Search

A male in his 70s presented to the emergency department with sudden-onset abdominal pain and syncope. While in the emergency department, he developed worsening hypotension and anaemia. A CT angiogram was suggestive of abdominal apoplexy (spontaneous intraperitoneal haemorrhage), which was treated successfully with embolisation of the bleeding vessels. Spontaneous bleeding was thought to be related to his initiation of apixaban 1 week previously. The patient made an excellent recovery and was transitioned back to oral anticoagulation.

The climate system responds to changes in the amount of atmospheric greenhouse gases or aerosols through rapid processes, triggered within hours and days, and through slower processes, where the full response may only be seen after centuries. In this paper, we aim to elucidate the mechanisms operating on time scales of hours to years to better understand the response of key climate quantities such as energy fluxes, temperature, and precipitation after a sudden increase in either carbon dioxide (CO2), black carbon (BC), or sulfate (SO4) aerosols. The results are based on idealized simulations from six global climate models. We find that the effect of changing ocean temperatures kicks in after a couple of months. Rapid precipitation reductions start occurring instantly and are established after just a few days. For BC, they constitute most of the equilibrium response. For CO2 and SO4, the magnitude of the precipitation response gradually increases as surface warming/cooling evolves, and for CO2, the sign of the response changes from negative to positive after 2 years. Rapid cloud adjustments are typically established within the first 24 h, and while the magnitude of cloud feedbacks for CO2 and SO4 increases over time, the geographical pattern of the equilibrium cloud change is present already after the first year. While there are model differences, our work underscores the overall similarity of the major time-varying processes and responses simulated by current global models and hence the robustness of key features of simulated responses to historical and future anthropogenic forcing. Significance Statement How does the climate system respond to a change in the amount of atmospheric greenhouse gases or aerosols? Some processes are rapid, responding within hours and days. Others are slow, and the full response to a forcing of the climate may only be seen after centuries. In this paper, we use six global climate models to investigate the time scales of climate responses to carbon dioxide, black carbon, and sulfate, focusing on key climate quantities, such as temperature, precipitation, and clouds. While there are ample model differences, our work underscores the overall similarity of the major time-varying processes and responses simulated by current global models and hence the robustness of key features of simulated responses to historical and future anthropogenic forcing.

The PROpel trial assessed the combination of olaparib+abiraterone acetate (AA) plus prednisone and androgen deprivation therapy (ADT) versus AA plus prednisone and ADT alone as first-line treatment for metastatic castration-resistant prostate cancer (mCPRP). To contextualize the progression free survival (PFS) benefit in PROpel, we performed a systematic review and quasi-individual patient data network meta-analysis on randomized controlled trials of first-line hormonal treatments for mCPRC. Meta-analysis was performed for the PROpel control arm and PREVAIL (enzalutamide) and COU-AA-302 (AA) treatment arms. Kaplan-Meier PFS curves were digitally reconstructed and differences in restricted mean survival time (ΔRMST) were computed. Combination therapy yielded longer PFS (24-mo ΔRMST 1.5 mo, 95% confidence interval 0.6-2.4) in comparison to novel hormonal treatments alone. However, the lack of mature overall survival data, higher complication rates, and higher health care costs are limitations of combination therapy. Ultimately, combining treatments, rather than molecularly targeted sequencing in cases of failure, might not be justified in unselected patients with mCRPC.Patient summaryA recent trial showed that for metastatic prostate cancer that does not respond to hormone treatment, combined therapy with two drugs (olaparib and abiraterone) may prolong survival free from cancer progression. We included these data in an analysis of three trials that confirmed a small benefit. This combination approach has higher complication rates and is more expensive, and longer-term results for overall survival are needed.

The contemporary methodological debate about justice has centered around a dispute about the value of so-called ideal theory. I argue that justice performs a social-guiding function, which explains how people should respond to their limited and fallible abilities to realize justice institutionally. My argument helps to re-orientate the contemporary methodological debate. The obvious disagreement between many prominent supporters and skeptics of ideal theory obscures the fact that they are united by a false assumption: the practical value of justice exclusively consists of its institution-guiding function. To capture the overlooked social-guiding function, a richer normative theory of justice is required; I show how such a theory can be supplied by “ideal-transitional” principles.

