Coherent optical phase transfer over a 32-km fiber with 1-s instability at 10−1710^{-17}

The phase coherence of an ultrastable optical frequency reference is fully maintained over actively stabilized fiber networks of lengths exceeding 30 km. For a 7-km link installed in an urban environment, the transfer instability is $6 \times 10^{-18}$ at 1-s. The excess phase noise of 0.15 rad, integrated from 8 mHz to 25 MHz, yields a total timing jitter of 0.085 fs. A 32-km link achieves similar performance. Using frequency combs at each end of the coherent-transfer fiber link, a heterodyne beat between two independent ultrastable lasers, separated by 3.5 km and 163 THz, achieves a 1-Hz linewidth.Comment: 4 pages, 4 figure

At risk of being risky: The relationship between "brain age" under emotional states and risk preference.

Developmental differences regarding decision making are often reported in the absence of emotional stimuli and without context, failing to explain why some individuals are more likely to have a greater inclination toward risk. The current study (N=212; 10-25y) examined the influence of emotional context on underlying functional brain connectivity over development and its impact on risk preference. Using functional imaging data in a neutral brain-state we first identify the "brain age" of a given individual then validate it with an independent measure of cortical thickness. We then show, on average, that "brain age" across the group during the teen years has the propensity to look younger in emotional contexts. Further, we show this phenotype (i.e. a younger brain age in emotional contexts) relates to a group mean difference in risk perception - a pattern exemplified greatest in young-adults (ages 18-21). The results are suggestive of a specified functional brain phenotype that relates to being at "risk to be risky.

Development of an acute ovine model of polycystic ovaries to assess the effect of ovarian denervation

Introduction: Polycystic ovary syndrome (PCOS) seems to be associated with increased ovarian sympathetic nerve activity and in rodent models of PCOS reducing the sympathetic drive to the ovary, through denervation or neuromodulation, improves ovulation rate. We hypothesised that sympathetic nerves work with gonadotropins to promote development and survival of small antral follicles to develop a polycystic ovary phenotype.Methods: Using a clinically realistic ovine model we showed a rich sympathetic innervation to the normal ovary and reinnervation after ovarian transplantation. Using needlepoint diathermy to the nerve plexus in the ovarian vascular pedicle we were able to denervate the ovary resulting in reduced intraovarian noradrenaline and tyrosine hydroxylase immunostained sympathetic nerves. We developed an acute polycystic ovary (PCO) model using gonadotrophin releasing hormone (GnRH) agonist followed infusion of follicle stimulating hormone (FSH) with increased pulsatile luteinising hormone (LH). This resulted in increased numbers of smaller antral follicles in the ovary when compared to FSH infusion suggesting a polycystic ovary.Results: Denervation had no effect of the survival or numbers of follicles in the acute PCO model and did not impact on ovulation, follicular and luteal hormone profiles in a normal cycle.Discussion: Although the ovary is richly inervated we did not find evidence for a role of sympathetic nerves in ovarian function or small follicle growth and surviva

Review of factors resulting in systemic biases in the screening, assessment, and treatment of individuals at clinical high-risk for psychosis in the United States

BACKGROUND: Since its inception, research in the clinical high-risk (CHR) phase of psychosis has included identifying and exploring the impact of relevant socio-demographic factors. Employing a narrative review approach and highlighting work from the United States, sociocultural and contextual factors potentially affecting the screening, assessment, and service utilization of youth at CHR were reviewed from the current literature. RESULTS: Existing literature suggests that contextual factors impact the predictive performance of widely used psychosis-risk screening tools and may introduce systemic bias and challenges to differential diagnosis in clinical assessment. Factors reviewed include racialized identity, discrimination, neighborhood context, trauma, immigration status, gender identity, sexual orientation, and age. Furthermore, racialized identity and traumatic experiences appear related to symptom severity and service utilization among this population. CONCLUSIONS: Collectively, a growing body of research from the United States and beyond suggests that considering context in psychosis-risk assessment can provide a more accurate appraisal of the nature of risk for psychosis, render more accurate results improving the field\u27s prediction of conversion to psychosis, and enhance our understanding of psychosis-risk trajectories. More work is needed in the U.S. and across the globe to uncover how structural racism and systemic biases impact screening, assessment, treatment, and clinical and functional outcomes for those at CHR

Let\u27s talk about antibiotics: A randomised trial of two interventions to reduce antibiotic misuse

BACKGROUND: Children with acute respiratory tract infections (ARTIs) receive ≈11.4 million unnecessary antibiotic prescriptions annually. A noted contributor is inadequate parent-clinician communication, however, efforts to reduce overprescribing have only indirectly targeted communication or been impractical. OBJECTIVES: Compare two feasible (higher vs lower intensity) interventions for enhancing parent-clinician communication on the rate of inappropriate antibiotic prescribing. DESIGN: Multisite, parallel group, cluster randomised comparative effectiveness trial. Data collected between March 2017 and March 2019. SETTING: Academic and private practice outpatient clinics. PARTICIPANTS: Clinicians (n=41, 85% of eligible approached) and 1599 parent-child dyads (ages 1-5 years with ARTI symptoms, 71% of eligible approached). INTERVENTIONS: All clinicians received 20 min ARTI diagnosis and treatment education. Higher intensity clinicians received an additional 50 min communication skills training. All parents viewed a 90 second antibiotic education video. MAIN OUTCOMES AND MEASURES: Inappropriate antibiotic treatment was assessed via blinded medical record review by study clinicians and a priori defined as prescriptions for the wrong diagnosis or use of the wrong agent. Secondary outcomes were revisits, adverse drug reactions (both assessed 2 weeks after the visit) and parent ratings of provider communication, shared decision-making and visit satisfaction (assessed at end of the visit on Likert-type scales). RESULTS: Most clinicians completed the study (n=38, 93%), were doctors (n=25, 66%), female (n=30, 78%) and averaged 8 years in practice. All parent-child dyad provided data for the main outcome (n=855 (54%) male, n=1043 (53%) CONCLUSIONS AND RELEVANCE: Rate of inappropriate prescribing was low in both arms. Clinician education coupled with parent education may be sufficient to yield low inappropriate antibiotic prescribing rates. The absence of a significant difference between groups indicates that communication principles previously thought to drive inappropriate prescribing may need to be re-examined or may not have as much of an impact in practices where prescribing has improved in recent years. TRIAL REGISTRATION NUMBER: NCT03037112

