Opportunities for financing sustainable development using complementary local currencies

Financing building retrofit projects that contribute to climate change mitigation has always represented a significant barrier. With 28% of global emissions coming from existing buildings, it is of paramount importance to carry out retrofit measures that lead to significant reduction of these emissions. Whilst this is perfectly possible to achieve with current methods and current technology, there is no sufficient conventional finance to carry out zero carbon retrofit at scale required for climate change mitigation. The article introduces an alternative and sustainable business model that creates new opportunities for financing zero carbon retrofit of buildings. It demonstrates that the value of solar energy falling on roofs of buildings can become a driver for new local economic systems, and discusses the requirements for practical application.Peer reviewedFinal Published versio

Giant optical anisotropy in a single InAs quantum dot in a very dilute quantum-dot ensemble

We present the experimental evidence of giant optical anisotropy in single InAs quantum dots. Polarization-resolved photoluminescence spectroscopy reveals a linear polarization ratio with huge fluctuations, from one quantum dot to another, in sign and in magnitude with absolute values up to 82%. Systematic measurements on hundreds of quantum dots coming from two different laboratories demonstrate that the giant optical anisotropy is an intrinsic feature of dilute quantum-dot arrays.Comment: submitted to Applied Physics Letter

DEVELOPMENT AND OPTIMIZATION OF CARVEDILOL FORMULATION USING EXPERIMENTAL DESIGN

The aim of this paper was to develop and optimize the carvedilol tablets formulation using the full factorial design. The content of binder (PVP K30), content of disintegrant (crospovidone) and main compression force were used as the independent variables. Tablets were prepared by wet granulation. The percentage of released carvedilol from prepared formulation after 10 minutes was defined as the response. It has been found that formulation with the low content of binding agents (4.8%), high content of disintegrant (4.5%) and compression force of 50 N has the best profile of drug. The optimal formulation was defined based on implementation of pharmaceuticaltechnological tests (testing strength, friability, disintegrating, contents of drug substance, drug release profiles). The stability of the optimal formulation with carvedilol was estimated using the aging tests

Fractal and stereological analyses of insulin-induced rat exocrine pancreas remodelling

Background: The effect of insulin on the endocrine pancreas has been the subject of extensive study, but quantitative morphometric investigations of the exocrine pancreas are scarce. This study was therefore undertaken to investigate the effect of acute and chronic insulin administration (two doses, 0.4 IU and 4 IU) on the morphology of rat pancreas acini. Materials and methods: Semi-fine sections stained with methylene blue and basic fuchsine or haematoxylin and eosin-stained 5-micrometer thick paraffin sections were used for fractal and stereological analysis of exocrine acini. Acute insulin treatment, independent of applied doses increased fractal dimension in line with decreased lacunarity of pancreas acini. Chronic low dose insulin decreased fractal dimension and increased lacunarity of pancreas acini, but a high dose had the opposite effect. The volume densities (Vv) of cytoplasm, granules and nucleus are affected differently: acute low dose and high chronic dose significantly decreased granules Vv, and in line increased cytoplasmic Vv, whereas other examined structures showed slight changes without statistical significance. Results: The results obtained from this investigation indicate that insulin treatment induced structural remodelling of the exocrine pancreas suggesting a substantial role of insulin in its functioning. Conclusions: Additionally, we showed that fine architectural changes in acini could be detected by fractal analysis, suggesting this method as an alternative or addition to routine stereology

Stability of quantized time-delay nonlinear systems: A Lyapunov-Krasowskii-functional approach

Lyapunov-Krasowskii functionals are used to design quantized control laws for nonlinear continuous-time systems in the presence of constant delays in the input. The quantized control law is implemented via hysteresis to prevent chattering. Under appropriate conditions, our analysis applies to stabilizable nonlinear systems for any value of the quantization density. The resulting quantized feedback is parametrized with respect to the quantization density. Moreover, the maximal allowable delay tolerated by the system is characterized as a function of the quantization density.Comment: 31 pages, 3 figures, to appear in Mathematics of Control, Signals, and System

Observation of multiple soliton generation mediated by amplification of asymmetries

We report the experimental observation of the formation of multiple optical quadratic solitons in a process mediated by the amplification of minute asymmetries in the diffraction properties of the input light. Experiments were conducted in phase-matched second-harmonic generation in a bulk crystal of periodically poled potassium titanyl phosphate pumped at 1064 nm. The different mechanisms that influence the process were investigated numerically, and the pulsed nature of the pump light was found to play a key role in the observed light distributions

Endothelial cell apoptosis in brown adipose tissue of rats induced by hyperinsulinaemia: the possible role of TNF-α

The aim of the present study was to investigate whether hyperinsulinaemia, which frequently precedes insulin resistance syndrome (obesity, diabetes), induces apoptosis of endothelial cells (ECs) in brown adipose tissue (BAT) and causes BAT atrophy and also, to investigate the possible mechanisms underlying ECs death. In order to induce hyperinsuli-naemia, adult male rats of Wistar strain were treated with high dose of insulin (4 U/kg, intraperitonely) for one or three days. Examinations at ultrastructural level showed apoptotic changes of ECs, allowing us to point out that changes mainly but not exclusively, occur in nuclei. Besides different stages of condensation and alterations of the chromatin, nuclear fragmentation was also observed. Higher number of ECs apoptotic nuclei in the BAT of hyperinsulinaemic rats was also confirmed by propidium iodide staining. Immunohistochemical localization of tumor necrosis factor-alpha (TNF-α) revealed increased expression in ECs of BAT of hyperinsulinaemic animals, indicating its possible role in insulin-induced apoptotic changes. These results suggest that BAT atrophy in hyperinsulinaemia is a result of endothelial and adipocyte apoptosis combined, rather than any of functional components alone

