Analysis of the yearly transition function in measles disease modeling.

Globally, there were an estimated 9.8 million measles cases and 207 500 measles deaths in 2019. As the effort to eliminate measles around the world continues, modeling remains a valuable tool for public health decision-makers and program implementers. This study presents a novel approach to the use of a yearly transition function that formulates mathematically the vaccine schedules for different age groups while accounting for the effects of the age of vaccination, the timing of vaccination, and disease seasonality on the yearly number of measles cases in a country. The methodology presented adds to an existing modeling framework and expands its analysis, making its utilization more adjustable for the user and contributing to its conceptual clarity. This article also adjusts for the temporal interaction between vaccination and exposure to disease, applying adjustments to estimated yearly counts of cases and the number of vaccines administered that increase population immunity. These new model features provide the ability to forecast and compare the effects of different vaccination timing scenarios and seasonality of transmission on the expected disease incidence. Although the work presented is applied to the example of measles, it has potential relevance to modeling other vaccine-preventable diseases.

Hepatitis C subtype distribution in chronically infected patients with mild liver fibrosis in France: the GEMHEP study.

Treatment options for Hepatitis C infection have greatly improved with direct-acting antiviral (DAA) combinations achieving high cure rates. Nevertheless, the cost of this treatment is still high and access to treatment in many countries has been preferentially reserved for patients with more severe fibrosis (F3 and F4). In this French nationwide study, we investigated the epidemiological characteristics and genotype distribution of hepatitis C virus (HCV) in treatment-naive patients with METAVIR fibrosis stages between F0 and F2 in order to identify patient profiles that became eligible for unrestricted treatment in a second period. Between 2015 and 2016 we collected data from nine French university hospitals on a total of 584 HCV positive patients with absent, mild or moderate liver fibrosis. The most represented genotypes were genotype 1b (159/584; 27.2%), followed by genotype 1a (150/584; 25.7%); genotype 3 (87/584: 14.9%); genotype 4 (80/584; 13.7%). Among genotype 4: 4a was predominantly encountered with 22 patients (27.5% of genotype 4). Genotypes 1b and 1a are currently the most frequent virus types present in treatment-naive patients with mild fibrosis in France. They can be readily cured using the available DAA. Nevertheless, non-a/non-d genotype 4 is also frequent in this population and clinical data on the efficacy of DAA on these subtypes is missing. The GEMHEP is the French group for study and evaluation of viral hepatitis on a national scale. Data collection on epidemiological and molecular aspects of viral hepatitis is performed on a regular basis in all main French teaching hospitals and serves as a basis for surveillance of these infections. Analysis and trends are regularly published on behalf of the GEMHEP group. Data collection was performed retrospectively over the 2015-2016 period, covering nine main university hospitals in France. A total of 584 hepatitis C positive patients were included in this study. Genotyping of the circulating viruses showed a high prevalence of genotypes 1b and 1a in our population. The epidemiology of hepatitis C is slowly changing in France, particularly as a consequence of the rise of 'non-a non-d' genotype 4 viruses mainly originating from African populations. More data concerning treatment efficacy of these genotypes is needed in order to guide clinical care.

Three-dimensional modeling and numerical predictions of multimodal nonlinear behavior in damaged concrete blocks.

In this paper, the multimodal nonlinear elastic behavior of concrete, which is representative of a consolidated granular material, is modeled numerically. Starting from a local three-dimensional softening law, the initial stiffness properties are re-estimated according to the local strain field. The experiments deal with samples of thermally damaged concrete blocks successively excited around their first three modes of vibration. The geometry of these samples cannot be described by a one-dimensional approximation in these experiments where compressional and shear motions are strongly coupled. Despite this added complexity, the nonlinear behavior for the three modes of vibration of the samples is well captured by the simulations using a single scalar nonlinear parameter appropriately integrated into the elasticity equations. It is shown that without sufficient attention paid to the latter, the conclusions would have brought erroneous statements such as nonlinearity dispersion or strain type dependence.

