Influenza vaccine coverage is low, and young children in need of 2 doses in a given season are at particular risk, with less than half receiving both doses. Text message vaccine reminders increase receipt of first dose of influenza vaccine.

Little is known about what types of text message reminders are most effective, including embedding educational information. We demonstrate that text message reminders increase timely receipt of the second dose of influenza vaccine and embedding health literacy information improves effectiveness. (Read the full article)

Frequency of influenza vaccination is low, partially because of missed opportunities to vaccinate. Barriers to implementing successful influenza vaccination reminders in the electronic health record include alert fatigue and incomplete vaccination information due to scattered records.

A noninterruptive, immunization information system–linked influenza vaccination reminder can increase vaccination late in the winter when fewer vaccine doses are usually administered. Tailoring the reminder to clinicians’ needs can increase its use. (Read the full article)

Previous studies found that 2010–2011 trivalent inactivated influenza vaccine (TIV) and 13-valent pneumococcal conjugate vaccine (PCV13) were associated with statistically significant increased risks of febrile seizures (FS) in the United States.

Estimated FS relative risks after TIV or PCV13 adjusted for DTaP were >1, although not statistically significant and lower than previous estimates. Same-day administration of TIV and PCV13 did not result in more FS compared with separate-day vaccination. (Read the full article)

Education Week reporters Alyson Klein and Sean Cavanagh discuss the races to watch.

To history buffs, the Covid-19 pandemic must seem eerily familiar, says Noah Smith.

I rapporti tra Gheddafi e Déby sono caratterizzati da una certa superficialità, dovuta alle tensioni passate e ai sospetti che nutrono l’uno per l’altro.

Omadacycline is a novel aminomethylcycline with activity against Gram-positive and -negative organisms, including Haemophilus influenzae, which is one of the leading causes of community-acquired bacterial pneumonia (CABP). The evaluation of antimicrobial agents against H. influenzae using standard murine infection models is challenging due to the low pathogenicity of this species in mice. Therefore, 24-hour dose-ranging studies using a one-compartment in vitro infection model were undertaken with the goal of characterizing the magnitude of the ratio of the area under the concentration-time curve (AUC) to the MIC (AUC/MIC ratio) associated with efficacy for a panel of five clinical H. influenzae isolates. These five isolates, which had MIC values of 1 or 2 mg/L, were exposed to omadacycline total-drug epithelial lining fluid (ELF) concentration-time profiles based on those observed in healthy volunteers following intravenous omadacycline administration. Relationships between change in log₁₀ colony forming units (CFU) from baseline at 24 hours and total-drug ELF AUC/MIC ratio for each isolate and the isolates pooled together were evaluated using Hill-type models and non-linear least squares regression. As evidenced by the high coefficient of determination (r²) of 0.88 to 0.98, total-drug ELF AUC/MIC ratio described the data well for each isolate and the isolates pooled together. The median total-drug ELF AUC/MIC ratio associated with net bacterial stasis and 1- and 2-log₁₀ CFU/mL reductions from baseline at 24 hours was 6.91, 8.91, and 11.1, respectively. These data were useful to support the omadacycline dosing regimens selected for the treatment of patients with CABP, as well as susceptibility breakpoints for H. influenzae.

Attention has been paid to H5N6 highly pathogenic avian influenza virus (HPAIV) because of its heavy burden on the poultry industry and human mortality. Since an influenza A virus carrying N6 neuraminidase (NA) has never spread in humans, the potential for H5N6 HPAIV to cause disease in humans and the efficacy of antiviral drugs against the virus need to be urgently assessed. We used non-human primates to elucidate the pathogenesis of H5N6 HPAIV as well as to determine the efficacy of antiviral drugs against the virus. H5N6 HPAIV infection led to high fever in cynomolgus macaques. The lung injury caused by the virus was severe with diffuse alveolar damage and neutrophil infiltration. In addition, an increase in IFN-α showed an inverse correlation with virus titers during the infection process. Oseltamivir was effective for reducing H5N6 HPAIV propagation, and continuous treatment with peramivir reduced virus propagation and severity of symptoms in the early stage. This study also showed the pathologically severe lung injury states in the cynomolgus macaques infected with H5N6 HPAIV, even in those that received early antiviral drug treatments, indicating the need for close monitoring and the need for further studies on the virus pathogenicity and new antiviral therapies.

