OBJECTIVE

The aim of this study was to examine the association of circulating retinol-binding protein 4 (RBP4) levels with β-cell function across the spectrum of glucose tolerance from normal to overt type 2 diabetes.

Autism spectrum disorders in children.

Maddalena Cavicchioli.

Source: Electronic Journal of Statistics, Volume 14, Number 1, 605--631.

Abstract:
The paper treats the modeling of stationary multivariate stochastic processes via a frequency domain model expressed in terms of cepstrum theory. The proposed model nests the vector exponential model of [20] as a special case, and extends the generalised cepstral model of [36] to the multivariate setting, answering a question raised by the last authors in their paper. Contemporarily, we extend the notion of generalised autocovariance function of [35] to vector time series. Then we derive explicit matrix formulas connecting generalised cepstral and autocovariance matrices of the process, and prove the consistency and asymptotic properties of the Whittle likelihood estimators of model parameters. Asymptotic theory for the special case of the vector exponential model is a significant addition to the paper of [20]. We also provide a mathematical machinery, based on matrix differentiation, and computational methods to derive our results, which differ significantly from those employed in the univariate case. The utility of the proposed model is illustrated through Monte Carlo simulation from a bivariate process characterized by a high dynamic range, and an empirical application on time varying minimum variance hedge ratios through the second moments of future and spot prices in the corn commodity market.

BACKGROUND AND OBJECTIVES:

Children with autism spectrum disorder (ASD) have a higher prevalence of epilepsy compared with general populations. In this pilot study, we prospectively identified baseline risk factors for the development of seizures in individuals with ASD and also identified characteristics sensitive to seizure onset up to 6 years after enrollment in the Autism Speaks Autism Treatment Network.

OBJECTIVES:

Our goals for this study were to characterize the frequency of agitation in patients with autism spectrum disorder (ASD) admitted to an inpatient pediatric medical unit and to identify risk factors associated with agitation.

BACKGROUND AND OBJECTIVES:

Guidelines suggest young children with autism spectrum disorder (ASD) receive intensive nonpharmacologic interventions. Additionally, associated symptoms may be treated with psychotropic medications. Actual intervention use by young children has not been well characterized. Our aim in this study was to describe interventions received by young children (3–6 years old) with ASD. The association with sociodemographic factors was also explored.

CONTEXT:

Recommendations conflict regarding universal application of formal screening instruments in primary care (PC) and PC-like settings for autism spectrum disorder (ASD).

Mixed prevalence rates of co-occurring psychiatric and neurodevelopmental conditions have been reported in children diagnosed with an autism spectrum disorder (ASD). ASD diagnoses remain fairly stable within a continuum, but some do not meet criteria for an ASD diagnosis years after initial diagnosis.

Co-occurring neurodevelopmental and psychiatric conditions may explain, in part, why the diagnosis of an ASD may change with age. (Read the full article)

The number of individuals diagnosed with autism spectrum disorders (ASDs) continues to increase in the United States and other developed countries. Most prevalence estimates indicate that ASD is diagnosed less commonly in Hispanic individuals compared with non-Hispanic (NH) white populations.

Prevalence of ASD in Arizona’s population-based cohort is higher than reported previously. Prevalence in the Hispanic population and NH white population increased significantly over time, with a significant decrease in the gap between Hispanic and NH white prevalence. (Read the full article)

Although several randomized trials have examined the efficacy of serotonin receptor inhibitors in the treatment of repetitive behaviors, there still remains clinical uncertainty as to whether these agents are effective in treating such behaviors in children and adults with autism spectrum disorders.

The goal of this meta-analysis was to examine randomized trials of serotonin receptor inhibitors for treating repetitive behaviors in autism spectrum disorders. Although a small but significant effect of these agents was observed, this effect is likely due to the selective publication of trial results. (Read the full article)

Previous research has identified low rates of employment and postsecondary education for youth with autism, but generalizability has been limited by small samples.

