Forelimb muscle and joint actions in Archosauria: Insights from Crocodylus johnstoni (Pseudosuchia) and Mussaurus patagonicus (Sauropodomorpha)

Many of the major locomotor transitions during the evolution of Archosauria, the lineage including crocodiles and birds as well as extinct Dinosauria, were shifts from quadrupedalism to bipedalism (and vice versa). Those occurred within a continuum between more sprawling and erect modes of locomotion and involved drastic changes of limb anatomy and function in several lineages, including sauropodomorph dinosaurs. We present biomechanical computer models of two locomotor extremes within Archosauria in an analysis of joint ranges of motion and the moment arms of the major forelimb muscles in order to quantify biomechanical differences between more sprawling, pseudosuchian (represented the crocodile Crocodylus johnstoni) and more erect, dinosaurian (represented by the sauropodomorph Mussaurus patagonicus) modes of forelimb function. We compare these two locomotor extremes in terms of the reconstructed musculoskeletal anatomy, ranges of motion of the forelimb joints and the moment arm patterns of muscles across those ranges of joint motion. We reconstructed the threedimensional paths of 30 muscles acting around the shoulder, elbow and wrist joints. We explicitly evaluate how forelimb joint mobility and muscle actions may have changed with postural and anatomical alterations from basal archosaurs to early sauropodomorphs. We thus evaluate in which ways forelimb posture was correlated with muscle leverage, and how such differences fit into a broader evolutionary context (i.e. transition from sprawling quadrupedalism to erect bipedalism and then shifting to graviportal quadrupedalism). Our analysis reveals major differences of muscle actions between the more sprawling and erect models at the shoulder joint. These differences are related not only to the articular surfaces but also to the orientation of the scapula, in which extension/flexion movements in Crocodylus (e.g. protraction of the humerus) correspond to elevation/depression in Mussaurus. Muscle action is highly influenced by limb posture, more so than morphology. Habitual quadrupedalism in Mussaurus is not supported by our analysis of joint range of motion, which indicates that glenohumeral protraction was severely restricted. Additionally, some active pronation of the manus may have been possible in Mussaurus, allowing semi-pronation by a rearranging of the whole antebrachium (not the radius against the ulna, as previously thought) via long-axis rotation at the elbow joint. However, the muscles acting around this joint to actively pronate it may have been too weak to drive or maintain such orientations as opposed to a neutral position in between pronation and supination. Regardless, the origin of quadrupedalism in Sauropoda is not only linked to manus pronation but also to multiple shifts of forelimb morphology, allowing greater flexion movements of the glenohumeral joint and a more columnar forelimb posture.Facultad de Ciencias Naturales y Muse

Evaluating the cost-effectiveness of existing needle and syringe programmes in preventing hepatitis C transmission in people who inject drugs

AIM: To evaluate the cost-effectiveness of needle and syringe programmes (NSPs) compared with no NSPs on hepatitis C virus (HCV) transmission in the United Kingdom. DESIGN: Cost-effectiveness analysis from a National Health Service (NHS)/health-provider perspective, utilizing a dynamic transmission model of HCV infection and disease progression, calibrated using city-specific surveillance and survey data, and primary data collection on NSP costs. The effectiveness of NSPs preventing HCV acquisition was based on empirical evidence. SETTING AND PARTICIPANTS: UK settings with different chronic HCV prevalence among people who inject drugs (PWID): Dundee (26%), Walsall (18%) and Bristol (45%) INTERVENTIONS: Current NSP provision is compared with a counterfactual scenario where NSPs are removed for 10 years and then returned to existing levels with effects collected for 40 years. MEASUREMENTS: HCV infections and cost per quality-adjusted life year (QALY) gained through NSPs over 50 years. FINDINGS: Compared with a willingness-to-pay threshold of £20 000 per QALY gained, NSPs were highly cost-effective over a time-horizon of 50 years and decreased the number of HCV incident infections. The mean incremental cost-effectiveness ratio was cost-saving in Dundee and Bristol, and £596 per QALY gained in Walsall, with 78, 46 and 40% of simulations being cost-saving in each city, respectively, with differences driven by coverage of NSP and HCV prevalence (lowest in Walsall). More than 90% of simulations were cost-effective at the willingness-to-pay threshold. Results were robust to sensitivity analyses, including varying the time-horizon, HCV treatment cost and numbers of HCV treatments per year. CONCLUSIONS: Needle and syringe programmes are a highly effective low-cost intervention to reduce hepatitis C virus transmission, and in some settings they are cost-saving. Needle and syringe programmes are likely to remain cost-effective irrespective of changes in hepatitis C virus treatment cost and scale-up

