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Background: The amygdala is highly implicated in an array of psychiatric disorders but is not accessible using currently available noninvasive neuromodulatory techniques. Low-intensity transcranial focused ultrasound (TFUS) is a neuromodulatory technique that has the capability of reaching subcortical regions noninvasively. Methods: We studied healthy older adult participants (N = 21, ages 48–79 years) who received TFUS targeting the right amygdala and left entorhinal cortex (active control region) using a 2-visit within-participant crossover design. Before and after TFUS, behavioral measures were collected via the State-Trait Anxiety Inventory and an emotional reactivity and regulation task utilizing neutral and negatively valenced images from the International Affective Picture System. Heart rate and self-reported emotional valence and arousal were measured during the emotional reactivity and regulation task to investigate subjective and physiological responses to the task. Results: Significant increases in both self-reported arousal in response to negative images and heart rate during emotional reactivity and regulation task intertrial intervals were observed when TFUS targeted the amygdala; these changes were not evident when the entorhinal cortex was targeted. No significant changes were found for state anxiety, self-reported valence to the negative images, cardiac response to the negative images, or emotion regulation. Conclusions: The results of this study provide preliminary evidence that a single session of TFUS targeting the amygdala may alter psychophysiological and subjective emotional responses, indicating some potential for future neuropsychiatric applications. However, more work on TFUS parameters and targeting optimization is necessary to determine how to elicit changes in a more clinically advantageous way.

The global prevalence of drug resistance has created an urgent need for the discovery of novel anti-infective drugs. The major source of antibiotics in current clinical practice is terrestrial actinobacteria; the less-exploited deep-sea actinobacteria may serve as an unprecedented source of novel natural products. In this study, we evaluated 50 actinobacteria strains derived from diverse deep water sponges and environmental niches for their anti-microbial activities against a panel of pathogens including Candida albicans, Clostridium difficile, Staphylococcus aureus, and methicillin-resistant S. aureus (MRSA), and Pseudomonas aeruginosa. More than half of the tested strains (27) were identified as active in at least one assay. The rare earth salt lanthanum chloride (LaCl3) was shown to be as an effective elicitor. Among the 27 strains, the anti-microbial activity of 15 were induced or enhanced by the addition of LaCl3. This part of study focused on one strain R818, in which potent antifungal activity was induced by the addition of LaCl3. We found that the LaCl3-activated metabolites in R818 are likely antimycin-type compounds. One of them, compound 1, has been purified. Spectroscopic analyses including HR-MS and 1D NMR indicated that this compound is urauchimycin D. The antifungal activity of compound 1 was confirmed with a minimal inhibitory concentration (MIC) of 25 μg/mL; the purified compound also showed a moderate activity against C. difficile. Additional notable strains are: strain N217 which showed both antifungal and antibacterial (including P. aeruginosa) activities and strain M864 which showed potent activity against C. difficile with an MIC value (0.125 μg/mL) lower than those of vancomycin and metronidazole. Our preliminary studies show that deep-sea actinobacteria is a promising source of anti-infective natural products.

Motivation Analysis of open chromatin regions across multiple samples from two or more distinct conditions can determine altered gene regulatory patterns associated with biological phenotypes and complex traits. The ATAC-seq assay allows for tractable genome-wide open chromatin profiling of large numbers of samples. Stable, broadly applicable genomic annotations of open chromatin regions are not available. Thus, most studies first identify open regions using peak calling methods for each sample independently. These are then heuristically combined to obtain a consensus peak set. Reconciling sample-specific peak results post hoc from larger cohorts is particularly challenging, and informative spatial features specific to open chromatin signals are not leveraged effectively. Results We propose a novel method, ROCCO , that determines consensus open chromatin regions across multiple samples simultaneously. ROCCO employs robust summary statistics and solves a constrained optimization problem formulated to account for both enrichment and spatial dependence of open chromatin signal data. We show this formulation admits attractive theoretical and conceptual properties as well as superior empirical performance compared to current methodology. Availability and implementation Source code, documentation, and usage demos for ROCCO are available on GitHub at: https://github.com/nolan-h-hamilton/ROCCO. ROCCO can also be installed as a stand-alone binary utility using pip/PyPI. [ABSTRACT FROM AUTHOR]

This research article is a collaborative set of reflections and provocations stemming from the National Science Foundation (NSF) funded workshop on STS as a Critical Pedagogy, hosted online during the summer of 2021 by Shannon N. Conley and Emily York at James Madison University. The workshop occurred over four separate sessions, bringing together forty participants (including six undergraduate students who contributed as both facilitators and research assistants). Participants self-organized into panels, leading the workshop collective to engage a host of questions, challenges, methods, and practices related to STS and critical pedagogy. Questions included the following. What characterizes critical STS pedagogies? How are critical STS pedagogies enabled and constrained by our institutional and disciplinary locations? What makes STS pedagogies travel? How might we imagine STS pedagogies otherwise? How do our pedagogies shape our research and engagement in the world? How might we critically interrogate the boundaries between research, teaching, service, and engagement, and what becomes visible when we do so?