Using national data, the authors of this study found that youth with autism are at high risk for no postsecondary education or employment, especially in the first 2 years after high school. Findings highlight the need for improved transition planning. (Read the full article)

Prevalence estimates for neurologic and neurodevelopmental disorders in children vary widely, and there is uncertainty as to what extent the individual disorders overlap. Most previous prevalence studies have been based on survey data and not on specialist-confirmed diagnoses.

This study used nationwide register data to determine the proportions of Norwegian children diagnosed with autism spectrum disorder, attention-deficit/hyperactivity disorder, epilepsy, and cerebral palsy and to study how the disorders overlap. All diagnoses were specialist-confirmed. (Read the full article)

Anecdotal accounts that suggest elopement behavior occurs in children with autism spectrum disorders (ASDs), that injuries and fatalities can result, and that associated family burden and stress are substantial. However, there has been little research characterizing the phenomenon or its frequency.

Nearly half of children with an ASD elope, and more than half of these "go missing." Elopement is associated with autism severity, and is often goal-directed. Addressing elopement behavior is an important aspect of intervention for many individuals with ASDs. (Read the full article)

Health care transition services assist youth with special health care needs (YSHCN) in transitioning to adult care without gaps in services or health insurance coverage. Less than half of YSHCN receive anticipatory assistance in this transition; receipt of these services for youth with autism spectrum disorder is unknown.

Youth with autism spectrum disorder receive transition services half as often as youth with special health care needs. Quality of health care is associated with increased receipt of health care transition services. Presence of comorbid conditions decreased receipt of transition services. (Read the full article)

Prenatal alcohol exposure causes a continuum of effects. The most severe phenotype, fetal alcohol syndrome, involves facial dysmorphism, growth deficits, and neurocognitive problems. The classic facial characteristics include short palpebral fissures, smooth philtrum, and thin upper vermillion.

This study develops novel strategies to help detect facial dysmorphism across the fetal alcohol spectrum, especially in children with heavy alcohol exposure but without classic facial characteristics. The methods show potential for identifying which of these children are cognitively affected. (Read the full article)

Children with autism spectrum disorder (ASD) and those with ADHD are at risk for problematic video game use. However, group differences in media use or in the factors associated with problematic video game use have not been studied.

Boys with ASD and ADHD demonstrated greater problematic video game use than did boys with typical development. Inattention was uniquely associated with problematic use for both groups, and role-playing game genre was associated with problematic use among the ASD group only. (Read the full article)

Latino children are diagnosed with autism spectrum disorders (ASDs) less often and later than white children. Primary care pediatricians (PCPs) may play an important role in early ASD identification for Latinos.

PCPs find it more difficult to assess for ASDs in Latinos with Spanish primary language, view Latino parents as less knowledgeable about ASDs, and experience frequent barriers to ASD diagnosis in Latino patients. Many PCPs do not offer recommended screenings in Spanish. (Read the full article)

Psychotropic use is common and increasing in children with mental disorders but little is known about the long-term patterns of psychotropic use and polypharmacy among commercially insured children with autism spectrum disorders.

Among 33 565 children with autism spectrum disorders, 64% used psychotropic medications and 35% had evidence of polypharmacy. Older children and those who had seizures, attention-deficit disorders, anxiety, bipolar disorder, or depression had increased risk of psychotropic use and polypharmacy. (Read the full article)

Previous studies have found links between prepregnancy BMI and/or pregnancy weight gain and autism spectrum disorders (ASD) risk. Several contributing factors to BMI and pregnancy weight gain (ie, prematurity, advanced maternal age, parental education, and parity) overlap with established ASD risk factors.

This study identifies an association between ASD risk and prenatal weight gain, but not prepregnancy BMI, and accounts for important confounding variables excluded in previous analyses. It provides the first within-mother comparison of these factors by including unaffected sibling controls. (Read the full article)

Recent guidelines for the management of childhood pneumonia recommend narrow-spectrum antimicrobial agents (eg, ampicillin) for most children; however, few studies have directly compared the effectiveness of narrow-spectrum agents to the broader spectrum third-generation cephalosporins commonly used among children hospitalized with pneumonia.

