A state-dependent delay equation with chaotic solutions

We exhibit a scalar-valued state-dependent delay differential equation x 0 (t) = f(x(t − d(xt))) that has a chaotic solution. This equation has continuous (semi-strictly) monotonic negative feedback, and the quantity t − d(xt) is strictly increasing along solutions

Corrigendum to "A state-dependent delay equation with chaotic solutions" - Electron. J. Qual. Theory Differ. Equ. 2019, No. 22, 1-20

We correct an error in “A state-dependent delay equation with chaotic solutions” [Electron. J. Qual. Theory Differ. Equ. 2019, No. 22, 1–20]

The effects of pelvic ring injuries on quality of life, physical, and mental health:results of a 2-year prospective cohort study

PURPOSE: Pelvic ring injuries are known to affect the patients' daily life in terms of physical functioning and quality of life (QoL). Still, prospective studies on the patient's perception over the first 2 years of rehabilitation are lacking. Therefore, patients cannot be properly informed about whether or when they will return to their pre-existing level of physical functioning and QoL. METHODS: A prospective longitudinal cohort study was performed over a 4-year period including all consecutive patients above 18 years who sustained a pelvic ring injury in a level 1 trauma center. Validated patient-reported outcome measures (PROMs) were used to assess physical functioning (SMFA) and QoL (EQ-5D) at baseline (recalled pre-injury score), 6 weeks, 3 months, 6 months, 1 year and 2 years after the injury. It was assessed whether patients had fully recovered by comparing follow-up scores to baseline PROMs. Binary logistic regression analysis was used to identify independent predictors for patients who did not fully recover. Most experienced difficulties at 3 months and 1 year were identified by analyzing the highest reported scores on individual items of the SMFA. RESULTS: A total of 297 patients with a pelvic ring injury were identified of which 189 were eligible for follow-up and 154 (82%) responded. Median SMFA function score at 3 months, 1 and 2 years was 70, 78 and 88, respectively, compared to 96 out of 100 before the injury. Median SMFA bother score was 67, 79 and 88, respectively. Median EQ-5D score at 3 months, 1 and 2 years was 0.61, 0.81 and 0.85, respectively, compared to 1 (maximum achievable) before the injury. After 1 and 2 years of follow-up, 61% and 75% of the patients fully "recovered" in physical functioning and 52% and 71% fully recovered in terms of QoL. Female gender and high-energy trauma were independent predictors for not fully recovering after 1 year. After 3 months of follow-up, 54% of patients reported severe difficulties with recreational activities, whereas after 1 year, most experienced difficulties (31% of patients) concerned heavy house or yard work. Moreover, after 3 months and 1 year, 44% and 27% of patients reported feeling physically disabled. CONCLUSION: Pelvic ring injuries have a large impact on the patients' daily life in the first 2 years of rehabilitation. Directly after the injury, physical functioning and QoL decrease strongly but then gradually improve over a 2-year period with about 75% of patients fully recovering. Female gender and high-energy trauma are shown to be independent predictors for not fully recovering. After 3 months, patients experience difficulties with both the physical and mental effects of the injury which continue to be present after 1 year

Evaluation of the Berlin polytrauma definition:A Dutch nationwide observational study