Associations of maternal arsenic exposure with adult fasting glucose and insulin resistance in the Strong Heart Study and Strong Heart Family Study

Experimental and prospective epidemiologic evidence suggest that arsenic exposure has diabetogenic effects. However, little is known about how family exposure to arsenic may affect risk for type 2 diabetes (T2D)-related outcomes in adulthood. We evaluated the association of both maternal and offspring arsenic exposure with fasting glucose and incident T2D in 466 participants of the Strong Heart Family Study. Total arsenic (ΣAs) exposure was calculated as the sum of inorganic arsenic (iAs) and methylated (MMA, DMA) arsenic species in maternal and offspring baseline urine. Median maternal ΣAs at baseline (1989-91) was 7.6 µg/g creatinine, while median offspring ΣAs at baseline (2001-03) was 4.5 µg/g creatinine. Median offspring glucose in 2006-2009 was 94 mg/dL, and 79 participants developed T2D. The fully adjusted mean difference (95% CI) for offspring glucose was 4.40 (-3.46, 12.26) mg/dL per IQR increase in maternal ΣAs vs. 2.72 (-4.91 to 10.34) mg/dL per IQR increase in offspring ΣAs. The fully adjusted odds ratio (95%CI) of incident T2D was 1.35 (1.07, 1.69) for an IQR increase in maternal ΣAs and 1.15 (0.92, 1.43) for offspring ΣAs. The association of maternal ΣAs with T2D outcomes were attenuated with adjustment for offspring adiposity markers. Familial exposure to arsenic, as measured in mothers 15-20 years before offspring follow-up, is associated with increased odds of offspring T2D. More research is needed to confirm findings and better understand the importance of family exposure to arsenic in adult-onset diabetes.This study was supported by the National Institute of EnvironmentalHealth Sciences, Unites States (P42ES010349, P30ES009089,R01ES028758, R01ES025216).N.T., P.F.-L., and A.N.-A. contributed to the preparation of researchdata and writing of the manuscript. N.T, M.J.S, A.D.-R., M.T.-P., M.G.-P., and A.N.-A. contributed to the statistical analysis. B.V.H., J.M., K.N.,J.G.U., and S.C. contributed as the primary investigators of the SHS andSHFS, and to the preparation of the research data. K.A.F. and W.G.contributed to the arsenic measurements in the SHS and SHFS partici-pants. A.N.-A. is the guarantor of this work and, as such, had full accessto all the data in the study and takes responsibility for the integrity ofthe data and the accuracy of the data analysis.S

Digging deeper into colonial palaeontological practices in modern day Mexico and Brazil

Scientific practices stemming from colonialism, whereby middle- and low-income countries supply data for high-income countries and the contributions of local expertise are devalued, are still prevalent today in the field of palaeontology. In response to these unjust practices, countries such as Mexico and Brazil adopted protective laws and regulations during the twentieth century to preserve their palaeontological heritage. However, scientific colonialism is still reflected in many publications describing fossil specimens recovered from these countries. Here, we present examples of ‘palaeontological colonialism’ from publications on Jurassic–Cretaceous fossils from NE Mexico and NE Brazil spanning the last three decades. Common issues that we identified in these publications are the absence of both fieldwork and export permit declarations and the lack of local experts among authorships. In Mexico, access to many fossil specimens is restricted on account of these specimens being housed in private collections, whereas a high number of studies on Brazilian fossils are based on specimens illegally reposited in foreign collections, particularly in Germany and Japan. Finally, we outline and discuss the wider academic and social impacts of these research practices, and propose exhaustive recommendations to scientists, journals, museums, research institutions and government and funding agencies in order to overcome these practices

Co-expression of CD39 and CD103 identifies tumor-reactive CD8 T cells in human solid tumors.

Identifying tumor antigen-specific T cells from cancer patients has important implications for immunotherapy diagnostics and therapeutics. Here, we show that CD103+CD39+ tumor-infiltrating CD8 T cells (CD8 TIL) are enriched for tumor-reactive cells both in primary and metastatic tumors. This CD8 TIL subset is found across six different malignancies and displays an exhausted tissue-resident memory phenotype. CD103+CD39+ CD8 TILs have a distinct T-cell receptor (TCR) repertoire, with T-cell clones expanded in the tumor but present at low frequencies in the periphery. CD103+CD39+ CD8 TILs also efficiently kill autologous tumor cells in a MHC-class I-dependent manner. Finally, higher frequencies of CD103+CD39+ CD8 TILs in patients with head and neck cancer are associated with better overall survival. Our data thus describe an approach for detecting tumor-reactive CD8 TILs that will help define mechanisms of existing immunotherapy treatments, and may lead to future adoptive T-cell cancer therapies