Imaging intact human organs with local resolution of cellular structures using hierarchical phase-contrast tomography.

Imaging intact human organs from the organ to the cellular scale in three dimensions is a goal of biomedical imaging. To meet this challenge, we developed hierarchical phase-contrast tomography (HiP-CT), an X-ray phase propagation technique using the European Synchrotron Radiation Facility (ESRF)'s Extremely Brilliant Source (EBS). The spatial coherence of the ESRF-EBS combined with our beamline equipment, sample preparation and scanning developments enabled us to perform non-destructive, three-dimensional (3D) scans with hierarchically increasing resolution at any location in whole human organs. We applied HiP-CT to image five intact human organ types: brain, lung, heart, kidney and spleen. HiP-CT provided a structural overview of each whole organ followed by multiple higher-resolution volumes of interest, capturing organotypic functional units and certain individual specialized cells within intact human organs. We demonstrate the potential applications of HiP-CT through quantification and morphometry of glomeruli in an intact human kidney and identification of regional changes in the tissue architecture in a lung from a deceased donor with coronavirus disease 2019 (COVID-19).

fMRI BOLD responses to film stimuli and their association with exhaled nitric oxide in asthma and health.

Little is known about central nervous system (CNS) responses to emotional stimuli in asthma. Nitric oxide in exhaled breath (FENO) is elevated in asthma due to allergic immune processes, but endogenous nitric oxide is also known to modulate CNS activity. We measured fMRI blood oxygen-dependent (BOLD) brain activation to negative (blood-injection-injury themes) and neutral films in 31 participants (15 with asthma). Regions-of-interest analysis was performed on key areas relevant to central adaptive control, threat processing, or salience networks, with dorsolateral prefrontal cortex (PFC), anterior insula, dorsal anterior cingulate cortex (dACC), amygdala, ventral striatum, ventral tegmentum, and periaqueductal gray, as well as top-down modulation of emotion, with ventrolateral and ventromedial PFC. Both groups showed less BOLD deactivation from fixation cross-baseline in the left anterior insula and bilateral ventromedial PFC for negative than neutral films, and for an additional number of areas, including the fusiform gyrus, for film versus recovery phases. Less deactivation during films followed by less recovery from deactivation was found in asthma compared to healthy controls. Changes in PCO2 did not explain these findings. FENO was positively related to BOLD activation in general, but more pronounced in healthy controls and more likely in neutral film processing. Thus, asthma is associated with altered processing of film stimuli across brain regions not limited to central adaptive control, threat processing, or salience networks. Higher levels of NO appear to facilitate CNS activity, but only in healthy controls, possibly due to allergy's masking effects on FENO.

The efficacy of citalopram or escitalopram in patients with asthma and major depressive disorder.

BACKGROUND: Major depressive disorder is common in people with asthma. Yet, few studies have evaluated depression treatment in those with asthma. OBJECTIVE: To explore the relationship between antidepressant use, depressive symptoms, and asthma control, pooled data from 3 randomized trials of either citalopram or escitalopram were assessed. METHODS: Linear fixed effects and binary logistic regression analyses were conducted with between-subject covariates including treatment group, (original) study, and demographics. The within-subject effect of visit, and a treatment group-visit (between-within) interaction effect, were also evaluated. Analyses were repeated in a high asthma exacerbation subgroup having at least 3 oral corticosteroid bursts in the previous 12 months. Outcomes included the Hamilton rating scale for depression (HAM-D17), the 7-item asthma control questionnaire (ACQ), and oral corticosteroid use (yes or no). RESULTS: In the pooled sample (n = 255), the antidepressant treatment group exhibited lower HAM-D17 overall (P ≤ .001) and a lower likelihood for oral corticosteroid use (P ≤ .001) relative to the placebo group. In the high-exacerbation subgroup (n = 96), treatment group participants had lower overall asthma control questionnaire (P = .004) and HAM-D17 scores (P ≤ .001), and a lower likelihood of oral corticosteroid use (P = .003), relative to placebo participants. All treatment group interaction effects were not significant. CONCLUSION: Citalopram or escitalopram exhibited efficacy in reducing depressive symptoms and the need for rescue oral corticosteroids in patients with asthma and major depressive disorder. Future work should determine whether selective serotonin reuptake inhibitors are effective at improving asthma outcomes in those with asthma who are not depressed. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00621946 and NCT01324700 (one study was conducted before ClinicalTrials.gov requirements).