By using data from 43 children’s hospitals in the United States, we demonstrate equivalent outcomes and costs for children hospitalized with pneumonia and treated empirically with either narrow- (ampicillin/penicillin) or broad-spectrum (ceftriaxone/cefotaxime) antimicrobial therapy. (Read the full article)

NF1 is the commonest single-gene neurodevelopmental disorder with known neurobiology and developmental impact on attention and cognition. Its impact on social functioning is described but poorly understood, with no population-based study of autism spectrum disorder (ASD) prevalence in the disorder.

This epidemiological study shows high prevalence of 25% ASD in NF1 not explained by learning difficulties. ASD should be considered during clinical practice with NF1. Further research into NF1 as a single-gene model of ASD is warranted. (Read the full article)

Children with autism spectrum disorders (ASD) or attention-deficit/hyperactivity disorder (ADHD) are at increased risk for sleep disturbances and excessive media use. However, the relationship between media use and sleep in children with ASD or ADHD has not been studied.

In-room access to screen-based media and video game hours were associated with less sleep among boys with ASD. The relationships between media use and sleep were much more pronounced among boys with ASD than among boys with ADHD or typical development. (Read the full article)

Individuals with autism spectrum disorders have a higher comorbidity burden than the general pediatric population, including higher rates of seizures, psychiatric illness, and gastrointestinal disorders.

Comorbidities do not occur evenly. Our clustering analysis reveals subgroups characterized by seizure, psychiatric disorders, and complex multisystem disorders including auditory and gastrointestinal disorders. Correlations between seizure, psychiatric disorders, and gastrointestinal disorders are validated on a sample from a second hospital. (Read the full article)

Previous analyses have documented increased health care costs for children with autism spectrum disorders but have not provided comprehensive estimates of the total economic burden.

There are substantial additional costs associated with caring for children with autism spectrum disorders, amounting to >$17 000 per child annually. Costs accrued outside of the health care system account for the majority of the financial burden. (Read the full article)

Maternal prepregnancy obesity is associated with an increased risk of neurodevelopmental disorders in children, but previous studies have not taken paternal obesity into account. This has precluded differentiation between the effects of intrauterine exposures and potential genetic associations.

Robust associations were demonstrated between paternal obesity and the risk of autistic disorder and Asperger disorder in children. This study is the first to implicate paternal obesity as a risk factor for autism, and replication is warranted. (Read the full article)

Serotonin is critical in early brain development, creating concerns regarding prenatal exposure to factors influencing serotonin levels, like selective serotonin reuptake inhibitors (SSRIs). Prenatal SSRI use was recently associated with autism; however, its association with other developmental delays is unclear.

This population-based case-control study in young children provides evidence that prenatal SSRI use may be a risk factor for autism and other developmental delays. However, underlying depression and its genetic underpinnings may be a confounder. (Read the full article)

Autism prevalence is reported to be highest among non-Hispanic white children, lower in Hispanic and African American/black children, and highly variable in Asian/Pacific Islanders. More comorbid intellectual disability and delays in expressive language have been observed among Hispanic and African American children.

Maternal nativity is a risk factor for childhood autism in US populations. We observed higher risk of severe autism phenotypes in children of foreign-born black, Central/South American, Filipino, and Vietnamese mothers and US-born African Americans and Hispanics compared with US-born whites. (Read the full article)

Most studies of fetal alcohol syndrome and fetal alcohol spectrum disorders (FASD) prevalence in the general population of the United States have been carried out using passive methods (surveillance or clinic-based studies), which underestimate rates of FASD.

Using active case ascertainment methods among children in a representative middle class community, rates of fetal alcohol syndrome and total FASD are found to be substantially higher than most often cited estimates for the general US population. (Read the full article)

Preterm birth and faster infant growth have been identified as independent risk factors for autism-spectrum disorders (ASD). However, associations between prematurity and ASD-related traits as a continuum and effects of infant growth among those born preterm are still little studied.

