Hadaean to Palaeoarchaean stagnant-lid tectonics revealed by zircon magnetism.

Plate tectonics is a fundamental factor in the sustained habitability of Earth, but its time of onset is unknown, with ages ranging from the Hadaean to Proterozoic eons1-3. Plate motion is a key diagnostic to distinguish between plate and stagnant-lid tectonics, but palaeomagnetic tests have been thwarted because the planet's oldest extant rocks have been metamorphosed and/or deformed4. Herein, we report palaeointensity data from Hadaean-age to Mesoarchaean-age single detrital zircons bearing primary magnetite inclusions from the Barberton Greenstone Belt of South Africa5. These reveal a pattern of palaeointensities from the Eoarchaean (about 3.9 billion years ago (Ga)) to Mesoarchaean (about 3.3 Ga) eras that is nearly identical to that defined by primary magnetizations from the Jack Hills (JH; Western Australia)6,7, further demonstrating the recording fidelity of select detrital zircons. Moreover, palaeofield values are nearly constant between about 3.9 Ga and about 3.4 Ga. This indicates unvarying latitudes, an observation distinct from plate tectonics of the past 600 million years (Myr) but predicted by stagnant-lid convection. If life originated by the Eoarchaean8, and persisted to the occurrence of stromatolites half a billion years later9, it did so when Earth was in a stagnant-lid regime, without plate-tectonics-driven geochemical cycling.

Differential interferon responses to influenza A and B viruses in primary ferret respiratory epithelial cells.

Influenza B viruses (IBV) cocirculate with influenza A viruses (IAV) and cause periodic epidemics of disease, yet antibody and cellular responses following IBV infection are less well understood. Using the ferret model for antisera generation for influenza surveillance purposes, IAV resulted in robust antibody responses following infection, whereas IBV required an additional booster dose, over 85% of the time, to generate equivalent antibody titers. In this study, we utilized primary differentiated ferret nasal epithelial cells (FNECs) which were inoculated with IAV and IBV to study differences in innate immune responses which may result in differences in adaptive immune responses in the host. FNECs were inoculated with IAV (H1N1pdm09 and H3N2 subtypes) or IBV (B/Victoria and B/Yamagata lineages) and assessed for 72 h. Cells were analyzed for gene expression by quantitative real-time PCR, and apical and basolateral supernatants were assessed for virus kinetics and interferon (IFN), respectively. Similar virus kinetics were observed with IAV and IBV in FNECs. A comparison of gene expression and protein secretion profiles demonstrated that IBV-inoculated FNEC expressed delayed type-I/II IFN responses and reduced type-III IFN secretion compared to IAV-inoculated cells. Concurrently, gene expression of Thymic Stromal Lymphopoietin (TSLP), a type-III IFN-induced gene that enhances adaptive immune responses, was significantly downregulated in IBV-inoculated FNECs. Significant differences in other proinflammatory and adaptive genes were suppressed and delayed following IBV inoculation. Following IBV infection, ex vivo cell cultures derived from the ferret upper respiratory tract exhibited reduced and delayed innate responses which may contribute to reduced antibody responses in vivo.IMPORTANCEInfluenza B viruses (IBV) represent nearly one-quarter of all human influenza cases and are responsible for significant clinical and socioeconomic impacts but do not pose the same pandemic risks as influenza A viruses (IAV) and have thus received much less attention. IBV accounts for greater severity and deaths in children, and vaccine efficacy remains low. The ferret can be readily infected with human clinical isolates and demonstrates a similar course of disease and immune responses. IBV, however, generates lower antibodies in ferrets than IAV following the challenge. To determine whether differences in initial innate responses following infection may affect the development of robust adaptive immune responses, ferret respiratory tract cells were isolated, infected with IAV/IBV, and compared. Understanding the differences in the initial innate immune responses to IAV and IBV may be important in the development of more effective vaccines and interventions to generate more robust protective immune responses.

Diploid-dominant life cycles characterize the early evolution of Fungi.

