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Caroli-de Gennes-Matricon Analogs in Full-Shell Hybrid Nanowires
No full textWe report tunneling spectroscopy of Andreev subgap states in hybrid nanowires with a thin superconducting full shell surrounding a semiconducting core. The combination of the quantized fluxoid of the shell and the Andreev reflection at the superconductor-semiconductor interface gives rise to analogs of Caroli-de Gennes-Matricon states found in Abrikosov vortices in type-II superconductors. Unlike in metallic superconductors, Caroli-de Gennes-Matricon analogs in full-shell hybrid nanowires manifest as one-dimensional Van Hove singularities with energy spacings comparable to the superconducting gap and independent of the Fermi energy, making them readily observable. Evolution of these analogs with axial magnetic field, skewed within the Little-Parks lobe structure, is consistent with theory and yields information about the radial distribution and angular momenta of the corresponding subbands
Co-encapsulating hydrophobic payloads and hydrophobic ion pairs in polymeric nanocarriers affects liquid crystalline mesophase packing and formation kinetics
No full textLiquid crystalline (LC) mesophases contain both polar and non-polar domains that enable co-loading of therapeutics with different physicochemical preparties into a single delivery vehicle. Understanding the relationship between formulation parameters, LC structure, and drug release is necessary to inform the rational design of these materials. This work interrogates the time scales over which LC phases assemble in polymeric nanocarrier cores as a function of composition. Nanocarrier formulations containing co-encapsulated hydrophilic (polymyxin B) and hydrophobic (vitamin E acetate, cholesterol, methyl oleate, or polycaprolactone) payloads were developed using Flash NanoPrecipitation with hydrophobic ion pairing using a confined impinging jets mixer. The mixer was integrated into a synchrotron small-angle X-ray scattering beamline to obtain spatiotemporally resolved kinetic data for the formation of internal liquid crystalline mesophases. The physical chemistries and concentrations of the hydrophobic counterion and the co-loaded hydrophobic molecule were found to significantly influence the assembly time of LC phases. For instance, in the presence of hydrophobic species such as vitamin E acetate or cholesterol, the time required for resolvable LC phase assembly was extended from seconds (for the case of only polymyxin B and a hydrophobic counterion) to several minutes. These time scales increased with increasing weight fraction of the hydrophobic molecule, suggesting physical interference during diffusion-mediated self-assembly of the LC phases. Our findings highlight how formulation composition plays a critical role in both the assembly timeline and the characteristics of the final product, which are essential to ensuring that the liquid crystal-mediated drug delivery system contains the intended critical quality attributes.</p
Flash Profile method, is it suitable for complex multi-layered products?:Application to strawberry-filled biscuits: a "SWEET project"
No full textComposite foods are consumed daily, but understanding their sensory properties is a major challenge. This study aims to evaluate the efficiency of Flash Profile (FP) method to characterize strawberry-filled biscuits properties, in a context of sugar reduction. Investigations were carried out on fillings (with/without added sugar, with/ without strawberry aroma), then biscuits (with sugar or maltitol or sorbitol, with/without vanilla aroma) and finally on the complex fruit-filled biscuits, corresponding to a progressive matrix complexification strategy. FP allowed a discrimination of the products for the 3 matrices according to their formulation and flavouring. Fruit fillings and biscuits were described with both flavour and texture attributes, whereas fruit-filled biscuits were mainly described with texture attributes. This texture predominance could result from complex changes of texture perceived during chewing. Panellists may also have focused on the first perceived characteristics or on the product's most distinguishing features to ease the task. FP was efficient to discriminate samples in each set of samples according to formulation. The characteristics allowing differentiation between samples varied depending on the matrix. Flavour attributes were mainly used for fluid matrices while texture was dominant for solid matrices. In our study, all panellists evaluated the 3 sets of products in the same order which could have influence their evaluation of complex products during the last session. Further investigations about the evaluation of complex solid products with FP may determine if texture is always dominant, even with a lower number of products
A LYM inequality for product measures
No full textThis note proves a version of Lubell–Yamamoto–Meshalkin inequality for general product measures.</p
Fetal exposure to a mixture of endocrine-disrupting chemicals and biomarkers of male fecundity:A population-based cohort study
No full textBackgroundFetal exposure to endocrine-disrupting chemicals (EDCs) has been associated with reduced male fecundity, but with few studies considering chemical mixtures.ObjectivesWe assessed the association between fetal exposure to a mixture of EDCs and biomarkers of male fecundity in young adulthood.Materials and methodsThe study population comprised 841 young adult males enrolled in the Fetal Programming of Semen Quality cohort, established as a male offspring sub-cohort within the Danish National Birth Cohort. Maternal blood samples were analyzed for concentrations of per- and polyfluoroalkyl substances (PFAS), phthalate metabolites, and triclosan. We used quantile g-computation to estimate the change in semen characteristics, testicular volume, and reproductive hormone levels with 95% confidence intervals (CI) per one-quartile increase in all chemicals within three chemical mixtures; an overall chemical