SARS-CoV-2 aerosol risk models for the Airplane Seating Assignment Problem.

Transmission of SARS-CoV-2 between passengers on airplanes is a significant concern and reducing the transmission of SARS-CoV-2 or other viruses aboard aircraft could save lives. Solving the Airplane Seating Assignment Problem (ASAP) produces seating arrangements that minimize transmission risks between passengers aboard an aircraft, but the chosen risk model affects the optimal seating arrangement. We analyze previous risk models and introduce two new risk models, masked and unmasked, based on previous experiments performed aboard real aircraft to test aerosol dispersion of SARS-CoV-2 sized particles. We make recommendations on when each risk model is applicable and the types of seating arrangements that are optimal for each risk model.

Non-COVID-19 excess deaths by age and gender in the United States during the first three months of the COVID-19 pandemic.

OBJECTIVES: The first three months of the COVID-19 pandemic has disrupted healthcare systems, creating an environment by which deaths have occurred that are not directly due to COVID-19, but have occurred owing to the healthcare and societal environment resulting from COVID-19. The objective of this research is to quantify such excess deaths, partitioned by age group and gender. STUDY DESIGN: This is a data analysis. METHODS: Excess deaths by age and gender are estimated using provisional death data available from the Centers for disease control and prevention (CDC) over the time period from March 1, 2020 through May 30, 2020. Previous year fatality and population data are used as the benchmark. RESULTS: Several of the eighteen age and gender cohorts experienced statistically significant excess deaths. The results also indicate that COVID-19 has been protective for one of the age and gender cohorts. CONCLUSIONS: There have been more excess deaths in several age group and gender cohorts during the first three months of the pandemic, beyond direct deaths directly attributable to COVID-19. These non-COVID-19 excess deaths are most apparent in the 25- to 44-year age group for women and 15- to 54-year age group for men. Further research is needed to assess the cause of such excess deaths and introduce safeguards to reduce such deaths in the future.

Use of proteomics to identify biomarkers associated with chronic kidney disease and long-term outcomes in patients with myocardial infarction.

BACKGROUND: Patients with chronic kidney disease (CKD) have poor outcomes following myocardial infarction (MI). We performed an untargeted examination of 175 biomarkers to identify those with the strongest association with CKD and to examine the association of those biomarkers with long-term outcomes. METHODS: A total of 175 different biomarkers from MI patients enrolled in the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) registry were analysed either by a multiple reaction monitoring mass spectrometry assay or by a multiplex assay (proximity extension assay). Random forests statistical models were used to assess the predictor importance of biomarkers, CKD and outcomes. RESULTS: A total of 1098 MI patients with a median estimated glomerular filtration rate of 85 mL min-1 /1.73 m2 were followed for a median of 3.2 years. The random forests analyses, without and with adjustment for differences in demography, comorbidities and severity of disease, identified six biomarkers (adrenomedullin, TNF receptor-1, adipocyte fatty acid-binding protein-4, TNF-related apoptosis-inducing ligand receptor 2, growth differentiation factor-15 and TNF receptor-2) to be strongly associated with CKD. All six biomarkers were also amongst the 15 strongest predictors for death, and four of them were amongst the strongest predictors of subsequent MI and heart failure hospitalization. CONCLUSION: In patients with MI, a proteomic approach could identify six biomarkers that best predicted CKD. These biomarkers were also amongst the most important predictors of long-term outcomes. Thus, these biomarkers indicate underlying mechanisms that may contribute to the poor prognosis seen in patients with MI and CKD.

Guidance for the decontamination of intracavity medical devices: the report of a working group of the Healthcare Infection Society.

BACKGROUND: Intracavity medical devices (ICMDs) are used in a wide variety of healthcare settings. The approach to their decontamination and the resources available also differ widely. Their potential for infection transmission is considerable. AIM: To produce a comprehensive risk assessment-based approach to the decontamination of ICMDs, accompanied by an adaptable audit tool.

Transverse relaxation of cerebrospinal fluid depends on glucose concentration.