We present a study of rotation across 30 square degrees of the Orion Star-forming Complex, following a $\sim$200 d photometric monitoring campaign by the Next Generation Transit Survey (NGTS). From 5749 light curves of Orion members, we report periodic signatures for 2268 objects and analyse rotation period distributions as a function of colour for 1789 stars with spectral types F0$-$M5. We select candidate members of Orion using $\textit{Gaia}$ data and assign our targets to kinematic sub-groups. We correct for interstellar extinction on a star-by-star basis and determine stellar and cluster ages using magnetic and non-magnetic stellar evolutionary models. Rotation periods generally lie in the range 1$-$10 d, with only 1.5 per cent of classical T Tauri stars or Class I/II young stellar objects rotating with periods shorter than 1.8 d, compared with 14 per cent of weak-line T Tauri stars or Class III objects. In period$-$colour space, the rotation period distribution moves towards shorter periods among low-mass (>M2) stars of age 3$-$6 Myr, compared with those at 1$-$3 Myr, with no periods longer than 10 d for stars later than M3.5. This could reflect a mass-dependence for the dispersal of circumstellar discs. Finally, we suggest that the turnover (from increasing to decreasing periods) in the period$-$colour distributions may occur at lower mass for the older-aged population: $\sim$K5 spectral type at 1$-$3 Myr shifting to $\sim$M1 at 3$-$6 Myr., This article has been accepted for publication in Monthly Notices of the Royal Astronomical Society. Published by Oxford University Press on behalf of the Royal Astronomical Society. 20 pages. 21 figures

International audience; Extensive research on nanosized ZnO has proven that its optical properties are challenging to control due to a number of possible defects producing various emissions in the visible range. Our group proposed a low-temperature, supercritical-fluid-driven synthesis of isotropic nanosized particles that exhibit a unique and unprecedentedly pure excitonic emission, comparable to that of single crystals. The present article reports the growth mechanism at the origin of the unexpectedly pure excitonic emission as well as a more detailed study of its optical properties at liquid helium temperatures. The ZnO phase is obtained via the thermal decomposition of an intermediate ZnO2 phase. No bulk defect luminescence is detected, and the synthesis route leaves a “ZnO2-like” surface able to neutralize the formation of surface defects, which can contribute to visible emissions. The luminescence measurements were performed at liquid helium temperature to enable the identification of excitons. The investigation of the photoluminescence properties confirms a strong excitonic emission in the UV region with no visible band and sheds light on a phonon coupling with the E2 high vibrational mode.

Spinal cord injury (SCI) results in significant loss of sublesional bone, adding to the comorbidity of SCI with an increased risk of fracture and post-fracture complications. Unfortunately, the effect of SCI on skeletal health is also likely to rise, as the average age of SCI has increased and there are well-known negative effects of age on bone. To date, however, the impact of age and age-associated inflammation (inflammaging) on skeletal health after SCI remains largely unknown. To address this, we compared bone parameters in young (3 month) and middle-aged (9 month) male and female rats with a moderate thoracic contusion injury, to age- and sex-matched sham-operated controls. Skeletal parameters, locomotor function, and serum cytokine levels were assessed at both subchronic (30 days) and chronic (180 days) time points post-injury. We hypothesized that SCI would lead to a dramatic loss of bone immediately after injury in all SCI groups, with inflammaging leading to greater loss in middle-aged SCI rats. We also predicted that whereas younger rats might re-establish bone properties in more chronic phases of SCI, middle-aged rats would not. Supporting these hypothesis, trabecular bone volume was significantly lower in male and young female SCI rats early after injury. Contrary to our hypothesis, however, there was greater loss of trabecular bone volume, relative to age-matched shams, in young compared with middle-aged SCI rats, with no effects of SCI on trabecular bone volume in middle-aged female rats. Moreover, despite recovery of weight-supported locomotor activity, bone loss persisted into the chronic phase of injury for the young rats. Bone formation rates were lower in young male SCI rats, regardless of the time since injury, whereas both young and middle-aged female SCI rats had lower bone formation in the subchronic but not the chronic phase of SCI. In middle-aged rats, SCI-induced higher osteoclast surfaces, which also persisted into the chronic phase of SCI in middle-aged females. Neither age nor SCI-induced increases in inflammation seemed to be associated with bone loss. In fact, SCI had more dramatic and persistent effects on bone in male rats, whereas aging and SCI elevated serum cytokines only in female rats. Overall, this study demonstrates SCI-induced loss of bone and altered bone turnover in male and female rats that persists into the chronic phase post-injury. The sex- and age-dependent variations in bone turnover and serum cytokines, however, underscore the need to further explore both mechanisms and potential therapeutics in multiple demographics.

