The complex circumstellar environment of supernova 2023ixf.

The early evolution of a supernova (SN) can reveal information about the environment and the progenitor star. When a star explodes in vacuum, the first photons to escape from its surface appear as a brief, hours-long shock-breakout flare1,2, followed by a cooling phase of emission. However, for stars exploding within a distribution of dense, optically thick circumstellar material (CSM), the first photons escape from the material beyond the stellar edge and the duration of the initial flare can extend to several days, during which the escaping emission indicates photospheric heating3. Early serendipitous observations2,4 that lacked ultraviolet (UV) data were unable to determine whether the early emission is heating or cooling and hence the nature of the early explosion event. Here we report UV spectra of the nearby SN 2023ixf in the galaxy Messier 101 (M101). Using the UV data as well as a comprehensive set of further multiwavelength observations, we temporally resolve the emergence of the explosion shock from a thick medium heated by the SN emission. We derive a reliable bolometric light curve that indicates that the shock breaks out from a dense layer with a radius substantially larger than typical supergiants.

Factors Associated With Ultrasound Color Doppler Twinkling by Breast Biopsy Markers: In Vitro and Ex Vivo Evaluation of 35 Commercially Available Markers.

BACKGROUND. Targeted axillary lymph node dissection after neoadjuvant systemic therapy (NST) for breast cancer depends on identifying marked metastatic lymph nodes. However, ultrasound visualization of biopsy markers is challenging. OBJECTIVE. The purpose of our study was to identify biopsy markers that show actionable twinkling in cadaveric breast and to assess the association of actionable twinkling with markers' surface roughness. METHODS. Commercial breast biopsy markers were evaluated for twinkling artifact in various experimental conditions relating to scanning medium (solid gel phantom, ultrasound coupling gel, cadaveric breast), transducer (ML6-15, 9L, C1-6), and embedding material (present vs absent). Markers were assigned twinkling scores from 0 (confident in no twinkling) to 4 (confident in exuberant twinkling); a score of 3 or greater represented actionable twinkling (sufficient confidence to rely solely on twinkling for target localization). Markers were hierarchically advanced to evaluation with increasingly complex media if showing at least minimal twinkling for a given medium. A 3D coherence optical profiler measured marker surface roughness. Mixed-effects proportional odds regression models assessed associations between twinkling scores and transducer and embedding material; Wilcoxon rank sum test evaluated associations between actionable twinkling and surface roughness. RESULTS. Thirty-five markers (21 with embedding material) were evaluated. Ten markers without embedding material advanced to evaluation in cadaveric breast. Higher twinkling scores were associated with presence of embedding material (odds ratio [OR] = 5.05 in solid gel phantom, 9.84 in coupling gel) and transducer (using the C1-6 transducer as reference; 9L transducer: OR = 0.36, 0.83, and 0.04 in solid gel phantom, ultrasound coupling gel, and cadaveric breast; ML6-15 transducer: OR = 0.07, 0.18, and 0.00 respectively; post hoc p between 9L and ML6-15: p < .001, p = .02, and p = .04). In cadaveric breast, three markers (Cork, Professional Q, MRI [Flex]) exhibited actionable twinkling for two or more transducers; surface roughness was significantly higher for markers with than without actionable twinkling for C1-6 (median values: 0.97 vs 0.35, p = .02) and 9L (1.75 vs 0.36; p = .002) transducers. CONCLUSION. Certain breast biopsy markers exhibited actionable twinkling in cadaveric breast. Twinkling was observed with greater confidence for the C1-6 and 9L transducers than the ML6-15 transducer. Actionable twinkling was associated with higher marker surface roughness. CLINICAL IMPACT. Use of twinkling for marker detection could impact preoperative or intraoperative localization after NST.

Associations of prenatal and childhood Pb exposure with allostatic load in adolescence: Findings from the ELEMENT cohort study.

