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Background: Cardiometabolic risk factors among youth are rising. Epigenetic age acceleration, a biomarker for aging and disease-risk, has been associated with adiposity in children, but its association with other cardiometabolic risk markers remains understudied. We employed data from the Health Outcomes and Measures of the Environment (HOME) study, a prospective pregnancy and birth cohort in the greater Cincinnati metropolitan area, to examine whether accelerated epigenetic age at birth as well as accelerated epigenetic age and faster pace of biological aging at age 12 years were associated with higher cardiometabolic risk in adolescents. Results: After adjusting for potential confounders, including estimated cell type proportions, epigenetic gestational age acceleration at birth, derived from the Bohlin, Knight, and Haftorn clocks using cord blood DNA methylation data, was not associated with cardiometabolic risk z-scores or individual cardiometabolic risk score components (visceral fat, leptin to adiponectin ratio, HOMA-IR, triglycerides to HDL-C ratio, HbA1c, or systolic blood pressure) at age 12 years. We also did not observe any associations of epigenetic age acceleration, calculated with Horvath's skin and blood, Hannum's, and Wu's epigenetic clocks using peripheral blood at age 12 years, with these same cardiometabolic risk markers. In contrast, faster pace of biological aging was associated with higher cardiometabolic risk [βs (95% CIs)] cardiometabolic risk score 0.25 (0.07, 0.42); visceral fat 0.21 (0.05, 0.38); and hemoglobin A1c 0.23 (0.05, 0.41) per standard deviation increase in pace of biological aging. Faster pace of biological aging was also positively associated with systolic blood pressure, triglycerides to HDL-C ratio, HOMA-IR, and leptin to adiponectin ratio, although these associations were not statistically significant. Conclusions: Our findings provide evidence that faster pace of biological aging was associated with higher cardiometabolic risk score, visceral fat, and HbA1c at age 12 years. Further research is needed to determine whether these associations persist from adolescence through adulthood. [ABSTRACT FROM AUTHOR]

Purpose: To investigate long-term astigmatism after combined nonpenetrating glaucoma surgery (NPGS) and implantation of the first miniaturized suprachoroidal intraocular pressure (IOP) sensor EYEMATE-SC. Setting: The study was conducted in 5 medical centers in 2 different countries. Design: Retrospective multicenter clinical study. Methods: Astigmatism of patients instrumented with the EYEMATE-SC IOP sensor was assessed over a follow-up period of 3 years. Refraction and corrected distance visual acuity (CDVA) were obtained preoperatively, after 6 months, 1, 2, and 3 years. A canaloplasty-operated patient cohort served as control. Astigmatism was evaluated using 3-dimensional power vector analysis involving the spherical equivalent M, and the Jackson crossed cylinder projections J0 and J45. Exclusion criteria included neovascular and angle-closure glaucoma, myopia, axial length outside 22 to 26 mm, other ocular diseases, prior glaucoma surgery, other ocular surgery within 6months (cataract surgery within 3 months) before NPGS, serious generalized conditions, and other active medical head/neck implants. Results: Multivariate analysis indicated no changes in astigmatism along the observation period in both the EYEMATE-SC (n = 24) and the canaloplasty (n = 24) group (P > .05 or nonsignificant after Bonferroni correction). Astigmatism was unchanged between the EYEMATE-SC and the canaloplasty group at all timepoints (P > .05). CDVA did not change along the observation period of 3 years in each of both groups (P > .05). Conclusions: Despite its suprachoroidal localization, this study indicated that the miniaturized EYEMATE-SC IOP sensor did not negatively affect long-term astigmatism after combined implantation with NPGS. [ABSTRACT FROM AUTHOR]

Resilience is a concept of growing interest because it can systematically inform prevention measures and psychosocial interventions for children and adolescents. The aim of this study was to explore resilience factors among young people who are victims of bullying and harassment (age 9 to 16 years old). In 2021 the burden of the pandemic lockdown became an additional adversity. The study used a repeated cross‐sectional design. Two datasets with a total of 2,211 participants from 2017 (N = 972) and 2021 (N = 1,239) were included. The strengths and difficulties questionnaire (SDQ) was applied to define the resilient and non‐resilient groups, and the quality‐of‐life questionnaire (KINDL) was used to map resilience factors. A total of 227 participants reported that they were being bullied, and 604 participants reported harassments from their peers. We used correlation and regression analyses to identify which factors predicted the highest resistance to the negative effects of bullying and harassment. The results were that 77.2% of the participants stayed resilient when facing these maladjustments, but this dropped to 61.7% during the pandemic. The most important resilience factors before the pandemic were the school environment, emotional well‐being, and good relations with their friends. The impact of these predictors changed during the pandemic. Emotional well‐being increased in strength, school environment was reduced, and friends did not predict resilience anymore. The effect sizes were generally large to medium. As it is common to experience adversity at some stage in life, it is vital for families, schools, social and healthcare workers to be aware of the factors associated with resilience. The results of this study may contribute towards an evidence base for developing plans to increase the capacity of resilience among young people. [ABSTRACT FROM AUTHOR]

Objective: To use a previously validated veterinary clinical examination sheet, Liverpool Osteoarthritis in Dogs (LOAD) questionnaire, combined with kinetic and kinematic gait analysis in dogs with/without mobility problems to demonstrate the capacity of a novel clinical metrology instrument ("GenPup-M") to detect canine mobility impairments. Design: Quantitative study. Animals: 62 dogs (31 with mobility impairments and 31 without mobility impairments). Procedure: The dogs' clinical history was obtained from owners and all dogs underwent a validated orthopaedic clinical examination. Mobility impairments were diagnosed in the mobility impaired group based on clinical history and orthopaedic examination. Owners were asked to complete GenPup-M along with a previously validated mobility questionnaire (Liverpool Osteoarthritis in Dogs (LOAD)) to identify construct validity. As a test of criterion validity, the correlation between instrument scores and the overall clinical examination scores, along with force-platform obtained peak vertical forces (PVF) were calculated. GenPup-M underwent internal consistency and factor analysis. Spatiotemporal parameters were calculated for dogs with/without mobility impairments to define the gait differences between these two groups. Results: Principal Component Analysis identified GenPup-M had two components with Eigenvalues >1 ("stiffness/ease of movement" and "willingness to be active/exercise"). Cronbach's α was used to test internal consistency of GenPup-M and was found to be "good" (0.87). There was a strong, positive correlation between GenPup-M and LOAD responses (r2 = 0.69, p<0.001) highlighting construct validity. Criterion validity was also shown when comparing GenPup-M to clinical examination scores (r2 = 0.74, p<0.001) and PVF (r2 = 0.43, p<0.001). Quantitative canine gait analysis showed that there were statistically significant differences between peak vertical forces (PVF) of mobility impaired and non-mobility impaired dogs (p<0.05). Analyses of PVF showed that non-mobility impaired dogs more evenly distributed their weight across all thoracic and pelvic limbs when compared to mobility impaired dogs. There were also consistent findings that mobility impaired dogs moved slower than non-mobility impaired dogs. Conclusion and clinical relevance: GenPup-M is a clinical metrology instrument (CMI) that can be completed by dog owners to detect all mobility impairments, including those that are early in onset, indicating the versatility of GenPup-M to assess dogs with and without mobility impairments. Results of the study found that GenPup-M positively correlated with all three objective measures of canine mobility and consequently showed criterion and construct validity. Owner-reported CMIs such as GenPup-M allow non-invasive scoring systems which veterinary surgeons and owners can use to allow communication and longitudinal assessment of a dog's mobility. It is anticipated that GenPup-M will be used by owners at yearly vaccinations/health checks, allowing identification of any subtle mobility changes, and enabling early intervention. [ABSTRACT FROM AUTHOR]

