HPV is the most common sexually transmitted infection in the United States. More than 50% of sexually active men and women will acquire HPV infection in their lifetime. In 2011, HPV was recommended for routine use among male adolescents.

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03 November 2016 This briefing analyses the characteristics of EU nationals living in Scotland, based on the 2015 Annual Population Survey. The briefing also reviews evidence relating to the economic contribution of migrants.

A national study of nearly 12,500 9th graders finds that two sessions of a 25-minute exercise on “growth mindset” can boost students’ grades and their willingness to take on challenging classes.

Sixteen design projects created by graphic design students at Pennsylvania College of Technology have been honored in the national Flux Student Design Competition.

OM Angola helps a war-ravaged society heal itself.

La fièvre des élections s’empare de l’Afrique centrale. Pour la seconde fois depuis la fin des guerres qui ont dévasté la région, les scrutins s’enchaînent au Burundi, au Rwanda, en République centrafricaine et au Congo.

While the prospect of Guinea's return to constitutional rule after its recent election is cause for hope, the recent resurgence of military takeovers in Africa may not yet have run its full course.

Dans de nombreux pays, le pétrole suscite des débats controversés sur son rôle de moteur de changements économiques, sociaux et géopolitiques. Depuis quelques années, les réflexions sur la question du pétrole ont démontré une corrélation négative entre son exploitation, le développement socioéconomique, la gouvernance et le regain des conflits dans les pays producteurs.

In numerous countries, the exploitation of oil has generated debate about its economic, social and geopolitical consequences.

The United Nations Security Council decided on 10 April to deploy a peacekeeping mission in the Central African Republic (CAR) which will take over the mission of the African Union (MISCA), which itself succeeded the mission of the Economic Community of Central African States (MICOPAX).

Since 2012, single low dose of primaquine (SLDPQ, 0.25mg/kg) has been recommended with artemisinin-based combination therapies, as first-line treatment of acute uncomplicated Plasmodium falciparum malaria, to interrupt its transmission, especially in low transmission settings of multidrug, including artemisinin, resistance. Policy makers in Cambodia have been reluctant to implement this recommendation due to primaquine safety concerns and lack of data on its efficacy.

In this randomized controlled trial, 109 Cambodians with acute uncomplicated P. falciparum malaria received dihydroartemisinin-piperaquine (DP) alone or combined with SLDPQ on the first treatment day. Transmission-blocking efficacy of SLDPQ was evaluated on Days 0, 1, 2, 3, 7, 14, 21, 28 and recrudescence by reverse transcriptase polymerase chain reaction (RT-PCR) (gametocyte prevalence) and membrane-feeding assays with Anopheles minimus mosquitoes (gametocyte infectivity). Without the influence of recrudescent infections, DP+SLDPQ reduced gametocyte carriage 3 fold compared to DP. Of 48 patients tested on Day 0, only three patients were infectious to mosquitoes (~6%). Post-treatment, three patients were infectious: on D14 (3.5%, 1/29), and on the first and seventh day of recrudescence (8.3%, 1/12 for each); this overall low infectivity precluded our ability to assess its transmission blocking efficacy.

Our study confirms effective gametocyte clearance of SLDPQ when combined with DP in multidrug resistant P. falciparum and the negative impact of recrudescent infections due to poor DP efficacy. Artesunate-mefloquine (ASMQ) has replaced DP and ASMQ-SLDPQ has been deployed to treat all P. falciparum symptomatic patients to further support the elimination of multidrug resistant P. falciparum in Cambodia.

Objectives: Antibiotic combination therapy is used for severe infections caused by multidrug-resistant (MDR) Gram-negative bacteria. Yet, data of which combinations are most effective is lacking. This study aimed to evaluate the in vitro efficacy of polymyxin B in combination with 13 other antibiotics against four clinical strains of MDR Pseudomonas aeruginosa.

Methods: We evaluated the interactions of polymyxin B in combination with amikacin, aztreonam, cefepime, chloramphenicol, ciprofloxacin, fosfomycin, meropenem, minocycline, rifampicin, temocillin, thiamphenicol or trimethoprim by automated time-lapse microscopy using predefined cut-off values indicating inhibition of growth (≤10⁶ CFU/mL) at 24 h. Promising combinations were subsequently evaluated in static time-kill experiments.