Interest of human papillomavirus DNA quantification and genotyping in paired cervical and urine samples to detect cervical lesions.

BACKGROUND: Cervical cancer is caused by persistent infection with high-risk human papillomavirus (HR-HPV). Conventional human papillomavirus (HPV) testing requires cervical sampling. However, vaginal and urine self-sampling methods are more acceptable for patients and result in increased participation when they are available in screening programs. In this context, we have developed a non-invasive screening method via the detection of HPV DNA in urine samples. PURPOSE: To compare HPV viral loads and genotypes in paired cervical and urine samples, and to assess correlation between virological and cytological results in women seeking gynecological consultation. METHODS: Paired urine and cervical specimens were collected and analyzed from 230 of 245 women participating in the previously described prospective PapU study. HPV DNA detection and quantification were performed using a real-time PCR method with short fragment PCR primers. Genotyping was carried out using the INNO-LiPA HPV genotyping assay. RESULTS: The prevalence of HPV in the 230 paired urine and cervical smear samples was 42 and 49 %, respectively. Overall agreement for HPV positivity and negativity between the paired samples was 90 % (κ = 0.80). High HPV viral load in both cervical and urine samples was associated with cytological abnormalities. HPV-positive women were mostly infected with HR-HPV types. The agreement between high- and low-risk HPV (LR-HPV) detection in both samples was 97 % (κ = 0.95 for HR-HPV and κ = 0.97 for LR-HPV). CONCLUSIONS: High concordance rates for HPV-DNA quantification and high/low-risk HPV genotyping in paired urine/cervical samples suggest that urinary HPV DNA testing could be useful for cervical lesion screening.

Quantitative linear and nonlinear resonance inspection techniques and analysis for material characterization: application to concrete thermal damage.

Developed in the late 1980s, Nonlinear Resonant Ultrasound Spectroscopy (NRUS) has been widely employed in the field of material characterization. Most of the studies assume the measured amplitude to be proportional to the strain amplitude which drives nonlinear phenomena. In 1D resonant bar experiments, the configuration for which NRUS was initially developed, this assumption holds. However, it is not true for samples of general shape which exhibit several resonance mode shapes. This paper proposes a methodology based on linear resonant ultrasound spectroscopy, numerical simulations and nonlinear resonant ultrasound spectroscopy to provide quantitative values of nonlinear elastic moduli taking into account the 3D nature of the samples. In the context of license renewal in the field of nuclear energy, this study aims at providing some quantitative information related to the degree of micro-cracking of concrete and cement based materials in the presence of thermal damage. The resonance based method is validated as regard with concrete microstructure evolution during thermal exposure.

Applying diffuse ultrasound under dynamic loading to improve closed crack characterization in concrete.

Recent studies show the ability of diffuse ultrasound to characterize surface breaking cracks in concrete. However, derived parameters are sensitive to the presence of partially opened zones along the crack whose pattern may differ from one sample to another. The aim of this letter is to study the variation of diffuse ultrasound parameters while the sample is driven by a low frequency bending load which alternatively opens and closes the crack, allowing to access supplementary information about its morphology. The results show the sensitivity of the method for various crack depths and highlight its potential for concrete nondestructive evaluation.

Attitudes and expectations of patients with neuromuscular diseases about their participation in a clinical trial.