Contribution of caregiver and child anxiety and depressive symptoms to child asthma-related quality of life.

BACKGROUND: Depression and anxiety negatively affect asthma-related quality of life (QoL). Yet, little is known regarding mood and asthma-related factors that best uniquely explain asthma-related QoL in children. OBJECTIVE: This cross-sectional study evaluated the unique variance explained by caregiver and child depressive and anxiety symptom severity in child asthma-related QoL, apart from that explained by demographics and asthma control. METHODS: Children aged 7 to 17 years with asthma (n = 205) and their caregivers with major depressive disorder were included. A 3-stage hierarchical linear regression analysis was conducted with the Pediatric Asthma Quality of Life Questionnaire total scores considered as the outcome. Predictors included demographic characteristics (stage 1); asthma control assessed by the Asthma Control Test (stage 2); and caregiver depression and anxiety (Hamilton Rating Scale for Depression and the Spielberger State/Trait Anxiety Scale) and child depression and anxiety (Children's Depression Inventory and the Screen for Child Anxiety-Related Disorders) (stage 3). RESULTS: Demographic characteristics accounted for only 5.5% of the Pediatric Asthma Quality of Life Questionnaire scores. Asthma control significantly increased variance explained in QoL to 32.6%, whereas caregiver and child depression and anxiety symptoms significantly increased variance explained to 42.6%. Child anxiety was found to uniquely explain the largest proportion of variance in QoL (rs2 = 0.584). CONCLUSION: After adjusting variance in QoL for demographic characteristics and asthma control, caregiver and child depression and anxiety measures significantly increased the proportion of variance explained in a child's asthma-related QoL. In addition to better asthma control, child and caregiver depression and anxiety should be addressed to increase child asthma-related QoL. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02809677.

A computational neuroimaging study of reinforcement learning and goal-directed exploration in schizophrenia spectrum disorders.

BACKGROUND: Prior evidence indicates that negative symptom severity and cognitive deficits, in people with schizophrenia (PSZ), relate to measures of reward-seeking and loss-avoidance behavior (implicating the ventral striatum/VS), as well as uncertainty-driven exploration (reliant on rostrolateral prefrontal cortex/rlPFC). While neural correlates of reward-seeking and loss-avoidance have been examined in PSZ, neural correlates of uncertainty-driven exploration have not. Understanding neural correlates of uncertainty-driven exploration is an important next step that could reveal insights to how this mechanism of cognitive and negative symptoms manifest at a neural level. METHODS: We acquired fMRI data from 29 PSZ and 36 controls performing the Temporal Utility Integration decision-making task. Computational analyses estimated parameters corresponding to learning rates for both positive and negative reward prediction errors (RPEs) and the degree to which participates relied on representations of relative uncertainty. Trial-wise estimates of expected value, certainty, and RPEs were generated to model fMRI data. RESULTS: Behaviorally, PSZ demonstrated reduced reward-seeking behavior compared to controls, and negative symptoms were positively correlated with loss-avoidance behavior. This finding of a bias toward loss avoidance learning in PSZ is consistent with previous work. Surprisingly, neither behavioral measures of exploration nor neural correlates of uncertainty in the rlPFC differed significantly between groups. However, we showed that trial-wise estimates of relative uncertainty in the rlPFC distinguished participants who engaged in exploratory behavior from those who did not. rlPFC activation was positively associated with intellectual function. CONCLUSIONS: These results further elucidate the nature of reinforcement learning and decision-making in PSZ and healthy volunteers.

Technology-based communication among Hurricane Maria survivors in the United States: a trans-territorial lens.