Most of the described species in kingdom Fungi are contained in two phyla, the Ascomycota and the Basidiomycota (subkingdom Dikarya). As a result, our understanding of the biology of the kingdom is heavily influenced by traits observed in Dikarya, such as aerial spore dispersal and life cycles dominated by mitosis of haploid nuclei. We now appreciate that Fungi comprises numerous phylum-level lineages in addition to those of Dikarya, but the phylogeny and genetic characteristics of most of these lineages are poorly understood due to limited genome sampling. Here, we addressed major evolutionary trends in the non-Dikarya fungi by phylogenomic analysis of 69 newly generated draft genome sequences of the zoosporic (flagellated) lineages of true fungi. Our phylogeny indicated five lineages of zoosporic fungi and placed Blastocladiomycota, which has an alternation of haploid and diploid generations, as branching closer to the Dikarya than to the Chytridiomyceta. Our estimates of heterozygosity based on genome sequence data indicate that the zoosporic lineages plus the Zoopagomycota are frequently characterized by diploid-dominant life cycles. We mapped additional traits, such as ancestral cell-cycle regulators, cell-membrane- and cell-wall-associated genes, and the use of the amino acid selenocysteine on the phylogeny and found that these ancestral traits that are shared with Metazoa have been subject to extensive parallel loss across zoosporic lineages. Together, our results indicate a gradual transition in the genetics and cell biology of fungi from their ancestor and caution against assuming that traits measured in Dikarya are typical of other fungal lineages.

Variation of terpene alkaloids in Daphniphyllum macropodum across plants and tissues.

Daphniphyllum macropodum produces alkaloids that are structurally complex with polycyclic, stereochemically rich carbon skeletons. Understanding how these compounds are formed by the plant may enable exploration of their biological function and bioactivities. We employed multiple metabolomics techniques, including a workflow to annotate compounds in the absence of standards, to compare alkaloid content across plants and tissues. Different alkaloid structural types were found to have distinct distributions between genotypes, between tissues and within tissues. Alkaloid structural types also showed different isotope labelling enrichments that matched their biosynthetic relationships. The work suggests that mevalonate derived 30-carbon alkaloids are formed in the phloem region before their conversion to 22-carbon alkaloids which accumulate in the epidermis. This sets the stage for further investigation into the biosynthetic pathway.

Multicentered study of patient outcomes after declined for early liver transplantation in severe alcohol-associated hepatitis.

BACKGROUND: Early liver transplantation for alcohol-associated hepatitis is controversial in part because patients may recover, and obviate the need for liver transplantation. METHODS: In this retrospective study among 5 ACCELERATE-AH sites, we randomly sampled patients evaluated and then declined for liver transplantation for alcohol-associated hepatitis. All had Model of End-Stage Liver Disease (MELD) >20 and <6 months of abstinence. Recompensation was defined as MELD <15 without variceal bleeding, ascites, or overt HE requiring treatment. Multilevel mixed effects linear regression was used to calculate probabilities of recompensation; multivariable Cox regression was used for mortality analyses. RESULTS: Among 145 patients [61% men; median abstinence time and MELD-Na was 33 days (interquartile range: 13-70) and 31 (interquartile range: 26-36), respectively], 56% were declined for psychosocial reasons. Probability of 30-day, 90-day, 6-month, and 1-year survival were 76% (95% CI, 68%-82%), 59% (95% CI, 50%-66%), 49% (95% CI, 40%-57%), and 46% (95% CI, 37%-55%), respectively. Probability of 1-year recompensation was low at 10.0% (95% CI, 4.5%-15.4%). Among patients declined because of clinical improvement, 1-year probability of recompensation was 28.0% (95% CI, 5.7%-50.3%). Among survivors, median MELD-Na at 30 days, 90 days, and 1-year were 29 (interquartile range: 22-38), 19 (interquartile range : 14-29), and 11 (interquartile range : 7-17). Increased MELD-Na (adjusted HR: 1.13, p <0.001) and age (adjusted HR: 1.03, p <0.001) were associated with early (≤90 d) death, and only history of failed alcohol rehabilitation (adjusted HR: 1.76, p =0.02) was associated with late death. CONCLUSIONS: Liver recompensation is infrequent among severe alcohol-associated hepatitis patients declined for liver transplantation. Higher MELD-Na and age were associated with short-term mortality, whereas only history of failed alcohol rehabilitation was associated with long-term mortality. The distinction between survival and liver recompensation merits further attention.

A prospective, pragmatic non-inferiority study of emergency intubation success with the single-use i-view versus standard reusable video laryngoscope.

