Do pediatricians manage influenza differently than internists?

<p>Abstract</p> <p>Background</p> <p>Little is known about how pediatricians or internists manage influenza symptoms. Recent guidelines on antiviral prescribing by the Centers for Disease Control and Prevention (CDC) make almost no distinction between adults and children. Our objective was to describe how pediatricians in two large academic medical institutions manage influenza and compare them to internists.</p> <p>Methods</p> <p>At the end of the 2003–4 influenza season, we conducted a cross sectional on-line survey of physician knowledge, attitudes and practices regarding rapid diagnostic testing and use of antiviral therapy for influenza at two large academic medical centers, one in Massachusetts and the other in Texas. We collected data on self-reported demographics, test use, prescribing practices, and beliefs about influenza and anti-influenza drugs.</p> <p>Results</p> <p>A total of 107 pediatricians and 103 internists completed the survey (response rate of 53%). Compared to internists, pediatricians were more likely to perform rapid testing (74% vs. 47%, p < 0.0001), to use amantadine (88% vs. 48%, p < 0.0001), to restrict their prescribing to high-risk patients (86% vs. 53%, p < 0.0001), and to believe that antiviral therapy could decrease mortality (38% vs. 22%, p = 0.01). Other beliefs about antiviral therapy did not differ statistically between the specialties. Internists were more likely to be unfamiliar with rapid testing or not to have it available.</p> <p>Conclusion</p> <p>Pediatricians and internists manage influenza differently. Evidence-based guidelines addressing the specific concerns of each group would be helpful.</p

Assessment of whole genome amplification-induced bias through high-throughput, massively parallel whole genome sequencing

BACKGROUND: Whole genome amplification is an increasingly common technique through which minute amounts of DNA can be multiplied to generate quantities suitable for genetic testing and analysis. Questions of amplification-induced error and template bias generated by these methods have previously been addressed through either small scale (SNPs) or large scale (CGH array, FISH) methodologies. Here we utilized whole genome sequencing to assess amplification-induced bias in both coding and non-coding regions of two bacterial genomes. Halobacterium species NRC-1 DNA and Campylobacter jejuni were amplified by several common, commercially available protocols: multiple displacement amplification, primer extension pre-amplification and degenerate oligonucleotide primed PCR. The amplification-induced bias of each method was assessed by sequencing both genomes in their entirety using the 454 Sequencing System technology and comparing the results with those obtained from unamplified controls. RESULTS: All amplification methodologies induced statistically significant bias relative to the unamplified control. For the Halobacterium species NRC-1 genome, assessed at 100 base resolution, the D-statistics from GenomiPhi-amplified material were 119 times greater than those from unamplified material, 164.0 times greater for Repli-G, 165.0 times greater for PEP-PCR and 252.0 times greater than the unamplified controls for DOP-PCR. For Campylobacter jejuni, also analyzed at 100 base resolution, the D-statistics from GenomiPhi-amplified material were 15 times greater than those from unamplified material, 19.8 times greater for Repli-G, 61.8 times greater for PEP-PCR and 220.5 times greater than the unamplified controls for DOP-PCR. CONCLUSION: Of the amplification methodologies examined in this paper, the multiple displacement amplification products generated the least bias, and produced significantly higher yields of amplified DNA

Derivation and external validation of a prediction model for pneumococcal urinary antigen test positivity in patients with community-acquired pneumonia

Abstract Objective: Derive and externally validate a prediction model for pneumococcal urinary antigen test (pUAT) positivity. Methods: Retrospective cohort study of adults admitted with community-acquired pneumonia (CAP) to 177 U.S. hospitals in the Premier Database (derivation and internal validation samples) or 12 Cleveland Clinic hospitals (external validation sample). We utilized multivariable logistic regression to predict pUAT positivity in the derivation dataset, followed by model performance evaluation in both validation datasets. Potential predictors included demographics, comorbidities, clinical findings, and markers of disease severity. Results: Of 198,130 Premier patients admitted with CAP, 27,970 (14.1%) underwent pUAT; 1962 (7.0%) tested positive. The strongest predictors of pUAT positivity were history of pneumococcal infection in the previous year (OR 6.99, 95% CI 4.27–11.46), severe CAP on admission (OR 1.76, 95% CI 1.56–1.98), substance abuse (OR 1.57, 95% CI 1.27–1.93), smoking (OR 1.23, 95% CI 1.09–1.39), and hyponatremia (OR 1.35, 95% CI 1.17–1.55). Negative predictors included IV antibiotic use in past year (OR 0.65, 95% CI 0.52–0.82), congestive heart failure (OR 0.72, 95% CI 0.63–0.83), obesity (OR 0.71, 95% CI 0.60–0.85), and admission from skilled nursing facility (OR 0.60, 95% CI 0.45–0.78). Model c-statistics were 0.60 and 0.67 in the internal and external validation cohorts, respectively. Compared to guideline-recommended testing of severe CAP patients, our model would have detected 23% more cases with 5% fewer tests. Conclusion: Readily available data can identify patients most likely to have a positive pUAT. Our model could be incorporated into automated clinical decision support to improve test efficiency and antimicrobial stewardship