Baloxavir marboxil, a prodrug of cap-dependent endonuclease inhibitor, baloxavir acid, reduces the time to improvement of influenza symptoms in patients infected with type A or B influenza virus. To characterize its pharmacokinetics, a population pharmacokinetic model for baloxavir acid was developed using 11846 plasma concentration data items from 1827 subjects including 2341 plasma concentration data items from 664 patients at high risk of influenza complications. A three-compartment model with first-order elimination and first-order absorption with lag time well described the plasma concentration data. Body weight and race were found to be the most important factors influencing clearance and volume of distribution. The exposures in high-risk patients were similar to those in otherwise healthy patients, and no pharmacokinetic difference was identified regarding any risk factors for influenza complications.

Exposure-response analyses were performed regarding the time to improvement of symptoms and the reduction in the influenza virus titer in high-risk patients. The analyses suggested that body weight-based dosage, 40 mg for patients weighing < 80 kg and 80 mg for patients weighing ≥ 80 kg, can shorten the time to improvement of influenza symptoms and reduce virus titer for both type A and B influenza virus regardless of the exposure levels of the high-risk patients as well as for the otherwise healthy influenza patients.

The results of our population pharmacokinetic and exposure-response analyses in patients with risk factors of influenza complications should provide useful information on the pharmacokinetic and pharmacodynamic characteristics of baloxavir marboxil and also for the optimization of dose regimens.

Treatment of Mycobacterium avium complex pulmonary disease (MAC-PD) is challenging partly due to high efflux pump expression. Thioridazine might block these efflux pumps. We explore thioridazine's efficacy against M. avium using minimum inhibitory concentrations (MICs), time-kill combination assays, ex vivo macrophage infection assays and efflux assays. Thioridazine is bactericidal against M. avium, inhibits intracellular growth at 2x MIC and blocks ethidium bromide efflux. However, its toxicity and low plasma concentrations, make it unlikely to add efficacy to MAC-PD therapy.

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.

Staphylococcus aureus osteomyelitis is a debilitating infection of bone. Treatment of osteomyelitis is impaired by the propensity of invading bacteria to induce pathologic bone remodeling that may limit antibiotic penetration to the infectious focus. The nonsteroidal anti-inflammatory drug diflunisal was previously identified as an osteoprotective adjunctive therapy for osteomyelitis, based on the ability of this compound to inhibit S. aureus quorum sensing and subsequent quorum-dependent toxin production. When delivered locally during experimental osteomyelitis, diflunisal significantly limits bone destruction without affecting bacterial burdens. However, because diflunisal's "quorum-quenching" activity could theoretically increase antibiotic recalcitrance, it is critically important to evaluate this adjunctive therapy in the context of standard of care antibiotics. The objective of this study is to evaluate the efficacy of vancomycin to treat osteomyelitis during local diflunisal treatment. We first determined that systemic vancomycin effectively reduces bacterial burdens in a murine model of osteomyelitis, and identified a dosing regimen that decreases bacterial burdens without eradicating infection. Using this dosing scheme, we found that vancomycin activity is unaffected by the presence of diflunisal in vitro and in vivo. Similarly, locally-delivered diflunisal still potently inhibits osteoblast cytotoxicity in vitro and bone destruction in vivo in the presence of sub-therapeutic vancomycin. However, we also found that the resorbable polyurethane foams used to deliver diflunisal serve as a nidus for infection. Taken together, these data demonstrate that diflunisal does not significantly impact standard of care antibiotic therapy for S. aureus osteomyelitis, but also highlight potential pitfalls encountered with local drug delivery.

Anidulafungin and micafungin were quantified in cerebrospinal fluid (CSF) of critically ill adults and in cerebral cortex of deceased patients. In CSF, anidulafungin levels (<0.01-0.66 μg/ml) and micafungin levels (<0.01-0.16 μg/ml) were lower than the simultaneous plasma concentrations (0.77-5.07 μg/ml and 1.21-8.70 μg/ml, respectively). In cerebral cortex, anidulafungin and micafungin levels were 0.21-2.34 μg/g and 0.18-2.88 μg/g, respectively. Thus, MIC values of several pathogenic Candida strains exceed concentrations in CSF and in brain.

Many transferable quinolone-resistance mechanisms have been already identified in Gram-negative bacteria. The plasmid-encoded 65 amino-acid long ciprofloxacin-modifying enzyme, namely CrpP, was recently identified in Pseudomonas aeruginosa. We analyzed a collection of 100 clonally-unrelated and multidrug-resistant P. aeruginosa clinical isolates among which 46 (46%) were found positive for crpP-like genes, encoding five CrpP variants conferring variable levels of reduced susceptibility to fluoroquinolones. Those crpP-like genes were chromosomally located, as part of PAGI-like pathogenicity genomic islands.

