Landau-Zener problem in a three-level neutrino system with non-linear time dependence

We consider the level-crossing problem in a three-level system with non-linearly time-varying Hamiltonian (time-dependence $t^{-3}$). We study the validity of the so-called independent crossing approximation in the Landau-Zener model by making comparison with results obtained numerically in density matrix approach. We also demonstrate the failure of the so-called "nearest zero" approximation of the Landau-Zener level-crossing probability integral.Comment: 11 pages, 3 figures. To be published in Physical Review

Markers of epidemiological success of methicillin-resistant Staphylococcus aureus isolates in European populations

Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) infections impose a considerable burden on health systems, yet there is remarkable variation in the global incidence and epidemiology of MRSA. The MACOTRA consortium aimed to identify bacterial markers of epidemic success of MRSA isolates in Europe using a representative MRSA collection originating from France, the Netherlands and the United Kingdom. Methods: Operational definitions of success were defined in consortium meetings to compose a balanced strain collection of successful and sporadic MRSA isolates. Isolates were subjected to antimicrobial susceptibility testing and whole-genome sequencing; genes were identified and phylogenetic trees constructed. Markers of epidemiological success were identified using genome-based time-scaled haplotypic density analysis and linear regression. Antimicrobial usage data from ESAC-Net was compared with national MRSA incidence data. Results: Heterogeneity of MRSA isolate collections across countries hampered the use of a unified operational definition of success; therefore, country-specific approaches were used to establish the MACOTRA strain collection. Phenotypic antimicrobial resistance varied within related MRSA populations and across countries. In time-scaled haplotypic density analysis, fluoroquinolone, macrolide and mupirocin resistance were associated with MRSA success, whereas gentamicin, rifampicin and trimethoprim resistance were associated with sporadicity. Usage of antimicrobials across 29 European countries varied substantially, and β-lactam, fluoroquinolone, macrolide and aminoglycoside use correlated with MRSA incidence. Discussion: Our results are the strongest yet to associate MRSA antibiotic resistance profiles and antibiotic usage with the incidence of infection and successful clonal spread, which varied by country. Harmonized isolate collection, typing, resistance profiling and alignment with antimicrobial usage over time will aid comparisons and further support country-specific interventions to reduce MRSA burden

Variations of CYP3A activity induced by antiretroviral treatment in HIV-1 infected patients.

OBJECTIVE: To measure the in vivo variations of CYP3A activity induced by anti-HIV drugs in human immunodeficiency virus (HIV)1-positive patients. METHODS: A low oral dose of midazolam (MID) (0.075 mg) was given to the patients and the 30-min total 1-OH midazolam (1-OHMID)/MID ratio was determined. Patients were phenotyped either before the introduction of antiretroviral treatments (control group, 90 patients) or after a variable period of antiretroviral treatment (56 patients). Twenty-one subjects underwent multiple phenotyping tests (before and during the course of the treatment). RESULTS: The median MID ratio was 3.51 in the control group (range 0.20-14.6). It was 5-fold higher in the group with efavirenz (28 patients; median, range: 16.0, 3.81-367; P < 0.0001), 13-fold lower with nelfinavir (18 patients; 0.27, 0.06-36.3; P < 0.0001), 17-fold lower with efavirenz + ritonavir (three patients; 0.21, 0.05-0.47; P = 0.006), 50-fold lower with ritonavir (four patients; 0.07, 0.06-0.17; P = 0.0007), and 7-fold lower with nevirapine + (ritonavir or nelfinavir or grapefruit juice) (three patients; 0.48, 0.03-1.83; P = 0.03). CYP3A activity was lower in the efavirenz + ritonavir group (P = 0.01) and in the ritonavir group (P = 0.04) than in the nelfinavir group, although already strongly inhibited in the latter. CONCLUSION: The low-dose MID phenotyping test was successfully used to measure the in vivo variations of CYP3A activity induced by antiretroviral drugs. Efavirenz strongly induces CYP3A activity, while ritonavir almost completely inhibits it. Nelfinavir strongly decreases CYP3A activity, but to a lesser extent than ritonavir. The inhibition of CYP3A by ritonavir or nelfinavir offsets the inductive effects of efavirenz or nevirapine administered concomitantly. Finally, no induction of CYP3A activity was noticeable after long-term administration of ritonavir at low dosages (200 mg/day b.i.d.) or of nelfinavir at standard dosages (2,500 mg/day b.i.d.)

MRSA surveillance programmes worldwide : moving towards a harmonised international approach

Multinational surveillance programmes for methicillin-resistant Staphylococcus aureus (MRSA) are dependent on national structures for data collection. This study aimed to capture the diversity of national MRSA surveillance programmes and to propose a framework for harmonisation of MRSA surveillance. The International Society of Antimicrobial Chemotherapy (ISAC) MRSA Working Group conducted a structured survey on MRSA surveillance programmes and organised a webinar to discuss the programmes’ strengths and challenges as well as guidelines for harmonisation. Completed surveys represented 24 MRSA surveillance programmes in 16 countries. Several countries reported separate epidemiological and microbiological surveillance. Informing clinicians and national policy-makers were the most common purposes of surveillance. Surveillance of bloodstream infections (BSIs) was present in all programmes. Other invasive infections were often included. Three countries reported active surveillance of MRSA carriage. Method- ology and reporting of antimicrobial susceptibility, virulence factors, molecular genotyping and epidemiological metadata varied greatly. Current MRSA surveillance programmes rely upon heterogeneous data collection systems, which hampers international epidemiological monitoring and research. To harmonise MRSA surveillance, we suggest improving the integration of microbiological and epidemiological data, implementation of central biobanks for MRSA isolate collection, and inclusion of a representative sample of skin and soft-tissue infection cases in addition to all BSI cases.peer-reviewe