PURPOSE: Rooted in a trans-territorial framework, the present study was designed to provide new evidence regarding the patterns of communication among Hurricane Maria survivors who migrated to the U.S. in the aftermath of the storm. METHODS: A total of 319 Hurricane Maria survivor adults ages 18 and older were recruited into the Adelante Boricua study between August 2020 and October 2021. Most participants had relocated to the U.S. between 2017 and 2018. We used latent profile analysis and multinomial regression to examine the relationship of technology-based communication with depressive symptoms, well-being, cultural connection, and migration stress. RESULTS: We identified a five-class solution, consisting of (1) moderate communication (32%), (2) disengaged (24%), (3) no social media (18%), (4) daily with family in Puerto Rico (6%), and (5) daily trans-territorial (13%) typologies. Participants in the disengaged class were more likely to report elevated depressive symptoms and limited English proficiency, lower prosocial behaviors, lower levels of religiosity, lower attendance at religious services in the U.S., and less engagement in social activities, compared to participants in the Moderate Communication class. CONCLUSION: Roughly one in four individuals in our sample reported very limited technology-based communication with friends/family in their sending and new-receiving communities. As technology and smartphones continue to become integrated into 21st-century life, it is vital that researchers explore how the tremendous potential for connectedness relates to trans-territorial crisis migrants' well-being and adaptation.

Association of serotonin reuptake inhibitors with asthma control.

Background: Clinical trials demonstrated that selective serotonin reuptake inhibitors (SSRI) can improve asthma control in patients with comorbid major depressive disorder (MDD) and that this effect may be greater than the effect of SSRIs on depression. These findings suggest that SSRIs may improve asthma control in patients without MDD. Objective: The current retrospective study examined the effect of SSRIs and serotonin and norepinephrine reuptake inhibitors (SNRI) on asthma control in adult patients. We hypothesized that patients would have fewer asthma exacerbations after treatment with an SSRI or SNRI. Methods: Electronic health record data of adult patients (N = 592) who were seen at a University of Texas Southwestern (UTSW) hospital or clinic and had (1) an SSRI or SNRI prescription, (2) a previous asthma diagnosis, and (3) no mood disorder diagnosis were extracted by using the UTSW Clinical Data Exchange Network. Wilcoxon signed rank tests were used to compare oral corticosteroid prescriptions and asthma-related emergency department (ED) visits and hospitalizations in the 12 months before and after the start of an SSRI/SNRI. Results: Therapy with SSRIs/SNRIs was associated with a significant decrease in oral corticosteroid use (p = 0.003), ED visits (p = 0.002), and hospitalizations (p < 0.001). Conclusion: Results from the current study add to the existing literature by demonstrating a reduced rate of severe exacerbations in patients with asthma by using an SSRI/SNRI without limiting the analytic sample to a high-illness-severity subgroup defined by symptoms of asthma or depression. Future work should include a prospective, placebo controlled study with individuals who have asthma and no comorbid mental health condition, verified by a mental health professional.

Occupational Therapy Practitioners' Implementation of Home Programs for Individuals Post Burn: An Initial Cross-Sectional Survey.

Occupational therapy practitioners who care for individuals post burn often prescribe home programs to facilitate continued progress toward occupational therapy goals. This study identified the components included in home programs, how practitioners create and prescribe home programs, and perceived supports and barriers to adherence in this population. Thirty-nine practitioners employed at American Burn Association-verified centers completed an online survey. Results suggest that home programs are primarily designed to address range of motion with less emphasis on function. The highest-ranked barriers to adherence were pain and lack of motivation while the highest-ranked supports were client motivation and family/caregiver support. Practitioners reported using handouts and demonstration frequently for delivery, with infrequent use of technology. Recommendations for incorporating evidence-based strategies into home program creation and administration are included.

Genomic Epidemiology of Salmonella enterica Circulating in Surface Waters Used in Agriculture and Aquaculture in Central Mexico.

