Novel in-frame deletion in MFSD8 gene revealed by trio whole exome sequencing in an Iranian affected with neuronal ceroid lipofuscinosis type 7: a case report

The neuronal ceroid lipofuscinoses are a group of neurodegenerative, lysosomal storage disorders. They are inherited as an autosomal recessive pattern with the exception of adult neuronal ceroid lipofuscinosis...

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The differential diagnosis of Helicobacter pylori negative gastritis

Abstract

Gastric biopsies are often submitted with as clinical question Helicobacter pylori (HP) infection. Regularly, the morphology suggests a HP infection but the organism is not detected in special stains. This review presents a practical approach to deal with such biopsies. The first step is to exclude a false negative result of the search for HP, by ensuring that both antral and oxyntic mucosa are present, by the use of sensitive stains, identification of marked reactive changes, such as intestinal, pseudo-pyloric, pancreatic metaplasia that may suggest a diagnosis of (HP associated or autoimmune) atrophic gastritis, and finally identification of signs of the use of proton pump inhibitors (PPI) as in such biopsies, HP may sometimes be found only within parietal cells. The differential diagnosis should include lymphocytic gastritis, other diseases affecting the stomach, such as inflammatory bowel disease (IBD), vasculitis, granulomatous disease, viral infection, such as cytomegalovirus (CMV) or more rarely Epstein-Barr virus (EBV) infection, or other bacterial infections, such as Enterococcus and Treponema pallidum. Clinical input may be required to ensure the patient is not taking medication that may cause gastritis, such as antibiotics used for HP eradication or common medications that cause a form of gastropathy. When these have been excluded, a known cause has not been found and in such a case, the term idiopathic focal/diffuse gastritis can be used.

https://ift.tt/2Q5e9ul

Association Between Type 2 Diabetes Mellitus and Hearing Loss Among Patients in a Coastal City of South India

Abstract

Diabetes mellitus (DM) is a metabolic culprit known to perpetuate several disease processes. The relationship between hearing loss (HL) and type 2 DM (T2DM) remains unclear despite the vast volume of research devoted to this topic. We conducted this study with the aim to evaluate HL among T2DM patients and to assess the relationship between severity of HL, glycosylated hemoglobin (HbA1c) levels and duration of T2DM. Design: a time bound descriptive crosssectional study. Setting: tertiary care hospital of South India. Subjects: subjects with T2DM, aged from 40 to 60 years (excluding hypertension, chronic noise exposure and history of smoking or ototoxicity) were included. Methods: Non-random convenience sampling. Details were gathered using a self-administered, semistructured questionnaire and the hearing was assessed by pure tone audiometry. Data was analysed using SPSS. A large proportion of the sampled population had audiological assessments suggestive of SensoriNeural HL (SNHL). 90.2% had a bilateral distribution of HL; however, only 39% of patients reported having any associated ear complaints. No statistically significant associations were obtained between severity of HL, glycaemic control, duration of diabetes or gender. Bilateral SNHL is a complication associated with T2DM. Duration and glycaemic control are independent variables and do not statistically influence the severity of HL. However, this study demonstrated that many patients with SNHL had no symptoms and also lacked awareness of HL in DM. Therefore routine assessment of hearing should be considered in the diabetic population.

https://ift.tt/2Q2RZbT

Association Between Type 2 Diabetes Mellitus and Hearing Loss Among Patients in a Coastal City of South India

Abstract

Diabetes mellitus (DM) is a metabolic culprit known to perpetuate several disease processes. The relationship between hearing loss (HL) and type 2 DM (T2DM) remains unclear despite the vast volume of research devoted to this topic. We conducted this study with the aim to evaluate HL among T2DM patients and to assess the relationship between severity of HL, glycosylated hemoglobin (HbA1c) levels and duration of T2DM. Design: a time bound descriptive crosssectional study. Setting: tertiary care hospital of South India. Subjects: subjects with T2DM, aged from 40 to 60 years (excluding hypertension, chronic noise exposure and history of smoking or ototoxicity) were included. Methods: Non-random convenience sampling. Details were gathered using a self-administered, semistructured questionnaire and the hearing was assessed by pure tone audiometry. Data was analysed using SPSS. A large proportion of the sampled population had audiological assessments suggestive of SensoriNeural HL (SNHL). 90.2% had a bilateral distribution of HL; however, only 39% of patients reported having any associated ear complaints. No statistically significant associations were obtained between severity of HL, glycaemic control, duration of diabetes or gender. Bilateral SNHL is a complication associated with T2DM. Duration and glycaemic control are independent variables and do not statistically influence the severity of HL. However, this study demonstrated that many patients with SNHL had no symptoms and also lacked awareness of HL in DM. Therefore routine assessment of hearing should be considered in the diabetic population.

https://ift.tt/2Q2RZbT

Carrie Owen Benefits from a New Minimally Invasive In-office Treatment for Nasal Polyposis

By the time she arrived in the office of rhinologist Martin J. Citardi, MD, Carrie Owen had lost her senses...

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Breathing Better After Surgery and a Novel Implant

Former Houstonian Kelly Krohn was among the first to benefit from a relatively new solution for nasal airway obstruction symptoms...

https://ift.tt/2NEI3ss

Six ORL Specialists Named Houstonia Top Doctors for 2018

Six members of the Department of Otorhinolaryngology-Head and Neck Surgery have been selected as Houstonia Top Doctors by physicians, physician...

https://ift.tt/2DrS9YZ

Dr. Amber Luong Selected Faculty Member of the Year by ORL Residents

Each year, otorhinolaryngology residents of the Department of Otorhinolaryngology-Head and Neck Surgery at McGovern Medical School at UTHealth have the...

https://ift.tt/2NzflJA

Human Vestibulo-Ocular Reflex Adaptation Training: Time Beats Quantity

Abstract

The vestibulo-ocular reflex (VOR) is the main gaze stabilising system during rapid head movements. The VOR is highly plastic and its gain (eye/head velocity) can be increased via training that induces an incrementally increasing retinal image slip error signal to drive VOR adaptation. Using the unilateral incremental VOR adaptation technique and horizontal active head impulses as the vestibular stimulus, we sought to determine the factors important for VOR adaptation including: the total training time, ratio and number of head impulses to each side (adapting and non-adapting sides; the adapting side was pseudo-randomised left or right) and exposure time to the visual target during each head impulse. We tested 11 normal subjects, each over 5 separate sessions and training protocols. The basic training protocol (protocol one) consisted of unilateral incremental VOR adaptation training lasting 15 min with the ratio of head impulses to each side 1:1. Each protocol varied from the basic. For protocol two, the ratio of impulses were in favour of the adapting side by 2:1. For protocol three, all head impulses were towards the adapting side and the training only lasted 7.5 min. For protocol four, all impulses were towards the adapting side and lasted 15 min. For protocol five, all head impulses were to the adapting side and the exposure time to the visual target during each impulse was doubled. We measured the active and passive VOR gains before and after the training. Albeit with small sample size, our data suggest that the total training time and the visual target exposure time for each head impulse affected adaptation, whereas the total number and repetition rate of head impulses did not. These data have implications for vestibular rehabilitation, suggesting that quality and duration of VOR adaptation exercises are more important than rapid repetition of exercises.

https://ift.tt/2NCnPPZ

Effect of atrazine on growth and production of AFB 1 in Aspergillus section Flavi strains isolated from maize soils

