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Summary Background The lymphocyte‐to‐monocyte ratio (LMR) is easily determined from the white blood cell count. Lymphocytes were previously investigated as a part of the neutrophil‐to‐lymphocyte ratio (NLR) in patients with atherosclerotic disease and an elevated NLR was negatively associated with cardiovascular endpoints. As monocytes play a leading role in the progression of atherosclerosis, especially in peripheral arterial occlusive disease (PAOD), we investigated LMR and its association with critical limb ischemia and other vascular endpoints in PAOD patients. Methods and Findings We evaluated 2121 PAOD patients treated at our institution from 2005 to 2010. LMR was calculated and the cohort was divided into tertiles according to the LMR. An optimal cut‐off value for the continuous LMR was calculated by applying a receiver operating curve analysis to discriminate between CLI and non‐CLI. In our cohort occurrence of CLI decreased significantly with an increase in LMR. An LMR of 3.1 was identified as an optimal cut‐off. Two groups were categorized, one with 1021 patients (LMR < 3.1) and a second one with 1100 patients (LMR ≥ 3.1). CLI was more frequent in LMR < 3.1 patients [426 (41.7%)] than in LMR ≥ 3.1 patients [254 (23.1%)] (p < 0.001), as was also the case with prior myocardial infarction [60 (9.5%) vs. 35 (3.2%), p = 0.003] and congestive heart failure [136 (13.3%) vs. 66 (6.0%), p < 0.001). As to inflammatory parameters, C‐reactive protein [median 9.0 mg/l (4.0–30.0) vs. median 4.0 mg/l (2.0–8.0)] and fibrinogen (median 438 mg/dl (350–563) vs. 372 mg/dl (316–459.5)] also differed significantly in the two patient groups (both p < 0.001). A LMR < 3.1 was associated with an odds ratio (OR) of 2.0 (95% CI 1.8–2.2, p < 0.001) for CLI, even after adjustment for other vascular risk factors. Conclusions A decreased LMR is significantly associated with a high risk for CLI and other vascular endpoints. The LMR is an easily determinable, broadly available and inexpensive marker that could be used to identify patients at high risk for vascular endpoints.

We present a case of a fetus acquiring two different balanced translocations from each parent and subsequent uniparental isodisomy from postzygotic loss of a paternal chromosome. Balanced chromosomal translocations occur in 0.14% of the population and increase the risk of other genetic abnormalities, such as uniparental disomy (UPD) and mosaicism. Preimplantation genetic testing (PGT) can identify some genetic abnormalities. Translocations t(6;21) and t(5;15) have been reported individually but never together in a viable fetus. A non-consanguineous couple who were known carriers of two different balanced translocations conceived via classic in vitro fertilization (IVF). They had a normal PGT completed. Chorionic villus sampling (CVS) revealed that the fetus had received t(6;21) from the mother and t(5;15) from the father. The probability of the fetus acquiring both translocations was 2.8%. CVS also revealed UPD of chromosome 14. Amniocentesis was performed, which was consistent with the CVS in detecting the balanced translocations but provided more information about the UPD, determining that it was a mosaic maternal uniparental isodisomy of chromosome 14 (UPD(14)mat). The couple underwent genetic counseling to discuss the above findings and ultimately decided on dilation and evacuation at 17 weeks of gestation. The likelihood of conception of this fetus and survival past the first trimester is extremely rare. These specific chromosomal translocations and (UPD(14)mat) have never been reported before. This case emphasizes the concomitant nature of imprinted genes, resulting in multiple genetically unique alterations. This report also highlights the limitations of PGT, CVS, and amniocentesis in being reproducibly consistent, which is important to discuss prior to IVF conception.

PurposeIntensive care unit (ICU) hospitalization is challenging for the family members of the patients. Most family members report some level of anxiety and depression, sometimes even resulting in post-traumatic stress disorder (PTSD). An association has been reported between lack of information and PTSD. This study had three aims: to quantify the psychological burden of family members of critically ill patients, to explore whether a website with specific information could reduce PTSD symptoms, and to ascertain whether a website with information about intensive care would be used.MethodA multicenter double-blind, randomized, placebo-controlled trial was carried out in Austria and Switzerland.ResultsIn total, 89 members of families of critically ill patients (mean age 47.3 ± 12.9 years, female n = 59, 66.3%) were included in the study. 46 relatives were allocated to the intervention website and 43 to the control website. Baseline Impact of Event Scale (IES) score was 27.5 ± 12.7. Overall, 50% showed clinically relevant PTSD symptoms at baseline. Mean IES score for the primary endpoint (~ 30 days after inclusion, T1) was 24 ± 15.8 (intervention 23.9 ± 17.9 vs. control 24.1 ± 13.5, p = 0.892). Hospital Anxiety and Depression Scale (HADS - Deutsch (D)) score at T1 was 12.2 ± 6.1 (min. 3, max. 31) and did not differ between groups. Use of the website differed between the groups (intervention min. 1, max. 14 vs. min. 1, max. 3; total 1386 “clicks” on the website, intervention 1021 vs. control 365). Recruitment was prematurely stopped in February 2020 due to coronavirus disease 2019 (COVID-19).ConclusionFamily members of critically ill patients often have significant PTSD symptoms and online information on critical illness did not result in reduced PTSD symptoms.

