Enhancing our understanding of short-term rental activity: A daily scrape-based approach for Airbnb listings.

The growth of the online short-term rental market, facilitated by platforms such as Airbnb, has added to pressure on cities' housing supply. Without detailed data on activity levels, it is difficult to design and evaluate appropriate policy interventions. Up until now, the data sources and methods used to derive activity measures have not provided the detail and rigour needed to robustly carry out these tasks. This paper demonstrates an approach based on daily scrapes of the calendars of Airbnb listings. We provide a systematic interpretation of types of calendar activity derived from these scrapes and define a set of indicators of listing activity levels. We exploit a unique period in short-term rental markets during the UK's first COVID-19 lockdown to demonstrate the value of this approach.

A chromosome-scale assembly for 'd'Anjou' pear.

Cultivated pear consists of several Pyrus species with Pyrus communis (European pear) representing a large fraction of worldwide production. As a relatively recently domesticated crop and perennial tree, pear can benefit from genome-assisted breeding. Additionally, comparative genomics within Rosaceae promises greater understanding of evolution within this economically important family. Here, we generate a fully phased chromosome-scale genome assembly of P. communis 'd'Anjou.' Using PacBio HiFi and Dovetail Omni-C reads, the genome is resolved into the expected 17 chromosomes, with each haplotype totaling nearly 540 Megabases and a contig N50 of nearly 14 Mb. Both haplotypes are highly syntenic to each other and to the Malus domestica 'Honeycrisp' apple genome. Nearly 45,000 genes were annotated in each haplotype, over 90% of which have direct RNA-seq expression evidence. We detect signatures of the known whole-genome duplication shared between apple and pear, and we estimate 57% of d'Anjou genes are retained in duplicate derived from this event. This genome highlights the value of generating phased diploid assemblies for recovering the full allelic complement in highly heterozygous crop species.

Genomic analysis of the rhesus macaque (Macaca mulatta) and the cynomolgus macaque (Macaca fascicularis) uncover polygenic signatures of reinforcement speciation.

Speciation can involve phases of divergent adaptation in allopatry and ecological/reproductive character displacement in sympatry or parapatry. Reproductive character displacement can result as a means of preventing hybridization, a process known as reinforcement speciation. In this study, we use whole-genome sequencing (WGS) of two closely related primate species that have experienced introgression in their history, the rhesus (Macaca mulatta) and cynomolgus (M. fascicularis) macaques, to identify genes exhibiting reproductive character displacement and other patterns consistent with reinforcement speciation. Using windowed scans of various population genetic statistics to identify signatures of reinforcement, we find 184 candidate genes associated with a variety of functions, including an overrepresentation of multiple neurological functions and several genes involved in sexual development and gametogenesis. These results are consistent with a variety of genes acting in a reinforcement process between these species. We also find signatures of introgression of the Y-chromosome that confirm previous studies suggesting male-driven introgression of M. mulatta into M. fascicularis populations. This study uses WGS to find evidence of the process of reinforcement in primates that have medical and conservation relevance.

Genetic characterization of Macaca arctoides: A highlight of key genes and pathways.

When compared to the approximately 22 other macaque species, Macaca arctoides has many unique phenotypes. These traits fall into various phenotypic categories, including genitalia, coloration, mating, and olfactory traits. Here we used a previously identified whole genome set of 690 outlier genes to look for possible genetic explanations of these unique traits. Of these, 279 genes were annotated miRNAs, which are non-coding. Patterns within the remaining outliers in coding genes were investigated using GO (n = 370) and String (n = 383) analysis, which showed many interconnected immune-related genes. Further, we compared the outliers to candidate pathways associated with M. arcotides' unique phenotypes, revealing 10/690 outlier genes that overlapped these four pathways: hedgehog signaling, WNT signaling, olfactory, and melanogenesis. Of these, genes in all pathways except olfactory had higher FST values than the rest of the genes in the genome based on permutation tests. Overall, our results point to many genes each having a small impact on phenotype, working in tandem to cause large systemic changes. Additionally, these results may indicate pleiotropy. This seems to be especially true with the development and coloration of M. arctoides. Our results highlight that development, melanogenesis, immune function, and miRNAs may be heavily involved in M. arctoides' evolutionary history.

