Mortality in hospitalized COVID-19 patients was associated with the COVID-19 admission rate during the first year of the pandemic in Sweden.

INTRODUCTION: Studies from the first pandemic wave found associations between COVID-19 hospital load and mortality. Here, we aimed to study if mortality of hospitalized COVID-19 patients was associated with the COVID-19 admission rate during a full year of the pandemic in Sweden. METHOD: Observational review of all patients admitted to hospital with COVID-19 in Sweden between March 2020 and February 2021 (n = 42,017). Primary outcome was 60-day all-cause mortality related to number of COVID-19 hospital admissions per month/100,000 inhabitants. Poisson regression was used to estimate the relative risk for death by month of admission, adjusting for pre-existing factors. RESULTS: The overall mortality was 17.4%. Excluding March 2020, mortality was clearly correlated to the number of COVID-19 admissions per month (coefficient of correlation ρ=.96; p<.0001). After adjustment for pre-existing factors, the correlation remained significant (ρ=.75, p=.02). Patients admitted in December (high admission rate and high mortality) had more comorbidities and longer hospital stays, and patients treated in intensive care units (ICU) had longer pre-ICU hospital stays and worse respiratory status on ICU admission than those admitted in July to September (low admission rate and low mortality). CONCLUSION: Mortality in hospitalized COVID-19 patients was clearly associated with the COVID-19 admission rate. Admission of healthier patients between pandemic waves and delayed ICU care during wave peaks could contribute to this pattern. The study supports measures to flatten-the-curve to reduce the number of COVID-19 patients admitted to hospital.

Mortality trends among hospitalised COVID-19 patients in Sweden: A nationwide observational cohort study.

BACKGROUND: It is important to know if mortality among hospitalised COVID-19 patients has changed as the pandemic has progressed. The aim of this study was to describe the dynamics over time of mortality among patients hospitalised for COVID-19 in Sweden, using nationwide data compiled by the Swedish National Board of Health and Welfare. METHODS: Observational cohort study where all patients hospitalised in Sweden between March 1 and September 30, 2020, with SARS-CoV-2 RNA positivity 14 days before to 5 days after admission and a discharge code for COVID-19 were included. Outcome was 60-day all-cause mortality. Patients were categorised according to month of hospital admission. Poisson regression was used to estimate the relative risk of death by month of admission, adjusting for, age, sex, comorbidities, care dependency, country of birth, healthcare region, and Simplified Acute Physiology, version 3 (patients in intensive care units; ICU). FINDINGS: A total of 17,140 patients were included, of which 2943 died within 60 days of admission. The overall 60-day mortality was thus 17·2% (95% CI, 16·6%-17·7%), and it decreased from 24·7% (95% CI, 23·0%-26·5%) in March to 10·4% (95% CI, 8·9%-12·1%) post-wave (July-September). Adjusted relative risk (RR) of death was 0·46 (95% CI, 0·39-0·54) post-wave, using March as reference. Corresponding RR for patients not admitted to ICU and those admitted to ICU were 0·49 (95% CI, 0·42-0·59) and 0·49 (95% CI, 0·33-0·72), respectively. The proportion of patients admitted to ICU decreased from 19·4% (95% CI, 17·9%-21·1%) in the March cohort to 8·9% (95% CI, 7·5%-10·6%) post-wave. INTERPRETATION: There was a gradual decline in mortality during the spring of 2020 in Swedish hospitalised COVID-19 patients, independent of baseline patient characteristics. Future research is needed to explain the reasons for this decline. The changing COVID-19 mortality should be taken into account when management and results of studies from the first pandemic wave are evaluated. FUNDING: This study was funded by Sweden's National Board of Health and Welfare.

Reconfigurable Mechanical Anisotropy in Self-Assembled Magnetic Superstructures.

Enhancement of mechanical properties in self-assembled superstructures of magnetic nanoparticles is a new emerging aspect of their remarkable collective behavior. However, how magnetic interactions modulate mechanical properties is, to date, not fully understood. Through a comprehensive Monte Carlo investigation, this study demonstrates how the mechanical properties of self-assembled magnetic nanocubes can be controlled intrinsically by the nanoparticle magnetocrystalline anisotropy (MA), as well as by the superstructure shape anisotropy, without any need for changes in structural design (i.e., nanoparticle size, shape, and packing arrangement). A low MA-to-dipolar energy ratio, as found in iron oxide and permalloy systems, favors isotropic mechanical superstructure stabilization, whereas a high ratio yields magnetically blocked nanoparticle macrospins which can give rise to metastable superferromagnetism, as expected in cobalt ferrite simple cubic supercrystals. Such full parallel alignment of the particle moments is shown to induce mechanical anisotropy, where the superior high-strength axis can be remotely reconfigured by means of an applied magnetic field. The new concepts developed here pave the way for the experimental realization of smart magneto-micromechanical systems (based, e.g., on the permanent super-magnetostriction effect illustrated here) and inspire new design rules for applied functional materials.

