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Functional characteristics of the jaw apparatus, for example bite force, in vertebrates is a combination of the skeleton and the musculature. In birds, bite force has been measured directly or calculated using various methods including summation of forces generated by the different elements of the jaw musculature. However, there have been no reports of the relationships between body size with the mass of the different muscle groups in a closely related group of birds. This study explored allometry in the different jaw muscle masses from parrot (Psittaciformes) species differing in body mass by 40-fold. It was hypothesised that the different muscle masses would exhibit isometry with body mass and skull size. Parrot heads were dissected and the masses of the individual muscle complexes were recorded. Data were subjected to phylogenetically-controlled regression analysis to document scaling effects with body mass and skull size. Most, but not all muscles, exhibited positive allometry with body mass but most were isometric with skull size. Consequently, as parrots get bigger, their skulls get proportionally longer, but that the muscles within the head isometrically scaled relative to the size of these proportionally larger skulls. The large muscles imply greater bite forces in parrots than have been reported to date, which seems to be associated with an increase in skull size to accommodate more muscles. It is unknown whether this pattern is applicable to other birds within specific orders or even across birds as a whole. There needs to be further investigation into the allometry of the morphological and functional properties of the avian jaw musculature.

Human DNA polymerase theta (Polθ), which is essential for microhomology-mediated DNA double strand break repair, has been proposed as an attractive target for the treatment of BRCA deficient and other DNA repair pathway defective cancers. As previously reported, we recently identified the first selective small molecule Polθ in vitro probe

Academic work is increasingly important to court rulings on the Second Amendment and firearms law more generally. This article highlights two recent trends in social science research that supplement the traditional focus on guns and physical harm. The first strand of research focuses on the changing ways that gun owners connect with firearms, with personal security, status, identity, and cultural markers being key reasons people offer for possessing firearms. The second strand focuses on broadening our understanding of the impact of guns on the public sphere beyond just physical safety. This research surfaces the ways that guns can create fear, intimidation, and social trauma; deter civic participation and the exercise of constitutional rights; and further entrench racial inequality. Expected final online publication date for the Annual Review of Law and Social Science, Volume 19 is October 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Introduction Inflatable penile prosthesis (IPP) is the gold-standard treatment for erectile dysfunction that is refractory to pharmacologic therapies. While complications occur in 1-10% of patients, there remains a paucity of data regarding the impact of intracorporal injections (ICI) on a more difficult IPP placement. Objective We sought to demonstrate correlation between prior ICI and increased difficult with IPP placement. We hope to use our data to help guide future pre-procedural planning as well as patient counseling. Methods The records of patients who underwent IPP placement via single surgeon between 2016 – 2021 were retrospectively reviewed. Baseline patient demographics in addition to history of priapism, shunt, presence of Peyronie’s disease (PD), ICI use and duration, and intraoperative details including need for multiple corporal dilations and corporal scarring were gathered. Exclusion criteria included patients with re-operative/revision IPPs, patients with 2-piece IPPs, and patients with semi-rigid IPPs. The associations were calculated using Chi-squared analysis and logistic regression. Results There were 96 patients that met inclusion criteria, with average age of 62 years. Half (48/96) had history of ICI use, with mean duration of 17.25 months (range 1-65). ICI was not associated with corporal scarring (p=0.51) or need for multiple dilations during IPP placement (p=0.46). Duration of ICI (comparing subgroups of < 20 months and >20 months) was not significantly different with respect to corporal scarring (p=0.343) or need for multiple dilations (p=0.839). History of priapism or shunt was not associated with corporal scarring (p=0.251). Patients with PD were more likely to require multiple dilations (p=0.033). Conclusions History of ICI and its duration were not associated with corporal scarring and increased intraoperative difficulty. Patients with a history of Peyronie’s disease were more likely to require multiple dilations. Other studied factors including ICI duration of >20 months, history of priapism, and history of shunt are NOT associated with corporal scarring or need for multiple dilations. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Boston Scientific

Dinosaur embryos cause a lot of excitement in the scientific literature and are often widely reported because of the general public's interest in dinosaur biology. Well-preserved, articulated oviraptorosaur embryos in eggs are usually interpreted as representing a stage of development close to hatching because of their large size and good level of skeletal ossification. Based on this evidence, a recent report suggested that the position of the one embryo's head was reminiscent of an avian-like hatching position. Here we explore how the developmental stage of well-preserved oviraptorosaur embryos can be estimated, rather than assumed. This will help in our understanding of their developmental biology and its evolutionary consequences. Using quantitative methods and comparison with modern crocodilian embryos, we show that all articulated oviraptorosaur embryos are small relative to the egg and most likely at a stage of development equivalent to around 50%–60% of the developmental period, that is, not even close to hatching. This conclusion is supported by the fact that many elements of the crocodilian skeleton are well ossified many weeks before hatching and the position of oviraptorosaur embryos’ heads was also comparable to a crocodilian embryo many days before hatching. Misunderstandings about the stage of the developmental biology of these well-preserved oviraptorosaur embryos hampers our understanding of the true nature of their reproductive biology. We urge a more conservative approach to their interpretation. This is important, because misunderstandings in the minds of the public about dinosaur biology are hard to counter once poorly evidenced ideas have been reported around the world.

