Sociodemographic predictors of perceived weight discrimination.

BACKGROUND: Perceived weight discrimination is associated with increased risk for chronic diseases and reduced life expectancy. Nevertheless, little is known about perceived weight discrimination in racial, ethnic, and sexual minority groups or in individuals at the intersections of those groups. The goal of this study was to identify sociodemographic predictors of perceived weight discrimination. SUBJECTS/METHODS: A diverse sample of adults (37% Black/African American, 36% Latino, 29% sexual minority) with a body mass index (BMI) ≥ 18.5 kg/m2 were recruited from a national US panel to complete an online survey (N = 2454). Perceived weight discrimination was assessed with the Stigmatizing Situations Survey-Brief (SSI-B). Using hierarchical linear regression analysis, SSI-B scores were predicted from the four sociodemographic characteristics of interest (gender, race, ethnicity, and sexual orientation) while controlling for BMI, age, education, and income (Step 1). At Step 2, all two-way interactions between the four sociodemographic characteristics were added to the model. RESULTS: At Step 1, higher SSI-B scores were observed for Latino (vs. non-Latino) adults, sexual minority (vs. heterosexual) adults, younger (vs. older) adults, adults with higher (vs. lower) levels of education, and adults with higher (vs. lower) BMI. At Step 2, race interacted with gender, ethnicity, and sexual orientation to predict SSI-B scores such that relatively higher scores were observed for non-Black women, Black men, adults who identified as Black and Latino, and non-Black sexual minority adults. CONCLUSIONS: Perceived weight discrimination varied across sociodemographic groups, with some subgroups reporting relatively high frequency. Black race appeared to be protective for some subgroups (e.g., Black women), but risk-enhancing for others (e.g., Black men, individuals who identified as Black and Latino). Additional research is needed to identify specific factors that cause certain sociodemographic groups -and indeed, certain individuals-to perceive higher levels of weight discrimination than others.

Computational Modelling for Managing Pathways to Cartilage Failure.

Over several decades the perception and therefore description of articular cartilage changed substantially. It has transitioned from being described as a relatively inert tissue with limited repair capacity, to a tissue undergoing continuous maintenance and even adaption, through a range of complex regulatory processes. Even from the narrower lens of biomechanics, the engagement with articular cartilage has changed from it being an interesting, slippery material found in the hostile mechanical environment between opposing long bones, to an intriguing example of mechanobiology in action. The progress revealing this complexity, where physics, chemistry, material science and biology are merging, has been described with increasingly sophisticated computational models. Here we describe how these computational models of cartilage as an integrated system can be combined with the approach of structural reliability analysis. That is, causal, deterministic models placed in the framework of the probabilistic approach of structural reliability analysis could be used to understand, predict, and mitigate the risk of cartilage failure or pathology. At the heart of this approach is seeing cartilage overuse and disease processes as a 'material failure', resulting in failure to perform its function, which is largely mechanical. One can then describe pathways to failure, for example, how homeostatic repair processes can be overwhelmed leading to a compromised tissue. To illustrate this 'pathways to failure' approach, we use the interplay between cartilage consolidation and lubrication to analyse the increase in expected wear rates associated with cartilage defects or meniscectomy.

Predicting oxygen tension along the ureter.

Continuous measurement of bladder urine oxygen tension (Po2) is a method to potentially detect renal medullary hypoxia in patients at risk of acute kidney injury (AKI). To assess its practicality, we developed a computational model of the peristaltic movement of a urine bolus along the ureter and the oxygen exchange between the bolus and ureter wall. This model quantifies the changes in urine Po2 as urine transits from the renal pelvis to the bladder. The model parameters were calibrated using experimental data in rabbits, such that most of the model predictions are within ±1 SE of the reported mean in the experiment, with the average percent difference being 7.0%. Based on parametric experiments performed using a model scaled to the geometric dimensions of a human ureter, we found that bladder urine Po2 is strongly dependent on the bolus volume (i.e., bolus volume-to-surface area ratio), especially at a volume less than its physiological (baseline) volume (<0.2 mL). For the model assumptions, changes in peristaltic frequency resulted in a minimal change in bladder urine Po2 (<1 mmHg). The model also predicted that there exists a family of linear relationships between the bladder-urine Po2 and pelvic urine Po2 for different input conditions. We conclude that it may technically be possible to predict renal medullary Po2 based on the measurement of bladder urine Po2, provided that there are accurate real-time measurements of model input parameters.NEW & NOTEWORTHY Measurement of bladder urine oxygen tension has been proposed as a new method to potentially detect the risk of acute kidney injury in patients. A computational model of oxygen exchange between urine bolus and ureteral tissue shows that it may be technically possible to determine the risk of acute kidney injury based on the measurement of bladder urine oxygen tension, provided that the measurement data are properly interpreted via a computational model.

