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Gamification has a strong track record of improving student engagement and learning in the chemical sciences. Meta-analyses of different approaches to gamification have highlighted that providing a game fiction, encouraging students to work in teams, and breaking games into smaller "quests" are particularly effective. Here, we aimed to increase students' engagement and learning with four analytical biochemistry techniques (high-performance liquid chromatography, sodium dodecyl sulfate polyacrylamide gel electrophoresis, Western blot, and mass spectrometry) by creating a game that required them to use every method to solve a "murder mystery". Our game was based on the popular games "Mafia" and "Among Us" and introduced an original game fiction relevant to our setting. Students attending the formative gamified session gave highly positive feedback. They indicated that they enjoyed the session and increased confidence in the methods involved. Free text comments praised many of the elements deliberately introduced into the game. To our surprise, the main criticism was that the session was not challenging enough. We developed a revised session that required students to undertake more detailed data interpretation, which students reported gave the expected increase in difficulty. All materials and code for running our session and generating new mysteries with original data are available online.

Mortality disparities among persons with intellectual disability are important to guide health-care practices. The objective was to evaluate mortality patterns of persons with intellectual disability in a nationwide study from 1976 to 2020. This study establishes a Danish nationwide cohort of persons with intellectual disability and age- and sex-matched reference cohort through linkage between several registers. We established a cohort of 79,114 persons with intellectual disability. Standardized mortality ratios were increased for persons with intellectual disability, most pronounced among younger persons and among females. Life expectancies were markedly lower; among persons with intellectual disability 63.6 years among females and 59.8 years among males in 2016-2020 compared to 82.4 and 78.7 years among females and males in the reference cohort. Life expectancies decreased with severity of intellectual disability. This study reports the establishment of a nationwide Danish cohort of persons with intellectual disability.

Abstract Negative attentional bias and alterations in positive affect dynamics constitute emotional vulnerability to depression. Attentional bias modification (ABM) aims to reduce emotional vulnerability to depression by fostering attentional deployment towards positive stimuli. In this randomized controlled trial, we examined whether ABM leads to changes in positive affect dynamics in a sample with an emotional vulnerability to depression (N = 65). Affect dynamics were measured based on experience sampling data gathered 14 days before and after ABM. During ABM, participants paid attention to pairs of emotional faces and responded to dots that were appearing in their place. There was an 87% chance for the dots to appear in place of the relatively more positive face, with the purpose to implicitly foster attentional focus on positive stimuli. In the control condition, there was a 50% chance of the dots to appear in place of the positive stimuli. Results showed that the lag-1 autocorrelation of affect (“inertia”) increased within the ABM group and decreased in the control group, but the findings were not robust and it was unclear whether ABM was the cause. There were no changes in the other affect dynamics indices. Improvements in depression during ABM were not associated with changes in affect dynamics, and affect dynamics post ABM did not predict depression symptoms six months later. In conclusion, the study showed no clear effect of ABM on affect dynamics.

Inspired by Graham Harman's philosophy of human access, and within the 'flattening ontology' of Object Oriented Ontology, Ring o' Roses is speculated about as a finite object with ontological independence from humans, repertoire, song, utility, and cultural context. Ring o' Roses playfully dances us through an introduction to OOO, and on to the idea of young children's early musical play as something different from its qualities and benefits. Indeed, the reality of musical play can be speculated about as ontologically irreducible, and as having a weird and vast, yet fragile, interior which is announced by allure. Allure is composed of charm, courage, and humour, and is responsible for causation.

The transmission electron microscope (TEM) is often considered the most complete characterization tool available to scientists who study materials' microstructure, crystallography, composition, chemistry, and functional properties. Consequently, significant investments have [...]

Abstract The role of serotonin in human behaviour is informed by approaches which allow in vivo modification of synaptic serotonin. However, characterising the effects of increased serotonin signalling in human models of behaviour is challenging given the limitations of available experimental probes, notably selective serotonin reuptake inhibitors. Here we use a now-accessible approach to directly increase synaptic serotonin in humans (a selective serotonin releasing agent) and examine its influence on domains of behaviour historically considered core functions of serotonin. Computational techniques, including reinforcement learning and drift diffusion modelling, explain participant behaviour at baseline and after week-long intervention. Reinforcement learning models reveal that increasing synaptic serotonin reduces sensitivity for outcomes in aversive contexts. Furthermore, increasing synaptic serotonin enhances behavioural inhibition, and shifts bias towards impulse control during exposure to aversive emotional probes. These effects are seen in the context of overall improvements in memory for neutral verbal information. Our findings highlight the direct effects of increasing synaptic serotonin on human behaviour, underlining its role in guiding decision-making within aversive and more neutral contexts, and offering implications for longstanding theories of central serotonin function.