Manogepix (APX001A) is the active moiety of the novel drug candidate fosmanogepix (APX001). We previously reported the broad-spectrum activity of manogepix but also observed a correlation between increased manogepix and fluconazole MICs. Here we extended this study and included isolates with acquired fluconazole resistance.

Isolates (n=835) were identified using CHROMagar, MALDI-TOF and, when needed, ITS-sequencing. EUCAST E.Def 7.3.1 susceptibility testing included manogepix, amphotericin B, anidulafungin, micafungin, fluconazole and voriconazole. Manogepix wildtype-upper-limit (WT-UL) values were established following EUCAST-principles for ECOFF setting allowing wildtype/non-wildtype classification. Drug-specific MIC correlations were investigated using Pearson's correlation.

Manogepix modal MICs were low (range 0.004-0.06 mg/L against 16/20 included species). Exceptions were C. krusei and C. inconspicua, and to a lesser extent C. kefyr and Pichia kluyveri. The activity was independent of Fks echinocandin hot-spot alterations (n=17). Adopting the WT-UL established for C. albicans, C. dubliniensis, C. glabrata, C. parapsilosis and C. tropicalis, 14/724 (1.9%) isolates were non-wildtype for manogepix. Twelve of these (85.7%) were also non-wildtype for fluconazole. A statistically significant correlation was observed between manogepix and fluconazole MICs for C. albicans, C. dubliniensis, C. glabrata, C. parapsilosis and C. tropicalis (Pearson r=0.401-0.575), but not between manogepix and micafungin or amphotericin B MICs for any species except C. tropicalis (r=0.519 for manogepix versus micafungin).

Broad-spectrum activity was confirmed for manogepix against contemporary yeast. However, a 1-4 two-fold-dilution increase in manogepix MICs is observed in a subset of isolates with acquired fluconazole resistance. Further studies on the potential underlying mechanism and implication for optimal dosing are warranted.

Treatment of exacerbations of chronic Pseudomonas aeruginosa infections in patients with cystic fibrosis (CF) is highly challenging due to hypermutability, biofilm formation and an increased risk of resistance emergence. We evaluated the impact of ciprofloxacin and meropenem as monotherapy and in combination in the dynamic in vitro CDC biofilm reactor (CBR). Two hypermutable P. aeruginosa strains, PAOmutS (MIC_{ciprofloxacin} 0.25 mg/L, MIC_meropenem 2 mg/L) and CW44 (MIC_{ciprofloxacin} 0.5 mg/L, MIC_meropenem 4 mg/L), were investigated for 120h. Concentration-time profiles achievable in epithelial lining fluid (ELF) following FDA-approved doses were simulated in the CBR. Treatments were ciprofloxacin 0.4g every 8h as 1h-infusions (80% ELF penetration), meropenem 6 g/day as continuous infusion (CI; 30% and 60% ELF penetration) and their combinations. Counts of total and less-susceptible planktonic and biofilm bacteria and MICs were determined. Antibiotic concentrations were quantified by UHPLC-PDA. For both strains, all monotherapies failed with substantial regrowth and resistance of planktonic (≥8log₁₀ CFU/mL) and biofilm (>8log₁₀ CFU/cm²) bacteria at 120h (MIC_{ciprofloxacin} up to 8 mg/L, MIC_meropenem up to 64 mg/L). Both combination treatments demonstrated synergistic bacterial killing of planktonic and biofilm bacteria of both strains from ~48h onwards and suppressed regrowth to ≤4log₁₀ CFU/mL and ≤6log₁₀ CFU/cm² at 120h. Overall, both combination treatments suppressed amplification of resistance of planktonic bacteria for both strains, and biofilm bacteria for CW44. The combination with meropenem at 60% ELF penetration also suppressed amplification of resistance of biofilm bacteria for PAOmutS. Thus, combination treatment demonstrated synergistic bacterial killing and resistance suppression against difficult-to-treat hypermutable P. aeruginosa strains.