Abstract

Atrazine is one of the most frequently used herbicides in Argentina for controlling broadleaf weeds and annual grasses. Currently, there is limited information on the impact of triazine herbicides on mycotoxin production and growth parameters of toxigenic fungi in maize. The objective of this study was to evaluate the effect of different concentrations of atrazine on the lag phase prior to growth, the growth rate, and on production of aflatoxin B₁ (AFB₁) of Aspergillus flavus and Aspergillus parasiticus strains, on maize meal extract agar (MMEA) under different water activities (a_W) and temperatures. A commercial formulation of atrazine was added to MMEA medium at 0, 5, 10, 50, or 100 mmol/l, adjusted to 0.98, 0.95, and 0.93 a_W, and incubated at 28 °C and 37 °C for 21 days. AFB₁ was determined by HPLC after 7, 14, and 21 days of incubation. In the control treatments, a significant increase in the time prior to growth was observed and as the a_W decreased, at both temperatures, the growth rate of the strains also decreased. A significant increase in growth rate was observed as the concentration of atrazine in the medium increased, for all a_W levels tested. The optimal conditions for the accumulation of AFB₁ in the control treatments were 0.98 a_W and 28 °C, after 7 days of incubation. As the concentration of herbicide increased, AFB₁ production also increased (P < 0.05). These results add to the knowledge about consequences with regard to aflatoxin production of the use of excessive atrazine doses in extensive maize culture.

https://ift.tt/2xzS40e

A Systematic Review of Evidence-Based Treatments for Prurigo Nodularis

This review provides evidence supporting some efficacy of topical agents and phototherapy in treatment of prurigo nodularis, while highlighting emerging therapeutic potential from modulation of neurokinin-1 receptor, interleukin-31 receptor, and κ-opioid receptor signaling. Higher-powered studies for prurigo nodularis treatments are needed.

https://ift.tt/2OPl6zc

Efficacy and safety assessment of expiratory positive airway pressure (EPAP) mask for OSAHS therapy

We have designed the expiratory positive airway pressure (EPAP) mask to provide a new sort of therapeutic strategies for Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS). And this study aims to assess the safety, efficacy and compliance of the EPAP therapy.

https://ift.tt/2O8GuT9

Prediction of tongue obstruction observed from drug induced sleep computed tomography by cephalometric parameters

To elucidate potential role of cephalometric measurements to predict tongue base obstruction as observed on drug Induced Sleep Computed Tomography (DIS-CT).

https://ift.tt/2Q312d0

Human Vestibulo-Ocular Reflex Adaptation Training: Time Beats Quantity

Abstract

The vestibulo-ocular reflex (VOR) is the main gaze stabilising system during rapid head movements. The VOR is highly plastic and its gain (eye/head velocity) can be increased via training that induces an incrementally increasing retinal image slip error signal to drive VOR adaptation. Using the unilateral incremental VOR adaptation technique and horizontal active head impulses as the vestibular stimulus, we sought to determine the factors important for VOR adaptation including: the total training time, ratio and number of head impulses to each side (adapting and non-adapting sides; the adapting side was pseudo-randomised left or right) and exposure time to the visual target during each head impulse. We tested 11 normal subjects, each over 5 separate sessions and training protocols. The basic training protocol (protocol one) consisted of unilateral incremental VOR adaptation training lasting 15 min with the ratio of head impulses to each side 1:1. Each protocol varied from the basic. For protocol two, the ratio of impulses were in favour of the adapting side by 2:1. For protocol three, all head impulses were towards the adapting side and the training only lasted 7.5 min. For protocol four, all impulses were towards the adapting side and lasted 15 min. For protocol five, all head impulses were to the adapting side and the exposure time to the visual target during each impulse was doubled. We measured the active and passive VOR gains before and after the training. Albeit with small sample size, our data suggest that the total training time and the visual target exposure time for each head impulse affected adaptation, whereas the total number and repetition rate of head impulses did not. These data have implications for vestibular rehabilitation, suggesting that quality and duration of VOR adaptation exercises are more important than rapid repetition of exercises.

https://ift.tt/2NCnPPZ

Management of Long-Standing Flaccid Facial Palsy

Chronic flaccid facial paralysis (FFP>2 years) may be approached with static and dynamic techniques. An horizontal zonal assessment evaluates the upper, middle, and lower thirds of the face. Surgery is tailored to an individual's deficits, goals, and health status. While dynamic reanimation is the gold standard for rehabilitation, there are cases in which static approaches are more appropriate or may be used as an adjunct to dynamic techniques. This article focuses on the surgical management of FFP primarily using static approaches to the individual zones of the face to create resting symmetry.

https://ift.tt/2zrToTU

Facial Rehabilitation

This article describes the most widely used clinician-graded and patient-reported outcome measures, and describes facial rehabilitation strategies for acute and chronic facial palsy, and rehabilitation following dynamic facial reanimation surgery. The multimodality rehabilitation of the facial palsy patient is determined by the extent of facial nerve injury, specific functional deficits, the presence of synkinesis, and the patient's individual goals. Appropriate intervention, including patient education, soft tissue mobilization, neuromuscular reeducation, and chemodenervation, decreases facial tension and improves facial muscle motor control, physical function, facial expression, and quality of life.

https://ift.tt/2N2fXCe

Leadership Driving Safety and Quality

Leaders in health care play a large role in successful achievement of quality and safety goals through an overt commitment to both quality and safety, fostering a culture of quality improvement and clear and consistent communication of goals and plans. Specific training for frontline providers, managers, and staff is critical in developing skilled leaders with a quality and safety orientation. Many models exist for organizational leadership development, and exemplars of quality and safety leadership have openly shared the keys to their successes for others to raise the bar.

https://ift.tt/2zsePEz

Reprocessing Standards for Medical Devices and Equipment in Otolaryngology

Stringent regulatory standards for reprocessing medical devices and equipment have proliferated in response to patient safety incidents in which improperly disinfected or contaminated endoscopes lead to large-scale disease transmission or outbreaks. This article details best practices in reprocessing reusable and single-use devices in otolaryngology, with particular attention to flexible fiberoptic endoscopes/nasophyarngoscopes, nasal speculums, and other clinic and operating room instruments. High-risk devices require sterilization, whereas lower risk devices may be reprocessed using various disinfection procedures. Reprocessing practices have implications for adequacy, efficiency, and cost. Nuanced understanding of procedures and their rationale ensures delivery of safe, ethical, and quality patient care.

https://ift.tt/2MZOoJN

Rifampin resistance in staphylococci after rifaximin intake for surgical prophylaxis in elective colorectal surgery. [Susceptibility]

The aim of our study was to determine whether rifampin-resistance emerges in human skin staphylococci after oral intake of rifaximin for surgical prophylaxis. Rifampin-resistant staphylococci appeared on the skin of 32 out of 74 patients (43.2%) two weeks after prophylactic treatment with rifaximin. In all cases the resistant strains were coagulase-negative staphylococci. The resistance was completely reverted after three months. This study shows the emergence of transient resistance to rifampin after rifaximin intake.

https://ift.tt/2O9pBHQ

In vivo efficacy of ellagic acid against Candida albicans in a Drosophila melanogaster infection model [Pharmacology]

The aim of this study was to evaluate the antifungal activity and the toxicity of ellagic acid (EA) using a Drosophila melanogaster model. Candida albicans was inoculated in Toll heterozygous flies. Survival curves were obtained for the evaluation of the antimicrobial effect and toxicity of EA. A protective effect of Drosophila melanogaster from fungal infection was observed at non-toxic concentrations. This study showed that EA is promising for the treatment of candidiasis.

https://ift.tt/2OM1xI5

Site-directed mutagenesis of the 1,3-{beta} glucan synthase catalytic subunit of Pneumocystis jirovecii and susceptibility assays suggest its sensitivity to caspofungin [Susceptibility]