Abstract The 5-2-1 criteria was developed to facilitate the identification and referral of patients with Parkinson’s Disease (PD) inadequately controlled by oral medications. The criterion was not developed to screen patients with PD for device-aided therapy eligibility. The robust design and validation of the 5-2-1 criteria minimizes over or inappropriate referrals, and supports physicians in the timely identification of patients with PD who may warrant further evaluation for treatment optimization. This response letter clarifies concerns raised by Moes et al.

ABSTRACT Acinetobacter baumannii is a leading cause of multidrug-resistant bacterial infections worldwide, and the capsular polysaccharide (CPS) is a major virulence determinant. A previous study of A. baumannii from intubated and asymptomatic patients admitted to the intensive care unit (ICU) at the Hospital for Tropical Diseases in Ho Chi Minh City in Vietnam revealed multiple lineages with diverse antibiotic resistance profiles and CPS biosynthesis loci. Here, we show that 48_n, an asymptomatic nasal carriage isolate belonging to ST142, is extensively antibiotic resistant and carries acquired resistance determinants accounting for the resistance profile. 48_n carries the novel KL71 CPS biosynthesis locus in the chromosome. The structure of the CPS produced by 48_n was established using 1H and 13C nuclear magnetic resonance spectroscopy, including two-dimensional 1Н,1Н COSY, 1Н,1Н TOCSY, 1Н,1Н ROESY, 1Н,13C HSQC, and 1Н,13C HMBC experiments, and confirmed by Smith degradation. Consistent with the genetic content of KL71, the K71 CPS was found to be made up of octasaccharide K units containing six l-rhamnose residues and one residue each of N-acetyl-d-glucosamine and d-glucuronic acid. K71 CPS was branched and closely related to the K74 CPS produced by BAL_309, an antibiotic susceptible ST142 isolate recovered from an intubated patient in the same ICU 7 years later. K71 and K74 differ only in the linkage between K units, and this is due to the replacement of a single gene at the K locus that codes for the Wzy polymerase.IMPORTANCEThe majority of Acinetobacter baumannii genomes sequenced and analyzed to develop an understanding of extensively drug-resistant (XDR) isolates belong to the globally disseminated CC2 clonal complex. While XDR isolates belonging to rarer lineages are often unexplored, detailed analyses could provide novel insights into the spread of resistance, as well as cell surface features such as the CPS that determine the specificity of non-antibiotic therapeutics required to treat XDR infections that resist antimicrobial chemotherapy. Here, we describe the properties of an XDR asymptomatic nasal carriage isolate recovered in Vietnam that belongs to ST142, a rarely encountered sequence type. We report the resistance profile and correlate this with detected resistance determinants. We also solve the structure of the CPS and reveal its relationship with CPS produced by other A. baumannii isolates.

The growing use of nitazene synthetic opioids heralds a new phase of the opioid crisis. However, limited information exists on the toxic effects of these drugs, aside from a propensity for respiratory depression. With restricted research availability of nitazenes, we used machine-learning-based tools to evaluate five nitazene compounds' interaction potential with the hERG potassium channel, a key drug antitarget in the heart. All nitazenes were predicted to inhibit hERG with low μM IC50 values. These findings indicate a potential for proarrhythmic hERG block by nitazene opioids, warranting detailed cardiac safety evaluations of these drugs.