Genome-Scale Phylogeny and Evolutionary Analysis of Ross River Virus Reveals Periodic Sweeps of Lineage Dominance in Western Australia, 1977-2014.

Ross River virus (RRV), an alphavirus of the Togaviridae family, is the most medically significant mosquito-borne virus of Australia. Past RRV phylogenetic and evolutionary analyses have been based on partial genome analyses only. Three geographically distinct RRV lineages, the Eastern, the Western, and the supposedly extinct North-Eastern lineage, were classified previously. We sought to expand on past phylogenies through robust genome-scale phylogeny to better understand RRV genetic diversity and evolutionary dynamics. We analyzed 106 RRV complete coding sequences, which included 13 genomes available on NCBI and 94 novel sequences derived for this study, sampled throughout Western Australia (1977-2014) and during the substantial Pacific Islands RRV epidemic (1979-1980). Our final data set comprised isolates sampled over 59 years (1959-2018) from a range of locations. Four distinct genotypes were defined, with the newly described genotype 4 (G4) found to be the contemporary lineage circulating in Western Australia. The prior geographical classification of RRV lineages was not supported by our findings, with evidence of geographical and temporal cocirculation of distinct genetic groups. Bayesian Markov chain Monte Carlo (MCMC) analysis revealed that RRV lineages diverged from a common ancestor approximately 94 years ago, with distinct lineages emerging roughly every 10 years over the past 50 years in periodic bursts of genetic diversity. Our study has enabled a more robust analysis of RRV evolutionary history and resolved greater genetic diversity that had been previously defined by partial E2 gene analysis.IMPORTANCE Ross River virus (RRV) causes the most common mosquito-borne infection in Australia and causes a significant burden of suffering to infected individuals as well as being a large burden to the Australian economy. The genetic diversity of RRV and its evolutionary history have so far only been studied using partial E2 gene analysis with a limited number of isolates. Robust whole-genome analysis has not yet been conducted. This study generated 94 novel near-whole-genome sequences to investigate the evolutionary history of RRV to better understand its genetic diversity through comprehensive whole-genome phylogeny. A better understanding of RRV genetic diversity will enable better diagnostics, surveillance, and potential future vaccine design.

The eardrums move when the eyes move: A multisensory effect on the mechanics of hearing.

Interactions between sensory pathways such as the visual and auditory systems are known to occur in the brain, but where they first occur is uncertain. Here, we show a multimodal interaction evident at the eardrum. Ear canal microphone measurements in humans (n = 19 ears in 16 subjects) and monkeys (n = 5 ears in three subjects) performing a saccadic eye movement task to visual targets indicated that the eardrum moves in conjunction with the eye movement. The eardrum motion was oscillatory and began as early as 10 ms before saccade onset in humans or with saccade onset in monkeys. These eardrum movements, which we dub eye movement-related eardrum oscillations (EMREOs), occurred in the absence of a sound stimulus. The amplitude and phase of the EMREOs depended on the direction and horizontal amplitude of the saccade. They lasted throughout the saccade and well into subsequent periods of steady fixation. We discuss the possibility that the mechanisms underlying EMREOs create eye movement-related binaural cues that may aid the brain in evaluating the relationship between visual and auditory stimulus locations as the eyes move.

Assessing the Burden of Laboratory-Confirmed Respiratory Syncytial Virus Infection in a Population Cohort of Australian Children Through Record Linkage.

