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Wind-driven shear stresses drive saltation and dust emissions over sand dunes. However, the complex topography of coastal dunes and practical difficulties in measuring shear stresses in the presence of blowing sand make a detailed view of this important information difficult to obtain. We combine computational fluid dynamics with field instrumentation and high resolution topographic data to investigate the shear stresses resulting from on-shore winds on the ground surface for a flat sloping beach area, nebkha foredune, and transverse dune at Oceano Dunes, CA. This approach allows for paired simulations over measured and modified topographies using the same boundary condition. Shear values from scenarios that account for the effects of vegetation and aerodynamic form separately are presented. Using available dust emissions data, an accounting of the emissions from the surface was performed. Sparse vegetation on the nebkha in the foredune was found to play a significant role in modulating the shear on the surface and initial boundary layer modification of the onshore wind profile.

Background Clinical trials are essential to evidence-based medicine. Their success relies on recruitment and retention of participants: problems with either can affect validity of results. Past research on improving trials has focused on recruitment, with less on retention, and even less considering retention at the point of recruitment, i.e., what retention-relevant information is shared during consent processes. The behaviour of trial staff communicating this information during consent is likely to contribute to retention. So, developing approaches to mitigate issues in retention at the point of consent is necessary. In this study, we describe the development of a behavioural intervention targeting the communication of information important to retention during the consent process. Methods We applied the Theoretical Domains Framework and Behaviour Change Wheel to develop an intervention aimed at changing the retention communication behaviours of trial staff. Building on findings from an interview study to understand the barriers/facilitators to retention communication during consent, we identified behaviour change techniques that could moderate them. These techniques were grouped into potential intervention categories and presented to a co-design group of trial staff and public partners to discuss how they might be packaged into an intervention. An intervention was presented to these same stakeholders and assessed for acceptability through a survey based on the Theoretical Framework of Acceptability. Results Twenty-six behaviour change techniques were identified with potential to change communication of retention-information at consent. Six trial stakeholders in the co-design group discussed means for implementing these techniques and agreed the available techniques could be most effective within a series of meetings focussed on best practices for communicating retention at consent. The proposed intervention was deemed acceptable through survey results. Conclusion We have developed an intervention aimed at facilitating the communication of retention at informed consent through a behavioural approach. This intervention will be delivered to trial staff and will add to the available strategies for trials to improve retention.

Objective We tested the hypothesis that targeted retinal laser photocoagulation (TPRP) to peripheral retinal ischaemia reduces the overall burden of aflibercept injections when treating diabetic macular oedema (DMO) over a 24-month period. Methods Prospective, double-masked, multicentre, randomised controlled trial in Australia comparing aflibercept monotherapy, following a treat-and-extend protocol, or combination therapy of aflibercept and TPRP for DMO. The aflibercept monotherapy group received placebo laser. The primary outcome measure was the mean number of intravitreal aflibercept injections for each group at 24 months. Secondary outcome included: mean change in central macular thickness (CMT) and vision at trial completion, the proportion of eyes whose DMO resolved and the mean injection treatment interval. Ocular and systemic adverse events were recorded. Results We enrolled 48 eyes of 47 patients; 27 eyes were randomised to combination therapy (aflibercept and TPRP) and 21 to aflibercept monotherapy. Thirty-two eyes (67%) completed the 2-year study. The number of intravitreal treatments given were similar for combination therapy (10.5 (SD 5.8) and monotherapy (11.8 (SD5.6)) (P = 0.44). The mean visual improvement (+4.0 (−1.8, 9.8) and +7.8 (2.6, 12.9) letters, P = 0.32), mean decrease in CMT (−154 (−222,−87) µm and −152 (−218,−86) µm, P = 0.96), proportion of eyes with CMT Conclusions Laser to areas of ischaemic peripheral retina does not reduce the burden of intravitreal aflibercept injections when treating diabetic macular oedema.