Abstract Lamotrigine is an effective mood stabiliser, largely used for the management and prevention of depression in bipolar disorder. The neuropsychological mechanisms by which lamotrigine acts to relieve symptoms as well as its neural effects on emotional processing remain unclear. The primary objective of this current study was to investigate the impact of an acute dose of lamotrigine on the neural response to a well-characterised fMRI task probing implicit emotional processing relevant to negative bias. 31 healthy participants were administered either a single dose of lamotrigine (300 mg, n = 14) or placebo (n = 17) in a randomized, double-blind design. Inside the 3 T MRI scanner, participants completed a covert emotional faces gender discrimination task. Brain activations showing significant group differences were identified using voxel-wise general linear model (GLM) nonparametric permutation testing, with threshold free cluster enhancement (TFCE) and a family wise error (FWE)-corrected cluster significance threshold of p

Abstract Lithium is an effective augmenting agent for depressed patients with inadequate response to standard antidepressant therapy, but numerous adverse effects limit its use. We previously reported that a lithium-mimetic agent, ebselen, promoted a positive emotional bias—an indicator of potential antidepressant activity in healthy participants. We therefore aimed to investigate the effects of short-term ebselen treatment on emotional processing and brain neurochemistry in depressed patients with inadequate response to standard antidepressants. We conducted a double-blind, placebo-controlled 7-day experimental medicine study in 51 patients with major depressive disorder who were currently taking antidepressants but had an inadequate response to treatment. Participants received either ebselen 600 mg twice daily for seven days or identical matching placebo. An emotional testing battery, magnetic resonance spectroscopy and depression and anxiety rating scales were conducted at baseline and after seven days of treatment. Ebselen did not increase the recognition of positive facial expressions in the depressed patient group. However, ebselen increased the response bias towards fear emotion in the signal detection measurement. In the anterior cingulate cortex, ebselen significantly reduced the concentrations of inositol and Glx (glutamate+glutamine). We found no significant differences in depression and anxiety rating scales between visits. Our study did not find any positive shift in emotional bias in depressed patients with an inadequate response to antidepressant medication. We confirmed the ability of ebselen to lower inositol and Glx in the anterior cingulate cortex. These latter effects are probably mediated through inhibition of inositol monophosphatase and glutaminase respectively.

Background: Current treatment of major depressive disorders still leave many patients with modest improvement. Attention Bias Modification (ABM) is an approach that may serve as an adjuvant therapy for subgroups of patients. We examined whether rumination, often found to be associated with a negative attentional bias, acts as a moderating variable in a computerized ABM procedure in participants with recurrent depression. Methods: A total of 301 patients were randomized to receive either active - or sham ABM twice daily for 14 days. A regression-based moderator analysis was applied to evaluate whether baseline brooding, from the Rumination Response Scale (RRS-B), moderated the effect of ABM on Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory II (BDI-II). Results: There was no significant interaction effect of ABM and RRS-B on HDRS or BDI-II at post-intervention or at 1 month follow-up. In addition, no correlation was found for pre-training attention bias and RRS-B. Limitations: : Generalizability is limited to individuals with non-clinical symptom scores. Conclusions: There was no moderator effect of brooding rumination on clinical depression scales in the largest clinical study on ABM to date.

Abstract Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) represent an in vitro model of cardiac function. Isolated iPSC-CMs, however, exhibit electrophysiological heterogeneity which hinders their utility in the study of certain cardiac currents. In the healthy adult heart, the current mediated by small conductance, calcium-activated potassium (SK) channels (ISK) is atrial-selective. Functional expression of ISK within atrial-like iPSC-CMs has not been explored thoroughly. The present study therefore aimed to investigate atrial-like iPSC-CMs as a model system for the study of ISK. iPSCs were differentiated using retinoic acid (RA) to produce iPSC-CMs which exhibited an atrial-like phenotype (RA-iPSC-CMs). Only 18% of isolated RA-iPSC-CMs responded to SK channel inhibition by UCL1684 and isolated iPSC-CMs exhibited substantial cell-to-cell electrophysiological heterogeneity. This variability was significantly reduced by patch clamp of RA-iPSC-CMs in situ as a monolayer (iPSC-ML). A novel method of electrical stimulation was developed to facilitate recording from iPSC-MLs via In situ Monolayer Patch clamp of Acutely Stimulated iPSC-CMs (IMPASC). Using IMPASC, > 95% of iPSC-MLs could be paced at a 1 Hz. In contrast to isolated RA-iPSC-CMs, 100% of RA-iPSC-MLs responded to UCL1684, with APD50 being prolonged by 16.0 ± 2.0 ms (p