Abstract We report the photon (PL), electron (CL) and X-ray (XEL) induced luminescence characteristics of high aspect ratio ultra-long (~ 50 µm) ZnO nanorods (NRs) and discuss the potential for fast X-ray detection based on the consistent and efficient visible emission (~ 580 nm) from ZnO NRs. Nanostructured ZnO scintillators were rearranged to form a vertically well-aligned NR design in order to help light absorption and coupling resulting in luminescent and fast scintillation properties. The design of the nanorod array combines the key advantages of a low-cost growth technique together with environmentally friendly and widely available materials. A low temperature hydrothermal method was adopted to grow ZnO NRs in one cycle growth and their structural, optical and X-ray scintillation properties were investigated. The relatively short (~ 10 µm) ZnO NRs emitting in the near-band-edge region were found to be almost insensitive to X-rays. On the other hand, the higher XEL response of long ZnO NRs, which is a key parameter for evaluation of materials to be used as scintillators for high quality X-ray detection and imaging, along with a decay time response in the order of ns confirmed promising scintillation properties for fast and high-resolution X-ray detector applications.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jet.2006.09.005 Byline: Nolan H. Miller (a), John W. Pratt (b), Richard J. Zeckhauser (a), Scott Johnson (c) Abstract: We consider the mechanism design problem when agents' types are multidimensional and continuous, and their valuations are interdependent. If there are at least three agents whose types satisfy a weak correlation condition, then for any decision rule and any E0 there exist balanced transfers that render truthful revelation a Bayesian E-equilibrium. A slightly stronger correlation condition ensures that there exist balanced transfers that induce a Bayesian Nash equilibrium in which agents' strategies are nearly truthful. Author Affiliation: (a) Kennedy School of Government, Harvard University, 79JFK St, Cambridge, MA 02138, USA (b) Harvard Business School, Harvard University, Boston, MA 02163, USA (c) Australian National University, Canberra ACT 0200, Australia Article History: Received 6 December 2004; Revised 11 September 2006

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jebo.2004.12.004 Byline: Alexander F. Wagner (a), Nolan H. Miller (b), Richard J. Zeckhauser (b) Keywords: Budgeting; Screening; Asymmetric information Abstract: How should an organization's center allocate resources to units under its control which are better informed? Even with conscientious productivity reviews, important information will remain asymmetrically held. If units value their own expenditures more than those of their peers, they will seek excess budgets and expenditures. Fortunately, budget authorities can infer productivities from units' expenditure patterns across spending categories and over time. Optimal screening budgets reward more productive units with greater overall budgets. Such screening provides significant welfare gains over traditional fixed or reallocable budgets. Empirical results for a large electricity and infrastructure provider fit an important version of the model. Author Affiliation: (a) Swiss Banking Institute, University of Zurich, Switzerland (b) John F. Kennedy School of Government, Harvard University, 79 JFK St., Cambridge, MA 02138, USA Article History: Received 28 January 2004; Revised 30 November 2004; Accepted 17 December 2004

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jhealeco.2005.12.007 Byline: Nolan H. Miller Keywords: Managed-care backlash; Provider incentives; Moral hazard Abstract: People distrust managed care organizations (MCOs) more than traditional health plans. This phenomenon has become known as 'managed-care backlash.' Using a model of the interaction between insurers, physicians, and patients, this paper identifies two possible motivations for MCO backlash. The first, which comes from traditional health plans' superior ability to credibly commit to providing better than least-cost care, is efficiency promoting. The second, which arises when patients are able to obtain higher-benefit treatments through reneging on their initial insurance contracts through 'doctor shopping,' may reduce efficiency. Author Affiliation: John F. Kennedy School of Government, Harvard University, Cambridge, MA 02138, United States Article History: Received 1 March 2004; Revised 1 June 2005; Accepted 1 December 2005

A method of devising the health benefits in an employer's compensation policy is presented. The method seeks to reduce cost implications.