BACKGROUND: Significant progress has been made towards an effective respiratory syncytial virus (RSV) vaccine. Age-stratified estimates of RSV burden are urgently needed for vaccine implementation. Current estimates are limited to small cohorts or clinical coding data only. We present estimates of laboratory-confirmed RSV across multiple severity levels. METHODS: We linked laboratory, perinatal, and hospital data of 469 589 children born in Western Australia in 1996-2012. Respiratory syncytial virus tests and detections were classified into community, emergency department (ED), and hospital levels to estimate infection rates. Clinical diagnoses given to children with RSV infection presenting to ED or hospitalized were identified. RESULTS: In 2000-2012, 10% (n = 45 699) of children were tested for RSV and 16% (n = 11 461) of these tested positive. Respiratory syncytial virus was detected in community, ED (both 0.3 per 1000 child-years), and hospital (2.4 per 1000 child-years) settings. Respiratory syncytial virus-confirmed rates were highest among children aged <3 months (31 per 1000 child-years). At least one third of children with RSV infection presenting to ED were diagnosed as other infection, other respiratory, or other (eg, agranulocytosis). CONCLUSIONS: Respiratory syncytial virus is pervasive across multiple severity levels and diagnoses. Vaccines targeting children <3 months must be prioritized. Given that most children are never tested, estimating the under-ascertainment of RSV infection is imperative.

Flight-Associated Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 Corroborated by Whole-Genome Sequencing.

To investigate potential transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during a domestic flight within Australia, we performed epidemiologic analyses with whole-genome sequencing. Eleven passengers with PCR-confirmed SARS-CoV-2 infection and symptom onset within 48 hours of the flight were considered infectious during travel; 9 had recently disembarked from a cruise ship with a retrospectively identified SARS-CoV-2 outbreak. The virus strain of those on the cruise and the flight was linked (A2-RP) and had not been previously identified in Australia. For 11 passengers, none of whom had traveled on the cruise ship, PCR-confirmed SARS-CoV-2 illness developed between 48 hours and 14 days after the flight. Eight cases were considered flight associated with the distinct SARS-CoV-2 A2-RP strain; the remaining 3 cases (1 with A2-RP) were possibly flight associated. All 11 passengers had been in the same cabin with symptomatic persons who had culture-positive A2-RP virus strain. This investigation provides evidence of flight-associated SARS-CoV-2 transmission.

Analysis of the critical determinants of renal medullary oxygenation.

We have previously developed a three-dimensional computational model of oxygen transport in the renal medulla. In the present study, we used this model to quantify the sensitivity of renal medullary oxygenation to four of its major known determinants: medullary blood flow (MBF), medullary oxygen consumption rate (V̇o2,M), hemoglobin (Hb) concentration in the blood, and renal perfusion pressure. We also examined medullary oxygenation under special conditions of hydropenia, extracellular fluid volume expansion by infusion of isotonic saline, and hemodilution during cardiopulmonary bypass. Under baseline (normal) conditions, the average medullary tissue Po2 predicted for the whole renal medulla was ~30 mmHg. The periphery of the interbundle region in the outer medulla was identified as the most hypoxic region in the renal medulla, which demonstrates that the model prediction is qualitatively accurate. Medullary oxygenation was most sensitive to changes in renal perfusion pressure followed by Hb, MBF, and V̇o2,M, in that order. The medullary oxygenation also became sensitized by prohypoxic changes in other parameters, leading to a greater fall in medullary tissue Po2 when multiple parameters changed simultaneously. Hydropenia did not induce a significant change in medullary oxygenation compared with the baseline state, while volume expansion resulted in a large increase in inner medulla tissue Po2 (by ~15 mmHg). Under conditions of cardiopulmonary bypass, the renal medulla became severely hypoxic, due to hemodilution, with one-third of the outer stripe of outer medulla tissue having a Po2 of <5 mmHg.

Stimulation of erythropoietin release by hypoxia and hypoxemia: similar but different.

Erythropoietin is released from the kidney in response to tissue hypoxia. Montero and Lundby found that increases in plasma erythropoietin induced by reducing arterial oxygen content in healthy humans were independent of arterial oxygen tension. Their observations accord with the established physiology of kidney oxygenation and can be predicted by a computational model of renal oxygen transport. However, model simulations indicate that the interpretation implicit in the title of their paper may be an oversimplification.