Salmonella enterica can survive in surface waters (SuWa), and the role of nonhost environments in its transmission has acquired increasing relevance. In this study, we conducted comparative genomic analyses of 172 S. enterica isolates collected from SuWa across 3 months in six states of central Mexico during 2019. S. enterica transmission dynamics were assessed using 87 experimental and 112 public isolates from Mexico collected during 2002 through 2019. We also studied genetic relatedness between SuWa isolates and human clinical strains collected in North America during 2005 through 2020. Among experimental isolates, we identified 41 S. enterica serovars and 56 multilocus sequence types (STs). Predominant serovars were Senftenberg (n = 13), Meleagridis, Agona, and Newport (n = 12 each), Give (n = 10), Anatum (n = 8), Adelaide (n = 7), and Infantis, Mbandaka, Ohio, and Typhimurium (n = 6 each). We observed a high genetic diversity in the sample under study, as well as clonal dissemination of strains across distant regions. Some of these strains are epidemiologically important (ST14, ST45, ST118, ST132, ST198, and ST213) and were genotypically close to those involved in clinical cases in North America. Transmission network analysis suggests that SuWa are a relevant source of S. enterica (0.7 source/hub ratio) and contribute to its dissemination as isolates from varied sources and clinical cases have SuWa isolates as common ancestors. Overall, the study shows that SuWa act as reservoirs of various S. enterica serovars of public health significance. Further research is needed to better understand the mechanisms involved in SuWa contamination by S. enterica, as well as to develop interventions to contain its dissemination in food production settings. IMPORTANCE Surface waters are heavily used in food production worldwide. Several human pathogens can survive in these waters for long periods and disseminate to food production environments, contaminating our food supply. One of these pathogens is Salmonella enterica, a leading cause of foodborne infections, hospitalizations, and deaths in many countries. This research demonstrates the role of surface waters as a vehicle for the transmission of Salmonella along food production chains. It also shows that some strains circulating in surface waters are very similar to those implicated in human infections and harbor genes that confer resistance to multiple antibiotics, posing a risk to public health. This study contributes to expand our current knowledge on the ecology and epidemiology of Salmonella in surface waters.

Association between headache and suicidality: An analysis of universal suicide screening data at a large urban county hospital.

BACKGROUND: Identifying individuals at increased risk of suicide is important, particularly those who present for treatment for nonpsychiatric chief complaints who may go undetected. It has been found that pain symptoms, such as headache, are associated with suicide, although this association requires further characterization. This study examined specific components of suicidality in relation to headache subtypes. METHODS: This study retrospectively reviewed 2,832,835 nonpsychiatric adult clinical encounters at a large county hospital, where a standardized suicide risk screening tool, the Columbia-Suicide Severity Rating Scale (C-SSRS), was universally implemented. The C-SSRS assesses specific components of suicidality: wish to be dead and suicidal ideation, method, intent, plan, and action. Multivariate logistic regressions were performed to assess the association between headache, as well as headache subtype (migraine, tension, or cluster), and each component of suicidality. RESULTS: There were significant positive associations between presenting with a headache and 2 specific components of suicidality: wish to be dead and suicidal action. Individuals with tension headache may have a lower risk of wishing to be dead compared to those with migraine and cluster headaches. CONCLUSIONS: The association of headaches with specific elements of sui-cidality demonstrates the potential yield of identification of suicide risk among individuals with nonpsychiatric presentations.

A progressively wetter climate in southern East Africa over the past 1.3 million years.

African climate is generally considered to have evolved towards progressively drier conditions over the past few million years, with increased variability as glacial-interglacial change intensified worldwide. Palaeoclimate records derived mainly from northern Africa exhibit a 100,000-year (eccentricity) cycle overprinted on a pronounced 20,000-year (precession) beat, driven by orbital forcing of summer insolation, global ice volume and long-lived atmospheric greenhouse gases. Here we present a 1.3-million-year-long climate history from the Lake Malawi basin (10°-14° S in eastern Africa), which displays strong 100,000-year (eccentricity) cycles of temperature and rainfall following the Mid-Pleistocene Transition around 900,000 years ago. Interglacial periods were relatively warm and moist, while ice ages were cool and dry. The Malawi record shows limited evidence for precessional variability, which we attribute to the opposing effects of austral summer insolation and the temporal/spatial pattern of sea surface temperature in the Indian Ocean. The temperature history of the Malawi basin, at least for the past 500,000 years, strongly resembles past changes in atmospheric carbon dioxide and terrigenous dust flux in the tropical Pacific Ocean, but not in global ice volume. Climate in this sector of eastern Africa (unlike northern Africa) evolved from a predominantly arid environment with high-frequency variability to generally wetter conditions with more prolonged wet and dry intervals.

