Ontogeny and pharmacogenetics: determinants of age-associated differences in drug clearance during human development

Development per se represents a continuum of biologic events that enable adaptation, somatic growth and eventually, reproduction. From a societal, psychosocial, behavioral and medical perspective, it is generally appreciated that infants and children are far different from adults and elderly. As well, pediatric patients suffer from conditions and diseases that in many instances are unique and have no true counterpart in adults. These particular differences are generally known and to a great degree, determine how infants, children and adolescents are provided for both within the context of medical care and in society. What remains often under-appreciated is the

Dark Matter And Bs→μ+μ−B_s \to \mu^+ \mu^- With Minimal SO10SO_{10} Soft SUSY Breaking

CMSSM boundary conditions are usually used when calculating cosmological dark matter densities. In this paper we calculate the cosmological density of dark matter in the MSSM using minimal $SO_{10}$ soft SUSY breaking boundary conditions. These boundary conditions incorporate several attractive features: they are consistent with $SO_{10}$ Yukawa unification, they result in a "natural" inverted scalar mass hierarchy and they reduce the dimension 5 operator contribution to the proton decay rate. With regards to dark matter, on the other hand, this is to a large extent an unexplored territory with large squark and slepton masses $m_{16}$, large $A_0$ and small $\{\mu, M_{1/2} \}$. We find that in most regions of parameter space the cosmological density of dark matter is considerably less than required by the data. However there is a well--defined, narrow region of parameter space which provides the observed relic density of dark matter, as well as a good fit to precision electroweak data, including top, bottom and tau masses, and acceptable bounds on the branching fraction of $B_s \to \mu^+ \mu^-$. We present predictions for Higgs and SUSY spectra, the dark matter detection cross section and the branching ratio ${\rm BR}(B_s\to \mu^+ \mu^-)$ in this region of parameter space.Comment: 15 pages, 5 figure

WHO global research priorities for antimicrobial resistance in human health

The WHO research agenda for antimicrobial resistance (AMR) in human health has identified 40 research priorities to be addressed by the year 2030. These priorities focus on bacterial and fungal pathogens of crucial importance in addressing AMR, including drug-resistant pathogens causing tuberculosis. These research priorities encompass the entire people-centred journey, covering prevention, diagnosis, and treatment of antimicrobial-resistant infections, in addition to addressing the overarching knowledge gaps in AMR epidemiology, burden and drivers, policies and regulations, and awareness and education. The research priorities were identified through a multistage process, starting with a comprehensive scoping review of knowledge gaps, with expert inputs gathered through a survey and open call. The priority setting involved a rigorous modified Child Health and Nutrition Research Initiative approach, ensuring global representation and applicability of the findings. The ultimate goal of this research agenda is to encourage research and investment in the generation of evidence to better understand AMR dynamics and facilitate policy translation for reducing the burden and consequences of AMR

The influence of geochemical variation among Globigerinoides ruber individuals on paleoceanographic reconstructions

Variation among individuals within species is a biological precondition for co-existence. Traditional geochemical analysis based on bulk averages from multiple planktic foraminifera individuals facilitates rapid data gathering but necessarily means the loss of large amounts of potentially crucial information into variability within a given sample. As the sensitivity of geochemical analysis improves, it is now feasible to build sufficiently powerful datasets to investigate paleoclimatic variation at the level of individual specimens. Here, we investigate geochemical and morphological variation among the sensu stricto, sensu lato and sensu lato extreme subspecies of the workhorse extant planktic foraminifera Globigerinoides ruber. Our experimental design distinguishes between subspecies and intraspecific variability as well as the repeatability of laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). We show that geochemical variability in Mg/Ca ratios is driven by differences in subspecies depth habitat and that ontogenetic trends in Mg/Ca ratios are evident in the final whorl, with the final chamber consistently showing depleted Mg/Ca. These ontogenetic trends are not driven by individual chamber or test size. The Mg/Ca value variance among individuals is ~100 times higher than the variance among repeated laser spot analyses of a signal chambers, directing laboratory protocols towards the need to sample ecologically and environmentally homogeneous samples. Our results emphasize that we can use LA-ICP-MS to quantify how individual variability aggregates to bulk results, and highlights that, with sufficient sample sizes, it is possible to reveal how intraspecific variability alters geochemical inference