A biological invasion modifies the dynamics of a host-parasite arms race.

By imposing novel selection pressures on both participants, biological invasions can modify evolutionary 'arms races' between hosts and parasites. A spatially replicated cross-infection experiment reveals strong spatial divergence in the ability of lungworms (Rhabdias pseudosphaerocephala) to infect invasive cane toads (Rhinella marina) in Australia. In areas colonized for longer than 20 years, toads are more resistant to infection by local strains of parasites than by allopatric strains. The situation reverses at the invasion front, where super-infective parasites have evolved. Invasion-induced shifts in genetic diversity and selective pressures may explain why hosts gain advantage over parasites in long-colonized areas, whereas parasites gain advantage at the invasion front.

The International Olympic Committee framework on fairness, inclusion and nondiscrimination on the basis of gender identity and sex variations does not protect fairness for female athletes.

The International Olympic Committee (IOC) recently published a framework on fairness, inclusion, and nondiscrimination on the basis of gender identity and sex variations. Although we appreciate the IOC's recognition of the role of sports science and medicine in policy development, we disagree with the assertion that the IOC framework is consistent with existing scientific and medical evidence and question its recommendations for implementation. Testosterone exposure during male development results in physical differences between male and female bodies; this process underpins male athletic advantage in muscle mass, strength and power, and endurance and aerobic capacity. The IOC's "no presumption of advantage" principle disregards this reality. Studies show that transgender women (male-born individuals who identify as women) with suppressed testosterone retain muscle mass, strength, and other physical advantages compared to females; male performance advantage cannot be eliminated with testosterone suppression. The IOC's concept of "meaningful competition" is flawed because fairness of category does not hinge on closely matched performances. The female category ensures fair competition for female athletes by excluding male advantages. Case-by-case testing for transgender women may lead to stigmatization and cannot be robustly managed in practice. We argue that eligibility criteria for female competition must consider male development rather than relying on current testosterone levels. Female athletes should be recognized as the key stakeholders in the consultation and decision-making processes. We urge the IOC to reevaluate the recommendations of their Framework to include a comprehensive understanding of the biological advantages of male development to ensure fairness and safety in female sports.

mTBI evaluation, management, and referral to allied healthcare: practices of first-line healthcare professionals.

PRIMARY OBJECTIVE: To gain an understanding of current evaluation practices, post-injury recommendations, and referrals to allied healthcare professions (AHP) by first-line healthcare professionals (FHPs) providing care for people with mild traumatic brain injury (mTBI). RESEARCH DESIGN: Survey study. METHODS AND PROCEDURES: Physicians, physician assistants, nurse practitioners, nurses, and athletic trainers (n = 126) completed an online survey, including Likert scale and free response question relating to mTBI evaluation, management, and referral practices. MAIN OUTCOMES AND RESULTS: FHPs surveyed reported being confident in their ability to evaluate patients with suspected mTBI, relying most heavily on patient-reported symptoms and physical signs as methods of evaluation. Most FHPs reported making recommendations to compensate for the symptoms experienced following mTBI diagnosis. In contrast, FHPs expressed challenges in the evaluation and management of symptoms associated with mTBI along with limited knowledge of and referrals to AHPs. CONCLUSIONS: Overall, FHPs feel confident in the diagnosis of mTBI but experience assessment and management challenges. AHPs are underutilized on mTBI management teams calling for a need for multidisciplinary collaboration on research, education, and rehabilitation efforts to optimally care for people experiencing mTBI symptoms.

Timing is everything: Circadian rhythms and their role in the control of sleep.

Sleep and the circadian clock are intertwined and have persisted throughout history. The suprachiasmatic nucleus (SCN) orchestrates sleep by controlling circadian (Process C) and homeostatic (Process S) activities. As a "hand" on the endogenous circadian clock, melatonin is critical for sleep regulation. Light serves as a cue for sleep/wake control by activating retino-recipient cells in the SCN and subsequently suppressing melatonin. Clock genes are the molecular timekeepers that keep the 24 h cycle in place. Two main sleep and behavioural disorder diagnostic manuals have now officially recognised the importance of these processes for human health and well-being. The body's ability to respond to daily demands with the least amount of effort is maximised by carefully timing and integrating all components of sleep and waking. In the brain, the organization of timing is essential for optimal brain physiology.