INTRODUCTION: Video laryngoscope (VL) technology improves first-pass success. The novel i-view VL device is inexpensive and disposable. We sought to determine the first-pass intubation success with the i-view VL device versus the standard reusable VL systems in routine use at each site. METHODS: We performed a prospective, pragmatic study at two major emergency departments (EDs) when VL was used. We rotated i-view versus reusable VL as the preferred device of the month based on an a priori schedule. An investigator-initiated interim analysis was performed. Our primary outcome was a first-pass success with a non-inferiority margin of 10% based on the per-protocol analysis. RESULTS: There were 93 intubations using the reusable VL devices and 81 intubations using the i-view. Our study was stopped early due to futility in reaching our predetermined non-inferiority margin. Operator and patient characteristics were similar between the two groups. The first-pass success rate for the i-view group was 69.1% compared to 84.3% for the reusable VL group. A non-inferiority analysis indicated that the difference (-15.1%) and corresponding 90% confidence limits (-25.3% to -5.0%) did not fall within the predetermined 10% non-inferiority margin. CONCLUSIONS: The i-view device failed to meet our predetermined non-inferiority margin when compared to the reusable VL systems with the study stopping early due to futility. Significant crossover occurred at the discretion of the intubating operator during the i-view month.

Interventions associated with survival after prehospital intubation in the deployed combat setting.

INTRODUCTION: Airway compromise is the second leading cause of potentially preventable death on the battlefield. Prehospital airway management is often unavoidable in a kinetic combat environment and expected to increase in future wars where timely evacuation will be unreliable and air superiority not guaranteed. We compared characteristics of survivors to non-survivors among combat casualties undergoing prehospital airway intubation. MATERIALS AND METHODS: We requested all Department of Defense Trauma Registry (DODTR) encounters during 2007-2023 with documentation of any airway intervention or assessment within the first 72-h after injury. We conducted a retrospective cohort study of all casualties with intubation documented in the prehospital setting. We used descriptive and inferential statistical analysis to compare survivors through 7 days post injury versus non-survivors. We constructed 3 multivariable logistic regression models to test for associations between interventions and 7-day survival after adjusting for injury severity score, mechanism of injury, and receipt of sedatives, paralytics, and blood products. RESULTS: There were 1377 of 48,301 patients with documentation of prehospital intubation in a combat setting. Of these, 1028 (75%) survived through 7 days post injury. Higher proportions of survivors received ketamine, paralytic agents, parenteral opioids, and parenteral benzodiazepines; there was no difference in the proportions of survivors versus non-survivors receiving etomidate. The multivariable models consistently demonstrated positive associations between 7-day survival and receipt of non-depolarizing paralytics and opioid analgesics. CONCLUSIONS: We found an association between non-depolarizing paralytic and opioid receipt with 7-day survival among patients undergoing prehospital intubation. The literature would benefit from future multi-center randomized controlled trials to establish optimal pharmacologic strategies for trauma patients undergoing prehospital intubation.

In-depth immunophenotyping reveals significant alteration of lymphocytes in buffalo with brucellosis.

Water buffalo (Bubalus bubalis) has a prominent position in the livestock industry worldwide but still suffers from limited knowledge on the mechanisms regulating the immune against infections, including brucellosis (BRC), one of the most significant neglected zoonotic diseases of livestock. Seventy-three buffalo were recruited for the study. Thirty-five were naturally infected with Brucella spp. The aims of the study were to (i) verify the cross-reactivity of 16 monoclonal antibodies (mAbs) developed against human, bovine, and ovine antigens; (ii) evaluate lymphocyte subset alterations in BRC positive buffalo; (iii) evaluate the use of the canonical discriminant analysis (CDA), with flow cytometric data, to discriminate BRC positive from negative animals. A new set of eight mAbs (anti CD3e, CD16, CD18, CD45R0, CD79a; CD172a) were shown to cross-react with water buffalo orthologous molecules. BRC positive animals presented a significant (p < 0.0001) decrease in the percentage of PBMC (29.5 vs. 40.3), total, T and B lymphocytes (23.0 vs. 35.5, 19.2 vs. 28.9, 2.6 vs. 5.7, respectively). In contrast, they showed an increase in percentage of granulocytes (65.2 vs. 55.1; p < 0.0001) and B lymphocytes CD21neg (22.9 vs. 16.1; p = 0.0067), a higher T/B lymphocyte ratio (10.3 vs. 6.4; p = 0.0011) and CD3+ /CD21+ (14.7 vs. 8.3; p = 0.0005) ratio. The CDA, applied to 33 different flow cytometric traits, allowed the discrimination of all BRC positive from negative buffalo. Although this is a preliminary study, our results show that flow cytometry can be used in a wide range of applications in livestock diseases, including in support of uncertain BRC diagnoses.