VLBW young adults reported higher levels of ASD-related traits, particularly traits related to poorer social skills. Within the VLBW group, faster growth in weight, height, and head circumference from birth to term was associated with lower levels of ASD-related traits. (Read the full article)

Many studies have suggested that autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are commonly co-occuring neurodevelopmental conditions.

In children with co-occurring ASD and ADHD, an initial ADHD diagnosis may be associated with delayed ASD diagnosis and a higher likelihood of ASD diagnosis older than 6 years of age. Clinicians should consider ASD when evaluating young children presenting with ADHD symptoms. (Read the full article)

Both short and long interpregnancy intervals are associated with increased risk of autism in second-born children. However, it is not known if the association is explained by unfavorable birth outcomes of the previous siblings.

Both short and long interpregnancy intervals increase risk of autism in second-born children independently of previous siblings being born premature, having low birth weight, or being born by cesarean delivery and independently of maternal antidepressant use 3 months before pregnancy. (Read the full article)

QPX7728 is a new ultra-broad-spectrum inhibitor of serine and metallo beta-lactamases from a class of cyclic boronates that gave rise to vaborbactam. The spectrum and mechanism of beta-lactamase inhibition by QPX7728 were assessed using purified enzymes from all molecular classes. QPX7728 inhibits class A ESBLs (IC₅₀ range 1-3 nM) and carbapenemases such as KPC (IC₅₀ 2.9±0.4 nM) as well as class C P99 (IC₅₀ of 22±8 nM) with a potency that is comparable or higher than recently FDA approved BLIs avibactam, relebactam and vaborbactam. Unlike those other BLIs, QPX7728 is also a potent inhibitor of class D carbapenemases such as OXA-48 from Enterobacteriaceae and OXA enzymes from A. baumannii (OXA-23/24/58, IC₅₀ range 1-2 nM) as well as MBLs such as NDM-1 (IC₅₀ 55±25 nM), VIM-1 (IC₅₀ 14±4 nM) and IMP-1 (IC₅₀ 610±70 nM). Inhibition of serine enzymes by QPX7728 is associated with progressive inactivation with a high efficiency k₂/K ranging from of 6.3 x 10⁴ (for P99) to 9.9 x 10⁵ M^-1 s^-1 (for OXA-23). This inhibition is reversible with variable stability of the QPX7728-beta-lactamase complexes with target residence time ranging from minutes to several hours: 5-20 minutes for OXA carbapenemases from A. baumanii, ~50 minutes for OXA-48 and 2-3 hours for KPC and CTX-M-15. QPX7728 inhibited all tested serine enzymes at 1:1 molar ratio. Metallo-beta-lactamases NDM, VIM, and IMP were inhibited by a competitive mechanism with fast-on-fast-off kinetics, with K_is of 7.5±2.1 nM, 32±14 nM and 240±30 nM for VIM-1, NDM-1 and IMP-1, respectively. QPX7728 ultra-broad-spectrum of BLI inhibition combined with its high potency enables combinations with multiple different beta-lactam antibiotics.

QPX7728 is an ultra-broad-spectrum boronic acid beta-lactamase inhibitor with potent inhibition of key serine and metallo beta-lactamases observed in biochemical assays. Microbiological studies using characterized strains were used to provide a comprehensive characterization of the spectrum of beta-lactamase inhibition by QPX7728. The MIC of multiple IV only (ceftazidime, piperacillin, cefepime, ceftolozane and meropenem) and orally bioavailable (ceftibuten, cefpodoxime, tebipenem) antibiotics alone and in combination with QPX7728 (4 μg/ml), as well as comparator agents, were determined against the panels of laboratory strains of P. aeruginosa and K. pneumoniae expressing over 55 diverse serine and metallo beta-lactamases. QPX7728 significantly enhanced the potency of antibiotics against the strains expressing Class A extended spectrum beta-lactamases (CTX-M, SHV, TEM, VEB, PER) and carbapenemases (KPC, SME, NMC-A, BKC-1), consistent with beta-lactamase inhibition demonstrated in biochemical assays. It also inhibits both plasmidic (CMY, FOX, MIR, DHA) and chromosomally encoded (P99, PDC, ADC) Class C beta-lactamases and Class D enzymes including carbapenemases such as OXA-48 from Enterobacteriaceae and OXA enzymes from Acinetobacter baumannii (OXA-23/24/72/58). QPX7728 is also a potent inhibitor of many class B metallo beta-lactamases (NDM, VIM, CcrA1, IMP, GIM but not SPM or L1). Addition of QPX7728 (4 μg/ml) reduced the MICs in a majority of strains to the level observed for the vector alone control, indicative of complete beta-lactamase inhibition. The ultra-broad-spectrum beta-lactamase inhibition profile makes QPX7728 a viable candidate for further development.