Strategic trade theory has been criticized on the grounds that its predictions are overly sensitive to modeling assumptions. Applying recent results in duopoly theory, this paper considers three-stage games in which governments choose subsidies, firms' owners choose incentive schemes for their managers, and then the managers compete in the product market. We show that if firms' owners have sufficient control over their managers' behavior, then the optimal strategic trade policy does not depend on the mode of product-market competition, i.e., whether firms compete by setting prices or quantities. Keywords: Strategic international trade; Delegation games JEL classification: F1; L1

Genomics, high-throughput screening and combinatorial chemistry promise dramatic productivity improvements in the drug-discovery process. However, without powerful informatics systems, these promised efficiencies are unlikely to be realized. High-throughput informatics systems have been used to design, register and track combinatorial libraries, and also to facilitate lead identification and the optimization process.

The achievement of efficient budget balance and limited liability remains possible under partnerships with joint monitoring. Budget balance and limited liability efficiency can be attained provided that there are at least three players, wherein one of them can monitor the activity of another player. Strategies used in attaining efficiency are proven effective in solving problems related to mechanism design.

Powassan virus (POWV) is an emerging tick-borne virus that causes severe meningoencephalitis in the United States, Canada, and Russia. Serology is generally the preferred diagnostic modality, but PCR on cerebrospinal fluid, blood, or urine has an important role, particularly in immunocompromised patients who are unable to mount a serologic response. Although the perceived poor sensitivity of PCR in the general population may be due to the biology of infection and health-seeking behavior (with short viremic periods that end before hospital presentation), limitations in assay design may also contribute. Genome sequences from clinical POWV cases are extremely scarce; PCR assay design has been informed by those available, but the numbers are limited. Larger numbers of genome sequences from tick-derived POWV are available, but it is not known if POWV genomes from human infections broadly mirror genomes from tick hosts, or if human infections are caused by a subset of more virulent strains. We obtained viral genomic data from 10 previously unpublished POWV human infections and showed that they broadly mirror the diversity of genome sequences seen in ticks, including all three major clades (lineage I, lineage II Northeast, and lineage II Midwest). These newly published clinical POWV genome sequences include the first confirmed lineage I infection in the United States, highlighting the relevance of all clades in human disease. An in silico analysis of published POWV PCR assays shows that many assays were optimized against a single clade and have mismatches that may affect their sensitivity when applied across clades. This analysis serves as a launching point for improved PCR design for clinical diagnostics and environmental surveillance.

Immune checkpoint inhibitors (ICIs) have revolutionized the field of oncology and transformed the management of many malignancies, especially for patients with metastatic disease. Dermatologic toxicities are among the most common immune-related adverse events (irAEs) of ICIs and can manifest in various ways. We report the case of a 56-year-old male with metastatic colorectal cancer treated with ipilimumab and nivolumab who then developed dermatologic abnormalities confined to the blue-ink regions of his long-standing multicolored tattoos on multiple areas of his body. The patient's reaction resolved after intralesional injection of triamcinolone acetonide. Tattoo reactions associated with ICI treatment are rare, and to our knowledge, there have been no published cases of dermatologic irAEs isolated to blue-pigmented areas of multicolored tattoos. It is of great importance to have awareness of the possibility of this type of reaction and to provide appropriate care for patients undergoing treatment with ICIs.

Background: Aorta and carotid intima-media thickness (IMT) is a measure of subclinical atherosclerosis and useful to assess cardiometabolic risk in the young. The in utero milieu may involve cardiometabolic programing and the development of cardiometabolic risk factors in children. Maternal smoking, alcohol consumption, and micronutrient deficiencies during pregnancy influence the development of the cardiovascular system through a process of DNA methylation.Aim: To explore an association between maternal smoking and alcohol consumption during pregnancy and intima media thickness in 5-year-old children for a low-income setting.Methods: Data were collected from 500 mother-child pairs at antenatal clinic visit, at birth, and at age 5 years. Anthropometric measurements were collected at birth and again at age 5 years. As well as clinical and ultrasound measurements at age 5 years. Clinical measurements, at age 5 years, included blood pressure, mean arterial pressure, and heart rate. Ultrasound measurements of the aorta and carotid arteries IMT were performed at age 5 years. Main outcome of interest was effect of dual teratogen exposure on the ultrasound measures IMT as indication of cardiometabolic risk.Results: cIMT was significantly higher in children exposed to both alcohol and nicotine during pregnancy compared to those not exposed (p = .008). In separate linear models, dual in utero exposure (beta = 0.12; p = .01) and male sex (beta = 0.14; p = .01) were associated with higher right cIMT values (F(6,445) = 5.20; R2 = 0.07, p < .01); male sex (beta = 0.13; p = .01) and low birth weight (beta = 0.07; p = .01) with higher left cIMT value (F(4,491) = 4.49; R2 = 0.04; p = .01); and males sex (beta = 0.11; p = .02) with higher aorta IMT (F(6,459) = 5.63; R2 = 0.07; p < .01). Significant positive correlations between maternal measures of adiposity, maternal MUAC (r = 0.10; p = .03), and maternal BMI (r = 0.12; p < .01) and right cIMT measurements adjusted for the BMI of the child at age 5 years as covariate. Blood pressure measurements at age 5 years were not significantly associated with IMT but, instead, correlated significantly and positively with the BMI of the child at age 5 years (p < .01).Conclusion: Children exposed to both maternal smoking and alcohol consumption during pregnancy presented with cardiometabolic risk factors 5 years after birth. In addition, maternal adiposity, male sex, and low birth weight were associated with higher IMT at age 5 years. [ABSTRACT FROM AUTHOR]