Spatially specific mechanisms and functions of the plant circadian clock.

Like many organisms, plants have evolved a genetic network, the circadian clock, to coordinate processes with day/night cycles. In plants, the clock is a pervasive regulator of development and modulates many aspects of physiology. Clock-regulated processes range from the correct timing of growth and cell division to interactions with the root microbiome. Recently developed techniques, such as single-cell time-lapse microscopy and single-cell RNA-seq, are beginning to revolutionize our understanding of this clock regulation, revealing a surprising degree of organ, tissue, and cell-type specificity. In this review, we highlight recent advances in our spatial view of the clock across the plant, both in terms of how it is regulated and how it regulates a diversity of output processes. We outline how understanding these spatially specific functions will help reveal the range of ways that the clock provides a fitness benefit for the plant.

Comparisons in the Health and Economic Assessments of Using Quadrivalent Versus Trivalent Influenza Vaccines: A Systematic Literature Review.

OBJECTIVES: Seasonal influenza vaccines protect against 3 (trivalent influenza vaccine [IIV3]) or 4 (quadrivalent influenza vaccine [IIV4]) viruses. IIV4 costs more than IIV3, and there is a trade-off between incremental cost and protection. This is especially the case in low- and middle-income countries (LMICs) with limited budgets; previous reviews have not identified studies of IIV4-IIV3 comparisons in LMICs. We summarized the literature that compared health and economic outcomes of IIV4 and IIV3, focused on LMICs. METHODS: We systematically searched 5 databases for articles published before October 6, 2021, that modeled health or economic effects of IIV4 versus IIV3. We abstracted data and compared findings among countries and models. RESULTS: Thirty-eight studies fit our selection criteria; 10 included LMICs. Most studies (N = 31) reported that IIV4 was cost-saving or cost-effective compared with IIV3; we observed no difference in health or economic outcomes between LMICs and other countries. Based on cost differences of influenza vaccines, only one study compared coverage of IIV3 with IIV4 and reported that the maximum IIV4 price that would still yield greater public health impact than IIV3 was 13% to 22% higher than IIV3. CONCLUSIONS: When vaccination coverage with IIV4 and IIV3 is the same, IIV4 tends to be not only more effective but more cost-effective than IIV3, even with relatively high price differences between vaccine types. Alternatively, where funding is limited as in most LMICs, higher vaccine coverage can be achieved with IIV3 than IIV4, which could result in more favorable health and economic outcomes.

Paleomagnetism indicates that primary magnetite in zircon records a strong Hadean geodynamo.

Determining the age of the geomagnetic field is of paramount importance for understanding the evolution of the planet because the field shields the atmosphere from erosion by the solar wind. The absence or presence of the geomagnetic field also provides a unique gauge of early core conditions. Evidence for a geomagnetic field 4.2 billion-year (Gy) old, just a few hundred million years after the lunar-forming giant impact, has come from paleomagnetic analyses of zircons of the Jack Hills (Western Australia). Herein, we provide new paleomagnetic and electron microscope analyses that attest to the presence of a primary magnetic remanence carried by magnetite in these zircons and new geochemical data indicating that select Hadean zircons have escaped magnetic resetting since their formation. New paleointensity and Pb-Pb radiometric age data from additional zircons meeting robust selection criteria provide further evidence for the fidelity of the magnetic record and suggest a period of high geomagnetic field strength at 4.1 to 4.0 billion years ago (Ga) that may represent efficient convection related to chemical precipitation in Earth's Hadean liquid iron core.

Leveraging International Influenza Surveillance Systems and Programs during the COVID-19 Pandemic.

A network of global respiratory disease surveillance systems and partnerships has been built over decades as a direct response to the persistent threat of seasonal, zoonotic, and pandemic influenza. These efforts have been spearheaded by the World Health Organization, country ministries of health, the US Centers for Disease Control and Prevention, nongovernmental organizations, academic groups, and others. During the COVID-19 pandemic, the US Centers for Disease Control and Prevention worked closely with ministries of health in partner countries and the World Health Organization to leverage influenza surveillance systems and programs to respond to SARS-CoV-2 transmission. Countries used existing surveillance systems for severe acute respiratory infection and influenza-like illness, respiratory virus laboratory resources, pandemic influenza preparedness plans, and ongoing population-based influenza studies to track, study, and respond to SARS-CoV-2 infections. The incorporation of COVID-19 surveillance into existing influenza sentinel surveillance systems can support continued global surveillance for respiratory viruses with pandemic potential.

