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The current study aimed to predict secondary school students' motivation toward sport injury prevention in 'in-school' and 'out-of-school' contexts, and their sport injury prevention behaviour at 3-month follow-up using the trans-contextual model (TCM). Hong Kong secondary school students (N = 1,566; mean age = 13.34 years, range = 11 to 19; female = 49.42%) were recruited. Participants were asked to complete a survey comprising previously-validated scales measuring TCM constructs at baseline, and a measure of sport injury prevention behaviour at follow-up three months later. Structural equation modeling (SEM) was used to examine the hypothesised paths among TCM constructs. A SEM specifying hypothesised paths among TCM variables showed acceptable fit with the data (χ2 (29) = 418.55, CFI = .93, TLI = .90, and RMSEA = .09, 90% CI [.09, .10], and SRMR = .05). Findings supported tenets of the TCM: the effects of perceived autonomy support from PE teachers on in-school autonomous motivation toward injury prevention, the trans-contextual relationship between students' 'in-school' and 'out-of-school' autonomous motivation toward injury prevention, and the effects of autonomous motivation toward injury prevention on social cognitive variables and subsequent sport injury prevention behaviours. Results supported the tenets proposed within the TCM in predicting students' 'in-school' and 'out-of-school' autonomous motivation toward sport injury prevention. Findings underscore the potential importance of autonomy support from PE teachers in facilitating students' sport injury prevention behaviours. Further longitudinal and intervention research is warranted to establish temporal and causal effects of TCM variables in sport injury prevention.
The current study tested the effects of an intervention based on the trans-contextual model (TCM) on secondary school PE students’ sport injury prevention behaviour, and on theory-based motivational and social cognition mediators. Participants were PE students (N=1,168; Mage=13.322±1.045, range=12 to 16; female=51.721%) who participated in a 3-month cluster-randomised controlled trial. Schools were randomly assigned to a treatment group, in which PE teachers received training to be more supportive of psychological needs in teaching sport injury prevention, or a control group, in which PE teachers received no training. Participants completed survey measures of TCM variables and self-reported sport injury prevention behaviour at baseline and at 3-month post-intervention follow-up. The proposed TCM model exhibited adequate fit with the data, χ2=143.080 (df=19), CFI=.956, TLI=.916, RMSEA=.078 [90% CI=.066 to .090], and SRMR=.058. We found positive, statistically significant direct intervention effects on changes in perceived psychological need support (β=.064, p=.020). We also found positive, significant direct (β=.086 to .599, p<.001) and indirect (β=.002 to .027, p=.020 to .032) intervention effects on changes in TCM variables and behaviours to prevent sport injuries. Our findings support the TCM as a useful framework for building an intervention for promoting sport injury prevention behaviours among secondary school students.
We experimentally observe the decay dynamics of deterministically created isolated monopoles in spin-1 Bose-Einstein condensates. As the condensate undergoes a change between magnetic phases, the isolated monopole gradually evolves into a spin configuration hosting a Dirac monopole in its synthetic magnetic field. We characterize in detail the Dirac monopole by measuring the particle densities of the spin states projected along different quantization axes. Importantly, we observe the spontaneous emergence of nodal lines in the condensate density that accompany the Dirac monopole. We also demonstrate that the monopole decay accelerates in weaker magnetic field gradients.
Objectives: The aim of this prospective study was to examine the utility of an integrated model comprising constructs from self-determination theory (SDT) and the theory of planned behavior (TPB) in predicting adherence to a post-surgery rehabilitation program in patients receiving anterior cruciate ligament (ACL) reconstruction. Constructs of the integrated model measured at baseline were expected to predict patients' rehabilitation adherence two months later. Method: Patients (N = 121, M age = 27.62, range = 18–53; 36.66% female) scheduled to have ACL reconstruction surgery within two months were recruited from a Hong Kong public hospital. At baseline and two-month follow-up, patients completed measures of perceived autonomy support from doctors and physiotherapists and treatment motivation from SDT, social cognition constructs from the TPB factors, and adherence to the postsurgery rehabilitation program recommended by their surgeon. Results: Path analysis displayed good goodness-of-fit of the proposed model with the data (χ2 = 11.47 (df = 9), CFI = 0.98, TLI = 0.93, RMSEA = 0.06 [90% CI = 0.00; 0.10]) after controlling for age, gender, time of surgery, post-surgery rehabilitation, and injury severity. Consistent with hypotheses, perceived autonomy support from physiotherapist and autonomous treatment motivation directly and indirectly predicted the TPB constructs and treatment adherence. However, there was no association between perceived autonomy support from doctors and autonomous motivation. Conclusion: The integrated model was effective in explaining the psychological processes that relate to medical adherence. Findings also highlight the importance of the autonomy support from physiotherapists and provide evidence for potential intervention targets.
Abstract Osteoarthritis (OA) is the most common form of arthritis, characterized by cartilage destruction, pain and inflammation in the joints. Existing medications can provide relief from the symptoms, but their effects on the progression of the disease are limited. TissueGene-C (TG-C) is a novel cell and gene therapy for the treatment of OA, comprising a mixture of human allogeneic chondrocytes and irradiated cells engineered to overexpress transforming growth factor-β1 (TGF-β1). This study aims to investigate the efficacy and mechanism of action of TG-C in a rat model of OA. Using the monosodium-iodoacetate (MIA) model of OA, we examined whether TG-C could improve OA symptoms and cartilage structure in rats. Our results showed that TG-C provided pain relief and cartilage structural improvement in the MIA OA model over 56 days. In parallel with these long-term effects, cytokine profiles obtained on day 4 revealed increased expression of interleukin-10 (IL-10), an anti-inflammatory cytokine, in the synovial lavage fluid. Moreover, the increased levels of TGF-β1 and IL-10 caused by TG-C induced the expression of arginase 1, a marker of M2 macrophages, and decreased the expression of CD86, a marker of M1 macrophages. These results suggest that TG-C exerts a beneficial effect on OA by inducing a M2 macrophage-dominant micro-environment. Cell therapy using TG-C may be a promising strategy for targeting the underlying pathogenic mechanisms of OA, reducing pain, improving function, and creating a pro-anabolic micro-environment. This environment supports cartilage structure regeneration and is worthy of further evaluation in future clinical trials.
Two studies were employed to test the reliability and validity of the Swimming Competence Questionnaire (SCQ) among primary school children. Study 1 was a cross-sectional survey in 4959 primary school children. Study 2 was a pre-post-test quasi-experiment among 1609 primary school children who underwent a 20-lesson learn-to-swim programme. In Study 1, exploratory structural equation modelling revealed excellent goodness-of-fit and scale reliability for a two-factor model comprising distance and skill factors, which supported the construct and convergent validity. SCQ scores were significantly and positively correlated with swimming outcomes (i.e., self-efficacy, intention, swimming frequency), which supported SCQ’s concurrent and criterion validity. Average variance extracted for the SCQ factors exceeded cut-off criteria supporting discriminant validity. In Study 2, pre-test SCQ scores correlated significantly and positively with the SCQ scores, self-efficacy, intention, and swimming frequency at post-test, which supported SCQ’s test-retest reliability and predictive validity. Positive intraclass correlation between SCQ scores and coach ratings at post-test provided evidence for SCQ’s inter-rater reliability. SCQ scores significantly improved at post-test, which supported SCQ’s ecological validity. In conclusion, findings indicate that the SCQ is a valid and reliable measure to assess primary school children’s swimming competence, in terms of swimming distance and basic water survival skills.
Doping attitude is an individual’s subjective evaluation (e.g., good or bad, useful or useless) toward the use of prohibited performance-enhancing substances or methods in sports. Research on doping attitude has traditionally relied on self-report questionnaire methods to measure the construct (Ntoumanis et al., 2014; Chan et al., 2015). However, as doping in sport is illegal (World AntiDoping Agency, 2015) and perceived as socially unacceptable, athletes who hold positive attitudes toward doping are less likely to reveal them to others. As a result explicit measures of doping attitude are susceptible to potential bias as athletes may respond in a socially desirable fashion (Petróczi and Aidman, 2009; Gucciardi et al., 2010). To counter such bias, implicit measures such as the implicit association test (IAT; Greenwald et al., 1998) have been developed to capture individuals’ non-conscious attitudes toward doping (Brand et al., 2014a,b; Schindler et al., 2015). The current paper aims to introduce a paper-and-pen IAT which could potentially serve as alternative method to the traditional computer-IAT for measuring athletes’ doping attitude.
We provide evidence that the chirality of collagen can give rise to strong second-harmonic generation circular dichroism (SHG-CD) responses in nonlinear microscopy. Although chirality is an intrinsic structural property of collagen, most of the previous studies ignore that property. We demonstrate chiral imaging of individual collagen fibers by using a laser scanning microscope and type-I collagen from pig ligaments. 100% contrast level of SHG-CD is achieved with sub-micrometer spatial resolution. As a new contrast mechanism for imaging chiral structures in bio-tissues, this technique provides information about collagen morphology and threedimensional orientation of collagen molecules.
Aims: Cardiorenal syndrome (CRS) is a common problem of great morbidity and mortality. Hydralazine–isosorbide dinitrate (H-ISDN) may be used in renal failure and may improve exercise capacity in heart failure (HF). Our proof-of-concept study aimed to evaluate early evidence of efficacy, safety, and feasibility of H-ISDN compared with standard of care in CRS. Methods and results: This multi-centre, single-blind, randomized trial in Singapore enrolled CRS patients, defined as chronic HF with concomitant renal failure [estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2]. The primary outcome was 6 min walk test (6MWT) distance measured at 6 months. Secondary outcomes included study feasibility; efficacy outcomes which included renal, cardiac, and endothelial functions, health-related quality of life using Short Form-36, clinical outcomes; and adverse events. Forty-four patients [71 ± 10 years; 75% male; median (inter-quartile range) N-terminal prohormone brain natriuretic peptide 1346 (481–2272) pg/mL] with CRS (left ventricular ejection fraction 42 ± 12% and eGFR 46 ± 15 ml/min/1.73 m2) were randomized into two equal groups. Of these, 39 (89%) had hypertension, 27 (61%) had diabetes mellitus, and 17 (39%) had atrial fibrillation. Six (27%) discontinued H-ISDN owing to intolerance and poor compliance. There was a trend towards improved 6MWT distance with H-ISDN compared with standard of care at 6 months (mean difference 27 m; 95% CI, −12 to 66), with little differences in secondary efficacy outcomes. Giddiness and hypotension occurred more frequently with H-ISDN, but HF hospitalizations and mortality were less. Conclusions: Our pilot study does not support the addition of H-ISDN on top of standard medical therapy to improve exercise capacity in patients with CRS.
Abstract In 2017, the Event Horizon Telescope (EHT) Collaboration succeeded in capturing the first direct image of the center of the M87 galaxy. The asymmetric ring morphology and size are consistent with theoretical expectations for a weakly accreting supermassive black hole of mass ∼6.5 × 109 M☉. The EHTC also partnered with several international facilities in space and on the ground, to arrange an extensive, quasi-simultaneous multi-wavelength campaign. This Letter presents the results and analysis of this campaign, as well as the multi-wavelength data as a legacy data repository. We captured M87 in a historically low state, and the core flux dominates over HST-1 at high energies, making it possible to combine core flux constraints with the more spatially precise very long baseline interferometry data. We present the most complete simultaneous multi-wavelength spectrum of the active nucleus to date, and discuss the complexity and caveats of combining data from different spatial scales into one broadband spectrum. We apply two heuristic, isotropic leptonic single-zone models to provide insight into the basic source properties, but conclude that a structured jet is necessary to explain M87’s spectrum. We can exclude that the simultaneous γ-ray emission is produced via inverse Compton emission in the same region producing the EHT mm-band emission, and further conclude that the γ-rays can only be produced in the inner jets (inward of HST-1) if there are strongly particle-dominated regions. Direct synchrotron emission from accelerated protons and secondaries cannot yet be excluded.
Abstract Monitoring the qualitative status of freshwaters is an important goal of the international community, as stated in the Sustainable Development Goal (SDGs) indicator 6.3.2 on good ambient water quality. Monitoring data are, however, lacking in many countries, allegedly because of capacity challenges of less-developed countries. So far, however, the relationship between human development and capacity challenges for water quality monitoring have not been analysed systematically. This hinders the implementation of fine-tuned capacity development programmes for water quality monitoring. Against this background, this study takes a global perspective in analysing the link between human development and the capacity challenges countries face in their national water quality monitoring programmes. The analysis is based on the latest data on the human development index and an international online survey amongst experts from science and practice. Results provide evidence of a negative relationship between human development and the capacity challenges to meet SDG 6.3.2 monitoring requirements. This negative relationship increases along the course of the monitoring process, from defining the enabling environment, choosing parameters for the collection of field data, to the analytics and analysis of five commonly used parameters (DO, EC, pH, TP and TN). Our assessment can be used to help practitioners improve technical capacity development activities and to identify and target investment in capacity development for monitoring.
Rationale Patients with anterior cruciate ligament (ACL) reconstruction often have poor adherence to post-surgery rehabilitation. Objective This study applied the integrated model of self-determination theory and the theory of planned behavior to examine the effects of a smartphone-delivered intervention on the recovery outcomes of patients with an ACL rupture during post-surgery rehabilitation period. Additionally, we explored the effects of the intervention on participants with different beliefs toward rehabilitation at baseline. Methods The randomized control trial recruited 96 eligible participants (M age = 27.82 years, SD = 8.73; female = 39%) who underwent ACL reconstruction surgery. Participants were randomly assigned to an intervention group (n = 41), which received standard post-surgical treatment (usual-care) and smartphone application (“ACL-Well”), or a usual-care control group (n = 55). The primary outcomes were recovery outcomes from ACL surgery measured by knee muscle strength and laxity, and subjective knee evaluation completed 4-month post-intervention. Secondary outcomes were the psychological and behavioral outcomes measured at baseline, at 2- and 4-month post-intervention. Results ANCOVA indicated no significant between-group differences in primary outcomes: knee muscle strength, knee laxity and subjective knee evaluation, Fs(1, 27 to 55) = 0.01 to 1.36, p = .25 to .99, η2 = 0.01 to 0.03. For the secondary outcomes, growth mixture modelling revealed self-determined treatment motivation declined significantly over the intervention period in the control group (M slope = −0.39 to −0.12, p = .01 to .04), but not in the intervention group (M slope = −0.19 to −0.08, p = .06 to .38). Conclusions The smartphone application fell short in promoting orthopedic outpatients' recovery outcomes. Yet, it shows some promises as a mean to maintain patients’ motivation and adherence to treatment.
Abstract One of the non-resonant techniques is the free-space measurement technique, which is popular due to its many advantages compared to the other techniques. It allows the transmission and reflection measurements without any physical contact with the sample. This paper discusses the free-space material measurement system in Ku-band which uses the NRW algorithm and Keysight (Formerly Agilent) 85071E software in determining the dielectric properties of materials. The permittivity and permeability of Teflon, FR4, PVC, ABS, Acrylic, polypropylene, polycarbonate, and epoxy were determined using free space measurement setup. For the first, a free-space measurement for Ku-Band is setup. It consists of a vector network analyzer, two horn antennas, sample holder, and Keysight 85071E software. The different role of transmission and reflection measurements on the achievable results is analyzed about experimental uncertainties and different noise scenarios. Results from the two strategies are analyzed and compared. Good agreement between simulation, measurement, and literature was obtained.
Abstract Objective: Sauna bathing is becoming a common activity in many countries and it has been linked to favorable health outcomes. However, there is limited data on the heart rate (HR) and heart rate variability (HRV) responses to an acute sauna exposure. Design: We conducted a single-group, longitudinal study utilizing a pre-post design to examine acute effects of sauna bathing on the autonomic nervous system as reflected by HRV. A total of 93 participants (mean [SD] age: 52.0 [8.8] years, 53.8% males) with cardiovascular risk factors were exposed to a single sauna session (duration: 30 min; temperature: 73 °C; humidity: 10–20%) and data on HRV variables were collected before, during and after sauna. Results: Time and frequency-domain HRV variables were significantly modified (p < 0.001) by the single sauna session, with most of HRV variables tending to return near to baseline values after 30 min recovery. Resting HR was lower at the end of recovery (68/min) compared to pre-sauna (77/min). A sauna session transiently diminished the vagal component, whereas the cooling down period after sauna decreased low frequency power (p < 0.001) and increased high frequency power in HRV (p < 0.001), favorably modulating the autonomic nervous system balance. Conclusions: This study demonstrates that a session of sauna bathing induces an increase in HR. During the cooling down period from sauna bathing, HRV increased which indicates the dominant role of parasympathetic activity and decreased sympathetic activity of cardiac autonomic nervous system. Future randomized controlled studies are needed to show if HR and HRV changes underpins the long-term cardiovascular effects induced by regular sauna bathing.
Abstract A large body of evidence demonstrates positive, graded effects of PA on cardiovascular disease (CVD) morbidity and mortality with increasing intensity compared with lower PA intensity. Running is often designated as a high-intensity PA with substantial evidence supporting its health benefits. Cross-country skiing is among the most demanding aerobic endurance exercises and requires engaging the upper- and lower-body. Cross-country skiing is often regarded as high-intensity PA, which has been associated with significant health benefits. However, a robust body of evidence identifying the dose-response relation between cross-country skiing volume and health outcomes is sparse. Therefore, this review aims to summarize the available evidence linking cross-country skiing with CVD morbidity and all-cause mortality; postulated pathways that may elucidate the relation between these associations; outline areas of ongoing uncertainty; and the implications for primary and secondary CVD prevention. To put the findings into perspective, we also summarized the evidence linking running with CVD morbidity and all-cause mortality. Though a head-to-head comparison is not available, the evidence indicates that performing PA as cross-country skiing associates with lower mortality risk when compared with that observed in those undertaking their PA as running. Potential adverse effects of extreme high weekly doses of cross-country skiing over decades may be cardiac arrhythmias, such as atrial fibrillation. Evidence suggests that cross-country skiing may reduce the risk of CVD events and all-cause mortality via anti-inflammatory pathways, improvements in endothelial function and reduced levels of CVD risk factors, such as lipids, glucose, and blood pressure; and enhancement of cardiorespiratory fitness.
Abstract A new and putatively endemic species of Hydroclathrus, Hydroclathrus rapanuii, is described from the geographically isolated Easter Island in the southeastern Pacific based on morphological and molecular phylogenetic data. It is distinguished from other Hydroclathrus by thalli of unevenly furrowed thin membranes, and angular, block-like plurangial sori. Our phylogenetic analyses indicated that H. rapanuii is closely related to the generitype Hydroclathrus clathratus. We also report on the morphology and phylogeny of Chnoospora minima from Easter I. and elsewhere in the Indo-Pacific Ocean, noting the previously unreported presence of hollow portions in its medulla. Although not collected from Easter I., we herein propose the recognition of two new genera, Dactylosiphon gen. nov. and Pseudochnoospora gen. nov., based on our three-gene phylogeny and their known morphologies and anatomies. Dactylosiphon is based on the three species currently assigned to Colpomenia (C. bullosa, C. durvillei, and C. wynnei) that are genetically and morphologically (i.e. thalli with erect and finger-like tubes arising from a common saccate base) distinct from other members of Colpomenia. The monotypic genus Pseudochnoospora is represented by the decumbent, branching, and interadhesive species currently known as Chnoospora implexa. With the above proposals, we further increase the genus-level diversity of Scytosiphonaceae in the Indo-Pacific Ocean.
Abstract The taxonomic status of the European Hoplodrina octogenaria (Goeze, 1781) is discussed and its partly sympatric sister species, Hoplodrina alsinides (Costantini, 1922) sp. rev., is separated and re-described based on morphological and molecular taxonomic evidence. The adults and their genitalia are illustrated and DNA barcodes, as well as genome-wide single nucleotide polymorphism data collected by fractional genome sequencing (ddRAD), of the two species are provided.
Abstract The seamless textual input in Augmented Reality (AR) is very challenging and essential for enabling user-friendly AR applications. Existing approaches such as speech input and vision-based gesture recognition suffer from environmental obstacles and the large default keyboard size, sacrificing the majority of the screen’s real estate in AR. In this paper, we propose MyoKey, a system that enables users to effectively and unobtrusively input text in a constrained environment of AR by jointly leveraging surface Electromyography (sEMG) and Inertial Motion Unit (IMU) signals transmitted by wearable sensors on a user’s forearm. MyoKey adopts a deep learning-based classifier to infer hand gestures using sEMG. In order to show the feasibility of our approach, we implement a mobile AR application using the Unity application building framework. We present novel interaction and system designs to incorporate information of hand gestures from sEMG and arm motions from IMU to provide seamless text entry solution. We demonstrate the applicability of MyoKey by conducting a series of experiments achieving the accuracy of 0.91 on identifying five gestures in real-time (Inference time: 97.43 ms).