The Swedish Neonatal Quality Register - contents, completeness and validity.

AIM: To describe the Swedish Neonatal Quality Register (SNQ) and to determine its completeness and agreement with other registers. METHODS: SNQ collects data for infants admitted to neonatal units during the first four postnatal weeks. Completeness and registers' agreement were determined cross-linking SNQ data with Swedish population registers (the Inpatient, Medical Birth and Cause of Death Registers) for a study period of five years. RESULTS: In total, 84 712 infants were hospitalised. A total of 52 806 infants occurred in both SNQ and the population registers; 28 692 were only found in the population registers, and 3214 infants were only found in SNQ. Between gestational weeks 24-34, completeness of SNQ was 98-99%. Below and above these gestational ages, completeness was lower. Infants missing in SNQ were term or near-term in 99% of the cases, and their diagnoses indicated conditions managed in maternity units, or re-admissions for acute infections, managed in paediatric units. For most diagnoses, the agreement between SNQ and population registers was high, but some (bronchopulmonary dysplasia and grade of hypoxic-ischaemic encephalopathy) were often missing in the population registers. CONCLUSION: SNQ completeness and agreement against other registers, especially for preterm infants, is excellent. SNQ is a valid tool for benchmarking, quality improvement and research.

Describing synchronization and topological excitations in arrays of magnetic spin torque oscillators through the Kuramoto model.

The collective dynamics in populations of magnetic spin torque oscillators (STO) is an intensely studied topic in modern magnetism. Here, we show that arrays of STO coupled via dipolar fields can be modeled using a variant of the Kuramoto model, a well-known mathematical model in non-linear dynamics. By investigating the collective dynamics in arrays of STO we find that the synchronization in such systems is a finite size effect and show that the critical coupling-for a complete synchronized state-scales with the number of oscillators. Using realistic values of the dipolar coupling strength between STO we show that this imposes an upper limit for the maximum number of oscillators that can be synchronized. Further, we show that the lack of long range order is associated with the formation of topological defects in the phase field similar to the two-dimensional XY model of ferromagnetism. Our results shed new light on the synchronization of STO, where controlling the mutual synchronization of several oscillators is considered crucial for applications.

Low-temperature growth of bismuth thin films with (111) facet on highly oriented pyrolytic graphite.

The epitaxial growth of artificial two-dimensional metals at interfaces plays a key role in fabricating heterostructures for nanoelectronics. Here, we present the growth of bismuth nanostructures on highly oriented pyrolytic graphite (HOPG) under ultrahigh vacuum (UHV) conditions, which was investigated thoroughly by a combination of scanning tunneling microscopy (STM), ultraviolet photoemission spectroscopy (UPS), X-ray photoelectron spectroscopy (XPS), and low energy electron diffraction (LEED). It was found that (111)-oriented bilayers are formed on as-cleaved high-quality HOPG at 140 K, which opens the possibility of making Bi(111) thin films on a semimetal, and this is a notable step forward from the earlier studies, which show that only Bi(110) facets could be formed at ultrathin thickness at room temperature. XPS investigation of both C 1s and Bi 4f reflects the rather weak bonding between the Bi film and the HOPG substrate and suggests a quasi layer-by-layer growth mode of Bi nanostructures on HOPG at low temperature. Moreover, the evolution of the valence band of the interface is recorded by UPS, and a transition from quantum well states to bulk-like features is observed at varying film thickness. Unlike semimetallic bulk bismuth, ultrathin Bi(111) films are expected to be topological insulators. Our study may therefore pave the way for the generation of high quality Bi nanostructures to be used in spin electronics.

Metabolomics: a tool for the diagnosis of GH deficiency and for monitoring GH replacement?

