Constraints on the Dark Matter Particle Mass from the Number of Milky Way Satellites

We have conducted N-body simulations of the growth of Milky Way-sized halos in cold and warm dark matter cosmologies. The number of dark matter satellites in our simulated Milky Ways decreases with decreasing mass of the dark matter particle. Assuming that the number of dark matter satellites exceeds or equals the number of observed satellites of the Milky Way we derive lower limits on the dark matter particle mass. We find with 95% confidence m_s > 13.3 keV for a sterile neutrino produced by the Dodelson and Widrow mechanism, m_s > 8.9 keV for the Shi and Fuller mechanism, m_s > 3.0 keV for the Higgs decay mechanism, and m_{WDM} > 2.3 keV for a thermal dark matter particle. The recent discovery of many new dark matter dominated satellites of the Milky Way in the Sloan Digital Sky Survey allows us to set lower limits comparable to constraints from the complementary methods of Lyman-alpha forest modeling and X-ray observations of the unresolved cosmic X-ray background and of dark matter halos from dwarf galaxy to cluster scales. Future surveys like LSST, DES, PanSTARRS, and SkyMapper have the potential to discover many more satellites and further improve constraints on the dark matter particle mass.Comment: 17 pages, 13 figures, replaced with final version published in Physical Review

Evolving natural history in Duchenne muscular dystrophy: implications for standard of care and experimental therapies

Duchenne muscular dystrophy (DMD) with an average global incidence of 1:5000 is an X-linked recessive disease, caused by mutations in the DMD gene encoding dystrophin. Lack of dystrophin isoforms results in progressive muscle weakness and cardiomyopathy, leading to loss of ambulation and premature death secondary to cardiac/respiratory complications. At present, there is no curative treatment. However, implementation of standards of care has significantly shifted life expectancy and the natural history of DMD has considerably evolved. Moreover, a number of promising therapeutic approaches are under development, some reaching phase II-III clinical trials. These experimental therapies will further contribute to the transformation of the disease trajectory. The projects of my thesis intended to address specific research questions, which have an impact not only on the clinical care of DMD patients, but also advice on clinical trial design. I studied the effect of steroid therapy on the motor function in DMD boys >7 years, more specifically profiling benefits and side effects of the most commonly used regimens: intermittent and daily prednisolone. I analysed the impact of starting steroids at an earlier age than what is standard of care. I explored the role of different dystrophin gene (DMD) genotypes in the motor progression of the disease, further defining the genotype-phenotype correlations. All results obtained are of particular interest for clinical trials of pharmaco-gene therapies targeting specific DMD mutations. Dystrophin isoforms also play an important role for the CNS and their lack causes morbidity in DMD. My investigations expanded the genotype-phenotype profile specifically in relation to neuropsychiatric co-morbidities in DMD. In conjunction with the CNS profile of DMD, I characterized abnormalities of retinal function and developed electroretinography as a potential and non-invasive CNS endpoint for future clinical trials. Addressing the non-ambulant DMD population, I studied quantitative magnetic resonance imaging and novel functional measures of the upper limb. These results allow for the first time to evaluate disease progression and response to treatment in non-ambulant DMD. All the results obtained in this thesis therefore enlarge our knowledge of the disease evolution under current standard treatment and contribute to trial readiness by developing new endpoints

Miniaturized peristaltic rotary pump for non-continuous drug dosing

Micro dosing pumps are the beating heart of infusion systems. Among many technologies to inject micro quantities of fluids, peristaltic pumps show high precision and the possibility to not alter the fluid properties. However, in real drug delivery applications, the continuous release behavior of typical peristaltic pumps is not favorable. In this paper, we investigate the intermittent performance of two prototypes of peristaltic pumps, based on four and five rollers, used to occlude the tube. The pump performances are reported for different rotation speeds and lag times between consecutive infusions. The proposed pumps showed a good volumetric precision (2.88 μL for the five rollers pump and 4.11 μL for the four rollers pump) without any dependency on rotation speed and lag time

Revising the Emergency Management Requirements for new generation reactors

The paper presents the application of a new risk-informed methodology for the identification of the Emergency Management Requirements (EMR) to a Generation II, Large size Reactor and a Generation III+ Small Modular Reactor. The results obtained in this test case demonstrate that the actual EMR is conservative, as expected, for the GenII reactor, while the new methodology could be applied for the definition of EMRs for the new generation Nuclear Power Plants, with a possible reduction of the emergency area without loss of safety level. By adopting both probabilistic and deterministic approaches, the study addresses possible accidents and corresponding release scenarios for the two types of reactor, calculates the areas where the accidents have an impact on the population and defines the new EMR considering the health effects on the population

The NorthStar Ambulatory Assessment in Duchenne muscular dystrophy: considerations for the design of clinical trials.