Objectives To identify whether the outcomes of neovascular age-related macular degeneration (nAMD), diabetic macular oedema (DMO) and retinal vein occlusion (RVO) in routine clinical practice have changed over time. Methods We analysed 12-month outcomes in treatment-naïve eyes that started aflibercept or ranibizumab for nAMD (3802 eyes), DMO (975 eyes), Branch RVO (BRVO, 357 eyes), Central RVO (CRVO, 371 eyes) and Hemi-RVO (HRVO, 54 eyes) from 2015 and 2019 tracked in the prospectively designed observational Fight Retinal Blindness! Registry. Results The mean VA change at 12-month for each year between 2015 and 2019 remained stable or otherwise showed no discernible trends over time in eyes with nAMD (+3.3 to +6 letters), DMO (+3.6 to +6.7 letters) and RVO (+10.3 to +11.7 letters for BRVO, +5.9 to +17.7 letters for CRVO and 10.2 to 20.7 letters for HRVO). The median number of VEGF-inhibitor injections in eyes that completed 12-month follow-up also remained stable at 8–9 for nAMD, 6–7 for DMO, 7–9 for RVO. Fewer eyes ( Conclusions Treatment patterns and outcomes for nAMD, DMO and RVO in routine clinical practice have stabilised over the past 5 years at levels inferior to those reported by the pivotal phase 3 studies. A conscious effort to treat these conditions more intensively, or with longer lasting agents, would likely improve outcomes further in our patients.

People can understand how human interaction unfolds and can pinpoint social attitudes such as showing interest or social engagement with a conversational partner. However, summarising this with a set of rules is difficult, as our judgement is sometimes subtle and subconscious. Hence, it is challenging to program Non-Player Characters (NPCs) to react towards social signals appropriately, which is important for immersive narrative games in Virtual Reality (VR). We collaborated with two game studios to develop an immersive machine learning (ML) pipeline for detecting social engagement. We collected data from participants-NPC interaction in VR, which was then annotated in the same immersive environment. Game design is a creative process and it is vital to respect designer’s creative vision and judgement. We therefore view annotation as a key part of the creative process. We trained a reinforcement learning algorithm (PPO) with imitation learning rewards using raw data (e.g. head position) and socially meaningful derived data (e.g. proxemics); we compared different ML configurations including pre-training and a temporal memory (LSTM). The pre-training and LSTM configuration using derived data performed the best (84% F1-score, 83% accuracy). The models using raw data did not generalise. Overall, this work introduces an immersive ML pipeline for detecting social engagement and demonstrates how creatives could use ML and VR to expand their ability to design more engaging experiences. Given the pipeline’s results for social engagement detection, we generalise it for detecting human-defined social attitudes.

To test the hypothesis that patients treated for neovascular age related macular degeneration (nAMD) with longer treatment intervals are more likely to persist with treatment.Data were obtained from the prospectively-defined Fight Retinal Blindness! registry. Treatment interval at 2 years was stratified based on the mean treatment interval over the three visits prior to and including the 2-year visit. Rates of non-persistence to follow-up were assessed from 2 to 5 years.Data from 1538 eyes were included. The overall rate of non-persistence was 51% at 5 years. Patients on longer treatment intervals (12-weeks) at 2 years were found to be less persistent to long-term follow-up. These eyes were found to have fewer active disease visits in the first 2 years (40%) than eyes treated at 4-weekly intervals (66%, p 0.001). In the multivariable analysis, better vision at 2 years was associated with a lower risk of non-persistence (hazards ratio [HR] [95% CI]: 0.95 [0.93, 0.97], P 0.001), while longer treatment intervals (HR [95% CI]: 1.31 [0.95, 1.8] and 1.54 [1.15, 2.06] for 12-week and 12-week intervals vs. 4-week intervals, respectively, P = 0.002) and older patients (HR [95% CI]: 1.03 [1.02, 1.04], p 0.001) were at higher risk of non-persistence.We found that patients on longer treatment intervals at 2 years were more likely to be non-persistent with treatment in later years. Reinforcing the need for ongoing treatment is important for patients on longer intervals who may feel complacent or that treatment is no longer effective, particularly if newer, longer lasting agents become widely available.