The echinocandin caspofungin inhibits the catalytic subunit Gsc1 of the enzymatic complex synthetizing 1,3-β glucan, an essential compound of the fungal wall. Studies in rodents showed that caspofungin is effective against Pneumocystis asci. However, its efficacy against asci of Pneumocystis jirovecii, the species infecting exclusively humans, remains controversial. The aim of this study was to assess the sensitivity to caspofungin of the P. jirovecii Gsc1 subunit, as well as of those of Pneumocystis carinii and Pneumocystis murina infecting respectively rats and mice. In absence of an established in vitro culture method for Pneumocystis species, we used functional complementation of the Saccharomyces cerevisiae gsc1 deletant. In the fungal pathogen Candida albicans, mutations leading to amino acid substitutions in Gsc1 confer resistance to caspofungin. We introduced the corresponding mutations into the Pneumocystis gsc1 genes using site-directed mutagenesis. In spot dilution tests, the sensitivity to caspofungin of the complemented strains decreased with the number of mutations introduced, suggesting that the wild-type enzymes are sensitive. The minimum inhibitory concentrations of caspofungin determined by E-test and Yeastone for strains complemented with Pneumocystis enzymes (respectively 0.125 and 0.12 microg/ml) were identical to those upon complementation with the enzyme of C. albicans for which caspofungin presents low MICs. However, they were lower than the MICs upon complementation with the enzyme of the resistant species Candida parapsilosis (0.19 and 0.25). Sensitivity levels of Gsc1 enzymes of the three Pneumocystis species were similar. Our results suggest that P. jirovecii is sensitive to caspofungin during infections, as P. carinii and P. murina.

https://ift.tt/2O9pBaO

A large, refractory nosocomial outbreak of Klebsiella pneumoniae carbapenemase (KPC)-producing Escherichia coli demonstrates carbapenemase gene outbreaks involving sink sites require novel approaches to infection control [Epidemiology and Surveillance]

Carbapenem-resistant Enterobacteriaceae (CRE) are a health threat, but effective control interventions remain unclear. Hospital wastewater sites are increasingly highlighted as important potential reservoirs. We investigated a large Klebsiella pneumoniae carbapenemase (KPC)-producing E. coli (KPC-EC) outbreak and wider CRE incidence trends over eight years in the Central Manchester Foundation NHS Trust (CMFT), UK, to determine the impact of Infection Prevention and Control measures.

Bacteriology and patient administration data (2009 to 2017) were linked; a subset of CMFT/regional KPC-EC isolates (n=268) was sequenced. Control interventions followed international guidelines and included cohorting, rectal screening (n=184,539 screens), environmental sampling, enhanced cleaning, and ward closure/plumbing replacement. Segmented regression of time trends of CRE detections was used to evaluate the impact of interventions on CRE incidence.

Genomic analysis (n=268 isolates) identified spread of a KPC-EC outbreak clone (ST216, strain-A; n=125) amongst patients and the environment, particularly on two cardiac wards (W3/W4), despite control measures. ST216 strain-A had caused an antecedent outbreak, and shared its KPC plasmids with other E. coli lineages and Enterobacteriaceae. CRE acquisition incidence declined after W3/W4 closure and plumbing replacement, suggesting an environmental contribution. However, W3/W4 wastewater sites were rapidly re-colonised with CRE and patient CRE acquisitions recurred, albeit at lower rates.

Patient relocation and plumbing replacement were associated with control of a clonal KPC-EC outbreak; however, environmental contamination with CRE and patient CRE acquisitions recurred rapidly following this intervention. The large numbers of cases and persistence of bla_KPC in E. coli, including pathogenic lineages, is a concern.

https://ift.tt/2OM1pZ7

Microbiological Analysis From a Phase 2 Randomized Study in Adults Evaluating Single Oral Doses of Gepotidacin in the Treatment of Uncomplicated Urogenital Gonorrhea Caused by Neisseria gonorrhoeae [Clinical Therapeutics]

We evaluated microbiological correlates of successful treatment of Neisseria gonorrhoeae isolates from a Phase 2 study of gepotidacin, a novel triazaacenaphthylene antibacterial, for therapy of uncomplicated urogenital gonorrhea. Culture, susceptibility testing, genotypic characterization, and frequency of resistance (FoR) were performed for selected isolates. Microbiological success was defined as culture-confirmed eradication of N. gonorrhoeae. Against 69 baseline urogenital isolates, gepotidacin MICs ranged from ≤0.06 to 1 µg/mL (MIC₉₀ = 0.5 µg/mL). For gepotidacin, the ratio of the area under the free-drug concentration-time curve to MIC (fAUC/MIC) was associated with therapeutic success. Success was 100% (61/61) at fAUC/MICs ≥48 and decreased to 63% (5/8) for fAUC/MICs ≤25. All 3 isolates from microbiological failures were ciprofloxacin-resistant, had a baseline gepotidacin MIC of 1 µg/mL, and carried a pre-existing ParC D86N mutation, a critical residue for gepotidacin binding. At test-of-cure, resistance to gepotidacin emerged in 2 isolates (MICs increased ≥32-fold) with an additional GyrA A92T mutation, also implicated in gepotidacin binding. Test-of-cure isolates had the same sequence type as the corresponding baseline isolates. For 5 selected baseline isolates, all carrying a ParC D86N mutation, in vitro FoR to gepotidacin was low (10^–9 to 10^–10); resistant mutants had the same A92T mutation as the 2 emergence of resistance isolates. Five participants with isolates with a ParC D86N mutation were successes. In summary, fAUC/MICs ≥48 predicted 100% microbiological success, including 3 isolates with the ParC D86N mutation (fAUC/MICs ≥97). Pharmacokinetic/pharmacodynamic determinations may help to evaluate new therapies for gonorrhea; further study of gepotidacin is warranted.

https://ift.tt/2O5vkOZ

The combination of fosfomycin plus meropenem is synergistic for Pseudomonas aeruginosa PA01 in a Hollow Fiber Infection Model (HFIM). [Experimental Therapeutics]

Treating high-density bacterial infections is a challenging clinical problem. We have a paucity of new agents that can address this problem. Pseudomonas aeruginosa is a particularly difficult pathogen to treat effectively because of the plethora of resistance mechanisms it carries.

Fosfomycin is an agent discovered circa 40 years ago. Recently it has been resurrected in the United States and studied for intravenous therapy. We hypothesized that to maximize its utility, it would require combination chemotherapy when used in a clinical circumstance in high bacterial burden infections.

We chose to examine the combination of meropenem plus fosfomycin. These agents were studied in the Hollow Fiber Infection Model. We utilized a fully factorial study design, looking at 2 doses of meropenem alone (1 and 2 g 8 hourly) and two doses of fosfomycin alone (6 and 8 g 8 hourly) as well as all possible combinations plus a no-treatment control.

We used a high dimensional model of 5 inhomogeneous differential equations with 5 system outputs to analyze all data simultaneously. Combination therapy outperformed all monotherapy regimens, with all combinations driving > 6 Log₁₀(CFU/ml) bacterial kill. Combination therapy was able to counterselect resistance emergence (meropenem mutants being killed by the combination as well as fosfomycin mutants being killed by the combination) in all regimens studied. The analysis demonstrated that the combination was significantly synergistic for bacterial cell kill and resistance suppression. Meropenem plus fosfomycin is a promising combination for therapy of high burden Pseudomonas aeruginosa infections and requires further study.

https://ift.tt/2OLkKJZ

AN ASSESSMENT OF QUALITY INDICATORS FOR APPROPRIATE ANTIBIOTIC USE [Epidemiology and Surveillance]

One of the critical elements of antimicrobial stewardship programs is the ability to measure the quality of antibiotic prescription. The aim of the present study was to evaluate the performance properties of a set of previously developed quality indicators (QIs) and to identify the potential room for improvement in antibiotic use in our setting. A monthly cross sectional point prevalence survey was conducted in a 400-bed acute care teaching hospital from June to November 2015. All adult patients treated at least 24 hours with antibiotic therapy for a suspected hospital or community-acquired bacterial infection were included. Performance scores (adherence, room for improvement, inter-observer reliability and applicability) were calculated for eight QIs.