Phase 1 study of fianlimab, a human lymphocyte activation gene-3 (LAG-3) monoclonal antibody, plus cemiplimab in advanced melanoma

Background: Concurrent LAG-3 blockade may enhance efficacy of anti-program cell death-1 (PD-1) therapies such as cemiplimab. We present updated safety and clinical activity data from patients with advanced melanoma treated concurrently with cemiplimab and fianlimab (NCT03005782). Methods: Patients were included with unresectable or metastatic melanoma (excluding uveal melanoma) who were anti-PD-ligand (L) 1 treatment naive (expansion cohort [EC] 6) or anti-PD-(L)1 experienced within 3 months of screening (EC7). Patients received fianlimab 1600 mg + cemiplimab 350 mg intravenously every 3 weeks for 12 months (optional extra 12 months if clinically indicated). Tumours were measured every 6 weeks for 24 weeks, then every 9 weeks. In EC6 (n = 40) and EC7 (n = 15), respectively (data cutoff 9th February 2022), median age was 69.5 and 59.0 years, and median treatment duration was 37.1 and 9.0 weeks. Results: In EC6 and EC7, respectively, incidence of Grade ≥3 treatment-emergent adverse events (TEAEs) were 38% and 47%, incidence of serious TEAEs was 33% and 33%, and 18% and 13% of patients discontinued treatment due to a TEAE. Adrenal insufficiency rate was 13% and 7% in EC6 and EC7, respectively; no instances led to treatment discontinuation. Investigator-assessed objective response rate was63%(six complete responses; 19 partial responses) in EC6 and 13% (two partial responses) in EC7. Kaplan-Meier estimate of median progression-free survival was 14.2 (95% CI: 5.6-not estimated) months in EC6 and 1.4 (95% CI: 1.3-7.7) months in EC7. Median duration of response was not reached in EC6 or EC7. Conclusion: Fianlimab plus cemiplimab in advanced melanoma had a similar safety profile to anti-PD-1 monotherapies. Clinical activity in anti-PD-(L)1-naive patients appeared higher than previously reported for anti-PD-1monotherapy or anti-LAG-3 plus anti-PD-1. A Phase 3 trial (NCT05352672) investigating fianlimab plus cemiplimab in advanced melanoma is ongoing

Cellular and humoral immune responses and protection against schistosomes induced by a radiation-attenuated vaccine in chimpanzees

The radiation-attenuated Schistosoma mansoni vaccine is highly effective in rodents and primates but has never been tested in humans, primarily for safety reasons. To strengthen its status as a paradigm for a human recombinant antigen vaccine, we have undertaken a small-scale vaccination and challenge experiment in chimpanzees (Pan troglodytes). Immunological, clinical, and parasitological parameters were measured in three animals after multiple vaccinations, together with three controls, during the acute and chronic stages of challenge infection up to chemotherapeutic cure. Vaccination induced a strong in vitro proliferative response and early gamma interferon production, but type 2 cytokines were dominant by the time of challenge. The controls showed little response to challenge infection before the acute stage of the disease, initiated by egg deposition. In contrast, the responses of vaccinated animals were muted throughout the challenge period. Vaccination also induced parasite-specific immunoglobulin M (IgM) and IgG, which reached high levels at the time of challenge, while in control animals levels did not rise markedly before egg deposition. The protective effects of vaccination were manifested as an amelioration of acute disease and overall morbidity, revealed by differences in gamma-glutamyl transferase level, leukocytosis, eosinophilia, and hematocrit. Moreover, vaccinated chimpanzees had a 46% lower level of circulating cathodic antigen and a 38% reduction in fecal egg output, compared to controls, during the chronic phase of infection

Prevalence and risk factors for Enterobacteriaceae in patients hospitalized with community-acquired pneumonia

N.J.S. is partially funded by the Department of Veterans Affairs, Quality Enhancement Research Initiative (QUERI) Partnered Evaluation Initiative Grant (HX002263-01A1).Background and objective : Enterobacteriaceae (EB) spp. family is known to include potentially multidrug-resistant (MDR) microorganisms, and remains as an important cause of community-acquired pneumonia (CAP) associated with high mortality. The aim of this study was to determine the prevalence and specific risk factors associated with EB and MDR-EB in a cohort of hospitalized adults with CAP. Methods : We performed a multinational, point-prevalence study of adult patients hospitalized with CAP. MDR-EB was defined when ≥3 antimicrobial classes were identified as non-susceptible. Risk factors assessment was also performed for patients with EB and MDR-EB infection. Results : Of the 3193 patients enrolled with CAP, 197 (6%) had a positive culture with EB. Fifty-one percent (n = 100) of EB were resistant to at least one antibiotic and 19% (n = 38) had MDR-EB. The most commonly EB identified were Klebsiella pneumoniae (n = 111, 56%) and Escherichia coli (n = 56, 28%). The risk factors that were independently associated with EB CAP were male gender, severe CAP, underweight (body mass index (BMI) < 18.5) and prior extended-spectrum beta-lactamase (ESBL) infection. Additionally, prior ESBL infection, being underweight, cardiovascular diseases and hospitalization in the last 12 months were independently associated with MDR-EB CAP. Conclusion : This study of adults hospitalized with CAP found a prevalence of EB of 6% and MDR-EB of 1.2%, respectively. The presence of specific risk factors, such as prior ESBL infection and being underweight, should raise the clinical suspicion for EB and MDR-EB in patients hospitalized with CAP.PostprintPeer reviewe