mixture, a PFAS mixture, and a non-persistent chemical mixture.ResultsFetal exposure to a one-quartile increase in the overall chemical mixture was associated with 4.0 million/mL lower sperm concentration (95% CI: −9.1, 1.1), 16.1 million lower total sperm count (95% CI: −33.8, 1.6), 0.5 mL smaller testicular volume (95% CI: −1.2, 0.3), 5% higher proportion of non-progressive and immotile spermatozoa (95% CI: 0.99, 1.11), and 7% higher concentration of FSH (95% CI: 0.99, 1.16), but with limited precision. Effect sizes were greatest in magnitude for sperm concentration and total sperm count. We observed somewhat similar associations for the PFAS mixture and no associations for the non-persistent chemical mixture.DiscussionResults suggest that fetal exposure to an overall mixture of EDCs may be adversely associated with several biomarkers of male fecundity, but findings are also compatible with null associations. These associations, if true, appeared to be driven by PFAS, but misclassification due to a single measurement of the phthalate metabolites and triclosan may have attenuated the results.Background: Fetal exposure to endocrine-disrupting chemicals (EDCs) has been associated with reduced male fecundity, but with few studies considering chemical mixtures. Objectives: We assessed the association between fetal exposure to a mixture of EDCs and biomarkers of male fecundity in young adulthood. Materials and methods: The study population comprised 841 young adult males enrolled in the Fetal Programming of Semen Quality cohort, established as a male offspring sub-cohort within the Danish National Birth Cohort. Maternal blood samples were analyzed for concentrations of per- and polyfluoroalkyl substances (PFAS), phthalate metabolites, and triclosan. We used quantile g-computation to estimate the change in semen characteristics, testicular volume, and reproductive hormone levels with 95% confidence intervals (CI) per one-quartile increase in all chemicals within three chemical mixtures; an overall chemical mixture, a PFAS mixture, and a non-persistent chemical mixture. Results: Fetal exposure to a one-quartile increase in the overall chemical mixture was associated with 4.0 million/mL lower sperm concentration (95% CI: −9.1, 1.1), 16.1 million lower total sperm count (95% CI: −33.8, 1.6), 0.5 mL smaller testicular volume (95% CI: −1.2, 0.3), 5% higher proportion of non-progressive and immotile spermatozoa (95% CI: 0.99, 1.11), and 7% higher concentration of FSH (95% CI: 0.99, 1.16), but with limited precision. Effect sizes were greatest in magnitude for sperm concentration and total sperm count. We observed somewhat similar associations for the PFAS mixture and no associations for the non-persistent chemical mixture. Discussion: Results suggest that fetal exposure to an overall mixture of EDCs may be adversely associated with several biomarkers of male fecundity, but findings are also compatible with null associations. These associations, if true, appeared to be driven by PFAS, but misclassification due to a single measurement of the phthalate metabolites and triclosan may have attenuated the results.</p
<i>Trichophyton indotineae</i>:Epidemiology, antifungal resistance and antifungal stewardship strategies
No full textThere has been a recent shift in the epidemiology of superficial fungal infections (tinea, dermatophytosis, dermatomycoses). Trichophyton indotineae is an emerging dermatophyte species of significant global concern for its contagious nature and antifungal drug resistance. This scoping review includes available clinical and laboratory assessments of T. indotineae to provide a comprehensive up-to-date overview of its epidemiology, clinical manifestations, diagnostic approaches, antifungal susceptibility patterns, resistance mechanisms and management strategies. We discuss T. indotineae resistance against standard and newer antifungals (terbinafine, griseofulvin and triazoles including fluconazole, itraconazole, voriconazole and posaconazole). In particular, the terbinafine susceptibility profile of T. indotineae can be linked to squalene epoxidase (SQLE) single-nucleotide variations. For diagnosis, it is not possible to separate T. indotineae from other members of the T. mentagrophytes complex (T. mentagrophytes and T. interdigitale) without access to molecular diagnostic methods. So, in patients presenting with extensive dermatophytoses, with a history of treatment resistance and/or recent travel, molecular diagnosis to confirm T. indotineae infection should be considered. Healthcare providers often face challenges in choosing between terbinafine and itraconazole treatments. While the use of terbinafine is limited due to resistance, itraconazole is hindered by erratic absorption, possible drug interactions and side effects as well as resistance in some cases. Newer treatments being investigated include super-bioavailable itraconazole, third-generation triazoles (voriconazole, posaconazole) and topical-oral combination regimens. The need for improved diagnostic accessibility, judicious antifungal prescribing, and implementing an effective antifungal stewardship program are highlighted.</p
Exposure to heat at work:development of a quantitative European job exposure matrix (heat JEM)
