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We evaluated antibiotic-prescribing across 111 mental health units in the Veterans’ Health Administration. We found that accurate diagnosis of urinary tract infections is a major area for improvement. Because non–mental-health clinicians were involved in most antibiotic-prescribing decisions, stewardship interventions for mental health patients should have a broad target audience to be effective.
Differential susceptibility theory stipulates that individuals vary in their susceptibility to environmental effects, often implying that the same individuals differ in the same way in their susceptibility to different environmental exposures. The latter point is addressed herein by evaluating the extent to which early-life harshness and unpredictability affect mother's psychological well-being and parenting, as well as their adolescent's life-history strategy, as reflected in number of sexual partners by age 15 years, drawing on data from the National Institute of Child Health and Human Development (NICHD) Study of Early Child Care and Youth Development. Results indicated that mothers whose well-being and parenting proved more susceptible to harshness also proved somewhat more susceptible to environmental unpredictability, with the same being true of adolescent sexual behavior. Nevertheless, findings caution against overgeneralizing sample-level findings to all individuals.
Authoritarian leaders around the world often fight against corruption in an effort to win public support. Conventional wisdom holds that this strategy works because leaders can signal their benevolent intentions by removing corrupt officials. We argue that fighting against corruption can undermine regime support. By revealing scandals of corrupt officials, corruption investigations can alter citizens' beliefs about public officials and lead to disenchantment about political institutions. We test this argument by examining how China's current anti-corruption campaign has changed citizens' public support for the government and the Communist Party. We analyze the results of two original surveys conducted before and during the campaign, and employ a difference-in-differences strategy to show that corruption investigations, at the margin, suppress respondents' support for the central government and party. We also examine our respondents' prior and posterior beliefs, and the results support our updating mechanism.
Transcranial direct current stimulation (tDCS) could be a side-effect-free alternative to psychostimulants in attention-deficit/hyperactivity disorder (ADHD). Although there is limited evidence for clinical and cognitive effects, most studies were small, single-session and stimulated left dorsolateral prefrontal cortex (dlPFC). No sham-controlled study has stimulated the right inferior frontal cortex (rIFC), which is the most consistently under-functioning region in ADHD, with multiple anodal-tDCS sessions combined with cognitive training (CT) to enhance effects. Thus, we investigated the clinical and cognitive effects of multi-session anodal-tDCS over rIFC combined with CT in double-blind, randomised, sham-controlled trial (RCT, ISRCTN48265228).
Fifty boys with ADHD (10–18 years) received 15 weekday sessions of anodal- or sham-tDCS over rIFC combined with CT (20 min, 1 mA). ANCOVA, adjusting for baseline measures, age and medication status, tested group differences in clinical and ADHD-relevant executive functions at posttreatment and after 6 months.
ADHD-Rating Scale, Conners ADHD Index and adverse effects were significantly lower at post-treatment after sham relative to anodal tDCS. No other effects were significant.
This rigorous and largest RCT of tDCS in adolescent boys with ADHD found no evidence of improved ADHD symptoms or cognitive performance following multi-session anodal tDCS over rIFC combined with CT. These findings extend limited meta-analytic evidence of cognitive and clinical effects in ADHD after 1–5 tDCS sessions over mainly left dlPFC. Given that tDCS is commercially and clinically available, the findings are important as they suggest that rIFC stimulation may not be indicated as a neurotherapy for cognitive or clinical remediation for ADHD.
On-site surveys of weed populations provide information on the relative occurrence and density of weeds that can be useful to growers in that region. Data generated by weed surveys can aid in the management of weed issues by monitoring the movement of problem weeds and forecasting areas susceptible to infestations. Currently, on-site surveys are often performed on a small scale, within single fields or counties. Questionnaire surveys are helpful for assessing relative abundance but do not always provide detailed information on weed distribution in time or space. A survey was conducted annually in Ohio from 2013 through 2017 in 49 counties with soybean [Glycine max (L.) Merr.] production to assess the late-season occurrence of horseweed [Conyza canadensis (L.) Cronquist]. The objectives of this research were to: (1) determine the frequency, level of infestation, and distribution of C. canadensis in soybean fields in the primary soybean-producing Ohio counties over 5 yr; and (2) identify significant spatial clusters or movement trends over time. Conyza canadensis was encountered in each county from 2013 through 2017. Spatial cores of interest, or counties identified as having significant levels of C. canadensis infestations or a lack thereof relative to surrounding counties, were identified in all years except 2017. The lowest frequency of C. canadensis encountered at all rating levels occurred in 2017, which coincided with second-highest frequency of infestations (highest density level) among years. There was no distinct distribution or pattern of C. canadensis movement within the state from year to year, but there was an increase in counties with infestations over time compared with the early years of the survey when many counties had few to no infestations. These results suggest that C. canadensis persists as a common and troublesome threat to Ohio soybean producers and that growers should continue making C. canadensis management a priority when developing weed control programs.