PURPOSE: To evaluate the biophysical processes that generate specific T2 values and their relationship to specific cerebrospinal fluid (CSF) content. MATERIALS AND METHODS: CSF T2s were measured ex vivo (14.1T) from isolated CSF collected from human, rat and non-human primate. CSF T2s were also measured in vivo at different field strength in human (3 and 7T) and rodent (1, 4.7, 9,4 and 11.7T) using different pulse sequences. Then, relaxivities of CSF constituents were measured, in vitro, to determine the major molecule responsible for shortening CSF T2 (2s) compared to saline T2 (3s). The impact of this major molecule on CSF T2 was then validated in rodent, in vivo, by the simultaneous measurement of the major molecule concentration and CSF T2. RESULTS: Ex vivo CSF T2 was about 2.0s at 14.1T for all species. In vivo human CSF T2 approached ex vivo values at 3T (2.0s) but was significantly shorter at 7T (0.9s). In vivo rodent CSF T2 decreased with increasing magnetic field and T2 values similar to the in vitro ones were reached at 1T (1.6s). Glucose had the largest contribution of shortening CSF T2in vitro. This result was validated in rodent in vivo, showing that an acute change in CSF glucose by infusion of glucose into the blood, can be monitored via changes in CSF T2 values. CONCLUSION: This study opens the possibility of monitoring glucose regulation of CSF at the resolution of MRI by quantitating T2.

GBA mutations in Parkinson disease: earlier death but similar neuropathological features.

BACKGROUND AND PURPOSE: Mutations in the glucocerebrosidase (GBA) gene are known to be a risk factor for Parkinson's disease (PD). Data on clinicopathological correlation are limited. The purpose of this study was to determine the clinicopathological findings that might distinguish PD cases with and without mutations in the GBA gene. METHODS: Data from the Arizona Study of Aging and Neurodegenerative Disorders were used to identify autopsied PD cases that did or did not have a GBA gene mutation. Clinical and neuropathological data were compared. RESULTS: Twelve PD cases had a GBA mutation and 102 did not. The GBA mutation cases died younger (76 vs. 81 years of age) but there was no difference in disease duration or clinical examination findings. No neuropathological differences were found in total or regional semi-quantitative scores for Lewy-type synucleinopathy, senile plaques, neurofibrillary tangles, white matter rarefaction or cerebral amyloid angiopathy scores. CONCLUSIONS: In longitudinally assessed, autopsied PD cases, those with GBA mutations had a younger age at death but there was no evidence for clinical or neuropathological differences compared to cases without GBA mutations. Due to the small GBA group size, small differences cannot be excluded.

Atypical experiences of captive chimpanzees (Pan troglodytes) are associated with higher hair cortisol concentrations as adults.

Experiences during early development are influential on the lives of human and non-human primates into adulthood. The population of captive chimpanzees in the USA can provide insight into this relationship, as collectively they have experienced a wide range of exposure to both conspecifics (those raised in natal groups) and humans (those raised as personal pets or performers). Our study investigated chimpanzee exposure to humans using a continuous measure of categorization, the chimpanzee-human interaction index, and the relationship between this experience and cortisol concentrations in adulthood. Historical records and hair samples were collected from 60 chimpanzees which were socially housed in 13 zoos and sanctuaries. We found that more human exposure throughout the life of a chimpanzee was associated with higher hair cortisol concentrations in adulthood. Sex was also a significant factor affecting cortisol concentration, with male chimpanzees having higher cortisol concentrations than female chimpanzees. These results build upon the extensive literature about aversive effects of atypical social histories for chimpanzees and emphasize to managers the importance of monitoring potential negative health consequences and social deficits these individuals may exhibit.

Parietal dysfunction during number processing in children with fetal alcohol spectrum disorders.

Number processing deficits are frequently seen in children prenatally exposed to alcohol. Although the parietal lobe, which is known to mediate several key aspects of number processing, has been shown to be structurally impaired in fetal alcohol spectrum disorders (FASD), effects on functional activity in this region during number processing have not previously been investigated. This fMRI study of 49 children examined differences in activation associated with prenatal alcohol exposure in five key parietal regions involved in number processing, using tasks involving simple addition and magnitude comparison. Despite generally similar behavioral performance, in both tasks greater prenatal alcohol exposure was related to less activation in an anterior section of the right horizontal intraparietal sulcus known to mediate mental representation and manipulation of quantity. Children with fetal alcohol syndrome and partial fetal alcohol syndrome appeared to compensate for this deficit by increased activation of the angular gyrus during the magnitude comparison task.

Serum proteomic analysis of a pre-symptomatic multiple sclerosis cohort.