The accumulation of fat, especially in visceral sites, is a significant risk factor for several chronic diseases with altered cardiometabolic homeostasis. We studied how intensive long-term weight loss and subsequent weight regain affect physiological changes, by longitudinally interrogating the lipid metabolism and white blood cell transcriptomic markers in healthy, normal-weight individuals. The current study examined 42 healthy, young (age: 27.5 ± 4.0 years), normal-weight (body mass index, BMI: 23.4 ± 1.7 kg/m2) female athletes, of which 25 belong to the weight loss and regain group (diet group), and 17 to the control group. Participants were evaluated, and fasting blood samples were drawn at three time points: at baseline (PRE); at the end of the weight loss period (MID: 21.1 ± 3.1 weeks after PRE); and at the end of the weight regain period (POST: 18.4 ± 2.9 weeks after MID). Following the weight loss period, the diet group experienced a ~73% reduction (~0.69 kg) in visceral fat mass (false discovery rate, FDR < 2.0 × 10−16), accompanied by anti-atherogenic effects on transcriptomic markers, decreased low-grade inflammation (e.g., as α1–acid glycoprotein (FDR = 3.08 × 10−13) and hs-CRP (FDR = 2.44 × 10−3)), and an increase in functionally important anti-atherogenic high-density lipoprotein -associated metabolites (FDR < 0.05). This occurred even though these values were already at favorable levels in these participants, who follow a fitness-lifestyle compared to age- and BMI-matched females from the general population (n = 58). Following the weight regain period, most of the observed beneficial changes in visceral fat mass, and metabolomic and transcriptomic profiles dissipated. Overall, the beneficial anti-atherogenic effects of weight loss can be observed even in previously healthy, normal-weight individuals.
Abstract A rapid shift from traditional Sanger sequencing-based molecular methods to the phylogenomic approach with large numbers of loci is underway. Among phylogenomic methods, restriction site associated DNA (RAD) sequencing approaches have gained much attention as they enable rapid generation of up to thousands of loci randomly scattered across the genome and are suitable for nonmodel species. RAD data sets however suffer from large amounts of missing data and rapid locus dropout along with decreasing relatedness among taxa. The relationship between locus dropout and the amount of phylogenetic information retained in the data has remained largely uninvestigated. Similarly, phylogenetic hypotheses based on RAD have rarely been compared with phylogenetic hypotheses based on multilocus Sanger sequencing, even less so using exactly the same species and specimens. We compared the Sanger-based phylogenetic hypothesis (8 loci; 6172 bp) of 32 species of the diverse moth genus Eupithecia (Lepidoptera, Geometridae) to that based on double-digest RAD sequencing (3256 loci; 726,658 bp). We observed that topologies were largely congruent, with some notable exceptions that we discuss. The locus dropout effect was strong. We demonstrate that number of loci is not a precise measure of phylogenetic information since the number of single-nucleotide polymorphisms (SNPs) may remain low at very shallow phylogenetic levels despite large numbers of loci. As we hypothesize, the number of SNPs and parsimony informative SNPs (PIS) is low at shallow phylogenetic levels, peaks at intermediate levels and, thereafter, declines again at the deepest levels as a result of decay of available loci. Similarly, we demonstrate with empirical data that the locus dropout affects the type of loci retained, the loci found in many species tending to show lower interspecific distances than those shared among fewer species. We also examine the effects of the numbers of loci, SNPs, and PIS on nodal bootstrap support, but could not demonstrate with our data our expectation of a positive correlation between them. We conclude that RAD methods provide a powerful tool for phylogenomics at an intermediate phylogenetic level as indicated by its broad congruence with an eight-gene Sanger data set in a genus of moths. When assessing the quality of the data for phylogenetic inference, the focus should be on the distribution and number of SNPs and PIS rather than on loci.
Abstract We studied the evolutionary relationship of two widely distributed parapatric butterfly species, Melitaea athalia and Melitaea celadussa, using the ddRAD sequencing approach, as well as genital morphology and mtDNA data. M. athalia was retrieved as paraphyletic with respect to M. celadussa. Several cases of mito-nuclear discordance and morpho-genetic mismatch were found in the contact zone. A strongly diverged and marginally sympatric clade of M. athalia from the Balkans was revealed. An in-depth analysis of genomic structure detected high levels of admixture between M. athalia and M. celadussa at the contact zone, though not reaching the Balkan clade. The demographic modelling of populations supported the intermediate genetic make-up of European M. athalia populations with regards to M. celadussa and the Balkan clade. However, the dissimilarity matrix of genotype data (PCoA) suggested the Balkan lineage having a genetic component that is unrelated to the athalia-celadussa group. Although narrowly sympatric, almost no signs of gene flow were found between the main M. athalia group and the Balkan clade. We propose two possible scenarios on the historical evolution of our model taxa and the role of the last glacial maximum in shaping their current distribution. Finally, we discuss the complexities regarding the taxonomic delimitation of parapatric taxa.
Objective: To examine prevalence of novel newborn types among 541 285 live births in 23 countries from 2000 to 2021. Design: Descriptive multi-country secondary data analysis. Setting: Subnational, population-based birth cohort studies (n = 45) in 23 low- and middle-income countries (LMICs) spanning 2000–2021. Population: Liveborn infants. Methods: Subnational, population-based studies with high-quality birth outcome data from LMICs were invited to join the Vulnerable Newborn Measurement Collaboration. We defined distinct newborn types using gestational age (preterm [PT], term [T]), birthweight for gestational age using INTERGROWTH-21st standards (small for gestational age [SGA], appropriate for gestational age [AGA] or large for gestational age [LGA]), and birthweight (low birthweight, LBW [<2500 g], nonLBW) as ten types (using all three outcomes), six types (by excluding the birthweight categorisation), and four types (by collapsing the AGA and LGA categories). We defined small types as those with at least one classification of LBW, PT or SGA. We presented study characteristics, participant characteristics, data missingness, and prevalence of newborn types by region and study. Results: Among 541 285 live births, 476 939 (88.1%) had non-missing and plausible values for gestational age, birthweight and sex required to construct the newborn types. The median prevalences of ten types across studies were T+AGA+nonLBW (58.0%), T+LGA+nonLBW (3.3%), T+AGA+LBW (0.5%), T+SGA+nonLBW (14.2%), T+SGA+LBW (7.1%), PT+LGA+nonLBW (1.6%), PT+LGA+LBW (0.2%), PT+AGA+nonLBW (3.7%), PT+AGA+LBW (3.6%) and PT+SGA+LBW (1.0%). The median prevalence of small types (six types, 37.6%) varied across studies and within regions and was higher in Southern Asia (52.4%) than in Sub-Saharan Africa (34.9%). Conclusions: Further investigation is needed to describe the mortality risks associated with newborn types and understand the implications of this framework for local targeting of interventions to prevent adverse pregnancy outcomes in LMICs.