Background: Abiraterone acetate plus prednisolone (herein referred to as abiraterone) or enzalutamide added at the start of androgen deprivation therapy improves outcomes for patients with metastatic prostate cancer. Here, we aimed to evaluate long-term outcomes and test whether combining enzalutamide with abiraterone and androgen deprivation therapy improves survival. Methods: We analysed two open-label, randomised, controlled, phase 3 trials of the STAMPEDE platform protocol, with no overlapping controls, conducted at 117 sites in the UK and Switzerland. Eligible patients (no age restriction) had metastatic, histologically-confirmed prostate adenocarcinoma; a WHO performance status of 0–2; and adequate haematological, renal, and liver function. Patients were randomly assigned (1:1) using a computerised algorithm and a minimisation technique to either standard of care (androgen deprivation therapy; docetaxel 75 mg/m 2 intravenously for six cycles with prednisolone 10 mg orally once per day allowed from Dec 17, 2015) or standard of care plus abiraterone acetate 1000 mg and prednisolone 5 mg (in the abiraterone trial) orally or abiraterone acetate and prednisolone plus enzalutamide 160 mg orally once a day (in the abiraterone and enzalutamide trial). Patients were stratified by centre, age, WHO performance status, type of androgen deprivation therapy, use of aspirin or non-steroidal anti-inflammatory drugs, pelvic nodal status, planned radiotherapy, and planned docetaxel use. The primary outcome was overall survival assessed in the intention-to-treat population. Safety was assessed in all patients who started treatment. A fixed-effects meta-analysis of individual patient data was used to compare differences in survival between the two trials. STAMPEDE is registered with ClinicalTrials.gov (NCT00268476) and ISRCTN (ISRCTN78818544). Findings: Between Nov 15, 2011, and Jan 17, 2014, 1003 patients were randomly assigned to standard of care (n=502) or standard of care plus abiraterone (n=501) in the abiraterone trial. Between July 29, 2014, and March 31, 2016, 916 patients were randomly assigned to standard of care (n=454) or standard of care plus abiraterone and enzalutamide (n=462) in the abiraterone and enzalutamide trial. Median follow-up was 96 months (IQR 86–107) in the abiraterone trial and 72 months (61–74) in the abiraterone and enzalutamide trial. In the abiraterone trial, median overall survival was 76·6 months (95% CI 67·8–86·9) in the abiraterone group versus 45·7 months (41·6–52·0) in the standard of care group (hazard ratio [HR] 0·62 [95% CI 0·53–0·73]; pinteraction=0·71) or between-trial heterogeneity (I 2 p=0·70). In the first 5 years of treatment, grade 3–5 toxic effects were higher when abiraterone was added to standard of care (271 [54%] of 498 vs 192 [38%] of 502 with standard of care) and the highest toxic effects were seen when abiraterone and enzalutamide were added to standard of care (302 [68%] of 445 vs 204 [45%] of 454 with standard of care). Cardiac causes were the most common cause of death due to adverse events (five [1%] with standard of care plus abiraterone and enzalutamide [two attributed to treatment] and one (

The addiction cycle has been proposed as a framework for understanding the progression of alcohol use disorder (AUD) in terms of psychological and biological domains, including reward drinking/incentive salience, relief drinking/negative emotionality, and loss of control/executive functioning impairment. To have utility in clinical practice, self-report measures of these domains that are applicable across sociodemographic groups and associated with clinical outcomes are needed. This study sought to validate domains from self-report measures and to test whether domains are measurement invariant across sociodemographic groups and associated with treatment outcomes.Secondary analysis of individuals with AUD (Fifteen self-report items were used as indicators of the addiction cycle domains, with sociodemographic differences in measurement by sex, age, race, education, and AUD symptoms. Relief/negative emotionality and reward/incentive salience were significantly associated with outcomes at 1 and 3 years following treatment, and executive functioning also predicted nonabstinent recovery at 3 years.The results support the utility of domains relevant to the addiction cycle in predicting AUD treatment outcomes and recovery among individuals who sought treatment for AUD. The addiction cycle domains were more strongly associated with outcomes than other measures clinicians might use to predict outcomes (e.g., AUD symptoms). Future research should continue to develop and refine the items and test whether the addiction cycle domains can inform treatment planning. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