The biological pathways which link lead (Pb) and long-term outcomes are unclear, though rodent models and a few human studies suggest Pb may alter the body's stress response systems, which over time, can elicit dysregulated stress responses with cumulative impacts. This study examined associations between prenatal and early childhood Pb exposure and adolescent allostatic load, an index of an individual's body burden of stress in multiple biological systems, and further examined sex-based associations. Among 391 (51% male) participants in the ELEMENT birth cohort, we related trimester-specific maternal blood Pb, 1-month postpartum maternal tibia and patella Pb, and child blood Pb at 12-24 months to an allostatic load index in adolescence comprised of biomarkers of cardiovascular, metabolic, neuroendocrine, and immune function. The results were overall mixed, with prenatal exposure, particularly maternal bone Pb, being positively associated with allostatic load, and early childhood Pb showing mixed results for males and females. In adjusted Poisson regression models, 1 mcg/g increase in tibia Pb was associated with a 1% change in expected allostatic load (IRR = 1.01; 95%CI 0.99, 1.02). We found a significant Pb × sex interaction (IRR = 1.05; 95%CI 1.01, 1.10); where males saw an increasing percent change in allostatic load as 12 month Pb levels increased compared to females who saw a decreasing allostatic load. Further examination of allostatic load will facilitate the determination of potential mechanistic pathways between developmental toxicant exposures and later-in-life cardiometabolic outcomes.

The possible involvement of sema3A and sema4A in the pathogenesis of multiple sclerosis.

BACKGROUND: Immune semaphorins are widely accepted to have functional impact on autoimmune diseases. OBJECTIVES: To assess the status of sema3A and sema4A in the pathogenesis of Multiple Sclerosis (MS). RESULTS: Sema3A expression on (T regulatory cells)Tregs was decreased in MS patients, compared to healthy controls (35.85 ± 16.7% vs 88.27 ± 3.8%; p ≤ 0.001). Serum levels of sema3A were decreased in MS patients 2.95 ± 0.43 vs 18.67 ± 5.7 ng/ml in healthy individuals; p ≤ 0.001. Sema4A serum levels were increased in MS patients compared to healthy individuals (12.99 ± 8.6 vs 5.83 ± 3.91 ng/ml; p ≤ 0.001). Sema3A and sema4A serum levels were found to be in negative/positive correlation with MS disease severity (rs = 0.62, rs = -0.49, respectively). CONCLUSION: We show that sema3A is a regulatory molecule in MS, whereas sema4A is a stimulatory one. Targeting sema3A and sema4A could become a potential therapeutic approach in MS.

"I must do this!": A latent profile analysis approach to understanding the role of irrational beliefs and motivation regulation in mental and physical health.

In the research concerning rational emotive behaviour therapy (REBT) in sport and exercise, irrational beliefs are proposed as a risk factor for health. Concurrent to this, researchers have also indicated that autonomous and controlled motivation, as proposed in organismic integration theory could, together with irrational beliefs, determine individual health. However, research is yet to align irrational beliefs and motivation, and explore how this alignment relates to mental health. The present two study paper identifies individual subgroups, drawn from data concerning irrational beliefs, motivation, and health (psychological distress, and physical health), in a sample of exercisers (study 1) and student athletes (study 2). We examined the latent profile structure of irrational beliefs and motivation, and how these latent profiles relate to psychological distress (studies 1 and 2), and physical health (study 2). Results indicate a two class profile whereby class 1 is characterised by high irrational beliefs, low self-determined motivation, and poor health outcomes. Class 2 is characterised by low irrational beliefs, high self-determined motivation, and better health outcomes. The findings are discussed in relation to the theoretical implications for REBT and organismic integration theory, and the practical implications for key stakeholders in the health of exercise participants and athletes.

Invasion of the body snatchers: the role of parasite introduction in host distribution and response to salinity in invaded estuaries.