Abstract Diazotrophic cyanobacteria such as Trichodesmium play a crucial role in the nitrogen budget of the oceans due to their capability to bind atmospheric nitrogen. Little is known about their interoceanic transport pathways and their distribution in upwelling regions. Trichodesmium has been detected using a Video Plankton Recorder (VPR) mounted on a remotely operated towed vehicle (TRIAXUS) in the southern and northern Benguela Upwelling System (BUS) in austral autumn, Feb/Mar 2019. The TRIAXUS, equipped with a CTD as well as fluorescence and nitrogen sensors, was towed at a speed of 8 kn on two onshore–offshore transects undulating between 5 and 200 m over distances of 249 km and 372 km, respectively. Trichodesmium was not detected near the coast in areas of freshly upwelled waters but was found in higher abundances offshore on both transects, mainly in subsurface water layers down to 80 m depth with elevated salinities. These salinity lenses can be related to northward moving eddies that most probably have been detached from the warm and salty Agulhas Current. Testing for interaction and species-habitat associations of Trichodesmium colonies with salinity yielded significant results, indicating that Trichodesmium may be transported with Agulhas Rings from the Indian Ocean into the Atlantic Ocean.

Abstract Immunotherapies targeting PD-1/PD-L1 are now widely used in the clinic to treat a variety of malignancies. While most of the research on T cell exhaustion and PD-1 blockade has been focused on conventional αβ T cells, the contribution of innate-like T cells such as γδ T cells to anti-PD-1/PD-L1 mediated therapy is limited. Here we show that tumor reactive γδ T cells respond to PD-1 blockade in a Merkel cell carcinoma (MCC) patient experiencing a complete response to therapy. We find clonally expanded γδ T cells in the blood and tumor after pembrolizumab treatment, and this Vγ2Vδ1 clonotype recognizes Merkel cancer cells in a TCR-dependent manner. Notably, the intra-tumoral γδ T cells in the MCC patient are characterized by higher expression of PD-1 and TIGIT, relative to conventional CD4 and CD8 T cells. Our results demonstrate that innate-like T cells could also contribute to an anti-tumor response after PD-1 blockade.

Abstract Background Thrice-daily physiotherapy immediately following surgical repair of hip fracture has been shown to be safe and to reduce total hospital length of stay. However, implementing this is challenging with respect to health service funding and staffing. A novel approach may be to utilize an alternative workforce (allied health staff and student physiotherapists) to deliver two of the three daily treatments. However, how patients and staff may view such an approach is unknown. Thus, the aim of this qualitative study was to explore the views of inpatients with surgical repair of a hip fracture, their carers, health care professionals, and physiotherapy students about the implementation and acceptability of thrice-daily physiotherapy, with two sessions delivered by the alternative workforce (the BOOST study). Methods Semi-structured interviews and focus groups with patients, carers, health professionals and physiotherapy students. All interviews were digitally recorded and transcribed via verbatim. The transcripts were coded, and the data analysed via inductive thematic analysis. Results A total of 37 interviews (32 one-to-one interviews and five focus group interviews) were analysed. Five main themes were identified: (1) individual perceptions of the intervention: inpatients/carer/staff/student, (2) implementation within the service and organisational context, (3) implementation strategies that were effective, (4) improvements to implementation strategies/barriers to implementation/unsuccessful strategies and (5) future directions of BOOST. Conclusions The qualitative data revealed that higher frequency physiotherapy was well-received by inpatients and that staff/students involved in providing care perceived it as a safe, acceptable and valuable practice. Implementation of higher daily frequency of physiotherapy using an alternative workforce may feasibly be adopted for inpatients following hip fracture surgery. Trial registration This study was approved by the Human Research Ethics Committee (HREC) of the Western Sydney Local Health District (2020/ETH02718). Mutual recognition of approval was subsequently obtained from Northern Sydney Local Health District HREC.

Abstract Background Hip fracture has a devastating impact on individuals and is an increasing burden for health systems and society. Compared to usual care, increased physiotherapy provision has demonstrated efficacy in improving patient and health service outcomes in this population. However, physiotherapy workforce challenges prevent sustained implementation. Methods Our aim was to evaluate the safety, feasibility, acceptability, effectiveness and implementation cost of thrice daily physiotherapy for patients in the acute care setting after hip fracture at two public hospitals. We added twice-daily exercise implemented by an alternative workforce, to usual care consisting of daily mobility practice by a physiotherapist. Sites identified their preferred alternative workforce, with pre-registration physiotherapy students and allied health assistants chosen. We used a mixed methods approach, using the Consolidated Framework for Implementation Research (CFIR) as a determinant framework to guide implementation planning and data collection. We compared hospital length of stay data to a reference cohort. Results We recruited 25 patients during the study period. Acute care hospital length of stay decreased from 11 days in the reference cohort to 8 days in the BOOST cohort (mean difference − 3.3 days, 95%CI -5.4 to -1.2 days, p = 0.003). Intervention fidelity was 72% indicating feasibility, no safety concerns were attributed to the intervention, and uptake was 96% of all eligible patients. The intervention was acceptable to patients, carers and healthcare providers. This intervention was cost-effective from the acute orthopaedic service perspective. Conclusion Higher daily frequency of physiotherapy can be safely, feasibly and effectively implemented by an alternative workforce for patients in the acute care setting following hip fracture surgery.

