Ergodic directional switching in mobile insect groups

We obtain a Fokker-Planck equation describing experimental data on the collective motion of locusts. The noise is of internal origin and due to the discrete character and finite number of constituents of the swarm. The stationary probability distribution shows a rich phenomenology including non-monotonic behavior of several order/disorder transition indicators in noise intensity. This complex behavior arises naturally as a result of the randomness in the system. Its counterintuitive character challenges standard interpretations of noise induced transitions and calls for an extension of this theory in order to capture the behavior of certain classes of biologically motivated models. Our results suggest that the collective switches of the group's direction of motion might be due to a random ergodic effect and, as such, they are inherent to group formation.Comment: Physical Review Focus 26, July 201

Onset of collective motion in locusts is captured by a minimal model

We present a minimal model to describe the onset of collective motion seen when a population of locusts are placed in an annular arena. At low densities motion is disordered, while at high densities locusts march in a common direction, which may reverse during the experiment. The data are well captured by an individual-based model, in which demographic noise leads to the observed density-dependent effects. By fitting the model parameters to equation-free coefficients, we give a quantitative comparison, showing time series, stationary distributions, and the mean switching times between states

A Characterization of Cancer Patients in Inpatient Rehabilitation Facilities: A Retrospective Cohort Study

OBJECTIVES: To identify the types of cancer patients admitted to inpatient medical rehabilitation and to describe their rehabilitation outcomes. DESIGN: Retrospective cohort study. SETTING: U.S. inpatient rehabilitation facilities (IRFs). PARTICIPANTS: Adult patients (N=27,952) with a malignant cancer diagnosis admitted to an IRF with a cancer-related impairment between October 2010 and September 2012 were identified from the Uniform Data System for Medical Rehabilitation database. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Demographic, medical, and rehabilitation characteristics for patients with various cancer tumor types were summarized using data collected from the Inpatient Rehabilitation Facility-Patient Assessment Instrument. Rehabilitation outcomes included the percentage of patients discharged to the community and acute care settings, and functional change from admission to discharge. Functional status was measured using the FIM instrument. RESULTS: Cancer patients constituted about 2.4% of the total IRF patient population. Cancer types included brain and nervous system (52.9%), digestive (12.0%), bone and joint (8.7%), blood and lymphatic (7.6%), respiratory (7.1%), and other (11.7%). Overall, 72% were discharged to a community setting, and 16.5% were discharged back to acute care. Patients with blood and lymphatic cancers had the highest frequency of discharge back to acute care (28%). On average, all cancer patient groups made significant functional gains during their IRF stay (mean FIM total change ± SD, 23.5±16.2). CONCLUSIONS: In a database representing approximately 70% of all U.S. patients in IRFs, we found that patients with a variety of cancer types are admitted to inpatient rehabilitation. Most cancer patients admitted to IRFs were discharged to a community setting and, on average, improved their function. Future research is warranted to understand the referral patterns of admission to postacute care rehabilitation and to identify factors that are associated with rehabilitation benefit in order to inform the establishment of appropriate care protocols

Quantifying Drug-Induced Bone Marrow Toxicity Using a Novel Haematopoiesis Systems Pharmacology Model.

Haematological toxicity associated with cancer therapeutics is monitored by changes in blood cell count, and their primary effect is on proliferative progenitors in the bone marrow. Using observations in rat bone marrow and blood, we characterize a mathematical model that comprises cell proliferation and differentiation of the full haematopoietic phylogeny, with interacting feedback loops between lineages in homeostasis as well as following carboplatin exposure. We accurately predicted the temporal dynamics of several mature cell types related to carboplatin-induced bone marrow toxicity and identified novel insights into haematopoiesis. Our model confirms a significant degree of plasticity within bone marrow cells, with the number and type of both early progenitors and circulating cells affecting cell balance, via feedback mechanisms, through fate decisions of the multipotent progenitors. We also demonstrated cross-species translation of our predictions to patients, applying the same core model structure and considering differences in drug-dependent and physiology-dependent parameters

A Pilot Genome-Wide Analysis Study Identifies Loci Associated With Response to Obeticholic Acid in Patients With NASH

A significantly higher proportion of patients with nonalcoholic steatohepatitis (NASH) who received obeticholic acid (OCA) had histological improvement relative to placebo in the FLINT (farnesoid X nuclear receptor ligand obeticholic acid for noncirrhotic, NASH treatment) trial. However, genetic predictors of response to OCA are unknown. We conducted a genome‐wide association study (GWAS) in FLINT participants to identify variants associated with NASH resolution and fibrosis improvement. Genotyping was performed using the Omni2.5 content GWAS chip. To avoid false positives introduced by population stratification, we focused our GWAS on white participants. Six regions on chromosomes 1, 4, 6, 7, 15, and 17 had multiple single nucleotide polymorphisms (SNPs) with suggestive association (P < 1 × urn:x-wiley:2471254X:media:hep41439:hep41439-math-0001) with NASH resolution. A sentinel SNP, rs75508464, near CELA3B on chromosome 1 was associated with NASH resolution, improvement in the nonalcoholic fatty liver disease activity score, portal inflammation, and fibrosis. Among individuals carrying this allele, 83% achieved NASH resolution with OCA compared with only 33% with placebo. Eight regions on chromosomes 1, 2, 3, 11, 13, and 18 had multiple SNPs associated with fibrosis improvement; of these, rs12130403 near TDRD10 on chromosome 1 was also associated with improvement in NASH and portal inflammation, and rs4073431 near ANO3 on chromosome 11 was associated with NASH resolution and improvement in steatosis. Multiple SNPs on chromosome 11 had suggestive association with pruritus, with rs1379650 near ANO5 being the top SNP. Conclusion: We identified several variants that may be associated with histological improvement and pruritus in individuals with NASH receiving OCA. The rs75508464 variant near CELA3B may have the most significant effect on NASH resolution in those receiving OCA