Imaging characteristics and CT sensitivity for pyogenic spinal infections.

BACKGROUND/OBJECTIVE: Contrast-enhanced magnetic resonance imaging (MRI) is the preferred imaging modality for diagnosing pyogenic spinal infection (PSI), but it is not always available. Our objective was to describe pyogenic spinal infection imaging characteristics in patients presenting to a community emergency department (ED) and estimate the computed tomography (CT) sensitivity for these infections. METHODS: We examined the MRI reports from a cohort of 88 PSI patients whom we enrolled in a prospective cohort study and report the prevalence of each PSI type (spinal epidural abscess/infection, vertebral osteomyelitis/discitis, septic facet, and paravertebral abscess/infection) according to contemporary nomenclature. In a 14 patient subcohort who underwent both CT and MRI studies, we report the sensitivity for each PSI from a post hoc blinded overread of the CT imaging by a single neuroradiologist. RESULTS: Of the 88 PSI patients, the median age was 55 years, and 31% were female. The PSI prevalence included: spinal epidural abscess/infection (SEA) in 61(69%), vertebral osteomyelitis/discitis (VO/D) in 54 (61%), septic facet (SF) in 15 (17%), and paravertebral abscess/infection (PVA) in 53 (60%). Of the SEAs, 82% (50/61) were associated with other spinal infections, while 18% (11/61) were isolated SEAs. The overall CT sensitivity in a masked overread was 79% (11/14) for any PSI, 83% (10/12) for any infection outside the spinal canal, and only 18% (2/11) for SEA. CONCLUSION: Patients found to have vertebral osteomyelitis/discitis, septic facet, and paravertebral infections frequently had a SEA coinfection. CT interpretation by a neuroradiologist had moderate sensitivity for infections outside the spinal canal but had low sensitivity for SEA.

Assessment of nationally recommended antibiotics for treatment of UTI in U.S.-Mexico border emergency departments.

BACKGROUND: Urinary tract infections (UTIs) seen in the emergency department are commonly treated as an outpatient with oral antibiotics. Given that antibiotics are available for over-the-counter purchase in Mexico, there is speculation that potential misuse and overuse of antibiotics in United States-Mexico border areas could lead to antibiotic resistance patterns that would render some empiric treatments for UTIs less effective. The purpose of this study was to examine the effectiveness of Infectious Disease Society of America (IDSA) guideline-recommended antibiotics for treatment of outpatient UTI diagnosed in the emergency department. Data were collected from a county hospital on the U.S.-Mexico border with a metropolitan area of over 2 million people. Secondary analysis included frequency of urine culture isolated, resistance rates of urine pathogens, and prescriber habits. METHODS: This study was a retrospective chart review of adult patients diagnosed and treated for UTI from August 1, 2019, to February 29, 2020. Culture results of included patients were analyzed against in vitro-tested antibiotics. Bacterial isolate frequency, resistance rates, and prescribing habits were collected. RESULTS: A total of 985 patient charts were reviewed, of which 520 patients met inclusion criteria for analysis of prescribing habits. Of these, 329 positive bacterial culture growths were included in the analysis of antibiotic resistance rates. Oral antibiotics with comparatively lower resistance rates were amoxicillin/clavulanate, cefdinir, cefuroxime, and nitrofurantoin. Oral antibiotics with notably high resistance rates included trimethoprim-sulfamethoxazole (TMP-SMX), tetracycline, ciprofloxacin, levofloxacin, and cephalexin. Nitrofurantoin was prescribed most frequently for outpatient treatment of UTI/cystitis (41.6%) while cephalexin was the most commonly prescribed antibiotic for outpatient treatment of pyelonephritis (50%). CONCLUSION: Our findings suggest that, while part of standard IDSA guidelines, fluoroquinolones and TMP-SMX are not ideal empiric antibiotics for treatment of outpatient UTI in the U.S.-Mexico border region studied due to high resistance rates. Although not listed as first line agents per current IDSA recommendations, 2nd and 3rd generation cephalosporins, and amoxicillin/clavulanate would be acceptable options given resistance patterns demonstrated in accordance with IDSA allowance for tailoring selection to local resistance. Nitrofurantoin appears to be consistent with recommendations and demonstrates a favorable resistance profile for treatment of outpatient UTI within this region.

