Dark Matter, Baryogenesis and Neutrino Oscillations from Right Handed Neutrinos

We show that, leaving aside accelerated cosmic expansion, all experimental data in high energy physics that are commonly agreed to require physics beyond the Standard Model can be explained when completing it by three right handed neutrinos that can be searched for using current day experimental techniques. The model that realises this scenario is known as Neutrino Minimal Standard Model (\nu MSM). In this article we give a comprehensive summary of all known constraints in the \nu MSM, along with a pedagogical introduction to the model. We present the first complete quantitative study of the parameter space of the model where no physics beyond the \nu MSM is needed to simultaneously explain neutrino oscillations, dark matter and the baryon asymmetry of the universe. This requires to track the time evolution of left and right handed neutrino abundances from hot big bang initial conditions down to temperatures below the QCD scale. We find that the interplay of resonant amplifications, CP-violating flavour oscillations, scatterings and decays leads to a number of previously unknown constraints on the sterile neutrino properties. We furthermore re-analyse bounds from past collider experiments and big bang nucleosynthesis in the face of recent evidence for a non-zero neutrino mixing angle \theta_{13}. We combine all our results with existing constraints on dark matter properties from astrophysics and cosmology. Our results provide a guideline for future experimental searches for sterile neutrinos. A summary of the constraints on sterile neutrino masses and mixings has appeared in arXiv:1204.3902 [hep-ph]. In this article we provide all details of our calculations and give constraints on other model parameters.Comment: We extended the discussion in several sections, in particular 2, 3 and 8, in response to comments we received after submission of version 1. We added appendix

First principle approach to leptogenesis

Baryogenesis via leptogenesis offers an elegant explanation of the origin of the baryon asymmetry of the universe by means of the CP-violating decay of heavy right-handed neutrinos in the early universe. This scenario has become very popular over the past decades due to its connection with neutrino physics. A precise computation of the baryon asymmetry produced in the leptogenesis scenario is difficult since it requires to follow the out-of-equilibrium evolution of the hot early universe. We present here a nonequilibrium quantum field theory approach to leptogenesis. This method is free of many problems inherent to the conventional approach based on the classical Boltzmann equation. Starting from first principles we derive a quantum-corrected Boltzmann equation for the asymmetry. The obtained equation is free of the double counting problem and incorporates consistently thermal corrections to the quasiparticles properties, in particular thermal masses and thermal widths. Finite width effects are taken into account through the extended quasiparticle approximation. We compare numerically the reaction densities obtained from the conventional and nonequilibrium quantum field theory approaches. We find that the enhancement due to thermal effects is partially compensated by the suppression due to thermal masses

Early intensification and autologous stem cell transplantation in patients with systemic AL amyloidosis: a single-centre experience

Primary systemic amyloidosis (AL amyloidosis) continues to have a very poor prognosis. Most therapeutic strategies remain unsatisfactory. Conventional chemotherapy is known to offer at best only moderate efficacy. Several studies have yielded higher complete response rates after high-dose chemotherapy and autologous stem cell transplantation (ASCT) in addition to improving outcomes in a subgroup of patients. However, the superiority of an intensive approach in AL amyloidosis has not been confirmed in a randomised trial. The precise role of ASCT remains unclear. We report our experience in 16 patients diagnosed with AL amyloidosis and treated in a multidisciplinary approach with high-dose melphalan and ASCT. Median age was 59 (39-71)years. The kidneys were predominantly affected in 75% of cases; two or more organs were affected in 38%. Median time from diagnosis to transplantation was 2 (1-4)months. Three patients (19%) developed acute renal failure and required transient dialysis. Transplant-related mortality was 6% after 100days. Haematological complete response (CR) was obtained in nine (56%) and organ response in six (38%) patients. Nine out of 12 patients (75%) with kidney involvement exhibited a sustained clinical benefit at 12months. Half of all the patients (n = 8) were alive after a median follow-up of 33months, including two in continuous CR. This suggests that high-dose chemotherapy and ASCT are still valid treatment options in AL amyloidosis and that a significant number of patients with renal involvement might benefit from this approac

Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension

High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to ~192,000 individuals, and used ~155,063 samples for independent replication. We identified 31 novel blood pressure or hypertension associated genetic regions in the general population, including three rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5mmHg/allele) than common variants. Multiple rare, nonsense and missense variant associations were found in A2ML1 and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention

Early intensification and autologous stem cell transplantation in patients with systemic AL amyloidosis: a single-centre experience.

