Evaluation of the Coverage of 3 Antibiotic Regimens for Neonatal Sepsis in the Hospital Setting Across Asian Countries.

Importance: High levels of antimicrobial resistance in neonatal bloodstream isolates are being reported globally, including in Asia. Local hospital antibiogram data may include too few isolates to meaningfully examine the expected coverage of antibiotic regimens. Objective: To assess the coverage offered by 3 antibiotic regimens for empirical treatment of neonatal sepsis in Asian countries. Design, Setting, and Participants: A decision analytical model was used to estimate coverage of 3 prespecified antibiotic regimens according to a weighted-incidence syndromic combination antibiogram. Relevant data to parameterize the models were identified from a systematic search of Ovid MEDLINE and Embase. Data from Asian countries published from 2014 onward were of interest. Only data on blood culture isolates from neonates with sepsis, bloodstream infection, or bacteremia reported from the relevant setting were included. Data analysis was performed from April 2019 to July 2019. Exposures: The prespecified regimens of interest were aminopenicillin-gentamicin, third-generation cephalosporins (cefotaxime or ceftriaxone), and meropenem. The relative incidence of different bacteria and their antimicrobial susceptibility to antibiotics relevant for determining expected concordance with these regimens were extracted. Main Outcomes and Measures: Coverage was calculated on the basis of a decision-tree model incorporating relative bacterial incidence and antimicrobial susceptibility of relevant isolates. Data on 7 bacteria most commonly reported in the included studies were used for estimating coverage, which was reported at the country level. Results: Data from 48 studies reporting on 10 countries and 8376 isolates were used. Individual countries reported 51 (Vietnam) to 6284 (India) isolates. Coverage varied considerably between countries. Meropenem was generally estimated to provide the highest coverage, ranging from 64.0% (95% credible interval [CrI], 62.6%-65.4%) in India to 90.6% (95% CrI, 86.2%-94.4%) in Cambodia, followed by aminopenicillin-gentamicin (from 35.9% [95% CrI, 27.7%-44.0%] in Indonesia to 81.0% [95% CrI, 71.1%-89.7%] in Laos) and cefotaxime or ceftriaxone (from 17.9% [95% CrI, 11.7%-24.7%] in Indonesia to 75.0% [95% CrI, 64.8%-84.1%] in Laos). Aminopenicillin-gentamicin coverage was lower than that of meropenem in all countries except Laos (81.0%; 95% CrI, 71.1%-89.7%) and Nepal (74.3%; 95% CrI, 70.3%-78.2%), where 95% CrIs for aminopenicillin-gentamicin and meropenem were overlapping. Third-generation cephalosporin coverage was lowest of the 3 regimens in all countries. The coverage difference between aminopenicillin-gentamicin and meropenem for countries with nonoverlapping 95% CrIs ranged from -15.9% in China to -52.9% in Indonesia. Conclusions and Relevance: This study's findings suggest that noncarbapenem antibiotic regimens may provide limited coverage for empirical treatment of neonatal sepsis in many Asian countries. Alternative regimens must be studied to limit carbapenem consumption

Fokker-Planck equation approach to optical bistability in the bad-cavity limit

In the general framework of the system size expansion of Van Kampen and Kubo, we consider the Fokker-Planck equation for a model of absorptive bistability in the bad-cavity limit. The physical system is described by the reduced atomic density operators after adiabatic elimination of the cavity field variables. Mapping of the master equation into c-number form according to the normal-ordering mapping scheme yields known results for the atomic fluctuations and correlation functions; however, it also leads to a Fokker-Planck equation with a non-positive-definite diffusion matrix. The symmetrical-order-mapping scheme eliminates this difficulty. The leading contribution to the system size expansion yields a Fokker-Planck equation for the symmetrical-ordered density function having a positive-definite diffusion matrix. The atomic expectation values and fluctuations previously derived from the quantum Langevin equations emerge naturally from this Fokker-Planck equation

Existence and multiplicity for fractional Dirichlet problem with γ(ξ)\gamma(\xi)-Laplacian equation and Nehari manifold