Forelimb muscle and joint actions in Archosauria: Insights from Crocodylus johnstoni (Pseudosuchia) and Mussaurus patagonicus (Sauropodomorpha)

Many of the major locomotor transitions during the evolution of Archosauria, the lineage including crocodiles and birds as well as extinct Dinosauria, were shifts from quadrupedalism to bipedalism (and vice versa). Those occurred within a continuum between more sprawling and erect modes of locomotion and involved drastic changes of limb anatomy and function in several lineages, including sauropodomorph dinosaurs. We present biomechanical computer models of two locomotor extremes within Archosauria in an analysis of joint ranges of motion and the moment arms of the major forelimb muscles in order to quantify biomechanical differences between more sprawling, pseudosuchian (represented the crocodile Crocodylus johnstoni) and more erect, dinosaurian (represented by the sauropodomorph Mussaurus patagonicus) modes of forelimb function. We compare these two locomotor extremes in terms of the reconstructed musculoskeletal anatomy, ranges of motion of the forelimb joints and the moment arm patterns of muscles across those ranges of joint motion. We reconstructed the threedimensional paths of 30 muscles acting around the shoulder, elbow and wrist joints. We explicitly evaluate how forelimb joint mobility and muscle actions may have changed with postural and anatomical alterations from basal archosaurs to early sauropodomorphs. We thus evaluate in which ways forelimb posture was correlated with muscle leverage, and how such differences fit into a broader evolutionary context (i.e. transition from sprawling quadrupedalism to erect bipedalism and then shifting to graviportal quadrupedalism). Our analysis reveals major differences of muscle actions between the more sprawling and erect models at the shoulder joint. These differences are related not only to the articular surfaces but also to the orientation of the scapula, in which extension/flexion movements in Crocodylus (e.g. protraction of the humerus) correspond to elevation/depression in Mussaurus. Muscle action is highly influenced by limb posture, more so than morphology. Habitual quadrupedalism in Mussaurus is not supported by our analysis of joint range of motion, which indicates that glenohumeral protraction was severely restricted. Additionally, some active pronation of the manus may have been possible in Mussaurus, allowing semi-pronation by a rearranging of the whole antebrachium (not the radius against the ulna, as previously thought) via long-axis rotation at the elbow joint. However, the muscles acting around this joint to actively pronate it may have been too weak to drive or maintain such orientations as opposed to a neutral position in between pronation and supination. Regardless, the origin of quadrupedalism in Sauropoda is not only linked to manus pronation but also to multiple shifts of forelimb morphology, allowing greater flexion movements of the glenohumeral joint and a more columnar forelimb posture.Facultad de Ciencias Naturales y Muse

The impact of direct-acting antivirals on hepatitis C viraemia among people who inject drugs in England; real-world data 2011–2018