In dynamic systems, organisms are faced with variable selective forces that may impose trade-offs. In estuaries, salinity is a strong driver of organismal diversity, while parasites shape species distributions and demography. We tested for trade-offs between low-salinity stress and parasitism in an invasive castrating parasite and its mud crab host along salinity gradients of two North Carolina rivers. We performed field surveys every six to eight weeks over 3 years to determine factors influencing parasite prevalence, host abundance, and associated taxa diversity. We also looked for signatures of low-salinity stress in the host by examining its response (time-to-right and gene expression) to salinity. We found salinity and temperature significantly affected parasite prevalence, with low-salinity sites (less than 10 practical salinity units (PSU)) lacking infection, and populations in moderate salinities at warmer temperatures reaching prevalence as high as 60%. Host abundance was negatively associated with parasite prevalence. Host gene expression was plastic to acclimation salinity, but several osmoregulatory and immune-related genes demonstrated source-dependent salinity response. We identified a genetic marker that was strongly associated with salinity against a backdrop of no neutral genetic structure, suggesting possible selection on standing variation. Our study illuminates how selective trade-offs in naturally dynamic systems may shape host evolutionary ecology.

Invasion history shapes host transcriptomic response to a body-snatching parasite.

By shuffling biogeographical distributions, biological invasions can both disrupt long-standing associations between hosts and parasites and establish new ones. This creates natural experiments with which to study the ecology and evolution of host-parasite interactions. In estuaries of the Gulf of Mexico, the white-fingered mud crab (Rhithropanopeus harrisii) is infected by a native parasitic barnacle, Loxothylacus panopaei (Rhizocephala), which manipulates host physiology and behaviour. In the 1960s, L. panopaei was introduced to the Chesapeake Bay and has since expanded along the southeastern Atlantic coast, while host populations in the northeast have so far been spared. We use this system to test the host's transcriptomic response to parasitic infection and investigate how this response varies with the parasite's invasion history, comparing populations representing (i) long-term sympatry between host and parasite, (ii) new associations where the parasite has invaded during the last 60 years and (iii) naïve hosts without prior exposure. A comparison of parasitized and control crabs revealed a core response, with widespread downregulation of transcripts involved in immunity and moulting. The transcriptional response differed between hosts from the parasite's native range and where it is absent, consistent with previous observations of increased susceptibility in populations lacking exposure to the parasite. Crabs from the parasite's introduced range, where prevalence is highest, displayed the most dissimilar response, possibly reflecting immune priming. These results provide molecular evidence for parasitic manipulation of host phenotype and the role of gene regulation in mediating host-parasite interactions.

A phase Ib/II and pharmacokinetic study of EP0057 (formerly CRLX101) in combination with weekly paclitaxel in patients with recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal cancer.

BACKGROUND: EP0057 (formerly CRLX101) is an investigational nanoparticle-drug conjugate (NDC) of a cyclodextrin-based polymer backbone plus camptothecin, a topoisomerase-1 inhibitor. Prior studies showed efficacy in recurrent or persistent, epithelial ovarian, fallopian tube or primary peritoneal cancer (EOC). METHODS: This phase Ib/2 trial assessed safety and efficacy of EP0057 Q2W plus weekly paclitaxel in patients with EOC. The recommended phase 2 dose (RP2D) was identified using a 3+3 design. The single-arm phase 2 assessed overall response (ORR) per RECIST 1.1 in patients previously treated with bevacizumab. Secondary objectives included progression free survival (PFS) and duration of response. RESULTS: The RP2D was established as 15 mg/m2 EP0057 Q2W plus 80 mg/m2 paclitaxel administered 3 weeks on/1 week off. Nine patients enrolled on phase 1b, with no DLTs; 21 additional patients enrolled on phase 2. All completed >1 cycle. Median age was 62 (44-76) years, 57% ≥3 prior therapies. For the primary analysis, 6/19 patients with prior bevacizumab had confirmed responses (ORR=31.6% (95% CI: 15.4% to 54.0%)) including one complete response (CR). Median PFS was 5.4 months. Most common grade 3/4 adverse events attributed to treatment were decreased neutrophil count (13, 43%) and anemia (3, 10%). CONCLUSIONS: Although the observed ORR was not statistically better than the historical control rate, EP0057 remains an interesting option for treatment of recurrent EOC. EP0057 exhibits high plasma drug retention, slow clearance, and controlled slow release of CPT from the polymer when administered alone and with paclitaxel. (NCT02389985) 242 words.