This paper is divided in two parts. In the first part, we prove coercivity results and minimization of the Euler energy functional. In the second part, we focus on the existence and multiplicity of a positive solution of fractional Dirichlet problem involving the $\gamma(\xi)$-Laplacian equation with non-negative weight functions in $\mathcal{H}^{\alpha,\beta;\chi}_{\gamma(\xi)}(\Lambda,\mathbb{R})$ using some variational techniques and Nehari manifold.Comment: 14 page

Quantum analysis of optical bistability and spectrum of fluctuations

We discuss the approach to equilibrium and the fluctuations of a bistable system under dynamical conditions such that the field variables can be eliminated adiabatically. The atomic system evolves under the action of the coherent pumping of an external field and of collective and incoherent relaxation processes. The competition between pumping and relaxation effects causes the atomic steady-state configurations to depend discontinuously on the strength of the driving field. We derive an explicit expression for the spectrum of the forward-scattered light, which exhibits hysteresis and a discontinuous dependence on the driving-field amplitude

Optical bistability: a self-consistent analysis of fluctuations and the spectrum of scattered light

The main purpose of this paper is to study the behavior of the atomic fluctuations and the spectrum of the light transmitted by an absorptive bistable device. To this end we develop an approximation scheme based on the so-called system-size expansion and apply it to the quantum-mechanical Langevin equations for the atomic fluctuation operators. The Bonifacio-Lugiato mean-field equations for bistability are derived from the lowest-order approximation to the system-size expansion, while the atomic correlation functions result from the next-higher-order expansion. The calculated spectrum of the transmitted light exhibits line narrowing near the bistable thresholds, discontinuous formation of sidebands along the high-transmission branch of the device, and hysteresis effects

Multi-Scale Simulation Modeling for Prevention and Public Health Management of Diabetes in Pregnancy and Sequelae

Diabetes in pregnancy (DIP) is an increasing public health priority in the Australian Capital Territory, particularly due to its impact on risk for developing Type 2 diabetes. While earlier diagnostic screening results in greater capacity for early detection and treatment, such benefits must be balanced with the greater demands this imposes on public health services. To address such planning challenges, a multi-scale hybrid simulation model of DIP was built to explore the interaction of risk factors and capture the dynamics underlying the development of DIP. The impact of interventions on health outcomes at the physiological, health service and population level is measured. Of particular central significance in the model is a compartmental model representing the underlying physiological regulation of glycemic status based on beta-cell dynamics and insulin resistance. The model also simulated the dynamics of continuous BMI evolution, glycemic status change during pregnancy and diabetes classification driven by the individual-level physiological model. We further modeled public health service pathways providing diagnosis and care for DIP to explore the optimization of resource use during service delivery. The model was extensively calibrated against empirical data.Comment: 10 pages, SBP-BRiMS 201

Assessment of retinal vascular calibres as a biomarker of disease activity in birdshot chorioretinopathy

Purpose Birdshot chorioretinopathy (BCR) is a potentially blinding ocular disorder involving the retinal vasculature and choroid without any systemic manifestations. The objective of the study was to describe vascular calibre changes in BCR and analyse the possibility of this optical biomarker for staging and monitoring disease activity in BCR. Methods This retrospective case–control study at a tertiary referral eye centre in the UK included 33 eyes from 21 patients with BCR and equal number of eyes from control subjects. Diagnosis of BCR was confirmed on fundus fluorescein and indocyanine green angiography. Vascular calibres were measured using validated semiautomated software. Results Patients with BCR had smaller retinal venular calibres central retinal venular equivalent (CRVE) than controls (211.3 versus 227.9 μm, p = 0.008). After adjusting for variables, the difference between the two groups for CRVE at baseline was statistically significant based on two different analysis methods. Central retinal venular equivalent (CRVE) was lower at the 6-month follow-up visit (206.2 versus 213.8 μm, p-value = 0.03), and arteriole-to-venule ratio was larger (0.74 versus 0.71, p = 0.04) in subjects with BCR. Arteriolar calibre (CRAE) remained the same. Conclusion This study provides novel insight into the pattern of vascular involvement in BCR. There was significant difference in the CRVE in patients with BCR. More studies are needed to correlate this data with visual function and treatment outcome and to validate the findings

Terahertz underdamped vibrational motion governs protein-ligand binding in solution

