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Reports of single center experience and studies of larger databases have identified several predictors of burn center mortality, including age, burn size, and inhalation injury. None of these analyses has been broad enough to allow benchmarking across burn centers. The purpose of this study was to derive a reliable, risk-adjusted, statistical model of mortality based on real-life experience at many burn centers in the U.S. We used the American Burn Association 2020 Full Burn Research Dataset, from the Burn Center Quality Platform (BCQP) to identify 130,729 subjects from July 2015 through June 2020 across 103 unique burn centers. We selected 22 predictor variables, from over 50 recorded in the dataset, based on completeness (at least 75% complete required) and clinical significance. We used gradient-boosted regression, a form of machine learning, to predict mortality and compared this to traditional logistic regression. Model performance was evaluated with AUC and PR curves. The CatBoost model achieved a test AUC of 0.980 with an average precision of 0.800. The logistic regression produced an AUC of 0.951 with an average precision of 0.664. While AUC, the measure most reported in the literature, is high for both models, the CatBoost model is markedly more sensitive, leading to a substantial improvement in precision. Using BCQP data, we can predict burn mortality allowing comparison across burn centers participating in BCQP. [ABSTRACT FROM AUTHOR]

Length of stay (LOS) is a frequently reported outcome after a burn injury. LOS benchmarking will benefit individual burn centers as a way to measure their performance and set expectations for patients. We sought to create a nationwide, risk-adjusted model to allow for LOS benchmarking based on the data from a national burn registry. Using data from the American Burn Association's Burn Care Quality Platform, we queried admissions from 7/2015 to 6/2020 and identified 130,729 records reported by 103 centers. Using 22 predictor variables, comparisons of unpenalized linear regression and Gradient boosted (CatBoost) regressor models were performed by measuring the R 2 and concordance correlation coefficient on the application of the model to the test dataset. The CatBoost model applied to the bootstrapped versions of the entire dataset was used to calculate O/E ratios for individual burn centers. Analyses were run on 3 cohorts: all patients, 10–20% TBSA, >20% TBSA. The CatBoost model outperformed the linear regression model with a test R 2 of 0.67 and CCC of 0.81 compared with the linear model with R 2=0.50, CCC=0.68. The CatBoost was also less biased for higher and lower LOS durations. Gradient-boosted regression models provided greater model performance than traditional regression analysis. Using national burn data, we can predict LOS across contributing burn centers while accounting for patient and center characteristics, producing more meaningful O/E ratios. These models provide a risk-adjusted LOS benchmarking using a robust data source, the first of its kind, for burn centers. [ABSTRACT FROM AUTHOR]

Like all fields of medicine, Infectious Diseases is rife with dogma that underpins much clinical practice. In this study, we discuss 2 specific examples of historical practice that have been overturned recently by numerous prospective studies: traditional durations of antimicrobial therapy and the necessity of intravenous (IV)-only therapy for specific infectious syndromes. These dogmas are based on uncontrolled case series from >50 years ago, amplified by the opinions of eminent experts. In contrast, more than 120 modern, randomized controlled trials have established that shorter durations of therapy are equally effective for many infections. Furthermore, 21 concordant randomized controlled trials have demonstrated that oral antibiotic therapy is at least as effective as IV-only therapy for osteomyelitis, bacteremia, and endocarditis. Nevertheless, practitioners in many clinical settings remain refractory to adopting these changes. It is time for Infectious Diseases to move beyond its history of eminent opinion-based medicine and truly into the era of evidenced-based medicine. [ABSTRACT FROM AUTHOR]

Taxonomic distinction of species forms the foundation of biodiversity assessments and conservation priorities. However, traditional morphological and/or genetics-based taxonomic assessments frequently miss the opportunity of elaborating on the ecological and functional context of species diversification. Here, we used 3D geometric morphometrics of the cranium to improve taxonomic differentiation and add ecomorphological characterization of a young cryptic divergence within the carnivorous marsupial genus Antechinus. Specifically, we used 168 museum specimens to characterize the recently proposed clades A. stuartii 'south', A. stuartii 'north' and A. subtropicus. Beyond slight differences attributable to overall size (and, therefore, not necessarily diagnostic), we also found clear allometry-independent shape variation. This allowed us to define new, easily measured diagnostic traits in the palate, which differentiate the three clades. Contrary to previous suggestions, we found no support for a latitudinal gradient as causing the differentiation between the clades. However, skull shape co-varied with temperature and precipitation seasonality, suggesting that the clades may be adapted to environmental variables that are likely to be impacted by climate change. Our study demonstrates the use of 3D geometric morphometrics to improve taxonomic diagnosis of cryptic mammalian species, while providing perspectives on the adaptive origins and potential future threats of mammalian diversity. [ABSTRACT FROM AUTHOR]

Background Respiratory syncytial virus (RSV) causes acute respiratory illness (ARI) and triggers exacerbations of cardiopulmonary disease. Estimates of incidence in hospitalized adults range widely, with few data on incidence in adults with comorbidities that increase the risk of severity. We conducted a prospective, population-based, surveillance study to estimate incidence of RSV hospitalization among adults overall and those with specific comorbidities. Methods Hospitalized adults aged ≥18 years residing in the surveillance area with ≥2 ARI symptoms or exacerbation of underlying cardiopulmonary disease were screened during the 2017–2018, 2018–2019, and 2019–2020 RSV seasons in 3 hospitals in Rochester, New York and New York City. Respiratory specimens were tested for RSV using polymerase chain reaction assays. RSV incidence per 100 000 was adjusted by market share. Results Active and passive surveillance identified 1099 adults hospitalized with RSV. Annual incidence during 3 seasons ranged from 44.2 to 58.9/100 000. Age-group–specific incidence ranged from 7.7 to 11.9/100 000, 33.5 to 57.5/100 000, and 136.9 to 255.6/100 000 in patients ages 18–49, 50–64, and ≥65 years, respectively. Incidence rates in patients with chronic obstructive pulmonary disease, coronary artery disease, and congestive heart failure were 3–13, 4–7, and 4–33 times, respectively, the incidence in patients without these conditions. Conclusions We found a high burden of RSV hospitalization in this large prospective study. Notable was the high incidence among older patients and those with cardiac conditions. These data confirm the need for effective vaccines to prevent RSV infection in older and vulnerable adults. [ABSTRACT FROM AUTHOR]