Direct‐acting antiviral (DAA) therapy for anybody with viraemic HCV infection has been scaled‐up in England since 2017. To assess early impacts, we investigated trends in, and factors associated with, HCV viraemia among people who inject drugs (PWID). We also examined trends in self‐reported treatment access. Bio‐behavioural data from an annual, national surveillance survey of PWID (2011–2018) estimated trends in viraemic prevalence among HCV antibody‐positive PWID. Multivariable logistic regression identified characteristics independently associated with viraemia. Trends in treatment access were examined for PWID with known infection. Between 2011 and 2016, viraemic prevalence among antibody‐positive PWID remained stable (2011, 57.7%; 2016, 55.8%) but decreased in 2017 (49.4%) and 2018 (50.4%) (both p < 0.001). After adjustment for demographic and behavioural characteristics, there remained significant reduction in viraemia in 2017 (adjusted odds ratio [aOR] 0.79, 95% CI 0.65–0.94) and 2018 (aOR 0.79, 95% CI 0.66–0.93) compared to 2016. Other factors associated with viraemia were male gender (aOR 1.68, 95% CI 1.53–1.86), geographical region, injecting in past year (aOR 1.26, 95% CI 1.13–1.41), imprisonment (aOR 1.14, 95% CI 1.04–1.31) and homelessness (aOR 1.17, 95% CI 1.04–1.31). Among non‐viraemic PWID with known infection, the proportion reporting ever receiving treatment increased in 2017 (28.7%, p < 0.001) and 2018 (38.9%, p < 0.001) compared to 2016 (14.5%). In conclusion, there has been a small reduction in HCV viraemia among antibody‐positive PWID in England since 2016, alongside DAA scale‐up, and some indication that treatment access has improved in the same period. Population‐level monitoring and focus on harm reduction is critical for achieving and evaluating elimination

Relationships of mass properties and body proportions to locomotor habit in terrestrial Archosauria

Abstract Throughout their 250 Myr history, archosaurian reptiles have exhibited a wide array of body sizes, shapes, and locomotor habits, especially in regard to terrestriality. These features make Archosauria a useful clade with which to study the interplay between body size, shape, and locomotor behavior, and how this interplay may have influenced locomotor evolution. Here, digital volumetric models of 80 taxa are used to explore how mass properties and body proportions relate to each other and locomotor posture in archosaurs. One-way, nonparametric, multivariate analysis of variance, based on the results of principal components analysis, shows that bipedal and quadrupedal archosaurs are largely distinguished from each other on the basis of just four anatomical parameters (p &lt; 0.001): mass, center of mass position, and relative forelimb and hindlimb lengths. This facilitates the development of a quantitative predictive framework that can help assess gross locomotor posture in understudied or controversial taxa, such as the crocodile-line Batrachotomus (predicted quadruped) and Postosuchus (predicted biped). Compared with quadrupedal archosaurs, bipedal species tend to have relatively longer hindlimbs and a more caudally positioned whole-body center of mass, and collectively exhibit greater variance in forelimb lengths. These patterns are interpreted to reflect differing biomechanical constraints acting on the archosaurian Bauplan in bipedal versus quadrupedal groups, which may have shaped the evolutionary histories of their respective members.</jats:p

Incarceration history and risk of HIV and hepatitis C virus acquisition among people who inject drugs: a systematic review and meta-analysis

