Systemic interindividual DNA methylation variants in cattle share major hallmarks with those in humans.

BACKGROUND: We recently identified ~ 10,000 correlated regions of systemic interindividual epigenetic variation (CoRSIVs) in the human genome. These methylation variants are amenable to population studies, as DNA methylation measurements in blood provide information on epigenetic regulation throughout the body. Moreover, establishment of DNA methylation at human CoRSIVs is labile to periconceptional influences such as nutrition. Here, we analyze publicly available whole-genome bisulfite sequencing data on multiple tissues of each of two Holstein cows to determine whether CoRSIVs exist in cattle. RESULTS: Focusing on genomic blocks with ≥ 5 CpGs and a systemic interindividual variation index of at least 20, our approach identifies 217 cattle CoRSIVs, a subset of which we independently validate by bisulfite pyrosequencing. Similar to human CoRSIVs, those in cattle are strongly associated with genetic variation. Also as in humans, we show that establishment of DNA methylation at cattle CoRSIVs is particularly sensitive to early embryonic environment, in the context of embryo culture during assisted reproduction. CONCLUSIONS: Our data indicate that CoRSIVs exist in cattle, as in humans, suggesting these systemic epigenetic variants may be common to mammals in general. To the extent that individual epigenetic variation at cattle CoRSIVs affects phenotypic outcomes, assessment of CoRSIV methylation at birth may become an important tool for optimizing agriculturally important traits. Moreover, adjusting embryo culture conditions during assisted reproduction may provide opportunities to tailor agricultural outcomes by engineering CoRSIV methylation profiles.

Inequities in the Training Environment and Health of Female Golfers Participating in the 2022 International Golf Federation World Amateur Team Championships.

OBJECTIVE: To assess health problems and training environment of female golfers participating in the 2022 World Amateur Team Championships (WATC) and to compare golfers (a) with and without health problems prior the WATC and (b) living and training in countries ranking in the upper versus lower 50% of the team results at the 2022 WATC. DESIGN: Cross-sectional cohort study using an anonymous questionnaire. SETTING: International Golf Federation WATC. PARTICIPANTS: One hundred sixty-two female golfers from 56 countries. INTERVENTIONS: N/A. MAIN OUTCOME MEASURES: Golfers' answers on the presence and characteristics of health problems, their training environment, and to the Oslo Sport Trauma Research Centre Questionnaire. RESULTS: Almost all golfers (n = 162; 96%) answered the questionnaire. In the 4 weeks before the WATC, 101 golfers (63.1%) experienced 186 musculoskeletal complaints, mainly at the lumbar spine/lower back, wrist, or shoulder. Just half of the golfers (50.6%) performed injury prevention exercises always or often. More than a third (37.4%) of the golfers reported illness complaints and 32.5% mental health problems in the 4 weeks preceding the WATC. General anxiety, performance anxiety, and low mood/depression were the most frequent mental health problems. Golfers with injury complaints rated their daily training environment poorer. Golfers ranking in the lower 50% at the WATC had significantly less support staff, rated their training environment poorer, and had a higher prevalence of illness complaints and mental health problems. CONCLUSIONS: Effective illness and injury prevention programs should be implemented and better access to education and health support in the daily training environment provided.

Multi-Level Precues for Guiding Tasks Within and Between Workspaces in Spatial Augmented Reality.

We explore Spatial Augmented Reality (SAR) precues (predictive cues) for procedural tasks within and between workspaces and for visualizing multiple upcoming steps in advance. We designed precues based on several factors: cue type, color transparency, and multi-level (number of precues). Precues were evaluated in a procedural task requiring the user to press buttons in three surrounding workspaces. Participants performed fastest in conditions where tasks were linked with line cues with different levels of color transparency. Precue performance was also affected by whether the next task was in the same workspace or a different one.

Digital adherence technologies to improve tuberculosis treatment outcomes in China: a cluster-randomised superiority trial.