Background Glioblastoma multiforme (GBM) is the most aggressive form of glioma. There is growing recognition that mitochondrial metabolism plays a role in cancer development. Metabolic syndrome is a risk factor for several cancers; however, the prevalence in GBM patients in New Zealand (NZ) is unknown. We hypothesized that patients with GBM would show a higher prevalence of metabolic syndrome compared to the general NZ population and that metabolic syndrome may be associated with worsened overall survival (OS) in GBM. Methods We performed a retrospective analysis in 170 patients diagnosed and treated for GBM between 2005 and 2020. Clinical and biochemical data were collected with regard to 5 metabolic criteria. OS was determined from the date of initial surgical diagnosis to the date of death or date of data acquisition. Results Of 170 patients, 31 (18.2%) met the diagnostic criteria for metabolic syndrome. The prevalence of metabolic syndrome in our cohort did not significantly differ from that of the general NZ population. However, OS in patients with metabolic syndrome was significantly worse compared to patients without metabolic syndrome (8.0 vs 13.0 months, P =.016). Patients who received a lower dexamethasone dose had significantly better survival outcomes (15.0 vs 5.0 months, P <.01). Differences in OS did not differ by gender or ethnicity. Conclusions We have shown that metabolic syndrome is associated with reduced OS in a NZ cohort of GBM patients. This finding further strengthens the possibility that a metabolic pathogenesis may underpin GBM. However, prospective clinical trials are needed. [ABSTRACT FROM AUTHOR]

Background We sought to determine the comparative efficacy of fosfomycin vs ertapenem for outpatient treatment of complicated urinary tract infections (cUTIs). Methods We conducted a multicenter, retrospective cohort study involving patients with cUTI treated with outpatient oral fosfomycin vs intravenous ertapenem at 3 public hospitals in Los Angeles County between January 2018 and September 2020. The primary outcome was resolution of clinical symptoms 30 days after diagnosis. Results We identified 322 patients with cUTI treated with fosfomycin (n = 110) or ertapenem (n = 212) meeting study criteria. The study arms had similar demographics, although patients treated with ertapenem more frequently had pyelonephritis or bacteremia while fosfomycin-treated patients had more retained catheters, nephrolithiasis, or urinary obstruction. Most infections were due to extended-spectrum β-lactamase–producing E. coli and Klebsiella pneumoniae , 80%–90% of which were resistant to other oral options. Adjusted odds ratios for clinical success at 30 days, clinical success at last follow-up, and relapse were 1.21 (95% CI, 0.68–2.16), 0.84 (95% CI, 0.46–1.52), and 0.94 (95% CI, 0.52–1.70) for fosfomycin vs ertapenem, respectively. Patients treated with fosfomycin had significant reductions in length of hospital stay and length of antimicrobial therapy and fewer adverse events (1 vs 10). Fosfomycin outcomes were similar irrespective of duration of lead-in intravenous (IV) therapy or fosfomycin dosing interval (daily, every other day, every third day). Conclusions These results would support the conduct of a randomized controlled trial to verify efficacy. In the meantime, they suggest that fosfomycin may be a reasonable stepdown from IV antibiotics for cUTI. [ABSTRACT FROM AUTHOR]

See, Phra bat somdet phra chao yuu hua lae somdet phra nang chao phra borom rachini nat set phrapat saharat amerika [HRH the King and HRH the Queen visit the United States of America], United States: IBM World Tech Corporation, 1960 Re-ordering the Cold War Cosmos: King Bhumibol's 1960 U.S. Tour: 265 Downloaded from https://academic.oup.com/dh/article/45/2/253/6056671 by 81695661, OUP on 19 March 2021 regional location. Matthew phillips Re-ordering the Cold War Cosmos: King Bhumibol's 1960 U.S. Tour From the early Cold War, U.S. aid poured into Thailand. Here I am referring specifically to the official account of the tour, Phra bat somdet phra chao yuu hua lae somdet phra nang chao phra borom rachini nat set phrapat saharat amerika [HM the King and HRH the Queen visit the United States of America], United States: IBM World Tech Corporation, 1960. [Extracted from the article]

Acinetobacter baumannii has among the highest rates of antibiotic resistance encountered in hospitals. New therapies are critically needed. We found that rifabutin has previously unrecognized hyperactivity against most strains of A. baumannii. Here we review the pharmacology and adverse effects of rifabutin to inform potential oral dosing strategies in patients with A. baumannii infections. Rifabutin demonstrates dose-dependent increases in blood levels up to 900 mg per day, but plateaus thereafter. Furthermore, rifabutin induces its own metabolism after prolonged dosing, lowering its blood levels. Pending future development of an intravenous formulation, a rifabutin oral dose of 900–1200 mg per day for 1 week is a rational choice for adjunctive therapy of A. baumannii infections. This dosage maximizes AUC24 to drive efficacy while simultaneously minimizing toxicity. Randomized controlled trials will be needed to definitively establish the safety and efficacy of rifabutin to treat A. baumannii infections. [ABSTRACT FROM AUTHOR]