The relative importance of reputation and pride as predictors of employee turnover in an academic medical center.

BACKGROUND: Past research shows a dual role of organizational reputation in an employment context. Prospective and current employees are affected by public perceptions of their employer, as affiliation with an employer widely known for its positive achievements boosts organization-based self-esteem whereas a poor reputation leads to decreased self-esteem and disassociation. Another key construct is engagement, which relates to employee enthusiasm and their attitude toward the organization and their interest in finding employment elsewhere. PURPOSE: The current study examined relationships between engagement, organizational pride, perceived departmental and institutional reputation, and turnover intentions in employees at an academic medical center. METHODS: Participants were 241 faculty, staff, and trainees (63.9% women) in a clinical department at an academic medical center who completed an anonymous online survey that contained the Utrecht Work Engagement Scale, as well as questions about pride, reputation, and turnover intentions. Relationships between engagement, organizational pride, perceived departmental and institutional reputation, and turnover intentions were explored. RESULTS: To determine whether employee engagement mediates the relationship between various predictors and turnover intentions, exploratory mediation models were examined. All of the variables were significantly correlated with each other. Perception of departmental reputation was more strongly associated with engagement, pride, and turnover intentions than was institutional reputation. Engagement fully mediated the relationship between perceived institutional reputation and turnover intentions and partially mediated relationships between departmental reputation and turnover intentions and between pride and turnover intentions. PRACTICE IMPLICATIONS: The findings suggest that perception of one's department may be more important to engagement and pride than perception of the larger institution. Furthermore, relationships between pride and reputation and turnover intentions in an academic medical center appear to be, at least partially, mediated through engagement. In contrast to common practice, turnover reduction efforts might be more effective if they enhance perceived departmental, rather than institutional, reputation.

Search for Coherent Elastic Scattering of Solar

We report on a search for nuclear recoil signals from solar ^{8}B neutrinos elastically scattering off xenon nuclei in XENON1T data, lowering the energy threshold from 2.6 to 1.6 keV. We develop a variety of novel techniques to limit the resulting increase in backgrounds near the threshold. No significant ^{8}B neutrinolike excess is found in an exposure of 0.6 t×y. For the first time, we use the nondetection of solar neutrinos to constrain the light yield from 1-2 keV nuclear recoils in liquid xenon, as well as nonstandard neutrino-quark interactions. Finally, we improve upon world-leading constraints on dark matter-nucleus interactions for dark matter masses between 3 and 11 GeV c^{-2} by as much as an order of magnitude.

Comparison of hospital course and outcome in hospital-acquired vs pre-existing delirium.

BACKGROUND: Delirium is a major source of morbidity in the inpatient hospital setting. This study examined differences between patients with delirium present prior to hospital admission and those with hospitalacquired delirium in several health outcomes. METHODS: A total of 12,529 patients on 2 inpatient units were included in this retrospective cohort study. Outcomes were assessed using chart review. Other variables were compared across groups and included in multivariate models predicting discharge location within the hospitalacquired delirium group. RESULTS: Of 709 patients with delirium, 83% had pre-admission prevalent and 17% had post-admission incident delirium. Compared with patients with preexisting delirium, patients with hospital-acquired delirium had greater hospital durations and mortality and were more likely to receive ICU care, more likely to receive multiple classes of medications, and less likely to be discharged home without home health services. Multivariate analysis in the hospital-acquired delirium group found that several variables independently predicted discharge location. CONCLUSIONS: Patients with hospital-acquired delirium had worse hospital outcomes and a more complicated hospital course than those with preexisting delirium. Administration of various medications, several demographic variables, and some hospital-related variables were independently associated with worse outcomes within the hospital-acquired delirium group. These results demonstrate that patients with hospitalacquired delirium are a vulnerable subgroup deserving special attention.