Abstract Branched-chain amino acids are critical metabolic intermediates that can indicate increased risk of cardiometabolic disease when levels are elevated or, alternatively, suggest sufficient mitochondrial energy metabolism and reserve in old age. The interpretation of BCAA levels can be context-dependent, and it remains unclear whether abnormal levels can inform prognosis. This prospective longitudinal study aimed to determine the interrelationship between mortality hazard and fasting serum BCAA levels among older men and women aged ≥65 years with or without hypertension and diabetes mellitus. At baseline (0Y), fasting serum BCAA concentration in 2997 community-living older men and women were measured. Approximately 14 years later (14Y), 860 study participants returned for repeat measurements. Deaths were analysed and classified into cardiovascular and non-cardiovascular causes using International Classification of Diseases codes. Survival analysis and multivariable Cox regression were performed. During a median follow-up of 17Y, 971 (78.6%) non-cardiovascular and 263 (21.4%) cardiovascular deaths occurred among 1235 (41.2%) deceased (median age, 85.8 years [IQR 81.7–89.7]). From 0Y to 14Y, BCAA levels declined in both sexes, whereas serum creatinine concentration increased (both p < 0.0001). In older adults without hypertension or diabetes mellitus, the relationship between mortality hazard and BCAA level was linear and above-median BCAA levels were associated with improved survival, whereas in the presence of cardiometabolic disease the relationship was U-shaped. Overall, adjusted Cox regression determined that each 10% increment in BCAA concentration was associated with a 7% (p = 0.0002) and 16% (p = 0.0057) reduction in mortality hazard estimated at 0Y and 14Y, respectively. Our findings suggested that abnormally high or low (dyshomeostatic) BCAA levels among older adults with hypertension and/or diabetes mellitus were associated with increased mortality, whereas in those with neither disease, increased BCAA levels was associated with improved survival, particularly in the oldest-old.
Objective Sauna bathing is becoming a common activity in many countries and it has been linked to favorable health outcomes. However, there is limited data on the heart rate (HR) and heart rate variability (HRV) responses to an acute sauna exposure. Design We conducted a single-group, longitudinal study utilizing a pre-post design to examine acute effects of sauna bathing on the autonomic nervous system as reflected by HRV. A total of 93 participants (mean [SD] age: 52.0 [8.8] years, 53.8% males) with cardiovascular risk factors were exposed to a single sauna session (duration: 30 min; temperature: 73 °C; humidity: 10–20%) and data on HRV variables were collected before, during and after sauna. Results Time and frequency-domain HRV variables were significantly modified (p < 0.001) by the single sauna session, with most of HRV variables tending to return near to baseline values after 30 min recovery. Resting HR was lower at the end of recovery (68/min) compared to pre-sauna (77/min). A sauna session transiently diminished the vagal component, whereas the cooling down period after sauna decreased low frequency power (p < 0.001) and increased high frequency power in HRV (p < 0.001), favorably modulating the autonomic nervous system balance. Conclusions This study demonstrates that a session of sauna bathing induces an increase in HR. During the cooling down period from sauna bathing, HRV increased which indicates the dominant role of parasympathetic activity and decreased sympathetic activity of cardiac autonomic nervous system. Future randomized controlled studies are needed to show if HR and HRV changes underpins the long-term cardiovascular effects induced by regular sauna bathing.
The purpose was to examine the effects of a round trip trans-American jet travel on performance, hormonal alterations, and recovery. Ten matched pairs of recreationally trained men were randomized to either a compression group (COMP) (n = 10; age: 23.1 ± 2.4 yr; height: 174.8 ± 5.3 cm; body mass: 84.9 ± 10.16 kg; body fat: 15.3 ± 6.0%) or control group (CONT) (n = 9; age: 23.2 ± 2.3 yr; height: 177.5 ± 6.3 cm; weight: 84.3 ± 8.99 kg; body fat: 15.1 ± 6.4%). Subjects flew directly from Hartford, CT to Los Angeles, CA 1 day before a simulated sport competition (SSC) designed to create muscle damage and returned the next morning on an overnight flight back home. Both groups demonstrated jet lag symptoms and associated decreases in sleep quality at all time points. Melatonin significantly (P < 0.05) increased over the first 2 days and then remained constant until after the SSC. Epinephrine, testosterone, and cortisol values significantly increased above resting values before and after the SSC with norepinephrine increases only after the SSC. Physical performances significantly decreased from control values on each day for the CONT group with COMP group exhibiting no significant declines. Muscle damage markers were significantly elevated following the SSC with the COMP group having significantly lower values while maintaining neuromuscular performance measures that were not different from baseline testing. Trans-American jet travel has a significant impact on parameters related to jet lag, sleep quality, hormonal responses, muscle tissue damage markers, and physical performance with an attenuation observed with extended wear compression garments.
Context. RadioAstron is a 10 m orbiting radio telescope mounted on the Spektr-R satellite, launched in 2011, performing Space Very Long Baseline Interferometry (SVLBI) observations supported by a global ground array of radio telescopes. With an apogee of 350 000 km, it is offering for the first time the possibility to perform μas-resolution imaging in the cm-band. Aims: The RadioAstron active galactic nuclei (AGN) polarization Key Science Project (KSP) aims at exploiting the unprecedented angular resolution provided by RadioAstron to study jet launching/collimation and magnetic-field configuration in AGN jets. The targets of our KSP are some of the most powerful blazars in the sky. Methods: We present observations at 22 GHz of 3C 273, performed in 2014, designed to reach a maximum baseline of approximately nine Earth diameters. Reaching an angular resolution of 0.3 mas, we study a particularly low-activity state of the source, and estimate the nuclear region brightness temperature, comparing with the extreme one detected one year before during the RadioAstron early science period. We also make use of the VLBA-BU-BLAZAR survey data, at 43 GHz, to study the kinematics of the jet in a 1.5-yr time window. Results: We find that the nuclear brightness temperature is two orders of magnitude lower than the exceptionally high value detected in 2013 with RadioAstron at the same frequency (1.4 × 1013 K, source-frame), and even one order of magnitude lower than the equipartition value. The kinematics analysis at 43 GHz shows that a new component was ejected 2 months after the 2013 epoch, visible also in our 22 GHz map presented here. Consequently this was located upstream of the core during the brightness temperature peak. Fermi-LAT observations for the period 2010-2014 do not show any γ-ray flare in conjunction with the passage of the new component by the core at 43 GHz. Conclusions: These observations confirm that the previously detected extreme brightness temperature in 3C 273, exceeding the inverse Compton limit, is a short-lived phenomenon caused by a temporary departure from equipartition. Thus, the availability of interferometric baselines capable of providing μas angular resolution does not systematically imply measured brightness temperatures over the known physical limits for astrophysical sources. The reduced image (FITS file) is only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/604/A111
Abstract Large-scale solid bodies on Earth such as volcanoes and man-made pyramids have been visualized with solid earth muography, and the recently invented technique, acqueous muography, has already demonstrated its capability to visualize ocean tides and tsunami. In this work, atmospheric muography, a technique to visualize and monitor the vertical profile of tropic cyclones (TCs) is presented for the first time. The density distribution and time-dependent behavior of several TCs which had approached Kagoshima, Japan, has been investigated with muography. The resultant time-sequential images captured their warm cores, and their movements were consistent with the TC trails and barometric pressure variations observed at meteorological stations. By combining multidirectional muographic images with barometric data, we anticipate that muography will become a useful tool to monitor the three-dimensional density distribution of a targeted mesoscale convective system.