Despite recent declines in the incidence of acute otitis media (AOM), more than 5 million cases and 5–6 million primary AOM visits still occur in young children in the United States, resulting in $4.4 billion direct medical costs annually. Our aims in this review are to describe the role of respiratory syncytial virus (RSV) in the etiology of AOM, discuss the prospect of prevention of RSV-associated AOM through immunization, and suggest future research strategies to assess the impact of immunization on RSV-associated AOM. [ABSTRACT FROM AUTHOR]

Since 2012 the number of recognized taxa in the Australian carnivorous marsupial genus Antechinus has increased from 10 to 15 species. The systematic relationships among these species and others in the genus are not well resolved. We undertook the first comprehensive, molecular systematic analysis of the genus, incorporating all known species and subspecies of Antechinus. Two mitochondrial (mtDNA) and four autosomal nuclear genes were sequenced. Four clades of Antechinus were consistently reconstructed in the concatenated and mtDNA analyses: (1) dusky antechinuses (A. arktos, A. swainsonii, A. vandycki and A. mimetes) and A. minimus ; (2) A. godmani ; (3) A. agilis, A. stuartii and A. subtropicus; (4) A. argentus, A. mysticus, A. adustus, A. flavipes, A. leo and A. bellus. The inclusion of A. adustus in clade 4 is surprising, because previous morphology-based studies suggested it was a member of clade 3. However, analysis of the nuclear dataset and multi-species coalescence analysis did not separate clades 3 and 4. Within clade 3, A. stuartii is not monophyletic and may be more appropriately classified as two species. Timing of cladogenesis is estimated for all 15 species of Antechinus, permitting us to posit an evolutionary scenario for the group. BEAST analysis dated the divergence of Antechinus from extant congeners to the Late Miocene and cladogenesis among all extant Antechinus to the Plio-Pleistocene. Wet, closed habitat was reconstructed as the most probable ancestral state for the genus Antechinus and the four main Antechinus clades. Overall, increasing aridity from the Miocene to the Pleistocene and a number of well-known biogeographic barriers to mesic species, appear to have driven speciation in Antechinus. [ABSTRACT FROM AUTHOR]

Combined "total evidence" analysis of molecular and morphological data offers the opportunity to objectively merge fossils into the tree of life, and challenges the primacy of solely DNA based phylogenetic and dating inference, even among modern taxa. To investigate the relative utility of DNA, morphology, and total evidence for evolutionary inference, we sequenced the first near-complete mitochondrial genomes from extinct Australian megafauna: a 40–50 thousand year old giant short-faced kangaroo (Simosthenurus occidentalis) and giant wallaby (Protemnodon anak). We analyzed the ancient DNA and fossil data alongside comparable data from extant species to infer phylogeny, divergence times, and ancestral body mass among macropods (kangaroos and wallabies). Our results confirm a close relationship between Protemnodon and the iconic kangaroo genus complex " Macropus", and unite the giant Simothenurus with the hare-sized Lagostrophus fasciatus (banded hare-wallaby), suggesting that the latter is the closest living link to the once diverse sthenurine kangaroo radiation. We find that large body size evolved multiple times among kangaroos, coincident with expansion of open woodland habitats beginning in the Late Miocene. In addition, our results suggest that morphological data mislead macropod phylogeny reconstruction and in turn can distort total evidence estimation of divergence dates. However, a novel result with potentially broad application is that the accuracy and precision of reconstructing ancestral body mass was improved by tracing body mass on morphological branch lengths. This is likely due to positive allometric correlation between morphological and body size variation—a relationship that may be masked or even misleadingly inverted with the temporal or molecular branch lengths that typically underpin ancestral body size reconstruction. Our study supports complementary roles for DNA and morphology in evolutionary inference, and opens a new window into the evolution of Australia's unique marsupial fauna. [ABSTRACT FROM AUTHOR]

The globin gene superfamily has been well-characterized in vertebrates, however, there has been limited research in early-diverging lineages, such as phylum Cnidaria. This study aimed to identify globin genes in multiple cnidarian lineages, and use bioinformatic approaches to characterize the evolution, structure, and expression of these genes. Phylogenetic analyses and in silico protein predictions showed that all cnidarians have undergone an expansion of globin genes, which likely have a hexacoordinate protein structure. Our protein modeling has also revealed the possibility of a single pentacoordinate globin lineage in anthozoan species. Some cnidarian globin genes displayed tissue and development specific expression with very few orthologous genes similarly expressed across species. Our phylogenetic analyses also revealed that eumetazoan globin genes form a polyphyletic relationship with vertebrate globin genes. Overall, our analyses suggest that a Ngb-like and GbX-like gene were most likely present in the globin gene repertoire for the last common ancestor of eumetazoans. The identification of a large-scale expansion and subfunctionalization of globin genes in actiniarians provides an excellent starting point to further our understanding of the evolution and function of the globin gene superfamily in early-diverging lineages. [ABSTRACT FROM AUTHOR]

The iconic Australasian kangaroos and wallabies represent a successful marsupial radiation. However, the evolutionary relationship within the two genera, Macropus and Wallabia, is controversial: mitochondrial and nuclear genes, and morphological data have produced conflicting scenarios regarding the phylogenetic relationships, which in turn impact the classification and taxonomy. We sequenced and analyzed the genomes of 11 kangaroos to investigate the evolutionary cause of the observed phylogenetic conflict. A multilocus coalescent analysis using ~14,900 genome fragments, each 10 kb long, significantly resolved the species relationships between and among the sister-genera Macropus and Wallabia. The phylogenomic approach reconstructed the swamp wallaby (Wallabia) as nested inside Macropus, making this genus paraphyletic. However, the phylogenomic analyses indicate multiple conflicting phylogenetic signals in the swamp wallaby genome. This is interpreted as at least one introgression event between the ancestor of the genus Wallabia and a now extinct ghost lineage outside the genus Macropus. Additional phylogenetic signals must therefore be caused by incomplete lineage sorting and/or introgression, but available statistical methods cannot convincingly disentangle the two processes. In addition, the relationships inside the Macropus subgenus M. (Notamacropus) represent a hard polytomy. Thus, the relationships between tammar, red-necked, agile, and parmawallabies remain unresolvable even with whole-genome data. Even if most methods resolve bifurcating trees from genomic data, hard polytomies, incomplete lineage sorting, and introgression complicate the interpretation of the phylogeny and thus taxonomy. [ABSTRACT FROM AUTHOR]