BACKGROUND: Drug-sensitive tuberculosis treatment requires 6 months of therapy, so adherence problems are common. Digital adherence technologies might improve tuberculosis treatment outcomes. We aimed to evaluate the effect of a daily reminder medication monitor, monthly review of adherence data by the health-care provider, and differentiated care for patients with adherence issues, on tuberculosis treatment adherence and outcomes. METHODS: We did a cluster-randomised superiority trial across four prefectures in China. 24 counties or districts (clusters) were randomly assigned (1:1) to intervention or control groups. We enrolled patients aged 18 years or older with GeneXpert-positive, rifampicin-sensitive pulmonary tuberculosis, who were receiving daily fixed-dose combination treatment. Patients in the intervention group received a medication monitor for daily drug-dosing reminders, monthly review of adherence data by health-care provider, and management of poor adherence; and patients in the control group received routine care (silent-mode monitor-measured adherence). Only the independent endpoints review committee who assessed endpoint data for some participants were masked to study group assignment. Patients were followed up (with sputum solid culture) at 12 and 18 months. The primary outcome was a composite of death, loss to follow-up, treatment failure, switch to multidrug-resistant tuberculosis treatment, or tuberculosis recurrence by 18 months from treatment start, analysed in the intention-to-treat population. Analysis accounted for study design with multiple imputation for the primary outcome. This trial is now complete and is registered with ISRCTN, 35812455. FINDINGS: Between Jan 26, 2017, and April 3, 2019, 15 257 patients were assessed for eligibility and 3074 were enrolled, 2686 (87%) of whom were included in the intention-to-treat population. 1909 (71%) of 2686 patients were male, 777 (29%) were female, and the median age was 44 years (IQR 29-58). By 18 months from treatment start, using multiple imputation for missing outcomes, 239 (16% [geometric mean of cluster-level proportion]) of 1388 patients in the control group and 224 (16%) of 1298 in the intervention group had a primary composite outcome event (289 [62%] of 463 events were loss to follow-up during treatment and 42 [9%] were tuberculosis recurrence). The intervention had no effect on risk of the primary composite outcome (adjusted risk ratio 1·01, 95% CI 0·73-1·40). INTERPRETATION: Our digital medication monitor intervention had no effect on unfavourable outcomes, which included loss to follow-up during treatment, tuberculosis recurrence, death, and treatment failure. There was a failure to change patient management following identification of treatment non-adherence at monthly reviews. A better understanding of adherence patterns and how they relate to poor outcomes, coupled with a more timely review of adherence data and improved implementation of differentiated care, may be required. FUNDING: Bill & Melinda Gates Foundation.

A method for evaluating population and infrastructure exposed to natural hazards: tests and results for two recent Tonga tsunamis.

Background: Coastal communities are highly exposed to ocean- and -related hazards but often lack an accurate population and infrastructure database. On January 15, 2022 and for many days thereafter, the Kingdom of Tonga was cut off from the rest of the world by a destructive tsunami associated with the Hunga Tonga Hunga Ha'apai volcanic eruption. This situation was made worse by COVID-19-related lockdowns and no precise idea of the magnitude and pattern of destruction incurred, confirming Tonga's position as second out of 172 countries ranked by the World Risk Index 2018. The occurrence of such events in remote island communities highlights the need for (1) precisely knowing the distribution of buildings, and (2) evaluating what proportion of those would be vulnerable to a tsunami. Methods and Results: A GIS-based dasymetric mapping method, previously tested in New Caledonia for assessing and calibrating population distribution at high resolution, is improved and implemented in less than a day to jointly map population clusters and critical elevation contours based on runup scenarios, and is tested against destruction patterns independently recorded in Tonga after the two recent tsunamis of 2009 and 2022. Results show that ~ 62% of the population of Tonga lives in well-defined clusters between sea level and the 15 m elevation contour. The patterns of vulnerability thus obtained for each island of the archipelago allow exposure and potential for cumulative damage to be ranked as a function of tsunami magnitude and source area. Conclusions: By relying on low-cost tools and incomplete datasets for rapid implementation in the context of natural disasters, this approach works for all types of natural hazards, is easily transferable to other insular settings, can assist in guiding emergency rescue targets, and can help to elaborate future land-use planning priorities for disaster risk reduction purposes. Supplementary Information: The online version contains supplementary material available at 10.1186/s40677-023-00235-8.