Primary systemic amyloidosis (AL amyloidosis) continues to have a very poor prognosis. Most therapeutic strategies remain unsatisfactory. Conventional chemotherapy is known to offer at best only moderate efficacy. Several studies have yielded higher complete response rates after high-dose chemotherapy and autologous stem cell transplantation (ASCT) in addition to improving outcomes in a subgroup of patients. However, the superiority of an intensive approach in AL amyloidosis has not been confirmed in a randomised trial. The precise role of ASCT remains unclear. We report our experience in 16 patients diagnosed with AL amyloidosis and treated in a multidisciplinary approach with high-dose melphalan and ASCT. Median age was 59 (39-71) years. The kidneys were predominantly affected in 75% of cases; two or more organs were affected in 38%. Median time from diagnosis to transplantation was 2 (1-4) months. Three patients (19%) developed acute renal failure and required transient dialysis. Transplant-related mortality was 6% after 100 days. Haematological complete response (CR) was obtained in nine (56%) and organ response in six (38%) patients. Nine out of 12 patients (75%) with kidney involvement exhibited a sustained clinical benefit at 12 months. Half of all the patients (n = 8) were alive after a median follow-up of 33 months, including two in continuous CR. This suggests that high-dose chemotherapy and ASCT are still valid treatment options in AL amyloidosis and that a significant number of patients with renal involvement might benefit from this approach

Large-scale releases and establishment of wMel Wolbachia in Aedes aegypti mosquitoes throughout the Cities of Bello, Medellín and Itagüí, Colombia.

BackgroundThe wMel strain of Wolbachia has been successfully introduced into Aedes aegypti mosquitoes and has been shown to reduce the transmission of dengue and other Aedes-borne viruses. Here we report the entomological results from phased, large-scale releases of Wolbachia infected Ae. aegypti mosquitoes throughout three contiguous cities located in the Aburrá Valley, Colombia.Methodology/principal findingsLocal wMel Wolbachia-infected Ae. aegypti mosquitoes were generated and then released in an initial release pilot area in 2015-2016, which resulted in the establishment of Wolbachia in the local mosquito populations. Subsequent large-scale releases, mainly involving vehicle-based releases of adult mosquitoes along publicly accessible roads and streets, were undertaken across 29 comunas throughout Bello, Medellín and Itagüí Colombia between 2017-2022. In 9 comunas these were supplemented by egg releases that were undertaken by staff or community members. By the most recent monitoring, Wolbachia was found to be stable and established at consistent levels in local mosquito populations (>60% prevalence) in the majority (67%) of areas.ConclusionThese results, from the largest contiguous releases of wMel Wolbachia mosquitoes to date, highlight the operational feasibility of implementing the method in large urban settings. Based on results from previous studies, we expect that Wolbachia establishment will be sustained long term. Ongoing monitoring will confirm Wolbachia persistence in local mosquito populations and track its establishment in the remaining areas

Successful introgression of wMel Wolbachia into Aedes aegypti populations in Fiji, Vanuatu and Kiribati.

Pacific Island countries have experienced periodic dengue, chikungunya and Zika outbreaks for decades. The prevention and control of these mosquito-borne diseases rely heavily on control of Aedes aegypti mosquitoes, which in most settings are the primary vector. Introgression of the intracellular bacterium Wolbachia pipientis (wMel strain) into Ae. aegypti populations reduces their vector competence and consequently lowers dengue incidence in the human population. Here we describe successful area-wide deployments of wMel-infected Ae. aegypti in Suva, Lautoka, Nadi (Fiji), Port Vila (Vanuatu) and South Tarawa (Kiribati). With community support, weekly releases of wMel-infected Ae. aegypti mosquitoes for between 2 to 5 months resulted in wMel introgression in nearly all locations. Long term monitoring confirmed a high, self-sustaining prevalence of wMel infecting mosquitoes in almost all deployment areas. Measurement of public health outcomes were disrupted by the Covid19 pandemic but are expected to emerge in the coming years

Release & monitoring of <i>w</i>Mel-infected <i>Ae</i>. <i>aegypti</i> within 12 areas of Port Vila, Vanuatu.

Each release area was divided into a grid with 100 x 100 meter squares. Grid squares lacking mosquito releases were omitted. Release gradient was determined by using GPS coordinates of each release event and assigning the number of wMel-infected mosquitos to a corresponding grid square. Monitoring numbers were determined in the same way. Map produced in QGIS version 3.16.1 using boundaries aggregated from the enumeration area boundaries freely available from the Pacific Data Hub (https://pacificdata.org/data/dataset/2016_vut_phc_admin_boundaries) and OpenMapTiles basemap layer (https://openmaptiles.org/) with CARTO light design (https://carto.com/)). (PNG)</p

Insecticide Resistance (IR) Profiles of Release Strains determined by WHO Biosaay.

A) Fiji release strain IR profile. B) Vanuatu release strain IR profile. C) Kiribati release strain IR profile. Each data point is the mean of five biological replicates (± s.d.) using approximately 20 mosquitoes per replicate. (TIFF)</p