In modern evolutionary divergence analysis the role of geological information extends beyond providing a timescale, to informing molecular rate variation across the tree. Here I consider the implications of this development. I use fossil calibrations to test the accuracy of models of molecular rate evolution for placental mammals, and reveal substantial misspecification associated with life history rate correlates. Adding further calibrations to reduce dating errors at specific nodes unfortunately tends to transfer underlying rate errors to adjacent branches. Thus, tight calibration across the tree is vital to buffer against rate model errors. I argue that this must include allowing maximum bounds to be tight when good fossil records permit, otherwise divergences deep in the tree will tend to be inflated by the interaction of rate errors and asymmetric confidence in minimum and maximum bounds. In the case of placental mammals I sought to reduce the potential for transferring calibration and rate model errors across the tree by focusing on well-supported calibrations with appropriately conservative maximum bounds. The resulting divergence estimates are younger than others published recently, and provide the long-anticipated molecular signature for the placental mammal radiation observed in the fossil record near the 66 Ma Cretaceous-Paleogene extinction event. [ABSTRACT FROM AUTHOR]

Objective: Acute Disseminated Encephalomyelitis (ADEM) often presents as an abrupt, brief, and intense attack causing widespread inflammation and demyelination to the central nervous system. Most patients typically make a complete neurological recovery; however, a few demonstrate long-term, persistent impairments. Method: A 64-year-old white female presented for a neuropsychological evaluation (2021) following a progressive one-year decline in her memory and motor abilities, which per family, reportedly overlay persisting residual deficits from an ADEM attack she had in 2010. Nearly 11 years following the attack, she reported continued reliance on her family in completing most of her instrumental, and even some basic activities of daily living since the attack. Initial neuroimaging following the attack (2010) revealed extensive bilateral white matter (WM) lesions, whereas current neuroimaging (2021) (despite not explicitly commenting on the resolution status of her lesions), continued to reveal widespread hyperintense signals in WM regions, progressing cerebral atrophy, and the possibility of superimposed normal pressure hydrocephalus (i.e. ventriculomegaly). Results: Her neuropsychological profile (with no prior baseline) was marked by substantial impairments in immediate and delayed verbal/visual memory, attention, language, motor abilities, visuospatial skills, executive functions, along with mild anxiety. Conclusions: This neurocognitive profile displayed atypical findings in patient recovery following an ADEM attack. Given the test results and the continued presence of extensive hyperintense signals in WM regions, it is possible her initial brain lesions (due to ADEM) remained unresolved. This, along with the possible intervening effects of new pathology (e.g. NPH and possible vascular changes) are likely exacerbating her existing deficits related to ADEM. [ABSTRACT FROM AUTHOR]

Objective: Individuals with Progressive Supranuclear Palsy (PSP) often experience cognitive decline, repeated falls, restricted gaze, bradykinesia, and depression/behavioral changes. Despite having certain distinguishing features neuroanatomically and neurologically, PSP continues to be difficult to classify and distinguish from some other more well-known neurodegenerative and movement-related disorders. Method: A 68-year-old white male presented for a neuropsychological evaluation (2022) initially after his neurologist became suspicious of him having cerebellar degeneration or multisystem atrophy. He reported a progressive one-year decline in memory, motor abilities, and executive functions, along with having personality changes and a loss of independence in his activities of daily living (ADLs). To complicate the differential diagnosis, an MRI of his brain from six months prior simply concluded "age-related changes". Upon revisiting this MRI and closer visual inspection, focal atrophy of the midbrain became apparent on a sagittal section, in addition to bilateral ischemic changes in the white matter. He was later diagnosed with PSP. Results: Despite demonstrating adequate performance on simple cognitive screening measures, he displayed marked behavioral disinhibition, executive/attention problems, visuospatial concerns, decreased motor abilities, and variable memory functioning that were found to impact his ability to carry out instrumental and even some basic ADLs. Conclusions: Cases such as this one requiring diagnostic clarification lend support to the "hummingbird sign" (midbrain atrophy) being a useful imaging marker in distinguishing PSP from other clinical disorders. Additionally, in contrast to other neurodegenerative disorders, frontal-executive deficits (e.g. disinhibition) were a particularly pronounced feature in his PSP neurocognitive profile, followed by milder difficulties in memory, language, and visuospatial functions. [ABSTRACT FROM AUTHOR]

Objective: This study analyzed differences in learning/acquisition and delayed recall between adult patients diagnosed with attention-deficit/hyperactivity disorder (ADHD) Predominantly Inattentive and Combined subtypes and a control group using the Rey Auditory Verbal Learning Test (RAVLT). Method: This cross-sectional study analyzed data from a consecutive series of patients referred specifically for purposes of ADHD diagnostic clarification. Each was administered the RAVLT, as part of an extensive evaluation, to assess for verbal learning and memory. 155 patients (40.8%) met DSM-5 criteria for ADHD-Inattentive subtype and 165 (43.4%) for ADHD-Combined subtype. Sixty (15.8%) who did not meet criteria for ADHD, but who were diagnosed with a primary depressive/anxiety disorder or received no diagnosis served as a control group. Results: There were significant main effects found between the three groups on all trials analyzed on the RAVLT (Trial 1, p=.016; Trial 5, p=.003; Total Trials, p=.000; Trial 6, p=.001; Trial 7, p=.000). Effect sizes ranged from.022-.042. Posthoc analysis revealed that the ADHD-C group performed significantly worse than both the control group and ADHD-I group in both acquisition and delayed memory. Frequency distributions of impaired performance revealed the ADHD-C group had the largest rate of impairments (12-23%) on this measure. The ADHD-I group demonstrated 6-19% impairments. The control group ranged from 3-10% impairments. Conclusion: Verbal memory impairments are much more likely in adult patients diagnosed with ADHD than those without the diagnosis. While the inattentive and combined subtypes of ADHD both demonstrate deficiencies in verbal memory performance, the rate of likely impairments is much greater amongst the combined subtype. [ABSTRACT FROM AUTHOR]