Simple Summary: Ageing sometimes leads to changes in the size, shape and structure of muscles. This impacts their ability to perform their functions and so leads to an increased likelihood of injuries and negatively impacts quality of life. This work attempts to investigate how the structure and performance of individual muscles of the human leg may change due to ageing, using a combination of magnetic resonance imaging and muscle strength testing in groups of aged (65+ years old) and young (18–40 years old) individuals. The results showed a larger difference in muscle structure and strength in the muscles that extend the knee (i.e., the quadriceps) between the age groups relative to other muscles, and these muscles also showed the strongest relationships between structure and strength. There was also greater variation in fibre lengths and variables linked to fibre type and quality within individual muscles in the aged group compared to the young group. Overall, these results show that even healthy ageing may cause large changes in muscle structure and decreases in performance and that the quadriceps muscles could be a target for exercises to reduce the negative effects of ageing. Even "healthy" muscle ageing is often associated with substantial changes in muscle form and function and can lead to increased injury risks and significant negative impacts on quality of life. However, the impacts of healthy muscle ageing on the fibre architecture and microstructure of different muscles and muscle groups throughout the lower limb, and how these are related to their functional capabilities, are not fully understood. Here, a previously established framework of magnetic resonance and diffusion tensor imaging was used to measure the muscle volumes, intramuscular fat, fibre lengths and physiological cross-sectional areas of 12 lower limb muscles in a cohort of healthily aged individuals, which were compared to the same data from a young population. Maximum muscle forces were also measured from an isokinetic dynamometer. The more substantial interpopulation differences in architecture and functional performance were located within the knee extensor muscles, while the aged muscles were also more heterogeneous in muscle fibre type and atrophy. The relationships between architecture and muscle strength were also more significant in the knee extensors compared to other functional groups. These data highlight the importance of the knee extensors as a potential focus for interventions to negate the impacts of muscle ageing. [ABSTRACT FROM AUTHOR]

Introduction: Despite the wide availability of clinical decision rules for imaging of the cervical spine after a traumatic injury (eg, NEXUSC-spine rule and Canadian C-spine rule), there is significant overutilization of computed tomography (CT) imaging in patients who are deemed to be at low risk for a clinically significant cervical spine injury by these clinical decision rules. The purpose of this study was to identify the major factors associated with the overuse of CT cervical spine imaging using a logistic regression model. Methods: This was a retrospective review of all adult patients who underwent CT cervical spine imaging for evaluation of a traumatic injury at a tertiary academic emergency department (ED) and three affiliate community EDs in January and February 2019. Weperformed multivariable logistic regression to identify factors associated with obtaining CT cervical spine imaging despite low-risk classification by the NEXUS C-spine Rule. Results: A total of 1,051 patients underwent CT cervical spine imaging for traumatic indications during the study period, and 889 patients were included in the analysis. Of these patients, 376 (42.3%) were negative by the NEXUS C-spine rule. Variables that were associated with increased likelihood of unnecessary imaging included age over 65, Emergency Severity Index (ESI) score 2 and 3, arrival as a walk-in, and anticoagulation status. Patients who presented to the tertiary academic ED had a significantly lower likelihood of unnecessary imaging. Twenty-one patients (2.4%) were found to have cervical spine fractures on imaging, two of whom were negative by the NEXUS C-spine rule, but neither had a clinically significant fracture. Conclusion: Cervical spine imaging is vastly overused in patients presenting to the ED with traumatic injuries, as adjudicated using the NEXUS C-spine rule as a reference standard. Older age, ESI level, arrival as a walk-in, and taking anticoagulation drugs were associated with overutilization of CT imaging. Conversely, presenting to the tertiary academic ED was associated with a lower likelihood of undergoing unnecessary imaging. This model can guide future interventions to optimize ED CT utilization and minimize unnecessary testing. [ABSTRACT FROM AUTHOR]

The Mars 2020 entry vehicle's thermal protection system included measurements of in-depth temperature on the heatshield and backshell, and surface heating on the backshell. This paper describes the flight data and resulting analysis: subsurface temperatures at 11 heatshield and 6 backshell locations, measured total heat flux at two backshell locations, and a radiometer on the backshell to measure shock layer radiation. All temperatures were within allowable material limits. Total surface heat flux was derived from the in-depth temperature measurements at the thermocouple locations. Turbulent boundary-layer conditions occurred at nine heatshield locations and the radiometer provided evidence that heating from shock layer radiation significantly exceeded convective heating on the backshell. Computational results on the reconstructed entry trajectory are compared to the flight data. After boundary-layer transition, total heat flux from algebraic turbulence model calculations qualitatively matches the reconstructed heating, but with lower peak magnitudes. On the backshell, laminar heat flux predictions generally exceed the as-flown values by less than 1 W/cm², with shock layer radiation predicted to contribute the majority of heating. At the radiometer location, the maximum predicted radiative heat flux exceeds the measurement, with the measured value likely suppressed by ablation products on the sapphire window. [ABSTRACT FROM AUTHOR]

Life-history traits have been described disproportionately for temperate-breeding birds. Efforts to conserve global biodiversity require a more holistic understanding of avian life-history theory across biomes and geographic locations. In this account, we present the first detailed description of the breeding biology of the Bornean Stubtail (Urosphena whiteheadi). We discuss the stubtail's breeding strategies in the context of life-history theory and contrast them with those of 4 other members of the same family breeding at higher latitudes and lower elevations. The Bornean Stubtail is a tropical montane passerine belonging to the Old World Cettiidae family and endemic to the island of Borneo. Compared to other Cettiidae warblers, the Bornean Stubtail has a small clutch of 2 eggs and a long incubation period of 23.0 ± 0.10 d. At our site, their open-cup nests were constructed of moss and placed on or near the ground on vertical features in rainforest understory. The nests experienced a daily survival rate of 0.939 ± 0.006 and daily predation rate of 0.054 ± 0.006. Mean fresh egg mass was 1.87 ± 0.012 g. Egg-laying began in mid-February and continued into May. The number of active nests increased until mid-March at which point it remained relatively consistent until mid-May when it began to taper off. Nest attentiveness during incubation was low with a very long off-bout of ∼7 h every day that decreased to ∼4 h later in incubation, explaining the species' long incubation period. In contrast, nestling provisioning rates increased steadily over the nestling period (mean 12.53 ± 0.24). Nestling growth followed a logistic trend commonly seen in passerines, and near-adult sizes were reached by fledging. Rasgos de historia de vida han sido descritos desproporcionalmente en aves de reproducción en sitios templados. Los esfuerzos de conservación de la biodiversidad global requieren un entendimiento más holístico de las teorías de historias de vida a través de distintos biomas y localidades geográficas. Por ello, presentamos la primera descripción detallada de la biología reproductiva de la buscarla-colicorta Urosphena whiteheadi. Discutimos las estrategias reproductivas de la colicorta en el contexto de la teoría de historias de vida y las contrastamos con otros 4 miembros de esa familia que se reproducen en grandes alturas y elevaciones más bajas. La buscarla-colicorta Urosphena whiteheadi es un ave paserina de montaña tropical que pertenece a la familia Cettidae del Viejo Mundo y que es endémica de la isla de Borneo. Comparada con otras buscarlas-colicortas de la familia Cetiidae, la buscarla-colicorta Urosphena whiteheadi tiene unas puestas pequeñas de 2 huevos y un periodo largo de incubación de 23 ± 0.1 días. En nuestro sitio, los nidos de copa abierta fueron construidos con musgo y colocados en o cerca del suelo en elementos verticales en el sotobosque forestal. Los nidos experimentaron una tasa diaria de supervivencia de 0.939 ± 0.006 y una depredación diaria de 0.054 ± 0.006. La masa promedio de huevos fue de 1.87 ± 0.012 g. La puesta de huevos inició a mediados de febrero y continuó hasta mayo. El número de nidos activos aumentó hasta mediados de marzo, luego se mantuvo relativamente contante hasta mediados de mayo cuando empezó a disminuir. La atención al nido durante la incubación fue baja con largos periodos de ausencia ∼7 h cada día que luego disminuyeron a ∼4 h posteriormente durante la incubación, lo que explica el largo periodo de incubación de la especie. En contraste, las tasas de aprovisionamiento del nido aumentaron constantemente durante el periodo de incubación (promedio 12.53 ± 0.24). El crecimiento del polluelo siguió una tendencia logística típicamente vista en aves paserinas y tallas cercanas a las de adulto fueron alcanzadas por los volantones. Palabras clave: ave paserina de bosque tropical, cambio climático, conteo de especies, grandes alturas, historia de vida, periodo de incubación, tamaño de puesta. [ABSTRACT FROM AUTHOR]

The ff15ipq protein force field is a fixed charge model built by automated tools based on the two charge sets of the implicitly polarized charge method: one set (appropriate for vacuum) for deriving bonded parameters and the other (appropriate for aqueous solution) for running simulations. The duality is intended to treat water-induced electronic polarization with an understanding that fitting data for bonded parameters will come from quantum mechanical calculations in the gas phase. In this study, we compare ff15ipq to two alternatives produced with the same fitting software and a further expanded data set but following more conventional methods for tailoring bonded parameters (harmonic angle terms and torsion potentials) to the charge model. First, ff15ipq-Qsolv derives bonded parameters in the context of the ff15ipq solution phase charge set. Second, ff15ipq-Vac takes ff15ipq's bonded parameters and runs simulations with the vacuum phase charge set used to derive those parameters. The IPolQ charge model and associated protocol for deriving bonded parameters are shown to be an incremental improvement over protocols that do not account for the material phases of each source of their fitting data. Both force fields incorporating the polarized charge set depict stable globular proteins and have varying degrees of success modeling the metastability of short (5-19 residues) peptides. In this particular case, ff15ipq-Qsolv increases stability in a number of α-helices, correctly obtaining 70% helical character in the K19 system at 275 K and showing appropriately diminishing content up to 325 K, but overestimating the helical fraction of AAQAA3 by 50% or more, forming long-lived α-helices in simulations of a β-hairpin, and increasing the likelihood that the disordered p53 N-terminal peptide will also form a helix. This may indicate a systematic bias imparted by the ff15ipq-Qsolv parameter development strategy, which has the hallmarks of strategies used to develop other popular force fields, and may explain some of the need for manual corrections in this force fields' evolution. In contrast, ff15ipq-Vac incorrectly depicts globular protein unfolding in numerous systems tested, including Trp cage, villin, lysozyme, and GB3, and does not perform any better than ff15ipq or ff15ipq-Qsolv in tests on short peptides. We analyze the free energy surfaces of individual amino acid dipeptides and the electrostatic potential energy surfaces of each charge model to explain the differences. [ABSTRACT FROM AUTHOR]

The article provides a detailed account of the breeding biology of the Bornean Stubtail (Urosphena whiteheadi), focusing on its reproductive traits and comparing them with other members of its family. Topics include the bird's breeding strategies and life-history traits, its nesting behavior and incubation period, and the differences observed in comparison to other Cettiidae warblers.

Objective: To improve food insecurity interventions, we sought to better understand the hypothesized bidirectional relationship between food insecurity and health care expenditures.Data Source: Nationally representative sample of the civilian noninstitutionalized population of the United States (2016-2017 Medical Expenditure Panel Survey [MEPS]).Study Design: In a retrospective longitudinal cohort, we conducted two sets of analyses: (a) two-part models to examine the association between food insecurity in 2016 and health care expenditures in 2017; and (b) logistic regression models to examine the association between health care expenditures in 2016 and food insecurity in 2017. We adjusted for demographic and socioeconomic variables as well as 2016 health care expenditures and food insecurity.Data Collection: Health care expenditures, food insecurity, and medical condition data from 10 886 adults who were included in 2016-2017 MEPS.Principal Findings: Food insecurity in 2016, compared with being food secure, was associated with both a higher odds of having any health care expenditures in 2017 (OR 1.29, 95% CI: 1.04 to 1.60) and greater total expenditures ($1738.88 greater, 95% CI: $354.10 to $3123.57), which represents approximately 25% greater expenditures. Greater 2016 health care expenditures were associated with slightly higher odds of being food insecure in 2017 (OR 1.007 per $1000 in expenditures, 95% CI: 1.002 to 1.012, P =0.01). Exploratory analyses suggested that poor health status may underlie the relationship between food insecurity and health care expenditures.Conclusions: A bidirectional relationship exists between food insecurity and health care expenditures, but the strength of either direction appears unequal. Higher health care expenditures are associated with a slightly greater risk of being food insecure (adjusted for baseline food insecurity status) but being food insecure is associated with substantially greater subsequent health care expenditures (adjusted for baseline health care expenditures). Interventions to address food insecurity and poor health may be helpful to break this cycle. [ABSTRACT FROM AUTHOR]

Human cytomegalovirus (HCMV) is a highly prevalent herpes virus which persists as a latent infection and has been detected in several different tumor types. HCMV disease is rare but may occur in high-risk settings, often manifesting as a pulmonary infection. To date HCMV has not been investigated in malignant pleural mesothelioma (MPM). In a consecutive case series of 144 MPM patients we evaluated two biomarkers of HCMV: IgG serostatus (defined as positive and negative) and DNAemia (>100 copies/mL of cell free HCMV DNA in serum). Approximately half of the MPM patient population was HCMV IgG seropositive (51%). HCMV DNAemia was highly prevalent (79%) in MPM and independent of IgG serostatus. DNAemia levels consistent with high level current infection (>1000 copies/mL serum) were present in 41% of patients. Neither IgG serostatus nor DNAemia were associated with patient survival. In tissues, we observed that HCMV DNA was present in 48% of tumors (n = 40) and only 29% of normal pleural tissue obtained from individuals without malignancy (n = 21). Our results suggest nearly half of MPM patients have a high level current HCMV infection at the time of treatment and that pleural tissue may be a reservoir for latent HCMV infection. These findings warrant further investigation to determine the full spectrum of pulmonary infections in MPM patients, and whether treatment for high level current HCMV infection may improve patient outcomes. [ABSTRACT FROM AUTHOR]

Strategies to regenerate cardiac tissue postinjury are limited and heart transplantation remains the only 'cure' for a failing heart. Extracellular vesicles (EVs), membrane-bound cell secretions important in intercellular signaling, have been shown to play a crucial role in regulating heart function. A mechanistic understanding of the role of EVs in the heart remains elusive due to the challenges in studying the native human heart. Tissue-on-a-chip platforms, comprising functional, physiologically relevant human tissue models, are an emerging technology that has yet to be fully applied to the study of EVs. In this review, we summarize recent advances in cardiac tissue-on-a-chip (CTC) platforms and discuss how they are uniquely situated to advance our understanding of EVs in cardiac disease and regeneration. Extracellular vesicles (EVs) play key roles in regulating cardiac physiology in health and disease. EVs from regenerative cell sources can stimulate functional recovery of injured hearts. Recent developments in cardiac tissue-on-a-chip (CTC) platforms have facilitated the in vitro replication of complex structures and functions of the adult human heart. Advanced CTCs now allow real-time functional readouts of tissue function, incorporate multiple human induced pluripotent stem cell (iPSC)-derived cell types, and include precise structural and environmental controls, which together provide an unprecedented ability to study myocardial disease states in vitro. Physiologically relevant CTCs represent effective models for the generation of new mechanistic insight into the role of EVs in cardiac function, disease, and repair, supporting the advancement of EV therapeutics towards clinical translation for treatment of heart disease. [ABSTRACT FROM AUTHOR]