AIM: This study aimed to gain a better understanding of the psychological impact of participating in a clinical trial for patients with Pompe disease (Acid Maltase Deficiency). Attitudes and expectations of adult patients with neuromuscular diseases regarding medical trials are as yet unreported. In order to learn about the psychological consequences of participating in a clinical trial, we conducted a prospective assessment of patients with late-onset Pompe Disease, a rare genetic condition, for which no treatment had been available before. This psychological study was carried out as an ancillary study to the randomized double-blind placebo-controlled trial described elsewhere (van der Ploeg et al., 2010). SUBJECTS AND METHODS: We assessed patients (n=8) at inclusion, and at 12 and 18 months for six psychological dimensions: depression (Beck Depression Inventory, BDI), hopelessness (Beck Hopelessness Scale, BHS), anxiety (STAI A-B), quality of life (Whoqol-26), social adjustment (S.A.S-self-report) and locus of control (IPC Levenson). We produced a self-administered questionnaire in order to assess the attitudes, motivations and expectations of patients during the trial. RESULTS: At 12 months, mean social adjustment (SAS-SR, P=0.02) had improved, and at 18 months mean depression score had improved as well (BDI, P=0.03). The quality of life of patients (Whoqol-26) remained unchanged. Throughout the study, patients were more likely to have an internal locus of control than an external one (IPC Levenson). The self-administered questionnaire showed that patients' expectations were disproportionate compared to the medical information they had received starting the trial. For all patients, the first motivation for being enrolled in a clinical trial was "to help research", for half of them the motivation was to "improve their health". Whether patients believed to be part of one group or another (placebo or treatment) depended on their subjective perception of improvement during the trial. CONCLUSION: Given the small sample size, the conclusions of this study are preliminary. However, findings do suggest that there is a positive psychological impact of participating in a treatment trial. Moreover, the patients' reactions upon unblinding have led us to recommend that patients be asked whether they would like their group assignation disclosed to them or not.

[Soft tissue infection associated with bacteremia caused by Shewanella putrefaciens]. / Dermohypodermite et bactériémie àShewanella putrefaciens.

Shewanella putrefaciens is rarely involved in human infectious disease. We report here a case of soft tissue infection with bacteremia on a patient with risk factors (liver cirrhosis, diabetes mellitus).

[Epidemiology of healthcare-associated infections due to MRSA in Brest University Hospital from 2004 to 2007. Impact of hydroalcoholic gel and antibiotics consumptions]. / Épidémiologie des infections nosocomiales à SARM au CHU de Brest du 1(er) janvier 2004 au 31 décembre 2007. Impact des consommations de produits hydroalcooliques et d'antibiotiques.

UNLABELLED: The fight against healthcare-associated infections is based on preventive measures of multidrug resistant bacteria diffusion. Hand hygiene is the simplest and the most effective preventive measure to reduce cross-transmission of infectious agents. Hydroalcoholic solutions for hand hygiene was recently introduced in the University Hospital of Brest (France). The aims of the study were: to describe the epidemiology of healthcare-associated infections due to methicillin-resistant Staphylococcus aureus (MRSA); to determine the annual consumptions of antistaphylococcal antibiotics; and to discuss the relation between consumption of antiseptic products or antibiotics and the epidemiology of MRSA. METHODS: A retrospective epidemiological and pharmaco-epidemiological study was realized from January 2004 to December 2007 in the University Hospital of Brest (France). It allowed to bring to light the cases of healthcare-associated infections due to MRSA and to quantify the consumptions of hang hygiene products and antistaphylococcal antibiotics. RESULTS: this retrospective study showed a decrease of healthcare-associated infections due to MRSA and an increase of the consumption of hydroalcoholic solutions. Antistaphylococcal resistance rates also decreased in a context of fall of the global antibiotics consumption in the hospital.

Microbubble cloud characterization by nonlinear frequency mixing.

In the frame of the fourth generation forum, France decided to develop sodium fast nuclear reactors. French Safety Authority requests the associated monitoring of argon gas into sodium. This implies to estimate the void fraction, and a histogram indicating the bubble population. In this context, the present letter studies the possibility of achieving an accurate determination of the histogram with acoustic methods. A nonlinear, two-frequency mixing technique has been implemented, and a specific optical device has been developed in order to validate the experimental results. The acoustically reconstructed histograms are in excellent agreement with those obtained using optical methods.

Effect of the presence and size of a localized nonlinear source in concrete.

The aim of the present letter is to identify the contribution of a macroscopic source of elastic nonlinearity in concrete, a medium which by nature is nonlinear, and belongs to the nonlinear mesoscopic class of materials. The influence of real, localized macro-cracks is characterized with respect to the intrinsic nonlinearity of the material. The influence of the size of the source on the amplitude of the measured nonlinearity is qualitatively demonstrated. A comparison is made between the changes in linear and nonlinear parameters.