Outcomes 1 and 2 Years After Moderate to Severe Traumatic Brain Injury: An International Comparative Study.

OBJECTIVE: This study compared traumatic brain injury (TBI) outcomes from 2 cohorts: the National Institute on Disability, Independent Living, and Rehabilitation Research Traumatic Brain Injury Model Systems (TBIMS) in the United States and Longitudinal Head Injury Outcome Study conducted in Victoria, Australia, by the Monash Epworth Rehabilitation Research Centre (MERRC). DESIGN: Cohort study with 1- and 2-year follow-up. SETTING: Acute trauma care and inpatient rehabilitation with follow-up. PARTICIPANTS: Patients (N=1056) with moderate-severe TBI admitted in 2000-2012 to inpatient rehabilitation after motor vehicle-related collisions, who completed follow-up, were matched using 1:2 matching algorithm based on age at injury, days of posttraumatic amnesia, and years education, resulting in groups of 352 (MERRC) and 704 patients (TBIMS). INTERVENTION: The cohorts had received acute trauma care and inpatient rehabilitation for a median 38 (MERRC) or 33 days (TBIMS). The MERRC group also had routine access to community-based support and rehabilitation for return to work or school, attendant care, and home help as justified, funded by an accident compensation system, whereas the TBIMS cohort had variable access to these services. MAIN OUTCOME MEASURES: Outcomes were assessed 1 and 2 years post injury in terms of employment, living situation, marital status, and Glasgow Outcome Scale-Extended (GOS-E) scores. RESULTS: At 2 years post injury, MERRC participants were more likely to be competitively employed. At both 1 and 2 years post injury, MERRC participants were more likely to be married and living independently. On GOS-E, the TBIMS group had higher percentages of patients in Lower Severe Disability/Vegetative State and Upper Good Recovery than MERRC participants, whereas the MERRC cohort had higher percentages of Lower Moderate Disability than TBIMS. CONCLUSIONS: Findings may suggest that routine provision of community-based supports could confer benefits for long-term TBI outcomes. Further studies documenting rehabilitation services are needed to explore this.

Development of an artificial intelligence-based assessment model for prediction of embryo viability using static images captured by optical light microscopy during IVF.