An increasing amount of technological solutions aiming to support emotion regulation are being developed for Autistic people. However, there remains a lack of understanding of user needs, and design factors which has led to poor usability and varied success. Furthermore, studies assessing the feasibility of emotion regulation technology via physiological signals for autistic people are increasingly showing promise, yet to date there has been no exploration of views from the autistic community on the benefits/challenges such technology may present in practice. Focus groups with autistic people and their allies were conducted to gain insight into experiences and expectations of technological supports aimed at supporting emotion regulation. Reflexive thematic analysis generated three themes: (1) communication challenges (2) views on emotion regulation technology (3) ‘how’ technology is implemented. Results provide meaningful insight into the socio-emotional communication challenges faced by autistic people, and explore the expectations of technology aimed at supporting emotion regulation.

While randomized controlled trials are essential to health research, many of these trials fail to recruit enough participants. Approaching recruitment through the lens of behavioral science can help trialists to understand influences on the decision to participate and use them to increase recruitment. Although this approach is promising, the use of behavioral influences during recruitment is in tension with the ethical principle of respect for persons, as at least some of these influences could be used to manipulate potential participants. In this paper, we examine this tension by discussing two types of behavioral influences: one example involves physician recommendations, and the other involves framing of information to exploit cognitive biases. We argue that despite the apparent tension with ethical principles, influencing trial participants through behavior change strategies can be ethically acceptable. However, we argue that trialists have a positive obligation to analyze their recruitment strategies for behavioral influences and disclose these upfront to the research ethics committee. But we also acknowledge that since neither trialists nor ethics committees are presently well equipped to perform these analyses, additional resources and guidance are needed. We close by outlining a path toward the development of such guidance.

Spindle formation in male meiosis relies on the canonical centrosome system, which is distinct from acentrosomal oocyte meiosis, but its specific regulatory mechanisms remain unknown. Herein, we report that DYNLRB2 (Dynein light chain roadblock-type-2) is a male meiosis-upregulated dynein light chain that is indispensable for spindle formation in meiosis I. In Dynlrb2 KO mouse testes, meiosis progression is arrested in metaphase I due to the formation of multipolar spindles with fragmented pericentriolar material (PCM). DYNLRB2 inhibits PCM fragmentation through two distinct pathways; suppressing premature centriole disengagement and targeting NuMA (nuclear mitotic apparatus) to spindle poles. The ubiquitously expressed mitotic counterpart, DYNLRB1, has similar roles in mitotic cells and maintains spindle bipolarity by targeting NuMA and suppressing centriole overduplication. Our work demonstrates that two distinct dynein complexes containing DYNLRB1 or DYNLRB2 are separately used in mitotic and meiotic spindle formations, respectively, and that both have NuMA as a common target.

Background This study explored the specialty preferences of China-educated international medical students (IMSs), who are mainly from low- and middle-income countries (LMICs) and constitute a potential medical workforce both for their home countries and foreign countries, and the influence of migration intentions on their specialty preferences. Methods A cross-sectional, questionnaire-based survey was conducted at 5 universities in China. The questionnaire link was distributed electronically among the IMSs at the 5 universities via emails. The questionnaire enquired IMSs’ demographic information, migration intentions and their specialty preferences. The Chi-square test was applied to determine the influence of the respondent’s gender, intention to practise in the home country and intention to practise in a high-income country on their specialty choices. The Chi-square test was also applied to determine the influence of the respondent’s gender, year of study and country of origin on their preferences for generalist-orientated or non-generalist orientated specialties. Results Altogether, 452 IMSs returned their responses, yielding a response rate of 64.1%. Approximately half of the IMSs planned to not return to their home country. The most selected specialty was general surgery and the least selected specialty was physical medicine and rehabilitation. No significant differences were evident in most specialty preferences between those who intended to return home and those who intended to stay abroad. Among the IMSs having intentions of returning to their home country, male students tended to choose a generalist-orientated specialty, while female students tended to choose a non-generalist-orientated specialty. Conclusion China-educated IMSs could play important roles in the primary care services as well as other shortage specialties both for their home countries or foreign countries. Therefore, it is recommended that governments in these countries plan migration and recruitment policies that cater for these studying-abroad medical students from LMICs, especially in this challenging time during the COVID-19 pandemic.

