Microglia modulate neurodegeneration in Alzheimer's and Parkinson's diseases

Dementia is a rapidly rising global health crisis that silently disables families and ends lives and livelihoods around the world. To date, however, no early biomarkers or effective therapies exist. It is now clear that brain microglia are more than mere bystanders or amyloid phagocytes; they can act as governors of neuronal function and homeostasis in the adult brain. Here, we highlight the fundamental role of microglia as tissue-resident macrophages in neuronal health. Then, we suggest how chronic impairment in microglia-neuron cross-talk may secure the permanence of the failure of synaptic and neuronal function and health in Alzheimer’s and Parkinson’s diseases. Understanding how to assess and modulate microglia-neuron interactions critical for brain health will be key to developing effective therapies for dementia

Structure in cohesive powders studied with spin-echo small angle\ud neutron scattering

Extracting structure and ordering information from the bulk of granular materials is a challenging task. Here we present Spin-Echo Small Angle Neutron Scattering Measurements in combination with computer simulations on a fine powder of silica, before and after uniaxial compression. The cohesive powder packing is modeled by using molecular dynamics simulations and the structure, in terms of the density–density correlation function, is calculated from the simulation and compared with experiment. In the dense case, both quantitative and qualitative agreement between measurement and simulations is observed, thus creating the desired link between experiment and computer simulation. Further simulations with appropriate attractive potentials and adequate preparation procedures are needed in order to capture the very loose-packed cohesive powders.\u

Low-frequency Pliocene climate variability in the eastern Nordic Seas

The Pliocene (5.3–2.6 Ma) is often described as a relatively stable climatic period, with warm temperatures characterizing high latitudes. New suborbital resolved stable isotope records from ODP Hole 642B in the Eastern Nordic Seas document that the Pliocene was not a stable period characterized by one climate. Rather, seven distinct climate phases, each lasting between 150,000 and 400,000 years, are identified and characterized in the time interval 5.1–3.1 Ma. Four of the transitions between the defined climate phases occurred close to an eccentricity minimum and a minimum in amplitude of change for Northern Hemisphere summer insolation, while two occurred around an eccentricity maximum and a maximum in amplitude in insolation change. Hence, a low frequency response of the Nordic Seas to insolation forcing is indicated. In addition, paleogeographic and related paleoceanographic changes, expansion of the Arctic sea ice cover and onset of NHG were important factors behind the evolving Pliocene low frequency variability in the eastern Nordic Seas. It is likely that the identified climate phases and transitions are important beyond the Nordic Seas, due to their association with changes to both insolation and paleogeography. Also, a strong and variable degree of diagenetic calcite overgrowth is documented for the planktic foraminifera, especially influencing the planktic δ18O results; the absolute values and amplitude of change cannot be taken at face value

The role of area level social deprivation on childhood and adolescent consultation rate in primary care:a population based, cohort study

BACKGROUND: Studies show that children and adolescents in the most socially deprived areas (SDA) consult their general practitioner (GP) more often than those in the least socially deprived areas (Non-SDA). Given that GPs see a wide range of diseases, it is important to know which clinical diagnoses are shaped by socioeconomic factors. The primary objective was to determine the association between area level social deprivation and consultation rates in a pediatric population. The secondary objective was to explore this association across a wide range of clinical diagnoses. METHODS: A cohort study using the Rijnmond Primary Care Database (RPCD) was conducted. Between 2013 and 2020, a total of 69,861 patients aged 0 to 17 years registered with a GP were analysed. A consultation was defined as patient contact and entry of a diagnosis using the International Classification of Primary Care (ICPC-1) code. Associations between consultation rates, ICPC-1 codes and area level social deprivation were explored using a Poisson regression model. The incidence risk ratio (IRR) and 95% confidence interval (CI) were reported. RESULTS: Over the 7-year study period the consultation rate of the study population was 3.8 per person-years. The top 5 reasons for children and adolescents to consult their GP was related to skin, respiratory, general unspecified, musculoskeletal and digestive symptoms or diagnoses. Consultation rate was higher in SDA group compared to Non-SDA group (IRR 1.20, 95% CI 1.19–1.20). Consultation rate for ICPC-1 code related to pregnancy and family planning was significantly lower in SDA group compared to Non-SDA group. Upon further exploration of this code, SDA group were less likely to consult for oral contraception and more likely to contact a GP for induced termination of pregnancy compared to Non-SDA group (IRR 0.36; 95% CI 0.33–0.44 and IRR 2.94; 95% CI 1.58–5.46 respectively). CONCLUSIONS: Overall, SDA group had higher GP consultation rates for the majority of clinical diagnoses except for pregnancy and family planning. In this latter category, adolescent females in SDA consulted less frequently for oral contraception. This study illustrates the need to understand the underlying health seeking behaviors of children and adolescents at different development phases of their lives. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12875-022-01873-x

Short-wavelength collective modes in a binary hard-sphere mixture

We use hard-sphere generalized hydrodynamic equations to discuss the extended hydrodynamic modes of a binary mixture. The theory presented here is analytic and it provides us with a simple description of the collective excitations of a dense binary mixture at molecular length scales. The behavior we predict is in qualitative agreement with molecular-dynamics results for soft-sphere mixtures. This study provides some insight into the role of compositional disorder in forming glassy configurations.Comment: Published; withdrawn since already published. Ordering in the archive gives misleading impression of new publicatio