Susceptibility Magnetic Resonance Imaging Correlates with Glial Density and Tau in the Substantia Nigra Pars Compacta.

BACKGROUND: Susceptibility magnetic resonance imaging (MRI) is sensitive to iron-related changes in the substantia nigra pars compacta (SNc), the key pathologic locus of parkinsonisms. It is unclear, however, if iron deposition in the SNc is associated with its neurodegeneration. OBJECTIVE: The objective of this study was to test whether susceptibility MRI metrics in parkinsonisms are associated with SNc neuropathologic features of dopaminergic neuron loss, gliosis, and α-synuclein and tau burden. METHODS: This retrospective study included 27 subjects with both in vivo MRI and postmortem data. Multigradient echo imaging was used to derive the apparent transverse relaxation rate (R2*) and quantitative susceptibility mapping (QSM) in the SNc. Archived midbrain slides that were stained with hematoxylin and eosin, anti-α-synuclein, and anti-tau were digitized to quantify neuromelanin-positive neuron density, glial density, and the percentages of area occupied by positive α-synuclein and tau staining. MRI-histology associations were examined using Pearson correlations and regression. RESULTS: Twenty-four subjects had postmortem parkinsonism diagnoses (Lewy body disorder, progressive supranuclear palsy, multiple system atrophy, and corticobasal degeneration), two had only Alzheimer's neuropathology, and one exhibited only mild atrophy. Among all subjects, both R2* and QSM were associated with glial density (r ≥ 0.67; P < 0.001) and log-transformed tau burden (r ≥ 0.53; P ≤ 0.007). Multiple linear regression identified glial density and log-transformed tau as determinants for both MRI metrics (R2 ≥ 0.580; P < 0.0001). Neither MRI metric was associated with neuron density or α-synuclein burden. CONCLUSIONS: R2* and QSM are associated with both glial density and tau burden, key neuropathologic features in the parkinsonism SNc. © 2023 International Parkinson and Movement Disorder Society.

Managed care updates of subscriber jail release to prompt community suicide prevention: clinical trial protocol.

BACKGROUND: Recent jail detention is a marker for trait and state suicide risk in community-based populations. However, healthcare providers are typically unaware that their client was in jail and few post-release suicide prevention efforts exist. This protocol paper describes an effectiveness-implementation trial evaluating community suicide prevention practices triggered by advances in informatics that alert CareSource, a large managed care organization (MCO), when a subscriber is released from jail. METHODS: This randomized controlled trial investigates two evidence-based suicide prevention practices triggered by CareSource's jail detention/release notifications, in a partial factorial design. The first phase randomizes ~ 43,000 CareSource subscribers who pass through any Ohio jail to receive Caring Contact letters sent by CareSource or to Usual Care after jail release. The second phase (running simultaneously) involves a subset of ~ 6,000 of the 43,000 subscribers passing through jail who have been seen in one of 12 contracted behavioral health agencies in the 6 months prior to incarceration in a stepped-wedge design. Agencies will receive: (a) notifications of the client's jail detention/release, (b) instructions for re-engaging these clients, and (c) training in suicide risk assessment and the Safety Planning Intervention for use at re-engagement. We will track suicide-related and service linkage outcomes 6 months following jail release using claims data. CONCLUSIONS: This design allows us to rigorously test two intervention main effects and their interaction. It also provides valuable information on the effects of system-level change and the scalability of interventions using big data from a MCO to flag jail release and suicide risk. TRIAL REGISTRATION: The trial is registered at clinicaltrials.gov (NCT05579600). Registered 27 June, 2023.

Hip and Knee Osteoarthritis, Not Nonsteroidal Anti-Inflammatory Drugs, are Linked to Cardiac Disease.