We report a case of a patient with 18p deletion syndrome and concurrent FZD4 (frizzled-4) mutation. A 6-month-old boy with known 18p deletion syndrome presented with abnormal eye movements in both eyes and an inability to track objects. The patient had a history of laryngomalacia, hypotonia, and developmental delay. Examination showed bilateral total exudative and traction retinal detachment with anomalous retinal vascular development noted on widefield fluorescein angiography. Genetic analysis identified a concurrent FZD4 mutation (c.205C>T [p.H69Y]). Both eyes underwent 25-gauge limbal vitrectomy, lensectomy, and membrane peeling, and the posterior pole successfully reattached with improvement in visual function. The 18p region contains the LAMA1 , TGIF1 , and APCDD1 genes, which are involved in the vascular basement membrane and Wnt/β-catenin signaling, which may have potentiated the particularly severe familial exudative vitreoretinopathy phenotype. We present the clinical findings, imaging analyses, and surgical management of concurrent 18p deletion syndrome and FDZ4 mutation. The overlap in molecular mechanisms of the multiple gene products may potentiate the severe phenotype. [ Ophthalmic Surg Lasers Imaging Retina 2023;54:284–290.]

The extent to which species ranges reflect intrinsic physiological tolerances is a major, unsolved question in evolutionary ecology. To date, consensus has been hindered by the limited tractability of experimental approaches across most of the tree of life. Here, we apply a macrophysiological approach to understand how hematological traits related to oxygen transport shape elevational ranges in a tropical biodiversity hotspot. Along Andean elevational gradients, we measured traits that affect blood oxygen-carrying capacity—total and cellular hemoglobin concentration and hematocrit—for 2,355 individuals of 136 bird species. We used these data to evaluate the influence of hematological traits on elevational ranges. First, we asked whether hematological plasticity is predictive of elevational range breadth. Second, we asked whether variance in hematological traits changed as a function of distance from the midpoint of the elevational range. We found that the correlation between hematological plasticity and elevational range breadth was slightly positive, consistent with a facilitative role for plasticity in elevational range expansion. We further found reduced local variation in hematological traits near elevational range limits and at high elevations, patterns consistent with intensified natural selection, reduced effective population size, or compensatory changes in other cardiohematological traits with increasing distance from species-specific optima for oxygen availability. Our findings suggest that constraints on hematological plasticity and local genetic adaptation to oxygen availability promote the evolution of the narrow elevational ranges that underpin tropical montane biodiversity.

Drinking motives, or reasons people choose to drink, are well-established risk factors for alcohol use and related negative consequences. Recent research has shown utility in a self-determination theory (SDT) approach for describing motivation for engaging in behaviors that reduce the harms associated with alcohol use (i.e., drinking responsibly). In the present study, we examined the relationship between drinking motives and motivations for drinking responsibly as well as their unique and incremental associations with alcohol-related outcomes (protective behavioral strategies [PBS], consumption, and negative consequences) in two samples of college student drinkers: (a) a random sample (n = 507) recruited from a Hispanic-Serving Institution on the U.S. border with Mexico (Mage = 22.84, SD = 5.84; 67.3% female; 90.9% Hispanic) and (b) a convenience sample (n = 2,808) from Psychology Department research participation pools at 10 universities in 8 U.S. states (Mage = 20.59, SD = 4.18; 72.9% female; 58.2% non-Hispanic White). Autonomous motivations (experience of volition and choice) for drinking responsibly were negatively correlated with drinking motives, but these correlations were small-to-medium in magnitude suggesting nonredundancy between the constructs. Drinking motives were risk factors for alcohol-related outcomes, especially alcohol-related problems, and autonomous motivations for drinking responsibly were protective factors for alcohol-related outcomes, especially PBS. Both motivational constructs predicted alcohol-related outcomes beyond the other, but drinking motives generally accounted for more variance. These findings suggest that integrating motivation in relation to both drinking and drinking responsibly may lead to a better understanding of alcohol-related behaviors and the associated negative consequences among college students. Implications for college drinking interventions are discussed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Cannabis use continues to escalate among emerging adults and college attendance may be a risk factor for use. Severe cases of cannabis use can escalate to a cannabis use disorder, which is associated with worse psychosocial functioning. Predictors of cannabis use consequences and cannabis use disorder symptom severity have been identified; however, they typically employ a narrow set of predictors and rely on linear models. Machine learning is well suited for exploratory data analyses of high-dimensional data. This study applied decision tree learning to identify predictors of cannabis user status, negative cannabis-related consequences, and cannabis use disorder symptoms. Undergraduate college students (N = 7000) were recruited from nine universities in nine states across the U.S. Among the 7 trees, 24 splits created by 15 distinct predictors were identified. Consistent with prior research, one's beliefs about cannabis were strong predictors of user status. Negative reinforcement cannabis use motives were the most consistent predictors of cannabis use disorder symptoms, and past month cannabis use was the most consistent predictor of probable cannabis use disorder. Typical frequency of cannabis use was the only predictor of negative cannabis-related consequences. Our results demonstrate that decision trees are a useful methodological tool for identifying targets for future clinical research.