BACKGROUND The Berlin polytrauma definition (BPD) was established to identify multiple injury patients with a high risk of mortality. The definition includes injuries with an Abbreviated Injury Scale score of >= 3 in >= 2 body regions (2AIS >= 3) combined with the presence of >= 1 physiological risk factors (PRFs). The PRFs are based on age, Glasgow Coma Scale, hypotension, acidosis, and coagulopathy at specific cutoff values. This study evaluates and compares the BPD with two other multiple injury definitions used to identify patients with high resource utilization and mortality risk, using data from the Dutch National Trauma Register (DNTR). METHODS The evaluation was performed based on 2015 to 2018 DNTR data. First, patient characteristics for 2AIS >= 3, Injury Severity Score (ISS) of >= 16, and BPD patients were compared. Second, the PRFs prevalence and odds ratios of mortality for 2AIS >= 3 patients were compared with those from the Deutsche Gesellschaft fur Unfallchirurgie Trauma Register. Subsequently, the association between PRF and mortality was assessed for 2AIS >= 3-DNTR patients and compared with those with an ISS of >= 16. RESULTS The DNTR recorded 300,649 acute trauma admissions. A total of 15,711 patients sustained an ISS of >= 16, and 6,263 patients had suffered a 2AIS >= 3 injury. All individual PRFs were associated with a mortality of >30% in 2AIS >= 3-DNTR patients. The increase in PRFs was associated with a significant increase in mortality for both 2AIS >= 3 and ISS >= 16 patients. A total of 4,264 patients met the BPDs criteria. Overall mortality (27.2%), intensive care unit admission (71.2%), and length of stay were the highest for the BPD group. CONCLUSION This study confirms that the BPD identifies high-risk patients in a population-based registry. The addition of PRFs to the anatomical injury scores improves the identification of severely injured patients with a high risk of mortality. Compared with the ISS >= 16 and 2AIS >= 3 multiple injury definitions, the BPD showed to improve the accuracy of capturing patients with a high medical resource need and mortality rate

Differential limit on the extremely-high-energy cosmic neutrino flux in the presence of astrophysical background from nine years of IceCube data

We report a quasi-differential upper limit on the extremely-high-energy (EHE) neutrino flux above $5\times 10^{6}$ GeV based on an analysis of nine years of IceCube data. The astrophysical neutrino flux measured by IceCube extends to PeV energies, and it is a background flux when searching for an independent signal flux at higher energies, such as the cosmogenic neutrino signal. We have developed a new method to place robust limits on the EHE neutrino flux in the presence of an astrophysical background, whose spectrum has yet to be understood with high precision at PeV energies. A distinct event with a deposited energy above $10^{6}$ GeV was found in the new two-year sample, in addition to the one event previously found in the seven-year EHE neutrino search. These two events represent a neutrino flux that is incompatible with predictions for a cosmogenic neutrino flux and are considered to be an astrophysical background in the current study. The obtained limit is the most stringent to date in the energy range between $5 \times 10^{6}$ and $5 \times 10^{10}$ GeV. This result constrains neutrino models predicting a three-flavor neutrino flux of $E_\nu^2\phi_{\nu_e+\nu_\mu+\nu_\tau}\simeq2\times 10^{-8}\ {\rm GeV}/{\rm cm}^2\ \sec\ {\rm sr}$at$10^9\ {\rm GeV}$. A significant part of the parameter-space for EHE neutrino production scenarios assuming a proton-dominated composition of ultra-high-energy cosmic rays is excluded.Comment: The version accepted for publication in Physical Review

Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND). a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension

Background: Although several disease-modifying treatments are available for relapsing multiple sclerosis, treatment effects have been more modest in progressive multiple sclerosis and have been observed particularly in actively relapsing subgroups or those with lesion activity on imaging. We sought to assess whether natalizumab slows disease progression in secondary progressive multiple sclerosis, independent of relapses. Methods: ASCEND was a phase 3, randomised, double-blind, placebo-controlled trial (part 1) with an optional 2 year open-label extension (part 2). Enrolled patients aged 18–58 years were natalizumab-naive and had secondary progressive multiple sclerosis for 2 years or more, disability progression unrelated to relapses in the previous year, and Expanded Disability Status Scale (EDSS) scores of 3·0–6·5. In part 1, patients from 163 sites in 17 countries were randomly assigned (1:1) to receive 300 mg intravenous natalizumab or placebo every 4 weeks for 2 years. Patients were stratified by site and by EDSS score (3·0–5·5 vs 6·0–6·5). Patients completing part 1 could enrol in part 2, in which all patients received natalizumab every 4 weeks until the end of the study. Throughout both parts, patients and staff were masked to the treatment received in part 1. The primary outcome in part 1 was the proportion of patients with sustained disability progression, assessed by one or more of three measures: the EDSS, Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9HPT). The primary outcome in part 2 was the incidence of adverse events and serious adverse events. Efficacy and safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01416181. Findings: Between Sept 13, 2011, and July 16, 2015, 889 patients were randomly assigned (n=440 to the natalizumab group, n=449 to the placebo group). In part 1, 195 (44%) of 439 natalizumab-treated patients and 214 (48%) of 448 placebo-treated patients had confirmed disability progression (odds ratio [OR] 0·86; 95% CI 0·66–1·13; p=0·287). No treatment effect was observed on the EDSS (OR 1·06, 95% CI 0·74–1·53; nominal p=0·753) or the T25FW (0·98, 0·74–1·30; nominal p=0·914) components of the primary outcome. However, natalizumab treatment reduced 9HPT progression (OR 0·56, 95% CI 0·40–0·80; nominal p=0·001). In part 1, 100 (22%) placebo-treated and 90 (20%) natalizumab-treated patients had serious adverse events. In part 2, 291 natalizumab-continuing patients and 274 natalizumab-naive patients received natalizumab (median follow-up 160 weeks [range 108–221]). Serious adverse events occurred in 39 (13%) patients continuing natalizumab and in 24 (9%) patients initiating natalizumab. Two deaths occurred in part 1, neither of which was considered related to study treatment. No progressive multifocal leukoencephalopathy occurred. Interpretation: Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component. Longer-term trials are needed to assess whether treatment of secondary progressive multiple sclerosis might produce benefits on additional disability components. Funding: Biogen