Three hundred sixty two patients were evaluated. Adherence to the whole set of QIs was accomplished in 14.1% of evaluable patients. The QIs with a higher room for improvement were: adequate request of blood cultures (60.6%), therapeutic drug monitoring (TDM) (59.1%), sequential antibiotic therapy within 72 hours (48.2%) and empirical antibiotic therapy according to the local guideline (30.4%). The rate of patients under unnecessary antibiotic treatment in the absence of clinical or microbiological evidence of infection after 5 days was 12.2%. All indicators scored kappa's ≥ 0.6, suggesting good inter-observer reliability. Low applicability (6.1% of reviewed patients) only was found for the TDM QI. The QIs analyzed were found to be applicable, showed a good inter-observer reliability and were useful tools to identify areas with potential room for improvement in antibiotic use.

https://ift.tt/2O5EsTI

A hyperactive form of the zinc cluster transcription factor Stb5 causes YOR1 overexpression and beauvericin resistance in Candida albicans [Mechanisms of Resistance]

Gain-of-function mutations in the zinc cluster transcription factors Mrr1, Tac1, and Upc2, which result in constitutive overexpression of their target genes, are a frequent cause of fluconazole resistance in the pathogenic yeast Candida albicans. In this study, we show that an activated form of another zinc cluster transcription factor, Stb5, confers resistance to the natural compound beauvericin by overexpression of YOR1, encoding an efflux pump of the ATP-binding cassette transporter superfamily. Beauvericin has recently been shown to potentiate the activity of azole drugs against C. albicans. Although Yor1 did not contribute to fluconazole resistance when C. albicans cells were treated with the drug alone, Stb5-mediated YOR1 overexpression diminished the synergistic effect of the fluconazole/beauvericin combination, thereby enhancing fluconazole resistance in beauvericin-treated C. albicans cells. Stb5-mediated YOR1 overexpression also suppressed the inhibition of hyphal growth, an important virulence trait of C. albicans, by beauvericin. Therefore, activating mutations in Stb5, which result in constitutive YOR1 overexpression, may enable C. albicans to acquire resistance to beauvericin and thereby overcome both the sensitization to azole drugs and the inhibition of morphogenesis caused by this compound.

https://ift.tt/2ONHmK2

In silico investigation of the decline in clinical efficacy of artemisinin combination therapies due to increasing artemisinin and partner drug resistance [Mechanisms of Resistance]

Antimalarial treatment currently relies on an artemisinin derivative and a longer acting partner drug. With the emergence of resistance to the artemisinin derivatives and the potential pressure this exerts on the partner drugs, the impact of resistance to each drug on efficacy needs to be investigated. An in silico exploration of dihydroartemisinin-piperaquine and mefloquine-artesunate, two commonly used artemisinin-based combination therapies in Southeast Asia, was performed. The percentage of treatment failures was simulated from a within-host pharmacokinetic-pharmacodynamic (PKPD) model assuming parasites developed increasing levels of (i) artemisinin derivative resistance or (ii) concomitant resistance to both the artemisinin derivative and partner drug. Because the exact nature of how resistant Plasmodium falciparum parasites respond to treatment is unknown, we examined the impact on treatment failure rates of artemisinin resistance that either: (i) reduced the maximal killing rate (k_max); (ii) increased the concentration of drug required for 50% killing (EC50); or (iii) shortened the window of parasite stages that are susceptible to artemisinin derivatives until it has no effect on the ring stages. The loss of the ring stage activity of the artemisinin derivative caused the greatest increase in the treatment failure rate, and this result held irrespective of whether partner drug resistance was assumed present or not. To capture the uncertainty around how artemisinin derivative and partner drug resistance impact the assumed concentration-killing effect relationship, a variety of changes to this relationship should be considered when using within-host PKPD models to simulate clinical outcomes to guide treatment strategies for resistant infections.

https://ift.tt/2O5vjKV

Predicting the Outcomes of New Short-Course Regimens for Multi-Drug Resistant Tuberculosis Using Intrahost and Pharmacokinetic-Pharmacodynamic Modelling [Epidemiology and Surveillance]

Short-course regimens for multi-drug resistant tuberculosis (MDR-TB) are urgently needed. Limited data suggest that the new drug, bedaquiline (BDQ), may have the potential to shorten MDR-TB treatment to less than six months when used in conjunction with standard anti-TB drugs. However, the feasibility of BDQ in shortening MDR-TB treatment duration remains to be established. Mathematical modelling provides a platform to investigate different treatment regimens and predict their efficacy. We developed a mathematical model to capture the immune response to TB inside a human host environment. This model was then combined with a pharmacokinetic-pharmacodynamic model to simulate various short-course BDQ-containing regimens. Our modelling suggests that BDQ could reduce MDR-TB treatment duration to just 18 weeks (four months) while still maintaining a very high treatment success rate (100% for daily BDQ for two weeks, or 95% for daily BDQ for one week during the intensive phase). The estimated time to bacterial clearance of these regimens ranges from 27 to 33 days. Our findings provide the justification for empirical evaluation of short-course BDQ-containing regimens. If short-course BDQ-containing regimens are found to improve outcomes then we anticipate clear cost-savings and a subsequent improvement in the efficiency of national TB programs.

https://ift.tt/2OLQkaw

Enterobacter cloacae complex ST-171 Isolates Expressing KPC-4 Carbapenemase Recovered from Canine Patients in Ohio, USA [Epidemiology and Surveillance]

Companion animals are likely relevant in the transmission of antimicrobial resistant bacteria in the community. Enterobacter xiangfangensis ST171, a clone that has been implicated in clusters of infections in humans, was isolated from two dogs with clinical disease in Ohio, U.S. The canine isolates contained IncHI2 plasmids encoding bla_KPC-4. Whole genome sequencing was used to put the canine isolates in phylogenetic context with available human ST171 sequences, as well as characterize their bla_KPC-4 plasmids.

https://ift.tt/2O5ElYi

The Activity of Moxifloxacin against Acid-Phase and Non-Replicative Persister Phenotype Phase Mycobacterium tuberculosis in a Hollow Fiber Infection Model [Experimental Therapeutics]

A major goal for improving tuberculosis therapy is to identify drug regimens with improved efficacy and shorter treatment durations. Shorter therapies improve patient adherence to the antibiotic regimens that, in turn, decreases resistance emergence.

M. tuberculosis exists in multiple metabolic states. At the initiation of therapy, the bulk of the population is in Log-Phase growth. Consequently, it is logical to focus initial therapy on these organisms. Moxifloxacin has good early bactericidal activity against Log-Phase growth bacteria and is a logical component of initial therapy. It would be optimal if this agent also possessed activity against Acid-Phase and Non-Replicative Persister (NRP) Phenotype organisms. We studied multiple exposures to moxifloxacin (equivalent to 200 mg-800 mg daily) in our Hollow Fiber Infection Model against strain H37Rv in Acid-Phase and against strain 18b in streptomycin starvation, which is a model for NRP-Phase organisms.

Moxifloxacin possesses good activity against Acid-Phase organisms, generating from 3.75 Log₁₀(CFU/ml) cell kill (200 mg daily) to 5.16 Log₁₀(CFU/ml) cell kill (800 mg daily) over the 28 days of the experiment.

Moxifloxacin also has activity against the streptomycin-starved strain 18b. The 400 to 800 mg daily regimens achieved extinction at day 28, while the no-treatment control still had 1.96 Log₁₀(CFU/ml) culturable. The lowest dose (200 mg daily) still had 0.7 Log₁₀(CFU/ml) measurable at day 28, a net kill of 1.26 Log₁₀(CFU/ml).