BACKGROUND: In 2005, the Food and Drug Administration placed a black-box warning (the most stringent warning for drugs) on all nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) stating that these agents may cause heart attacks and/or strokes. No level I evidence demonstrates that nonselective NSAIDs increase cardiovascular risk. An alternative hypothesis is that hip and knee osteoarthritis (OA) indirectly causes cardiovascular disease (CVD) through decreased activity and NSAIDs are correlated with CVD as an arthritis treatment. METHODS: Systematic reviews were conducted to find observational studies evaluating the association of hip and/or knee OA, CVD, activity, walking, and step counts. The systematic review found studies correlating hip and/or knee OA and CVD morbidity incidence (n = 2); CVD morbidity prevalence (n = 6); odds ratios, relative risks, or hazard ratios of CVD morbidity (n = 11); relative risk, standardized mortality ratios, or hazard ratios of CVD mortality (n = 14); and all-cause mortality hazard ratios associated with NSAID use (n = 3). RESULTS: Hip OA (5 studies), knee OA (9 studies), and hip and knee OA (6 studies) are linked to an increased risk of CVD morbidity and mortality. Cardiac risk increases with validated disability scores, use of walking aids, walking difficulties, longer follow-up times, younger ages of OA onset, numbers of joints involved, and OA severities. No study linked NSAID use to cardiac disease. CONCLUSIONS: All studies with more than 10-year follow-up linked cardiac disease with hip and knee OA. No study linked nonselective NSAID use to CVD. The Food and Drug Administration should reconsider the black-box warnings on naproxen, ibuprofen, and celecoxib.

Two-year outcomes following the HIDOC program: expanding outpatient care delivery to meet the needs of medically complex, high-utilizing patients with a broader interprofessional care team.

This article describes the Highly Individualized Dedicated Onsite Care (HIDOC) intensive primary care program implemented at a university clinic, comprising (a) care by an interprofessional team, (b) new logistical capacity, and (c) clinician skills training. Measured outcomes include Emergency Department (ED) visits and hospitalizations at a university and a community hospital over 2 years, using a within-subjects design. We demonstrate decreased hospitalizations at the University Hospital, and a decrease in ED visits at both sites. Team-based strategies to provide intensive primary care can decrease utilization, allowing for greater continuity of care.

nMAT3 is an essential maturase splicing factor required for holo-complex I biogenesis and embryo development in Arabidopsis thaliana plants.

Group-II introns are self-splicing mobile genetic elements consisting of catalytic intron-RNA and its related intron-encoded splicing maturase protein cofactor. Group-II sequences are particularly plentiful within the mitochondria of land plants, where they reside within many critical gene loci. During evolution, the plant organellar introns have degenerated, such as they lack regions that are are required for splicing, and also lost their evolutionary related maturase proteins. Instead, for their splicing the organellar introns in plants rely on different host-acting protein cofactors, which may also provide a means to link cellular signals with respiratory functions. The nuclear genome of Arabidopsis thaliana encodes four maturase-related factors. Previously, we showed that three of the maturases, nMAT1, nMAT2 and nMAT4, function in the excision of different group-II introns in Arabidopsis mitochondria. The function of nMAT3 (encoded by the At5g04050 gene locus) was found to be essential during early embryogenesis. Using a modified embryo-rescue method, we show that nMAT3-knockout plants are strongly affected in the splicing of nad1 introns 1, 3 and 4 in Arabidopsis mitochondria, resulting in complex-I biogenesis defects and altered respiratory activities. Functional complementation of nMAT3 restored the organellar defects and embryo-arrested phenotypes associated with the nmat3 mutant line. Notably, nMAT3 and nMA4 were found to act on the same RNA targets but have no redundant functions in the splicing of nad1 transcripts. The two maturases, nMAT3 and nMAT4 are likely to cooperate together in the maturation of nad1 pre-RNAs. Our results provide important insights into the roles of maturases in mitochondria gene expression and the biogenesis of the respiratory system during early plant life.