No full textObjective With climate change exacerbating occupational heat stress, objective and systematic exposure assessment is essential for epidemiological studies. We developed a job exposure matrix (JEM) to assign occupational heat stress exposure across Europe. Methods Aligned with the International Organization for Standardization (ISO: 7243, 8996 and 9920), the heat JEM provides region- and year-specific estimates of annual heat stress hours by job title, using the International Standard Classification of Occupations 1988 for Europe [ISCO-88(COM)]. Heat stress was defined as wet bulb globe temperature effective (WBGT(eff)) exceeding WBGT reference (WBGT(ref)). Outdoor and indoor WBGT were determined using historical, region-specific hourly meteorological data (temperature, radiation, humidity, wind speed) across Europe, between 1970 and 2024. WBGT values were adjusted for job-specific clothing to obtain WBGT(eff). WBGT(ref) was based on metabolic rate, calculated using body surface area and job-specific physical activity, and adjusted for acclimatization status. Further adjustments were made for the job title-specific presence of local heat and cooling sources, time spent indoors versus outdoors, and working schedules. Results The number of annual hours workers experience heat stress is highest among jobs involving local heat sources and physical demanding tasks, especially when work clothing is mandatory. Southern Europe has a higher annual heat stress burden compared to other regions. Exposure varies across calendar years and is substantially higher among unacclimatized versus acclimatized workers. Conclusions Incorporating job-, region-, and year-specific factors, the heat JEM provides a harmonized tool for studying occupational heat stress. Its transparent framework allows for updates with new data and extensions to other years and regions
Astatine-211—Towards In Vivo Stable Astatine-211 Labeled Radiopharmaceuticals and Their (Pre)Clinical Applications
No full textTargeted radioligand therapy has emerged as a promising treatment option for eradicating advanced cancer forms. α-Emitters are considered particularly promising as they can obliterate (micro)-metastases. The α-emitter astatine-211 (211At) has experienced increased interest due to its favorable decay properties. As a result, various 211At-astatination strategies have been developed to address challenges associated with working with this “halogenic metalloid.” This review summarizes efforts to produce and scale 211At, describes its physicochemical properties, discusses the advantages and disadvantages of using a radionuclide with a half-life of 7.2 h and outlines procedures for astatinating radiopharmaceuticals. Moreover, a key focus of this review is to rationalize strategies aimed at minimizing in vivo deastatination. A brief overview of on-going (pre)clinical development with 211At-labeled radiopharmaceuticals is provided. Astatinated radiopharmaceuticals will play a pivotal role in cancer management in the near future when challenges related to scalability and in vivo stability have been addressed and clinical studies have shown the benefit of 211At compared to longer-lived therapeutic radionuclides.</p
Cost-effectiveness of atrial fibrillation screening programmes across European nations
No full textAimsDue to the ageing population in Europe, a significant increase in the incidence of atrial fibrillation (AF) is anticipated. This is predicted to have a detrimental impact on public health costs, particularly among the elderly, because of an increased number of stroke cases. Early detection of AF is crucial for initiating treatment with oral anticoagulants (OACs) to reduce the risk of stroke. This study aims to assess the cost-effectiveness of implementing AF screening programmes in eight European countries: Denmark, Germany, Ireland, Italy, the Netherlands, Serbia, Spain, and Sweden.Methods and resultsThe analysis concerned invitation to AF population screening for 75-year-olds. A Markov cohort model was used, considering the prevalence of AF, screening yield, the use of different OACs, estimated clinical events, mortality, quality of life and costs. The model used country-specific parameters to produce specific cost-effectiveness estimates. Probabilistic sensitivity analyses were conducted to assess the impact of parametric uncertainties on the results. Inviting 75-year-olds to AF screening proved to be cost-effective across all eight countries analysed. In all countries, the strategy was dominant, meaning that quality-adjusted life-years were gained at lower costs. The time to financial break-even ranged from 6 to 14 years.ConclusionThis study indicates that population-based AF screening of 75-year-olds is a cost-effective strategy across eight European countries, meaning that adoption of such a strategy has the potential to make healthcare systems in these countries more efficient. The heterogeneity among European countries suggests that AF screening programmes may need to be tailored to the specific healthcare systems and conditions of each nation.Aims Due to the ageing population in Europe, a significant increase in the incidence of atrial fibrillation (AF) is anticipated. This is predicted to have a detrimental impact on public health costs, particularly among the elderly, because of an increased number of stroke cases. Early detection of AF is crucial for initiating treatment with oral anticoagulants (OACs) to reduce the risk of stroke. This study aims to assess the cost-effectiveness of implementing AF screening programmes in eight European countries: Denmark, Germany, Ireland, Italy, the Netherlands, Serbia, Spain, and Sweden.Methods and results The analysis concerned invitation to AF population screening for 75-year-olds. A Markov cohort model was used, considering the prevalence of AF, screening yield, the use of different OACs, estimated clinical events, mortality, quality of life and costs. The model used country-specific parameters to produce specific cost-effectiveness estimates. Probabilistic sensitivity analyses were conducted to assess the impact of parametric uncertainties on the results. Inviting 75-year-olds to AF screening proved to be cost-effective across all eight countries analysed. In all countries, the strategy was dominant, meaning that quality-adjusted life-years were gained at lower costs. The time to financial break-even ranged from 6 to 14 years.Conclusion This study indicates that population-based AF screening of 75-year-olds is a cost-effective strategy across eight European countries, meaning that adoption of such a strategy has the potential to make healthcare systems in these countries more efficient. The heterogeneity among European countries suggests that AF screening programmes may need to be tailored to the specific healthcare systems and conditions of each nation