The contribution of viruses and bacteria to community-acquired pneumonia in vaccinated children: a case-control study.

INTRODUCTION: Respiratory pathogens associated with childhood pneumonia are often detected in the upper respiratory tract of healthy children, making their contribution to pneumonia difficult to determine. We aimed to determine the contribution of common pathogens to pneumonia adjusting for rates of asymptomatic detection to inform future diagnosis, treatment and preventive strategies. METHODS: A case-control study was conducted among children <18 years in Perth, Western Australia. Cases were children hospitalised with radiologically confirmed pneumonia; controls were healthy children identified from outpatient and local immunisation clinics. Nasopharyngeal swabs were collected and tested for 14 respiratory viruses and 6 bacterial species by Polymerase chain reaction (PCR). For each pathogen, adjusted odds ratio (aOR; 95% CI) was calculated using multivariate logistic regression and population-attributable fraction (95% CI) for pneumonia was estimated. RESULTS: From May 2015 to October 2017, 230 cases and 230 controls were enrolled. At least one respiratory virus was identified in 57% of cases and 29% of controls (aOR: 4.7; 95% CI: 2.8 to 7.8). At least one bacterial species was detected in 72% of cases and 80% of controls (aOR: 0.7; 95% CI: 0.4 to 1.2). Respiratory syncytial virus (RSV) detection was most strongly associated with pneumonia (aOR: 58.4; 95% CI: 15.6 to 217.5). Mycoplasma pneumoniae was the only bacteria associated with pneumonia (aOR: 14.5; 95% CI: 2.2 to 94.8). We estimated that RSV, human metapneumovirus (HMPV), influenza, adenovirus and Mycoplasma pneumoniae were responsible for 20.2% (95% CI: 14.6 to 25.5), 9.8% (5.6% to 13.7%), 6.2% (2.5% to 9.7%), 4% (1.1% to 7.1%) and 7.2% (3.5% to 10.8%) of hospitalisations for childhood pneumonia, respectively. CONCLUSIONS: Respiratory viruses, particularly RSV and HMPV, are major contributors to pneumonia in Australian children.

Divergent Human-Origin Influenza Viruses Detected in Australian Swine Populations.

Global swine populations infected with influenza A viruses pose a persistent pandemic risk. With the exception of a few countries, our understanding of the genetic diversity of swine influenza viruses is limited, hampering control measures and pandemic risk assessment. Here we report the genomic characteristics and evolutionary history of influenza A viruses isolated in Australia from 2012 to 2016 from two geographically isolated swine populations in the states of Queensland and Western Australia. Phylogenetic analysis with an expansive human and swine influenza virus data set comprising >40,000 sequences sampled globally revealed evidence of the pervasive introduction and long-term establishment of gene segments derived from several human influenza viruses of past seasons, including the H1N1/1977, H1N1/1995, H3N2/1968, and H3N2/2003, and the H1N1 2009 pandemic (H1N1pdm09) influenza A viruses, and a genotype that contained gene segments derived from the past three pandemics (1968, reemerged 1977, and 2009). Of the six human-derived gene lineages, only one, comprising two viruses isolated in Queensland during 2012, was closely related to swine viruses detected from other regions, indicating a previously undetected circulation of Australian swine lineages for approximately 3 to 44 years. Although the date of introduction of these lineages into Australian swine populations could not be accurately ascertained, we found evidence of sustained transmission of two lineages in swine from 2012 to 2016. The continued detection of human-origin influenza virus lineages in swine over several decades with little or unpredictable antigenic drift indicates that isolated swine populations can act as antigenic archives of human influenza viruses, raising the risk of reemergence in humans when sufficient susceptible populations arise.IMPORTANCE We describe the evolutionary origins and antigenic properties of influenza A viruses isolated from two separate Australian swine populations from 2012 to 2016, showing that these viruses are distinct from each other and from those isolated from swine globally. Whole-genome sequencing of virus isolates revealed a high genotypic diversity that had been generated exclusively through the introduction and establishment of human influenza viruses that circulated in past seasons. We detected six reassortants with gene segments derived from human H1N1/H1N1pdm09 and various human H3N2 viruses that circulated during various periods since 1968. We also found that these swine viruses were not related to swine viruses collected elsewhere, indicating independent circulation. The detection of unique lineages and genotypes in Australia suggests that isolated swine populations that are sufficiently large can sustain influenza virus for extensive periods; we show direct evidence of a sustained transmission for at least 4 years between 2012 and 2016.