• Children spent the majority of outdoor time in open space location/activity type. • Play in fixed equipment location/activity type resulted in high activity intensity. • Both location and activity type similarly predicted activity intensity. Understanding the context of children's schoolyard activity can inform approaches by which to increase physical activity participation. Two major approaches exist for assessing this context- based on location or activity type. Location-based methods (e.g., Global Positioning Systems) may miss variations in activity type if children participate in multiple types of activities in each location (e.g., children engage in something other than playing with sand in a sandbox). Activity-type based methods for contextualizing activity (e.g., Observational System for Recording Physical Activity in Children, OSRAC) capture activity type, but not location, and children might participate in the same type(s) of activities in multiple schoolyard locations. The purpose of this study was to compare location- vs activity type-based approaches to characterizing children's schoolyard behavior. Preschoolers' (N = 50) schoolyard location and activity type (based on OSRAC) were video-coded and matched with physical activity monitor data (counts/s) for 1 outdoor period (~43 min). The results showed that multiple activities occurred within each location (median = 5), but the predominant activity typically matched the expected activity type (e.g., 66.9% fixed equipment play in the fixed equipment location). Children spent the majority of their time in open space (type or location; 37.6%–48.9%), but there were differences in the setting that promoted the most physical activity (teacher arranged type, but fixed equipment location). Activity types elicited varying physical activity levels depending on location (e.g., open space activities in open spaces vs on paths: 40.9 vs 60.7 counts/s). Activity type- and location-based approaches provide some similar, but potentially additive information about schoolyard behavior, which is an important methodological consideration for future studies. [ABSTRACT FROM AUTHOR]

Diagnostic and therapeutic priorities vary for the 8 types of infection reviewed. [ABSTRACT FROM AUTHOR]

A central concept of evolutionary biology, supported by broad scale allometric analyses, asserts that changing morphology should induce downstream changes in locomotor kinematics and energetics, and by inference selective fitness. However, if these mechanistic relationships exist at local intraspecific scales, where they could provide substrate for fundamental microevolutionary processes, is unknown. Here, analyses of selectively-bred duck breeds demonstrate that distinct body shapes incur kinematic shifts during walking, but these do not translate into differences in energetics. A combination of modular relationships between anatomical regions, and a trade-off between limb flexion and trunk pitching, are shown to homogenise potential functional differences between the breeds, accounting for this discrepancy between form and function. This complex interplay between morphology, motion and physiology indicates that understanding evolutionary links between the avian body plan and locomotor diversity requires studying locomotion as an integrated whole and not key anatomical innovations in isolation. Duck breeds selectively bred for disparate body shapes are found to walk with different limb kinematics but incur similar energetic costs. This is attributed to the interplay of dynamic kinematic and modular anatomical processes. [ABSTRACT FROM AUTHOR]

Adverse cardiac outcomes in COVID-19 patients, particularly those with preexisting cardiac disease, motivate the development of human cell-based organ-on-a-chip models to recapitulate cardiac injury and dysfunction and for screening of cardioprotective therapeutics. Here, we developed a heart-on-a-chip model to study the pathogenesis of SARS-CoV-2 in healthy myocardium established from human induced pluripotent stem cell (iPSC)-derived cardiomyocytes and a cardiac dysfunction model, mimicking aspects of preexisting hypertensive disease induced by angiotensin II (Ang II). We recapitulated cytopathic features of SARS-CoV-2-induced cardiac damage, including progressively impaired contractile function and calcium handling, apoptosis, and sarcomere disarray. SARS-CoV-2 presence in Ang II-treated hearts-on-a-chip decreased contractile force with earlier onset of contractile dysfunction and profoundly enhanced inflammatory cytokines compared to SARS-CoV-2 alone. Toward the development of potential therapeutics, we evaluated the cardioprotective effects of extracellular vesicles (EVs) from human iPSC which alleviated the impairment of contractile force, decreased apoptosis, reduced the disruption of sarcomeric proteins, and enhanced beta-oxidation gene expression. Viral load was not affected by either Ang II or EV treatment. We identified MicroRNAs miR-20a-5p and miR-19a-3p as potential mediators of cardioprotective effects of these EVs. [ABSTRACT FROM AUTHOR]

Erythema, skin thickening, and scales typify most cases, but other patterns exist. Tx choices may differ, depending on how much body surface area is covered. [ABSTRACT FROM AUTHOR]

Functional reconstructions of extinct animals represent a crucial step towards understanding palaeocological interactions, selective pressures and macroevolutionary patterns in the fossil record. In recent years, computational approaches have revolutionised the field of 'evolutionary biomechanics' and have, in general, resulted in convergence of quantitative estimates of performance on increasingly narrow ranges for well studied taxa. Studies of body mass and locomotor performance of Tyrannosaurus rex – arguably the most intensively studied extinct animal – typify this pattern, with numerous independent studies predicting similar body masses and maximum locomotor speeds for this animal. In stark contrast to this trend, recent estimates of maximum bite force in T. rex vary considerably (> 50%) despite use of similar quantitative methodologies. Herein we demonstrate that the mechanistic causes of these disparate predictions are indicative of important and underappreciated limiting factors in biomechanical reconstructions of extinct organisms. Detailed comparison of previous models of T. rex bite force reveals that estimations of muscle fibre lengths and architecture are the principal source of disagreement between studies, and therefore that these parameters represents the greatest source of uncertainty in these reconstructions, and potentially therefore extinct animals generally. To address the issue of fibre length and architecture estimation in extinct animals we present data tabulated from the literature of muscle architecture from over 1100 muscles measured in extant terrestrial animals. Application of this dataset in a reanalysis of T. rex bite force emphasises the need for more data on jaw musculature from living carnivorous animals, alongside increased sophistication of modelling approaches. In the latter respect we predict that implementing limits on skeletal loading into musculoskeletal models will narrow predictions for T. rex bite force by excluding higher‐end estimates. [ABSTRACT FROM AUTHOR]

Background A short-course regimen of 3 months of weekly rifapentine and isoniazid (3HP) has recently been recommended by the World Health Organization as an alternative to at least 6 months of daily isoniazid (isoniazid preventive therapy [IPT]) for prevention of tuberculosis (TB). The contexts in which 3HP may be cost-effective compared to IPT among people living with human immunodeficiency virus are unknown. Methods We used a Markov state transition model to estimate the incremental cost-effectiveness of 3HP relative to IPT in high-burden settings, using a cohort of 1000 patients in a Ugandan HIV clinic as an emblematic scenario. Cost-effectiveness was expressed as 2017 US dollars per disability-adjusted life year (DALY) averted from a healthcare perspective over a 20-year time horizon. We explored the conditions under which 3HP would be considered cost-effective relative to IPT. Results Per 1000 individuals on antiretroviral therapy in the reference scenario, treatment with 3HP rather than IPT was estimated to avert 9 cases of TB and 1 death, costing $9402 per DALY averted relative to IPT. Cost-effectiveness depended strongly on the price of rifapentine, completion of 3HP, and prevalence of latent TB. At a willingness to pay of $1000 per DALY averted, 3HP is likely to be cost-effective relative to IPT only if the price of rifapentine can be greatly reduced (to approximately $20 per course) and high treatment completion (85%) can be achieved. Conclusions 3HP may be a cost-effective alternative to IPT in high-burden settings, but cost-effectiveness depends on the price of rifapentine, achievable completion rates, and local willingness to pay. [ABSTRACT FROM AUTHOR]

