Stimulated Raman adiabatic passage in Tm3+:YAG

International audienceWe report on the experimental demonstration of stimulated Raman adiabatic passage in a Tm 3+ : YAG crystal. Tm 3+ : YAG is a promising material for use in quantum information processing applications, but as yet there are few experimental investigations of coherent Raman processes in this material. We investigate the effect of inhomogeneous broadening and Rabi frequency on the transfer efficiency and the width of the two-photon spectrum. Simulations of the complete Tm 3+ : YAG system are presented along with the corresponding experimental results

Generalizing boundaries for triangular designs, and efficacy estimation at extended follow-ups.

BACKGROUND: Visceral leishmaniasis (VL) is a parasitic disease transmitted by sandflies and is fatal if left untreated. Phase II trials of new treatment regimens for VL are primarily carried out to evaluate safety and efficacy, while pharmacokinetic data are also important to inform future combination treatment regimens. The efficacy of VL treatments is evaluated at two time points, initial cure, when treatment is completed and definitive cure, commonly 6 months post end of treatment, to allow for slow response to treatment and detection of relapses. This paper investigates a generalization of the triangular design to impose a minimum sample size for pharmacokinetic or other analyses, and methods to estimate efficacy at extended follow-up accounting for the sequential design and changes in cure status during extended follow-up. METHODS: We provided R functions that generalize the triangular design to impose a minimum sample size before allowing stopping for efficacy. For estimation of efficacy at a second, extended, follow-up time, the performance of a shrinkage estimator (SHE), a probability tree estimator (PTE) and the maximum likelihood estimator (MLE) for estimation was assessed by simulation. RESULTS: The SHE and PTE are viable approaches to estimate an extended follow-up although the SHE performed better than the PTE: the bias and root mean square error were lower and coverage probabilities higher. CONCLUSIONS: Generalization of the triangular design is simple to implement for adaptations to meet requirements for pharmacokinetic analyses. Using the simple MLE approach to estimate efficacy at extended follow-up will lead to biased results, generally over-estimating treatment success. The SHE is recommended in trials of two or more treatments. The PTE is an acceptable alternative for one-arm trials or where use of the SHE is not possible due to computational complexity. TRIAL REGISTRATION: NCT01067443 , February 2010

Citizen-led sampling to monitor phosphate levels in freshwater environments using a simple paper microfluidic device

Contamination of waterways is of increasing concern, with recent studies demonstrating elevated levels of antibiotics, antidepressants, household, agricultural and industrial chemicals in freshwater systems. Thus, there is a growing demand for methods to rapidly and conveniently monitor contaminants in waterways. Here we demonstrate how a combination of paper microfluidic devices and handheld mobile technology can be used by citizen scientists to carry out a sustained water monitoring campaign. We have developed a paper-based analytical device and a 3 minute sampling workflow that requires no more than a container, a test device and a smartphone app. The contaminant measured in these pilots are phosphates, detectable down to 3 mg L-1. Together these allow volunteers to successfully carry out cost-effective, high frequency, phosphate monitoring over an extended geographies and periods

Orthogeriatric co-management: differences in outcome between major and minor fractures

PURPOSE: Literature shows that orthogeriatric co-management improves the outcomes of patients with hip fractures. Corresponding research with more diverse fragility fracture groups is lacking. Therefore, an examination was performed prospectively as a 2 year-follow-up on an orthogeriatric co-managed ward, comparing relevant outcome parameters for major and minor fragility fractures. METHODS: All patients treated on an orthogeriatric co-managed ward from February 2014 to January 2015 were included and their injuries, orthogeriatric parameters such as the Barthel Index (BI), Parker Mobility Score (PMS) and place of residence (POR). Patients were separated into two groups of either immobilizing major (MaF) or non-immobilizing minor (MiF) fractures. 2 years later, a follow-up was conducted via telephone calls and questionnaires mailed to patients and/or their relatives. RESULTS: 740 (574 major vs. 166 minor injuries) patients were initially assessed, with a follow-up rate of 78.9%. The in-house, 1-year, and 2-year-mortality rates were 2.7, 27.4, and 39.2%, respectively. Mortality was significantly higher for MaF in the short term, but not after 2 years. On average, during the observation period, patients regained their BI by 36.7 points (95% CI: 33.80–39.63) and PMS was reduced by 1.4 points (95% CI: 1.16–1.68). No significant differences were found in the readmission rate, change in BI, PMS or POR between the MaF and MiF groups. CONCLUSION: The relevance of orthogeriatric treatment to improving functional and socioeconomic outcomes was confirmed. The similarity of the results from both fracture groups emphasizes the need for a multidisciplinary approach also for minor fractures. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00068-022-01974-3

Inhibition of Female and Male Human Detrusor Smooth Muscle Contraction by the Rac Inhibitors EHT1864 and NSC23766