Combination of clinical symptoms and blood biomarkers can improve discrimination between bacterial or viral community-acquired pneumonia in children.

BACKGROUND: Differentiating bacterial from viral pneumonia is important for guiding targeted management and judicious use of antibiotics. We assessed if clinical characteristics and blood inflammatory biomarkers could be used to distinguish bacterial from viral pneumonia. METHODS: Western Australian children (≤17 years) hospitalized with radiologically-confirmed community-acquired pneumonia were recruited and clinical symptoms and management data were collected. C-reactive protein (CRP), white cell counts (WCC) and absolute neutrophil counts (ANC) were measured as part of routine care. Clinical characteristics and biomarker levels were compared between cases with definite bacterial pneumonia (clinical empyema and/or bacteria detected in blood or pleural fluid), presumed viral pneumonia (presence of ≥1 virus in nasopharyngeal swab without criteria for definite bacterial pneumonia), and other pneumonia cases (pneumonia in the absence of criteria for either definite bacterial or presumed viral pneumonia). The area-under-curve (AUC) of the receiver operating characteristic (ROC) curve for varying biomarker levels were used to characterise their utility for discriminating definite bacterial from presumed viral pneumonia. For biomarkers with AUC > 0.8 (fair discriminator), Youden index was measured to determine the optimal cut-off threshold, and sensitivity, specificity, predictive values (positive and negative) were calculated. We investigated whether better discrimination could be achieved by combining biomarker values with the presence/absence of symptoms. RESULTS: From May 2015 to October 2017, 230 pneumonia cases were enrolled: 30 with definite bacterial pneumonia, 118 with presumed viral pneumonia and 82 other pneumonia cases. Differences in clinical signs and symptoms across the groups were noted; more definite bacterial pneumonia cases required intravenous fluid and oxygen supplementation than presumed viral or other pneumonia cases. CRP, WCC and ANC were substantially higher in definite bacterial cases. For a CRP threshold of 72 mg/L, the AUC of ROC was 0.82 for discriminating definite bacterial pneumonia from presumed viral pneumonia. Combining the CRP with either the presence of fever (≥38οC) or the absence of rhinorrhea improved the discrimination. CONCLUSIONS: Combining elevated CRP with the presence or absence of clinical signs/ symptoms differentiates definite bacterial from presumed viral pneumonia better than CRP alone. Further studies are required to explore combination of biomarkers and symptoms for use as definitive diagnostic tool.

A model of oxygen transport in the rat renal medulla.

The renal medulla is prone to hypoxia. Medullary hypoxia is postulated to be a leading cause of acute kidney injury, so there is considerable interest in predicting the oxygen tension in the medulla. Therefore we have developed a computational model for blood and oxygen transport within a physiologically normal rat renal medulla, using a multilevel modeling approach. For the top-level model we use the theory of porous media and advection-dispersion transport through a realistic three-dimensional representation of the medulla's gross anatomy to describe blood flow and oxygen transport throughout the renal medulla. For the lower-level models, we employ two-dimensional reaction-diffusion models describing the distribution of oxygen through tissue surrounding the vasculature. Steady-state model predictions at the two levels are satisfied simultaneously, through iteration between the levels. The computational model was validated by simulating eight sets of experimental data regarding renal oxygenation in rats (using 4 sets of control groups and 4 sets of treatment groups, described in 4 independent publications). Predicted medullary tissue oxygen tension or microvascular oxygen tension for control groups and for treatment groups that underwent moderate perturbation in hemodynamic and renal functions is within ±2 SE values observed experimentally. Diffusive shunting between descending and ascending vasa recta is predicted to be only 3% of the oxygen delivered. The validation tests confirm that the computational model is robust and capable of capturing the behavior of renal medullary oxygenation in both normal and early-stage pathological states in the rat.