Coadministration of Melatonin and Insulin Improves Diabetes-Induced Impairment of Rat Kidney Function.

INTRODUCTION: The present study was designed to evaluate the therapeutic efficacy of melatonin and insulin coadministration in diabetes-induced renal injury in rats. RESEARCH DESIGN AND METHODS: Diabetes was achieved by giving streptozotocin (15 mg/kg) for 6 consecutive days. The diabetic condition was confirmed by assessing the blood glucose level; animals having blood glucose levels above 250 mg were considered as diabetic. Following the confirmation, animals were randomly divided into different experimental groups, viz group I served as the control (CON), group II diabetic (D), group III D+melatonin (MEL), group IV D+insulin (INS), group V D+MEL+INS, group VI D+glibenclamide (GB), group VII CON+MEL, group VIII CON+INS, and group IX CON+GB. Following the completion of the experimental period, animals were sacrificed, blood was collected via a retro-orbital puncture, and kidneys were harvested. Diabetic rats exhibited a significant increment in blood glucose and biochemical indexes of renal injury (tubular disruption, swollen glomeruli with loss of glomerular spaces, and distortion of the endothelial lining) including augmented levels of serum creatinine, urea, uric acid, Na+, and K+, and inhibition/suppression of the activity of glutathione (GSH) peroxidase, GSH reductase, glucose-6-phosphate dehydrogenase, and GSH-S-transferase in the renal cortex. RESULTS: By examining thiobarbiturate reactive substances, reduced GSH, superoxide dismutase activity, and catalase activity in the renal cortex of control and diabetic rats, it was documented that treatment with melatonin or insulin alone or in combination showed a significant ad integrum recovery of GSH-dependent antioxidative enzymatic activities. Melatonin and insulin coadministration caused greater reductions in circulating tumor necrosis factor-α, tumor growth factor-ß1, interleukin (IL)-1ß, and IL-6 levels in diabetic rats, whereas IL-10 levels increased, as compared to each treatment alone. Diabetic rats showed a significant increase in the expression of both MT1 and MT2 melatonin receptor genes. Melatonin or insulin treatment alone or in combination resulted in significant restoration of the relative expression of both melatonin receptors in the renal cortex. CONCLUSION: The coadministration of exogenous melatonin and insulin abolished many of the deleterious effects of type 1 diabetes on rat renal function.

In an arms race between host and parasite, a lungworm's ability to infect a toad is determined by host susceptibility not parasite preference.

Evolutionary arms races can alter both parasite infectivity and host resistance, and it is difficult to separate the effects of these twin determinants of infection outcomes. We used a co-introduced, invasive host-parasite system (the lungworm Rhabdias pseudosphaerocephala and cane toads Rhinella marina), where rapid adaptation and dispersal have led to population differences in infection resistance. We quantified behavioural responses of parasite larvae to skin-chemical cues of toads from different invasive populations, and rates at which juvenile hosts became infected following standardized exposure to lungworms. Chemical cues from toad skin altered host-seeking behaviour by parasites, similarly among populations. The number of infection attempts (parasite larvae entering the host's body) also did not differ between populations, but rates of successful infection (establishment of adult worm in host lungs) were higher for range-edge toads than for range-core conspecifics. Thus, lower resistance to parasite infection in range-edge juvenile toads appears to be due to less effective immune defences of the host rather than differential behavioural responses of the parasite. In this ongoing host-parasite arms race, changing outcomes appear to be driven by shifts in host immunocompetence.

Detecting the Inverted-U in fMRI Studies of Schizophrenia: A Comparison of Three Analysis Methods.