Periodic salbutamol in facioscapulohumeral muscular dystrophy: a randomized controlled trial.

OBJECTIVE: To evaluate the effects on muscle strength of salbutamol administered for 6 months using a periodic regimen in patients presenting with facioscapulohumeral muscular dystrophy (FSHD). DESIGN: Placebo-controlled double-blind randomized study. SETTING: Three clinical centers involved in neuromuscular disorders. PARTICIPANTS: Ambulatory patients (N=112), 56 per group, with genetically confirmed FSHD, age 18 to 60 years. INTERVENTIONS: Salbutamol (sustained released formulation) administered orally at a daily dose of 16 mg using a periodic dosage regimen (3 wks on, 1 wk off). MAIN OUTCOME MEASURES: Muscle strength was assessed with quantitative muscle testing (QMT), manual muscle testing (MMT), and timed motor tests. Patients were evaluated at baseline, and 3 and 6 months later. Plasma drug assays were carried out at each visit. RESULTS: There was no significant change with periodic use of salbutamol in the total composite QMT z-score, MMT score, or timed motor tests. Salbutamol was well tolerated. Lack of efficacy did not seem to be related to plasma concentrations, which were within the expected range. CONCLUSIONS: Results from this study and previous controlled trials preclude at present the use of salbutamol as routine treatment for FSHD, even if we cannot exclude improvement from anabolic effects with a longer duration of treatment.

[Ventricular dysfunction during acute fever in Dakar, Senegal. Clinical data and serological studies]. / Dysfonction ventriculaire aiguë fébrile à Dakar. Données cliniques et enquête sérologique.

During a study, the authors observed clinical and ultrasound evidence of "ventricular dysfunction during acute fever" due to ue to "severe acute myocarditis" supports therapeutic management since 4/8 patients in this study were infected either by Chlamydia (CT and especially CP) or by Mycoplasma pneumoniae, that are both sensitive to antimicrobial therapy using macrolides. Five of 8 patients presented coinfection with 2 and even 3 infectious agents (CP-enterovirus-adenovirus).

Arthroscopically assisted reduction of acute acromioclavicular joint dislocation using a single double-button device: Medium-term clinical and radiological outcomes.

INTRODUCTION: Double-button devices for endoscopic management of acute acromioclavicular joint dislocation (ACJD) provide satisfactory short-term functional and radiological results. However, little exists in the literature regarding the long- and medium-term results of these implants, especially regarding the evolution of the acromioclavicular joint (ACJ). HYPOTHESIS: Satisfactory and steady long- and medium-term outcomes can be achieved in patients with acute ACJD undergoing endoscopically assisted ACJ repair using a single double-button device. MATERIAL AND METHOD: A retrospective single-center study was conducted in patients with acute Rockwood III and IV ACJD treated endoscopically with a single double-button device from October 2008 to October 2010, allowing a minimum 5-year follow-up. Functional evaluation used Constant and Quick-DASH scores. Clinical evidence of dislocation recurrence was combined with bilateral Zanca views to assess coracoclavicular distance. Acromioclavicular osteoarthritis was evaluated on the Paxinos test and Zanca views. RESULTS: Nineteen of the 25 operated patients were seen at a mean 76.9±8.5 months' follow-up. Mean age was 34.4±8.3 years. Mean Constant and Quick-DASH scores were 96.2±5.1 and 0.9±1.6 points, respectively. Four patients had a recurrence of their initial dislocation, 3 of whom had positive Paxinos test, whereas the 15 patients without recurrence had a negative test (p=0.004). Five patients had radiological evidence of ACJ osteoarthritis: all 4 patients with recurrence and 1 without (p=0.001). CONCLUSION: Long- and medium-term radioclinical outcome of endoscopically assisted management of acute ACJD using a single double-button device seems to be satisfactory and steady over time. Recurrence of the initial dislocation appears to be related to onset of degenerative ACJ arthropathy. LEVEL OF EVIDENCE: Therapeutic type IV-Retrospective case series.