In low-income countries, prospective data on combined effects of in utero teratogen exposure are lacking and necessitates new research. The aim of the present study was to explore the effect of in utero teratogen exposure on the size of the kidneys and pancreas 5 years after birth in a low-income paediatric population. Data was collected from 500 mother–child pairs from a low-income setting. Anthropometric measurements included body weight, (BW) body height, mid-upper arm and waist circumference (WC). Clinical measurements included blood pressure (BP), mean arterial pressure and heart rate. Ultrasound measurements included pancreas, and kidney measurements at age 5 years. The main outcome of interest was the effect of maternal smoking and alcohol consumption on ultrasound measurements of organ size at age 5 years. Left and right kidney length measurements were significantly lower in smoking exposed children compared to controls (p = 0.04 and p = 0.03). Pancreas body measurements were significantly lower in smoking exposed children (p = 0.04). Multiple regression analyses were used to examine the associations between the independent variables (IDVs), maternal age, body mass index (BMI), mid-upper arm circumference (MUAC) and BW of the child, on the dependent variables (DVs) kidney lengths and kidney volumes. Also, the association between in utero exposure to alcohol and nicotine and pancreas size. WC was strongest (r = 0.28; p < 0.01) associated with pancreas head [F (4, 454) = 13.44; R2 = 0.11; p < 0.01] and tail (r = 0.30; p < 0.01) measurements at age 5 years, with in utero exposure, sex of the child and BMI as covariates. Kidney length and pancreas body measurements are affected by in utero exposure to nicotine at age 5 years and might contribute to cardiometabolic risk in later life. Also, findings from this study report on ultrasound reference values for kidney and pancreas measurements of children at age 5 years from a low-income setting. [ABSTRACT FROM AUTHOR]

We estimate how the mortality effects of temperature vary across U.S. climate regions to assess local and national damages from projected climate change. Using 22 years of Medicare data, we find that both cold and hot days increase mortality. However, hot days are less deadly in warm places while cold days are less deadly in cool places. Incorporating this heterogeneity into end-of-century climate change assessments reverses the conventional wisdom on climate damage incidence: cold places bear more, not less, of the mortality burden. Allowing places to adapt to their future climate substantially reduces the estimated mortality effects of climate change. [ABSTRACT FROM AUTHOR]

Investigating Protostellar Accretion (IPA) is a JWST Cycle 1 GO program that uses NIRSpec integral field units and MIRI Medium Resolution Spectrograph to obtain 2.9–28 μ m spectral cubes of young, deeply embedded protostars with luminosities of 0.2–10,000 L _⊙ and central masses of 0.15–12 M _⊙ . In this Letter, we report the discovery of a highly collimated atomic jet from the Class 0 protostar IRAS 16253−2429, the lowest-luminosity source ( L _bol = 0.2 L _⊙ ) in the IPA program. The collimated jet is detected in multiple [Fe ii ] lines and [Ne ii ], [Ni ii ], and H i lines but not in molecular emission. The atomic jet has a velocity of about 169 ± 15 km s ^−1 , after correcting for inclination. The width of the jet increases with distance from the central protostar from 23 to 60 au, corresponding to an opening angle of 2.°6 ± 0.°5. By comparing the measured flux ratios of various fine-structure lines to those predicted by simple shock models, we derive a shock speed of 54 km s ^−1 and a preshock density of 2.0 × 10 ^3 cm ^−3 at the base of the jet. From these quantities and using a suite of jet models and extinction laws, we compute a mass-loss rate between 0.4 and 1.1 ×10 ^−10 M _⊙ yr ^−1 . The low mass-loss rate is consistent with simultaneous measurements of low mass accretion rate (2.4 ± 0.8 × 10 ^−9 M _⊙ yr ^−1 ) for IRAS 16253−2429 from JWST observations, indicating that the protostar is in a quiescent accretion phase. Our results demonstrate that very low-mass protostars can drive highly collimated, atomic jets, even during the quiescent phase.