Objective: Hashimoto encephalopathy (HE) is a rare neurological condition with pathophysiology associated with elevated autoimmune anti-thyroid antibodies. The condition, associated with Hashimoto's thyroiditis, is found more commonly in women. Clinical presentations of HE vary significantly, with cognitive deficit and generalized seizures as the most prominent manifestations. While there is robust literature illustrating HE in female populations, literature on HE in male patients, particularly with dominant motoric features, remains limited. Methods: A 52-year-old, right-handed, Caucasian male presented for evaluation reporting difficulties with short-term memory, word-finding, disorientation, and motor deficits. The patient exhibited significant motor symptoms including myotonia, micrographia, fasciculations and paresthesias, phantosmia, and myoclonic jerking, beginning in 2017 with progressive decline. Relevant medical history includes Hashimoto thyroiditis (2021), focal temporal EEG abnormalities (2021), dystonia (2021), and migraines. Prior to presenting concerns, the patient was otherwise generally healthy. Neuroimaging (MRI) revealed increased signal intensity in the subcortical white matter of the right frontal lobe. He was dependent in several instrumental activities of daily living. Results: His premorbid baseline was estimated to be in the average range. His neurocognitive profile was marked by mild impairments in immediate and delayed verbal memory and recognition paradigms, whereas he demonstrated moderate impairments in processing speed and motor functioning. Conculsion: Taken together, his neurocognitive profile, clinical history, and functional independence are consistent with the clinical presentation of HE. His cognitive deficits and epileptiform activity are consistent with prominent manifestations of HE, whereas his pronounced motoric features are seemingly aberrant in HE. Furthermore, post-steroidal treatment revealed increased cognitive proficiency on a single mental status examination. [ABSTRACT FROM AUTHOR]

Objective: Combining multiple embedded performance validity tests (PVTs) can produce similar classification accuracy to freestanding PVTs. However, there is a lack of research on the incremental predictive power of various combinations of PVTs. Thus, we compared eight embedded PVTs to assess those that best predict classification accuracy on the Dot Counting Test (DCT). Method: Sample included 225 patients (mean age=45.96; mean education=13.96; 56% female, 44% male; 35% White, 40% Black, 17% Hispanic, 5% Asian, 2% Other) undergoing neuropsychological evaluation that included multiple embedded PVTs, including: Brief Visuospatial Memory Test-Revised Recognition Discrimination (BVMT-R RD), Stroop Color and Word Test Word Reading T-Score (Stroop-T), Trail Making Test Part A T-Score (TMT-A), Rey Auditory Verbal Learning Test (RAVLT) Forced Choice, RAVLT Effort Score, Digit Span Age Corrected Scaled Score, Reliable Digit Span, and Letter Fluency T-Score. Patients were classified into valid/invalid groups based on four independent criterion PVTs. Results: A forward stepwise logistic regression was performed to predict DCT pass/fail using the aforementioned embedded PVTs as predictors. The model was achieved in three steps (p<.05); Step 1: BVMT-R RD (Classification Accuracy=87.6%; Nagelkerke R2 =.30), Step 2: BVMT-R RD + Stroop-T (Classification Accuracy=89.6%; Nagelkerke R2 =.44); Step 3: BVMT-R RD + Stroop-T + TMT-A (Classification Accuracy=90.1%; Nagelkerke R2 =.49). Conclusion: BVMT-R RD + Stroop-T + TMT-A reliably predicted the DCT pass/fail group. Thus, this combination of embedded PVTs may be reliable predictors of validity classification when time prohibits delivery of freestanding PVTs, such as the DCT. [ABSTRACT FROM AUTHOR]

Objective: Increasing evidence suggests that adverse childhood experiences (ACEs) predict neurocognitive dysfunction, possibly through direct (e.g. brain structure/function changes) and indirect (e.g. increased psychopathology risk) pathways. However, extant studies have focused on young and older adults, with limited understanding as to how ACEs affect cognitive health in mid-adulthood. Therefore, this study compared adults with high vs. low ACE scores on measures of cognitive performance and psychopathology. Method: This cross-sectional study included 211 adult patients (46.9% female; Mage = 44.9, SD = 17.1; Meducation = 13.8, SD = 3.0) consecutively referred for outpatient neuropsychological evaluation within a large, Midwestern academic medical center. A series one-way analysis of variances (ANOVAs) were conducted to compare high vs. low ACE groups on the Test of Premorbid Functioning (TOPF), Digit Span (DS), Trail Making Test-Part B (TMT-B), Rey Auditory Verbal Learning Test (RAVLT; Immediate and Long Delayed Recall), Beck Depression Inventory-II (BDI-II), and Beck Anxiety Inventory (BAI) scores. Results: Significant group differences were detected for BDI-II and BAI scores, F(1,159) = 18.38, p.05. Non-significant cognitive measure findings cannot be attributed to group differences in premorbid functioning, as TOPF score also did not significantly differ by ACE group, p > 0.05. Conclusions: Results of this investigation suggest that greater ACEs increase risk of depression and anxiety, but not neurocognitive dysfunction, in adulthood. [ABSTRACT FROM AUTHOR]