Genetic diversity of the hepatitis C virus: impact and issues in the antiviral therapy.

The hepatitis C Virus (HCV) presents a high degree of genetic variability which is explained by the combination of a lack of proof reading by the RNA dependant RNA polymerase and a high level of viral replication. The resulting genetic polymorphism defines a classification in clades, genotypes, subtypes, isolates and quasispecies. This diversity is known to reflect the range of responses to Interferon therapy. The genotype is one of the predictive parameters currently used to define the antiviral treatment strategy and the chance of therapeutic success. Studies have also reported the potential impact of the viral genetic polymorphism in the outcome of antiviral therapy in patients infected by the same HCV genotype. Both structural and non structural genomic regions of HCV have been suggested to be involved in the Interferon pathway and the resistance to antiviral therapy. In this review, we first detail the viral basis of HCV diversity. Then, the HCV genetic regions that may be implicated in resistance to therapy are described, with a focus on the structural region encoded by the E2 gene and the non-structural genes NS3, NS5A and NS5B. Both mechanisms of the Interferon resistance and of the new antiviral drugs are described in this review.

Evaluation of quantitative PCR for early diagnosis of Pseudomonas aeruginosa infection in cystic fibrosis: a prospective cohort study.

OBJECTIVES: Early detection of Pseudomonas aeruginosa lung positivity is a key element in cystic fibrosis (CF) management. PCR has increased the accuracy of detection of many microorganisms. Clinical relevance of P. aeruginosa quantitative PCR (qPCR) in this context is unclear. Our aim was to determine P. aeruginosa qPCR sensitivity and specificity, and to assess the possible time saved by qPCR in comparison with standard practice (culture). METHODS: A multicentre cohort study was conducted over a 3-year period in 96 patients with CF without chronic P. aeruginosa colonization. Sputum samples were collected at each visit. Conventional culture and two-step qPCR (oprL qPCR and gyrB/ecfX qPCR) were performed for 707 samples. The positivity criteria were based on the qPCR results, defined in a previous study as follow: oprL qPCR positivity alone if bacterial density was <730 CFU/mL or oprL qPCR combined with gyrB/ecfX qPCR if bacterial density was ≥730 CFU/mL. RESULTS: During follow up, 36 of the 96 patients with CF were diagnosed on culture as colonized with P. aeruginosa. This two-step qPCR displayed a sensitivity of 94.3% (95% CI 79.7%-98.6%), and a specificity of 86.3% (95% CI 83.4%-88.7%). It enabled P. aeruginosa acquisition to be diagnosed earlier in 20 patients, providing a median detection time gain of 8 months (interquartile range 3.7-17.6) for them. CONCLUSIONS: Implementing oprL and gyrB/ecfX qPCR in the management of patients with CF allowed earlier detection of first P. aeruginosa lung positivity than culture alone.

Immune restoration under HAART in patients chronically infected with HIV-1: diversity of T, B, and NK immune responses.

The aim of the study was to follow prospectively the humoral, cellular and innate immune responses under HAART and to verify if a functional restoration of the B lymphocytes could be evaluated by measuring the anti-HIV-1 IgG antibodies avidity index (AI). Eleven HIV-1 infected and immunosuppressed patients were included in the study. Viral load, naive and memory B-cells, CD4 and CD8 T-cells and NK-cells counts, and anti-HIV-1 IgG AI were determined during the follow-up (18 months). Ten patients were sustained responders under HAART and showed a quantitative restoration of the CD4 T-cell counts (+269 x 10(6)/L). The AI decreased for ten subjects (-11%, p = 0.006) but very slowly and continuously. A quantitative restoration of the humoral immune response began, mainly concerning the naive B-cells (+110 x 10(6)/L). Apart from one patient, the CD8 T-cell subset approached the reference values of healthy subjects either by decreasing or increasing their cell levels. No homogeneous evolution was described concerning the NK-cell subset, apart from trend towards increasing in patients with opportunistic infection (range, +58 to +291 x 10(6)/L). Our study, which evaluated simultaneously for the first time to our knowledge the cellular, humoral and innate immune responses showed that HAART induced a large diversity of immune restoration patterns in responder patients. However, the AI measure appears to be a weak marker to evaluate an immune restoration in chronic HIV-1 infected patients under HAART.