The formation of shear bands during high strain deformation processes is known to promote grain refinement and better mechanical response. However, the literature on how shear bands affect corrosion of aluminum alloys, supported by relevant microstructure characterizations is scarce. Here we provide insight into precipitate aggregation phenomena in a partially recrystallized microstructure. We elucidate how shear bands affect the material’s corrosion susceptibility and degradation mechanism. Our results demonstrate that shear bands, in ultra-fine grained aluminum alloys, are preferential sites for pitting and intergranular corrosion due to particle segregation. [ABSTRACT FROM AUTHOR]

Abstract: The collection and dissemination of vertebrate ichnological data is struggling to keep up with techniques that are becoming commonplace in the wider palaeontological field. A standard protocol is required to ensure that data is recorded, presented and archived in a manner that will be useful both to contemporary researchers, and to future generations. Primarily, our aim is to make the 3D capture of ichnological data standard practice, and to provide guidance on how such 3D data can be communicated effectively (both via the literature and other means) and archived openly and in perpetuity. We recommend capture of 3D data, and the presentation of said data in the form of photographs, false‐colour images, and interpretive drawings. Raw data (3D models of traces) should always be provided in a form usable by other researchers (i.e. in an open format). If adopted by the field as a whole, the result will be a more robust and uniform literature, supplemented by unparalleled availability of datasets for future workers. [ABSTRACT FROM AUTHOR]

Atmospheric chemistry is fueled by a large annual influx of nonmethane volatile organic compounds (NMVOC). These compounds influence ozone formation, lead to secondary organic aerosol production, and play a significant role for the oxidizing capacity of the atmosphere. The anthropogenic NMVOC budget is considerably uncertain due to the diversity of urban emission sources. Here, we present comprehensive observations of urban NMVOC eddy covariance fluxes using a newly designed proton-transfer-reaction quadrupole interface time-of-flight mass spectrometer. We found emission fluxes of a surprisingly large pool of oxygenated NMVOCs (OVOCs) with an appreciable fraction of higher oxidized OVOCs that cannot be explained by known fast photochemical turnaround or current primary emission estimates. Measured OVOC/NMVOC bulk flux ratios are two to four times higher than inferred from aggregated anthropogenic emission inventories. Extrapolating these results would double the global anthropogenic NMVOC flux. In view of globally accelerating urbanization, our study highlights the need to reevaluate the influence of anthropogenic NMVOC on atmospheric chemistry, human health, and the climate system. [ABSTRACT FROM AUTHOR]

Purpose:To discuss low-dose radiation-induced risks to male fertility focusing on potential mechanisms of low-dose radiation-induced damage on spermatogenesis, epidemiological studies of environmental radiation effects on sperm parameters and transgenerational effects following exposure of spermatogonial stem cells (SSCs). Background:Spermatogenesis produces mature male gametes, spermatozoa, which fertilize their counterpart female gametes, oocytes. The robust maintenance system of spermatogenesis is essential for genomic conservation; however, male fertility can be readily impacted by exposure to environmental, chemical and physical factors including ionizing radiation. The mammalian testes are known to be radiosensitive yet the underlying molecular mechanisms of low-dose radiation-induced risks for spermatogenesis remain unclear. Furthermore, evidence characterizing transgenerational effects following exposure of SSCs remain controversial. Conclusions:Current concerns over the possible effects of low-dose radiation exposure on spermatogenesis requires further elucidation that may be resolved comparing and integrating observed experimental and epidemiological data. [ABSTRACT FROM PUBLISHER]

Introduction: The aim of this study was to evaluate the outcome of the modified Carlevale intraocular lens (IOL) fixation technique, using two different vitrectomy ports (23- vs. 27-gauge) as anchor fixation. Methods: Retrospective, consecutive study of 282 eyes (282 patients) who underwent a secondary IOL implantation using the Carlevale IOL (Soleko IOL Division, Italy) with two anchor haptics for intrascleral implantation with either 23- or 27-gauge (G) port. Results: Transient post-operative ocular hypotonia (intraocular pressure ≤5 mm Hg) was observed less in the 27-G group (13 vs. 4 patients, p = 0.057) three requiring additional tunnel sutures (2 cases for 23-G; 1 case 27-G). Post-operative vitreous haemorrhage was recorded more often in the 23-G group (8 vs. 1 patient, p = 0.034), but all cases in both groups resolved without intervention. Visual acuity did improve post-operatively in the two groups. No post-operative complications such as retinal detachment, endophthalmitis, and IOL-dislocation tilt were observed in the follow-up. Conclusion: The 27-G modified technique for sutureless intrascleral implantation is simple and effective and causes less post-operative hypotony. [ABSTRACT FROM AUTHOR]

There has been growing interest in the use of nanomaterials for a range of biomedical applications over the last number of years. In particular, gold nanoparticles (GNPs) possess a number of unique properties that make them ideal candidates as radiosensitizers on the basis of their strong photoelectric absorption coefficient and ease of synthesis. However, despite promising preclinical evidence in vitro supported by a limited amount of in vivo experiments, along with advances in mechanistic understanding, GNPs have not yet translated into the clinic. This may be due to disparity between predicted levels of radiosensitization based on physical action, observed biological response and an incomplete mechanistic understanding, alongside current experimental limitations. This paper provides a review of the current state of the field, highlighting the potential underlying biological mechanisms in GNP radiosensitization and examining the barriers to clinical translation. [ABSTRACT FROM AUTHOR]

Over the past two decades, there has been a significant evolution in the technologies and techniques employed within the radiation oncology environment. Over the same period, extensive research into the use of nanotechnology in medicine has highlighted a range of potential benefits to its incorporation into clinical radiation oncology. This short communication describes key tools and techniques that have recently been introduced into specific stages of a patient's radiotherapy pathway, including diagnosis, external beam treatment and subsequent follow-up. At each pathway stage, consideration is given towards how nanotechnology may be combined with clinical developments to further enhance their benefit, with some potential opportunities for future research also highlighted. Prospective challenges that may influence the introduction of nanotechnology into clinical radiotherapy are also discussed, indicating the need for close collaboration between academic and clinical staff to realise the full clinical benefit of this exciting technology. [ABSTRACT FROM AUTHOR]

Perfluorooctanoic acid (PFOA), a perfluoroalkyl substance, is commonly detected in the serum of pregnant women and may impact fetal development via epigenetic re-programming. In a pilot study, we explored associations between serum PFOA concentrations during pregnancy and offspring peripheral leukocyte DNA methylation at delivery in women with high (n = 22, range: 12–26 ng/mL) and low (n = 22, range: 1.1–3.1 ng/mL) PFOA concentrations. After adjusting for cell type, child sex, and income, we did not find differences in CpG methylation in the two exposure groups that reached epigenome-wide significance. Among the 20 CpGs with the lowest p-values we found that seven CpG sites in three genes differed by exposure status. In a confirmatory cluster analysis, these 20 CpGs clustered into two groups that perfectly identified exposure status. Future studies with larger sample sizes should confirm these findings and determine if PFOA-associated changes in DNA methylation underlie potential health effects of PFOA. [ABSTRACT FROM AUTHOR]