Results: All strains were intermediate or resistant to polymyxin B, anti-pseudomonal β-lactams, ciprofloxacin and amikacin. Genes encoding β-lactamases (e.g., bla_PAO and bla_OXA-50) and mutations associated with permeability and efflux were detected in all strains. In the time-lapse microscopy experiments, positive interactions were found with 39 of 52 antibiotic combination/bacterial strain setups. Enhanced activity was found against all four strains with polymyxin B used in combination with aztreonam, cefepime, fosfomycin, minocycline, thiamphenicol and trimethoprim. Time kill experiments showed additive or synergistic activity with 27 of the 39 tested polymyxin B combinations, most frequently with aztreonam, cefepime, and meropenem.

Conclusion: Positive interactions were frequently found with the tested combinations, also against strains that harboured several resistance mechanisms to the single drugs and with antibiotics that are normally not active against P. aeruginosa. Further study is needed to explore the clinical utility of these combinations.

Ibrexafungerp (formerly SCY-078) is a semisynthetic triterpenoid and potent (1->3)-β-D-glucan synthase inhibitor. We investigated the in vitro activity, pharmacokinetics, and in vivo efficacy of ibrexafungerp (SCY) alone and in combination with anti-mould triazole isavuconazole (ISA) against invasive pulmonary aspergillosis (IPA). The combination of ibrexafungerp and isavuconazole in in vitro studies resulted in an additive and synergistic interactions against Aspergillus spp. Plasma concentration-time curves of ibrexafungerp were compatible with linear dose proportional profile. In vivo efficacy was studied in a well established persistently neutropenic NZW rabbit model of experimental IPA. Treatment groups included untreated rabbits (UC) and rabbits receiving ibrexafungerp at 2.5(SCY2.5) and 7.5(SCY7.5) mg/kg/day, isavuconazole at 40(ISA40) mg/kg/day, or combinations of SCY2.5+ISA40 and SCY7.5+ISA40. The combination of SCY+ISA produced in vitro synergistic interaction. There was significant in vivo reduction of residual fungal burden, lung weights, and pulmonary infarct scores in SCY2.5+ISA40, SCY7.5+ISA40, and ISA40-treatment groups vs that of SCY2.5-treated, SCY7.5-treated and UC (p<0.01). Rabbits treated with SCY2.5+ISA40 and SCY7.5+ISA40 had prolonged survival in comparison to that of SCY2.5-, SCY7.5-, ISA40-treated or UC (p<0.05). Serum GMI and (1->3)-β-D-glucan levels significantly declined in animals treated with the combination of SCY7.5+ISA40 in comparison to those treated with SCY7.5 or ISA40 (p<0.05). Ibrexafungerp and isavuconazole combination demonstrated prolonged survival, decreased pulmonary injury, reduced residual fungal burden, lower GMI and (1->3)-β-D-glucan levels in comparison to those of single therapy for treatment of IPA. These findings provide an experimental foundation for clinical evaluation of the combination of ibrexafungerp and an anti-mould triazole for treatment of IPA.

KBP-7072 is a semi-synthetic aminomethylcycline with broad-spectrum activity against Gram-positive and Gram-negative pathogens including multidrug resistant bacterial strains. The pharmacokinetics (PK) of KBP-7072 after oral and intravenous (IV) administration of single and multiple doses were investigated in animal models including during fed and fasted states and also evaluated the protein binding and excretion characteristics. In Sprague-Dawley (SD) rats, Beagle dogs, and CD-1 mice, KBP-7072 demonstrated a linear PK profile after administration of single oral and IV and multiple oral doses. Oral bioavailability ranged from 12% to 32%. Mean T_max ranged from 0.5 to 4 hours, and mean half-life ranged from approximately 6 to 11 hours. Administration of oral doses in the fed state resulted in a marked reduction in C_max and AUC compared with dosing in fasted animals. The mean bound fractions of KBP-7072 were 77.5%, 69.8%, 64.5%, 69.3%, and 69.2% in mouse, rat, dog, monkey, and human plasma, respectively. Following a single 22.5 mg/kg oral dose of KBP-7072 in SD rats, cumulative excretion in feces was 64% and in urine was 2.5% of the administered dose. The PK results in animal models are consistent with single and multiple ascending dose studies in healthy volunteers and confirm the suitability of KBP-7072 for once daily oral and IV administration in clinical studies.

Mycobacterium abscessus lung infections remain difficult to treat. Recent studies have recognized the power of new combinations of antibiotics such as bedaquiline and imipenem although in vitro data have questioned this combination. We report that the efficacy of the bedaquiline plus imipenem treatment relies essentially on the activity of bedaquiline in a C3HeB/FeJ mice model of infection with a rough variant of M. abscessus. The addition of imipenem contributed at clearing the infection in the spleen.