The Relationship Between State Mental Health Agency and Medicaid Spending with Outcomes.

Little is known about relationships between state mental health expenditures and outcomes. This analysis evaluated relationships between spending and income across the states and mental health outcomes. Relationships between state per capita SMHA and Medicaid mental health spending, as well as median household income, percent of residents on Medicaid and Mental Health America (MHA) ranking, suicide and incarceration rates were assessed using correlations and multiple regressions. Median household income predicted MHA overall and youth ranking. Per capita Medicaid mental health spending predicted MHA prevalence ranking. Median household income and Medicaid spending predicted access to care ranking and incarcerations. Median income, Medicaid spending and percent receiving Medicaid predicted suicide rate. The findings suggest median household income may, in some cases, predict mental health treatment quality and outcomes more strongly than spending. However, the relationship with per capita mental health Medicaid spending on outcomes is also noteworthy.

Vaccines for COVID-19.

Since the emergence of COVID-19, caused by the SARS-CoV-2 virus at the end of 2019, there has been an explosion of vaccine development. By 24 September 2020, a staggering number of vaccines (more than 200) had started preclinical development, of which 43 had entered clinical trials, including some approaches that have not previously been licensed for human vaccines. Vaccines have been widely considered as part of the exit strategy to enable the return to previous patterns of working, schooling and socializing. Importantly, to effectively control the COVID-19 pandemic, production needs to be scaled-up from a small number of preclinical doses to enough filled vials to immunize the world's population, which requires close engagement with manufacturers and regulators. It will require a global effort to control the virus, necessitating equitable access for all countries to effective vaccines. This review explores the immune responses required to protect against SARS-CoV-2 and the potential for vaccine-induced immunopathology. We describe the profile of the different platforms and the advantages and disadvantages of each approach. The review also addresses the critical steps between promising preclinical leads and manufacturing at scale. The issues faced during this pandemic and the platforms being developed to address it will be invaluable for future outbreak control. Nine months after the outbreak began we are at a point where preclinical and early clinical data are being generated for the vaccines; an overview of this important area will help our understanding of the next phases.

ß Decay of

The interpretation of observations of cooling neutron star crusts in quasipersistent x-ray transients is affected by predictions of the strength of neutrino cooling via crust Urca processes. The strength of crust Urca neutrino cooling depends sensitively on the electron-capture and ß-decay ground-state-to-ground-state transition strengths of neutron-rich rare isotopes. Nuclei with a mass number of A=61 are predicted to be among the most abundant in accreted crusts, and the last remaining experimentally undetermined ground-state-to-ground-state transition strength was the ß decay of ^{61}V. This Letter reports the first experimental determination of this transition strength, a ground-state branching of 8.1_{-3.1}^{+4.0}%, corresponding to a log ft value of 5.5_{-0.2}^{+0.2}. This result was achieved through the measurement of the ß-delayed γ rays using the total absorption spectrometer SuN and the measurement of the ß-delayed neutron branch using the neutron long counter system NERO at the National Superconducting Cyclotron Laboratory at Michigan State University. This method helps to mitigate the impact of the pandemonium effect in extremely neutron-rich nuclei on experimental results. The result implies that A=61 nuclei do not provide the strongest cooling in accreted neutron star crusts as expected by some predictions, but that their cooling is still larger compared to most other mass numbers. Only nuclei with mass numbers 31, 33, and 55 are predicted to be cooling more strongly. However, the theoretical predictions for the transition strengths of these nuclei are not consistently accurate enough to draw conclusions on crust cooling. With the experimental approach developed in this work, all relevant transitions are within reach to be studied in the future.

Mechanisms, screening modalities and treatment options for individuals with non-alcoholic fatty liver disease and type 2 diabetes.