Drug-primed reinstatement of cocaine seeking in rats is thought to reflect relapse-like behavior and is mediated by the integration of signals from mesocorticolimbic dopaminergic projections and corticostriatal glutamatergic innervation. Cocaine-primed reinstatement can also be attenuated by systemic administration of dopamine β-hydroxylase (DBH) inhibitors, which prevent norepinephrine (NE) synthesis, or by α1-adrenergic receptor (α1AR) antagonists, indicating functional modulation by the noradrenergic system. In the present study, we sought to further discern the role of NE in cocaine-seeking behavior by determining whether α1AR activation can induce reinstatement on its own or is sufficient to permit cocaine-primed reinstatement in the absence of all other AR signaling, and identifying the neuroanatomical substrate within the mesocorticolimbic reward system harboring the critical α1ARs. We found that while intracerebroventricular infusion of the α1AR agonist phenylephrine did not induce reinstatement on its own, it did overcome the blockade of cocaine-primed reinstatement by the DBH inhibitor nepicastat. Furthermore, administration of the α1AR antagonist terazosin in the medial prefrontal cortex (mPFC), but not the ventral tegmental area (VTA) or nucleus accumbens (NAc) shell, attenuated cocaine-primed reinstatement. Combined, these data indicate that α1AR activation in the mPFC is required for cocaine-primed reinstatement, and suggest that α1AR antagonists merit further investigation as pharmacotherapies for cocaine dependence. [ABSTRACT FROM AUTHOR]

Grape Phylloxera, Daktulosphaira vitifoliae, is a gall-forming insect that feeds on the leaves and roots of many Vitis species. The roots of the cultivated V. vinifera cultivars and hybrids are highly susceptible to grape phylloxera feeding damage. The native range of this insect covers most of North America, and it is particularly abundant in the eastern and central United States. Phylloxera was introduced from North America to almost all grape-growing regions across five of the temperate zone continents. It devastated vineyards in each of these regions causing large-scale disruptions to grape growers, wine makers and national economies. In order to understand the population diversity of grape phylloxera in its native range, more than 500 samples from 19 States and 34 samples from the introduced range (northern California, Europe and South America) were genotyped with 32 simple sequence repeat markers. STRUCTURE, a model based clustering method identified five populations within these samples. The five populations were confirmed by a neighbor-joining tree and principal coordinate analysis (PCoA). These populations were distinguished by their Vitis species hosts and their geographic locations. Samples collected from California, Europe and South America traced back to phylloxera sampled in the northeastern United States on V. riparia, with some influence from phylloxera collected along the Atlantic Coast and Central Plains on V. vulpina. Reproductive statistics conclusively confirmed that sexual reproduction is common in the native range and is combined with cyclical parthenogenesis. Native grape phylloxera populations were identified to be under Hardy-Weinberg equilibrium. The identification of admixed samples between many of these populations indicates that shared environments facilitate sexual reproduction between different host associated populations to create new genotypes of phylloxera. This study also found that assortative mating might occur across the sympatric range of the V. vulpina west and V. cinerea populations. [ABSTRACT FROM AUTHOR]

In conclusion, the single peripheral triangular mark is a simple and cost-saving supplementation for the EDM preparation with the liquid-bubble technique to ensure the correct orientation of the graft intraoperatively, resulting in significantly reduced graft turning and, therefore, reduced Re-DMEK rate. Dear Editor, The correct anatomical anterior-posterior orientation of the endothelial Descemet's membrane graft (EDM) is a significant but preventable cause of primary graft failure and graft detachment in DMEK (Descemet membrane endothelial keratoplasty) (Bachmann et al. 2010). [Extracted from the article]

A strategy for the conjugation of alcohol-containing payloads to antibodies has been developed and involves the methylene alkoxy carbamate (MAC) self-immolative unit. A series of MAC β-glucuronide model constructs were prepared to evaluate stability and enzymatic release, and the results demonstrated high stability at physiological pH in a substitution- dependent manner. All the MAC model compounds efficiently released alcohol drug surrogates under the action of β-glucuronidase. To assess the MAC technology for ADCs, the potent microtubule-disrupting agent auristatin E (AE) was incorporated through the norephedrine alcohol. Conjugation of the MAC β-glucuronide AE drug linker to the anti-CD30 antibody cAC10, and an IgG control antibody, gave potent and immunologically specific activities in vitro and in vivo. These studies validate the MAC self-immolative unit for alcoholcontaining payloads within ADCs, a class that has not been widely exploited. [ABSTRACT FROM AUTHOR]

A strategy for the conjugation of alcohol-containing payloads to antibodies has been developed and involves the methylene alkoxy carbamate (MAC) self-immolative unit. A series of MAC b-glucuronide model constructs were prepared to evaluate stability and enzymatic release, and the results demonstrated high stability at physiological pH in a substitution- dependent manner. All the MAC model compounds efficiently released alcohol drug surrogates under the action of β-glucuronidase. To assess the MAC technology for ADCs, the potent microtubule-disrupting agent auristatin E (AE) was incorporated through the norephedrine alcohol. Conjugation of the MAC β-glucuronide AE drug linker to the anti-CD30 antibody cAC10, and an IgG control antibody, gave potent and immunologically specific activities in vitro and in vivo. These studies validate the MAC self-immolative unit for alcoholcontaining payloads within ADCs, a class that has not been widely exploited. [ABSTRACT FROM AUTHOR]

Ultrasonic nondestructive testing of steel forgings aims at the detection and classification of material inhomogeneities to ensure the components fitness for use. Due to the high price and safety critical nature of large forgings for turbomachinery, there is great interest in the application of imaging algorithms to inspection data. However, small flaw indications that cannot be sufficiently resolved have to be characterized using amplitude-based quantification. One such method is the distance gain size method, which converts the maximum echo amplitudes into the diameters of penny-shaped equivalent size reflectors. The approach presented in this contribution combines the synthetic aperture focusing technique (SAFT) with an iterative inversion scheme to locate and quantify small flaws in a more reliable way. Ultrasonic inspection data obtained in a pulse–echo configuration are reconstructed by means of an Synthetic Focusing Technique (SAFT). From the reconstructed data, the amount and approximate location of small flaws are extracted. These predetermined positions, along with the constrained defect model of a penny-shaped crack, provide the initial parametrization for an elastodynamic simulation based on the Kirchhoff approximation. The identification of the optimal parameter set is achieved through an iteratively regularized Gauss–Newton method. By testing the characterization method on a series of flat-bottom holes under laboratory conditions, we demonstrate that the procedure is applicable over a wide range of defect sizes. To show suitability for large forging inspection, we additionally evaluate the inspection data of a large generator shaft forging of 0.6-m diameter. [ABSTRACT FROM PUBLISHER]

The article discusses arguments that if employers may record their employees, then people as employers of the policy should also be able to record the police when in public. It notes that the monitoring of police activity has become cheaper and feasible due to the advent of inexpensive audio recording equipment, video cameras and high-resolution photography. It points out that the proposed interaction between citizens and police is rooted in the employment relationship.

Summary MGG_03307 is a lectin isolated from Magnaporte oryzae , a fungus that causes devastating rice blast disease. Its function is associated with protecting M. oryzae from the host immune response in plants. To provide the structural basis of how MGG_03307 protects the fungus, crystal structures of its CVNH-LysM module were determined in the absence and presence of GlcNAc-containing cell wall chitin constituents, which can act as pathogen-associated molecular patterns. Our structures revealed that glycan binding is accompanied by a notable conformational change in the LysM domain and that GlcNAc 3 and GlcNAc 4 are accommodated similarly. GlcNAc 5 and GlcNAc 6 interact with the LysM domain in multiple conformations, as evidenced by solution nuclear magnetic resonance studies. No dimerization of MoCVNH3 via its LysM domain was observed upon binding to GlcNAc 6 , unlike in multiple LysM domain-containing proteins. Importantly, we define a specific consensus binding mode for the recognition of GlcNAc oligomers by single LysM domains. [ABSTRACT FROM AUTHOR]

Objective To understand the association between lower urinary tract symptoms (LUTS) and risk of bladder cancer in a large cohort of men. Methods Using data from the Health Professionals Follow-up Study, we examined risk of bladder cancer in relation to severity of LUTS among 30,183 men. During the follow-up period from 1996 until 2010, 476 newly diagnosed cases of bladder cancer occurred. The Cox proportional hazards regression was used to adjust for potential confounders. Results Among men with severe LUTS, risk of bladder cancer was 64% higher (relative risk [RR], 1.64; 95% confidence interval [CI], 0.87-3.08) compared with men who reported no LUTS. Subjects with both voiding and storage dysfunction had a significantly higher risk of bladder cancer (RR, 1.60; 95% CI, 1.00-2.56). Among individual urinary symptoms, urinary hesitancy was strongly associated with bladder cancer; those who experienced urinary hesitancy at least 50% of the time had more than twice the risk of bladder cancer (RR, 2.21; 95% CI, 1.29-3.78). Conclusion Our findings suggest that LUTS, especially urinary hesitancy, are associated with the development of bladder cancer in men. [ABSTRACT FROM AUTHOR]

Background: The impact of cell-composition effects in analysis of DNA methylation data is now widely appreciated. With the availability of a reference data set consisting of DNA methylation measurements on isolated cell types, it is possible to impute cell proportions and adjust for them, but there is increasing interest in methods that adjust for cell composition effects when reference sets are incomplete or unavailable. Results: In this article we present a theoretical basis for one such method, showing that the total effect of a phenotype on DNA methylation can be decomposed into orthogonal components, one representing the effect of phenotype on proportions of major cell types, the other representing either subtle effects in composition or global effects at focused loci, and that it is possible to separate these two types of effects in a finite data set. We demonstrate this principle empirically on nine DNA methylation data sets, showing that the first few principal components generally contain a majority of the information on cell-type present in the data, but that later principal components nevertheless contain information about a small number of loci that may represent more focused associations. We also present a new method for determining the number of line artermstointerpretas cell-mixture effects and demonstrate robustness to the choice of this parameter. Conclusions: Taken together, our work demonstrates that reference-free algorithms for cell-mixture adjustment can produce biologically valid results, separating cell-mediated epigenetic effects (i.e. apparent effects arising from differences in cell composition) from those that are not cell mediated, and that in general the interpretation of associations evident from DNA methylation should be carefully considered. [ABSTRACT FROM AUTHOR]

HPV infection is a causal agent in many epithelial cancers, yet our understanding of genetic susceptibility to HPV infection and resultant cancer risk is limited. Epidermodysplasia Verruciformis is a rare condition of extreme susceptibility to cutaneous HPV infection primarily attributable to mutations in TMC6 and TMC8. Genetic variation in the TMC6/TMC8 region has been linked to beta-type HPV infection and squamous cell carcinoma of the skin, cervical cancer, HPV persistence and progression to cervical cancer. Here, we have tested the hypothesis that the common TMC8 SNP rs7208422 is associated with high-risk HPV infection and risk of head and neck squamous cell carcinoma (HNSCC). Seropositivity to the HPV L1 protein (HPV16, 18, 11, 31, 33, 35, 45, 52, 58) was measured in 514 cases and 452 population-based controls. Genotype was significantly associated with seropositivity to HPV18 L1 (OR TT vs AA = 0.48, 95% CI = 0.22–0.99) and borderline significantly associated with HPV16 L1 (OR TT vs AA = 0.58, 95% CI = 0.22–1.17). There was a consistent inverse association between TMC8 genotype and infection with other HPV types, including statistically significant associations for HPV31 and HPV52. Consistent with these results, the variant T genotype was associated with a reduced risk of HNSCC (ORAT: 0.63, 95% CI 0.45–0.89, ORTT: 0.54, 95% CI 0.36–0.81), even among subjects seronegative for all HPV types (ORAT: 0.71, 95% CI 0.45–1.11, ORTT: 0.54, 95% CI 0.31–0.93). Our data indicate that common genetic variation in TMC8 is associated with high-risk HPV infection and HNSCC etiology. [ABSTRACT FROM AUTHOR]

Purpose: To determine differences in overall tumor responses measured by volumetric assessment and bioluminescence imaging (BLI) following exposure to uniform and non-uniform radiation fields in an ectopic prostate tumor model. Materials and methods: Bioluminescent human prostate tumor xenografts were established by subcutaneous implantation into male mice. Tumors were irradiated with uniform or non-uniform field configurations using conventional in vivo irradiation procedures performed using a 225 kVp generator with custom lead shielding. Tumor responses were measured using Vernier calipers and by BLI using an in vivo imaging system. Survival was defined as the time to quadroupling of pre-treatment tumor volume. Results: The correlation between BLI and tumor volume measurements was found to be different for un-irradiated ( R = 0.61), uniformly irradiated ( R = 0.34) and partially irradiated ( R = 0.30) tumors. Uniformly irradiated tumors resulted in an average tumor growth delay of 60 days with median survival of 75 days, compared to partially irradiated tumors which showed an average growth delay of 24 days and median survival of 38 days. Conclusions: Correlation between BLI and tumor volume measurements is lower for partially irradiated tumors than those exposed to uniform dose distributions. The response of partially irradiated tumors suggests non-uniformity in response beyond physical dose distribution within the target volume. Dosimetric uncertainty associated with conventional in vivo irradiation procedures prohibits their ability to accurately determine tumor response to non-uniform radiation fields and stresses the need for image guided small animal radiation research platforms. [ABSTRACT FROM AUTHOR]

Background HPV infection is an established risk factor for oropharyngeal cancer, and it has been proposed that cigarette smoking may potentiate HPV infection in the oral epithelium. We sought to test the hypothesis that cigarette smoking increases HPV infection in an HPV16 serology study of cancer-free individuals. Methods Subjects were participants in a risk factor study for head and neck cancer, and were required to have no prior history of either HNSCC or any other cancer. Tobacco use and other risk factor data were gathered through interviewer-assisted questionnaires, while serology was conducted in a blinded fashion using a glutathione S-transferase capture enzyme-linked immunosorbent assay (ELISA) to detect antibodies against HPV16 L1, E1, E2, E4, E6 and E7 proteins. The differences in tobacco use by HPV serology were evaluated by ANOVA; and the reported odds ratios and 95% confidence intervals were determined by using unconditional logistic regression. Results We found no overall association of HPV16 serological markers with smoking. However, when the data were stratified by median age, smoking was positively associated with seropositivity for the HPV16 L1 capsid antigen in the younger controls while the older controls were less likely to be HPV16 L1 positive if they smoked (pinteraction < 0.002). There was no similar association of smoking and age with serological response to the early proteins (i.e E6, E7). Conclusions Exposure to HPV16 capsid protein (L1) is increased among relatively younger adults who smoke and diminished among older smokers. However, this pattern is not accompanied by a differential susceptibility for active infection (as determined by the early gene proteins such as E6 and E7) among young and older smokers. [ABSTRACT FROM AUTHOR]

Traditional radiotherapy of bulky tumors has certain limitations. Spatially fractionated radiation therapy (GRID) and intensity modulated radiotherapy (IMRT) are examples of advanced modulated beam therapies that help in significant reductions in normal tissue damage. GRID refers to the delivery of a single high dose of radiation to a large treatment area that is divided into several smaller fields, while IMRT allows improved dose conformity to the tumor target compared to conventional three-dimensional conformal radiotherapy. In this review, we consider spatially fractionated radiotherapy approaches focusing on GRID and IMRT, and present complementary evidence from different studies which support the role of radiation induced signaling effects in the overall radiobiological rationale for these treatments. [ABSTRACT FROM AUTHOR]

