Tuberculosis in people of Ukrainian origin in the European Union and the European Economic Area, 2019 to 2022.

Approximately five million Ukrainians were displaced to the EU/EEA following the Russian invasion of Ukraine. While tuberculosis (TB) notification rates per 100,000 Ukrainians in the EU/EEA remained stable, the number of notified TB cases in Ukrainians increased almost fourfold (mean 2019-2021: 201; 2022: 780). In 2022, 71% cases were notified in three countries, and almost 20% of drug-resistant TB cases were of Ukrainian origin. Targeted healthcare services for Ukrainians are vital for early diagnosis and treatment, and preventing transmission

Striped periodic minimizers of a two-dimensional model for martensitic phase transitions

In this paper we consider a simplified two-dimensional scalar model for the formation of mesoscopic domain patterns in martensitic shape-memory alloys at the interface between a region occupied by the parent (austenite) phase and a region occupied by the product (martensite) phase, which can occur in two variants (twins). The model, first proposed by Kohn and Mueller, is defined by the following functional: $${\cal E}(u)=\beta||u(0,\cdot)||^2_{H^{1/2}([0,h])}+ \int_{0}^{L} dx \int_0^h dy \big(|u_x|^2 + \epsilon |u_{yy}| \big)$$ where $u:[0,L]\times[0,h]\to R$ is periodic in $y$ and $u_y=\pm 1$ almost everywhere. Conti proved that if $\beta\gtrsim\epsilon L/h^2$ then the minimal specific energy scales like $\sim \min\{(\epsilon\beta/L)^{1/2}, (\epsilon/L)^{2/3}\}$, as $(\epsilon/L)\to 0$. In the regime $(\epsilon\beta/L)^{1/2}\ll (\epsilon/L)^{2/3}$, we improve Conti's results, by computing exactly the minimal energy and by proving that minimizers are periodic one-dimensional sawtooth functions.Comment: 29 pages, 3 figure

Froth-like minimizers of a non local free energy functional with competing interactions

We investigate the ground and low energy states of a one dimensional non local free energy functional describing at a mean field level a spin system with both ferromagnetic and antiferromagnetic interactions. In particular, the antiferromagnetic interaction is assumed to have a range much larger than the ferromagnetic one. The competition between these two effects is expected to lead to the spontaneous emergence of a regular alternation of long intervals on which the spin profile is magnetized either up or down, with an oscillation scale intermediate between the range of the ferromagnetic and that of the antiferromagnetic interaction. In this sense, the optimal or quasi-optimal profiles are "froth-like": if seen on the scale of the antiferromagnetic potential they look neutral, but if seen at the microscope they actually consist of big bubbles of two different phases alternating among each other. In this paper we prove the validity of this picture, we compute the oscillation scale of the quasi-optimal profiles and we quantify their distance in norm from a reference periodic profile. The proof consists of two main steps: we first coarse grain the system on a scale intermediate between the range of the ferromagnetic potential and the expected optimal oscillation scale; in this way we reduce the original functional to an effective "sharp interface" one. Next, we study the latter by reflection positivity methods, which require as a key ingredient the exact locality of the short range term. Our proof has the conceptual interest of combining coarse graining with reflection positivity methods, an idea that is presumably useful in much more general contexts than the one studied here.Comment: 38 pages, 2 figure

The Substitutions L50F, E166A, and L167F in SARS-CoV-2 3CLpro Are Selected by a Protease Inhibitor In Vitro and Confer Resistance To Nirmatrelvir.

The SARS-CoV-2 main protease (3CLpro) has an indispensable role in the viral life cycle and is a therapeutic target for the treatment of COVID-19. The potential of 3CLpro-inhibitors to select for drug-resistant variants needs to be established. Therefore, SARS-CoV-2 was passaged in vitro in the presence of increasing concentrations of ALG-097161, a probe compound designed in the context of a 3CLpro drug discovery program. We identified a combination of amino acid substitutions in 3CLpro (L50F E166A L167F) that is associated with a >20× increase in 50% effective concentration (EC50) values for ALG-097161, nirmatrelvir (PF-07321332), PF-00835231, and ensitrelvir. While two of the single substitutions (E166A and L167F) provide low-level resistance to the inhibitors in a biochemical assay, the triple mutant results in the highest levels of resistance (6× to 72×). All substitutions are associated with a significant loss of enzymatic 3CLpro activity, suggesting a reduction in viral fitness. Structural biology analysis indicates that the different substitutions reduce the number of inhibitor/enzyme interactions while the binding of the substrate is maintained. These observations will be important for the interpretation of resistance development to 3CLpro inhibitors in the clinical setting. IMPORTANCE Paxlovid is the first oral antiviral approved for treatment of SARS-CoV-2 infection. Antiviral treatments are often associated with the development of drug-resistant viruses. In order to guide the use of novel antivirals, it is essential to understand the risk of resistance development and to characterize the associated changes in the viral genes and proteins. In this work, we describe for the first time a pathway that allows SARS-CoV-2 to develop resistance against Paxlovid in vitro. The characteristics of in vitro antiviral resistance development may be predictive for the clinical situation. Therefore, our work will be important for the management of COVID-19 with Paxlovid and next-generation SARS-CoV-2 3CLpro inhibitors

Salmonella-Induced Mucosal Lectin RegIIIβ Kills Competing Gut Microbiota

Intestinal inflammation induces alterations of the gut microbiota and promotes overgrowth of the enteric pathogen Salmonella enterica by largely unknown mechanisms. Here, we identified a host factor involved in this process. Specifically, the C-type lectin RegIIIβ is strongly upregulated during mucosal infection and released into the gut lumen. In vitro, RegIIIβ kills diverse commensal gut bacteria but not Salmonella enterica subspecies I serovar Typhimurium (S. Typhimurium). Protection of the pathogen was attributable to its specific cell envelope structure. Co-infection experiments with an avirulent S. Typhimurium mutant and a RegIIIβ-sensitive commensal E. coli strain demonstrated that feeding of RegIIIβ was sufficient for suppressing commensals in the absence of all other changes inflicted by mucosal disease. These data suggest that RegIIIβ production by the host can promote S. Typhimurium infection by eliminating inhibitory gut microbiota

Partial two-way mirror: International organization budget transparency

This paper evaluates the budget transparency of international organizations. Building on IMF, OECD, IPSAS, and Open Budget Survey standards for sovereign-state budget transparency, we create a 93-item budget transparency measure reflective of international organization characteristics. International organizations are important global dispensers of accumulated knowledge. This includes the purveying of advice on member state budget transparency. Despite this role, we find only partial budget transparency among our surveyed international organizations. Nonetheless, the international organization financial management and accountability practices were more transparent than their budget process or budget disclosure

Researchers urge international organisations to lift veil of secrecy

Australia must do more to persuade international organisations (IOs) like the United Nations to be more transparent and accountable, a Murdoch University researcher has said

Following the Money: How Transparent are the World's International Organisations?

International organisations such as the World Bank and the International Monetary Fund lead the global push for state budget accountability but a new study suggests such organisations may need to begin improving their own transparency