Fossils provide the principal basis for temporal calibrations, which are critical to the accuracy of divergence dating analyses. Translating fossil data into minimum and maximum bounds for calibrations is the most important--often least appreciated--step of divergence dating. Properly justified calibrations require the synthesis of phylogenetic, paleontological, and geological evidence and can be difficult for nonspecialists to formulate. The dynamic nature of the fossil record (e.g., new discoveries, taxonomic revisions, updates of global or local stratigraphy) requires that calibration data be updated continually lest they become obsolete. Here, we announce the Fossil Calibration Database (http://fossilcalibrations.org), a new open-access resource providing vetted fossil calibrations to the scientific community. Calibrations accessioned into this database are based on individual fossil specimens and follow best practices for phylogenetic justification and geochronological constraint. The associated Fossil Calibration Series, a calibration-themed publication series at Palaeontologia Electronica, will serve as a key pipeline for peer-reviewed calibrations to enter the database. [ABSTRACT FROM AUTHOR]

Marsupials exhibit great diversity in ecology and morphology. However, compared with their sister group, the placental mammals, our understanding of many aspects of marsupial evolution remains limited. We use 101 mitochondrial genomes and data from 26 nuclear loci to reconstruct a dated phylogeny including 97% of extant genera and 58% of modern marsupial species. This tree allows us to analyze the evolution of habitat preference and geographic distributions of marsupial species through time. We found a pattern of mesic-adapted lineages evolving to use more arid and open habitats, which is broadly consistent with regional climate and environmental change. However, contrary to the general trend, several lineages subsequently appear to have reverted from drier to more mesic habitats. Biogeographic reconstructions suggest that current views on the connectivity between Australia and New Guinea/Wallacea during the Miocene and Pliocene need to be revised. The antiquity of several endemic New Guinean clades strongly suggests a substantially older period of connection stretching back to the Middle Miocene and implies that New Guinea was colonized by multiple clades almost immediately after its principal formation. [ABSTRACT FROM PUBLISHER]

The Monte Carlo software CASINO has been expanded with new modules for the simulation of complex beam scanning patterns, for the simulation of cathodoluminescence (CL), and for the calculation of electron energy deposition in subregions of a three-dimensional (3D) volume. Two examples are presented of the application of these new capabilities of CASINO. First, the CL emission near threading dislocations in gallium nitride (GaN) was modeled. The CL emission simulation of threading dislocations in GaN demonstrated that a better signal-to-noise ratio was obtained with lower incident electron energy than with higher energy. Second, the capability to simulate the distribution of the deposited energy in 3D was used to determine exposure parameters for polymethylmethacrylate resist using electron-beam lithography (EBL). The energy deposition dose in the resist was compared for two different multibeam EBL schemes by changing the incident electron energy. [ABSTRACT FROM PUBLISHER]

The article discusses a study of Bayesian estimation of substitution rates from simulated ancient deoxyribonucleic acid (aDNA) sequences data with low information content. The relationship between sequence variation and estimated rate under a range of simulation conditions, including various rates and sequence lengths is analyzed. It notes the influence of population size on rate estimation. Results identified several factors determining the performance of rate estimation such as sequence variability, ages of the sequences and genealogic structure.

The discoloring interaction between the artist’s pigments cadmium yellow and the copper-containing malachite, an interaction that is conjectured to cause black spotting in oil paintings of the 19th and early 20th centuries, was examined using X-ray mapping and scatter diagram analysis. The application of these coupled techniques confirmed that copper sulfide phases were produced during discoloration reaction. Scatter diagram analysis indicated that two copper sulfide stoichiometries (CuS and Cu3S2) were present as reaction products where previously only crystalline CuS (covellite) had been identified by X-ray diffraction. The results demonstrate the potential of X-ray mapping coupled with scatter diagram analysis for the identification of both crystalline and X-ray amorphous phases produced by such complex heterogeneous interactions and their applicability to the investigation of interactions of artists’ pigments. [ABSTRACT FROM AUTHOR]

Ratites are large, flightless birds and include the ostrich, rheas, kiwi, emu, and cassowaries, along with extinct members, such as moa and elephant birds. Previous phylogenetic analyses of complete mitochondrial genome sequences have reinforced the traditional belief that ratites are monophyletic and tinamous are their sister group. However, in these studies ratite monophyly was enforced in the analyses that modeled rate heterogeneity among variable sites. Relaxing this topological constraint results in strong support for the tinamous (which fly) nesting within ratites. Furthermore, upon reducing base compositional bias and partitioning models of sequence evolution among protein codon positions and RNA structures, the tinamou–moa clade grouped with kiwi, emu, and cassowaries to the exclusion of the successively more divergent rheas and ostrich. These relationships are consistent with recent results from a large nuclear data set, whereas our strongly supported finding of a tinamou–moa grouping further resolves palaeognath phylogeny. We infer flight to have been lost among ratites multiple times in temporally close association with the Cretaceous–Tertiary extinction event. This circumvents requirements for transient microcontinents and island chains to explain discordance between ratite phylogeny and patterns of continental breakup. Ostriches may have dispersed to Africa from Eurasia, putting in question the status of ratites as an iconic Gondwanan relict taxon. [ABSTRACT FROM PUBLISHER]

The article compares the various calibration techniques for phylogenetic estimation of evolutionary divergent times and explains how they can be used to capture and utilize the temporal information contained in the fossil record, biogeographic events and radiometric dates. It discusses the various issues and difficulties concerning calibration methodology. It also presents a brief case study examining the effects of using different calibration techniques.

The article discusses the evidence for time dependency of molecular rate estimates. The author points out that long-term changes in the genetic composition of a population occur by the fixation of new mutations, a process known as substitution. He then concludes that the time dependency of rates may be problematic for the estimation of recent divergence times, but the weight of evidence suggests that it should not be ignored.