With the emergence of experimental therapies for Duchenne muscular dystrophy (DMD), it is fundamental to understand the natural history of this disorder to properly design clinical trials. The aims of this study were to assess the effects produced on motor function by different DMD genotypes and early initiation of glucocorticoids

Adhesion and proliferation of skeletal muscle cells on single layer poly(lactic acid) ultra-thin films

An increasing interest in bio-hybrid systems and cell-material interactions is evident in the last years. This leads towards the development of new nano-structured devices and the assessment of their biocompatibility. In the present study, the development of free-standing single layer poly(lactic acid) (PLA) ultra-thin films is described, together with the analysis of topography and roughness properties. The biocompatibility of the PLA films has been tested in vitro, by seeding C2C12 skeletal muscle cells, and thus assessing cells shape, density and viability after 24, 48 and 72 h. The results show that free-standing flexible PLA nanofilms represent a good matrix for C2C12 cells adhesion, spreading and proliferation. Early differentiation into myotubes is also allowed. The biocompatibility of the novel ultra-thin films as substrates for cell growth promotes their application in the fields of regenerative medicine, muscle tissue engineering, drug delivery, and-in general-in the field of bio-hybrid devices

Retrieval of magnetic medical microrobots from the bloodstream

Untethered magnetic microrobots hold the potential to penetrate hard-to-reach areas of the human body and to perform therapy in a controlled way. In the past decade, impressive advancements have been made in this field but the clinical adoption of magnetoresponsive microrobots is still hampered by safety issues. A tool appointed for magnetic microrobots retrieval within body fluids could enable a real paradigm change, fostering their clinical translation.By starting from the general problem to retrieve magnetic microrobots injected into the bloodstream, the authors introduce a magnetic capture model that allows to design retrieval tools for magnetic cores of different diameters (down to 10 nm) and in different environmental conditions (fluid speed up to 7 cms-1). The model robustness is demonstrated by the design and testing of a retrieval catheter. In its optimal configuration, the catheter includes 27 magnets and fits a 12 F catheter. The model provides a good prediction of capture efficiency for 250 nm magnetic particles (experimental data: 77.6%, model prediction: 65%) and a very good prediction for 500 nm particles (experimental data: 93.6%, model prediction: 94%). The results support the proposed model-based design approach, which can be extended to retrieve other magnetoresponsive agents from body compartments

Preliminary Feasibility Study of a Water Space Reactor with an Innovative Reactivity Control System

Power limitation represents a major issue within space applications aimed to human settlements on solar system planets. Among these planets, Mars is considered the most attractive because of its nearness to the Earth and the probable presence of minerals which can be used by the settlers to live off the land. In this frame, small size nuclear power plants can be an interesting solution to overcome the energy supply problem. This paper presents a preliminary feasibility study of a 100 kWe self-pressurized water space reactor, with the aim to design a system characterized by compactness, intrinsic safety and simplicity of the main reactor control components. To this end an innovative reactivity control system, based on the control of the primary coolant mass flow rate, was adopted. The introduction of this system in the reactor design required a comprehensive core neutronics analysis in order to properly quantify the effect of the coolant on the reactor behaviour also as a function of the fuel burn-up. Here only the main results of this analysis, concerning neutron flux profiles and multiplication factors, are discussed. Moreover preliminary results on long term reactivity control are presented, showing the possibility to operate the reactor for as long as 7 years with no need of human intervention

Breakfast skipping, weight, cardiometabolic risk, and nutrition quality in children and adolescents: A systematic review of randomized controlled and intervention longitudinal trials

Breakfast skipping increases with age, and an association with a high risk of being overweight (OW) and of obesity (OB), cardiometabolic risk, and unhealthy diet regimen has been demonstrated in observational studies with children and adults. Short-term intervention trials in adults reported conflicting results. The purpose of this systematic review was to summarize the association of breakfast skipping with body weight, metabolic features, and nutrition quality in the groups of young people that underwent randomized controlled (RCT) or intervention longitudinal trials lasting more than two months. We searched relevant databases (2000–2021) and identified 584 articles, of which 16 were suitable for inclusion. Overall, 50,066 children and adolescents were in-cluded. No studies analyzed cardiometabolic features. Interventions were efficacious in reducing breakfast skipping prevalence when multi-level approaches were used. Two longitudinal studies reported a high prevalence of OW/OB in breakfast skippers, whereas RCTs had negligible effects. Ten studies reported a lower-quality dietary intake in breakfast skippers. This review provides in-sight into the fact that breakfast skipping is a modifiable marker of the risk of OW/OB and unhealthy nutritional habits in children and adolescents. Further long-term multi-level intervention studies are needed to investigate the relationship between breakfast, nutrition quality, chronotypes, and cardiometabolic risk in youths