Introduction: Lower urinary tract symptoms (LUTS) due to overactive bladder (OAB) are caused by spontaneous detrusor contractions. Medical treatment with muscarinic receptor antagonists or β3-adrenoceptor agonists aims to inhibit detrusor contractions, but overall results are unsatisfactory. Consequently, improved understanding of bladder smooth muscle contraction and identification of novel compounds for its inhibition are needed to develop alternative options. A role of the GTPase Rac1 for smooth muscle contraction has been reported from the prostate, but is unknown in the human detrusor. Here, we examined effects of the Rac inhibitors NSC23766, which may also antagonize muscarinic receptors, and EHT1864 on contraction of human detrusor tissues. Methods: Female and male human detrusor tissues were obtained from radical cystectomy. Effects of NSC23766 (100 µM) and EHT1864 (100 µM) on detrusor contractions were studied in an organ bath. Results: Electric field stimulation induced frequency-dependent contractions of detrusor tissues, which were inhibited by NSC23766 and EHT1864. Carbachol induced concentration-dependent contractions. Concentration response curves for carbachol were shifted to the right by NSC23766, reflected by increased EC50 values, but unchanged Emax values. EHT1864 reduced carbachol-induced contractions, resulting in reduced Emax values for carbachol. The thromboxane analog U46619 induced concentration-dependent contractions, which remained unchanged by NSC23766, but were reduced by EHT1864. Conclusions: NSC23766 and EHT1864 inhibit female and male human detrusor contractions. NSC23766, but not EHT1864 competitively antagonizes muscarinic receptors. In addition to neurogenic and cholinergic contractions, EHT1864 inhibits thromboxane A2-induced detrusor contractions. The latter may be promising, as the origin of spontaneous detrusor contractions in OAB is noncholinergic. In vivo, both compounds may improve OAB-related LUTS

Staphyphage: Biorisk Reduction in MRSA Research

Staphylococcus aureus is an opportunistic human pathogen that has the ability to cause both health care-associated and community-acquired infections [1]. It has been identified as one of the ‘high priority pathogen’ by the World Health Organization (WHO) [5] The infections were once, easily treated with antibiotics before resistance against beta-lactams (eg. Methicillin) and glycopeptides (eg. Vancomycin) began to emerge over the years and caused an increase in mortality and morbidity rates in patients infected with S. aureus [2,3]. This has led to an increased interest in the exploration of the use of bacteriophage as an alternative approach way to combat MRSA because a bacteriophage has bacteriolytic mechanism independent from those of any known antibiotics [5]. The availability of a virulent and broad spectrum bacteriophage against MRSA may significantly reduce the overall biorisk as it acts as an effective treatment in case of exposure

Evaluation of the efficacy of bacteriophages against Staphylococcus aureus

Staphylococcus aureus (S. aureus) is an opportunistic human pathogen that has the ability to cause both health care-associated and community-acquired infections (Chambers, 2001). The infections were once, easily treated with antibiotics before resistance against beta-lactams (eg. Methicillin) and glycopeptides (eg. Vancomycin) began to emerge over the years and caused an increase in mortality and morbidity rates in patients infected with S. aureus (Boucher & Corey, 2008, Howe et al., 1998). This has led to an increased interest in the exploration of the use of bacteriophages as a way to combat multi-drug resistant organisms because bacteriophages has bacteriolytic mechanism independent from those of any known antibiotics (Matsuzaki et al., 2005)

Could bacteriophages isolated from the sewage be the solution to methicillin-resistant Staphylococcus aureus?

Introductions: The emergence of multidrug-resistant bacteria such as Methicillin-Resistant Staphylococcus aureus (MRSA) complicates the treatment of the simplest infection. Although glycopeptides such as vancomycin still proves to be effective in treating MRSA infections, the emergence of vancomycin-resistant strains limits the long term use of this antibiotic. Bacteriophages are ubiquitous bacterial viruses which is capable of infecting and killing bacteria including its antibiotic-resistant strains. Bactericidal bacteriophages use mechanisms that is distinct from antibiotics and is not affected by the antibioticresistant phenotypes. Objectives: The study was undertaken to evaluate the possibility to isolate bacteriolytic bacteriophages against S.aureus from raw sewage water and examine their efficacy as antimicrobial agents in vitro. Methodology: Bacteriophages were isolated from the raw sewage using the agar overlay method. Isolated bacteriophages were plaque purified to obtain homogenous bacteriophage isolates. The host range of the bacteriophages was determined using the spot test assay against the 25 MRSA and 36 MSSA isolates obtained from the Sarawak General Hospital. Staphylococcus saprophyticus, Staphylococcus sciuri and Staphylococcus xylosus were included as non-SA controls. The identity of the bacteriophages was identified via Transmission Electron Microscopy and genomic size analysis. Their stability at different pH and temperature were elucidated. Results: A total of 10 lytic bacteriophages infecting S.aureus were isolated and two of them namely ΦNUSA-1 and ΦNUSA-10 from the family of Myoviridae and Siphoviridae respectively exhibited exceptionally broad host range against >80% of MRSA and MSSA tested. Both bacteriophages were specific to S.aureus and stable at both physiologic pH and temperature. Conclusion: This study demonstrated the abundance of S.aureus specific bacteriophages in raw sewage. Their high virulence against both MSSA and MRSA is an excellent antimicrobial characteristic which can be exploited for bacteriophage therapy against MRSA