Three-dimensional morphometric analysis of the renal vasculature.

Vascular topology and morphology are critical in the regulation of blood flow and the transport of small solutes, including oxygen, carbon dioxide, nitric oxide, and hydrogen sulfide. Renal vascular morphology is particularly challenging, since many arterial walls are partially wrapped by the walls of veins. In the absence of a precise characterization of three-dimensional branching vascular geometry, accurate computational modeling of the intrarenal transport of small diffusible molecules is impossible. An enormous manual effort was required to achieve a relatively precise characterization of rat renal vascular geometry, highlighting the need for an automated method for analysis of branched vasculature morphology to allow characterization of the renal vascular geometry of other species, including humans. We present a semisupervised method for three-dimensional morphometric analysis of renal vasculature images generated by computed tomography. We derive quantitative vascular attributes important to mass transport between arteries, veins, and the renal tissue and present methods for their computation for a three-dimensional vascular geometry. To validate the algorithm, we compare automated vascular estimates with subjective manual measurements for a portion of rabbit kidney. Although increased image resolution can improve outcomes, our results demonstrate that the method can quantify the morphological characteristics of artery-vein pairs, comparing favorably with manual measurements. Similar to the rat, we show that rabbit artery-vein pairs become less intimate along the course of the renal vasculature, but the total wrapped mass transfer coefficient increases and then decreases. This new method will facilitate new quantitative physiological models describing the transport of small molecules within the kidney.

Effect of collagen length distribution and timing for repair on the active TGF-ß concentration in tendon.

The composition of extracellular matrix (ECM) in tendon depends on the secretion profile of resident cells known as tenocytes. For tissues with a mechanical role like tendon, mechanical strain is known to play an important role in determining the secretion profile of resident cells. Previously we explored the idea of estimating average concentrations of ECM molecules as a function of tendon strain magnitude and number of loading cycles. Specifically, we developed a model of the mechanical fatigue damage of tendon collagen fibers and introduced elementary cell responses (ECRs) by which local cellular-level responses to the strain environment, combined with the fatigue damage model, were scaled up to predict tissue-level responses. Using this approach, we demonstrated that the proposed model is capable of estimating average concentrations of ECM molecules that qualitatively accord with experimental observations. In this study, we increase model realism by extending this approach to consider the implications of a non-uniform collagen fiber distribution, and the influence of time delay on repair of damaged collagen fibers. Using this approach, we focus the study on the average tenocyte secretion profile for active transforming growth factor beta (TGF-ß), and discover that increasing fiber length dispersion and/or increasing repair delay leads to increasing active TGF-ß concentrations, and reduced sensitivity of average concentration profile of TGF-ß to tendon strain.

A pseudo-three-dimensional model for quantification of oxygen diffusion from preglomerular arteries to renal tissue and renal venous blood.

To assess the physiological significance of arterial-to-venous (AV) oxygen shunting, we generated a new pseudo-three-dimensional computational model of oxygen diffusion from intrarenal arteries to cortical tissue and veins. The model combines the 11 branching levels (known as "Strahler" orders) of the preglomerular renal vasculature in the rat, with an analysis of an extensive data set obtained using light microscopy to estimate oxygen mass transfer coefficients for each Strahler order. Furthermore, the AV shunting model is now set within a global oxygen transport model that includes transport from arteries, glomeruli, peritubular capillaries, and veins to tissue. While a number of lines of evidence suggest AV shunting is significant, most importantly, our AV oxygen shunting model predicts AV shunting is small under normal physiological conditions (~0.9% of total renal oxygen delivery; range 0.4-1.4%), but increases during renal ischemia, glomerular hyperfiltration (~2.1% of total renal oxygen delivery; range 0.84-3.36%), and some cardiovascular disease states (~3.0% of total renal oxygen delivery; range 1.2-4.8%). Under normal physiological conditions, blood Po2 is predicted to fall by ~16 mmHg from the root of the renal artery to glomerular entry, with AV oxygen shunting contributing ~40% and oxygen diffusion from arteries to tissue contributing ~60% of this decline. Arterial Po2 is predicted to fall most rapidly from Strahler order 4, under normal physiological conditions. We conclude that AV oxygen shunting normally has only a small impact on renal oxygenation, but may exacerbate renal hypoxia during renal ischemia, hyperfiltration, and some cardiovascular disease states.