Paper Trails: Following the Money

In many recent elections, the candidates who raise the most money have a better shot at winning, so candidates must raise millions of dollars to win an election. A top question to consider in all elections: Where is the money coming from? Posting about the financing behind federal elections from In All Things - an online hub committed to the claim that the life, death, and resurrection of Jesus Christ has implications for the entire world. http://inallthings.org/paper-trails-following-the-money

Searching for eV-scale sterile neutrinos with eight years of atmospheric neutrinos at the IceCube neutrino telescope

We report in detail on searches for eV-scale sterile neutrinos, in the context of a 3+1 model, using eight years of data from the IceCube neutrino telescope. By analyzing the reconstructed energies and zenith angles of 305,735 atmospheric $\nu_\mu$ and $\bar{\nu}_\mu$ events we construct confidence intervals in two analysis spaces: $\sin^2 (2\theta_{24})$ vs. $\Delta m^2_{41}$ under the conservative assumption $\theta_{34}=0$; and $\sin^2(2\theta_{24})$ vs. $\sin^2 (2\theta_{34})$ given sufficiently large $\Delta m^2_{41}$ that fast oscillation features are unresolvable. Detailed discussions of the event selection, systematic uncertainties, and fitting procedures are presented. No strong evidence for sterile neutrinos is found, and the best-fit likelihood is consistent with the no sterile neutrino hypothesis with a p-value of 8\% in the first analysis space and 19\% in the second.Comment: This long-form paper is a companion to the letter "An eV-scale sterile neutrino search using eight years of atmospheric muon neutrino data from the IceCube Neutrino Observatory". v2: update other experiments contours on results plo

An eV-scale sterile neutrino search using eight years of atmospheric muon neutrino data from the IceCube Neutrino Observatory

The results of a 3+1 sterile neutrino search using eight years of data from the IceCube Neutrino Observatory are presented. A total of 305,735 muon neutrino events are analyzed in reconstructed energy-zenith space to test for signatures of a matter-enhanced oscillation that would occur given a sterile neutrino state with a mass-squared differences between 0.01\,eV$^2$ and 100\,eV$^2$. The best-fit point is found to be at $\sin^2(2\theta_{24})=0.10$ and $\Delta m_{41}^2 = 4.5{\rm eV}^2$, which is consistent with the no sterile neutrino hypothesis with a p-value of 8.0\%.Comment: 11 pages, 5 figures. This letter is supported by the long-form paper "Searching for eV-scale sterile neutrinos with eight years of atmospheric neutrinos at the IceCube neutrino telescope," also appearing on arXiv. Digital data release available at: https://github.com/icecube/HE-Sterile-8year-data-releas

GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors

Objective: Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and crossvalidated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS metaanalysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures. Methods: This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses. Results: Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values &lt;5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors. Conclusions: This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.</p