Multiplex Real-Time Reverse Transcription PCR for Influenza A Virus, Influenza B Virus, and Severe Acute Respiratory Syndrome Coronavirus 2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019, and the outbreak rapidly evolved into the current coronavirus disease pandemic. SARS-CoV-2 is a respiratory virus that causes symptoms similar to those caused by influenza A and B viruses. On July 2, 2020, the US Food and Drug Administration granted emergency use authorization for in vitro diagnostic use of the Influenza SARS-CoV-2 Multiplex Assay. This assay detects influenza A virus at 102.0, influenza B virus at 102.2, and SARS-CoV-2 at 100.3 50% tissue culture or egg infectious dose, or as few as 5 RNA copies/reaction. The simultaneous detection and differentiation of these 3 major pathogens increases overall testing capacity, conserves resources, identifies co-infections, and enables efficient surveillance of influenza viruses and SARS-CoV-2.

SCGid: a consensus approach to contig filtering and genome prediction from single-cell sequencing libraries of uncultured eukaryotes.

MOTIVATION: Whole-genome sequencing of uncultured eukaryotic genomes is complicated by difficulties in acquiring sufficient amounts of tissue. Single-cell genomics (SCG) by multiple displacement amplification provides a technical workaround, yielding whole-genome libraries which can be assembled de novo. Downsides of multiple displacement amplification include coverage biases and exacerbation of contamination. These factors affect assembly continuity and fidelity, complicating discrimination of genomes from contamination and noise by available tools. Uncultured eukaryotes and their relatives are often underrepresented in large sequence data repositories, further impairing identification and separation. RESULTS: We compare the ability of filtering approaches to remove contamination and resolve eukaryotic draft genomes from SCG metagenomes, finding significant variation in outcomes. To address these inconsistencies, we introduce a consensus approach that is codified in the SCGid software package. SCGid parallelly filters assemblies using different approaches, yielding three intermediate drafts from which consensus is drawn. Using genuine and mock SCG metagenomes, we show that our approach corrects for variation among draft genomes predicted by individual approaches and outperforms them in recapitulating published drafts in a fast and repeatable way, providing a useful alternative to available methods and manual curation. AVAILABILITY AND IMPLEMENTATION: The SCGid package is implemented in python and R. Source code is available at http://www.github.com/amsesk/SCGid under the GNU GPL 3.0 license. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Etiologies and management of haemophagocytic lymphohistiocytosis: is it time for an updated protocol and targeted treatments?

OBJECTIVE: The objective of this study was to analyse the features, therapeutic approaches, and outcomes for adult patients with haemophagocytic lymphohistiocytosis (HLH) at a single centre. METHODS: This study was a retrospective chart review of all patients >18 years of age diagnosed with HLH according to HLH-2004 or H-score criteria at Ochsner Medical Center-New Orleans between 2013 and 2019. RESULTS: A total of 29 patients with HLH met inclusion criteria. A total of 7 patients had an underlying malignancy, 12 had an autoimmune disease, 2 were transplant patients, and 2 had a combination of malignancy, autoimmune disease, or immunodeficiency. A total of 6 patients developed HLH precipitated by infection alone. All 29 patients presented with fever. A total of 28 (97%) patients met H-score criteria, and only 20 (67%) met HLH-2004 criteria. Fifteen patients were treated with the HLH-2004 protocol. Of those treated with the HLH-2004 protocol, 73% (11/15) died, 8% (1/15) had recurrence of HLH, and 20% (3/15) had resolution of HLH. A total of 14 patients were treated with targeted therapy. Of those treated with targeted therapy, 93% (13/14) had resolution of HLH and 1 died. Targeted therapy included pulse steroids, tocilizumab, anakinra, IVIG, CSA, rituximab, and/or CYC in addition to antiviral or antibiotic therapy. CONCLUSION: Our findings suggested that the rheumatologic patient population responded well to a targeted therapeutic approach and poorly to the HLH-2004 protocol. Whether the poor outcomes found with the use of the HLH-2004 protocol are secondary to the protocol itself or the aggressive nature of malignancy-associated HLH is unclear. Further studies are needed to develop tailored therapeutic regimens.

Refusal of Cancer-Directed Surgery in Patients with Colon Cancer: Risk Factors of Refusal and Survival Data.