STUDY QUESTION: Can an artificial intelligence (AI)-based model predict human embryo viability using images captured by optical light microscopy? SUMMARY ANSWER: We have combined computer vision image processing methods and deep learning techniques to create the non-invasive Life Whisperer AI model for robust prediction of embryo viability, as measured by clinical pregnancy outcome, using single static images of Day 5 blastocysts obtained from standard optical light microscope systems. WHAT IS KNOWN ALREADY: Embryo selection following IVF is a critical factor in determining the success of ensuing pregnancy. Traditional morphokinetic grading by trained embryologists can be subjective and variable, and other complementary techniques, such as time-lapse imaging, require costly equipment and have not reliably demonstrated predictive ability for the endpoint of clinical pregnancy. AI methods are being investigated as a promising means for improving embryo selection and predicting implantation and pregnancy outcomes. STUDY DESIGN, SIZE, DURATION: These studies involved analysis of retrospectively collected data including standard optical light microscope images and clinical outcomes of 8886 embryos from 11 different IVF clinics, across three different countries, between 2011 and 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: The AI-based model was trained using static two-dimensional optical light microscope images with known clinical pregnancy outcome as measured by fetal heartbeat to provide a confidence score for prediction of pregnancy. Predictive accuracy was determined by evaluating sensitivity, specificity and overall weighted accuracy, and was visualized using histograms of the distributions of predictions. Comparison to embryologists' predictive accuracy was performed using a binary classification approach and a 5-band ranking comparison. MAIN RESULTS AND THE ROLE OF CHANCE: The Life Whisperer AI model showed a sensitivity of 70.1% for viable embryos while maintaining a specificity of 60.5% for non-viable embryos across three independent blind test sets from different clinics. The weighted overall accuracy in each blind test set was >63%, with a combined accuracy of 64.3% across both viable and non-viable embryos, demonstrating model robustness and generalizability beyond the result expected from chance. Distributions of predictions showed clear separation of correctly and incorrectly classified embryos. Binary comparison of viable/non-viable embryo classification demonstrated an improvement of 24.7% over embryologists' accuracy (P = 0.047, n = 2, Student's t test), and 5-band ranking comparison demonstrated an improvement of 42.0% over embryologists (P = 0.028, n = 2, Student's t test). LIMITATIONS, REASONS FOR CAUTION: The AI model developed here is limited to analysis of Day 5 embryos; therefore, further evaluation or modification of the model is needed to incorporate information from different time points. The endpoint described is clinical pregnancy as measured by fetal heartbeat, and this does not indicate the probability of live birth. The current investigation was performed with retrospectively collected data, and hence it will be of importance to collect data prospectively to assess real-world use of the AI model. WIDER IMPLICATIONS OF THE FINDINGS: These studies demonstrated an improved predictive ability for evaluation of embryo viability when compared with embryologists' traditional morphokinetic grading methods. The superior accuracy of the Life Whisperer AI model could lead to improved pregnancy success rates in IVF when used in a clinical setting. It could also potentially assist in standardization of embryo selection methods across multiple clinical environments, while eliminating the need for complex time-lapse imaging equipment. Finally, the cloud-based software application used to apply the Life Whisperer AI model in clinical practice makes it broadly applicable and globally scalable to IVF clinics worldwide. STUDY FUNDING/COMPETING INTEREST(S): Life Whisperer Diagnostics, Pty Ltd is a wholly owned subsidiary of the parent company, Presagen Pty Ltd. Funding for the study was provided by Presagen with grant funding received from the South Australian Government: Research, Commercialisation and Startup Fund (RCSF). 'In kind' support and embryology expertise to guide algorithm development were provided by Ovation Fertility. J.M.M.H., D.P. and M.P. are co-owners of Life Whisperer and Presagen. Presagen has filed a provisional patent for the technology described in this manuscript (52985P pending). A.P.M. owns stock in Life Whisperer, and S.M.D., A.J., T.N. and A.P.M. are employees of Life Whisperer.

A core competency framework for prostate cancer peer navigation.

PURPOSE: Trained peer navigators can offer valuable peer support and mentorship to cancer patients and caregivers due to their highly relevant and unique perspective about the disease experience. In order to define the role of prostate cancer (PC) peer navigators within the cancer care system, it is important to establish the essential competencies of a PC peer navigator. We systematically identified and verified a set of core competencies for PC peer navigators and present a competency framework for PC peer navigators. METHODS: In phase 1, we conducted formative research consisting of a literature review and environmental scan as well as a secondary analysis of qualitative interviews. In phase 2, we drafted and mapped competencies. Finally in phase 3, expert stakeholders completed an anonymous survey to indicate whether they endorsed the competencies and to rank the importance of each competency to the peer navigator role. Open-ended feedback was also provided for each competency. RESULTS: Six core competency domains emerged: (1) self as navigator, (2) communication, (3) knowledge/information, (4) facilitate patient-centred care, (5) eHealth/technology, and (6) caregiver needs. Forty-seven core competency statements were mapped to these domains. Expert stakeholders (n = 27) included cancer survivors, caregivers, and healthcare providers. Most (89%) of core competency statements were endorsed by stakeholders and received high priority ratings, whereas only five of the competencies were less uniformly endorsed. CONCLUSIONS: This is the first attempt to list core competencies for PC peer navigators and may offer guidance for standardizing the PC peer navigator role and training.

National Institute on Disability, Independent Living, and Rehabilitation Research Burn Model System: Review of Program and Database.

The Burn Model System (BMS) centers program was created in 1994 to evaluate the long-term outcomes of burn injuries. As part of this multicenter program, a comprehensive longitudinal database was developed to facilitate the study of a number of functional and psychosocial outcomes after burn injury. In this article, we provide an overview of the data collection procedures, measures selection process, and an overview of the participant data collected between 1994 and 2016. Surveys were administered during hospitalization and at 6, 12, and 24 months after discharge, and in the most recent funding cycle, data collection at every 5 years postinjury was added. More than 7200 people with burn injury were eligible to participate in the BMS National Longitudinal Database. Of these, >5900 (82%) were alive at discharge and consented to follow-up data collection. The BMS National Longitudinal Database represents a large sample of people with burn injury, including information on demographic characteristics, injury characteristics, and health outcomes. The database is publicly available and can be used to examine the effect of burn injury on long-term outcomes.

Point-of-care lung ultrasound in patients with COVID-19 - a narrative review.

Ultrasound imaging of the lung and associated tissues may play an important role in the management of patients with COVID-19-associated lung injury. Compared with other monitoring modalities, such as auscultation or radiographic imaging, we argue lung ultrasound has high diagnostic accuracy, is ergonomically favourable and has fewer infection control implications. By informing the initiation, escalation, titration and weaning of respiratory support, lung ultrasound can be integrated into COVID-19 care pathways for patients with respiratory failure. Given the unprecedented pressure on healthcare services currently, supporting and educating clinicians is a key enabler of the wider implementation of lung ultrasound. This narrative review provides a summary of evidence and clinical guidance for the use and interpretation of lung ultrasound for patients with moderate, severe and critical COVID-19-associated lung injury. Mechanisms by which the potential lung ultrasound workforce can be deployed are explored, including a pragmatic approach to training, governance, imaging, interpretation of images and implementation of lung ultrasound into routine clinical practice.

Return to Productivity Projections for Individuals With Moderate to Severe TBI Following Inpatient Rehabilitation: A NIDILRR TBIMS and CDC Interagency Collaboration.

OBJECTIVE: Return to work and school following traumatic brain injury (TBI) is an outcome of central importance both to TBI survivors and to society. The current study estimates the probability of returning to productivity over 5 years following moderate to severe brain injury. DESIGN: A secondary longitudinal analysis using random effects modeling, that is, individual growth curve analysis based on a sample of 2542 population-weighted individuals from a multicenter cohort study. SETTING: Acute inpatient rehabilitation facilities. PARTICIPANTS: Individuals 16 years and older with a primary diagnosis of TBI who were engaged in school or work at the time of injury. MAIN OUTCOME MEASURES: Participation in productive activity, defined as employment or school, as reported during follow-up telephone interviews at 1, 2, and 5 years postinjury. RESULTS: Baseline variables, age of injury, race, level of education and occupational category at the time of injury, disability rating at hospital discharge, substance abuse status, and rehabilitation length of stay, are significantly associated with probability of return to productivity. Individual-level productivity trajectories generally indicate that the probability of returning to productivity increases over time. CONCLUSIONS: Results of this study highlight the importance of preinjury occupational status and level of education in returning to productive activity following moderate to severe TBI.

Functional Outcome Trajectories Following Inpatient Rehabilitation for TBI in the United States: A NIDILRR TBIMS and CDC Interagency Collaboration.