Interpretation of fossil material using comparative anatomy often relies on relationships predicted from data collected from extant species. Some years ago, it was suggested that femur length of birds could be predicted from egg mass but this relationship was counter-intuitive because egg mass is usually related to a measure of body size. The original analysis was also not phylogenetically controlled. This study used the same data to determine phylogenetically controlled relationships for body mass versus egg mass, and egg mass versus femur length. Further analysis showed that order was important in the prediction of egg mass from either body mass or femur length. For some orders, the single regression estimate through all data significantly over-, or under-estimated egg mass. This problem was more pronounced for femur length compared with body mass. Extrapolation of the relationship between femur length and egg mass for large extinct birds seemed to be provide useful data for the Gastornithidae but under-estimated egg mass for other large bird species of a variety of families. Use of equations derived from extant birds to gain insight into the reproductive biology of extinct species needs to be undertaken with great care.

BackgroundLarge reductions in the global malaria burden have been achieved in the last decades, but plateauing funding poses a challenge for progressing towards the ultimate goal of malaria eradication. We aimed to determine the optimal strategy to allocate global resources to achieve this goal.MethodsUsing previously published mathematical models ofPlasmodium falciparumandPlasmodium vivaxtransmission incorporating insecticide-treated nets (ITNs) as an illustrative intervention, we sought to identify the global funding allocation that maximized impact under defined objectives and across a range of global funding budgets.ResultsWe found that the optimal strategy for case reduction closely mirrored an allocation framework that prioritizes funding for high-transmission settings, resulting in total case reductions of 76% (optimal strategy) and 66% (prioritizing high-transmission settings) at intermediate budget levels. Allocation strategies that had the greatest impact on case reductions were associated with lesser near-term impacts on the global population at risk, highlighting a trade-off between reducing burden and “shrinking the map” through a focus on near-elimination settings. The optimal funding distribution prioritized high ITN coverage in high-transmission settings endemic forP. falciparumonly, while maintaining lower levels in low-transmission settings. However, at high budgets, 62% of funding was targeted to low-transmission settings co-endemic forP. falciparumandP. vivax.ConclusionsThese results support current global strategies to prioritize funding to high-burdenP. falciparum-endemic settings in sub-Saharan Africa to minimize clinical malaria burden and progress towards elimination but highlight competing goals of reducing the global population at risk and addressing the burden ofP. vivax.

Transmission-blocking interventions can play an important role in combating malaria worldwide. Recently, a highly potent Plasmodium falciparum transmission-blocking monoclonal antibody (TB31F) was demonstrated to be safe and efficacious in malaria-naive volunteers. Here we predict the potential public health impact of large-scale implementation of TB31F alongside existing interventions. We developed a pharmaco-epidemiological model, tailored to 2 settings of differing transmission intensity with already established insecticide-treated nets and seasonal malaria chemoprevention interventions. Community-wide annual administration (at 80% coverage) of TB31F over a 3-year period was predicted to reduce clinical incidence by 54% (381 cases averted per 1000 people per year) in a high-transmission seasonal setting, and 74% (157 cases averted per 1000 people per year) in a low-transmission seasonal setting. Targeting school-aged children gave the largest reduction in terms of cases averted per dose. An annual administration of the transmission-blocking monoclonal antibody TB31F may be an effective intervention against malaria in seasonal malaria settings.

Background & aimsFALCON 1 was a phase IIb study of pegbelfermin in patients with non-alcoholic steatohepatitis (NASH) and stage 3 fibrosis. This FALCON 1 post hoc analysis aimed to further assess the effect of pegbelfermin on NASH-related biomarkers, correlations between histological assessments and non-invasive biomarkers, and concordance between the week 24 histologically assessed primary endpoint response and biomarkers.MethodsBlood-based composite fibrosis scores, blood-based biomarkers, and imaging biomarkers were evaluated for patients with available data from FALCON 1at baseline through week 24. SomaSignal tests assessed protein signatures of NASH steatosis, inflammation, ballooning, and fibrosis in blood. Linear mixed-effect models were fit for each biomarker. Correlations and concordance were assessed between blood-based biomarkers, imaging, and histological metrics.ResultsAt week 24, pegbelfermin significantly improved blood-based composite fibrosis scores (ELF, FIB-4, APRI), fibrogenesis biomarkers (PRO-C3 and PC3X), adiponectin, CK-18, hepatic fat fraction measured by MRI-proton density fat fraction, and all four SomaSignal NASH component tests. Correlation analyses between histological and non-invasive measures identified four main categories: steatosis/metabolism, tissue injury, fibrosis, and biopsy-based metrics. Concordant and discordant effects of pegbelfermin on the primary endpoint vs. biomarker responses were observed; the most clear and concordant effects were on measures of liver steatosis and metabolism. A significant association between hepatic fat measured histologically and by imaging was observed in pegbelfermin arms.ConclusionsPegbelfermin improved NASH-related biomarkers most consistently through improvement of liver steatosis, though biomarkers of tissue injury/inflammation and fibrosis were also improved. Concordance analysis shows that non-invasive assessments of NASH support and exceed the improvements detected by liver biopsy, suggesting that greater consideration should be given to the totality of available data when evaluating the efficacy of NASH therapeutics.Clinical trial numberPost hoc analysis of NCT03486899.Impact and implicationsFALCON 1 was a study of pegbelfermin vs. placebo in patients with non-alcoholic steatohepatitis (NASH) without cirrhosis; in this study, patients who responded to pegbelfermin treatment were identified through examination of liver fibrosis in tissue samples collected through biopsy. In the current analysis, non-invasive blood- and imaging-based measures of fibrosis, liver fat, and liver injury were used to determine pegbelfermin treatment response to see how they compared with the biopsy-based results. We found that many of the non-invasive tests, particularly those that measured liver fat, identified patients who responded to pegbelfermin treatment, consistent with the liver biopsy findings. These results suggest that there may be additional value in using data from non-invasive tests, along with liver biopsy, to evaluate how well patients with NASH respond to treatment.