OBJECTIVE: Cognitive tasks are used to probe neuronal activity during functional magnetic resonance imaging (fMRI) to detect signs of aberrant cognitive functioning in patients diagnosed with schizophrenia (SZ). However, nonlinear (inverted-U-shaped) associations between neuronal activity and task difficulty can lead to misinterpretation of group differences between patients and healthy comparison subjects (HCs). In this paper, we evaluated a novel method for correcting these misinterpretations based on conditional performance analysis. METHOD: Participants included 25 HCs and 27 SZs who performed a working memory (WM) task (N-back) with 5 load conditions while undergoing fMRI. Neuronal activity was regressed onto: 1) task load (i.e., parametric task levels), 2) marginal task performance (i.e., performance averaged over all load conditions), or 3) conditional task performance (i.e., performance within each load condition). RESULTS: In most regions of interest, conditional performance analysis uniquely revealed inverted-U-shaped neuronal activity in both SZs and HCs. After accounting for conditional performance differences between groups, we observed few difference in both the pattern and level of neuronal activity between SZs and HCs within regions that are classically associated with WM functioning (e.g., posterior dorsolateral prefrontal and parietal association cortices). However, SZs did show aberrant activity within the anterior dorsolateral prefrontal cortex. CONCLUSIONS: Interpretations of differences in neuronal activity between groups, and of associations between neuronal activity and performance, should be considered within the context of task performance. Whether conditional performance-based differences reflect compensation, dedifferentiation, or other processes is not a question that is easily resolved by examining activation and performance data alone.

Altered Reinforcement Learning from Reward and Punishment in Anorexia Nervosa: Evidence from Computational Modeling.

OBJECTIVES: Anorexia nervosa (AN) is associated with altered sensitivity to reward and punishment. Few studies have investigated whether this results in aberrant learning. The ability to learn from rewarding and aversive experiences is essential for flexibly adapting to changing environments, yet individuals with AN tend to demonstrate cognitive inflexibility, difficulty set-shifting and altered decision-making. Deficient reinforcement learning may contribute to repeated engagement in maladaptive behavior. METHODS: This study investigated learning in AN using a probabilistic associative learning task that separated learning of stimuli via reward from learning via punishment. Forty-two individuals with Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 restricting-type AN were compared to 38 healthy controls (HCs). We applied computational models of reinforcement learning to assess group differences in learning, thought to be driven by violations in expectations, or prediction errors (PEs). Linear regression analyses examined whether learning parameters predicted BMI at discharge. RESULTS: AN had lower learning rates than HC following both positive and negative PE (p < .02), and were less likely to exploit what they had learned. Negative PE on punishment trials predicted lower discharge BMI (p < .001), suggesting individuals with more negative expectancies about avoiding punishment had the poorest outcome. CONCLUSIONS: This is the first study to show lower rates of learning in AN following both positive and negative outcomes, with worse punishment learning predicting less weight gain. An inability to modify expectations about avoiding punishment might explain persistence of restricted eating despite negative consequences, and suggests that treatments that modify negative expectancy might be effective in reducing food avoidance in AN.

Establishing diagnostic reference levels for pediatric fluoroscopic examinations in a tertiary hospital.

BACKGROUND: Diagnostic reference levels (DRLs) identify unusually high patient radiation exposures and are required for dose optimisation. DRLs for pediatric fluoroscopic examinations are not widely determined in Australia. OBJECTIVE: Our objectives were to establish DRLs for pediatric fluoroscopic examinations in a South Australian tertiary hospital and compare these to previously published data and to explore relationships between patient dose area product (DAP), age and fluoroscopy times. MATERIALS AND METHODS: Dose data from 365 pediatric patients undergoing 5 fluoroscopic examinations were retrospectively collected for a 3-year period commencing January 2018 to develop local DRLs. Relationships between DAP, age and fluoroscopy time were explored using scatterplots, Spearman's correlation, and regression analyses. RESULTS: Local DRLs were significantly lower than data published previously, possibly reflecting technological and procedural advancements. Each 1-year increase in patient age was associated with a 0.77 µGy·m2 increase in DAP for barium meal and follow-through studies (95% confidence interval [CI]=0.055, 1.48) (P=0.04), and a 1.37 µGy·m2 increase in DAP for barium swallow studies (95% CI=0.61, 2.12) (P<0.001). A low correlation was demonstrated between DAP and fluoroscopy time for micturating cystourethrography studies (r=0.35, 95% CI=0.15, 0.51, P<0.001) and barium meal and follow-through studies (r=0.37, 95% CI= -0.011, 0.65, P=0.05). Age and fluoroscopy time were not significantly related. CONCLUSION: This study provides updated Australian pediatric fluoroscopic DRLs, with the intention of promoting a national database for benchmarking pediatric doses. The local DRLs can be used for dose comparisons and optimisation between facilities.