Do Physicians Underrecognize Obesity?

Objectives: A physician&apos;s advice is among the strongest predictors of efforts toward weight management made by obese patients, yet only a minority receives such advice. One contributor could be the physician&apos;s failure to recognize true obesity. The objectives of this study were to assess physicians&apos; ability to recognize obesity and to identify factors associated with recognition and documentation of obesity. Methods: Internal medicine residents and attending physicians at three academic urban primary care clinics and their adult patients participated in a study using recognition and documentation of patient obesity as the main measures. Results: A total of 52 physicians completed weight assessments for 400 patients. The mean patient age was 51 years, 56% were women, 77% were Hispanic, and 67% had one or more obesity-related comorbidity. There were 192 (48%) patients, of whom 66% were correctly identified by physicians as being obese, 86% of those with a body mass index (BMI) Q35, but only 49% of those with a BMI of 30 to 34.9 (P G 0.0001). Fewer obese Hispanic patients were identified than were non-Hispanic patients (62% vs 76%; P = 0.03). No physician characteristics were significantly associated with recognition of obesity. Physicians documented obesity as a problem for 51% of patients. Attending physicians documented obesity more frequently than did residents (64% vs 43%, odds ratio 2.5, 95% confidence interval 1.3Y4.6) and normal-weight physicians documented obesity more frequently than overweight physicians (58% vs 41%, odds ratio 2.0, 95% confidence interval 1.0Y4.0). Documentation was more common for patients with a BMI Q35 and for non-Hispanics. Documentation was not more common for patients with obesity-related comorbidities. Conclusions: Physicians have difficulty recognizing obesity unless patients&apos; BMI is Q35. Training physicians to recognize true obesity may increase rates of documentation, a first step toward treatment

Stellar population gradients in the cores of nearby field E+A galaxies

We have selected a sample of local E+A galaxies from the Sloan Digital Sky Survey (SDSS) Data Release 7 for follow up integral field spectroscopy with the Wide Field Spectrograph (WiFeS) on the ANU 2.3-m telescope. The sample was selected using the Halpha line in place of the [OII]3727 line as the indicator of on-going star formation (or lack thereof). This allowed us to select a lower redshift sample of galaxies than available in the literature since the [OII]3727 falls off the blue end of the wavelength coverage in the SDSS for the very lowest redshift objects. This low redshift selection means that the galaxies have a large angular to physical scale which allows us to resolve the central ~1kpc region of the galaxies; the region where stellar population gradients are expected. Such observations have been difficult to make using other higher redshift samples because even at redshifts z~0.1 the angular to physical scale is similar to the resolution provided by ground based seeing. Our integral field spectroscopy has enabled us to make the first robust detections of Balmer line gradients in the centres of E+A galaxies. Six out of our sample of seven, and all the galaxies with regular morphologies, are observed to have compact and centrally-concentrated Balmer line absorption. This is evidence for compact young cores and stellar population gradients which are predicted from models of mergers and tidal interactions which funnel gas into the galaxy core. Given the generally isolated nature of our sample this argues for the galaxies being seen in the late stage of a merger where the progenitors have already coalesced.Comment: accepted to MNRA

NGDEEP Epoch 1: Spatially Resolved Hα\alpha Observations of Disk and Bulge Growth in Star-Forming Galaxies at z∼z \sim 0.6-2.2 from JWST NIRISS Slitless Spectroscopy