Neural oscillatory activities in basal ganglia have prominent roles in cognitive processes. However, the characteristics of oscillatory activities during cognitive tasks have not been extensively explored in human Globus Pallidus internus (GPi). This study aimed to compare oscillatory characteristics of GPi between dystonia and Parkinson's Disease (PD). A dystonia and a PD patient performed the Intra-Extra-Dimension shift (IED) task during both on and off-medication states. During the IED task, patients had to correctly choose between two visual stimuli containing shapes or lines based on a hidden rule via trial and error. Immediate auditory and visual feedback was provided upon the choice to inform participants if they chose correctly. Bilateral GPi Local Field Potentials (LFP) activity was recorded via externalized DBS leads. Transient high gamma activity (~ 100–150 Hz) was observed immediately after feedback in the dystonia patient. Moreover, these bursts were phase synchronous between left and right GPi with an antiphase clustering of phase differences. In contrast, no synchronous high gamma activity was detected in the PD patient with or without dopamine administration. The off-med PD patient also displayed enhanced low frequency clusters, which were ameliorated by medication. The current study provides a rare report of antiphase homotopic synchrony in human GPi, potentially related to incorporating and processing feedback information. The absence of these activities in off and on-med PD patient indicates the potential presence of impaired medication independent feedback processing circuits. Together, these findings suggest a potential role for GPi’s synchronized activity in shaping feedback processing mechanisms required in cognitive tasks.

Background Trials in pre-hospital trauma care are relatively uncommon. There are logistical and methodological challenges related to designing and delivering trials in this setting. Previous studies have assessed challenges reported in individual trials rather than across the pre-hospital trial landscape to identify over-arching factors. The aim of this study was to investigate the challenges and opportunities related to the set-up, design and conduct of pre-hospital trauma trials from across the pre-hospital trial landscape and a specific pre-hospital trauma feasibility study. Methods Semi-structured interviews were conducted with two cohorts of participants: research personnel who had experience of pre-hospital trials, either through direct involvement in conduct or through strategic oversight of national initiatives (n = 7), and clinical staff (n = 16) involved in recruitment to a pre-hospital trauma feasibility study. Thematic analyses were used to assess the barriers and enablers of conducting pre-hospital trauma trials. Two frameworks (The Capability Opportunity Motivation—Behaviour and the Theoretical Domains Framework) were used to guide analyses. Results The barriers and enablers reported were relevant to several TDF domains and COM-B components. Across both cohorts, challenges associated with opportunities were reported and included the lack of research experience amongst pre-hospital staff, team dynamics within a rotating shift schedule, and the involvement of external organisations with diverse institutional priorities and infrastructures (e.g. Air Ambulances). The infrequency of eligible cases was also reported to affect the trial design, set-up, and conduct. Other barriers reported related to clinical equipoise amongst staff and institutional pressures, which affected motivation. Conclusions This study has highlighted that pre-hospital trials face many context-specific but also generic challenges. Pre-hospital trauma trial teams could consider the findings to develop targeted, behaviourally focused, solutions to the challenges identified in order to enhance the set-up and conduct of trials in this setting. Trial registration NCT04145271. Trial registration date: October 30, 2019. Note that this paper does not report results from a specific trial but does include participants who were involved in the conduct of a registered pre-hospital feasibility study.