Adaptive Reset Techniques for Haptic Retargeted Interaction.

This article presents a set of adaptive reset techniques for use with haptic retargeting systems focusing on interaction with hybrid virtual reality interfaces that align with a physical interface. Haptic retargeting between changing physical and virtual targets requires a reset where the physical and virtual hand positions are re-aligned. We present a modified Point technique to guide the user in the direction of their next interaction such that the remaining distance to the target is minimized upon completion of the reset. This, along with techniques drawn from existing work are further modified to consider the angular and translational gain of each redirection and identify the optimal position for the reset to take place. When the angular and translational gain is within an acceptable range, the reset can be entirely omitted. This enables continuous retargeting between targets removing interruptions from a sequence of retargeted interactions. These techniques were evaluated in a user study which showed that adaptive reset techniques can provide a significant decrease in task completion time, travel distance, and the number of user errors.

The Role of the Hand Surgery Consultant in the Care of the Amateur and Professional Golfer.

Golf is unique in this compendium of sports-related hand and wrist injury management. It is the only sport where the ball is stationary and there is no opponent against whom the player is defending. This distinctive sport dates to the 15th century in Scotland and is one of the oldest sports, but it is one where technology has changed many of the fundamental elements-from the "playing field (through advanced in agronomy) and the equipment (club and ball technology).

Event Related Brain Responses Reveal the Impact of Spatial Augmented Reality Predictive Cues on Mental Effort.

This article presents the results from a Spatial Augmented Reality (SAR) study which evaluated the cognitive cost of several predictive cues. Participants performed a validated procedural button pressing task, where the predictive cue annotations guided them to the upcoming task. While existing research has evaluated predictive cues based on their performance and self-rated mental effort, actual cognitive cost has yet to be investigated. To measure the user's brain activity, this study utilized electroencephalogram (EEG) recordings. Cognitive load was evaluated by measuring brain responses for a secondary auditory oddball task, with reduced brain responses to oddball tones expected when cognitive load in the primary task is highest. A simple monitor n-back task and procedural task comparing monitor versus SAR were conducted, followed by a version of the procedural task comparing the SAR predictive cues. Results from the brain responses were able to distinguish between performance enhancing cues with a high and low cognitive load. Electrical brain responses also revealed that having an arc or arrow guide towards the upcoming task required the least amount of mental effort.

Emerging Therapeutics, Technologies, and Drug Development Strategies to Address Patient Nonadherence and Improve Tuberculosis Treatment.

Imperfect medication adherence remains the biggest predictor of treatment failure for patients with tuberculosis. Missed doses during treatment lead to relapse, tuberculosis resistance, and further spread of disease. Understanding individual patient phenotypes, population pharmacokinetics, resistance development, drug distribution to tuberculosis lesions, and pharmacodynamics at the site of infection is necessary to fully measure the impact of adherence on patient outcomes. To decrease the impact of expected variabilityin drug intake on tuberculosis outcomes, an improvement in patient adherence and new forgiving regimens that protect against missed doses are needed. In this review, we summarize emerging technologies to improve medication adherence in clinical practice and provide suggestions on how digital adherence technologies can be incorporated in clinical trials and practice and the drug development pipeline that will lead to more forgiving regimens and benefit patients suffering from tuberculosis.

International consensus statement: methods for recording and reporting of epidemiological data on injuries and illnesses in golf.