BACKGROUND AND PURPOSE: Susceptibility to multiple sclerosis (MS) is determined by environmental and genetic factors, but the cause remains unknown. Changes to the proteome prior to first symptom onset may reflect the underlying pathophysiology of the disease. METHODS: This preliminary study utilized pre-symptomatic and post-symptomatic serum from a sample of 100 incident population-based US military veterans with MS along with 100 matched healthy controls. All samples were obtained from the Department of Defense Serum Repository. Multidimensional protein identification technology tandem mass spectrometry analysis was performed on tryptic peptides of lectin-captured glycosylated serum proteins following albumin/immunoglobulin G depletion. Identified proteins were analyzed with the Ingenuity Pathway Analysis program. RESULTS: The mean intervals between first symptom onset and the collection of pre-symptomatic and post-symptomatic sera were -6.0 and +1.1 years, respectively. Pre-symptomatic proteins from the MS group were differentially regulated compared with both control groups indicating that proteomic changes are detected prior to symptom onset. Pathway analysis showed that proteins involved in the complement and coagulation pathways and lipid transport are significantly altered in the serum of subjects with MS compared with healthy donors. CONCLUSIONS: Compared with healthy controls, differential proteomic changes were noted in the serum of patients with MS that preceded the onset of symptomatic disease. Further work is in progress to confirm or refute these findings.

Seatbelt usage: is there an association with obesity?

Wearing a seatbelt can prevent motor vehicle crash deaths. While primary seatbelt laws are designed to encourage vehicle passengers to wear seatbelts by allowing law enforcement officers to issue tickets when passengers do not wear seatbelts, discomfort may discourage obese individuals from wearing a seatbelt. The objective of this study is to assess the association between state-level obesity and seatbelt usage rates in the US, and to examine the possible role played by seatbelt laws in these associations. The strength of the association between obesity rates, seatbelt usage, and primary seatbelt laws at the state level is investigated using data from 2006 to 2011. Linear regression analysis is employed. This model estimates that increasing the obesity rate by 1% in a state where a primary seatbelt law (by which law enforcement officers can issue a ticket when seatbelts are not worn) is in effect is associated with a 0.06% decrease in seatbelt usage. However the same percentage of increase in the obesity rate in a state where no primary seatbelt law is in effect is associated with a 0.55% decrease in seatbelt usage. The magnitude of the statistical association between state obesity rates and state-level seatbelt usage is related to the existence of a primary seatbelt law, such that obesity has less impact on seatbelt usage in states where primary seatbelt laws are in effect.

Lunar and terrestrial planet formation in the Grand Tack scenario.

We present conclusions from a large number of N-body simulations of the giant impact phase of terrestrial planet formation. We focus on new results obtained from the recently proposed Grand Tack model, which couples the gas-driven migration of giant planets to the accretion of the terrestrial planets. The giant impact phase follows the oligarchic growth phase, which builds a bi-modal mass distribution within the disc of embryos and planetesimals. By varying the ratio of the total mass in the embryo population to the total mass in the planetesimal population and the mass of the individual embryos, we explore how different disc conditions control the final planets. The total mass ratio of embryos to planetesimals controls the timing of the last giant (Moon-forming) impact and its violence. The initial embryo mass sets the size of the lunar impactor and the growth rate of Mars. After comparing our simulated outcomes with the actual orbits of the terrestrial planets (angular momentum deficit, mass concentration) and taking into account independent geochemical constraints on the mass accreted by the Earth after the Moon-forming event and on the time scale for the growth of Mars, we conclude that the protoplanetary disc at the beginning of the giant impact phase must have had most of its mass in Mars-sized embryos and only a small fraction of the total disc mass in the planetesimal population. From this, we infer that the Moon-forming event occurred between approximately 60 and approximately 130 Myr after the formation of the first solids and was caused most likely by an object with a mass similar to that of Mars.

A tensor-based morphometry analysis of regional differences in brain volume in relation to prenatal alcohol exposure.

Reductions in brain volumes represent a neurobiological signature of fetal alcohol spectrum disorders (FASD). Less clear is how regional brain tissue reductions differ after normalizing for brain size differences linked with FASD and whether these profiles can predict the degree of prenatal exposure to alcohol. To examine associations of regional brain tissue excesses/deficits with degree of prenatal alcohol exposure and diagnosis with and without correction for overall brain volume, tensor-based morphometry (TBM) methods were applied to structural imaging data from a well-characterized, demographically homogeneous sample of children diagnosed with FASD (n = 39, 9.6-11.0 years) and controls (n = 16, 9.5-11.0 years). Degree of prenatal alcohol exposure was significantly associated with regionally pervasive brain tissue reductions in: (1) the thalamus, midbrain, and ventromedial frontal lobe, (2) the superior cerebellum and inferior occipital lobe, (3) the dorsolateral frontal cortex, and (4) the precuneus and superior parietal lobule. When overall brain size was factored out of the analysis on a subject-by-subject basis, no regions showed significant associations with alcohol exposure. FASD diagnosis was associated with a similar deformation pattern, but few of the regions survived FDR correction. In data-driven independent component analyses (ICA) regional brain tissue deformations successfully distinguished individuals based on extent of prenatal alcohol exposure and to a lesser degree, diagnosis. The greater sensitivity of the continuous measure of alcohol exposure compared with the categorical diagnosis across diverse brain regions underscores the dose dependence of these effects. The ICA results illustrate that profiles of brain tissue alterations may be a useful indicator of prenatal alcohol exposure when reliable historical data are not available and facial features are not apparent.