Moxifloxacin is an attractive agent for early therapy, as it possesses activity against three metabolic states of M. tuberculosis.

https://ift.tt/2OOJilg

"Electrocardiographic safety of repeated monthly dihydroartemisinin-piperaquine as a candidate for mass drug administration" [Clinical Therapeutics]

Background: Mass drug administration (MDA) of sequential rounds of antimalarial drugs is being considered as a tool for malaria elimination. As an effective and long-acting antimalarial, Dihydroartemisinin-piperaquine (DHA/PQP) appears suitable as a candidate for MDA. However, absence of cardiac safety data following repeated administration hinders its use in the extended schedules proposed for MDA.

Methods: We conducted an interventional study in Lihir Island, Papua New Guinea, with healthy individuals aged 3 to 60 years who received a standard 3-day course of DHA/PQP on 3 consecutive months. Twelve-lead electrocardiography (ECG) readings were conducted pre-dose and 4h after the final dose of each month. The primary safety endpoint was QTc (using Fridericia's correction; QTcF) prolongation from baseline to 4h post-dosing. We compared the difference in prolongation between the third course post-dose and the first course post-dose.

Results: Of 84 enrolled participants, 69 (82%) completed all treatment courses and ECG measurements. The average increase in QTcF was 19.6 ms (SD 17.8) and 17.1 ms (SD 17.1) for the first-course and third-course post-dosing ECGs [risk difference -2.4 (95%CI - 6.9 to 2.1), p=0.285], respectively. We recorded QTcF prolongation >60 ms from baseline in 3 (4.3%) and 2 (2.9%) participants after the first course and third course (p=1.00), respectively. No participants had QTcF intervals >500 ms at any time point.

Conclusions: Three consecutive monthly courses of DHA/PQP were as safe as a single course. The absence of cumulative cardiotoxicity with repeated dosing support the use of monthly DHA/PQP as part of malaria elimination strategies.

https://ift.tt/2O9mX4M

In vitro activity of ceftazidime-avibactam and aztreonam-avibactam against OXA-48-carrying Enterobacteriaceae isolated as part of the International Network for Optimal Resistance Monitoring (INFORM) global surveillance program, 2012 to 2015 [Epidemiology and Surveillance]

Enterobacteriaceae producing the Ambler class D OXA-48 carbapenemase combined with additional resistance mechanisms, such as permeability defects or co-carriage of class A, B or C β-lactamases, can become highly resistant to most β-lactams currently in use, including carbapenems. A total of 45,872 Enterobacteriaceae clinical isolates collected in 39 countries as part of the International Network for Optimal Resistance Monitoring (INFORM) global surveillance study in 2012 to 2015 were tested for susceptibility to β-lactams and comparator agents by Clinical and Laboratory Standards Institute broth microdilution methodology and screened for the presence of β-lactamases. bla_OXA-48 and bla_OXA-48-like were detected in 333 isolates across 14 species of Enterobacteriaceae collected in 20 countries across the globe. Few agents tested were effective in vitro against the overall collection of OXA-48-producers (n=265), with tigecycline (MIC₉₀, 2 µg/mL; 92.5% susceptible), ceftazidime-avibactam (MIC₉₀, 4 µg/mL; 92.5% susceptible) and aztreonam-avibactam (MIC₉₀, 0.5 µg/mL; 99.6% of isolates testing with MIC ≤8 µg/mL) demonstrating the greatest activity. Similarly, colistin (MIC₉₀, 1 µg/mL; 94.2% susceptible), tigecycline (MIC₉₀, 2 µg/mL; 92.6% susceptible), ceftazidime-avibactam (MIC₉₀, >128 µg/mL; 89.7% susceptible), and aztreonam-avibactam (MIC₉₀, 4 µg/mL; 100% of isolates testing with MIC ≤8 µg/mL) were most active against OXA-48-like positive isolates (n=68). The in vitro activity of ceftazidime-avibactam was improved against the subset of metallo-β-lactamase (MBL)-negative, OXA-48- and OXA-48-like-positive isolates (99.2% and 100% susceptible, respectively). The data reported here support the continued investigation of ceftazidime-avibactam and aztreonam-avibactam for treatment of infections caused by carbapenem-resistant Enterobacteriaceae carrying OXA-48 and OXA-48-like β-lactamases in combination with serine- or metallo-β-lactamases.

https://ift.tt/2OUQqMY

Detection of carbapenemases-producing Enterobacteriaceae in positive blood culture using Immunochromatographic RESIST-4 O.K.N.V assay [Epidemiology and Surveillance]

We evaluated the performances of the RESIST-4.O.K.N.V assay (Coris®) on 98 isolates to detect OXA-48-like, KPC-, NDM- and VIM-type carbapenemases directly on positive human blood cultures. OXA-48-like and KPC-type isolates were correctly detected but detection of NDM and VIM-type was weak and variable. We show that repeating the test on a 4-hour subculture improves the detection of NDM- and VIM-type to 100%.

https://ift.tt/2O4auQ4

Investigating sulfoxide to sulfone conversion as a prodrug strategy for a PI4K inhibitor in a humanized mouse model of malaria [Experimental Therapeutics]

The in vivo antimalarial efficacies of two PI4K inhibitors, a 3,5-diaryl-2-aminopyrazine sulfoxide and its corresponding sulfone metabolite, were evaluated in the NOD-scid IL2R^null (NSG) murine malaria disease model of Plasmodium falciparum infection. We hypothesized that the sulfoxide would serve as a more soluble prodrug for the sulfone, which would lead to improved drug exposure on oral dosing. Both compounds had similar efficacy (ED₉₀ 0.1 mg.kg^–1) across a quadruple-dose regimen. Pharmacokinetic profiling revealed rapid sulfoxide clearance via conversion to the sulfone with the latter identified as the major active metabolite. When the sulfoxide was dosed, the exposure of the sulfone achieved was as much as 2.9-fold higher than when the sulfone was directly dosed, thereby demonstrating that the sulfoxide served as an effective prodrug for the treatment of malaria.

https://ift.tt/2ORyTWl

TRPM2 modulates neutrophil attraction to murine tumor cells by regulating CXCL2 expression

Abstract

In recent years, immune cells were shown to play critical roles in tumor growth and metastatic progression. In this context, neutrophils were shown to possess both pro- and anti-tumor properties. To exert their anti-tumor effect, neutrophils need to migrate towards, and form physical contact with tumor cells. Neutrophils secrete H₂O₂ in a contact-dependent mechanism, thereby inducing a lethal Ca²⁺ influx via the activation of the H₂O₂-dependent TRPM2 Ca²⁺ channel. Here, we explored the mechanism regulating neutrophil chemoattraction to tumor cells. Interestingly, we found that TRPM2 plays a role in this context as well, since it regulates the expression of potent neutrophil chemoattractants. Consequently, cells expressing reduced levels of TRPM2 are not approached by neutrophils. Together, these observations demonstrate how tumor cells expressing reduced levels of TRPM2 evade neutrophil cytotoxicity in two interrelated mechanisms—downregulation of neutrophil chemoattractants and blocking of the apoptotic Ca²⁺-dependent cascade. These observations demonstrate a critical role for TRPM2 in neutrophil-mediated immunosurveillance and identify cells expressing low levels of TRPM2, as a potential target for cancer therapy.

https://ift.tt/2PX8Ixk

Working with NCI Divisions, Offices and Centers to Advance Global Cancer Research

The Center for Global Health is partnering with NCI divisions, offices, and centers, and partners around the world to recognize World Cancer Research Day (WCRD) on September 24. WCRD is a global initiative to increase awareness about the importance of cancer research and the dedication of cancer researchers worldwide.

https://ift.tt/2NAfCft

Molecular Expression of Mg2+ regulator TRPM7 and CNNM4 in rat odontoblasts

Publication date: Available online 23 September 2018

Source: Archives of Oral Biology

Author(s): Jonghwa Won, Ji Hyun Kim, Seog Bae Oh

Abstract

Objective

Magnesium, the second most abundant cation in cellular fluid, is critical for mineralization of hard tissues. Among the molecules involved in cellular Mg²⁺ homeostasis, functional impairment of Mg²⁺ permeable ion channel TRPM7 or Mg²⁺ transporter CNNM4 have been found to result in severe hypomineralization of the enamel and dentin. However, molecular expressions of TRPM7, CNNM4 and their respective homologues have not been fully investigated in adult odontoblasts.