Practitioner Experiences Responding to Suicide Risk for Survivors of Human Trafficking in the Philippines.

Human trafficking survivors experience elevated suicide risk in comparison to the general population. Anti-trafficking service providers in the Philippines have identified capacity building in suicide prevention as a critical priority given the insufficient number of trained mental health professionals and lack of culturally adapted evidence-based interventions in the Philippines. We conducted a focused ethnography exploring the experiences of non-mental health professionals working in the anti-human trafficking sector in the Philippines in responding to suicidality among survivors of human trafficking (n = 20). Themes included: emotional burden on service providers, manifestations of stigma regarding suicide, lack of clarity regarding risk assessment, lack of mental health services and support systems, transferring responsibility to other providers, and the need for training, supervision, and organizational systems. We discuss implications for training service providers in the anti-human trafficking sector, as well as cultural adaptation of suicide prevention interventions with human trafficking survivors in the Philippines.

Testing of full face snorkel masks to examine recreational snorkeler deaths.

A recent rise in snorkeling-related deaths in Hawaii has inspired several bans on full face snorkel masks (FFSMs). However, while there are theories to explain the deaths, little physiological data exists about the way the FFSMs provide gas to an exercising subject. To evaluate the safety of the FFSM concept, this study was designed to test how use of a full face snorkel mask (FFSM) may be physiologically different than use of a conventional snorkel, and to assess if any of those differences could lead to increased risk for the snorkeler. Ten (10) volunteer human subjects were tested using a variety of commercially available FFSMs, with real-time monitoring of blood oxygen saturation (SpO2), inspired airway pressure, and inspired and expired levels of carbon dioxide and oxygen. Two of the three FFSM design types were shown not to function as advertised, but none of the masks provided physiologically problematic gas supplies to the snorkelers. While this testing yielded no conclusive "smoking gun" to explain the snorkeler deaths, some of the mask models showed patterns of increasing breathing resistance with water intrusion because of a shared design characteristic, and this increased resistance could potentially create elevated levels of respiratory distress to snorkelers during real-world use.

Using Community-Based System Dynamics to Address Structural Racism in Community Health Improvement.

CONTEXT: Structural racism is a profound determinant of health resulting in pervasive health inequities for people of color. Despite the recognition of structural racism as a complex, dynamic system, we lack a shared vision of the system that would enable identification of solutions for equitable systems transformation. POLICY: Through a public health-led community health improvement planning process, a cross-sector consortium implemented community-based system dynamics to provide a systems science lens to guide efforts to eliminate structural racism. IMPLEMENTATION: In group model building sessions involving diverse stakeholders, community-based system dynamics was used to bring together cross-sector stakeholders to create causal loop diagrams of the system of structural racism. Participants identified potential leverage points for actionable focus to eliminate structural racism. EVALUATION: Causal loop diagrams of structural racism generated through group model building demonstrate complex dynamics in the areas of criminal justice, education and economic opportunity, health and health care, quality of life, racial trauma and healing, and a promising system transformative solution through perspective transformation. DISCUSSION: Community-based system dynamics, employed in the context of local community health improvement planning, engages stakeholders in systems thinking through sharing lived experience to create system maps of structural racism and identify leverage points and transportable solutions that foster health equity. These informal maps serve as the foundation for formal computer simulation models that will guide systemic action on high-yield, community-driven solutions to eliminate structural racism.