Viral infections in pregnancy: advice for healthcare workers.

BACKGROUND: Healthcare workers (HCWs) have the potential for increased exposure to infectious disease resulting from the provision of patient care. Pregnancy can confer specific problems in some infections for the mother and her unborn child. AIMS: To discuss the viral infections encountered in the UK that constitute a particular risk to the pregnant HCW: human immunodeficiency virus, hepatitis B virus, hepatitis C virus, varicella-zoster virus, herpes simplex virus, human parvovirus B19, cytomegalovirus, rubella, measles, enteroviruses, mumps and influenza. Evidence for nosocomial transmission, clinical aspects specific to pregnancy, and recommendations to protect the pregnant HCW at work are included. METHODS: Medline, EMBASE and Pubmed were searched using a list of keywords specific to each viral infection, including 'nosocomial', 'occupational' and 'healthcare workers'. References from the bibliographies of articles identified were reviewed for relevant material. FINDINGS: The evidence for increased risk in the healthcare setting for many of these infections, outside of outbreaks, is weak, possibly because of the application of standard protective infection control measures or because risk of community exposure is greater. The pregnant HCW should be advised on protective behaviour in both settings. Potential interventions include vaccination and reducing the likelihood of exposure through universal precautions, infection control and redeployment. CONCLUSION: Protection of the pregnant HCW is the responsibility of the individual, antenatal care provider and employer, and is made possible through awareness of the risks and potential interventions both before and after exposure. If exposure occurs or if the HCW develops an infective illness, urgent specialist advice is required.

Occurrence of multinucleated hepatocytes in cynomolgus monkeys (Macaca fascicularis) from different geographical regions.

Multinucleated hepatocytes (MNHs) have been occasionally reported in macaques, as well as chimpanzees and gorillas, as an incidental finding. However, information is sparse on variations in incidence in the cynomolgus macaque (Macaca fascicularis). A survey was conducted to assess the occurrence of MNHs in the liver of stock (nonstudy) animals from SNBL SRC (Alice, TX) and SNBL USA (Everett, WA) submitted for diagnostic purposes. A total of 215 cynomolgus monkeys originally from Cambodia (61), China (5), Indonesia (125), and Mauritius (24) were used for this investigation. From each animal, usually 2 liver samples were processed for histopathology with 2 sections in each slide. An MNH was defined as a hepatocyte with 3 or more nuclei. A threshold of 3 MNHs was selected for the Multinucleated Hepatocyte Grading System: 0 = not remarkable (≤3 MNHs counted from 2-4 liver sections), minimal = 4 to 15 MNHs, mild = 16 to 30 MNHs, moderate = 31 to 59 MNHs, and severe ≥60 MNHs. The incidence of MNHs was 60 of 86 (70%) in males and 72 of 129 (56%) in females for a total overall incidence of 132 of 215 animals (61%). Affected hepatocytes were frequently observed close to the capsule and generally had 3 to 8 nuclei per hepatocyte but as many as 15 occurred in a single cell. Awareness of the incidence of MNHs in cynomolgus monkeys is important for potential use as background data in preclinical safety and toxicity evaluation studies.

Oligoclonal bands in multiple sclerosis reactive against two herpesviruses and association with magnetic resonance imaging findings.

BACKGROUND: Two human herpesviruses, human herpesvirus 6 (HHV-6), and Epstein-Barr virus (EBV), have been repeatedly linked to multiple sclerosis (MS). OBJECTIVE: The aim of this study was to investigate HHV-6 and EBV reactive oligoclonal bands (OCBs), and viral DNA in the intrathecal compartment in MS. METHODS: The reactivity of OCBs in cerebrospinal fluid (CSF) for EBV and HHV-6 antigens and stability of virus reactive OCBs over time were studied in a well-characterized MS patient cohort. Associations between virus reactive OCBs and viral DNA in CSF (and any clinical and/or radiological findings) were investigated. RESULTS: Of patients with MS, 38% had OCBs reactive to either one of the viruses studied, compared to none in the patients with other inflammatory neurological diseases (p=0.005). The banding pattern of virus reactive OCBs remained the same over time. Furthermore, MS patients with viral DNA in CSF had more contrast enhancing lesions (CELs). CONCLUSION: The stable presence of herpesvirus reactive OCBs in CSF further strengthens the association of MS with these viruses. The finding that herpesviruses might be linked to the appearance of active lesions warrants investigation of new therapeutic strategies to treat these viruses in MS.