Epidemiological studies of injury in elite and recreational golfers have lacked consistency in methods and definitions employed and this limits comparison of results across studies. In their sports-generic statement, the Consensus Group recruited by the IOC (2020) called for sport-specific consensus statements. On invitation by International Golf Federation, a group of international experts in sport and exercise medicine, golf research and sports injury/illness epidemiology was selected to prepare a golf-specific consensus statement. Methodological stages included literature review and initial drafting, online feedback from the consensus group, revision and second draft, virtual consensus meetings and completion of final version. This consensus statement provides golf-specific recommendations for data collection and research reporting including: (i) injury and illness definitions, and characteristics with golf-specific examples, (ii) definitions of golf-specific exposure measurements and recommendations for the calculation of prevalence and incidence, (iii) injury, illness and exposure report forms for medical staff and for golfers, and (iv) a baseline questionnaire. Implementation of the consensus methodology will enable comparison among golf studies and with other sports. It facilitates analysis of causative factors for injuries and illness in golf, and can also be used to evaluate the effects of prevention programmes to support the health of golfers.

There Is No Spoon: Evaluating Performance, Space Use, and Presence with Expert Domain Users in Immersive Analytics.

Immersive analytics turns the very space surrounding the user into a canvas for data analysis, supporting human cognitive abilities in myriad ways. We present the results of a design study, contextual inquiry, and longitudinal evaluation involving professional economists using a Virtual Reality (VR) system for multidimensional visualization to explore actual economic data. Results from our preregistered evaluation highlight the varied use of space depending on context (exploration vs. presentation), the organization of space to support work, and the impact of immersion on navigation and orientation in the 3D analysis space.

Conveying spatial awareness cues in xR collaborations.

Spatial Augmented Reality (SAR) systems can be suitably combined with other existing Extended Reality (xR) technologies to support collaboration. In existing strategies, users unencumbered by a viewing technology, such as a tablet interface or a head-mounted display, must rely on the transmission of their collaborators' positioning through interpreting a first-person camera view. This design creates a seam between a user's experience of the augmented physical environment in SAR, and their collaborators' experience inside the virtual environment. To assist in development and evaluation of spatial cues to support spatial awareness in SAR environments, an egocentric spatial-communication taxonomy is presented given two determining dimensions, a cue's attachment (physical/virtual) and animation (local/world). We developed four egocentric cues which characterize the four independent dimensions of the matrix: arrow, path, glow, and radial, and a single exocentric world in miniature visualization. Our study shows that virtual attachment cues are preferred, providing the highest accuracy, highest performance when collaborators are occluded, and produce the least mental effort when used with a single virtual collaborator. For multiple collaborators however, the virtual attached, world animated radial cue produces significant increases in mental load and reductions in preference, demonstrating the impact of visual augmentation clutter. The single exocentric visualization produced higher levels of head movement, and poorer accuracy, however the novelty of the visualization produced positive qualitative results.

Assessment of Bowel End Perfusion After Mesenteric Division: Eye Versus SPY.

BACKGROUND: Anastomotic complications related to tissue ischemia cause morbidity in gastrointestinal (GI) surgery. Surgeons' standard practice to predict bowel perfusion is inspection of mesenteric perfusion before anastomosing bowel ends. Augmenting this assessment with fluorescent imaging is under study. A standardized system to evaluate this imaging has not yet been developed. This study compared the surgeon's intraoperative assessment to a novel GI-specific imaging analysis method. MATERIALS AND METHODS: Forty-nine consecutive patients undergoing open or laparoscopic-assisted bowel resections were enrolled. After mesenteric division, the surgeon marked the site for bowel transection. Near-infrared fluorescence imaging was performed on the marked bowel ends. Imaging analysis identified theoretical transection sites based on the quantification of arterial and microvascular inflow (Perfusion) and venous outflow (Timing). The primary outcome was the measured disparity between the site marked by the surgeon using current standard of care parameters and the imaging-determined site. No clinical outcomes were assessed. RESULTS: Seventy-two bowel end segments from 46 patients were analyzed. Disparity was found in 11 of 72 (15%) bowel end segments. In five (7%), the disparity was due to either Perfusion or Timing (single), and in six (8%), due to both Perfusion and Timing (combined). In the single disparity group, the median disparity distance was 2.0 cm by Perfusion and 4.0 cm by Timing, and in the combined group, 3.8 cm by Perfusion and 3.5 cm by Timing. Disparity (either single or combined) was in 25% of colon and 11.5% of small bowel (P = NS). Combined and single disparity had equivalent lengths of disparity distance (P = NS). CONCLUSIONS: Imaging coupled with this GI-specific analysis provides objective, real-time, and interpretable data of intramural blood supply. A 15% disparity rate from current clinical practice was observed.

Superman vs Giant: A Study on Spatial Perception for a Multi-Scale Mixed Reality Flying Telepresence Interface.

The advancements in Mixed Reality (MR), Unmanned Aerial Vehicle, and multi-scale collaborative virtual environments have led to new interface opportunities for remote collaboration. This paper explores a novel concept of flying telepresence for multi-scale mixed reality remote collaboration. This work could enable remote collaboration at a larger scale such as building construction. We conducted a user study with three experiments. The first experiment compared two interfaces, static and dynamic IPD, on simulator sickness and body size perception. The second experiment tested the user perception of a virtual object size under three levels of IPD and movement gain manipulation with a fixed eye height in a virtual environment having reduced or rich visual cues. Our last experiment investigated the participant's body size perception for two levels of manipulation of the IPDs and heights using stereo video footage to simulate a flying telepresence experience. The studies found that manipulating IPDs and eye height influenced the user's size perception. We present our findings and share the recommendations for designing a multi-scale MR flying telepresence interface.

A Comparison of Predictive Spatial Augmented Reality Cues for Procedural Tasks.

Previous research has demonstrated that Augmented Reality can reduce a user's task response time and mental effort when completing a procedural task. This paper investigates techniques to improve user performance and reduce mental effort by providing projector-based Spatial Augmented Reality predictive cues for future responses. The objective of the two experiments conducted in this study was to isolate the performance and mental effort differences from several different annotation cueing techniques for simple (Experiment 1) and complex (Experiment 2) button-pressing tasks. Comporting with existing cognitive neuroscience literature on prediction, attentional orienting, and interference, we hypothesized that for both simple procedural tasks and complex search-based tasks, having a visual cue guiding to the next task's location would positively impact performance relative to a baseline, no-cue condition. Additionally, we predicted that direction-based cues would provide a more significant positive impact than target-based cues. The results indicated that providing a line to the next task was the most effective technique for improving the users' task time and mental effort in both the simple and complex tasks.

Narrative and Spatial Memory for Jury Viewings in a Reconstructed Virtual Environment.

This paper showcases one way of how virtual reconstruction can be used in a courtroom. The results of a pilot study on narrative and spatial memory are presented in the context of viewing real and virtual copies of a simulated crime scene. Based on current court procedures, three different viewing options were compared: photographs, a real life visit, and a 3D virtual reconstruction of the scene viewed in a Virtual Reality headset. Participants were also given a written narrative that included the spatial locations of stolen goods and were measured on their ability to recall and understand these spatial relationships of those stolen items. The results suggest that Virtual Reality is more reliable for spatial memory compared to photographs and that Virtual Reality provides a compromise for when physical viewing of crime scenes are not possible. We conclude that Virtual Reality is a promising medium for the court.

Evaluation of a medication monitor-based treatment strategy for drug-sensitive tuberculosis patients in China: study protocol for a cluster randomised controlled trial.