The diagnostic value of insulin-like growth factor 1 (IGF1) for GH deficiency (GHD) in adults is not optimal. Molecular profiling could be used for biomarker discovery. The aim of this pilot study was to compare the serum metabolome between GHD patients and healthy controls, and identification of potential markers for diagnosis and/or for individual GH dosing. A total of ten patients with GHD, median age of 55 years and BMI of 27 kg/m(2), were compared with ten healthy age- and gender-matched controls. The serum metabolic profiles were generated using gas chromatography-coupled mass spectroscopy on fasting samples taken in the morning from the controls and at baseline and during 6 months of GH replacement in the patients with GHD. The difference in low-molecular weight compounds (LMC) distinguished the healthy controls from GHD patients. Among 285 measured metabolites, 13 were identified as being most important in differentiating GHD patients from controls. Of these, 11 could not be structurally annotated but many were classified as lipids. The difference in the LMC pattern persisted despite normalisation of IGF1 following GH replacement. GH replacement increased the levels of specific fatty acid compounds and decreased the levels of certain amino acids. No metabolite changed in response to GH treatment, to the same extent as IGF1. The measurement of 285 metabolites resulted in a unique pattern in GHD, but changes in the metabolite patterns during GH treatment were limited. The utility of metabolomics to find new markers in GHD and GH replacement remains to be further elucidated.

Use of lung weight as biomarker for assessment of lung toxicity in rat inhalation studies.

Subacute inhalation study (1 week or 2 weeks) is an important process for screening out inhaled compounds causing lung irritation. To investigate whether the lung weight can be used as an indicator for acute lung injury, we have analyzed retrospectively the lung weight data from 30 studies in rats exposed to dry powder inhalation. The lung weight change was correlated with lung histopathology in the majority of studies (25 of 30), showing as either both changed or both unchanged. The sensitivity and specificity of using the weight change in lungs as biomarker for predicting lung histopathology in these studies were over 80%. The pattern of lung weight change was often similar in the 1- to 2- week studies and the 4-week studies. Our analysis of covariance model showed that a study with 40 rats (5 males + 5 females/group and 4 groups) could detect lung weight change greater than 10% to 20% of control value. These results suggested that lung weight is a useful indicator for identifying acute lung toxic effect by inhaled compounds in these subacute inhalation studies.

Automated annotation and quantification of metabolites in 1H NMR data of biological origin.

In (1)H NMR metabolomic datasets, there are often over a thousand peaks per spectrum, many of which change position drastically between samples. Automatic alignment, annotation, and quantification of all the metabolites of interest in such datasets have not been feasible. In this work we propose a fully automated annotation and quantification procedure which requires annotation of metabolites only in a single spectrum. The reference database built from that single spectrum can be used for any number of (1)H NMR datasets with a similar matrix. The procedure is based on the generalized fuzzy Hough transform (GFHT) for alignment and on Principal-components analysis (PCA) for peak selection and quantification. We show that we can establish quantities of 21 metabolites in several (1)H NMR datasets and that the procedure is extendable to include any number of metabolites that can be identified in a single spectrum. The procedure speeds up the quantification of previously known metabolites and also returns a table containing the intensities and locations of all the peaks that were found and aligned but not assigned to a known metabolite. This enables both biopattern analysis of known metabolites and data mining for new potential biomarkers among the unknowns.

Sex-dependent hepatic transcripts and metabolites in the development of glucose intolerance and insulin resistance in Zucker diabetic fatty rats.

Male Zucker diabetic fatty (mZDF) rats spontaneously develop type 2 diabetes, whereas females only become diabetic when fed a diabetogenic high-fat diet (high-fat-fed female ZDF rat, HF-fZDF). The aim of this study was to investigate if differences in liver functions could provide clues to this sex difference. Non-diabetic obese fZDF rats were compared with either mZDF or HF-fZDF regarding hepatic molecular profiles, to single out those components that might be protective in the females. High-fat feeding in fZDF led to enhanced weight gain, increased blood glucose and insulin levels, reduced insulin sensitivity and a trend towards reduced glucose tolerance, indicative of a prediabetic state. mZDF rats were diabetic, with low levels of insulin, high levels of glucose, reduced insulin sensitivity and impaired glucose tolerance. Transcript profiling and capillary electrophoresis time-of-flight mass spectrometry were used to indentify hepatic transcripts and metabolites that might be related to this. Many diet-induced alterations in transcript and metabolite levels in female rats were towards a 'male-like' phenotype, including reduced lipogenesis, increased fatty acid (FA) oxidation and increased oxidative stress responses. Alterations detected at the level of hepatic metabolites, indicated lower capacity for glutathione (GSH) production in male rats, and higher GSH turnover in females. Taken together, this could be interpreted as if anabolic pathways involving lipogenesis and lipid output might limit the degree of FA oxidation and oxidative stress in female rats. Together with a greater capacity to produce GSH, these hepatic sex differences might contribute to the sex-different development of diabetes in ZDF rats.