Increased accumulation of CD16+ monocytes at local sites of inflammation in patients with chronic kidney disease.

Patients with chronic kidney disease (CKD) display a high prevalence of cardiovascular events and acute infections. Potential effector cells are the CD16(+) monocytes, known to be increased in the peripheral circulation in CKD. The aim of this study was to assess the expression of CD16 and CX3 CR1 on peripheral and in vivo extravasated monocytes in patients with CKD (GFR < 20 ml/min × 1.73 m²) using flow cytometry. In vivo extravasated monocytes were collected from a local inflammatory site, induced by a skin blistering technique. Soluble markers were assessed by Luminex. The number of CD16(+) monocytes was significantly higher in patients with CKD compared with healthy subjects, both in the peripheral circulation (P < 0.05) and at the site of induced inflammation (P < 0.001). Patients with CKD displayed significantly higher concentration of soluble CX3 CL1 both in the peripheral circulation (P < 0.01) and in the interstitial fluid (P < 0.001). In addition, patients with CKD had a significantly higher concentration of TNF-α in the peripheral circulation (P < 0.001). On the contrary, at the inflammatory site, concentrations of both TNF-α and IL-10 were significantly lower in patients with CKD compared with healthy controls (P < 0.05 for both). In conclusion, patients with CKD have an increased percentage of CD16(+) monocytes in both circulation and at the inflammatory site, and this finding is in concurrence with simultaneous changes in CX3 CR1. Together with distorted TNF-α and IL-10 levels, this may have potential impact on the altered inflammatory response in CKD.

The human urinary microbiome; bacterial DNA in voided urine of asymptomatic adults.

The urinary microbiome of healthy individuals and the way it alters with ageing have not been characterized and may influence disease processes. Conventional microbiological methods have limited scope to capture the full spectrum of urinary bacterial species. We studied the urinary microbiota from a population of healthy individuals, ranging from 26 to 90 years of age, by amplification of the 16S rRNA gene, with resulting amplicons analyzed by 454 pyrosequencing. Mid-stream urine (MSU) was collected by the "clean-catch" method. Quantitative PCR of 16S rRNA genes in urine samples, allowed relative enumeration of the bacterial loads. Analysis of the samples indicates that females had a more heterogeneous mix of bacterial genera compared to the male samples and generally had representative members of the phyla Actinobacteria and Bacteroidetes. Analysis of the data leads us to conclude that a "core" urinary microbiome could potentially exist, when samples are grouped by age with fluctuation in abundance between age groups. The study also revealed age-specific genera Jonquetella, Parvimonas, Proteiniphilum, and Saccharofermentans. In conclusion, conventional microbiological methods are inadequate to fully identify around two-thirds of the bacteria identified in this study. Whilst this proof-of-principle study has limitations due to the sample size, the discoveries evident in this sample data are strongly suggestive that a larger study on the urinary microbiome should be encouraged and that the identification of specific genera at particular ages may be relevant to pathogenesis of clinical conditions.

Mechanical and tribological behavior of silicon nitride and silicon carbon nitride coatings for total joint replacements.

Total joint replacements currently have relatively high success rates at 10-15 years; however, increasing ageing and an active population places higher demands on the longevity of the implants. A wear resistant configuration with wear particles that resorb in vivo can potentially increase the lifetime of an implant. In this study, silicon nitride (SixNy) and silicon carbon nitride (SixCyNz) coatings were produced for this purpose using reactive high power impulse magnetron sputtering (HiPIMS). The coatings are intended for hard bearing surfaces on implants. Hardness and elastic modulus of the coatings were evaluated by nanoindentation, cohesive, and adhesive properties were assessed by micro-scratching and the tribological performance was investigated in a ball-on-disc setup run in a serum solution. The majority of the SixNy coatings showed a hardness close to that of sintered silicon nitride (~18 GPa), and an elastic modulus close to that of cobalt chromium (~200 GPa). Furthermore, all except one of the SixNy coatings offered a wear resistance similar to that of bulk silicon nitride and significantly higher than that of cobalt chromium. In contrast, the SixCyNz coatings did not show as high level of wear resistance.