Minimal cubic cones via Clifford algebras

We construct two infinite families of algebraic minimal cones in $R^{n}$. The first family consists of minimal cubics given explicitly in terms of the Clifford systems. We show that the classes of congruent minimal cubics are in one to one correspondence with those of geometrically equivalent Clifford systems. As a byproduct, we prove that for any $n\ge4$, $n\ne 16k+1$, there is at least one minimal cone in $R^{n}$ given by an irreducible homogeneous cubic polynomial. The second family consists of minimal cones in $R^{m^2}$, $m\ge2$, defined by an irreducible homogeneous polynomial of degree $m$. These examples provide particular answers to the questions on algebraic minimal cones posed by Wu-Yi Hsiang in the 1960's.Comment: Final version, corrects typos in Table

Effects of electrical stimulation of dorsal raphe nucleus on neuronal response properties of barrel cortex layer IV neurons following long-term sensory deprivation

Abstract: Objective To evaluate the effect of electrical stimulation of dorsal raphe nucleus (DRN) on response properties of layer IV barrel cortex neurons following long-term sensory deprivation. Methods: Male Wistar rats were divided into sensory-deprived (SD) and control (unplucked) groups. In SD group, all vibrissae except the D2 vibrissa were plucked on postnatal day one, and kept plucked for a period of 60 d. After that, whisker regrowth was allowed for 8-10 d. The D2 principal whisker (PW) and the D1 adjacent whisker (AW) were either deflected singly or both deflected in a serial order that the AW was deflected 20 ms before PW deflection for assessing lateral inhibition, and neuronal responses were recorded from layer IV of the D2 barrel cortex. DRN was electrically stimulated at inter-stimulus intervals (ISIs) ranging from 0 to 800 ms before whisker deflection. Results: PW-evoked responses increased in the SD group with DRN electrical stimulation at ISIs of 50 ms and 100 ms, whereas AW-evoked responses increased at ISI of 800 ms in both groups. Whisker plucking before DRN stimulation could enhance the responsiveness of barrel cortex neurons to PW deflection and decrease the responsiveness to AW deflection. DRN electrical stimulation significantly reduced this difference only in PW-evoked responses between groups. Besides, no DRN stimulation-related changes in response latency were observed following PW or AW deflection in either group. Moreover, condition test (CT) ratio increased in SD rats, while DRN stimulation did not affect the CT ratio in either group. There was no obvious change in 5-HT2A receptor protein density in barrel cortex between SD and control groups. Conclusion: These results suggest that DRN electrical stimulation can modulate information processing in the SD barrel cortex

Froude supercritical flow processes and sedimentary structures: new insights from experiments with a wide range of grain sizes

Recognition of Froude supercritical flow deposits in environments that range from rivers to the ocean floor has triggered a surge of interest in their flow processes, bedforms and sedimentary structures. Interpreting these supercritical flow deposits is especially important because they often represent the most powerful flows in the geological record. Insights from experiments are key to reconstruct palaeo‐flow processes from the sedimentary record. So far, all experimentally produced supercritical flow deposits are of a narrow grain‐size range (fine to medium sand), while deposits in the rock record often consist of a much wider grain‐size distribution. This paper presents results of supercritical‐flow experiments with a grain‐size distribution from clay to gravel. These experiments show that cyclic step instabilities can produce more complex and a larger variety of sedimentary structures than the previously suggested backsets and ‘scour and fill’ structures. The sedimentary structures are composed of irregular lenses, mounds and wedges with backsets and foresets, as well as undulating planar to low‐angle upstream and downstream dipping laminae. The experiments also demonstrate that the Froude number is not the only control on the sedimentary structures formed by supercritical‐flow processes. Additional controls include the size and migration rate of the hydraulic jump and the substrate cohesion. This study further demonstrates that Froude supercritical flow promotes suspension transport of all grain sizes, including gravels. Surprisingly, it was observed that all grain sizes were rapidly deposited just downstream of hydraulic jumps, including silt and clay. These results expand the range of dynamic mud deposition into supercritical‐flow conditions, where local transient shear stress reduction rather than overall flow waning conditions allow for deposition of fines. Comparison of the experimental deposits with outcrop datasets composed of conglomerates to mudstones, shows significant similarities and highlights the role of hydraulic jumps, rather than overall flow condition changes, in producing lithologically and geometrically complex stratigraphy

Adult-onset autoinflammation caused by somatic mutations in UBA1:A Dutch case series of patients with VEXAS

Background: A novel autoinflammatory syndrome was recently described in male patients who harbored somatic mutations in the X-chromosomal UBA1 gene. These patients were characterized by adult-onset, treatment-refractory inflammation with fever, cytopenia, dysplastic bone marrow, vacuoles in myeloid and erythroid progenitor cells, cutaneous and pulmonary inflammation, chondritis, and vasculitis, which is abbreviated as VEXAS. Objective: This study aimed to (retrospectively) diagnose VEXAS in patients who had previously been registered as having unclassified autoinflammation. We furthermore aimed to describe clinical experiences with this multifaceted, complex disease. Methods: A systematic reanalysis of whole-exome sequencing data from a cohort of undiagnosed patients with autoinflammation from academic hospitals in The Netherlands was performed. When no sequencing data were available, targeted Sanger sequencing was applied in cases with high clinical suspicion of VEXAS. Results: A total of 12 male patients who carried mutations in UBA1 were identified. These patients presented with adult-onset (mean age 67 years, range 47-79 years) autoinflammation with systemic symptoms, elevated inflammatory parameters, and multiorgan involvement, most typically involving the skin and bone marrow. Novel features of VEXAS included interstitial nephritis, cardiac involvement, stroke, and intestinal perforation related to treatment with tocilizumab. Although many types of treatment were initiated, most patients became treatment-refractory, with a high mortality rate of 50%. Conclusion: VEXAS should be considered in the differential diagnosis of males with adult-onset autoinflammation characterized by systemic symptoms and multiorgan involvement. Early diagnosis can prevent unnecessary diagnostic procedures and provide better prognostic information and more suitable treatment options, including stem cell transplantation

Application of non-HDL cholesterol for population-based cardiovascular risk stratification: results from the Multinational Cardiovascular Risk Consortium.