Abstract Several known breast cancer susceptibility genes with moderate‐to‐high risk alleles encode proteins involved in DNA damage response (DDR). As these explain less than half of the hereditary breast cancer cases, additional predisposing alleles are likely to be discovered. Many of the previous studies utilizing massive parallel sequencing have focused on the protein‐truncating variants, and the role of rare missense mutations has remained poorly addressed. To identify novel susceptibility factors, we have systematically analyzed the data from our parallel sequencing of 796 DDR genes in 189 Northern Finnish hereditary breast cancer patients for rare missense variants, predicted as deleterious. Thirty‐five variants were studied here for the disease association using Finnish breast cancer case (n = 492–2,035) and control (n = 277–1,539) cohorts. As a result, two missense variants in genes involved in DNA replication, RECQL p.I156M and POLG p.L392V, the former involving genomic and the latter mitochondrial DNA replication, showed significant association with risk of breast cancer. Rare RECQL p.I156M allele was observed in breast cancer cases only (6/1,946, 0.3%, p = 0.043), whereas POLG p.L392V was two times more frequent in breast cancer cases (53/2,238, 2.4%) compared to controls (18/1,539, 1.2%, OR = 2.1, 95% CI 1.2–3.5, p = 0.010). Based on the current genetic data, both RECQL p.I156M and POLG p.L392V represent novel breast cancer predisposing alleles.
Understanding the formation of relativistic jets in active galactic nuclei remains an elusive problem 1 .This is partly because observational tests of jet formation models suffer from the limited angular resolution of ground-based very-long-baseline interferometry that has thus far been able to probe the structure of the jet acceleration and collimation region in only two sources 2,3 . Here, we report observations of 3C84 (NGC 1275)-the central galaxy of the Perseus cluster-made with an interferometric array including the orbiting radio telescope of the RadioAstron 4 mission. The data transversely resolve the edge-brightened jet in 3C84 only 30 μas from the core, which is ten times closer to the central engine than was possible in previous ground-based observations 5 and allows us to measure the jet collimation profile from ~102 to ~104 gravitational radii (r g) from the black hole. The previously found 5, almost cylindrical jet profile on scales larger than a few thousand r g is seen to continue at least down to a few hundred r g from the black hole, and we find a broad jet with a transverse radius of â‰250 r g at only 350 r g from the core. This implies that either the bright outer jet layer goes through a very rapid lateral expansion on scales â‰102 r g or it is launched from the accretion disk.
Abstract During early pregnancy in the mouse, nidatory estrogen (E2) stimulates endometrial receptivity by activating a network of signaling pathways that is not yet fully characterized. Here, we report that bone morphogenetic proteins (BMPs) control endometrial receptivity via a conserved activin receptor type 2 A (ACVR2A) and SMAD1/5 signaling pathway. Mice were generated to contain single or double conditional deletion of SMAD1/5 and ACVR2A/ACVR2B receptors using progesterone receptor (PR)-cre. Female mice with SMAD1/5 deletion display endometrial defects that result in the development of cystic endometrial glands, a hyperproliferative endometrial epithelium during the window of implantation, and impaired apicobasal transformation that prevents embryo implantation and leads to infertility. Analysis of Acvr2a-PRcre and Acvr2b-PRcre pregnant mice determined that BMP signaling occurs via ACVR2A and that ACVR2B is dispensable during embryo implantation. Therefore, BMPs signal through a conserved endometrial ACVR2A/SMAD1/5 pathway that promotes endometrial receptivity during embryo implantation.
Abstract Muography uses muons naturally produced in the interactions between cosmic rays and atmosphere for imaging and characterization of density differences and time-sequential changes in solid (e.g. rocks) and liquid (e.g. melts ± dissolved gases) materials in scales from tens of metres to up to a few kilometres. In addition to being useful in discovering the secrets of the pyramids, ore prospecting and surveillance of nuclear sites, muography successfully images the internal structure of volcanoes. Several field campaigns have demonstrated that muography can image density changes relating to magma ascent and descent, magma flow rate, magma degassing, the shape of the magma body, an empty conduit diameter, hydrothermal activity and major fault lines. In addition, muography is applied for long-term volcano monitoring in a few selected volcanoes around the world. We propose using muography in volcano monitoring in conjunction with other existing techniques for predicting volcanic hazards. This approach can provide an early indication of a possible future eruption and potentially the first estimate of its scale by producing direct evidence of magma ascent through its conduit in real time. Knowing these issues as early as possible buy critically important time for those responsible for the local alarm and evacuation protocols.
Background: Postoperative acute kidney injury (AKI) is a common complication of major gastrointestinal surgery with an impact on short- and long-term survival. No validated system for risk stratification exists for this patient group. This study aimed to validate externally a prognostic model for AKI after major gastrointestinal surgery in two multicentre cohort studies. Methods: The Outcomes After Kidney injury in Surgery (OAKS) prognostic model was developed to predict risk of AKI in the 7 days after surgery using six routine datapoints (age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker). Validation was performed within two independent cohorts: a prospective multicentre, international study (‘IMAGINE’) of patients undergoing elective colorectal surgery (2018); and a retrospective regional cohort study (‘Tayside’) in major abdominal surgery (2011–2015). Multivariable logistic regression was used to predict risk of AKI, with multiple imputation used to account for data missing at random. Prognostic accuracy was assessed for patients at high risk (greater than 20 per cent) of postoperative AKI. Results: In the validation cohorts, 12.9 per cent of patients (661 of 5106) in IMAGINE and 14.7 per cent (106 of 719 patients) in Tayside developed 7-day postoperative AKI. Using the OAKS model, 558 patients (9.6 per cent) were classified as high risk. Less than 10 per cent of patients classified as low-risk developed AKI in either cohort (negative predictive value greater than 0.9). Upon external validation, the OAKS model retained an area under the receiver operating characteristic (AUC) curve of range 0.655–0.681 (Tayside 95 per cent c.i. 0.596 to 0.714; IMAGINE 95 per cent c.i. 0.659 to 0.703), sensitivity values range 0.323–0.352 (IMAGINE 95 per cent c.i. 0.281 to 0.368; Tayside 95 per cent c.i. 0.253 to 0.461), and specificity range 0.881–0.890 (Tayside 95 per cent c.i. 0.853 to 0.905; IMAGINE 95 per cent c.i. 0.881 to 0.899). Conclusion: The OAKS prognostic model can identify patients who are not at high risk of postoperative AKI after gastrointestinal surgery with high specificity.