Chronic hypercapnia (CH) is a hallmark of chronic lung disease, and CH increases the risk for acute-on-chronic exacerbations leading to greater hypoxemia/hypercapnia and poor health outcomes. However, the role of hypercapnia per se (duration and severity) in determining an individual's ability to tolerate further hypercapnic exacerbations is unknown. Our primary objective herein was to test the hypothesis that mild-to-moderate CH (arterial [Formula: see text] ∼50-70 mmHg) increases susceptibility to pathophysiological responses to severe acute COlt;subgt;2lt;/subgt; challenges. Three groups (GR) of adult female goats were studied during 14 days of exposure to room air (lt;igt;GR 1lt;/igt;; control) or 6% inspired COlt;subgt;2lt;/subgt; (lt;igt;GR 2lt;/igt;; mild CH), or 7 days of 6% inspired COlt;subgt;2lt;/subgt; followed by 7 days of 8% inspired COlt;subgt;2lt;/subgt; (lt;igt;GR 3lt;/igt;; moderate CH). Consistent with previous reports, there were no changes in physiological parameters inlt;igt;GR 1lt;/igt; (RA control), but mild CH (lt;igt;GR 2lt;/igt;) increased steady-state ventilation and transiently suppressed COlt;subgt;2lt;/subgt;/[Hlt;supgt;+lt;/supgt;] chemosensitivity. Further increasing InCOlt;subgt;2lt;/subgt; from 6% to 8% (lt;igt;GR 3lt;/igt;) transiently increased ventilation and arterial [Hlt;supgt;+lt;/supgt;]. Similar to mild CH, moderate CH increased ventilation to levels greater than predicted. However, in contrast to mild CH, acute ventilatory chemosensitivity was suppressed throughout the duration of moderate CH, and the arterial - mixed expired COlt;subgt;2lt;/subgt; gradient became negative. These data suggest that moderate CH limits physiological responses to acute severe exacerbations and provide evidence of recruitment of extrapulmonary systems (i.e., gastric COlt;subgt;2lt;/subgt; elimination) during times of moderate-severe hypercapnia.lt;bgt;NEWamp;amp; NOTEWORTHYlt;/bgt; Moderate levels of chronic hypercapnia (CH; ∼70 mmHg) in healthy adult female goats elicited similar steady-state physiological adaptations compared with mild CH (∼55 mmHg). However, unlike mild CH, moderate CH chronically suppressed acute COlt;subgt;2lt;/subgt;/[Hlt;supgt;+lt;/supgt;] chemosensitivity and reversed the arterial to mixed expired COlt;subgt;2lt;/subgt; gradient. These findings suggest that moderate CH suppresses vital mechanisms of ventilatory control and recruits additional physiological systems (i.e., gastric COlt;subgt;2lt;/subgt; release) to help buffer excess COlt;subgt;2lt;/subgt;.

The design and implementation of adaptive chemical reaction networks, capable of adjusting their behavior over time in response to experience, is a key goal for the fields of molecular computing and DNA nanotechnology. Mainstream machine learning research offers powerful tools for implementing learning behavior that could one day be realized in a wet chemistry system. Here we develop an abstract chemical reaction network model that implements the backpropagation learning algorithm for a feedforward neural network whose nodes employ the nonlinear “leaky rectified linear unit” transfer function. Our network directly implements the mathematics behind this well-studied learning algorithm, and we demonstrate its capabilities by training the system to learn a linearly inseparable decision surface, specifically, the XOR logic function. We show that this simulation quantitatively follows the definition of the underlying algorithm. To implement this system, we also report ProBioSim, a simulator that enables arbitrary training protocols for simulated chemical reaction networks to be straightforwardly defined using constructs from the host programming language. This work thus provides new insight into the capabilities of learning chemical reaction networks and also develops new computational tools to simulate their behavior, which could be applied in the design and implementations of adaptive artificial life.