CYP450 enzymes are involved in biotransformation of chloroquine (CQ), but the role of the different metabolism profiles of this drug has not been properly investigated in relation to P. vivax recurrences. To investigate the influence of CYPs genotypes associated with CQ-metabolism on early recurrence rates of P. vivax, a case-control study was carried out. Cases included patients presenting an early recurrence (CQ-recurrent), defined as recurrence during the first 28 days after initial infection, plasma concentrations of CQ plus desethylchloroquine (DCQ, the major CQ metabolite) higher than 100 ng/mL. A control (CQ-responsive) with no parasite recurrence over the follow-up was also included. CQ and DCQ plasma levels were measured on Day 28. CQ CYPs (CYP2C8, CYP3A4 and CYP3A5) genotypes were determined by real-time PCR. An ex vivo study was conducted to verify CQ and DCQ efficacy in P. vivax isolates. The frequency of alleles associated with normal and slow metabolism was similar between the cases and controls for CYP2C8 (OR=1.45, 95% CI=0.51-4.14, p=0.570), CYP3A4 (OR=2.38, 95% CI=0.92-6.19, p=0.105) and CYP3A5 (OR=4.17, 95% CI=0.79-22.04, p=1.038) genes. DCQ levels were higher than CQ, regardless of the genotype. Regarding the DCQ/CQ rate, there was no difference between groups or between those patients who had a normal or mutant genotype. DCQ and CQ showed similar efficacy ex vivo. CYPs genotypes had no influence on early recurrence rates. Similar efficacy of CQ and DCQ ex vivo could explain the absence of therapeutic failure, despite presence of alleles associated with slow metabolism.

A signature program at Penn State Greater Allegheny, implemented to give students, faculty and staff the digital skills to communicate, solve problems and create new knowledge, is front and center in the University’s remote learning period.

Richard A. Ehrenkranz
Apr 1, 2006; 117:1253-1261
ARTICLES

John Penders
Aug 1, 2006; 118:511-521
ARTICLES

Some of the most important pre-literacy skills begin in infancy. This timeline shows examples of the milestones children meet on their path to fluent reading.

For the 2020 RHSU Public Influence finale, we reveal the top 10 finishers for various academic disciplines, as well as the top junior faculty in the country.

A new research study, released just a few days before the U.S. military killed a top Iranian military commander and escalated international tensions, looked at connections between sudden national security crises and education policymaking in Washington.

The flu season has started here in the U.S., and according to the Centers for Disease Control and Prevention (CDC) data it has caused 214 deaths in the first week of 2020. Is this number higher, or lower, than usual? When does the flu season start, and how long does [...]

The post How to prepare (your graphs) for flu season appeared first on Graphically Speaking.

After two unprofitable forays into augmented reality hardware, Snap is doubling down on its social camera eyewear with the $380 Spectacles 3 glasses featuring more 3D capabilities.

On view from December 6, 2019 – January 10, 2020 Free opening reception on Friday, December 6 at 5 p.m. Wilmington, Del. (November 26, 2019) – Curiosity and Flux, an exhibition of abstract paintings by Shawn Faust, will be on view in the Mezzanine Gallery from December 6, 2019 – January 10, 2020. The artist […]

Brands are tapping regional influencers for higher engagement.

According to a study by Broadcast Audience Research Council India and Nielsen India, there has been a 44% increase in time spent on social media in the week of March 28 - April 3 over a sample pre-covid period in January and February.

DOVER – Delaware authorities are urging poultry and bird owners to be vigilant in the wake of avian influenza cases reported in Oregon and Washington state. “Though it’s far away at the moment, we know that avian influenza can spread rapidly,” said Delaware State Veterinarian Dr. Heather Hirst, who heads the Delaware Department of Agriculture’s […]

To protect against the spread of avian influenza, the Delaware Department of Agriculture is prohibiting waterfowl entries in the poultry competitions at the Delaware State Fair next month. "This action is being taken out of an abundance of caution to guard against the spread of avian influenza," said Delaware State Veterinarian Dr. Heather Hirst. There have been no East Coast cases of the disease. There are no immediate public health concerns, and poultry and eggs which are properly prepared and cooked are still safe to eat.

The Division of Public Health (DPH) is reporting two more flu-related deaths that occurred during the last two weeks of February, bringing the 2017-2018 season death total to 30. This number breaks the previous single-season record of 28 flu-related deaths, set in 2014-2015. The deceased were both females, 83 and 84 years old, from New Castle and Kent counties, respectively. Both had multiple underlying health conditions.

Statewide flu totals in Delaware decreased for the third week in a row, according to the Division of Public Health (DPH). During the week ending March 10, DPH reports 290 laboratory-confirmed flu cases, down from the prior week’s total of 381 confirmed cases. The latest numbers increase the total number of influenza cases for the season to 7,433. DPH is also reporting one additional flu-related death, a 62-year-old female from New Castle County with multiple underlying health conditions, bringing the number of flu-related deaths for the 2017-2018 flu season to 31.