The Impacts of Benefit Sanctions: A Scoping Review of the Quantitative Research Evidence.

In recent decades, the use of conditionality backed by benefit sanctions for those claiming unemployment and related benefits has become widespread in the social security systems of high-income countries. Critics argue that sanctions may be ineffective in bringing people back to employment or indeed harmful in a range of ways. Existing reviews largely assess the labour market impacts of sanctions but our understanding of the wider impacts is more limited. We report results from a scoping review of the international quantitative research evidence on both labour market and wider impacts of benefit sanctions. Following systematic search and screening, we extract data for 94 studies reporting on 253 outcome measures. We provide a narrative summary, paying attention to the ability of the studies to support causal inference. Despite variation in the evidence base and study designs, we found that labour market studies, covering two thirds of our sample, consistently reported positive impacts for employment but negative impacts for job quality and stability in the longer term, along with increased transitions to non-employment or economic inactivity. Although largely relying on non-experimental designs, wider-outcome studies reported significant associations with increased material hardship and health problems. There was also some evidence that sanctions were associated with increased child maltreatment and poorer child well-being. Lastly, the review highlights the generally poor quality of the evidence base in this area, with few studies employing research methods designed to identify the causal impact of sanctions, especially in relation to wider impacts.

Evolution of genes involved in the unusual genitals of the bear macaque, Macaca arctoides.

Genital divergence is thought to contribute to reproductive barriers by establishing a "lock-and-key" mechanism for reproductive compatibility. One such example, Macaca arctoides, the bear macaque, has compensatory changes in both male and female genital morphology as compared to close relatives. M. arctoides also has a complex evolutionary history, having extensive introgression between the fascicularis and sinica macaque species groups. Here, phylogenetic relationships were analyzed via whole-genome sequences from five species, including M. arctoides, and two species each from the putative parental species groups. This analysis revealed ~3x more genomic regions supported placement in the sinica species group as compared to the fascicularis species group. Additionally, introgression analysis of the M. arctoides genome revealed it is a mosaic of recent polymorphisms shared with both species groups. To examine the evolution of their unique genital morphology further, the prevalence of candidate genes involved in genital morphology was compared against genome-wide outliers in various population genetic metrics of diversity, divergence, introgression, and selection, while accounting for background variation in recombination rate. This analysis identified 67 outlier genes, including several genes that influence baculum morphology in mice, which were of interest since the bear macaque has the longest primate baculum. The mean of four of the seven population genetic metrics was statistically different in the candidate genes as compared to the rest of the genome, suggesting that genes involved in genital morphology have increased divergence and decreased diversity beyond expectations. These results highlight specific genes that may have played a role in shaping the unique genital morphology in the bear macaque.

Application of a novel haplotype-based scan for local adaptation to study high-altitude adaptation in rhesus macaques.

When natural populations split and migrate to different environments, they may experience different selection pressures that can lead to local adaptation. To capture the genomic patterns of a local selective sweep, we develop XP-nSL, a genomic scan for local adaptation that compares haplotype patterns between two populations. We show that XP-nSL has power to detect ongoing and recently completed hard and soft sweeps, and we then apply this statistic to search for evidence of adaptation to high altitude in rhesus macaques. We analyze the whole genomes of 23 wild rhesus macaques captured at high altitude (mean altitude > 4000 m above sea level) to 22 wild rhesus macaques captured at low altitude (mean altitude < 500 m above sea level) and find evidence of local adaptation in the high-altitude population at or near 303 known genes and several unannotated regions. We find the strongest signal for adaptation at EGLN1, a classic target for convergent evolution in several species living in low oxygen environments. Furthermore, many of the 303 genes are involved in processes related to hypoxia, regulation of ROS, DNA damage repair, synaptic signaling, and metabolism. These results suggest that, beyond adapting via a beneficial mutation in one single gene, adaptation to high altitude in rhesus macaques is polygenic and spread across numerous important biological systems.

Mitonuclear conflict in a macaque species exhibiting phylogenomic discordance.

Speciation and hybridization are intertwined processes in the study of evolution. Hybridization between sufficiently diverged populations can result in genomic conflict within offspring, causing reduced viability and fertility, thus increasing divergence between populations. Conflicts between mitochondrial and nuclear genes are increasingly found to play a role in this process in various systems. We examine the possibility of this conflict in the bear macaque, Macaca arctoides (Primates: Cercopithecidae), a primate species exhibiting mitonuclear discordance due to extensive hybridization with species in the sinica and fascicularis groups. Here, divergence, introgression and natural selection of mitonuclear genes (N = 160) relative to nuclear control genes (N = 144) were analysed to determine whether there are evolutionary processes involved in resolving the potential conflict caused by mitonuclear discordance. Nucleotide divergence of mitonuclear genes is increased relative to control nuclear genes between M. arctoides and the species sharing its nuclear ancestry (p = 0.007), consistent with genetic conflict. However, measures of introgression and selection do not identify large-scale co-introgression or co-evolution as means to resolve mitonuclear conflict. Nonetheless, mitochondrial tRNA synthetases stand out in analyses using dN/dS and extended branch lengths as potential targets of selection. The methodology implemented provides a framework that can be used to examine the effects of mitonuclear co-introgression and co-evolution on a genomic scale in a variety of systems.

Linkage of national health and social care data: a cross-sectional study of multimorbidity and social care use in people aged over 65 years in Scotland.

BACKGROUND: little is known about the relationship between multimorbidity and social care use (also known as long-term care). The aim of this study was to assess the relationship between receipt of formal social care services and multimorbidity. METHODS: this retrospective data linkage, observational study included all individuals over the age of 65 in the population of Scotland in financial years 2014-15 and 2015-16 (n = 975,265). The main outcome was receipt of social care measured by presence in the Scottish Social Care Survey. Logistic regression models were used to assess the influence of multimorbidity, age, sex and socioeconomic position on the outcome reporting average marginal effects (AME). FINDINGS: 93.3% of those receiving social care had multimorbidity, 16.2% of those with multimorbidity received social care compared with 3.7% of those without. The strongest magnitudes of AME for receiving social care were seen for age and multimorbidity (respectively, 50 and 18% increased probability comparing oldest to youngest and most severe multimorbidity to none). A 5.5% increased probability of receiving social care was observed for the most-deprived compared with the least-deprived. INTERPRETATION: higher levels of social care receipt are observed in those with increasing age, severe multimorbidity and living in more deprived areas. Multimorbidity does not fully moderate the relationship between social care receipt and either age or deprivation.

Investigation of 2D Rainbow Metamaterials for Broadband Vibration Attenuation.

Phononic crystals (PnCs) and metamaterials are widely investigated for vibration suppression owing to the bandgaps, within which, wave propagation is prohibited or the attenuation level is above requirements. The application of PnCs and metamaterials is, however, limited by the widths of bandgaps. The recently developed rainbow structures consisting of spatially varied profiles have been shown to generate wider bandgaps than periodic structures. Inspired by this design strategy, rainbow metamaterials composed of nonperiodic mass blocks in two-dimensional (2D) space were proposed in the present study. The blocks were connected by curved beams and tessellated with internal voids to adjust their masses. In order to demonstrate the effects of the rainbow design, two 2D metamaterials, with periodic and nonperiodic units, respectively, were investigated and manufactured using additive manufacturing technologies. Receptance functions, i.e., displacement frequency response functions, of the manufactured metamaterials were calculated with finite element models and measured with a testing system containing a mechanical shaker, an impedance head, and a laser Doppler vibrometer. The obtained numerical and experimental results showed that the metamaterial with rainbow blocks has extended bandgaps compared with the periodic metamaterial.