Design

Expressions of TRPM6, TRPM7, CNNM1, CNNM2, CNNM3, CNNM4 were screened in acutely dissociated rat odontoblasts by single cell RT-PCR. Among these candidates, expression levels of TRPM7 and CNNM4 were compared along the odontoblast layer by immunohistochemical analysis. Finally, the coexpression pattern of TRPM7 and CNNM4 in subcellular regions was examined by immunocytochemical analysis.

Results

ScRT-PCR revealed high expression rate of TRPM7 and CNNM4 in odontoblasts, with CNNM4 detected almost exclusively in TRPM7-positive odontoblasts. However, CNNM2 and CNNM3 were detected in only a small population of odontoblasts, and TRPM6 and CNNM1 were not detected even in the pulp tissue. Immunohistochemical analysis revealed higher CNNM4 expression in the apical odontoblast layer than the coronal area, in contrast to the ubiquitous expression of TRPM7. Lastly, immunocytochemical analysis revealed colocalization of CNNM4 with TRPM7 in the odontoblastic process.

Conclusions

CNNM4 and TRPM7 may serve as main Mg²⁺ regulators in odontoblasts, possibly with selective involvement of CNNM4 in apical dentin formation or mineralization. Colocalization of TRPM7 and CNNM4 in the odontoblastic process suggest functional coupling of these two molecules to maintain Mg²⁺ homeostasis.

https://ift.tt/2zr6tNy

Null Cell Adenoma of the Pituitary: Pseudo-rosettes Say It Best When Immunohistochemistry Says Nothing At All!

Abstract

Null cell adenoma is composed of adenohypophyseal cells that show no evidence of any specific cell type differentiation by immunohistochemistry or transcription factors like pituitary-specific positive transcription factor 1 and steroidogenic factor 1. Though rare, pituitary ependymoma and germinoma are also known to occur at sellar region and in such instances, it is challenging to differentiate them from a pituitary null cell adenoma featuring papillary architecture and perivascular pseudo-rosettes. We describe a case of an elderly diabetic lady presenting with headache and blurring of vision for past 3 months due to a sellar tumour. The histology was diagnostically challenging with notable presence of numerous perivascular pseudo-rosettes and negative immunoreactivity for all pituitary hormones. The differential diagnosis and importance of ancillary techniques is discussed.

https://ift.tt/2PWwiu6

Analytic and clinical validity of thyroid nodule mutational profiling using droplet digital polymerase chain reaction

Abstract

Background

Recent guidelines for the management of thyroid nodules incorporate mutation testing as an adjunct for surgical decision-making, however current tests are costly with limited accuracy. Droplet digital PCR (ddPCR) is an ultrasensitive method of nucleic acid detection that is particularly useful for identifying gene mutations. This study aimed to assess the analytic and clinical validity of RAS and BRAF ddPCR mutational testing as a diagnostic tool for thyroid fine needle aspirate biopsy (FNAB).

Methods

Patients with thyroid nodules meeting indication for FNAB were prospectively enrolled from March 2015 to September 2017. In addition to clinical protocol, an additional FNAB was obtained for ddPCR. Optimized ddPCR probes were used to detect mutations including HRASG12 V, HRASQ61K, HRASQ61R, NRASQ61R, NRASQ61K and BRAFV600E. The diagnostic performance of BRAF and RAS mutations was assessed individually or in combination with Bethesda classification against final surgical pathology.

Results

A total of 208 patients underwent FNAB and mutational testing with the following Bethesda cytologic classification: 26.9% non-diagnostic, 55.2% benign, 5.3% FLUS/AUS, 2.9% FN/SPN, 2.4% SFM and 7.2% malignant. Adequate RNA was obtained from 91.3% (190) FNABs from which mutations were identified in 21.1% of HRAS, 11.5% of NRAS and 7.4% of BRAF. Malignant cytology or BRAFV600E was 100% specific for malignancy. Combining cytology with ddPCR BRAF600E mutations testing increased the sensitivity of Bethesda classification from 41.7 to 75%. Combined BRAFV600E and Bethesda results had a positive predictive value (PPV) of 100% and negative predictive value (NPV) of 89.7% for thyroid malignancy in our cohort.

Conclusions

DdPCR offers a novel and ultrasensitive method of detecting RAS and BRAF mutations from thyroid FNABs. BRAFV600E mutation testing by ddPCR may serve as a useful adjunct to increase sensitivity and specificity of thyroid FNAB.

https://ift.tt/2pvCwWG

Quality of occlusal outcome following space closure in cases of lower second premolar aplasia using lingual orthodontic molar mesialization without maxillary counterbalancing extraction

Abstract

Background

Controlled space closure in cases of isolated lower second premolar aplasia (ILSPA) without maxillary counterbalancing extraction is challenging. Anterior anchorage loss may occur during space closure resulting in compromised occlusal results in terms of an absence of proper canine guidance during laterotrusive mandible movements.

In order to evaluate the effectiveness of Herbst telescope anchorage in combination with double-cable, pull mechanics and a completely customized lingual appliance for orthodontic space management in cases of ILSPA, we tested the null hypothesis that there is a significant deterioration in the sagittal canine relationship towards an Angle-Class-II occlusion expressed as a loss of anterior anchorage following space closure with molar mesialization.

Methods

Twenty-five consecutively de-bonded subjects (female / male 17 / 8; aged at T0 (start of MB Tx) 12.3 to 20.6 years; mean age 15.0 / SD 1.7 years) were included in this retrospective analysis using the inclusion criteria of least of one lower second premolar aplasia; completed treatment with a totally customized lingual appliance (CCLA) in combination with Herbst telescopes. Exclusion criteria were the absence of counterbalancing maxillary extractions, as well as additional tooth aplasia other than lower second premolars. A total of 33 single, lower premolar aplasia space closures (right / left sided 17 / 16) were assessed using plaster casts and intra-oral photographs scaled to the plaster casts, at bonding (T0), Herbst insertion (T1), following gap closure (T2) and de-bonding (T3). Parallelism of roots was controlled by panoramic x-rays at T3.

Results

The mean aplasia space at T0 was 7.5 mm (SD 2.6). Complete space closure was achieved in all 33 situations. The null hypothesis was rejected. There was a significant improvement in the initial canine relationships (mean 3.5 mm distal occlusion at T0) to a mean 0.1 mm at T3. When evaluated against the individual treatment plan, the following amounts of planned improvements were achieved: space closure 100%, canine relationship 97.5%, overjet 93.9%, overbite 96.4%, parallel roots in space closure site 93.9%.

Conclusion

Herbst telescope anchorage in combination with double-cable pull mechanics and a CCLA for orthodontic space closure can deliver predictable, high-quality treatment results.

https://ift.tt/2MX7hwZ

Phase 1-2a Study of EBNA1 Inhibitor, VK-2019, in Patients With Epstein-Barr Virus-positive Nasopharyngeal Cancer

Conditions:   Nasopharyngeal Carcinoma;   Nasopharyngeal Cancer
Intervention:   Drug: VK-2019
Sponsors:   Troy Messick;   Stanford University;   National Cancer Institute (NCI)
Not yet recruiting

https://ift.tt/2xM299D

Diagnostic Accuracy of Salivary DNA Integrity Index in Oral Malignant and Premalignant Lesions

Conditions:   Oral Cancer;   Oral Lichen Planus;   Oral Leukoplakia
Intervention:   Diagnostic Test: DNA Integrity Index
Sponsor:   Cairo University
Not yet recruiting

https://ift.tt/2QUM3De

Interventions for Patients With Alzheimer's Disease and Dysphagia

Conditions:   Dementia;   Dysphagia
Interventions:   Device: Isometric tongue strengthening;   Drug: Biotene
Sponsor:   University of Wisconsin, Madison
Recruiting

https://ift.tt/2xKeknm

Perioperative Analgesia Using Gabapentin in Head and Neck Cancer Surgery: A Randomized Controlled Trial

Conditions:   Cancer of Head and Neck;   Narcotic Use
Interventions:   Drug: Gabapentin;   Drug: Placebo - Concentrate
Sponsor:   University of California, Davis
Not yet recruiting

https://ift.tt/2QULQ2U

Null Cell Adenoma of the Pituitary: Pseudo-rosettes Say It Best When Immunohistochemistry Says Nothing At All!