There are minimal data directly comparing plasma neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) in aging and neurodegenerative disease research. We evaluated associations of plasma NfL and plasma GFAP with brain volume and cognition in two independent cohorts of older adults diagnosed as clinically normal (CN), mild cognitive impairment (MCI), or Alzheimer’s dementia.
We studied 121 total participants (Cohort 1: n = 50, age 71.6 ± 6.9 years, 78% CN, 22% MCI; Cohort 2: n = 71, age 72.2 ± 9.2 years, 45% CN, 25% MCI, 30% dementia). Gray and white matter volumes were obtained for total brain and broad subregions of interest (ROIs). Neuropsychological testing evaluated memory, executive functioning, language, and visuospatial abilities. Plasma samples were analyzed in duplicate for NfL and GFAP using single molecule array assays (Quanterix Simoa). Linear regression models with structural MRI and cognitive outcomes included plasma NfL and GFAP simultaneously along with relevant covariates.
Higher plasma GFAP was associated with lower white matter volume in both cohorts for temporal (Cohort 1: β = −0.33, p = .002; Cohort 2: β = −0.36, p = .03) and parietal ROIs (Cohort 1: β = −0.31, p = .01; Cohort 2: β = −0.35, p = .04). No consistent findings emerged for gray matter volumes. Higher plasma GFAP was associated with lower executive function scores (Cohort 1: β = −0.38, p = .01; Cohort 2: β = −0.36, p = .007). Plasma NfL was not associated with gray or white matter volumes, or cognition after adjusting for plasma GFAP.
Plasma GFAP may be more sensitive to white matter and cognitive changes than plasma NfL. Biomarkers reflecting astroglial pathophysiology may capture complex dynamics of aging and neurodegenerative disease.
Pareiasaurs were globally distributed, abundant, herbivorous parareptiles with the basal-most members found only in the mid-Permian of South Africa. These basal forms form a monophyletic group and were locally abundant and became extinct at the top of the Tapinocephalus Assemblage Zone at the end of the Guadalupian. Four species of basal pareiasaurs are currently recognised: Bradysaurus baini, B. seeleyi, Embrithosaurus schwarzi and Nochelesaurus alexanderi, but they are all poorly understood and there remains historic uncertainty as to their validity. In this paper, our second contribution designed to improve understanding of the basal group, we present the first detailed cranial description and updated diagnosis for Nochelesaurus alexanderi and demonstrate that it is a distinct taxon based on one cranial autapomorphy, a large transversely wide postparietal, and a combination of cranial characters. Within the local group of mid-Permian pareiasaurs, we recognise new dental features of Nochelesaurus alexanderi: non-symmetrical marginal cusp arrangements on upper and lower teeth resulting from an extra basal mesial cusp; an incipient horizontal cingulum on lower jaw teeth, sometimes with one or two tiny medial cingular cusps; and up to ten marginal cusps. Our study demonstrates that tooth morphology and orientation, cranial ornamentation, morphology of the cheek bosses, shape of the postfrontal and postparietal, and morphology of the distal paroccipital process of the opisthotic are the most useful to identify South African mid-Permian pareiasaurs.