Background Pseudomonas aeruginosa infections are a serious threat in intensive care units (ICUs). The aim of this confirmatory, randomized, multicenter, placebo-controlled, double-blind, phase 2/3 study was to assess the efficacy, immunogenicity, and safety of IC43 recombinant Pseudomonas aeruginosa vaccine in non-surgical ICU patients. Methods Eight hundred patients aged 18 to 80 years admitted to the ICU with expected need for mechanical ventilation for ≥ 48 h were randomized 1:1 to either IC43 100 μg or saline placebo, given in two vaccinations 7 days apart. The primary efficacy endpoint was all-cause mortality in patients 28 days after the first vaccination. Immunogenicity and safety were also evaluated. Findings All-cause mortality rates at day 28 were 29.2% vs 27.7% in the IC43 and placebo groups, respectively ( P  = .67). Overall survival (Kaplan-Meier survival estimates, P  = .46) and proportion of patients with ≥ one confirmed P. aeruginosa invasive infection or respiratory tract infection also did not differ significantly between both groups. The geometric mean fold increase in OprF/I titers was 1.5 after the first vaccination, 20 at day 28, after the second vaccination, and 2.9 at day 180. Significantly more patients in the placebo group (96.5%) had ≥ one adverse event (AE) versus the IC43 100 μg group (93.1%) ( P  = .04). The most frequently reported severe AEs in the IC43 and placebo groups were respiratory failure (6.9% vs 5.7%, respectively), septic shock (4.1% vs 6.5%), cardiac arrest (4.3% vs 5.7%), multiorgan failure (4.6% vs 5.5%), and sepsis (4.6% vs 4.2%). No related serious AEs were reported in the IC43 group. Interpretation The IC43 100 μg vaccine was well tolerated in this large population of medically ill, mechanically ventilated patients. The vaccine achieved high immunogenicity but provided no clinical benefit over placebo in terms of overall mortality. Trial registration https://clinicaltrials.gov ( NCT01563263 ). Registration was sent to ClinicalTrials.gov on March 14, 2012, but posted by ClinicalTrials.gov on March 26, 2012. The first subject was included in the trial on March 22, 2012.

This paper discusses the implementation and performance of an array of gas-phase chemistry solvers for the state-of-the-science GEOS-Chem global chemical transport model. The implementation is based on the Kinetic PreProcessor (KPP). Two perl parsers automatically generate the needed interfaces between GEOS-Chem and KPP, and allow access to the chemical simulation code without any additional programming effort. This work illustrates the potential of KPP to positively impact global chemical transport modeling by providing additional functionality as follows. (1) The user can select a highly efficient numerical integration method from an array of solvers available in the KPP library. (2) KPP offers a wide variety of user options for studies that involve changing the chemical mechanism (e.g., a set of additional reactions is automatically translated into efficient code and incorporated into a modified global model). (3) This work provides access to tangent linear, continuous adjoint, and discrete adjoint chemical models, with applications to sensitivity analysis and data assimilation.

We present results from an analysis looking for dark matter annihilation in the Sun with the IceCube neutrino telescope. Gravitationally trapped dark matter in the Sun’s core can annihilate into Standard Model particles making the Sun a source of  GeV neutrinos. IceCube is able to detect neutrinos with energies >100 GeV while its low-energy infill array DeepCore extends this to >10 GeV. This analysis uses data gathered in the austral winters between May 2011 and May 2014, corresponding to 532 days of livetime when the Sun, being below the horizon, is a source of up-going neutrino events, easiest to discriminate against the dominant background of atmospheric muons. The sensitivity is a factor of two to four better than previous searches due to additional statistics and improved analysis methods involving better background rejection and reconstructions. The resultant upper limits on the spin-dependent dark matter-proton scattering cross section reach down to 1.46 × 10 - 5  pb for a dark matter particle of mass 500 GeV annihilating exclusively into τ + τ - particles. These are currently the most stringent limits on the spin-dependent dark matter-proton scattering cross section for WIMP masses above 50 GeV.

Lorentz symmetry is a fundamental spacetime symmetry underlying both the standard model of particle physics and general relativity. This symmetry guarantees that physical phenomena are observed to be the same by all inertial observers. However, unified theories, such as string theory, allow for violation of this symmetry by inducing new spacetime structure at the quantum gravity scale. Thus, the discovery of Lorentz symmetry violation could be the first hint of these theories in nature. Here we report the results of the most precise test of spacetime symmetry in the neutrino sector to date. We use high-energy atmospheric neutrinos observed at the IceCube Neutrino Observatory to search for anomalous neutrino oscillations as signals of Lorentz violation. We find no evidence for such phenomena. This allows us to constrain the size of the dimension-four operator in the standard-model extension for Lorentz violation to the \\[10^-28\\] level and to set limits on higher-dimensional operators in this framework. These are among the most stringent limits on Lorentz violation set by any physical experiment.

We present a search for a neutrino signal from dark matter self-annihilations in the Milky Way using the IceCube Neutrino Observatory (IceCube). In 1005 days of data we found no significant excess of neutrinos over the background of neutrinos produced in atmospheric air showers from cosmic ray interactions. We derive upper limits on the velocity averaged product of the dark matter self-annihilation cross section and the relative velocity of the dark matter particles ⟨ σ A v ⟩ . Upper limits are set for dark matter particle candidate masses ranging from 10 GeV up to 1 TeV while considering annihilation through multiple channels. This work sets the most stringent limit on a neutrino signal from dark matter with mass between 10 and 100 GeV, with a limit of 1.18 · 10 - 23 cm 3 s - 1 for 100 GeV dark matter particles self-annihilating via τ + τ - to neutrinos (assuming the Navarro–Frenk–White dark matter halo profile).