ABSTRACT Ornithischian dinosaurs were primitively bipedal with forelimbs modified for grasping, but quadrupedalism evolved in the clade on at least three occasions independently. Outside of Ornithischia, quadrupedality from bipedal ancestors has only evolved on two other occasions, making this one of the rarest locomotory transitions in tetrapod evolutionary history. The osteological and myological changes associated with these transitions have only recently been documented, and the biomechanical consequences of these changes remain to be examined. Here, we review previous approaches to understanding locomotion in extinct animals, which can be broadly split into form-function approaches using analogy based on extant animals, limb-bone scaling, and computational approaches. We then carry out the first systematic attempt to quantify changes in locomotor muscle function in bipedal and quadrupedal ornithischian dinosaurs. Using three-dimensional computational modelling of the major pelvic locomotor muscle moment arms, we examine similarities and differences among individual taxa, between quadrupedal and bipedal taxa, and among taxa representing the three major ornithischian lineages (Thyreophora, Ornithopoda, Marginocephalia). Our results suggest that the ceratopsid Chasmosaurus and the ornithopod Hypsilophodon have relatively low moment arms for most muscles and most functions, perhaps suggesting poor locomotor performance in these taxa. Quadrupeds have higher abductor moment arms than bipeds, which we suggest is due to the overall wider bodies of the quadrupeds modelled. A peak in extensor moment arms at more extended hip angles and lower medial rotator moment arms in quadrupeds than in bipeds may be due to a more columnar hindlimb and loss of medial rotation as a form of lateral limb support in quadrupeds. We are not able to identify trends in moment arm evolution across Ornithischia as a whole, suggesting that the bipedal ancestry of ornithischians did not constrain the development of quadrupedal locomotion via a limited number of functional pathways. Functional anatomy appears to have had a greater effect on moment arms than phylogeny, and the differences identified between individual taxa and individual clades may relate to differences in locomotor performance required for living in different environments or for clade-specific behaviours. [ABSTRACT FROM AUTHOR]

The Mars Science Laboratory heat shield was designed to withstand a fully turbulent heat pulse using information from ground testing and computational analysis on a preflight design trajectory. Instrumentation on the flight heat shield measured in-depth temperatures to permit reconstruction of the surface heating. The data indicate that boundary-layer transition occurred at five of seven measurement locations before peak heating. Data oscillations at three pressure measurement locations may also indicate transition. This paper presents the heat shield temperature and pressure data, possible explanations for the timing of boundary-layer transition, and a comparison of reconstructed and computational heating on the actual trajectory. A smooth-wall boundary-layer Reynolds number that was used to predict transition is compared with observed transition at various heat shield locations. A single transition Reynolds number criterion does not uniformly explain the timing of boundary-layer transition observed during flight. A roughness-based Reynolds number suggests that transition due to discrete or distributed roughness elements occurred. However, the distributed roughness height from acreage heat shield material would have needed to be larger than expected. The instrumentation confirmed the predicted location of maximum turbulent heat flux near the lee-side shoulder. The reconstructed heat flux at that location is bounded by smooth-wall turbulent convective heating, indicating that a significant augmentation due to surface roughness did not occur. Turbulent heating on the downstream side of the heat shield nose exceeded smooth-wall convective levels, assuming a supercatalytic surface, indicating that roughness may have augmented heating. The stagnation region heating also exceeded calculated convective heating; the cause of elevated heating may be attributed to a combination of shock-layer radiation and a heating augmentation of unknown origin that was also evident in ground test data. [ABSTRACT FROM AUTHOR]

Recent advances in computer hardwareand software have made rigorousevaluation of current biomolecular force fields using microsecond-scalesimulations possible. Force fields differ in their treatment of electrostaticinteractions, including the formation of salt bridges in proteins.Here we conducted an extensive evaluation of salt bridge interactionsin the latest AMBER, CHARMM, and OPLS force fields, using microsecond-scalemolecular dynamics simulations of amino acid analogues in explicitsolvent. We focused on salt bridges between three different pairsof oppositely charged amino acids: Arg/Asp, Lys/Asp, and His(+)/Asp.Our results reveal considerable variability in the predicted KAvalues of the salt bridges for these forcefields, as well as differences from experimental data: almost allof the force fields overestimate the strengths of the salt bridges.When amino acids are represented by side-chain analogues, the AMBERff03 force field overestimates the KAvaluesthe least, while for complete amino acids, the AMBER ff13α forcefield yields the lowest KAvalue, mostlikely caused by an altered balance of side-chain/side-chain and side-chain/backbonecontacts. These findings confirm the notion that the implicit incorporationof solvent polarization improves the accuracy of modeling salt bridgeinteractions. [ABSTRACT FROM AUTHOR]

Recent studies have concluded that Viking-era entry system deceleration technologies are extremely difficult to scale for progressively larger payloads (tens of metric tons) required for human Mars exploration. Supersonic retropropulsion is one of a few developing technologies that may enable future human-scale Mars entry systems. However, in order to be considered as a viable technology for future missions, supersonic retropropulsion will require significant maturation beyond its current state. This paper proposes major milestones for advancing the component technologies of supersonic retropropulsion such that it can be reliably used on Mars technology demonstration missions to land larger payloads than are currently possible using Viking-based systems. The development roadmap includes technology gates that are achieved through ground-based testing and high-fidelity analysis, culminating with subscale flight testing in Earth's atmosphere that demonstrates stable and controlled flight. The component technologies requiring advancement include large engines (100s of kilonewtons of thrust) capable of throttling and gimbaling, entry vehicle aerodynamics and aerothermodynamics modeling, entry vehicle stability and control methods, reference vehicle systems engineering and analyses, and high-fidelity models for entry trajectory simulations. Finally, a notional schedule is proposed for advancing the technology from suborbital free-flight tests at Earth through larger and more complex system-level technology demonstrations and precursor missions at Mars. [ABSTRACT FROM AUTHOR]

It is inevitable that some important specimens will become lost or damaged over time, conservation is therefore of vital importance. The Paluxy River dinosaur tracksite is among the most famous in the world. In 1940, Roland T. Bird described and excavated a portion of the site containing associated theropod and sauropod trackways. This excavated trackway was split up and housed in different institutions, and during the process a portion was lost or destroyed. We applied photogrammetric techniques to photographs taken by Bird over 70 years ago, before the trackway was removed, to digitally reconstruct the site as it was prior to excavation. The 3D digital model offers the opportunity to corroborate maps drawn by R.T. Bird when the tracksite was first described. More broadly, this work demonstrates the exciting potential for digitally recreating palaeontological, geological, or archaeological specimens that have been lost to science, but for which photographic documentation exists. [ABSTRACT FROM AUTHOR]

Several species of S proteobacteria are capable of reducing insoluble metal oxides as well as other extracellular electron acceptors. These bacteria play a critical role in the cycling of minerals in subsurface environments, sediments, and ground-water. In some species of bacteria such as Geobacter sulfurreducens, the transport of electrons is proposed to be facilitated by filamentous fibers that are referred to as bacterial nanowires. These nanowires are polymeric assemblies of proteins belonging to the type IVa family of pilin proteins and are mainly comprised of one subunit protein, PilA. Here, we report the high resolution solution NMR structure of the PilA protein from G. sulfurreducens determined in detergent micelles. The protein is >85% α-helical and exhibits similar architecture to the N-terminal regions of other non-conductive type IVa pilins. The detergent micelle interacts with the first 21 amino acids of the protein, indicating that this region likely associates with the bacterial inner membrane prior to fiber formation. A model of the G. sulfurreducens pilus fiber is proposed based on docking of this structure into the fiber model of the type IVa pilin from Neisseria gonorrhoeae. This model provides insight into the organization of aromatic amino acids that are important for electrical conduction. [ABSTRACT FROM AUTHOR]