INTRODUCTION: Colon cancer is the third leading cause of cancer-related deaths. Although there have been numerous advancements in treatment options, electing to undergo surgery is a difficult decision, and some patients may be hesitant to undergo surgery. We sought to understand the risk factors associated with refusal of surgery and predictors of mortality in patients with colon cancer. METHODS: We retrospectively reviewed the Surveillance, Epidemiology, and End Results database for patients diagnosed with colon cancer from 1995 to 2015. We stratified patients according to whether they underwent surgery or refused recommended surgery. We analyzed numerous demographic, surgical, and oncologic variables and performed univariate analysis to assess predictors for refusal of surgery as well as survival and mortality risk in those refusing surgery. RESULTS: Our analysis included 288,322 patients with primary colon cancer where 284,591 (98.7%) underwent cancer-direct surgery and 3731 (1.3%) refused recommended surgery. Those refusing cancer directed surgery were more likely to be > 70 years old, non-Hispanic black patients, and have distant staged cancer (all p < 0.001). In those refusing surgery, risks for mortality included older age, female gender, widowhood, higher grade or distant-staged cancer, and a positive CEA. CONCLUSIONS: Disparities in care related to patient race, gender, and insurance status were related to patients who refused surgical interventions. This study helps to identify patients who are more likely to refuse surgery and may assist in navigating conversations with patients who are contemplating treatment options.

Extensive hybridization and past introgression between divergent lineages in a quasi-clonal hermaphroditic fish: Ramifications for species concepts and taxonomy.

Extreme inbreeding is expected to reduce the incidence of hybridization, serving as a prezygotic barrier. Mangrove rivulus is a small killifish that reproduces predominantly by self-fertilization, producing highly homozygous lines throughout its geographic range. The Bahamas and Caribbean are inhabited by two highly diverged phylogeographic lineages of mangrove rivulus, Kryptolebias marmoratus and a 'Central clade' closely related to K. hermaphroditus from Brazil. The two lineages are largely allopatric, but recently were found in syntopy on San Salvador, Bahamas, where a single hybrid was reported. To better characterize the degree of hybridization and the possibility of secondary introgression, here we conducted a detailed genetic analysis of the contact zone on San Salvador. Two mixed populations were identified, one of which contained sexually mature hybrids. The distribution of heterozygosity at diagnostic microsatellite loci in hybrids showed that one of these hybrids was an immediate offspring from the K. marmoratus x Central clade cross, whereas the remaining five hybrids were products of reproduction by self-fertilization for 1-3 generations following the initial cross. Two hybrids had mitochondrial haplotypes of K. marmoratus and the remaining four hybrids had a haplotype of the Central clade, indicating that crosses go in both directions. In hybrids, alleles of parental lineages were represented in equal proportions suggesting lack of recent backcrossing to either of the parental lineages. However, sympatric populations of two lineages were less diverged than allopatric populations, consistent with introgression. Results are discussed in terms of applicability of the biological species concept for isogenic, effectively clonal, organisms.

Seoul Virus Infection and Spread in United States Home-Based Ratteries: Rat and Human Testing Results From a Multistate Outbreak Investigation.

BACKGROUND: During 2017, a multistate outbreak investigation occurred after the confirmation of Seoul virus (SEOV) infections in people and pet rats. A total of 147 humans and 897 rats were tested. METHODS: In addition to immunoglobulin (Ig)G and IgM serology and traditional reverse-transcription polymerase chain reaction (RT-PCR), novel quantitative RT-PCR primers/probe were developed, and whole genome sequencing was performed. RESULTS: Seventeen people had SEOV IgM, indicating recent infection; 7 reported symptoms and 3 were hospitalized. All patients recovered. Thirty-one facilities in 11 US states had SEOV infection, and among those with ≥10 rats tested, rat IgG prevalence ranged 2%-70% and SEOV RT-PCR positivity ranged 0%-70%. Human laboratory-confirmed cases were significantly associated with rat IgG positivity and RT-PCR positivity (P = .03 and P = .006, respectively). Genomic sequencing identified >99.5% homology between SEOV sequences in this outbreak, and these were >99% identical to SEOV associated with previous pet rat infections in England, the Netherlands, and France. Frequent trade of rats between home-based ratteries contributed to transmission of SEOV between facilities. CONCLUSIONS: Pet rat owners, breeders, and the healthcare and public health community should be aware and take steps to prevent SEOV transmission in pet rats and to humans. Biosecurity measures and diagnostic testing can prevent further infections.