Abstract We performed an analysis of high-energy particle emission from the Sun in two extreme solar particle events observed even with ground-based neutron monitors (NMs). We model particle transport and interactions from near-Sun source through the solar wind and the Earth’s magnetosphere and atmosphere in order to make a deep analysis of the events. The time profile of the proton source at the Sun is deduced and compared with observed electromagnetic emissions. Several complementary to each other data sets are studied jointly with the broadband dynamic radio spectra, EUV images as well as other data available for both events. We find a common scenario for both eruptions, including the flare’s dual impulsive phase, the coronal mass ejection (CME)-launch-associated burst and the late low-frequency type III radio bursts at the time of the relativistic proton injection into the interplanetary medium. The analysis supports the idea that the two considered events start with emission of relativistic protons previously accelerated during the flare and CME launch, then trapped in large-scale magnetic loops and later released by the expanding CME.
We present RadioAstron space-based very long baseline interferometry (VLBI) observations of the nearby radio galaxy 3C 84 (NGC 1275) at the centre of the Perseus cluster. The observations were carried out during a perigee passage of the Spektr-R spacecraft on September 21a-22, 2013 and involved a global array of 24 ground radio telescopes observing at 5 GHz and 22 GHz, together with the Space Radio Telescope (SRT). Furthermore, the Very Long Baseline Array (VLBA) and the phased Very Large Array (VLA) observed the source quasi-simultaneously at 15 GHz and 43 GHz. Fringes between the ground array and the SRT were detected on baseline lengths up to 8.1 times the Eartha-s diameter, providing unprecedented resolution for 3C 84 at these wavelengths. We note that the corresponding fringe spacing is 125 μas at 5 GHz and 27 μas at 22 GHz. Our space-VLBI images reveal a previously unseen sub-structure inside the compact âà1 pc long jet that was ejected about ten years earlier. In the 5 GHz image, we detected, for the first time, low-intensity emission from a cocoon-like structure around the restarted jet. Our results suggest that the increased power of the young jet is inflating a bubble of hot plasma as it carves its way through the ambient medium of the central region of the galaxy. Here, we estimate the minimum energy stored in the mini-cocoon, along with its pressure, volume, expansion speed, and the ratio of heavy particles to relativistic electrons, as well as the density of the ambient medium. About half of the energy delivered by the jet is dumped into the mini-cocoon and the quasi-spherical shape of the bubble suggests that this energy may be transferred to a significantly larger volume of the interstellar medium than what would be accomplished by the well-collimated jet on its own. The pressure of the hot mini-cocoon also provides a natural explanation for the almost cylindrical jet profile seen in the 22 GHz RadioAstron image.
Abstract Background: Data on psychiatric disorders in survivors born very preterm (VP; <32 weeks) or very low birthweight (VLBW; <1500 g) are sparse. We compared rates of psychiatric diagnoses between VP/VLBW and term-born, normal birthweight (term/NBW) control participants. Methods: This individual participant data (IPD) meta-analysis pooled data from eligible groups in the Adults born Preterm International Collaboration (APIC). Inclusion criteria included: 1) VP/VLBW group (birth weight <1500 g and/or gestational age <32 weeks), 2) normal birth weight/term-born control group (birth weight >2499 g and/or gestational age ≥37 weeks), and 3) structured measure of psychiatric diagnoses using DSM or ICD criteria. Diagnoses of interest were Attention Deficit Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), Anxiety Disorder, Mood Disorder, Disruptive Behaviour Disorder (DBD), Eating Disorder, and Psychotic Disorder. A systematic search for eligible studies was conducted (PROSPERO Registration Number 47555). Findings: Data were obtained from 10 studies (1385 VP/VLBW participants, 1780 controls), using a range of instruments and approaches to assigning diagnoses. Those born VP/VLBW had ten times higher odds of meeting criteria for ASD (odds ratio [OR] 10·6, 95% confidence interval [CI] 2·50, 44·7), five times higher odds of meeting criteria for ADHD (OR 5·42, 95% CI 3·10, 9·46), twice the odds of meeting criteria for Anxiety Disorder (OR 1·91, 95% CI 1·36, 2·69), and 1·5 times the odds of meeting criteria for Mood Disorder (OR 1·51, 95% CI 1·08, 2·12) than controls. This pattern of findings was consistent within age (<18 years vs. ≥18 years) and sex subgroups. Interpretation: Our data suggests that individuals born VP/VLBW might have higher odds of meeting criteria for certain psychiatric disorders through childhood and into adulthood than term/NBW controls. Further research is needed to corroborate our results and identify factors associated with psychiatric disorders in individuals born VP/VLBW.
Abstract Hydrogenated titanium dioxide has attracted intensive research interests in pollutant removal applications due to its high photocatalytic activity. Herein, we demonstrate hydrogenated TiO2 nanofibers (H:TiO2 NFs) with a core-shell structure prepared by the hydrothermal synthesis and subsequent heat treatment in hydrogen flow. H:TiO2 NFs has excellent solar light absorption and photogenerated charge formation behavior as confirmed by optical absorbance, photo-Kelvin force probe microscopy and photoinduced charge carrier dynamics analyses. Photodegradation of various organic dyes such as methyl orange, rhodamine 6G and brilliant green is shown to take place with significantly higher rates on our novel catalyst than on pristine TiO2 nanofibers and commercial nanoparticle based photocatalytic materials, which is attributed to surface defects (oxygen vacancy and Ti3+ interstitial defect) on the hydrogen treated surface. We propose three properties/mechanisms responsible for the enhanced photocatalytic activity, which are: (1) improved absorbance allowing for increased exciton generation, (2) highly crystalline anatase TiO2 that promotes fast charge transport rate, and (3) decreased charge recombination caused by the nanoscopic Schottky junctions at the interface of pristine core and hydrogenated shell thus promoting long-life surface charges. The developed H:TiO2 NFs can be helpful for future high performance photocatalysts in environmental applications.
Abstract Dental caries and periodontitis account for a vast burden of morbidity and healthcare spending, yet their genetic basis remains largely uncharacterized. Here, we identify self-reported dental disease proxies which have similar underlying genetic contributions to clinical disease measures and then combine these in a genome-wide association study meta-analysis, identifying 47 novel and conditionally-independent risk loci for dental caries. We show that the heritability of dental caries is enriched for conserved genomic regions and partially overlapping with a range of complex traits including smoking, education, personality traits and metabolic measures. Using cardio-metabolic traits as an example in Mendelian randomization analysis, we estimate causal relationships and provide evidence suggesting that the processes contributing to dental caries may have undesirable downstream effects on health.