Low-frequency collective vibrational modes in proteins have been proposed as being responsible for efficiently directing biochemical reactions and biological energy transport. However, evidence of the existence of delocalized vibrational modes is scarce and proof of their involvement in biological function absent. Here we apply extremely sensitive femtosecond optical Kerr-effect spectroscopy to study the depolarized Raman spectra of lysozyme and its complex with the inhibitor triacetylchitotriose in solution. Underdamped delocalized vibrational modes in the terahertz frequency domain are identified and shown to blue-shift and strengthen upon inhibitor binding. This demonstrates that the ligand-binding coordinate in proteins is underdamped and not simply solvent-controlled as previously assumed. The presence of such underdamped delocalized modes in proteins may have significant implications for the understanding of the efficiency of ligand binding and protein–molecule interactions, and has wider implications for biochemical reactivity and biological function

Phase II study of TP300 in patients with advanced gastric or gastro-oesophageal junction adenocarcinoma

Background TP300, a recently developed synthetic camptothecin analogue, is a highly selective topoisomerase I inhibitor. A phase I study showed good safety and tolerability. As camptothecins have proven active in oesophago-gastric adenocarcinomas, in this phase II study we assessed the efficacy and safety of TP300 in patients with gastric or gastro-oesophageal junction (GOJ) adenocarcinomas. Methods Eligible patients had metastatic or locally advanced gastric or Siewert Types II or III GOJ inoperable adenocarcinoma. Patients were chemotherapy naïve unless this had been administered in the perioperative setting. TP300 was administered as a 1-h intravenous infusion every 3 weeks (a cycle) for up to 6 cycles at a starting dose of 8 mg/m2 with intra-patient escalation to 10 mg/m2 from cycle 2 in the absence of dose-limiting toxicity. Tumour responses (RECIST 1.1) were assessed every 6 weeks. Toxicity was recorded by NCI-CTCAE version 3.0. Using a modified two-stage Simon design (Stage I and II), a total of 43 patients were to be included providing there were 3 of 18 patients with objective response in Stage I of the study. Results In Stage I of the study 20 patients (14 males, 6 females), median age 67 years (range 40 − 82), performance status ECOG 0/1, with GC [14] or GOJ carcinoma [6] were enrolled. Of the 16 evaluable patients, 11 received the planned dose increase to 10 mg/m2 at cycle 2, 2 decreased to 6 mg/m2, and 3 continued on 8 mg/m2. There were no objective responses after 2 cycles of treatment. Twelve patients had stable disease for 1 − 5 months and 4 had progressive disease. Median progression free survival (PFS) was 4.1 months (CI [1.6 − 4.9]), median time to progression (TTP) was 2.9 months (CI [1.4 − 4.2]). Grade 3/4 toxicities (worst grade all cycles) included 7 patients (35 %) with neutropenia, 4 patients (20 %) with anaemia, 2 patients (10 %) with thrombocytopenia, and 3 patients (15 %) with fatigue. This study was terminated at the end of Stage I due to a lack of the required (3/18) responders. Conclusions This study of TP300 showed good drug tolerability but it failed to demonstrate sufficient efficacy as measured by radiological response. Trial registration EU-CTR 2009-012097-12 2009-09-0

Snake bite mimicking brain death

A 6 year old girl woke up with pain and increasing swelling over the left hand and difficulty in breathing. On examination, she had swelling of the left forearm and hand, flaccid quadriparesis and was in respiratory failure requiring mechanical ventilation. Two clean puncture wounds were identified on the left thumb. A provisional diagnosis of snake bite with severe envenomation was made and she was given anti snake venom therapy. Over a period of about 4 hours her weakness progressed. She became areflexic, developed internal and external ophthalmoplegia and loss of other brain stem reflexes mimicking brain death. Mechanical ventilation was continued despite features suggestive of brain stem dysfunction. About 36 hours after ventilation she showed a flicker of movement of her fingers and gradually the power improved. She was weaned off the ventilator and extubated after 5 days. External ophthalmoplegia is an established association with cobra envenomation, but, this combination of internal and external ophthalmoplegia can mimic brain death and pose a dilemma to the caregivers regarding continuation of therapy