ABSTRACT IMPACT: The first-line chemotherapies used to treat leishmaniasis are highly toxic intravenous antimonials yet drug resistance has begun to develop, causing the use of oral treatment options with high price tags; there is a strong need for new, safe, and effective chemotherapeutic agents to treat leishmaniasis. OBJECTIVES/GOALS: This study was conducted in order to identify novel chemical compounds that exhibit anti-leishmanial activity and to further characterize their efficacy and toxicity in in vitro and in vivo systems in the hopes of future chemotherapeutic developments. METHODS/STUDY POPULATION: A total of 28 unique 1,4-diaryl-pyrazolo-pyridinone (1,4-DAPP) compounds were synthesized and anti-leishmanial efficacy and host cell toxicity were determined using L. donovani mCherry-expressing amastigotes and THP-1 macrophages. Additional pharmacokinetic analyses of a potent 1,4-DAPP compound were conducted, revealing a potential metabolite structure. A select group of the novel compounds were screened in a cutaneous leishmaniasis (CL) murine model using L. major mCherry-expressing parasites and female Balb/C mice. The treatment consisted of 10 intralesional injections of compound over a period of 4 weeks, while lesion growth was monitored via fluorescence and manual measurements. RESULTS/ANTICIPATED RESULTS: Four experimental compounds had IC50 values less than 5 micromolar, providing similar anti-leishmanial activity to Miltefosine. Compound 9279817 had a clearance almost twice the rate of normal hepatic blood flow and had a relatively high volumes of distribution, indicating this compound is rapidly cleared and distributes into tissues. In vitro rat liver microsome assays suggest a rapid metabolism of 9279817 and MS/MS results suggest this metabolite is most likely formed via oxidation of the sulfur on the lower aryl ring. This sulfoxide metabolite has similar efficacy as the parent compound and does not exhibit toxicity in vitro. Three of the experimental compounds behaved similarly to the antimony positive control in the murine CL model. DISCUSSION/SIGNIFICANCE OF FINDINGS: This study revealed a novel structural class of compounds that have anti-leishmanial activity. Experiments show compounds with similar efficacy to Miltefosine while having significantly less cytotoxicity, suggesting that the 1,4-DAPP structural class could be further developed as a potential chemotherapeutic.
The new genus Sinuicella, an early successional lichen, was found on bare soil in Oregon, USA. The thallus is minute fruticose, grey to nearly black, branching isotomic dichotomous, branches round, 20–90 μm wide in water mount. The cortex is composed of interlocking cells shaped like jigsaw puzzle pieces. Spores are hyaline, 1-septate, 25–40(–50) × 6.5–9(–11) μm. Maximum likelihood phylogenetic analyses on multilocus data sets, first spanning the entire order Peltigerales and then restricted to Peltigeraceae with extended sampling from Solorina and Peltigera, revealed the placement of Sinuicella outside of currently recognized genera, sister to Peltigera, with high support. Based on the phylogenetic, morphological and ecological distinctness of Sinuicella, we formally introduce a new genus represented by the single species S. denisonii. The cyanobiont of S. denisonii is Nostoc from phylogroup XL, Clade 2, Subclade 3 based on the rbcLX marker.
AU in days of therapy per 1,000 patient days and microbiologic data from 2015 and 2016 were collected from 26 hospitals. The prevalences of Pseudomonas aeruginosa, extended-spectrum β-lactamase (ESBL)–producing bacteria, methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE) were calculated and compared to the average prevalence of all hospitals in the network. This proportion was used to calculate the adjusted AU (a-AU) for various categories of antimicrobials. For example, a-AU of antipseudomonal β-lactams (APBL) was the AU of APBL divided by (prevalence of P. aeruginosa at that hospital divided by the average prevalence of P. aeruginosa). Hospitals were categorized by bed size and ranked by AU and a-AU, and the rankings were compared.
Most hospitals in 2015 and 2016, respectively, moved ≥2 positions in the ranking using a-AU of APBL (15 of 24, 63%; 22 of 26, 85%), carbapenems (14 of 23, 61%; 22 of 25; 88%), anti-MRSA agents (13 of 23, 57%; 18 of 26, 69%), and anti-VRE agents (18 of 24, 75%; 15 of 26, 58%). Use of a-AU resulted in a shift in quartile of hospital ranking for 50% of APBL agents, 57% of carbapenems, 35% of anti-MRSA agents, and 75% of anti-VRE agents in 2015 and 50% of APBL agents, 28% of carbapenems, 50% of anti-MRSA agents, and 58% of anti-VRE agents in 2016.
The a-AU considerably changes how hospitals compare among each other within a network. Adjusting AU by microbiological burden allows for a more balanced comparison among hospitals with variable baseline rates of resistant bacteria.
Due to shortages of N95 respirators during the coronavirus disease 2019 (COVID-19) pandemic, it is necessary to estimate the number of N95s required for healthcare workers (HCWs) to inform manufacturing targets and resource allocation.
We developed a model to determine the number of N95 respirators needed for HCWs both in a single acute-care hospital and the United States.