Australasian marsupials include three major radiations, the insectivorous/carnivorous Dasyuromorphia, the omnivorous bandicoots (Peramelemorphia), and the largely herbivorous diprotodontians. Morphologists have generally considered the bandicoots and diprotodontians to be closely related, most prominently because they are both syndactylous (with the 2nd and 3rd pedal digits being fused). Molecular studies have been unable to confirm or reject this Syndactyla hypothesis. Here we present new mitochondrial (mt) genomes from a spiny bandicoot ( Echymipera rufescens ) and two dasyurids, a fat-tailed dunnart ( Sminthopsis crassicaudata ) and a northern quoll ( Dasyurus hallucatus ). By comparing trees derived from pairwise base-frequency differences between taxa with standard (absolute, uncorrected) distance trees, we infer that composition bias among mt protein-coding and RNA sequences is sufficient to mislead tree reconstruction. This can explain incongruence between trees obtained from mt and nuclear data sets. However, after excluding major sources of compositional heterogeneity, both the “reduced-bias” mt and nuclear data sets clearly favor a bandicoot plus dasyuromorphian association, as well as a grouping of kangaroos and possums (Phalangeriformes) among diprotodontians. Notably, alternatives to these groupings could only be confidently rejected by combining the mt and nuclear data. Elsewhere on the tree, Dromiciops appears to be sister to the monophyletic Australasian marsupials, whereas the placement of the marsupial mole ( Notorycte s) remains problematic. More generally, we contend that it is desirable to combine mt genome and nuclear sequences for inferring vertebrate phylogeny, but as separately modeled process partitions. This strategy depends on detecting and excluding (or accounting for) major sources of nonhistorical signal, such as from compositional nonstationarity. [Base composition; combined data; marsupial; mitochondrial genome; phylogeny.] [ABSTRACT FROM AUTHOR]

Background The population-based incidence and burden of community-onset non-influenza respiratory viruses associated with hospitalization in adults has not been systematically assessed. Methods On admission, patients with respiratory symptoms are tested for respiratory viruses by multiplex polymerase chain reaction (BioFire FilmArray Respiratory Panel) as per standard of care at our university teaching hospital (1160 beds). A retrospective study was performed to identify adults who had influenza, parainfluenza virus (PIV), respiratory syncytial virus (RSV), human metapneumovirus (hMPV), or adenovirus (AV) detected within 3 days of admission from October 2017 to October 2018. To calculate population-based incidence per 100,000 persons (using 2010 US Census data), the number of cases was adjusted by the hospital's percent market share for zip codes as determined by New York State's all payer data reporting system. To improve the incidence estimate's reliability, only cases living in zip codes for which the hospital had ≥ 60% market share were included. We compared median length of stay (LOS), ICU admission, and in-hospital mortality associated with each virus. Results Influenza A (H3) had the highest overall incidence followed by Influenza B and RSV. For each virus, the highest incidence was observed in adults ≥ 65 years old (figure). Overall, 12.9% of cases were hospitalized in the ICU and 4.7% died during hospitalization (table). AV, hMPV, and RSV were associated with the longest LOS. AV, PIV, and RSV were associated with the largest proportion of ICU admissions and deaths. Conclusion While Influenza A (H3) and Influenza B were associated with the highest population-based incidence, non-influenza respiratory viruses caused substantial morbidity in older adults. Compared with influenza viruses, AV, PIV, and RSV were associated with greater severity determined by ICU admissions and death. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Respiratory syncytial virus (RSV) infection has been increasingly recognized as an important cause of acute respiratory illness (ARI) and a trigger for exacerbation of underlying cardiopulmonary disease in adults. Incidence of hospitalized RSV infection remains uncertain as adults have not been systematically screened. Previous incidence estimates, derived primarily from modeling studies, have ranged from 84 to 190/100K population in adults > 65 years of age. Accurate burden data are critical to inform RSV vaccine development for adults. We used active surveillance among hospitalized adults to determine population-based incidence rates of RSV infection. Methods Hospitalized adults ≥ 18 years old residing in the surveillance area with >2 ARI symptoms or exacerbation of underlying cardiopulmonary disease were screened for eligibility during October 2017–April 2018 and October 2018 to April 2019 in 3 hospitals in Rochester, NY and New York City. Respiratory specimens were tested for RSV using PCR assays. RSV incidence per 100,000 persons (per 2010 US Census data) was adjusted by percent market share for study hospitals in their catchment area. Results In total, 8,217 hospitalized adults residing in the surveillance area that met the surveillance case definition were tested for RSV; 768 (9.4%) were positive. Adults were aged 18–49 (12%), 50–64 (30%), and ≥65 years old (58%); 55% were female. RSV infection incidence varied from year 1 to year 2 and was highest in patients aged ≥65 years old (table). Conclusion This is the largest prospective RSV incidence study to date. Preliminary results indicate that the incidence of RSV infection may be higher than previously reported, especially in urban-dwelling adults > 65 years of age. Results confirm the need for vaccines to prevent RSV infections in older adults. Disclosures All Authors: No reported Disclosures. [ABSTRACT FROM AUTHOR]