This study produced a high-accuracy remotely piloted aircraft system (RPAS) imagery classification method for identifying the invasive reed Phragmites australis (Cav.) Trin. Ex Steud subsp. australis using random forest (RF) machine learning. RPAS imagery was collected in the spring and fall of 2019 using a fixed-wing RPAS equipped with a visible spectrum camera (eBee X, S.O.D.A. 3D; senseFly) in Long Point, Ontario, Canada. Imagery was used to produce separate early and late season classifications and a bi-temporal classification which used imagery from both dates. The overall accuracy achieved for each was 97%, 96%, and 91%, respectively. Digital surface models (DSMs) were the most important variable for identifying Phragmites in all classifications due to their greater height when compared to surrounding herbaceous vegetation. The bi-temporal classification, which utilized change in DSM value during the growing season, resulted in an estimated 47.8% new growth of Phragmites and appeared to capture sparse growth better than traditional classification differencing alone. This study highlights the promising use of high-resolution DSMs produced from RPAS imagery to classify invasive Phragmites and monitor within-year patch expansions.

Undergraduate students on track for medical school are often required to take general physics lab courses. Many of these students carry an attitude of obligation into these courses which can make it challenging for instructors to engage students in course material. We address the question: How does engaging with medically based models in introductory physics labs affect pre-med undergraduate perceptions of the modeling process and their perceptions of science? We redesigned an electricity and magnetism lab in an introductory physics lab course, where approximately 70% of the undergraduates reported plans to attend medical school. We situated the lab in the mechanics of MRI magnetic resonance and collected data on the participants’ experiences through surveys and lab submissions. As a part of the analysis, we modified a rubric to evaluate engagement in modeling and applied grounded coding theory to the survey responses to develop themes of the participants’ understanding of scientific modeling. The participants’ understanding and engagement in scientific modeling increased during the newly developed lab and remained high for subsequent labs. We recommend that instructors of undergraduate nonmajor labs consider the demographic of their student population and design lab experiences situated within their interests and focus on central science practices like modeling.

Mycotoxin cocontamination is a severe threat to health and economic security worldwide. The mycotoxins aflatoxin B1 (AFB1), zearalenone (ZEN), deoxynivalenol, T-2 toxin, fumonisin B1, and ochratoxin A are of particular concern due to their substantial toxicity. Lac-W is a laccase with the unique property of degrading these six mycotoxins in the absence of redox mediators. Nevertheless, their degradation rates are low. This work aims to improve the ability of Lac-W to degrade these six mycotoxins and to elucidate its detoxification mechanism. Including redox mediators increased the Lac-W degradation efficiency drastically, and completely degraded AFB1 and ZEN within one hour. Additionally, Lac-W-AS has good temperature, pH, and ions adaptability in ZEN degradation. Lac-W-AS reduced the ZEN toxicity because ZEN degradation products significantly restored the bioluminescence intensity of Vibrio fischeri. A Lac-W-AS-mediated oxidation product of ZEN was structurally characterized as 15-OH-ZEN by UHPLC-MS/MS. Linear sweep voltammetry showed that AS affected the potential of Lac-W and accelerated the oxidation of ZEN. Finally, the combination of mediators (acetosyringone and 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonate)) improved the degradation rate of mycotoxins. This work highlights that the combination of Lac-W with mediators serves as a good candidate for degrading multi-mycotoxin contaminants in food and feedstuff.

This article is personal and rather anecdotal as it is an attempt to sum up my experience of 30 years of Ofsted inspections. The key questions remain what they always were. How do you deal with the sometimes conflicting requirements of support and accountability, objectivity and impartiality, styles of inspection, reporting and grading? Perhaps most importantly, how do you try to ensure that inspection leads to improvement?