For an acute-care hospital with 400 all-cause monthly admissions, the number of N95 respirators needed to manage COVID-19 patients admitted during a month ranges from 113 (95% interpercentile range [IPR], 50–229) if 0.5% of admissions are COVID-19 patients to 22,101 (95% IPR, 5,904–25,881) if 100% of admissions are COVID-19 patients (assuming single use per respirator, and 10 encounters between HCWs and each COVID-19 patient per day). The number of N95s needed decreases to a range of 22 (95% IPR, 10–43) to 4,445 (95% IPR, 1,975–8,684) if each N95 is used for 5 patient encounters. Varying monthly all-cause admissions to 2,000 requires 6,645–13,404 respirators with a 60% COVID-19 admission prevalence, 10 HCW–patient encounters, and reusing N95s 5–10 times. Nationally, the number of N95 respirators needed over the course of the pandemic ranges from 86 million (95% IPR, 37.1–200.6 million) to 1.6 billion (95% IPR, 0.7–3.6 billion) as 5%–90% of the population is exposed (single-use). This number ranges from 17.4 million (95% IPR, 7.3–41 million) to 312.3 million (95% IPR, 131.5–737.3 million) using each respirator for 5 encounters.
We quantified the number of N95 respirators needed for a given acute-care hospital and nationally during the COVID-19 pandemic under varying conditions.
After the failures of 1858 and 1865, the Atlantic was finally spanned by a submarine cable in 1866. A boom in cable laying ensued as British firms built a global cable network would remain a bulwark of British imperial and commercial power well into the twentieth century. The surging cable industry created a demand for electrical knowledge that stimulated the emergence of physics teaching laboratories in Britain. These laboratories turned out scientists, engineers, and teachers trained in precision electrical measurement—essentially cable testing room techniques. The cable enterprise also set the direction of British electrical research in the late nineteenth century, including the reception and articulation of Maxwell’s field theory. In the early 1880s a circle of young “Maxwellians” emerged in Britain, among them Oliver Heaviside, a former cable engineer who had taken up Maxwell’s theory as a tool to address signalling problems. Guided by ideas about energy flow and signal propagation, in 1884 Heaviside recast the long list of equations Maxwell had given in his Treatise into the compact set now universally known as “Maxwell’s equations.” The form of Maxwell’s field theory that passed into textbooks in the 1890s was rooted in important ways in the global cable network.
"When the first underground and submarine telegraph cables were laid around 1850, engineers noticed that sharp signals sent in at one end emerged at the other badly blurred and appreciably delayed. This “retardation” grew worse on longer cables and threatened to make operation of the proposed 2000-mile Atlantic line unprofitably slow. Retardation presented British physicists and engineers with both an intriguing physical phenomenon and a serious practical problem, and they studied it closely from the 1850s on.
Latimer Clark, a prominent British cable engineer, brought retardation to Michael Faraday’s attention late in 1853, and Faraday’s published account of the phenomenon served to publicize both retardation and the ideas about the electromagnetic field that he invoked to explain it. Faraday’s paper led William Thomson (later Lord Kelvin) to reprint two papers on field theory he had written in the 1840s, and later in 1854 a related cable question prompted Thomson to work out what became the accepted mathematical theory of signal transmission. Moreover, it was at just this time, and largely under Thomson’s guidance, that James Clerk Maxwell first took up the study of electricity, with results that were to transform electromagnetic theory."
James Clerk Maxwell’s field theory of electromagnetism had important and previously unrecognized roots in the cable industry of the mid-nineteenth century. When he took up electrical physics in 1854, the subject was permeated by a concern with cable problems. Guided by William Thomson, Maxwell soon adopted Faraday’s field approach, which in 1861 he sought to embody in a mechanical model of the electromagnetic ether. Seeking evidence to bolster the electromagnetic theory of light to which this model had led him, Maxwell joined the British Association Committee on Electrical Standards, which had been formed in 1861 largely to meet the needs of the submarine telegraph industry. Maxwell’s work on the committee between 1862 and 1864 brought home to him the value of framing his theory in terms of quantities he could measure in the laboratory—particularly the “ratio of units”—rather than relying on a hypothetical mechanism. Maxwell’s shift from his mechanical ether model of 1861 to his seemingly abstract “Dynamical Theory of the Electromagnetic Field” of 1864 thus reflected the often overlooked role concerns rooted in cable telegraphy played in the evolution of his thinking.