QPX7728 is an ultra-broad-spectrum boronic acid beta-lactamase inhibitor that demonstrates inhibition of key serine and metallo beta-lactamases at a nano molar range in biochemical assays with purified enzymes. The broad-spectrum inhibitory activity of QPX7728 observed in biochemical experiments translates into enhancement of the potency of many beta-lactams against strains of target pathogens producing beta-lactamases. The impact of bacterial efflux and permeability on inhibitory potency were determined using isogenic panels of KPC-3 producing isogenic strains of K. pneumoniae and P. aeruginosa and OXA-23-producing strains of A. baumannii with various combinations of efflux and porin mutations. QPX7728 was minimally affected by multi-drug resistance efflux pumps in either Enterobacteriaceae, or in non-fermenters such as P. aeruginosa or A. baumannii. In P. aeruginosa, the potency of QPX7728 was further enhanced when the outer membrane is permeabilized. The potency of QPX7728 in P. aeruginosa is not affected by inactivation of the carbapenem porin OprD. While changes in OmpK36 (but not OmpK35) reduced the potency of QPX7728 (8-16-fold), QPX7728 (4 μg/ml) nevertheless completely reversed KPC-mediated meropenem resistance in strains with porin mutations, consistent with a lesser effect of these mutations on the potency of QPX7728 compared to other agents. The ultra-broad-spectrum beta-lactamase inhibition profile combined with enhancement of the activity of multiple beta-lactam antibiotics with varying sensitivity to the intrinsic resistance mechanisms of efflux and permeability indicate QPX7728 is a useful inhibitor for use with multiple beta-lactam antibiotics.

Klebsiella pneumoniae that produce extended spectrum beta lactamases (ESBLs) are a persistent public health threat. There are relatively few therapeutic options and there is undue reliance on carbapenems. Alternative therapeutic options are urgently required. A combination of cefepime and the novel beta lactamase inhibitor enmetazobactam is being developed for treatment of serious infections caused by ESBL-producing organisms. The pharmacokinetics-pharmacodynamics (PK-PD) of cefepime-enmetazobactam against ESBL-producing K. pneumoniae was studied in a neutropenic murine pneumonia model. Dose ranging studies were performed. Dose fractionation studies were performed to define the relevant PD index for the inhibitor. The partitioning of cefepime and enmetazobactam into the lung was determined by comparing area under the concentration time curve (AUC) in plasma and epithelial lining fluid. The magnitude of drug exposure for cefepime-enmetazobactam required for logarithmic killing in the lung was defined using 3 ESBL-producing strains. Cefepime 100 mg/kg q8h i.v. had minimal antimicrobial effect. When this background regimen of cefepime was combined with enmetazobactam half-maximal effect was induced with enmetazobactam 4.71 mg/kg q8h i.v. The dose fractionation study suggest both fT>threshold and fAUC:MIC are potentially relevant PD indices. The AUC_ELF:AUC_plasma for cefepime and enmetazobactam was 73.4% and 61.5%, respectively. A ≥2-log kill in the lung was achieved with a plasma and ELF cefepime fT>MIC of ≥20% and enmetazobactam fT>2 mg/L of ≥20% of the dosing interval. These data and analyses provide the underpinning evidence for the combined use of cefepime and enmetazobactam for nosocomial pneumonia.