Introductory clifford analysis

In this chapter an introduction is given to Clifford analysis and the underlying Clifford algebras. The functions under consideration are defined on Euclidean space and take values in the universal real or complex Clifford algebra, the structure and properties of which are also recalled in detail. The function theory is centered around the notion of a monogenic function, which is a null solution of a generalized Cauchy–Riemann operator, which is rotation invariant and factorizes the Laplace operator. In this way, Clifford analysis may be considered as both a generalization to higher dimension of the theory of holomorphic functions in the complex plane and a refinement of classical harmonic analysis. A notion of monogenicity may also be associated with the vectorial part of the Cauchy–Riemann operator, which is called the Dirac operator; some attention is paid to the intimate relation between both notions. Since a product of monogenic functions is, in general, no longer monogenic, it is crucial to possess some tools for generating monogenic functions: such tools are provided by Fueter’s theorem on one hand and the Cauchy–Kovalevskaya extension theorem on the other hand. A corner stone in this function theory is the Cauchy integral formula for representation of a monogenic function in the interior of its domain of monogenicity. Starting from this representation formula and related integral formulae, it is possible to consider integral transforms such as Cauchy, Hilbert, and Radon transforms, which are important both within the theoretical framework and in view of possible applications

Decay-assisted collinear resonance ionization spectroscopy: Application to neutron-deficient francium

This paper reports on the hyperfine-structure and radioactive-decay studies of the neutron-deficient francium isotopes $^{202-206}$Fr performed with the Collinear Resonance Ionization Spectroscopy (CRIS) experiment at the ISOLDE facility, CERN. The high resolution innate to collinear laser spectroscopy is combined with the high efficiency of ion detection to provide a highly-sensitive technique to probe the hyperfine structure of exotic isotopes. The technique of decay-assisted laser spectroscopy is presented, whereby the isomeric ion beam is deflected to a decay spectroscopy station for alpha-decay tagging of the hyperfine components. Here, we present the first hyperfine-structure measurements of the neutron-deficient francium isotopes $^{202-206}$Fr, in addition to the identification of the low-lying states of $^{202,204}$Fr performed at the CRIS experiment.Comment: Accepted for publication with Physical Review

Laser spectroscopy of francium isotopes at the borders of the region of reflection asymmetry

The magnetic dipole moments and changes in mean-square charge radii of the neutron-rich $^{218m,219,229,231}\text{Fr}$ isotopes were measured with the newly-installed Collinear Resonance Ionization Spectroscopy (CRIS) beam line at ISOLDE, CERN, probing the $7s~^{2}S_{1/2}$ to $8p~^{2}P_{3/2}$ atomic transition. The $\delta\langle r^{2}\rangle^{A,221}$ values for $^{218m,219}\text{Fr}$ and $^{229,231}\text{Fr}$ follow the observed increasing slope of the charge radii beyond $N~=~126$. The charge radii odd-even staggering in this neutron-rich region is discussed, showing that $^{220}\text{Fr}$ has a weakly inverted odd-even staggering while $^{228}\text{Fr}$ has normal staggering. This suggests that both isotopes reside at the borders of a region of inverted staggering, which has been associated with reflection-asymmetric shapes. The $g(^{219}\text{Fr}) = +0.69(1)$ value supports a $\pi 1h_{9/2}$ shell model configuration for the ground state. The $g(^{229,231}\text{Fr})$ values support the tentative $I^{\pi}(^{229,231}\text{Fr}) = (1/2^{+})$ spin, and point to a $\pi s_{1/2}^{-1}$ intruder ground state configuration.Comment: Accepted for publication with Physical Review

Incidence and management of Osgood-Schlatter disease in general practice:retrospective cohort study

BACKGROUND: Osgood–Schlatter disease (OSD) is a non-traumatic knee problem that is primarily observed in sports-active children and adolescents aged 8–15 years. AIM: To determine the incidence of OSD and to gain an insight into the management of children and adolescents with OSD in general practice. DESIGN AND SETTING: A retrospective cohort study was conducted using a healthcare database containing full electronic health records of over 200 000 patients in general practice in and around the Dutch city of Rotterdam. METHOD: Patients with a new diagnosis of OSD from 1 January 2012 to 31 December 2017 were extracted using a search algorithm based on International Classification of Primary Health Care coding and search terms in free text. Data on the management of OSD were manually interpreted. RESULTS: The mean incidence over the study period was 3.8 (95% confidence interval [CI] = 3.5 to 4.2) per 1000 person–years in those aged 8–18 years. Boys had a higher incidence rate of 4.9 (95% CI = 4.3 to 5.5) compared with girls (2.7, 95% CI = 2.3 to 3.2). Peak incidence was at 12 years of age for boys and 11 years for girls. Advice was the most commonly applied strategy (55.1%), followed by rest (21.0%), referral for imaging (19.5%), and physiotherapy (13.4%). CONCLUSION: To the authors’ knowledge, for the first time the incidence of OSD has been calculated using GP electronic medical files. There is a discrepancy, especially for imaging and referral to a medical specialist, between the current Dutch general practice guidelines and how GPs actually manage the condition in clinical practice