Non-alcoholic fatty liver disease (NAFLD) exists as a spectrum of disease ranging from excessive accumulation of fat within the liver (simple steatosis), inflammation (non-alcoholic steatohepatitis) through to fibrosis, cirrhosis and end-stage liver disease. There is also an increased risk of hepatocellular carcinoma. The principal risk factor for NAFLD is overweight or obesity, along with type 2 diabetes, and NAFLD itself is also a risk factor for incident type 2 diabetes. Overweight/obesity is synergistic with alcohol consumption in causing progressive and insidious liver damage. Recent consensus advocates a change in nomenclature from NAFLD to 'metabolic associated fatty liver disease' (MAFLD), reflective of the associated metabolic abnormalities (insulin resistance/type 2 diabetes and metabolic syndrome components). Additional extra-hepatic manifestations of NAFLD include cardiovascular disease, chronic kidney disease and certain cancers. Unlike other micro- and macrovascular complications of type 2 diabetes, systematic screening or surveillance protocols have not been widely adopted in routine diabetes care to assess for presence/severity of NAFLD. Various screening tools are available (non-invasive tests and biochemical indices) combined with imaging techniques (e.g. transient elastography) to detect steatosis and more importantly advanced fibrosis/cirrhosis to facilitate appropriate surveillance. Liver biopsy may be sometimes necessary. Treatment options for type 2 diabetes, including lifestyle interventions (dietary change and physical activity), glucose-lowering therapies and metabolic surgery, can modulate hepatic steatosis and to a lesser extent fibrosis. Awareness of the impact of liver disease on the choice of glucose-lowering medications in individuals with type 2 diabetes is also critical.

Association of Megestrol Use With the Development of New Psychiatric Diagnoses.

OBJECTIVE: To analyze the risk of megestrol, a glucocorticoid and progesterone receptor agonist used to enhance appetite, on the development of a new psychiatric diagnosis. DESIGN AND PARTICIPANTS: Deidentified data of megestrol (n = 706) and propensity score-matched comparison (age, gender, and body mass index) patients (n = 2,118) from January 1, 2001 to June 30, 2018 were obtained from the UT Southwestern patient database. Data were analyzed using a series of conditional binary logistic regressions controlling for comorbidities, pre-existing psychiatric disorders, and number of patient encounters. SETTING: A large academic medical center database of megestrol-treated patients and matched comparison patients was used. MEASUREMENTS AND RESULTS: The regression model showed that megestrol was significantly associated with developing a new psychiatric diagnosis (B = 1.28, Wald χ21 = 83.12, odds ratio [OR] = 3.60, p <0.001). In subgroup analyses, development of cognitive (B = 2.42, Wald χ21 = 16.09, OR = 11.30, p <0.001), mood (B = 1.31, Wald χ21 = 40.38, OR = 3.70, p <0.001), and anxiety (B = 1.72, Wald χ21 = 45.28, OR = 5.60, p <0.001) disorders were also associated with megestrol use. CONCLUSIONS: Patients taking megestrol were significantly more likely to develop a new psychiatric diagnosis than comparison patients. Highest risks were associated with the development of cognitive diagnoses. The findings suggest that megestrol, like other glucocorticoid agonists, is associated with an increased risk of developing a psychiatric disorder. This risk should be considered when determining the risk-to-benefit ratio of megestrol use in patients.

Dynamically important magnetic fields near accreting supermassive black holes.

Accreting supermassive black holes at the centres of active galaxies often produce 'jets'--collimated bipolar outflows of relativistic particles. Magnetic fields probably play a critical role in jet formation and in accretion disk physics. A dynamically important magnetic field was recently found near the Galactic Centre black hole. If this is common and if the field continues to near the black hole event horizon, disk structures will be affected, invalidating assumptions made in standard models. Here we report that jet magnetic field and accretion disk luminosity are tightly correlated over seven orders of magnitude for a sample of 76 radio-loud active galaxies. We conclude that the jet-launching regions of these radio-loud galaxies are threaded by dynamically important fields, which will affect the disk properties. These fields obstruct gas infall, compress the accretion disk vertically, slow down the disk rotation by carrying away its angular momentum in an outflow and determine the directionality of jets.