively and quantitatively) from VSFG spectra.

Assessing the difference in learning gain between a mixed reality application and drawing screencasts in neuroanatomy.

Augmented, mixed, and virtual reality applications and content have surged into the higher education arena, thereby allowing institutions to engage in research and development projects to better understand their efficacy within curricula. However, despite the increasing interest, there remains a lack of robust empirical evidence to justify the mainstream acceptance of this approach as an effective and efficient learning tool. In this study, the impact of a mixed reality application focused on long spinal cord sensory and motor pathways is explored in comparison to an existing resource already embedded within an active curriculum (e.g., anatomy drawing screencasts). To assess the changes in learner gain, a quasi-randomized control trial with a pre- and post-test methodology was used on a cohort of Year 2 medical students, with both the absolute and normalized gain calculated. Similar patterns of learner gain were observed between the two groups; only the multiple-choice questionnaires were shown to be answered significantly higher with the screencast group. This study adds important empirical data to the emerging field of immersive technologies and the specific impact on short-term knowledge gain for neuroanatomy teaching, specifically that of long sensory and motor pathways. Despite the limitations of the study, it provides important additional data to the field and intends to support colleagues across the education landscape in making evidence-informed decisions about the value of including such resources into their curricula.

Tutorials in vibrational sum frequency generation spectroscopy. II. Designing a broadband vibrational sum frequency generation spectrometer.

In this Tutorial series, we aim to provide an accessible introduction to vibrational sum frequency generation (VSFG) spectroscopy, targeted toward people entering the VSFG world without a rigorous formal background in optical physics or nonlinear spectroscopy. In this article, we describe in depth how a broadband VSFG spectrometer is designed and constructed, using the instrument in SurfLab, Aarhus University, as an illustrative case. Detailed information about specific instrumentation (together with reasons why things are the way they are) is given throughout. This information is often omitted in other descriptions of such instrumentation and so will be invaluable to people new to the field.