BACKGROUND: The relevance of blood lipid concentrations to long-term incidence of cardiovascular disease and the relevance of lipid-lowering therapy for cardiovascular disease outcomes is unclear. We investigated the cardiovascular disease risk associated with the full spectrum of bloodstream non-HDL cholesterol concentrations. We also created an easy-to-use tool to estimate the long-term probabilities for a cardiovascular disease event associated with non-HDL cholesterol and modelled its risk reduction by lipid-lowering treatment. METHODS: In this risk-evaluation and risk-modelling study, we used Multinational Cardiovascular Risk Consortium data from 19 countries across Europe, Australia, and North America. Individuals without prevalent cardiovascular disease at baseline and with robust available data on cardiovascular disease outcomes were included. The primary composite endpoint of atherosclerotic cardiovascular disease was defined as the occurrence of the coronary heart disease event or ischaemic stroke. Sex-specific multivariable analyses were computed using non-HDL cholesterol categories according to the European guideline thresholds, adjusted for age, sex, cohort, and classical modifiable cardiovascular risk factors. In a derivation and validation design, we created a tool to estimate the probabilities of a cardiovascular disease event by the age of 75 years, dependent on age, sex, and risk factors, and the associated modelled risk reduction, assuming a 50% reduction of non-HDL cholesterol. FINDINGS: Of the 524 444 individuals in the 44 cohorts in the Consortium database, we identified 398 846 individuals belonging to 38 cohorts (184 055 [48·7%] women; median age 51·0 years [IQR 40·7-59·7]). 199 415 individuals were included in the derivation cohort (91 786 [48·4%] women) and 199 431 (92 269 [49·1%] women) in the validation cohort. During a maximum follow-up of 43·6 years (median 13·5 years, IQR 7·0-20·1), 54 542 cardiovascular endpoints occurred. Incidence curve analyses showed progressively higher 30-year cardiovascular disease event-rates for increasing non-HDL cholesterol categories (from 7·7% for non-HDL cholesterol <2·6 mmol/L to 33·7% for ≥5·7 mmol/L in women and from 12·8% to 43·6% in men; p<0·0001). Multivariable adjusted Cox models with non-HDL cholesterol lower than 2·6 mmol/L as reference showed an increase in the association between non-HDL cholesterol concentration and cardiovascular disease for both sexes (from hazard ratio 1·1, 95% CI 1·0-1·3 for non-HDL cholesterol 2·6 to <3·7 mmol/L to 1·9, 1·6-2·2 for ≥5·7 mmol/L in women and from 1·1, 1·0-1·3 to 2·3, 2·0-2·5 in men). The derived tool allowed the estimation of cardiovascular disease event probabilities specific for non-HDL cholesterol with high comparability between the derivation and validation cohorts as reflected by smooth calibration curves analyses and a root mean square error lower than 1% for the estimated probabilities of cardiovascular disease. A 50% reduction of non-HDL cholesterol concentrations was associated with reduced risk of a cardiovascular disease event by the age of 75 years, and this risk reduction was greater the earlier cholesterol concentrations were reduced. INTERPRETATION: Non-HDL cholesterol concentrations in blood are strongly associated with long-term risk of atherosclerotic cardiovascular disease. We provide a simple tool for individual long-term risk assessment and the potential benefit of early lipid-lowering intervention. These data could be useful for physician-patient communication about primary prevention strategies. FUNDING: EU Framework Programme, UK Medical Research Council, and German Centre for Cardiovascular Research

Mechanisms underlying a thalamocortical transformation during active tactile sensation

During active somatosensation, neural signals expected from movement of the sensors are suppressed in the cortex, whereas information related to touch is enhanced. This tactile suppression underlies low-noise encoding of relevant tactile features and the brain’s ability to make fine tactile discriminations. Layer (L) 4 excitatory neurons in the barrel cortex, the major target of the somatosensory thalamus (VPM), respond to touch, but have low spike rates and low sensitivity to the movement of whiskers. Most neurons in VPM respond to touch and also show an increase in spike rate with whisker movement. Therefore, signals related to self-movement are suppressed in L4. Fast-spiking (FS) interneurons in L4 show similar dynamics to VPM neurons. Stimulation of halorhodopsin in FS interneurons causes a reduction in FS neuron activity and an increase in L4 excitatory neuron activity. This decrease of activity of L4 FS neurons contradicts the "paradoxical effect" predicted in networks stabilized by inhibition and in strongly-coupled networks. To explain these observations, we constructed a model of the L4 circuit, with connectivity constrained by in vitro measurements. The model explores the various synaptic conductance strengths for which L4 FS neurons actively suppress baseline and movement-related activity in layer 4 excitatory neurons. Feedforward inhibition, in concert with recurrent intracortical circuitry, produces tactile suppression. Synaptic delays in feedforward inhibition allow transmission of temporally brief volleys of activity associated with touch. Our model provides a mechanistic explanation of a behavior-related computation implemented by the thalamocortical circuit

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362