OBJECTIVE: To describe trajectories of functioning up to 5 years after traumatic brain injury (TBI) that required inpatient rehabilitation in the United States using individual growth curve models conditioned on factors associated with variability in functioning and independence over time. DESIGN: Secondary analysis of population-weighted data from a multicenter longitudinal cohort study. SETTING: Acute inpatient rehabilitation facilities. PARTICIPANTS: A total of 4624 individuals 16 years and older with a primary diagnosis of TBI. MAIN OUTCOME MEASURES: Ratings of global disability and supervision needs as reported by participants or proxy during follow-up telephone interviews at 1, 2, and 5 years postinjury. RESULTS: Many TBI survivors experience functional improvement through 1 and 2 years postinjury, followed by a decline in functioning and decreased independence by 5 years. However, there was considerable heterogeneity in outcomes across individuals. Factors such as older age, non-White race, lower preinjury productivity, public payer source, longer length of inpatient rehabilitation stay, and lower discharge functional status were found to negatively impact trajectories of change over time. CONCLUSIONS: These findings can inform the content, timing, and target recipients of interventions designed to maximize functional independence after TBI.

Genotyping-by-Sequencing for Analysis of the Genetic Variation of Podosphaera xanthii, Incitant of Cucurbit Powdery Mildew.

This research was conducted to identify species causing powdery mildew on cucurbits and to determine genetic variations among isolates of the pathogen. We collected 109 isolates from six cucurbit species hosts (Cucumis melo, Cucumis sativus, Cucurbita maxima, Cucurbita moschata, Cucurbita pepo, and Lagenaria siceraria) in California, Illinois, Indiana, Michigan, New York, Texas, Washington, and Wisconsin in the United States and in Italy. By sequencing the internal transcribed spacer region of the nuclear rDNA of these 109 isolates, Podosphaera xanthii was found as the only species causing powdery mildew on cucurbits in the United States. Genotyping-by-sequencing was applied to these 109 isolates to investigate their genetic diversity, which showed a trend of isolates clustering from New York and Italy. In addition, the virulence of 36 isolates was compared and a significant difference (P < 0.0001) was found among them. Furthermore, results of the virulence tests of 28 isolates from Illinois showed significant effects of collection years, hosts, and locations on the virulence of the isolates.

A proof-of-principle study of the short-term effects of 3,4-methylenedioxymethamphetamine (MDMA) on tinnitus and neural connectivity.

Background: This study was conducted to investigate the short-term behavioural and neurophysiological effects of 3,4-methylenedioxymethamphetamine (MDMA) on tinnitus perception.Methods: A double-blind randomized controlled cross-over design. Part 1. Behavioural measures of tinnitus following 30 mg MDMA or placebo administration (N = 5 participants) and Part 2. Behavioural measures of tinnitus and correlations between pairs of apriori regions of interest (ROI) using resting-state functional magnetic resonance imaging (rs-fMRI) before and after 70 mg of MDMA or placebo (N = 8 participants).Results: The results to MDMA were similar to placebo. For the 70 mg dose, there was a significant reduction after 4 h in annoyance and ignore ratings. RsMRI showed decreased connectivity compared with placebo administration between the left hippocampal, right hippocampal, left amygdala and right amygdala regions, and between the right posterior parahippocampal cortex and the left amygdala after two hours of 70 mg MDMA administration. Increased connectivity compared to placebo administration was found post MDMA between the right post-central gyrus and right posterior and superior temporal gyrus, and between the thalamus and frontoparietal network.Conclusions: Following 70 mg of MDMA two tinnitus rating scales significantly improved. There was, however, a placebo effect. Compared with placebo the rsMRI following the MDMA showed reductions in connectivity between the amygdala, hippocampus and parahippocampal gyrus. There is sufficient proof of concept to support future investigation of MDMA as a treatment for tinnitus.

Direct Constraints on the Ultralight Boson Mass from Searches of Continuous Gravitational Waves.