Abstract

Null cell adenoma is composed of adenohypophyseal cells that show no evidence of any specific cell type differentiation by immunohistochemistry or transcription factors like pituitary-specific positive transcription factor 1 and steroidogenic factor 1. Though rare, pituitary ependymoma and germinoma are also known to occur at sellar region and in such instances, it is challenging to differentiate them from a pituitary null cell adenoma featuring papillary architecture and perivascular pseudo-rosettes. We describe a case of an elderly diabetic lady presenting with headache and blurring of vision for past 3 months due to a sellar tumour. The histology was diagnostically challenging with notable presence of numerous perivascular pseudo-rosettes and negative immunoreactivity for all pituitary hormones. The differential diagnosis and importance of ancillary techniques is discussed.

https://ift.tt/2PWwiu6

Consensus-Based Sorting of Neuronal Spike Waveforms

Fournier, J; Mueller, CM; Shein-Idelson, M; Hemberger, M; Laurent, G; (2016) Consensus-Based Sorting of Neuronal Spike Waveforms. PLoS ONE , 11 (8) , Article e0160494. 10.1371/journal.pone.0160494 . Green open access

https://ift.tt/2I9rsHi

Night work and risk of common mental disorders: Analyzing observational data as a non-randomized pseudo trial

Beltagy, MS; Pentti, J; Vahtera, J; Kivimäki, M; (2018) Night work and risk of common mental disorders: Analyzing observational data as a non-randomized pseudo trial. Scandinavian Journal of Work, Environment and Health , 44 (5) pp. 512-520. 10.5271/sjweh.3733 . Green open access

https://ift.tt/2puQxnz

Out of sight and maybe mined: legacies of marine contamination in a circular economy

Styan, CA; Vandeleur, H; (2018) Out of sight and maybe mined: legacies of marine contamination in a circular economy. In: Proceedings of the Unmaking Waste 2018. Zero Waste SA Research Centre for Sustainable Design and Behaviour, School of Art, Architecture and Design, University of South Australia: Adelaide, South Australia. (In press). Green open access

https://ift.tt/2IcdYuz

Quantitative mass spectrometry for human melanocortin peptides in vitro and in vivo suggests prominent roles for β-MSH and desacetyl α-MSH in energy homeostasis

Kirwan, P; Kay, RG; Brouwers, B; Herranz-Pérez, V; Jura, M; Larraufie, P; Jerber, J; ... Merkle, FT; + view all Kirwan, P; Kay, RG; Brouwers, B; Herranz-Pérez, V; Jura, M; Larraufie, P; Jerber, J; Pembroke, J; Bartels, T; White, A; Gribble, FM; Reimann, F; Farooqi, IS; O'Rahilly, S; Merkle, FT; - view fewer (2018) Quantitative mass spectrometry for human melanocortin peptides in vitro and in vivo suggests prominent roles for β-MSH and desacetyl α-MSH in energy homeostasis. Molecular Metabolism 10.1016/j.molmet.2018.08.006 . (In press). Green open access

https://ift.tt/2puQ3hf

The legacies of the Royal Institution

James, FAJL; (2018) The legacies of the Royal Institution. Physics Today , 71 (8) pp. 36-43. 10.1063/PT.3.3996 .

https://ift.tt/2IaWBtS

Cross-Phase Determination of Ultralow Frequency Wave Harmonic Frequencies and Their Associated Plasma Mass Density Distributions

Wharton, SJ; Wright, DM; Yeoman, TK; James, MK; Sandhu, JK; (2018) Cross-Phase Determination of Ultralow Frequency Wave Harmonic Frequencies and Their Associated Plasma Mass Density Distributions. Journal of Geophysical Research: Space Physics 10.1029/2018JA025487 . (In press). Green open access

https://ift.tt/2puPNyN

Resolving the internal and basal geometry of ice masses using imaging phase-sensitive radar

Young, TJ; Schroeder, DM; Christoffersen, P; Lok, LB; Nicholls, KW; Brennan, PV; Doyle, SH; ... Hubbard, A; + view all Young, TJ; Schroeder, DM; Christoffersen, P; Lok, LB; Nicholls, KW; Brennan, PV; Doyle, SH; Hubbard, B; Hubbard, A; - view fewer (2018) Resolving the internal and basal geometry of ice masses using imaging phase-sensitive radar. Journal of Glaciology , 64 (246) pp. 649-660. 10.1017/jog.2018.54 . Green open access

https://ift.tt/2I9rpv6

Search for heavy resonances decaying to a photon and a hadronically decaying Z/W/H boson in pp collisions at root s=13 TeV with the ATLAS detector