Evangelicals need help from Charles Haddon Spurgeon (1834‒1892) in cultivating an ethic fueled by the rescuing work of Christ. This 19th-century Victorian-era pastor from a London megachurch helped provide a gospel compass that directed Christians in both the head and the heart in their approach to the troubles of society. His work assists American evangelicals in this part of the 21st century by addressing some of the significant issues of the present time: patriotism/nationalism, racism, and religious liberty. This book analyzes the sermons of Charles Spurgeon to construct a gospel-centered ethic toward the vulnerable and downtrodden of society. Many of the events and situations that marked his day parallels the circumstances of the present day. Spurgeon's approach (from both preaching and writing) provides the present evangelical world with a necessary template to move forward biblically and ethically.

The large particle sizes of railway ballast and rock fill have meant that conventional techniques used to measure the small-strain stiffness of finer geomaterials have not been adopted, with the consequence that their stiffnesses are poorly defined. In a series of tests on a UK railway ballast, simple adaptations were made to existing local strain measuring systems to account for the larger particle sizes. The study showed that the small-strain stiffnesses are different in second loading compared to virgin loading, but multiple cycles had little further effect on the stiffness. The large particle size was found rarely to have any detrimental effect on the quality of the strain measurements and the two independent measurements of axial strain taken at diametrically opposite locations were generally as consistent as for finer grained soils. As for other soils, the ‘external’ measurements of strain across the apparatus platens were of little use in determining stiffness. The presence of water did not have a significant effect on the behaviour, and this was confirmed by inter-particle loading tests on single particle contacts. Despite the use of lubricated end platens, there was a significant barrelling of the sample at large shear strains so that the internal measurement of the volumetric change diverged from the external measurement at large strains. The very small volumetric strains that occurred during isotropic loading meant that each sample could only be used to obtain one measurement of the virgin loading stiffness.

Two studies examined the change in self-efficacy of practitioners after attending Triple P training and the moderators that affect training outcomes. Study 1 used a large multidisciplinary sample of health, education, and welfare practitioners (N = 37,235) came from 30 countries around the world, which all participate in a Triple P professional training course during 2012–2019. This study assessed practitioners’ overall self-efficacy and their consultation skills efficacy prior to training, immediately following training, and at six- to eight-weeks follow-up. Participants reported significant improvements of their overall self-efficacy and their consultation skills self-efficacy. There were significantly small differences based on practitioners’ gender, disciplines, education levels, and country location. Study 2 examined the training outcomes of videoconference-based training (following the COVID-19 pandemic) compared to in-person training (N = 6867). No significant differences were found between videoconference and in-person training on any outcome measure. Implications for the global dissemination of evidence-based parenting programs as part of a comprehensive public health response to COVID-19 was discussed.

Kwang-Kuo Hwang provides numerous recommendations for how to develop an indigenous cultural psychology. These recommendations may be understood to suggest proceeding according to three stages: (1) beginning with philosophical reflection on the meaning of modernization and exploring the topics of reality and structure (where such reflections ground one’s subsequent development of meta-models concerning self and social interaction), (2) adopting such meta-models as a hermeneutic for interpreting texts associated with one’s cultural tradition, and (3) conducting experimental studies on the basis of hypotheses derived from such cultural interpretations. Hwang’s philosophy is valuable in that it exemplifies a postmodern approach to cultural psychology that integrates traditional pre-modern forms of wisdom with modern methods of scientific investigation.

BACKGROUND: We describe the investigation of a nosocomial outbreak of rapidly growing mycobacteria (RGM) infections and the results of mitigation efforts after 8 years. METHODS: A cluster of RGM cases in a Kentucky hospital in 2013 prompted an investigation into RGM surgical site infections following joint replacement surgery. A case-control study was conducted to identify risk factors. RESULTS: Eight cases were identified, 5 caused by M. wolinskyi and 3 by M. goodii. The case-control study showed the presence of a particular nurse in the operating room was significantly associated with infection. Environmental sampling at the nurse’s home identified an outdoor hot tub as the likely source of M. wolinskyi, confirmed by pulsed-field gel electrophoresis and whole genome sequencing. The hot tub reservoir was eliminated, and hospital policies were revised to correct infection control lapses. No new cases of RGM infections have been identified as of 2021. DISCUSSION: Breaches in infection control practices at multiple levels may have led to a chain of infection from a nurse’s hot tub to surgical sites via indirect person-to-person transmission from a colonized health care worker (HCW). CONCLUSIONS: The multifactorial nature of the outbreak’s cause highlights the importance of overlapping or redundant layers of protection preventing patient harm. Future investigations of RGM outbreaks should consider the potential role of colonized HCWs as a transmission vector.