We study the H$\alpha$ equivalent width, EW(H$\alpha$), maps of 19 galaxies at $0.6 < z < 2.2$ in the Hubble Ultra Deep Field (HUDF) derived from NIRISS slitless spectroscopy as part of the Next Generation Deep Extragalactic Exploratory Public (NGDEEP) Survey. Our galaxies mostly lie on the star-formation main sequence with a stellar mass range of $\mathrm{10^9 - 10^{11} M_\odot}$, and are therefore characteristic of "typical" star-forming galaxies at these redshifts. Leveraging deep HST and JWST broad-band images, spanning 0.4-4 $\mu$m, we perform spatially-resolved fitting of the spectral energy distributions (SEDs) for these galaxies and construct specific star formation rate (sSFR) and stellar-mass-weighted age maps. We compare these to the EW(H$\alpha$) maps with a spatial resolution of $\sim$1 kpc. The pixel-to-pixel EW(H$\alpha$) increases with increasing sSFR and with decreasing age, with the average trend slightly different from the relations derived from integrated fluxes of galaxies from the literature. Quantifying the radial profiles of EW(H$\alpha$), sSFR, and age, the majority (84%) of galaxies show positive EW(H$\alpha$) gradients, positive sSFR gradients, and negative age gradients, in line with the the inside-out quenching scenario. A few galaxies (16%) show inverse (and flat) trends possibly due to merging or starbursts. Comparing the distributions of EW(H$\alpha$) and sSFR to the star formation history models as a function of galactocentric radius, the central region of galaxies (e.g., their bulges) have experienced, at least one, rapid star-formation episodes, which leads to the formation of bulge, while their outer regions (e.g., disks) grow in a more steady-state. These results demonstrate the ability to study resolved star formation in distant galaxies with JWST NIRISS.Comment: 22 pages, 11 figure

Comprehensive resequence analysis of a 97 kb region of chromosome 10q11.2 containing the MSMB gene associated with prostate cancer

Genome-wide association studies of prostate cancer have identified single nucleotide polymorphism (SNP) markers in a region of chromosome 10q11.2, harboring the microseminoprotein-β (MSMB) gene. Both the gene product of MSMB, the prostate secretory protein 94 (PSP94) and its binding protein (PSPBP), have been previously investigated as serum biomarkers for prostate cancer progression. Recent functional work has shown that different alleles of the significantly associated SNP in the promoter of MSMB found to be associated with prostate cancer risk, rs10993994, can influence its expression in tumors and in vitro studies. Since it is plausible that additional variants in this region contribute to the risk of prostate cancer, we have used next-generation sequencing technology to resequence a ~97-kb region that includes the area surrounding MSMB (chr10: 51,168,025–51,265,101) in 36 prostate cancer cases, 26 controls of European origin, and 8 unrelated CEPH individuals in order to identify additional variants to investigate in functional studies. We identified 241 novel polymorphisms within this region, including 142 in the 51-kb block of linkage disequilibrium (LD) that contains rs10993994 and the proximal promoter of MSMB. No sites were observed to be polymorphic within the exons of MSMB

Synergistic TLR2/6 and TLR9 Activation Protects Mice against Lethal Influenza Pneumonia

Lower respiratory tract infections caused by influenza A continue to exact unacceptable worldwide mortality, and recent epidemics have emphasized the importance of preventative and containment strategies. We have previously reported that induction of the lungs' intrinsic defenses by aerosolized treatments can protect mice against otherwise lethal challenges with influenza A virus. More recently, we identified a combination of Toll like receptor (TLR) agonists that can be aerosolized to protect mice against bacterial pneumonia. Here, we tested whether this combination of synthetic TLR agonists could enhance the survival of mice infected with influenza A/HK/8/68 (H3N2) or A/California/04/2009 (H1N1) influenza A viruses. We report that the TLR treatment enhanced survival whether given before or after the infectious challenge, and that protection tended to correlate with reductions in viral titer 4 d after infection. Surprisingly, protection was not associated with induction of interferon gene expression. Together, these studies suggest that synergistic TLR interactions can protect against influenza virus infections by mechanisms that may provide the basis for novel therapeutics

Label-Free Optical Detection of Biomolecular Translocation through Nanopore Arrays

In recent years, nanopores have emerged as exceptionally promising single-molecule sensors due to their ability to detect biomolecules at subfemtomole levels in a label-free manner. Development of a high-throughput nanopore-based biosensor requires multiplexing of nanopore measurements. Electrical detection, however, poses a challenge, as each nanopore circuit must be electrically independent, which requires complex nanofluidics and embedded electrodes. Here, we present an optical method for simultaneous measurements of the ionic current across an array of solid-state nanopores, requiring no additional fabrication steps. Proof-of-principle experiments are conducted that show simultaneous optical detection and characterization of ssDNA and dsDNA using an array of pores. Through a comparison with electrical measurements, we show that optical measurements are capable of accessing equivalent transmembrane current information