The Division of Public Health (DPH) is announcing two laboratory-confirmed cases of influenza, just three weeks before the official start of the 2018-2019 flu season, which begins September 30.

Officials pushing vaccination message after flu spreads statewide and first flu-related hospitalization is confirmed  DOVER (Sept. 19, 2018) — While the “official” start of flu season is still two weeks away, the Division of Public Health (DPH) is urging residents not to wait to get vaccinated. Four cases of the flu now have been confirmed, […]

Delaware Governor John Carney, Lt. Governor Bethany Hall-Long, Department of Health and Social Services (DHSS) Secretary Dr. Kara Odom Walker and Department of Transportation (DelDOT) Secretary Jennifer Cohan were among hundreds who lined up to receive their annual flu vaccine Tuesday in Dover.

The Delaware Division of Public Health (DPH) is reporting the state's first laboratory-confirmed case of influenza in a child for the 2018-2019 flu season. The case involves a 5-year-old from Sussex County. This brings the total number of flu cases this season to six, as of Oct. 5, 2018.

The Division of Public Health (DPH) is reporting the first flu-related deaths of the 2018-2019 flu season. A 65-year-old man who was infected with Influenza A passed away last week, making him the first person to die due to flu complications this season. In addition, a 73-year-old man and a 77-year-old woman, both also infected with Influenza A, passed away within the last week. All three individuals were Sussex County residents and all had underlying health conditions.

DOVER  — The number of laboratory-confirmed flu cases continues to increase in Delaware, and the Division of Public Health (DPH) is announcing three recent flu-related deaths, bringing the total number of deaths for the 2018-2019 season thus far to eight. The most recent victim is an 83-year-old man from New Castle County, with underlying health […]

DOVER (March 1, 2019) — Although the overall number of laboratory-confirmed flu cases in Delaware this flu season remains lower than the total number of cases reported at the same time last year, the number of flu-related deaths has continued to increase during the 2018-2019 flu season. As of February 16, 2019, the most recent […]

Although it is late in the 2018-2019 flu season, and total weekly influenza cases have begun to decrease, flu activity in Delaware and across the U.S. remains elevated with an increase in the number of influenza A (H3N2) viruses circulating over the last month.

The 2019-2020 flu season has officially arrived, and to kick off the state’s influenza prevention efforts, the Division of Public Health (DPH) will hold two free flu vaccination clinics for the public.

DOVER – The Delaware Division of Public Health (DPH) is announcing the state’s first laboratory-confirmed case of influenza for the 2019-2020 flu season. The case, which also marks Delaware’s first pediatric case of the season, involves an 8-year-old from New Castle County. “The flu is here,” said DPH Director Dr. Karyl Rattay. “Now that we […]

The Delaware Division of Public Health (DPH) is reporting the state’s first laboratory-confirmed cases of influenza in Kent and Sussex counties, for the 2019-2020 flu season. The Kent County case involves a 26-year-old female, while the Sussex County case involves a 7-year-old male. This brings the total number of flu cases this season to three. The first confirmed flu case for New Castle County was announced last week.

DOVER – The Division of Public Health (DPH) is reminding Delawareans to protect themselves and those around them this influenza season by getting vaccinated as DPH announces the first two flu-related deaths of the 2019-2020 flu season. A 68-year-old woman infected with influenza A, and a 65-year-old man infected with influenza B, passed away this […]

DOVER – As the number of confirmed influenza cases in Delaware continues to rise, the Division of Public Health (DPH) is announcing two recent flu-related deaths, bringing the total number of deaths for the 2019-2020 season thus far to four. The most recent victim is a 29-year-old New Castle County man diagnosed with influenza B […]

Advanced analytics programs can incorporate geospatial data. Learn how such data can be used to augment local marketing plans

As of February 15, 2020, there have been 5,047 confirmed cases of influenza in Delaware, including 267 hospitalizations. These numbers reflect only the number of lab-confirmed cases; the actual number of cases circulating statewide is likely much higher. By comparison, at the same time in the 2018-2019 season, there were 3,264 flu cases in Delaware, including 537 hospitalizations, and 13 flu-related deaths.

  Download PDF When developing games and simulations, you may want your users to be able to influence assets that are active in a physics simulation. In this article, you learn how to develop a Unity...

The panel included Anna Lockwood, Head of Global Sales – Telstra; Sally Hancock, Managing Partner, Y Sport and Former Chair of Women in Sport; Aarti Dabas, former head of Media Rights for the ICC, and iSportconnect Chief Executive Officer Sree Varma.