BACKGROUND: Active surveillance (AS) is recommended for low-risk and some intermediate-risk prostate cancer. Uptake and practice of AS vary significantly across different settings, as does the experience of surveillance-from which tests are offered, and to the levels of psychological support. OBJECTIVE: To explore the current best practice and determine the most important research priorities in AS for prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: A formal consensus process was followed, with an international expert panel of purposively sampled participants across a range of health care professionals and researchers, and those with lived experience of prostate cancer. Statements regarding the practice of AS and potential research priorities spanning the patient journey from surveillance to initiating treatment were developed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Panel members scored each statement on a Likert scale. The group median score and measure of consensus were presented to participants prior to discussion and rescoring at panel meetings. Current best practice and future research priorities were identified, agreed upon, and finally ranked by panel members. RESULTS AND LIMITATIONS: There was consensus agreement that best practice includes the use of high-quality magnetic resonance imaging (MRI), which allows digital rectal examination (DRE) to be omitted, that repeat standard biopsy can be omitted when MRI and prostate-specific antigen (PSA) kinetics are stable, and that changes in PSA or DRE should prompt MRI ± biopsy rather than immediate active treatment. The highest ranked research priority was a dynamic, risk-adjusted AS approach, reducing testing for those at the least risk of progression. Improving the tests used in surveillance, ensuring equity of access and experience across different patients and settings, and improving information and communication between and within clinicians and patients were also high priorities. Limitations include the use of a limited number of panel members for practical reasons. CONCLUSIONS: The current best practice in AS includes the use of high-quality MRI to avoid DRE and as the first assessment for changes in PSA, with omission of repeat standard biopsy when PSA and MRI are stable. Development of a robust, dynamic, risk-adapted approach to surveillance is the highest research priority in AS for prostate cancer. PATIENT SUMMARY: A diverse group of experts in active surveillance, including a broad range of health care professionals and researchers and those with lived experience of prostate cancer, agreed that best practice includes the use of high-quality magnetic resonance imaging, which can allow digital rectal examination and some biopsies to be omitted. The highest research priority in active surveillance research was identified as the development of a dynamic, risk-adjusted approach.

Hindbrain growth hormone secretagogue receptor (GHSR) agonism increases food intake, yet the underlying neural mechanisms remain unclear. The functional effects of hindbrain GHSR antagonism by its endogenous antagonist liver-expressed antimicrobial peptide 2 (LEAP2) are also yet unexplored. To test the hypothesis that hindbrain GHSR agonism attenuates the food intake inhibitory effect of gastrointestinal (GI) satiation signals, ghrelin (at a feeding subthreshold dose) was administered to the fourth ventricle (4V) or directly to the nucleus tractus solitarius (NTS) before systemic delivery of the GI satiation signal cholecystokinin (CCK). Also examined, was whether hindbrain GHSR agonism attenuated CCK-induced NTS neural activation (c-Fos immunofluorescence). To investigate an alternate hypothesis that hindbrain GHSR agonism enhances feeding motivation and food seeking, intake stimulatory ghrelin doses were administered to the 4V and fixed ratio 5 (FR-5), progressive ratio (PR), and operant reinstatement paradigms for palatable food responding were evaluated. Also assessed were 4V LEAP2 delivery on food intake and body weight (BW) and on ghrelin-stimulated feeding. Both 4V and NTS ghrelin blocked the intake inhibitory effect of CCK and 4V ghrelin blocked CCK-induced NTS neural activation. Although 4V ghrelin increased low-demand FR-5 responding, it did not increase high-demand PR or reinstatement of operant responding. Fourth ventricle LEAP2 reduced chow intake and BW and blocked hindbrain ghrelin-stimulated feeding. Data support a role for hindbrain GHSR in bidirectional control of food intake through mechanisms that include interacting with the NTS neural processing of GI satiation signals but not food motivation and food seeking.