Cities are drivers of the global economy, containing products and industries that emit many chemicals. Here, we use the Multimedia Urban Model (MUM) to estimate atmospheric emissions and fate of organophosphate esters (OPEs) from 19 global mega or major cities, finding that they collectively emitted ~81,000 kg yr−1 of ∑10OPEs in 2018. Typically, polar “mobile” compounds tend to partition to and be advected by water, while non-polar “bioaccumulative” chemicals do not. Depending on the built environment and climate of the city considered, the same compound behaves like either a mobile or a bioaccumulative chemical. Cities with large impervious surface areas, such as Kolkata, mobilize even bioaccumulative contaminants to aquatic ecosystems. By contrast, cities with large areas of vegetation fix and transform contaminants, reducing loadings to aquatic ecosystems. Our results therefore suggest that urban design choices could support policies aimed at reducing chemical releases to the broader environment without increasing exposure for urban residents.

Deprescribing is the process by which medications are reduced without compromising safety to the patient (Jude et al. in 2022 Diabetes Ther 13: 619–634, 2022). The purpose of this narrative review is to discuss deprescribing as a topic, firstly discussing the benefits and pitfalls to such pharmacological interventions along with the current barriers and enablers to such a controversial topic, and then discussing deprescribing with respect to preventive medications, namely those that reduce the long term impacts of a condition or disease. Research that has previously focused on reducing polypharmacy has highlighted the benefits of such interventions, including reduction of adverse reactions or complications, improved patient satisfaction and quality of life, and improved cost effectiveness and drug compliance. Some potential harms that have been highlighted include an increased number of complications, increased symptoms of previously dampened conditions, and negligible changes in patient satisfaction that have stressed the importance of this intervention being patient centred and individualized to each patient. The implementation of deprescribing processes could drastically change the way people think about deprescribing and could be extremely beneficial to older patients living with type 2 diabetes worldwide. Developments in preventive medication deprescribing could pave the way for this intervention to become more common place improving the quality of life in patient’s final years.

Several neurological disorders, such as myotonic dystrophy are caused by expansions of short tandem repeats (STRs) which can be difficult to detect by molecular tools. Methodological advances have made repeat expansion (RE) detection with whole genome sequencing (WGS) feasible. We recruited a multi-generational family (family A) ascertained for genetic studies of autism spectrum disorder. WGS was performed on seven children from four nuclear families from family A and analyzed for REs of STRs known to cause neurological disorders. We detected an expansion of a heterozygous intronic CCTG STR in CNBP in two siblings. This STR causes myotonic dystrophy type 2 (DM2). The expansion did not segregate with the ASD phenotype. Repeat-primed PCR showed that the DM2 CCTG motif was expanded above the pathogenic threshold in both children and their mother. On subsequent examination, the mother had mild features of DM2. We show that screening of STRs in WGS datasets has diagnostic utility, both in the clinical and research domain, with potential management and genetic counseling implications.

Background Chyle leaks following oesophagectomy are a frustrating complication of surgery with considerable morbidity. The use of near infra-red (NIR) fluorescence in surgery is an emerging technology and the use of fluorescence to identify the thoracic duct has been demonstrated in animal work and early human case reports. This study evaluated the use mesenteric and enteral administration of indocyanine green (ICG) in humans to identify the thoracic duct during oesophagectomy. Methods Patients undergoing oesophagectomy were recruited to the study. Administration of ICG via an enteral route or mesenteric injection was evaluated. Fluorescence was assessed using a NIR fluorescence enabled laparoscope system with a visual scoring system and signal to background ratios. Visualisation of the thoracic duct under white light and NIR fluorescence was compared as well as any identification of active chyle leak. Patients were followed up post-operatively for adverse events and chyle leak. Results 20 patients received ICG and were included in the study. The enteral route failed to fluoresce the thoracic duct. Mesenteric injection (17 patients) identified the thoracic duct under fluorescence prior to white light in 70% of patients with a mean signal to background ratio of 5.35. In 6 participants, a possible active chyle leak was identified under fluorescence with 4 showing active chyle leak from what was identified as the thoracic duct. Conclusion This study demonstrates that ICG administration via mesenteric injection can highlight the thoracic duct during oesophagectomy and may be a potential technology to reduce chyle leak following surgery. Clinical trial registration Clinical trials.gov (NCT03292757).