A total of 2,283 Salmonella spp. isolates were recovered from 18,334 samples including patients with diarrhea, food of animal origin and pets across 5 provinces of China. The highest prevalence of Salmonella spp. was detected in chicken meats (39.3%, 486/1,237). Fifteen serogroups and 66 serovars were identified, with Typhimurium and Enteritidis being the most dominant. Most (85.5%, 1,952/2,283) isolates exhibited resistant to ≥ 1 antimicrobial and 56.4% were multi-drug resistant (MDR). A total of 222 isolates harbored extended-spectrum β-lactamases (ESBLs), 200 of which were CTX-M-type that were mostly detected from chicken meat and turtle fecal. Overall, eight bla_CTX-M genes were identified, with bla_CTX-M-65, bla_CTX-M-123, bla_CTX-M-14, bla_CTX-M-79, and bla_CTX-M-130 being the most prevalent. Totally, 166 of the 222 ESBL-producing isolates had amino acid substitutions in GyrA (S83Y, S83F, D87G, D87N, and D87Y) and ParC (and S80I), whilst the PMQR-encoding genes oqxA/B, qepA, and qnrB/S were detected in almost all isolates. Of the fifteen sequence types (STs) identified in the 222 ESBLs, ST17, ST11, ST34, and ST26 ranked among the top 5 in the number of isolates. Our study revealed considerable serovars diversity, high prevalence of co-occurrence of MDR determinants, including CTX-M-type ESBLs, QRDRs mutations and PMQR genes. This is the first report of CTX-M-130 Salmonella spp. from patients with diarrhea and QRDRs mutations from turtle fecal samples. Our study emphasizes the importance of actions, both in the health care settings and in the veterinary medicine sector, to control the dissemination of MDR, especially the CTX-M Salmonella spp. isolates.

Seasonal and pandemic influenza causes 650,000 deaths annually in the world. The emergence of drug-resistance to specific anti-influenza drugs such as oseltamivir and baloxavir marboxil highlights the urgency of novel anti-influenza chemical entity discovery. In this study, we report a series of novel thiazolides derived from an FDA-approved drug nitazoxanide with antiviral activity against influenza and a broad range of viruses. The preferred candidates 4a and 4d showed significantly enhanced anti-influenza potentials with 10-fold improvement, compared with nitazoxanide, and were effective against a variety of influenza subtypes including oseltamivir-resistant strains. Notably, the combination using of compounds 4a/4d and oseltamivir carboxylate or zanamivir displayed synergistic antiviral effect against oseltamivir-resistant strain. Mode of action analysis demonstrated that compounds 4a/4d acted at the late phase of viral infection cycle through inhibiting viral RNA transcription and replication. Further experiments showed that treatment with compounds 4a/4d significantly inhibited influenza virus infection in human lung organoids, suggesting the druggability of the novel thiazolides. In-depth transcriptome analysis revealed a series of up-regulated cellular genes that may contribute to the antiviral activities of 4a/4d. Together, our study pointed the optimization direction of nitazoxanide as anti-influenza drug, and discovered two novel-structured candidates 4a/4d with relatively broad-spectrum antiviral potential.

While for the latter the companies, including Vodafone Idea, have sought the facility to pay in installments spread over some 20 years which is currently before the SC, there's been no such demand for current payments.

Objective

To assess possible adverse effects on breastfed infants of mothers receiving monoclonal antibodies (MAbs) during pregnancy and/or lactation.