Sex-different hepaticglycogen content and glucose output in rats.

BACKGROUND: Genes involved in hepatic metabolism have a sex-different expression in rodents. To test whether male and female rat livers differ regarding lipid and carbohydrate metabolism, whole-genome transcript profiles were generated and these were complemented by measurements of hepatic lipid and glycogen content, fatty acid (FA) oxidation rates and hepatic glucose output (HGO). The latter was determined in perfusates from in situ perfusion of male and female rat livers. These perfusates were also analysed using nuclear magnetic resonance (NMR) spectroscopy to identify putative sex-differences in other liver-derived metabolites. Effects of insulin were monitored by analysis of Akt-phosphorylation, gene expression and HGO after s.c. insulin injections. RESULTS: Out of approximately 3 500 gene products being detected in liver, 11% were significantly higher in females, and 11% were higher in males. Many transcripts for the production of triglycerides (TG), cholesterol and VLDL particles were female-predominant, whereas genes for FA oxidation, gluconeogenesis and glycogen synthesis were male-predominant. Sex-differences in mRNA levels related to metabolism were more pronounced during mild starvation (12 h fasting), as compared to the postabsorptive state (4 h fasting). No sex-differences were observed regarding hepatic TG content, FA oxidation rates or blood levels of ketone bodies or glucose. However, males had higher hepatic glycogen content and higher HGO, as well as higher ratios of insulin to glucagon levels. Based on NMR spectroscopy, liver-derived lactate was also higher in males. HGO was inhibited by insulin in parallel with increased phosphorylation of Akt, without any sex-differences in insulin sensitivity. However, the degree of Thr172-phosphorylated AMP kinase (AMPK) was higher in females, indicating a higher degree of AMPK-dependent actions. CONCLUSIONS: Taken together, males had higher ratios of insulin to glucagon levels, higher levels of glycogen, lower degree of AMPK phosphorylation, higher expression of gluconeogenic genes and higher hepatic glucose output. Possibly these sex-differences reflect a higher ability for the healthy male rat liver to respond to increased energy demands.

Design, synthesis and evaluation of peptide inhibitors of Mycobacterium tuberculosis ribonucleotide reductase.

Mycobacterium tuberculosis ribonucleotide reductase (RNR) is a potential target for new antitubercular drugs. Herein we describe the synthesis and evaluation of peptide inhibitors of RNR derived from the C-terminus of the small subunit of M. tuberculosis RNR. An N-terminal truncation, an alanine scan and a novel statistical molecular design (SMD) approach based on the heptapeptide Ac-Glu-Asp-Asp-Asp-Trp-Asp-Phe-OH were applied in this study. The alanine scan showed that Trp5 and Phe7 were important for inhibitory potency. A quantitative structure relationship (QSAR) model was developed based on the synthesized peptides which showed that a negative charge in positions 2, 3, and 6 is beneficial for inhibitory potency. Finally, in position 5 the model coefficients indicate that there is room for a larger side chain, as compared to Trp5.

Electron transfer-induced dynamics of oxygen molecules on the TiO2(110) surface.

Diffusion of oxygen molecules on transition metal oxide surfaces plays a vital role for the understanding of catalysis and photocatalysis on these materials. By means of time-resolved scanning tunneling microscopy, we provide evidence for a charge transfer-induced diffusion mechanism for O2 molecules adsorbed on a rutile TiO2(110) surface. The O2 hopping rate depended on the number of surface donors (oxygen vacancies), which determines the density of conduction band electrons. These results may have implications for the understanding of oxidation processes on metal oxides in general.

Oxygen-mediated diffusion of oxygen vacancies on the TiO2(110) surface.

Defects such as oxygen vacancies play a crucial role in the surface properties of transition metal oxides. By means of time-resolved, high-resolution scanning tunneling microscopy, we unraveled an adsorbate-mediated diffusion mechanism of oxygen vacancies on rutile TiO2(110). Adsorbed oxygen molecules mediate vacancy diffusion through the loss of an oxygen atom to a vacancy and the sequential capture of an oxygen atom from a neighboring bridging oxygen row, leading to an anisotropic oxygen vacancy diffusion pathway perpendicular to the bridging oxygen rows.