BACKGROUND: Treatment for drug-sensitive tuberculosis (TB) is taken for at least 6 months and problems with adherence are common. Therefore, there is substantial interest in the possible use of eHealth interventions to support patients to take their treatment. Electronic medication monitors have been shown to improve adherence to TB medication, but the impact on clinical outcomes is unknown. We aim to evaluate the impact of a medication monitor-based treatment strategy for drug-sensitive TB patients on a composite poor outcome measured over 18 months from start of TB treatment. METHODS/DESIGN: We will conduct an open, pragmatic, cluster randomised superiority trial, with 24 counties/districts in three provinces in China, randomised 1:1 to implement the intervention or standard of care. Adults (aged ≥ 18 years) with a new episode of GeneXpert-positive and rifampicin-sensitive pulmonary TB, who plan to be in the study area for the next 18 months, and will receive daily fixed-dose combination tablets for 6 months of treatment are eligible. The intervention is centred around a medication monitor that holds a 1-month supply of medication and has three key functions: as an audio and visual reminder for patients to take their daily medication; reminds patients of upcoming monthly visit; and records date and time whenever the box is opened. At the monthly follow-up visit, the doctor downloads these data to generate a graphical display of the last month's adherence record for discussion with the patient and potentially to switch the patient to more intensive management. The primary outcome is a composite poor outcome measured over 18 months from start of TB treatment, defined as either of poor outcome at the end of treatment (death, treatment failure, or loss to follow-up) or subsequent recurrence (culture positive for TB at 12 or 18 months or re-starting TB treatment in the follow-up period). An economic evaluation will also be conducted as part of this study. DISCUSSION: This trial will assess whether a medication monitor-based treatment strategy can improve clinical outcomes for TB patients. Several trials of other eHealth interventions for TB treatment are ongoing and are summarised in this paper. This trial will provide an important part of the emerging evidence base for the potential of eHealth to improve TB treatment outcomes. TRIAL REGISTRATION: This trial was registered with Current Controlled Trials (identifier: ISRCTN35812455 ). Registered on May 19, 2016.

A cross-sectional study of the filarial and Leishmania co-endemicity in two ecologically distinct settings in Mali.

BACKGROUND: Filariasis and leishmaniasis are two neglected tropical diseases in Mali. Due to distribution and associated clinical features, both diseases are of concern to public health. The goal of this study was to determine the prevalence of co-infection with filarial (Wuchereria bancrofti and Mansonella perstans) and Leishmania major parasites in two ecologically distinct areas of Mali, the Kolokani district (villages of Tieneguebougou and Bougoudiana) in North Sudan Savanna area, and the district of Kolondieba (village of Boundioba) in the South Sudan Savanna area. METHODS: The prevalence of co-infection (filarial and Leishmania) was measured based on (i) Mansonella perstans microfilaremia count and/or filariasis immunochromatographic test (ICT) for Wuchereria bancrofti-specific circulating antigen, and (ii) the prevalence of delayed type hypersensitivity (DTH) responses to Leishmania measured by leishmanin skin test (LST). RESULTS: In this study, a total of 930 volunteers between the age of 18 and 65 were included from the two endemic areas of Kolokani and Kolondieba. In general, in both areas, filarial infection was more prevalent than Leishmania infection with an overall prevalence of 15.27% (142/930) including 8.7% (81/930) for Mansonella perstans and 8% (74/930) for Wuchereria bancrofti-specific circulating antigen. The prevalence of Leishmania major infection was 7.7% (72/930) and was significantly higher in Tieneguebougou and Bougoudiana (15.05%; 64/425) than in Boundioba (2.04%; 8/505) (χ2 = 58.66, P < 0.0001). Among the filarial infected population, nearly 10% (14/142) were also positive for Leishmania with an overall prevalence of co-infection of 1.50% (14/930) varying from 2.82% (12/425) in Tieneguebougou and Bougoudiana to 0.39% (2/505) in Boundioba (P = 0.0048). CONCLUSION: This study established the existence of co-endemicity of filarial and Leishmania infections in specific regions of Mali. Since both filarial and Leishmania infections are vector-borne with mosquitoes and sand flies as respective vectors, an integrated vector control approach should be considered in co-endemic areas. The effect of potential interaction between filarial and Leishmania parasites on the disease outcomes may be further studied.