Superradiance can trigger the formation of an ultralight boson cloud around a spinning black hole. Once formed, the boson cloud is expected to emit a nearly periodic, long-duration, gravitational-wave signal. For boson masses in the range (10^{-13}-10^{-11}) eV, and stellar mass black holes, such signals are potentially detectable by gravitational-wave detectors, like Advanced LIGO and Virgo. In this Letter, we present full band upper limits for a generic all-sky search for periodic gravitational waves in LIGO O2 data, and use them to derive-for the first time-direct constraints on the ultralight scalar boson field mass.

Injectable Catalyst-Free Poly(Propylene Fumarate) System Cross-Linked by Strain Promoted Alkyne-Azide Cycloaddition Click Chemistry for Spine Defect Filling.

A new PPF-BCN/hyPCL32-N3 injectable system that can be cross-linked by catalyst-free, strain promoted alkyne-azide cycloaddition (SPAAC) click chemistry was developed for tissue engineering applications. The system consisted of two components: PPF-BCN, poly(propylene fumarate) (PPF) functionalized with (1R,8S,9s)-bicyclo[6.1.0]non-4-yn-9-ylmethanol (BCN-OH), and hyPCL32-N3, a hyper-branched 32-arm poly(ε-caprolactone) (PCL) dendrimer functionalized with azide as the cross-linker core. Fast SPAAC click reaction allowed the desired gelation of the system without using any toxic initiator or catalyst. Compared to the conventional injectable formulation, e.g., poly(methyl methacrylate) (PMMA), our PPF-BCN/hyPCL32-N3 (abbreviated as PFCL-Click) injectable system showed enhanced biocompatibility and low heat generation during cross-linking. After reaction, the cross-linked PFCL-Click scaffolds supported excellent proliferation and differentiation of preosteoblast cells on the surface. The PFCL-Click system can be successfully injected into vertebral bodies of rabbit spine and can be monitored by X-ray imaging after incorporating zirconium dioxide (ZrO2) powder. With these unique advantages, this injectable system has promising potential for bone defect repair and other tissue engineering and regenerative medicine applications.

Axonal water fraction as marker of white matter injury in primary-progressive multiple sclerosis: a longitudinal study.

BACKGROUND AND PURPOSE: Diffuse white matter (WM) injury is prominent in primary-progressive multiple sclerosis (PP-MS) pathology and is a potential biomarker of disease progression. Diffusion kurtosis imaging allows the quantification of non-Gaussian water diffusion, providing metrics with high WM pathological specificity. The aim of this study was to characterize the pathological changes occurring in the normal-appearing WM of patients with PP-MS at baseline and at 1-year follow-up and to assess their impact on disability and short-term disease progression. METHODS: A total of 26 patients with PP-MS and 20 healthy controls were prospectively enrolled. Diffusion kurtosis imaging single-shot echo-planar imaging (EPI) was acquired on a 3-T scanner (Philips Achieva, Best, The Netherlands) (voxel size, 2 × 2 × 2 mm3 , 30 directions for each b-value = 1000, 2000 s/mm2 and one b = 0 s/mm2 ). A two-compartment biophysical model of WM tract integrity was used to derive spatial maps of axonal water fraction (AWF), intra-axonal diffusivity, extra-axonal axial and radial diffusivities (De,axial , De,radial ) and tortuosity from the following WM tracts: corpus callosum (CC), corticospinal tract (CST) and posterior thalamic radiation (PTR). RESULTS: At baseline, patients with PP-MS showed a widespread decrease of AWF, tortuosity and De,axial and an increase of De,radial in CC, CST and PTR (P ranging from 0.001 to 0.036). At 1-year follow-up, a significant AWF decrease was detected in the body of CC (P = 0.048), PTR (P = 0.008) and CST (P = 0.044). Baseline AWF values in CST significantly discriminated progressed from non-progressed patients (P = 0.021; area under the curve, 0.854). CONCLUSION: Based on its change over time and its relationship with disease progression, among the analyzed metrics, AWF seems the most sensitive metric of WM tissue damage in PP-MS and therefore it could be considered as a marker for monitoring disease progression.