Accounting for oxygen in the renal cortex: a computational study of factors that predispose the cortex to hypoxia.

We develop a pseudo-three-dimensional model of oxygen transport for the renal cortex of the rat, incorporating both the axial and radial geometry of the preglomerular circulation and quantitative information regarding the surface areas and transport from the vasculature and renal corpuscles. The computational model was validated by simulating four sets of published experimental studies of renal oxygenation in rats. Under the control conditions, the predicted cortical tissue oxygen tension ([Formula: see text]) or microvascular oxygen tension (µPo2) were within ±1 SE of the mean value observed experimentally. The predicted [Formula: see text] or µPo2 in response to ischemia-reperfusion injury, acute hemodilution, blockade of nitric oxide synthase, or uncoupling mitochondrial respiration, were within ±2 SE observed experimentally. We performed a sensitivity analysis of the key model parameters to assess their individual or combined impact on the predicted [Formula: see text] and µPo2 The model parameters analyzed were as follows: 1) the major determinants of renal oxygen delivery ([Formula: see text]) (arterial blood Po2, hemoglobin concentration, and renal blood flow); 2) the major determinants of renal oxygen consumption (V̇o2) [glomerular filtration rate (GFR) and the efficiency of oxygen utilization for sodium reabsorption (ß)]; and 3) peritubular capillary surface area (PCSA). Reductions in PCSA by 50% were found to profoundly increase the sensitivity of [Formula: see text] and µPo2 to the major the determinants of [Formula: see text] and V̇o2 The increasing likelihood of hypoxia with decreasing PCSA provides a potential explanation for the increased risk of acute kidney injury in some experimental animals and for patients with chronic kidney disease.

Characterization of Fitzroy River Virus and Serologic Evidence of Human and Animal Infection.

In northern Western Australia in 2011 and 2012, surveillance detected a novel arbovirus in mosquitoes. Genetic and phenotypic analyses confirmed that the new flavivirus, named Fitzroy River virus, is related to Sepik virus and Wesselsbron virus, in the yellow fever virus group. Most (81%) isolates came from Aedes normanensis mosquitoes, providing circumstantial evidence of the probable vector. In cell culture, Fitzroy River virus replicated in mosquito (C6/36), mammalian (Vero, PSEK, and BSR), and avian (DF-1) cells. It also infected intraperitoneally inoculated weanling mice and caused mild clinical disease in 3 intracranially inoculated mice. Specific neutralizing antibodies were detected in sentinel horses (12.6%), cattle (6.6%), and chickens (0.5%) in the Northern Territory of Australia and in a subset of humans (0.8%) from northern Western Australia.

Adaptive Remodeling of Achilles Tendon: A Multi-scale Computational Model.

While it is known that musculotendon units adapt to their load environments, there is only a limited understanding of tendon adaptation in vivo. Here we develop a computational model of tendon remodeling based on the premise that mechanical damage and tenocyte-mediated tendon damage and repair processes modify the distribution of its collagen fiber lengths. We explain how these processes enable the tendon to geometrically adapt to its load conditions. Based on known biological processes, mechanical and strain-dependent proteolytic fiber damage are incorporated into our tendon model. Using a stochastic model of fiber repair, it is assumed that mechanically damaged fibers are repaired longer, whereas proteolytically damaged fibers are repaired shorter, relative to their pre-damage length. To study adaptation of tendon properties to applied load, our model musculotendon unit is a simplified three-component Hill-type model of the human Achilles-soleus unit. Our model results demonstrate that the geometric equilibrium state of the Achilles tendon can coincide with minimization of the total metabolic cost of muscle activation. The proposed tendon model independently predicts rates of collagen fiber turnover that are in general agreement with in vivo experimental measurements. While the computational model here only represents a first step in a new approach to understanding the complex process of tendon remodeling in vivo, given these findings, it appears likely that the proposed framework may itself provide a useful theoretical foundation for developing valuable qualitative and quantitative insights into tendon physiology and pathology.