Long-range transport of black carbon from South Asia to the Tibetan plateau and its deposition on glaciers directly enhances glacier melt. Here we find South Asian black carbon also has an indirect effect on the plateau’s glaciers shrinkage by acting to reduce the water supply over the southern Tibetan plateau. Black carbon enhances vertical convection and cloud condensation, which results in water vapor depletion over the Indian subcontinent that is the main moisture flux source for the southern Tibetan plateau. Increasing concentrations of black carbon causes a decrease in summer precipitation over the southern Tibetan plateau, resulting in 11.0% glacier deficit mass balance on average from 2007 to 2016; this loss rises to 22.1% in the Himalayas. The direct (accelerated melt) and indirect (mass supply decrease) effects of black carbon are driving the glacial mass decline of the so-called “Asian Water Tower”.

The common final pathway to blindness in many forms of retinal degeneration is the death of the light-sensitive primary retinal neurons. However, the normally light-insensitive second- and third-order neurons persist optogenetic gene therapy aims to restore sight by rendering such neurons light-sensitive. Here, we investigate whether bReaChES, a newly described high sensitivity Type I opsin with peak sensitivity to long-wavelength visible light, can restore vision in a murine model of severe early-onset retinal degeneration. Intravitreal injection of an adeno-associated viral vector carrying the sequence for bReaChES downstream of the calcium calmodulin kinase IIα promoter resulted in sustained retinal expression of bReaChES. Retinal ganglion cells (RGCs) expressing bReaChES generated action potentials at light levels consistent with bright indoor lighting (from 13.6 log photons cm−2 s−1). They could also detect flicker at up to 50 Hz, which approaches the upper temporal limit of human photopic vision. Topological response maps of bReaChES-expressing RGCs suggest that optogenetically activated RGCs may demonstrate similar topographical responses to RGCs stimulated by photoreceptor activation. Furthermore, treated dystrophic mice displayed restored cortical neuronal activity in response to light and rescued behavioral responses to a looming stimulus that simulated an aerial predator. Finally, human surgical retinal explants exposed to the bReaChES treatment vector demonstrated transduction. Together, these findings suggest that intravitreal gene therapy to deliver bReaChES to the retina may restore vision in human retinal degeneration in vivo at ecologically relevant light levels with spectral and temporal response characteristics approaching those of normal human photopic vision.

Background The way information about potential harms of trial intervention is shared within participant information leaflets (PILs) varies widely and can cause subjective ‘nocebo’ harms. This study aimed to develop principles to improve the composition of information about potential trial intervention benefits and harms within PILs so that variability and avoidable harms are reduced. Methods We conducted a two-round modified online Delphi survey, followed by a consensus meeting. For the first round of the survey, 27 statements were developed based on previous research and relevant guidance from the UK, the USA and the World Health Organization. Participants included members from each of the following stakeholder groups: patient and public representatives, research ethics committee members, industry representatives, medico-legal experts, psychologists and trial managers. Each participant was asked to rate their degree of agreement or disagreement with each statement on a 9-point Likert scale. In the second round, participants were invited to reappraise their ratings after reviewing the results of the first round. Finally, two members from each stakeholder group participated in a meeting to confirm those statements for which there was agreement. Results Two hundred and fifty participants completed round 1, and 201 participants completed round 2. In round 1, consensus was reached for 16 statements. In round 2, consensus was reached for an additional three statements. The consensus meeting confirmed the survey results and consolidated the statements. This process resulted in seven principles: (1) all potential harms of a given intervention should be listed, (2) all potential harms should be separated into serious and less serious, (3) it must be made explicit that not all potential harms are known, (4) all potential benefits should be listed, (5) all potential benefits and harms need to be compared with what would happen if the participant did not take part in the trial, (6) suitable visual representations should be added where appropriate and (7) information regarding potential benefits and harms should not be presented apart by one or more pages. Conclusions Our modified Delphi process successfully generated seven principles that can and should be used to guide how information is conveyed to patients in information leaflets regarding potential trial benefits and harms.