Aaboud, M; Aad, G; Abbott, B; Abdinov, O; Abeloos, B; Abidi, SH; AbouZeid, OS; ... Zwalinski, L; + view all Aaboud, M; Aad, G; Abbott, B; Abdinov, O; Abeloos, B; Abidi, SH; AbouZeid, OS; Abraham, NL; Abramowicz, H; Abreu, H; Abulaiti, Y; Acharya, BS; Adachi, S; Adamczyk, L; Adelman, J; Adersberger, M; Adye, T; Affolder, AA; Afik, Y; Agheorghiesei, C; Aguilar-Saavedra, JA; Ahmadov, F; Aielli, G; Akatsuka, S; Akesson, TPA; Akilli, E; Akimov, A; Alberghi, GL; Albert, J; Albicocco, P; Alconada Verzini, MJ; Alderweireldt, S; Aleksa, M; Aleksandrov, IN; Alexa, C; Alexander, G; Alexopoulos, T; Alhroob, M; Ali, B; Alimonti, G; Alison, J; Alkire, SP; Allaire, C; Allbrooke, BMM; Allen, BW; Allport, PP; Aloisio, A; Alonso, A; Alonso, F; Alpigiani, C; Alshehri, AA; Alstaty, M; Gonzalez, BA; Alvarez Piqueras, D; Alviggi, MG; Amadio, BT; Amaral Coutinho, Y; Ambroz, L; Amelung, C; Amidei, D; Amor Dos Santos, SP; Amoroso, S; Amrouche, CS; Anastopoulos, C; Ancu, LS; Andari, N; Andeen, T; Anders, CF; Anders, JK; Anderson, KJ; Andreazza, A; Andrei, V; Angelidakis, S; Angelozzi, I; Angerami, A; Anisenkov, A; Annovi, A; Antel, C; Anthony, MT; Antonelli, M; Antrim, DJA; Anulli, F; Aoki, M; Bella, LA; Arabidze, G; Arai, Y; Araque, JP; Araujo Ferraz, V; Araujo Pereira, R; Arce, ATH; Ardell, RE; Arduh, FA; Arguin, J-F; Argyropoulos, S; Armbruster, AJ; Armitage, LJ; Arnaez, O; Arnold, H; Arratia, M; Arslan, O; Artamonov, A; Artoni, G; Artz, S; Asai, S; Asbah, N; Ashkenazi, A; Asimakopoulou, EM; Asquith, L; Assamagan, K; Astalos, R; Atkin, RJ; Atkinson, M; Atlay, NB; Augsten, K; Avolio, G; Avramidou, R; Axen, B; Ayoub, MK; Azuelos, G; Baas, AE; Baca, MJ; Bachacou, H; Bachas, K; Backes, M; Bagnaia, P; Bahmani, M; Bahrasemani, H; Bailey, AJ; Baines, JT; Bajic, M; Baker, OK; Bakker, PJ; Gupta, DB; Baldin, EM; Balek, P; Balli, F; Balunas, WK; Banas, E; Bandyopadhyay, A; Banerjee, S; Bannoura, AAE; Barak, L; Barbe, WM; Barberio, EL; Barberis, D; Barbero, M; Barillari, T; Barisits, M-S; Barkeloo, J; Barklow, T; Barlow, N; Barnea, R; Barnes, SL; Barnett, BM; Barnett, RM; Barnovska-Blenessy, Z; Baroncelli, A; Barone, G; Barr, AJ; Barranco Navarro, L; Barreiro, F; da Costa, JBG; Bartoldus, R; Barton, AE; Bartos, P; Basalaev, A; Bassalat, A; Bates, RL; Batista, SJ; Batlamous, S; Batley, JR; Battaglia, M; Bauce, M; Bauer, F; Bauer, KT; Bawa, HS; Beacham, JB; Beattie, MD; Beau, T; Beauchemin, PH; Bechtle, P; Beck, HC; Beck, HP; Becker, K; Becker, M; Becot, C; Beddall, A; Beddall, AJ; Bednyakov, VA; Bedognetti, M; Bee, CP; Beermann, TA; Begalli, M; Begel, M; Behera, A; Behr, JK; Bell, AS; Bella, G; Bellagamba, L; Bellerive, A; Bellomo, M; Belotskiy, K; Belyaev, NL; Benary, O; Benchekroun, D; Bender, M; Benekos, N; Benhammou, Y; Noccioli, EB; Benitez, J; Benjamin, DP; Benoit, M; Bensinger, JR; Bentvelsen, S; Beresford, L; Beretta, M; Berge, D; Kuutmann, EB; Berger, N; Bergsten, LJ; Beringer, J; Berlendis, S; Bernard, NR; Bernardi, G; Bernius, C; Bernlochner, FU; Berry, T; Berta, P; Bertella, C; Bertoli, G; Bertram, IA; Bertsche, C; Besjes, GJ; Bylund, OB; Bessner, M; Besson, N; Bethani, A; Bethke, S; Betti, A; Bevan, AJ; Beyer, J; Bianchi, RMB; Biebel, O; Biedermann, D; Bielski, R; Bierwagen, K; Biesuz, N; Biglietti, M; Billoud, TR; Bindi, M; Bingul, A; Bini, C; Biondi, S; Bisanz, T; Bittrich, C; Bjergaard, DM; Black, JE; Black, KM; Blair, RE; Blazek, T; Bloch, I; Blocker, C; Blue, A; Blumenschein, U; Blunier, D; Bobbink, GJ; Bobrovnikov, VS; Bocchetta, SS; Bocci, A; Bock, C; Boerner, D; Bogavac, D; Bogdanchikov, AG; Bohm, C; Boisvert, V; Bokan, P; Bold, T; Boldyrev, AS; Bolz, AE; Bomben, M; Bona, M; Bonilla, JS; Boonekamp, M; Borisov, A; Borissov, G; Bortfeldt, J; Bortoletto, D; Bortolotto, V; Boscherini, D; Bosman, M; Bossio Sola, JD; Boudreau, J; Bouhova-Thacker, E; Boumediene, D; Bourdarios, C; Boutle, SK; Boveia, A; Boyd, J; Boyko, IR; Bozson, AJ; Bracinik, J; Brahimi, N; Brandt, A; Brandt, G; Brandt, O; Braren, F; Bratzler, U; Brau, B; Brau, JE; Madden, WDB; Brendlinger, K; Brennan, AJ; Brenner, L; Brenner, R; Bressler, S; Brickwedde, B; Briglin, DL; Bristow, TM; Britton, D; Britzger, D; Brock, I; Brock, R; Brooijmans, G; Brooks, T; Brooks, WK; Brost, E; Broughton, JH; de Renstrom, PAB; Bruncko, D; Bruni, A; Bruni, G; Bruni, LS; Bruno, S; Brunt, BH; Bruschi, M; Bruscino, N; Bryant, P; Bryngemark, L; Buanes, T; Buat, Q; Buchholz, P; Buckley, AG; Budagov, IA; Buehrer, F; Bugge, MK; Bulekov, O; Bullock, D; Burch, TJ; Burdin, S; Burgard, CD; Burger, AM; Burghgrave, B; Burka, K; Burke, S; Burmeister, I; Burr, JTP; Buescher, D; Buescher, V; Buschmann, E; Bussey, P; Butler, JM; Buttar, CM; Butterworth, JM; Butti, P; Buttinger, W; Buzatu, A; Buzykaev, AR; Cabras, G; Cabrera Urban, S; Caforio, D; Cai, H; Cairo, VMM; Cakir, O; Calace, N; Calafiura, P; Calandri, A; Calderini, G; Calfayan, P; Callea, G; Caloba, LP; Calvente Lopez, S; Calvet, D; Calvet, S; Calvet, TP; Calvetti, M; Toro, RC; Camarda, S; Camarri, P; Cameron, D; Armadans, RC; Camincher, C; Campana, S; Campanelli, M; Camplani, A; Campoverde, A; Canale, V; Bret, MC; Cantero, J; Cao, T; Cao, Y; Garrido, MDMC; Caprini, I; Caprini, M; Capua, M; Carbone, RM; Cardarelli, R; Cardillo, FC; Carli, I; Carli, T; Carlino, G; Carlson, BT; Carminati, L; Carney, RMD; Caron, S; Carquin, E; Carra, S; Carrillo-Montoya, GD; Casadei, D; Casado, MP; Casha, AF; Casolino, M; Casper, DW; Castelijn, R; Castillo Gimenez, V; Castro, NF; Catinaccio, A; Catmore, JR; Cattai, A; Caudron, J; Cavaliere, V; Cavallaro, E; Cavalli, D; Cavalli-Sforza, M; Cavasinni, V; Celebi, E; Ceradini, F; Cerda Alberich, L; Cerqueira, AS; Cerri, A; Cerrito, L; Cerutti, F; Cervelli, A; Cetin, SA; Chafaq, A; Chakraborty, D; Chan, SK; Chan, WS; Chan, YL; Chang, P; Chapman, JD; Charlton, DG; Chau, CC; Barajas, CAC; Che, S; Chegwidden, A; Chekanov, S; Chekulaev, S; Chelkov, GA; Chelstowska, MA; Chen, C; Chen, CH; Chen, H; Chen, J; Chen, S; Chen, SJ; Chen, X; Chen, Y; Chen, Y-H; Cheng, HC; Cheng, HJ; Cheplakov, A; Cheremushkina, E; El Moursli, RC; Cheu, E; Cheung, K; Chevalier, L; Chiarella, V; Chiarelli, G; Chiodini, G; Chisholm, AS; Chitan, A; 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Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data (vol 8, 1300, 2018)

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The lessons of policy learning: types, triggers, hindrances and pathologies

Dunlop, CA; Radaelli, CM; (2018) The lessons of policy learning: types, triggers, hindrances and pathologies. Policy & Politics , 46 (2) pp. 255-272. 10.1332/030557318X15230059735521 . Green open access

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Deformations of Conically Singular Cayley Submanifolds

Moore, K; (2018) Deformations of Conically Singular Cayley Submanifolds. Journal of Geometric Analysis 10.1007/s12220-018-0074-7 . (In press). Green open access

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Evidence for the Higgs boson decay to a bottom quark-antiquark pair

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Physics Letters B , 780 pp. 501-532. 10.1016/j.physletb.2018.02.050 . Green open access

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