Host defense or parasite cue: Skin secretions mediate interactions between amphibians and their parasites.

Amphibian skin secretions (substances produced by the amphibian plus microbiota) plausibly act as a first line of defense against parasite/pathogen attack, but may also provide chemical cues for pathogens. To clarify the role of skin secretions in host-parasite interactions, we conducted experiments using cane toads (Rhinella marina) and their lungworms (Rhabdias pseudosphaerocephala) from the range-core and invasion-front of the introduced anurans' range in Australia. Depending on the geographical area, toad skin secretions can reduce the longevity and infection success of parasite larvae, or attract lungworm larvae and enhance their infection success. These striking differences between the two regions were due both to differential responses of the larvae, and differential effects of the skin secretions. Our data suggest that skin secretions play an important role in host-parasite interactions in anurans, and that the arms race between a host and parasite can rapidly generate spatial variation in critical features of that interaction.

Decoupling of Global Brain Activity and Cerebrospinal Fluid Flow in Parkinson's Disease Cognitive Decline.

BACKGROUND: Deposition and spreading of misfolded proteins (α-synuclein and tau) have been linked to Parkinson's disease cognitive dysfunction. The glymphatic system may play an important role in the clearance of these toxic proteins via cerebrospinal fluid (CSF) flow through perivascular and interstitial spaces. Recent studies discovered that sleep-dependent global brain activity is coupled to CSF flow, which may reflect glymphatic function. OBJECTIVE: The objective of this current study was to determine if the decoupling of brain activity-CSF flow is linked to Parkinson's disease cognitive dysfunction. METHODS: Functional and structural MRI data, clinical motor (Unified Parkinson's Disease Rating Scale), and cognitive (Montreal Cognitive Assessment [MoCA]) scores were collected from 60 Parkinson's disease and 58 control subjects. Parkinson's disease patients were subgrouped into those with mild cognitive impairment (MoCA < 26), n = 31, and those without mild cognitive impairment (MoCA ≥ 26), n = 29. The coupling strength between the resting-state global blood-oxygen-level-dependent signal and associated CSF flow was quantified, compared among groups, and associated with clinical and structural measurements. RESULTS: Global blood-oxygen-level-dependent signal-CSF coupling decreased significantly (P < 0.006) in Parkinson's disease patients showing mild cognitive impairment, compared with those without mild cognitive impairment and controls. Reduced global blood-oxygen-level-dependent signal-CSF coupling was associated with decreased MoCA scores present in Parkinson's disease patients (P = 0.005) but not in controls (P = 0.65). Weaker global blood-oxygen-level-dependent signal-CSF coupling in Parkinson's disease patients also was associated with a thinner right entorhinal cortex (Spearman's correlation, -0.36; P = 0.012), an early structural change often seen in Alzheimer's disease. CONCLUSIONS: The decoupling between global brain activity and associated CSF flow is related to Parkinson's disease cognitive impairment. © 2021 International Parkinson and Movement Disorder Society.

Flows of X-ray gas reveal the disruption of a star by a massive black hole.

Tidal forces close to massive black holes can violently disrupt stars that make a close approach. These extreme events are discovered via bright X-ray and optical/ultraviolet flares in galactic centres. Prior studies based on modelling decaying flux trends have been able to estimate broad properties, such as the mass accretion rate. Here we report the detection of flows of hot, ionized gas in high-resolution X-ray spectra of a nearby tidal disruption event, ASASSN-14li in the galaxy PGC 043234. Variability within the absorption-dominated spectra indicates that the gas is relatively close to the black hole. Narrow linewidths indicate that the gas does not stretch over a large range of radii, giving a low volume filling factor. Modest outflow speeds of a few hundred kilometres per second are observed; these are below the escape speed from the radius set by variability. The gas flow is consistent with a rotating wind from the inner, super-Eddington region of a nascent accretion disk, or with a filament of disrupted stellar gas near to the apocentre of an elliptical orbit. Flows of this sort are predicted by fundamental analytical theory and more recent numerical simulations.