Virucidal activity of a new hand disinfectant with reduced ethanol content: comparison with other alcohol-based formulations.

A new formula with reduced ethanol content (55%) in combination with 10% propan-1-ol, 5.9% propan-1.2-diol, 5.7% butan-1.3-diol and 0.7% phosphoric acid exhibited a broad spectrum of virucidal activity. In quantitative suspension tests, with and without protein load, this formulation reduced the infectivity titre of seven enveloped (influenza A and B, herpes simplex 1 and 2, bovine corona, respiratory syncytial, vaccinia, hepatitis B, bovine viral diarrhoea) and four non-enveloped (hepatitis A, polio, rota, feline calici) viruses >10(3)-fold within 30s. In comparative testing, only 95% ethanol showed similar levels of activity. In fingerpad tests, the formulation produced a log10 reduction factor of the titre of poliovirus type 1 (Sabin) of 3.04 in 30s compared with 1.32 by 60% propan-2-ol. Testing against feline calicivirus produced a log10 reduction factor of 2.38 by the test formulation; in contrast, the log10 reduction factors with 70% ethanol and 70% propan-1-ol were 0.68 and 0.70, respectively.

[A motor function measurement scale for neuromuscular diseases - description and validation study]. / La mesure de fonction motrice, outil d'évaluation clinique des maladies neuromusculaires. Etude de validation.

A new scale for motor function measurement has been developed for neuromuscular diseases. After the study of a preliminary and a first version, the validation study included 303 patients, aged 6 to 62 years. Seventy-two patients had Duchenne muscular dystrophy, 32 Becker muscular dystrophy, 30 limb-girdle muscular dystrophy, 39 facio-scapulo-humeral dystrophy, 29 myotonic dystrophy, 21 congenital myopathy, 10 congenital muscular dystrophy, 35 spinal muscular atrophy and 35 hereditary neuropathy. The sensitivity for change was evaluated with 152 patients one year after. The scale comprised 32 items, in three dimensions: standing position and transfers, axial and proximal motor function, distal motor function. High correlations (>0.80) were found between the total score and other scores: Vignos and Brooke grades, Functional Independence Measure, the global severity of disability evaluated with visual analog scales by physicians and physiotherapists. This scale is reliable, does not require any special equipment and is well accepted by patients. It takes an average of 36 min (range 8-75) to complete the scale. Preliminary results of the second evaluation showed good sensitivity to change since last visit, considering rating by patient, investigator or physiotherapist. Also, significant differences in scores are obtained with the greatest deterioration observed in Duchenne patients.

Dynamic acousto-elastic test using continuous probe wave and transient vibration to investigate material nonlinearity.

This study demonstrates the feasibility of the dynamic acousto-elastic effect of a continuous high frequency wave for investigating the material nonlinearity upon transient vibration. The approach is demonstrated on a concrete sample measuring 15×15×60cm(3). Two ultrasonic transducers (emitter and receiver) are placed at its middle span. A continuous high frequency wave of 500kHz propagates through the material and is modulated with a hammer blow. The position of the hammer blow on the sample is configured to promote the first bending mode of vibration. The use of a continuous wave allows discrete time extraction of the nonlinear behavior by a short-time Fourier transform approach, through the simultaneous comparison of a reference non-modulated signal and an impact-modulated signal. The hammer blow results in phase shifts and variations of signal amplitude between reference and perturbed signals, which are driven by the resonant frequency of the sample. Finally, a comprehensive analysis of the relaxation mechanisms (modulus and attenuation recovery) is conducted to untangle the coupled fast and slow hysteretic effects.