Bystander Exposure to Ultra-Low-Volume Insecticide Applications Used for Adult Mosquito Management

A popular and effective management option for adult mosquitoes is the use of insecticides applied by ultra-low-volume (ULV) equipment. However, there is a paucity of data on human dermal exposure to insecticides applied by this method. The objective of the current study was to estimate dermal exposures to the insecticide active ingredient permethrin using water- (Aqua-Reslin®) and oil-based (Permanone® 30-30) formulations with passive dosimetry. No significant differences in deposition of permethrin were observed between years, distance from the spray source, front or back of the body, or the placement of the patches on the body. However, exposure to Aqua-Reslin was significantly greater than Permanone 30-30 and average concentrations deposited on the body were 4.2 and 2.1 ng/cm2, respectively. The greater deposition of Aqua-Reslin is most likely due to the higher density of the water-based formulation which causes it to settle out faster than the lighter oil-based formulation of Permanone 30-30. The estimated average absorbed dermal exposure for permethrin from Aqua-Reslin and Permanone 30-30 was 0.00009 and 0.00005 mg/kg body weight, respectively. We also found that ground deposition of ULV insecticides can be used as a surrogate for estimating dermal exposure. The estimated exposures support the findings of previous risk assessments that exposure to ULV applications used for mosquito management are below regulatory levels of concern

Comparison of Proteomic and Transcriptomic Profiles in the Bronchial Airway Epithelium of Current and Never Smokers

Although prior studies have demonstrated a smoking-induced field of molecular injury throughout the lung and airway, the impact of smoking on the airway epithelial proteome and its relationship to smoking-related changes in the airway transcriptome are unclear.Airway epithelial cells were obtained from never (n = 5) and current (n = 5) smokers by brushing the mainstem bronchus. Proteins were separated by one dimensional polyacrylamide gel electrophoresis (1D-PAGE). After in-gel digestion, tryptic peptides were processed via liquid chromatography/ tandem mass spectrometry (LC-MS/MS) and proteins identified. RNA from the same samples was hybridized to HG-U133A microarrays. Protein detection was compared to RNA expression in the current study and a previously published airway dataset. The functional properties of many of the 197 proteins detected in a majority of never smokers were similar to those observed in the never smoker airway transcriptome. LC-MS/MS identified 23 proteins that differed between never and current smokers. Western blotting confirmed the smoking-related changes of PLUNC, P4HB1, and uteroglobin protein levels. Many of the proteins differentially detected between never and current smokers were also altered at the level of gene expression in this cohort and the prior airway transcriptome study. There was a strong association between protein detection and expression of its corresponding transcript within the same sample, with 86% of the proteins detected by LC-MS/MS having a detectable corresponding probeset by microarray in the same sample. Forty-one proteins identified by LC-MS/MS lacked detectable expression of a corresponding transcript and were detected in <or=5% of airway samples from a previously published dataset.1D-PAGE coupled with LC-MS/MS effectively profiled the airway epithelium proteome and identified proteins expressed at different levels as a result of cigarette smoke exposure. While there was a strong correlation between protein and transcript detection within the same sample, we also identified proteins whose corresponding transcripts were not detected by microarray. This noninvasive approach to proteomic profiling of airway epithelium may provide additional insights into the field of injury induced by tobacco exposure

GA4GH: International policies and standards for data sharing across genomic research and healthcare.

The Global Alliance for Genomics and Health (GA4GH) aims to accelerate biomedical advances by enabling the responsible sharing of clinical and genomic data through both harmonized data aggregation and federated approaches. The decreasing cost of genomic sequencing (along with other genome-wide molecular assays) and increasing evidence of its clinical utility will soon drive the generation of sequence data from tens of millions of humans, with increasing levels of diversity. In this perspective, we present the GA4GH strategies for addressing the major challenges of this data revolution. We describe the GA4GH organization, which is fueled by the development efforts of eight Work Streams and informed by the needs of 24 Driver Projects and other key stakeholders. We present the GA4GH suite of secure, interoperable technical standards and policy frameworks and review the current status of standards, their relevance to key domains of research and clinical care, and future plans of GA4GH. Broad international participation in building, adopting, and deploying GA4GH standards and frameworks will catalyze an unprecedented effort in data sharing that will be critical to advancing genomic medicine and ensuring that all populations can access its benefits

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease