Objectives/Goals: The gut microbiome and its metabolites, such as short-chain fatty acids (SCFA), are dysregulated in rheumatoid arthritis (RA); however, the significance of this observation and its implications in pathogenesis and therapeutics is unclear. Here, we explore the role of the SCFA, butyrate, in treatment efficacy in new-onset rheumatoid arthritis. Methods/Study Population: We designed a proof-of-principle study to determine the effects of butyrate supplementation in new-onset RA (NORA) patients that fulfilled 2010 ACR/EULAR RA criteria. We evaluated the effects of methotrexate (MTX) plus butyrate in NORA (n = 17; 1 gm butyrate, 3 times daily) compared to MTX alone (n = 19) over 4 months. MTX responders were defined by a change in disease activity score (DAS)-28 ESR of > 1.8 at 4 months. Fecal samples were collected at baseline and followed up for 16s rRNA sequencing and metabolite quantification by 1H NMR spectroscopy. Unpaired-t, paired-t, Wilcox and Fisher’s exact test were performed as appropriate. Results/Anticipated Results: MTX responders in the MTX-only group had a higher concentration of fecal butyrate than nonresponders at baseline (p = 0.045). Fecal butyrate concentration decreased over time in treatment responders in MTX group (p = 0.05), whereas butyrate concentration remained similar in MTX/butyrate group. Prior to treatment, both MTX and MTX/butyrate groups demonstrated similar levels of gut bacterial alpha diversity (Shannon index), yet only the MTX/butyrate group demonstrated a significant increase in alpha diversity by 4 months (p = 0.022). LefSe analysis demonstrated increased abundances of Bacteroides, Clostridium, and Phascolarctobacterium in responders in the MTX/butyrate group by 4 months. Ten (52.6%) patients in MTX and 11 (64.7%) in MTX/butyrate group were considered MTX responders by 4 months (p = 0.516). Discussion/Significance of Impact: Butyrate supplementation increased gut microbial diversity in patients and led to increased abundance of Bacteroides, which has been implicated in efficacy of methotrexate, a first line medication in rheumatoid arthritis. Butyrate may have implications for the maximization of therapeutic effectiveness in rheumatoid arthritis.

Few studies have examined the genetic population structure of vector-borne microparasites in wildlife, making it unclear how much these systems can reveal about the movement of their associated hosts. This study examined the complex host–vector–microbe interactions in a system of bats, wingless ectoparasitic bat flies (Nycteribiidae), vector-borne microparasitic bacteria (Bartonella) and bacterial endosymbionts of flies (Enterobacterales) across an island chain in the Gulf of Guinea, West Africa. Limited population structure was found in bat flies and Enterobacterales symbionts compared to that of their hosts. Significant isolation by distance was observed in the dissimilarity of Bartonella communities detected in flies from sampled populations of Eidolon helvum bats. These patterns indicate that, while genetic dispersal of bats between islands is limited, some non-reproductive movements may lead to the dispersal of ectoparasites and associated microbes. This study deepens our knowledge of the phylogeography of African fruit bats, their ectoparasites and associated bacteria. The results presented could inform models of pathogen transmission in these bat populations and increase our theoretical understanding of community ecology in host–microbe systems.

This conversation article brings together six of the original contributors to the 1993 Getting the Big Picture special issue of the British Journal for the History of Science. The contributors introduce their personal memories of the 1991 conference panel which formed the basis of that special issue. They also discuss the wider intellectual, institutional and political contexts of writing the history of science during the 1980s and 1990s, before concluding with reflections on the future of the discipline. The conversation was held live online via Microsoft Teams in March 2023. A professional transcript was produced by Sarah King. The transcript was then edited by James Poskett for length and clarity, before final edits were made by the contributors.

Wildlife conservation on private land is an important approach that is increasingly utilized to protect biodiversity and can help contribute to the 30 by 30 target of the Global Biodiversity Framework. In 2018, a Chilean non-profit conservation organization launched a land conservation programme aiming to build long-term partnerships with private landowners to protect critical habitat for threatened amphibians in Chilean Patagonia. Here we describe a new locality record of the micro-endemic, Endangered Barrio's frog Insuetophrynus acarpicus found at a site that joined the programme in 2020. Barrio's frog is ranked 11th in the list of Evolutionarily Distinct and Globally Endangered amphibians. Our systematic literature search showed that most aspects of the natural history and ecology of this species are unknown, limiting our ability to provide actionable science to inform its conservation. The newly described Barrio's frog population is the eighth known locality of this species and one of only three occurring within a protected area. Habitat quality assessments indicated optimal conditions for most of the measured habitat parameters in the high-gradient stream where the species occurs. This case study illustrates that long-term partnerships between private landowners and conservationists can be used as an effective tool to protect the habitat of highly threatened amphibians.

Microscopic examination of blood smears remains the gold standard for laboratory inspection and diagnosis of malaria. Smear inspection is, however, time-consuming and dependent on trained microscopists with results varying in accuracy. We sought to develop an automated image analysis method to improve accuracy and standardization of smear inspection that retains capacity for expert confirmation and image archiving. Here, we present a machine learning method that achieves red blood cell (RBC) detection, differentiation between infected/uninfected cells, and parasite life stage categorization from unprocessed, heterogeneous smear images. Based on a pretrained Faster Region-Based Convolutional Neural Networks (R-CNN) model for RBC detection, our model performs accurately, with an average precision of 0.99 at an intersection-over-union threshold of 0.5. Application of a residual neural network-50 model to infected cells also performs accurately, with an area under the receiver operating characteristic curve of 0.98. Finally, combining our method with a regression model successfully recapitulates intraerythrocytic developmental cycle with accurate lifecycle stage categorization. Combined with a mobile-friendly web-based interface, called PlasmoCount, our method permits rapid navigation through and review of results for quality assurance. By standardizing assessment of Giemsa smears, our method markedly improves inspection reproducibility and presents a realistic route to both routine lab and future field-based automated malaria diagnosis.

Over recent decades, Chinese giant salamanders Andrias spp. have declined dramatically across much of their range. Overexploitation and habitat degradation have been widely cited as the cause of these declines. To investigate the relative contribution of each of these factors in driving the declines, we carried out standardized ecological and questionnaire surveys at 98 sites across the range of giant salamanders in China. We did not find any statistically significant differences between water parameters (temperature, dissolved oxygen, ammonia, nitrite, nitrate, salinity, alkalinity, hardness and flow rate) recorded at sites where giant salamanders were detected by survey teams and/or had been recently seen by local respondents, and sites where they were not detected and/or from which they had recently been extirpated. Additionally, we found direct and indirect evidence that the extraction of giant salamanders from the wild is ongoing, including within protected areas. Our results support the hypothesis that the decline of giant salamanders across China has been primarily driven by overexploitation. Data on water parameters may be informative for the establishment of conservation breeding programmes, an initiative recommended for the conservation of these species.

Darwin's frogs Rhinoderma darwinii and Rhinoderma rufum are the only known species of amphibians in which males brood their offspring in their vocal sacs. We propose these frogs as flagship species for the conservation of the Austral temperate forests of Chile and Argentina. This recommendation forms part of the vision of the Binational Conservation Strategy for Darwin's Frogs, which was launched in 2018. The strategy is a conservation initiative led by the IUCN SSC Amphibian Specialist Group, which in 2017 convened 30 governmental, non-profit and private organizations from Chile, Argentina and elsewhere. Darwin's frogs are iconic examples of the global amphibian conservation crisis: R. rufum is categorized as Critically Endangered (Possibly Extinct) on the IUCN Red List, and R. darwinii as Endangered. Here we articulate the conservation planning process that led to the development of the conservation strategy for these species and present its main findings and recommendations. Using an evidence-based approach, the Binational Conservation Strategy for Darwin's Frogs contains a comprehensive status review of Rhinoderma spp., including critical threat analyses, and proposes 39 prioritized conservation actions. Its goal is that by 2028, key information gaps on Rhinoderma spp. will be filled, the main threats to these species will be reduced, and financial, legal and societal support will have been achieved. The strategy is a multi-disciplinary, transnational endeavour aimed at ensuring the long-term viability of these unique frogs and their particular habitat.

Although rationalization about one's own beliefs and actions can improve an individual's future decisions, beliefs can provide other benefits unrelated to their epistemic truth value, such as group cohesion and identity. A model of resource-rational cognition that accounts for these benefits may explain unexpected and seemingly irrational thought patterns, such as belief polarization.

This article presents a detailed account (provenance, codicology and contents) of Surrey History Centre, Woking, MS LM/1 083191/35, a late Restoration manuscript of lyra-viol and keyboard music. Originally from the papers of the More-Molyneux family of Loseley Park, LM/1083191135 is a source of otherwise unknown music by John Moss and Gerhard Diesineer. Two of the lyra-viol pieces in particular demonstrate that the Waking manuscript dates to at least 1687 or 1688, making it the latest known English source of viol music in tablature. The primary purpose of the manuscript seems to have been didactic. It was copied by a single scribe, who was evidently a musician actively engaged with the popular music and current political events of mid- to late-1680s London. LM/1083191/35 allows us a rare glimpse into the amateur musical world of 1680s London.

Radiocarbon accelerator mass spectrometric (AMS) dates on the acid-insoluble fraction from 38 core tops from the western Ross Sea, Antarctica, are used to address these questions: (1) What are the apparent ages of sediments at or close to the present sediment/water interface? (2) Is there a statistically significant pattern to the spatial distribution of core top ages? and (3) Is there a “correction factor” that can be applied to these age determinations to obtain the best possible Holocene (downcore) chronologies? Ages of core top sediments range from 2000 to 21,000 14C yr B.P. Some “old” core top dates are from piston cores and probably represent the loss of sediment during the coring process, but some core top samples >6000 14C yr B.P. may represent little or no Holocene deposition. Four possible sources of variability in dates ≤6000 14C yr B.P. (n = 28) are associated with (1) different sample preparation methods, (2) different sediment recovery systems, (3) different geographic regions, and (4) within-sample lateral age variability. Statistical analysis on an a posteriori design indicates that geographic area is the major cause of variability; there is a difference in mean surface sediment age of nearly 2000 yr between sites in the western Ross Sea and sites east of Ross Bank in south-central Ross Sea. The systematic variability in surface age between areas may be attributed to: (a) variable sediment accumulation rates (SAR) (surface age is inversely related to SAR), (b) differences in the percentage of reworked (dead) carbon between each area, and/or (c) differences in the CO2 exchange between the ocean and the atmosphere.

Finch trichomonosis is an emerging infectious disease affecting European passerines caused by a clonal strain of Trichomonas gallinae. Migrating chaffinches (Fringilla coelebs) were proposed as the likely vector of parasite spread from Great Britain to Fennoscandia. To test for such parasite carriage, we screened samples of oesophagus/crop from 275 Apodiform, Passeriform and Piciform birds (40 species) which had no macroscopic evidence of trichomonosis (i.e. necrotic ingluvitis). These birds were found dead following the emergence of trichomonosis in Great Britain, 2009–2012, and were examined post-mortem. Polymerase chain reactions were used to detect (ITS1/5·8S rRNA/ITS2 region and single subunit rRNA gene) and to subtype (Fe-hydrogenase gene) T. gallinae. Trichomonas gallinae was detected in six finches [three chaffinches, two greenfinches (Chloris chloris) and a bullfinch (Pyrrhula pyrrhula)]. Sequence data had 100% identity to the European finch epidemic A1 strain for each species. While these results are consistent with finches being vectors of T. gallinae, alternative explanations include the presence of incubating or resolved T. gallinae infections. The inclusion of histopathological examination would help elucidate the significance of T. gallinae infection in the absence of macroscopic lesions.

Populations of blue-footed boobies in the Galápagos Islands have declined by at least 50% compared with numbers recorded during the 1960s. Recently, concern has been expressed about potential adverse effects of introduced blood parasites; in particular, malarial parasites (i.e. Plasmodium sp.), which are frequently pathogenic and can cause mortality and morbidity in birds, and blood parasites of the genus Haemoproteus, which can reduce fitness. We screened blue-footed boobies at six breeding colonies within Galápagos for both genera of parasite. At two sites, we also investigated whether there was any relationship between infection status and physiological condition or breeding success. We found a high prevalence of Haemoproteus spp. in adults and chicks using PCR, although none was found on blood smears. We found no evidence of Plasmodium. Effects of parasitism on the condition of birds were limited. Also, there was no evidence that infection with Haemoproteus adversely affected breeding success or chick growth. Our results suggest that poor success of breeding birds was not strongly associated with Haemoproteus infection. However, regular colony monitoring and examination of dead birds are necessary to assess whether acute Haemoproteus infection might be responsible for some mortality, particularly of chicks.

Massive stars are some of the most important objects in the Universe, shaping the evolution of galaxies, creating chemical elements, and hence shaping the evolution of the Universe. However, the processes by which they form, and how they shape their environment during their birth processes, are not well understood. We are using NH3 data from the “The H2O Southern Galactic Plane Survey” (HOPS) to define the positions of dense cores/clumps of gas in the southern Galactic plane that are likely to form stars. We did a comparative study with different methods for finding clumps and found Fellwalker to be the best for this dataset. We detected ~ 500 clumps with mean kinetic temperature ~ 20 K and virial mass ~ 680 solar masses.

The Chinese giant salamander Andrias davidianus is endemic to China and is Critically Endangered, largely because of overexploitation for food. This species is an expensive delicacy in China, and a rapidly growing industry to farm the species has developed throughout much of the country, centred on the Qinling Mountain region of Shaanxi Province. During a 2010 workshop on Chinese giant salamander conservation, which involved a range of stakeholders from across China, it became clear that the conservation community knew little about the salamander farming industry and whether it posed actual or potential threats or opportunities for conservation of the Chinese giant salamander. We therefore conducted a series of investigations to understand the industry better. Our results indicate that although farming of Chinese giant salamanders has the potential to be a positive development for conservation by supplying market demand with farmed animals, it is currently more likely to threaten than support conservation of the species, with continued overexploitation and the potential added impacts of infectious disease and genetic pollution arising from farming practices such as movement of animals across the country and the release of untreated farm wastewater and farmed salamanders to the wild.