Abstract Background: Relatlimab plus nivolumab (anti–lymphocyte-activation gene 3 plus anti–programmed death 1 [anti–LAG-3+anti–PD-1]) has been approved by the FDA as a first-line therapy for stage III/IV melanoma, but its detailed effect on the immune system is unknown. Methods: We evaluated blood samples from 40 immunotherapy-naive or prior immunotherapy–refractory patients with metastatic melanoma treated with anti–LAG-3+anti–PD-1 in a phase I trial using single-cell RNA and T cell receptor sequencing (scRNA+TCRαβ-Seq) combined with other multiomics profiling. Results: The highest LAG3 expression was noted in NK cells, Tregs, and CD8+ T cells, and these cell populations underwent the most significant changes during the treatment. Adaptive NK cells were enriched in responders and underwent profound transcriptomic changes during the therapy, resulting in an active phenotype. LAG3+ Tregs expanded, but based on the transcriptome profile, became metabolically silent during the treatment. Last, higher baseline TCR clonality was observed in responding patients, and their expanding CD8+ T cell clones gained a more cytotoxic and NK-like phenotype. Conclusion: Anti–LAG-3+anti–PD-1 therapy has profound effects on NK cells and Tregs in addition to CD8+ T cells. Trial registration: ClinicalTrials.gov (NCT01968109) Funding : Cancer Foundation Finland, Sigrid Juselius Foundation, Signe and Ane Gyllenberg Foundation, Relander Foundation, State funding for university-level health research in Finland, a Helsinki Institute of Life Sciences Fellow grant, Academy of Finland (grant numbers 314442, 311081, 335432, and 335436), and an investigator-initiated research grant from BMS.
Abstract Objective: To summarize proceedings of a workshop convened to discuss the current state of science in the disease of osteoarthritis (OA), identify the knowledge gaps, and examine the developmental and regulatory challenges in bringing these products to market. Design: Summary of the one-day workshop held virtually on June 22nd, 2021. Results: Speakers selected by the Planning Committee presented data on the current approach to assessment of OA therapies, biomarkers in OA drug development, and the assessment of disease progression and long-term benefit. Conclusions: Demonstrated by numerous failed clinical trials, OA is a challenging disease for which to develop therapeutics. The challenge is magnified by the slow time of onset of disease and the need for clinical trials of long duration and/or large sample size to demonstrate the effect of an intervention. The OA science community, including academia, pharmaceutical companies, regulatory agencies, and patient communities, must continue to develop and test better clinical endpoints that meaningfully reflect disease modification related to long-term patient benefit.
Abstract Histopathologic assessment is indispensable for diagnosing colorectal cancer (CRC). However, manual evaluation of the diseased tissues under the microscope cannot reliably inform patient prognosis or genomic variations crucial for treatment selections. To address these challenges, we develop the Multi-omics Multi-cohort Assessment (MOMA) platform, an explainable machine learning approach, to systematically identify and interpret the relationship between patients’ histologic patterns, multi-omics, and clinical profiles in three large patient cohorts (n = 1888). MOMA successfully predicts the overall survival, disease-free survival (log-rank test P-value<0.05), and copy number alterations of CRC patients. In addition, our approaches identify interpretable pathology patterns predictive of gene expression profiles, microsatellite instability status, and clinically actionable genetic alterations. We show that MOMA models are generalizable to multiple patient populations with different demographic compositions and pathology images collected from distinctive digitization methods. Our machine learning approaches provide clinically actionable predictions that could inform treatments for colorectal cancer patients.
Abstract Meteorological-tsunami-like (or meteotsunami-like) periodic oscillation was muographically detected with the Tokyo-Bay Seafloor Hyper-Kilometric Submarine Deep Detector (TS-HKMSDD) deployed in the underwater highway called the Trans-Tokyo Bay Expressway or Tokyo Bay Aqua-Line (TBAL). It was detected right after the arrival of the 2021 Typhoon-16 that passed through the region 400 km south of the bay. The measured oscillation period and decay time were respectively 3 h and 10 h. These measurements were found to be consistent with previous tide gauge measurements. Meteotsunamis are known to take place in bays and lakes, and the temporal and spatial characteristics of meteotsunamis are similar to seismic tsunamis. However, their generation and propagation mechanisms are not well understood. The current result indicates that a combination of muography and trans-bay or trans-lake underwater tunnels will offer an additional tool to measure meteotsunamis at locations where tide gauges are unavailable.
Abstract Tidal measurements are of great significance since they may provide us with essential data to apply towards protection of coastal communities and sea traffic. Currently, tide gauge stations and laser altimetry are commonly used for these measurements. On the other hand, muography sensors can be located underneath the seafloor inside an undersea tunnel where electric and telecommunication infrastructures are more readily available. In this work, the world’s first under-seafloor particle detector array called the Tokyo-bay Seafloor Hyper-Kilometric Submarine Deep Detector (TS-HKMSDD) was deployed underneath the Tokyo-Bay seafloor for conducting submarine muography. The resultant 80-day consecutive time-sequential muographic data were converted to the tidal levels based on the parameters determined from the first-day astronomical tide height (ATH) data. The standard deviation between ATH and muographic results for the rest of a 79-day measurement period was 12.85 cm. We anticipate that if the length of the TS-HKMSDD is extended from 100 m to a full-scale as large as 9.6 km to provide continuous tidal information along the tunnel, this muography application will become an established standard, demonstrating its effectiveness as practical tide monitor for this heavy traffic waterway in Tokyo and in other important sea traffic areas worldwide.
Abstract Coronal holes are the observational manifestation of the solar magnetic field open to the heliosphere and are of pivotal importance for our understanding of the origin and acceleration of the solar wind. Observations from space missions such as the Solar Dynamics Observatory now allow us to study coronal holes in unprecedented detail. Instrumental effects and other factors, however, pose a challenge to automatically detect coronal holes in solar imagery. The science community addresses these challenges with different detection schemes. Until now, little attention has been paid to assessing the disagreement between these schemes. In this COSPAR ISWAT initiative, we present a comparison of nine automated detection schemes widely applied in solar and space science. We study, specifically, a prevailing coronal hole observed by the Atmospheric Imaging Assembly instrument on 2018 May 30. Our results indicate that the choice of detection scheme has a significant effect on the location of the coronal hole boundary. Physical properties in coronal holes such as the area, mean intensity, and mean magnetic field strength vary by a factor of up to 4.5 between the maximum and minimum values. We conclude that our findings are relevant for coronal hole research from the past decade, and are therefore of interest to the solar and space research community.
Alpha particles with energies on the order of megaelectronvolts will be the main source of plasma heating in future magnetic confinement fusion reactors. Instead of heating fuel ions, most of the energy of alpha particles is transferred to electrons in the plasma. Furthermore, alpha particles can also excite Alfvénic instabilities, which were previously considered to be detrimental to the performance of the fusion device. Here we report improved thermal ion confinement in the presence of megaelectronvolts ions and strong fast ion-driven Alfvénic instabilities in recent experiments on the Joint European Torus. Detailed transport analysis of these experiments reveals turbulence suppression through a complex multi-scale mechanism that generates large-scale zonal flows. This holds promise for more economical operation of fusion reactors with dominant alpha particle heating and ultimately cheaper fusion electricity.