Poverty and the re-growth of private renting in the UK, 1994-2018.

Over the last two decades, private renting has undergone a major revival in the UK, more than doubling its share within the housing system. Young adults increasingly remain in the sector into their 30s, giving rise to the term 'Generation Rent'. Using data from the UK's Family Resources Survey, this article shows how reliance on the sector varies by poverty status, particularly for young adults and children. In 2017/18, 42 per cent of adults under 40 in low-income poverty lived in private renting, compared with just 26 per cent of non-poor. This is almost double the proportion of 20 years earlier. Private renting is now home to more poor adults under 40 than owner occupation and social renting combined. In addition, one in three children in poverty (36 per cent) now lives in private renting, three times the level of 20 years ago. For both adults and children, rates are even higher in London and the South. Although rates of increase have slowed in recent years, this dramatic shift in the housing circumstances of those in poverty has a number of implications for housing and social policy which have not yet been sufficiently recognised.

Reconsidering the Relationship between Air Pollution and Deprivation.

This paper critically examines the relationship between air pollution and deprivation. We argue that focusing on a particular economic or social model of urban development might lead one to erroneously expect all cities to converge towards a particular universal norm. A naive market sorting model, for example, would predict that poor households will eventually be sorted into high pollution areas, leading to a positive relationship between air pollution and deprivation. If, however, one considers a wider set of theoretical perspectives, the anticipated relationship between air pollution and deprivation becomes more complex and idiosyncratic. Specifically, we argue the relationship between pollution and deprivation can only be made sense of by considering processes of risk perception, path dependency, gentrification and urbanization. Rather than expecting all areas to eventually converge to some universal norm, we should expect the differences in the relationship between air pollution and deprivation across localities to persist. Mindful of these insights, we propose an approach to modeling which does not impose a geographically fixed relationship. Results for Scotland reveal substantial variations in the observed relationships over space and time, supporting our argument.

Discovery of biaryl inhibitors of H+/K+ ATPase.

We report the identification of a novel biaryl template for H(+)/K(+) ATPase inhibition. Evaluation of critical SAR features within the biaryl imidazole framework and the use of pharmacophore modelling against known imidazopyridine and azaindole templates suggested that the geometry of the molecule is key to achieving activity. Herein we present our work optimising the potency of the molecule through modifications and substitutions to each of the ring systems. In particular sub-micromolar potency is achieved with (4b) presumably through a proposed intramolecular hydrogen bond that ensures the required imidazole basic centre is appropriately located.

Evaluation of basic, heterocyclic ring systems as templates for use as potassium competitive acid blockers (pCABs).

A variety of basic, heterocyclic templates has been reported as potassium-competitive, acid pump antagonists. Herein, we report a comparison of potencies of these templates and others to establish which offers the best start point for further systematic optimisation. Modifications were carried out to improve the developability profile of the more potent 1H-pyrrolo[2,3-c]pyridine template, affording molecules with improved overall in vitro characteristics versus the reported clinical candidate AR-H047108, and comparable to the clinically efficacious AZD-0865.

Orally active C-6 heteroaryl- and heterocyclyl-substituted imidazo[1,2-a]pyridine acid pump antagonists (APAs).

Acid pump antagonists (APAs) such as the imidazo[1,2-a]pyridine AZD-0865 2 have proven efficacious at low oral doses in acid related gastric disorders. Herein we describe some of the broader SAR in this class of molecule and detail the discovery of an imidazo[1,2-a]pyridine 15 which has excellent efficacy in animal models of gastric acid secretion following oral administration, as well as a good overall developability profile. The discovery strategy focuses on use of heteroaryl and heterocyclic substituents at the C-6 position and optimization of developability characteristics through modulation of global physico-chemical properties.