Carbapenem pharmacokinetic profiles are significantly changed in critically ill patients because of the drastic variability of the patients' physiological parameters. Published population PK studies have mainly focused on specific diseases and the majority of these studies had small sample sizes. The aim of this study was to develop a population PK model of imipenem in critically ill patients that estimated the influence of various clinical and biological covariates and the use of Extracorporeal Membrane Oxygenation (ECMO) and Continuous Renal Replacement Therapy (CRRT). A two-compartment population PK model with Creatinine clearance (CrCL), body weight (WT), and ECMO as fixed effects was developed using the non-linear mixed effect model (NONMEM). A Monte Carlo simulation was performed to evaluate various dosing schemes and different levels of covariates based on the pharmacokinetic/pharmacodynamic index (f%T>MIC) for the range of clinically relevant minimum inhibitory concentrations(MICs). The results showed that there may be insufficient drug use in the clinical routine drug dose regimen, and 750mg Q6h could achieve a higher treatment success rate. The blood concentrations of imipenem in ECMO patients were lower than that of non-ECMO patients, therefore dosage may need to be increased. The dosage may need adjustment for patients with CrCL ≤ 70ml/min, but dose should be lowered carefully to avoid the insufficient drug exposure. Dose adjustment is not necessary for patients within the WT ranging from 50-80 kg. Due to the large variation in PK profile of imipenem in critically ill patients, TDM should be carried out to optimize drug regimens.

Chagas disease, caused by the protozoan Trypanosoma cruzi, is one of the main causes of death due to cardiomyopathy and heart failure in Latin American countries. The treatment of Chagas disease is directed at eliminating the parasite, decreasing the probability of cardiomyopathy, and disrupting the disease transmission cycle. Benznidazole (BZ) and nifurtimox (NFX) are recognized as effective drugs for the treatment of Chagas disease by the World Health Organization, but both have high toxicity and limited efficacy, especially in the chronic disease phase. At low doses, aspirin (ASA) has been reported to protect against T. cruzi infection. We evaluated the effectiveness of BZ in combination with ASA at low doses during the acute disease phase and evaluated cardiovascular aspects and cardiac lesions in the chronic phase. ASA treatment prevented the cardiovascular dysfunction (hypertension and tachycardia) and typical cardiac lesions. Moreover, BZ+ASA-treated mice had a smaller cardiac fibrotic area than that in BZ-treated mice. These results were associated with an increase in the number of eosinophils and reticulocytes and level of nitric oxide in the plasma and cardiac tissue of ASA-treated mice relative to respective controls. These effects of ASA and BZ+ASA in chronically infected mice were inhibited by pretreatment with the LXA₄ receptor antagonist, Boc-2, indicating that the protective effects of ASA are mediated by ASA-triggered lipoxin. These results emphasize the importance of exploring new drug combinations for treatments of acute phase of Chagas disease that are beneficial for chronic patients.

Methicillin-resistant Staphylococcus aureus (MRSA) has grown to become a major burden on healthcare systems. The cumulation of limited therapeutic options and worsened patient outcomes with persistent MRSA bacteremia has driven research in optimizing its initial management. The guidelines published by the Infectious Disease of America currently recommend combination therapy for refractory MRSA bacteremia, but the utility of combining antibiotics from the start of therapy is under investigation. The alternative strategy of early use of a β-lactam antibiotics in combination with vancomycin upon initial MRSA bacteremia detection has shown promise. While this concept has gained international attention, providers should give this strategy serious consideration prior to implementation. The objective of this review is to examine retrospective and prospective evidence for early combination with vancomycin and β-lactam antibiotics, as well as explore potential consequences of combination therapy.

A new protocol using aerosolized hydrogen peroxide to decontaminate N95 respirators could allow them to be safely reused in hospital settings. The protocol, optimized by a team of Penn State researchers, inactivates viruses without deforming or damaging the respirator and could help hospitals overcome the current respirator shortage due to the COVID-19 pandemic.

Olivia M. Vaz
Feb 1, 2020; 145:e20190620-e20190620
ARTICLES

Google removes the free WireGuard app from the Play Store for having a donation button, reigniting a debate over whether its policy hurts the open-source community.