Background People who inject drugs (PWID) experience a high prevalence of incarceration and might be at high risk of HIV and hepatitis C virus (HCV) infection during or after incarceration. We aimed to assess whether incarceration history elevates HIV or HCV acquisition risk among PWID. Methods In this systematic review and meta-analysis, we searched MEDLINE, Embase, and PsycINFO databases for studies in any language published from Jan 1, 2000 until June 13, 2017 assessing HIV or HCV incidence among PWID. We included studies that measured HIV or HCV incidence among community-recruited PWID. We included only studies reporting original results and excluded studies that evaluated incident infections by self-report. We contacted authors of cohort studies that met the inclusion or exclusion criteria, but that did not report on the outcomes of interest, to request data. We extracted and pooled data from the included studies using random-effects meta-analyses to quantify the associations between recent (past 3, 6, or 12 months or since last follow-up) or past incarceration and HIV or HCV acquisition (primary infection or reinfection) risk among PWID. We assessed the risk of bias of included studies using the Newcastle-Ottawa Scale. Between-study heterogeneity was evaluated using the I2 statistic and the P-value for heterogeneity. Findings We included published results from 20 studies and unpublished results from 21 studies. These studies originated from Australasia, western and eastern Europe, North and Latin America, and east and southeast Asia. Recent incarceration was associated with an 81% (relative risk [RR] 1·81, 95% CI 1·40–2·34) increase in HIV acquisition risk, with moderate heterogeneity between studies (I2=63·5%; p=0·001), and a 62% (RR 1·62, 95% CI 1·28–2·05) increase in HCV acquisition risk, also with moderate heterogeneity between studies (I2=57·3%; p=0·002). Past incarceration was associated with a 25% increase in HIV (RR 1·25, 95% CI 0·94–1·65) and a 21% increase in HCV (1·21, 1·02–1·43) acquisition risk. Interpretation Incarceration is associated with substantial short-term increases in HIV and HCV acquisition risk among PWID and could be a significant driver of HCV and HIV transmission among PWID. These findings support the need for developing novel interventions to minimise the risk of HCV and HIV acquisition, including addressing structural risks associated with drug laws and excessive incarceration of PWID

Biomechanics of Running Indicates Endothermy in Bipedal Dinosaurs

One of the great unresolved controversies in paleobiology is whether extinct dinosaurs were endothermic, ectothermic, or some combination thereof, and when endothermy first evolved in the lineage leading to birds. Although it is well established that high, sustained growth rates and, presumably, high activity levels are ancestral for dinosaurs and pterosaurs (clade Ornithodira), other independent lines of evidence for high metabolic rates, locomotor costs, or endothermy are needed. For example, some studies have suggested that, because large dinosaurs may have been homeothermic due to their size alone and could have had heat loss problems, ectothermy would be a more plausible metabolic strategy for such animals.Here we describe two new biomechanical approaches for reconstructing the metabolic rate of 14 extinct bipedal dinosauriforms during walking and running. These methods, well validated for extant animals, indicate that during walking and slow running the metabolic rate of at least the larger extinct dinosaurs exceeded the maximum aerobic capabilities of modern ectotherms, falling instead within the range of modern birds and mammals. Estimated metabolic rates for smaller dinosaurs are more ambiguous, but generally approach or exceed the ectotherm boundary.Our results support the hypothesis that endothermy was widespread in at least larger non-avian dinosaurs. It was plausibly ancestral for all dinosauriforms (perhaps Ornithodira), but this is perhaps more strongly indicated by high growth rates than by locomotor costs. The polarity of the evolution of endothermy indicates that rapid growth, insulation, erect postures, and perhaps aerobic power predated advanced “avian” lung structure and high locomotor costs

Association between growth and Pan I genotype within Atlantic cod (Gadus morhua) full sib families

Studies of the pantophysin (Pan I*) locus in Atlantic cod Gadus morhua and other marine gadoids indicate that the locus is under positive selection; in Atlantic cod, genotypic variation at this locus has been linked to differences in growth. Here, we present preliminary data comparing the growth and condition of different Atlantic cod Pan I* genotypes within families held under seminatural mesocosm conditions. Larvae from three full-sibling families carrying Pan I*bb or Pan I*ab genotypes were reared for 10 weeks in two mesocosms. Multivariate analysis of variance indicated that larvae carrying the Pan I*ab genotype exhibited significantly higher standard length, dry weight, and RNA: DNA ratio (condition factor) than did larvae that carried the Pan I*bb genotype, potentially indicating selection. The influence of linked loci cannot be excluded; indeed, the absence of a significant correlation between genotype and growth in one family may substantiate this. The lack of differences in survival among genotypes indicates that moderate selective effects are acting primarily through size-specific mortality and fecundity. The proposed putative fitness effects, together with documented marked geographic differentiation in the wild, have implications for Atlantic cod population structure, effective migration rates, recruitment, and local adaptation, which are of particular relevance in a species threatened by continuing exploitation and rising sea temperatures