We have sequenced four new mitochondrial genomes to improve the stability of the tree for placental mammals; they are two insectivores (a gymnure, Echinosorex gymnurus and Formosan shrew Soriculus fumidus); a Formosan lesser horseshoe bat (Rhinolophus monoceros); and the New Zealand fur seal (Arctocephalus forsteri). A revision to the hedgehog sequence (Erinaceus europaeus) is also reported. All five are from the Laurasiatheria grouping of eutherian mammals. On this new data set there is a strong tendency for the hedgehog and its relative, the gymnure, to join with the other Laurasiatherian insectivores (mole and shrews). To quantify the stability of trees from this data we define, based on nuclear sequences, a major four-way split in Laurasiatherians. This ([Xenarthra, Afrotheria], [Laurasiatheria, Supraprimates]) split is also found from mitochondrial genomes using either protein-coding or RNA (rRNA and tRNA) data sets. The high similarity of the mitochondrial and nuclear-derived trees allows a quantitative estimate of the stability of trees from independent data sets, as detected from a triplet Markov analysis. There are significant changes in the mutational processes within placental mammals that are ignored by current tree programs. On the basis of our quantitative results, we expect the evolutionary tree for mammals to be resolved quickly, and this will allow other problems to be solved. [ABSTRACT FROM PUBLISHER]

Objective A rare mutation in the PDCD10 gene causes cerebral cavernous malformations, which can result in multiple brain hemorrhages and hundreds of lesions. Up to 50% of individuals with the PDCD10 mutation remain symptom-free throughout their lives; however, others can suffer from seizures or focal neurologic deficits. Participant: A 67-year-old Caucasian male presented for a neuropsychological re-evaluation (2020) following a progressive decline in his memory and attention dating back 20 years. A baseline neuropsychological evaluation was obtained 7 years ago. Relevant medical history included a 5 mm left falcine meningioma, epilepsy, obstructive sleep apnea, hypertension, and type II diabetes. Neuroimaging revealed over 250 scattered lesions that had advanced over the past 7 years, particularly in the paramedian pontine reticular formation, left inferior cerebellum, and right middle frontal gyrus. Results His neurocognitive profile was marked by mild impairments in immediate verbal memory. The remainder of his cognitive profile was average. Compared to his 2013 evaluation, he showed only a minimal decline in verbal memory, but he showed slight improvements in the domains of executive functioning, visuospatial abilities, and language. Conclusion Despite the marked progression of lesions documented on current neuroimaging, aside from immediate verbal memory problems the patient's neurocognitive functioning was relatively well-preserved. He even exhibited minor improvements within several domains. Given the patient's current neurocognitive status, this case illustrates the importance of comprehensive neuropsychological testing in cases that would appear more severe based on neuroimaging data alone. Relatedly, progression of neuropathological disease burden on neuroimaging is not necessarily accompanied by consistent progression of neuropsychological dysfunction. [ABSTRACT FROM AUTHOR]

Objective Studies that have used semantic fluency tasks to guide differential diagnosis of Alzheimer's disease (ad) and vascular dementia (VaD) typically only examine the total number of words produced, which has yielded conflicting results. The present study examined whether other indices of semantic fluency (i.e. clustering and switching), which are thought to better isolate the components of semantic memory and executive functioning abilities, would discriminate among ad , VaD, and mild cognitive impairment (MCI). Method A retrospective sample of 156 patients (mean age = 78.64; 76.3% female, 23.7% male; 26.9% White, 71.2% Black, 1.9% Other) who completed a comprehensive neuropsychological evaluation as part of a workup related to memory concerns and were diagnosed with ad , VaD, or MCI was utilized. Separate univariate analyses of variance were used to examine group differences on three indices of semantic fluency (animals): total words, mean cluster size, and number of switches. Results There was a significant main effect of group for total words [F(2,153) = 7.09, p = 0.001], mean cluster size [F(2, 153) = 3.44, p = 0.035] and number of switches [F(2,153) = 3.36, p = 0.037]. Bonferroni post-hoc tests revealed that the ad and VaD groups produced significantly fewer total words than the MCI group, the ad group produced significantly smaller clusters than the VaD group, and the VaD group produced significantly fewer switches than the MCI group. Conclusion Observed group differences suggest that clustering and switching may aid in discriminating between dementia etiologies. Future studies may benefit from examining the association between these fluency indices and performance on executive functioning and semantic knowledge tasks to better understand these findings. [ABSTRACT FROM AUTHOR]

Background Respiratory syncytial virus (RSV) infection is a common cause of acute respiratory infection (ARI) in adults. Prospective surveillance enables collection of representative data on demographic and clinical characteristics. Few data of this kind are available for adults hospitalized with RSV infection. We used active population-based surveillance to identify patients with laboratory-confirmed RSV infection and evaluated demographic characteristics and clinical outcomes. Methods Hospitalized adults ≥ 18 years old residing in a predefined catchment area with ≥ 2 ARI symptoms or exacerbation of underlying cardiopulmonary disease were screened for eligibility during October 2017–April 2018 and October 2018–April 2019 in 3 hospitals in Rochester, NY and New York City. Respiratory specimens were tested for RSV using PCR assays. Clinical and demographic data were abstracted from the medical record. Multivariate analysis was used to evaluate the relationship of patient characteristics with clinical outcomes. Results 8,217 hospitalized adults were screened and 9.4% positive for RSV infection. Preliminary clinical and demographic data were available for 348 patients including 14% 18–49 years, 28% 50–64 years and 58% > 65 years. Mean age was 68 years and 60% were female (Figure 1). Patients had a mean of 3 co-morbidities, with diabetes (40%), chronic obstructive pulmonary disease (30%), chronic kidney disease (28%), congestive heart failure (28%), coronary artery disease (25%) and asthma (24%) the most common co-morbidities (Figure 2). Median hospital length of stay was 6 days (IQR 4–10), 13% of patients were admitted to the ICU, 5% were mechanically ventilated and 5% died during admission and 12% within 6 months. In multivariate analysis having > 3 comorbidities, cardiac disease or a lower baseline functional status measured by activities of daily living scores was significantly associated with 6-month mortality. Conclusion The majority of hospitalized patients with RSV infection were older adults with ≥ 3 chronic comorbid conditions. Baseline functional status may be predictive of worse clinical outcomes in patients with RSV infection. These insights into patient characteristics and clinical outcomes will provide information for prevention programs. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]