Two Penn State University Libraries employees at Berks Thun Library, Penn State Berks, have been awarded the American Library Association’s 2020 Emerging Technologies Section 2020 Best Emerging Technology Application (BETA) Award, which recognizes a technology application that directly benefits library users.

Hongyan “Red” Yuan, an instructional designer at Penn State Berks and member of the board of the Reading Chinese Association (RCA), recently helped to coordinate the donation of 1,500 surgical masks to Penn State Health St. Joseph.

Three Berks Thun Library employees received the 2020 Innovation in College Librarianship Award from the College Libraries Section of the Association of College & Research Libraries, a division of the American Library Association. The award honors librarians who demonstrate a capacity for innovation in working with or serving undergraduates or instructors in the areas of programs, services, and operations, or creating innovations for library colleagues that facilitate their ability to better serve the library’s community.

Graham A. Colditz
Jul 1, 1995; 96:29-35
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Richard A. Ehrenkranz
Dec 1, 2005; 116:1353-1360
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National High Blood Pressure Education Program Working Group on Hypertension Control in Children and Adolescents
Oct 1, 1996; 98:649-658
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Cynthia L. Ogden
Jan 1, 2002; 109:45-60
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Betty R. Vohr
Jun 1, 2000; 105:1216-1226
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A new structure begins next year, incorporating UEFA Nations League-style groups in a two-season cycle.

Bridget O’Donnell, assistant director of student engagement at Penn State Brandywine, has been recognized as Advisor of the Year by the Association for the Promotion of Campus Activities.

The Ratline: Love, Lies and Justice on the Trail of a Nazi Fugitive

Michael Mann, distinguished professor of atmospheric sciences and director of Penn State's Earth System Science Center at Penn State, has been elected to the National Academy of Sciences, recognizing distinguished and continuing achievements in original research. Membership in the NAS is one of the highest honors given to a scientist or engineer in the United States.

Bernadette Lear, Penn State University Libraries behavioral sciences and education librarian and coordinator of library instruction at the Penn State Harrisburg Library, has been elected vice chair/chair elect of the Library History Round Table, a membership group of the American Library Association.

The arts, geography, economics, and foreign languages will lose their place in the testing line-up as the National Assessment of Educational Progress is being streamlined to cut costs.

The Coronavirus and International Affairs Roundtable, taking place 9:30 a.m. Friday, April 17, via Zoom, will bring together experts in law and international affairs from Asia, Europe, the Middle East, North America, and the Caribbean to discuss the broader impact of COVID-19.

Rebecca Mattson, head of faculty and research services for the H. Laddie Montague Jr. Law Library, Penn State University Libraries, and professor of legal research at Penn State Law at University Park, has been elected vice chair/chair elect of the Research Instruction and Patron Services Special Interest Section of the American Association of Law Libraries.

Following UN Special Representative for Libya Bernardino León’s announcement of a new Government of National Accord, Joost Hiltermann, Crisis Group’s Middle East and North Africa Program Director, had the following reaction.

The International Crisis Group congratulates the members of the Tunisian National Dialogue Quartet as this year’s recipient of the Nobel Peace Prize. It is an apt recognition of its achievement in allowing the spirit of inclusion and compromise to triumph over the polarisation and violence that has been all too prevalent in the region, and of the central role civil society can play at moments of crisis.

The National Education Policy Center and Education Deans for Justice and Equity released a joint statement on Thursday, claiming that "there is no settled science of reading."

Holyrood’s Economy, Energy and Fair Work Committee is to have an inquiry into the role of Scottish Development International (SDI) in developing a Scotland that competes on the international stage.

In India and China, indigenous drug manufacturers market arbitrarily combined parenteral β-lactam and β-lactamase inhibitors (BL-BLIs). In these fixed-dose combinations, sulbactam or tazobactam is indiscriminately combined with parenteral cephalosporins, with BLI doses kept in ratios similar to those for the approved BL-BLIs. Such combinations have been introduced into clinical practice without mandatory drug development studies involving pharmacokinetic/pharmacodynamic, safety, and efficacy assessments being undertaken. Such unorthodox combinations compromise clinical outcomes and also potentially contribute to resistance development.

In the wake of falling reading scores on the test known as the Nation's Report Card, 12 major education groups are calling on schools to adopt evidence-based reading instruction.

The National Education Policy Center and Education Deans for Justice and Equity released a joint statement on Thursday, claiming that "there is no settled science of reading."

As of today, the terminal sections of Schönefeld Airport have new designations: K, L, M Departures, M Arrivals and Q.

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.