Klebsiella species are problematic pathogens in neonatal units and may cause outbreaks, for which the sources of transmission may be challenging to elucidate. We describe the use of whole-genome sequencing (WGS) to investigate environmental sources of transmission during an outbreak of extended-spectrum-β-lactamase (ESBL)-producing Klebsiella michiganensis colonizing neonates. Ceftriaxone-resistant Klebsiella spp. isolated from neonates (or their mothers) and the hospital environment were included. Short-read sequencing (Illumina) and long-read sequencing (MinION; Oxford Nanopore Technologies) were used to confirm species taxonomy, to identify antimicrobial resistance genes, and to determine phylogenetic relationships using single-nucleotide polymorphism profiling. A total of 21 organisms (10 patient-derived isolates and 11 environmental isolates) were sequenced. Standard laboratory methods identified the outbreak strain as an ESBL-producing Klebsiella oxytoca, but taxonomic assignment from WGS data suggested closer identity to Klebsiella michiganensis. Strains isolated from multiple detergent-dispensing bottles were either identical or closely related by single-nucleotide polymorphism comparison. Detergent bottles contaminated by K. michiganensis had been used for washing milk expression equipment. No new cases were identified once the detergent bottles were removed. Environmental reservoirs may be an important source in outbreaks of multidrug-resistant organisms. WGS, in conjunction with traditional epidemiological investigation, can be instrumental in revealing routes of transmission and guiding infection control responses.

The IR Biotyper is a new automated typing system based on Fourier-transform infrared (FT-IR) spectroscopy that gives results within 4 h. We aimed (i) to use the IR Biotyper to retrospectively analyze an outbreak of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-KP) in a neonatal intensive care unit and to compare results to BOX-PCR and whole-genome sequencing (WGS) results as the gold standard and (ii) to assess how the cutoff values used to define clusters affect the discriminatory power of the IR Biotyper. The sample consisted of 18 isolates from 14 patients. Specimens were analyzed in the IR Biotyper using the default analysis settings, and spectra were analyzed using OPUS 7.5 software. The software contains a feature that automatically proposes a cutoff value to define clusters; the cutoff value defines up to which distance the spectra are considered to be in the same cluster. Based on FT-IR, the outbreak represented 1 dominant clone, 1 secondary clone, and several unrelated clones. FT-IR results, using the cutoff value generated by the accompanying software after 4 replicates, were concordant with WGS for all but 1 isolate. BOX-PCR was underdiscriminatory compared to the other two methods. Using the cutoff value generated after 12 replicates, the results of FT-IR and WGS were completely concordant. The IR Biotyper can achieve the same typeability and discriminatory power as genome-based methods. However, to attain this high performance requires either previous, strain-dependent knowledge about the optimal technical parameters to be used or validation by a second method.

Tilorone is a 50-year-old synthetic small-molecule compound with antiviral activity that is proposed to induce interferon after oral administration. This drug is used as a broad-spectrum antiviral in several countries of the Russian Federation. We have recently described activity in vitro and in vivo against the Ebola virus. After a broad screening of additional viruses, we now describe in vitro activity against Chikungunya virus (CHIK) and Middle Eastern respiratory syndrome coronavirus (MERS-CoV).

A fosfomycin-resistant and carbapenemase (OXA-48)-producing Klebsiella pneumoniae isolate was recovered, and whole-genome sequencing revealed ISEcp1-bla_CTX-M-14b tandemly inserted upstream of the chromosomally encoded lysR-fosA locus. Quantitative evaluation of the expression of lysR and fosA genes showed that this insertion brought a strong hybrid promoter leading to overexpression of the fosA gene, resulting in fosfomycin resistance. This work showed the concomitant acquisition of resistance to broad-spectrum cephalosporins and fosfomycin due to a single genetic event.

BACKGROUND AND PURPOSE:

In the medicolegal literature, notching of the corpus callosum has been reported to be associated with fetal alcohol spectrum disorders. Our purpose was to analyze the prevalence of notching of the corpus callosum in a fetal alcohol spectrum disorders group and a healthy population to determine whether notching occurs with increased frequency in the fetal alcohol spectrum disorders population.

The Department of Justice announced today that it will require Verizon and four of the nation’s largest cable companies—Comcast, Time Warner Cable, Bright House Networks and Cox Communications—to make changes to a series of agreements concerning both the sale of bundled wireless and wireline services, and the formation of a technology research joint venture. The department said that, if left unaltered, the agreements would have harmed competition by diminishing the companies’ incentive to compete, resulting in higher prices and lower quality for consumers.